Activation of int-1 and int-2 loci in GRf mammary tumors.

PubMed

Gray, D A; Jackson, D P; Percy, D H; Morris, V L

1986-10-30

The Mtv-2 locus is known to be associated with a high mammary tumor incidence (97%) and early development of mammary tumors (3-13 months) in GR mice. However, it was not previously known whether the provirus which resides at the Mtv-2 locus is tumorigenic in and of itself or whether reintegration of proviruses generated from Mtv-2 is required for tumorigenesis. Foster-nursing GR mice on C57/BL mice eliminates the milk-borne source of GR virus, and allows the study of Mtv-2 derived proviruses alone. Using this approach, we have tested predictions which follow from the "positional" versus "reintegrational" models of tumorigenesis. Specifically, we have examined tumors from primary foster-nursed (GRf) mice to determine if MMTV proviruses derived from Mtv-2 were scattered randomly throughout the genome or were clustered in the vicinity of the int-1 and int-2 loci, which are thought to be associated with mammary tumorigenesis. It was found that the majority of spontaneous GRf mammary tumors that were tested have MMTV proviral integrations in either or both of the int-1 and int-2 loci and have transcription of either or both of the int loci. Tumors induced by Mtv-2, therefore, appear to have arisen via a mechanism similar to the activation of the int loci by exogenous (milk-borne) MMTV proviruses.

Disruption or Excision of Provirus as an Approach to HIV Cure.

PubMed

Jerome, Keith R

2016-12-01

An effective approach to HIV cure will almost certainly require a combination of strategies, including some means of reducing the latent HIV reservoir. Because the integrated HIV provirus represents the major source of viral persistence and reactivation, one attractive approach is the direct targeting of provirus for disruption or excision using targeted endonucleases, such as CRISPR/Cas9, zinc finger nucleases, TAL effector nucleases, or meganucleases (homing endonucleases). This article highlights some of the challenges for successful endonuclease therapy for HIV, including optimization of enzyme activity and specificity, the possible emergence of viral resistance, and most importantly, efficient in vivo delivery of the enzymes to a sufficient portion of the latent reservoir.

Long-term follow up of feline leukemia virus infection and characterization of viral RNA loads using molecular methods in tissues of cats with different infection outcomes.

PubMed

Helfer-Hungerbuehler, A Katrin; Widmer, Stefan; Kessler, Yvonne; Riond, Barbara; Boretti, Felicitas S; Grest, Paula; Lutz, Hans; Hofmann-Lehmann, Regina

2015-02-02

It is a remarkable feature for a retrovirus that an infection with feline leukemia virus (FeLV) can result in various outcomes. Whereas some cats contain the infection and show a regressive course, others stay viremic and succumb to the infection within a few years. We hypothesized, that differences in the infection outcome might be causally linked to the viral RNA and provirus loads within the host and these loads therefore may give additional insight into the pathogenesis of the virus. Thus, the goals of the present study were to follow-up on experimentally infected cats and investigate tissues from cats with different infection outcomes using sensitive, specific TaqMan real-time PCR and reverse transcriptase (RT)-PCR. Nineteen experimentally FeLV-A/Glasgow-1-infected cats were categorized into having regressive, progressive or reactivated FeLV infection according to follow-up of FeLV p27 antigen detection in the blood. Remarkably, regressively infected cats showed detectable provirus and viral RNA loads in almost all of the 27 tested tissues, even many years after virus exposure. Moreover, some regressively infected cats reactivated the infection, and these cats had intermediate to high viral RNA and provirus tissue loads. The highest loads were found in viremic cats, independent of their health status. Tissues that represented sites of virus replication and shedding revealed the highest viral RNA and provirus loads, while the lowest loads were present in muscle and nerve tissues. A supplementary analysis of 20 experimentally infected cats with progressive infection revealed a median survival time of 3.1 years (range from 0.6 to 6.5 years); ∼70% (n=14) of these cats developed lymphoma, while leukemia and non-regenerative anemia were observed less frequently. Our results demonstrate that the different infection outcomes are associated with differences in viral RNA and provirus tissue loads. Remarkably, no complete clearance of FeLV viral RNA or provirus was detected in cats with regressive infection, even up to 12 years after exposure. In several cases FeLV reactivation could be observed. Thus, retroviruses integrated as provirus into the host's genome, could not be eliminated completely by the host and maintained their full potential for replication and reactivation. Copyright © 2014 Elsevier B.V. All rights reserved.

Acetylation of the human T-cell leukemia virus type 1 Tax oncoprotein by p300 promotes activation of the NF-{kappa}B pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lodewick, Julie; Lamsoul, Isabelle; Polania, Angela

The oncogenic potential of the HTLV-1 Tax protein involves activation of the NF-{kappa}B pathway, which depends on Tax phosphorylation, ubiquitination and sumoylation. We demonstrate that the nuclei of Tax-expressing cells, including HTLV-1 transformed T-lymphocytes, contain a pool of Tax molecules acetylated on lysine residue at amino acid position 346 by the transcriptional coactivator p300. Phosphorylation of Tax on serine residues 300/301 was a prerequisite for Tax localization in the nucleus and correlated with its subsequent acetylation by p300, whereas sumoylation, resulting in the formation of Tax nuclear bodies in which p300 was recruited, favored Tax acetylation. Overexpression of p300 markedlymore » increased Tax acetylation and the ability of a wild type HTLV-1 provirus, -but not of a mutant provirus carrying an acetylation deficient Tax gene-, to activate gene expression from an integrated NF-{kappa}B-controlled promoter. Thus, Tax acetylation favors NF-{kappa}B activation and might play an important role in HTLV-1-induced cell transformation.« less

Ancient DNA identification of early 20th century simian T-cell leukemia virus type 1.

PubMed

Calvignac, Sébastien; Terme, Jean-Michel; Hensley, Shannon M; Jalinot, Pierre; Greenwood, Alex D; Hänni, Catherine

2008-06-01

The molecular identification of proviruses from ancient tissues (and particularly from bones) remains a contentious issue. It can be expected that the copy number of proviruses will be low, which magnifies the risk of contamination with retroviruses from exogenous sources. To assess the feasibility of paleoretrovirological studies, we attempted to identify proviruses from early 20th century bones of museum specimens while following a strict ancient DNA methodology. Simian T-cell leukemia virus type 1 sequences were successfully obtained and authenticated from a Chlorocebus pygerythrus specimen. This represents the first clear evidence that it will be possible to use museum specimens to better characterize simian and human T-tropic retrovirus genetic diversity and analyze their origin and evolution, in greater detail.

Gp120 binding with DC-SIGN induces reactivation of HIV-1 provirus via the NF-κB signaling pathway

PubMed Central

Jin, Changzhong; Li, Jie; Cheng, Linfang; Liu, Fumin; Wu, Nanping

2016-01-01

The reactivation mechanism of latent human immunodeficiency virus type 1 (HIV-1) infection is unclear, especially in dendritic cells (DC). DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) binds with HIV-1 and other pathogens to activate the extracellular regulated protein kinase (ERK) and nuclear factor-kappa B (NF-κB) pathways and regulate cytokine expression. We hypothesized that DC-SIGN-induced signaling pathways may activate HIV-1 provirus. To investigate this hypothesis, we generated a model by transfecting 293T cells with a DC-SIGN expression plasmid and an HIV-1 5′ long terminal repeat (LTR) reporter plasmid, and then stimulated the 293T cells with HIV-1 gp120 protein, wild-type HIV-1 or VSV-G-pNL4.3 pseudotype virus (without gp120 protein). It was found that the HIV-1 5′LTR was reactivated by HIV-1 gp120 in DC-SIGN-expressing 293T cells. Then the HIV-1 chronically infected CEM-Bru cells were transfected with DC-SIGN expression plasmid and stimulated by HIV-1 gp120 protein. It was found that early and late HIV-1 provirus replication was reactivated by the HIV-1 gp120/DC-SIGN stimulation. We then investigated the involvement of the ERK, p38 mitogen-activated protein kinases and NF-κB signaling pathways in HIV-1 gp120/DC-SIGN-induced activation of HIV-1 provirus by inhibiting the pathways specifically. Our results indicated that HIV-1 gp120/DC-SIGN stimulation reactivates latent HIV-1 provirus via the NF-κB signal pathway. PMID:26837416

ENDOGENOUS RETROVIRUSES MOBILIZED DURING FRIEND MURINE LEUKEMIA VIRUS INFECTION

PubMed Central

Hansen, Ethan; Hendrick, Duncan; Malik, Frank; Evans, Leonard H.

2016-01-01

We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses. PMID:27657834

Evaluation of viremia, proviral load and cytokine profile in naturally feline immunodeficiency virus infected cats treated with two different protocols of recombinant feline interferon omega.

PubMed

Leal, Rodolfo O; Gil, Solange; Duarte, Ana; McGahie, David; Sepúlveda, Nuno; Niza, Maria M R E; Tavares, Luís

2015-04-01

This study assesses viremia, provirus and blood cytokine profile in naturally FIV-infected cats treated with two distinct protocols of interferon omega (rFeIFN-ω). Samples from FIV-cats previously submitted to two single-arm studies were used: 7/18 received the licensed/subcutaneous protocol (SC) while 11/18 were treated orally (PO). Viremia, provirus and blood mRNA expression of interleukin (IL)-1, IL-4, IL-6, IL-10, IL-12p40, Interferon-γ and Tumor Necrosis Factor-α were monitored by Real-Time qPCR. Concurrent plasma levels of IL-6, IL-12p40 and IL-4 were assessed by ELISA. IL-6 plasma levels decreased in the SC group (p = 0.031). IL-6 mRNA expression (p = 0.037) decreased in the PO group, albeit not sufficiently to change concurrent plasma levels. Neither viremia nor other measured cytokines changed with therapy. Proviral load increased in the SC group (p = 0.031), which can be justified by a clinically irrelevant increase of lymphocyte count. Independently of the protocol, rFeIFN-ω seems to act on innate immunity by reducing pro-inflammatory stimulus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitative PCR for HTLV-1 provirus in adult T-cell leukemia/lymphoma using paraffin tumor sections.

PubMed

Kato, Junki; Masaki, Ayako; Fujii, Keiichiro; Takino, Hisashi; Murase, Takayuki; Yonekura, Kentaro; Utsunomiya, Atae; Ishida, Takashi; Iida, Shinsuke; Inagaki, Hiroshi

2016-11-01

Detection of HTLV-1 provirus using paraffin tumor sections may assist the diagnosis of adult T-cell leukemia/lymphoma (ATLL). For the detection, non-quantitative PCR assay has been reported, but its usefulness and limitations remain unclear. To our knowledge, quantitative PCR assay using paraffin tumor sections has not been reported. Using paraffin sections from ATLLs and non-ATLL T-cell lymphomas, we first performed non-quantitative PCR for HTLV-1 provirus. Next, we determined tumor ratios and carried out quantitative PCR to obtain provirus copy numbers. The results were analyzed with a simple regression model and a novel criterion, cut-off using 95 % rejection limits. Our quantitative PCR assay showed an excellent association between tumor ratios and the copy numbers (r = 0.89, P < 0.0001). The 95 % rejection limits provided a statistical basis for the range for the determination of HTLV-1 involvement. Its application suggested that results of non-quantitative PCR assay should be interpreted very carefully and that our quantitative PCR assay is useful to estimate the status of HTLV-1 involvement in the tumor cases. In conclusion, our quantitative PCR assay using paraffin tumor sections may be useful for the screening of ATLL cases, especially in HTLV-1 non-endemic areas where easy access to serological testing for HTLV-1 infection is limited. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

An indicator gene to demonstrate intracellular transposition of defective retroviruses.

PubMed Central

Heidmann, T; Heidmann, O; Nicolas, J F

1988-01-01

An indicator gene for detection and quantitation of RNA-mediated transposition was constructed (neoRT). It was inserted into a Moloney murine leukemia provirus (Mo-MLV) deleted for the envelope gene to test for intracellular transposition of defective retroviruses [Mo-MLV(neo)RT]. NeoRT contains the selectable neo gene (which confers resistance to the drug G418), inactivated by a polyadenylylation sequence inserted between the neo promotor and coding sequence. The polyadenylylation sequence is flanked (on the antisense strand of the DNA) by a donor and an acceptor splice site so as to be removed upon passage of the provirus through an RNA intermediate. 3T3 cells transfected with the defective Mo-MLV(neo)RT provirus are sensitive to G418. After trans-complementation with Mo-MLV, viral transcripts confer resistance to G418 upon infection of test cells. In the resistant cells, the polyadenylylation sequence has been removed, as a result in most cases of precise splicing of the intronic domain. Retrotransposition of the defective Mo-MLV(neo)RT provirus was demonstrated by submitting transfected G418-sensitive clones to selection. Between 1 and 10 G418-resistant clones were obtained per 10(7) cells. Several possess additional copies, with evidence for precise removal of the intronic domain. By using target test cells in coculture experiments, extracellular intermediates of retrotransposition could not be detected. Images PMID:2832848

Comparative Analysis of Measures of Viral Reservoirs in HIV-1 Eradication Studies

PubMed Central

Lysenko, Elena S.; Bosch, Ronald J.; Lai, Jun; Chioma, Stanley; Emad, Fatemeh; Abdel-Mohsen, Mohamed; Hoh, Rebecca; Hecht, Frederick; Hunt, Peter; Somsouk, Ma; Wong, Joseph; Johnston, Rowena; Siliciano, Robert F.; Richman, Douglas D.; O'Doherty, Una; Palmer, Sarah; Deeks, Steven G.; Siliciano, Janet D.

2013-01-01

HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy (HAART). The best characterized reservoir is a small, difficult-to-quantify pool of resting memory CD4+ T cells carrying latent but replication-competent viral genomes. Because strategies targeting this latent reservoir are now being tested in clinical trials, well-validated high-throughput assays that quantify this reservoir are urgently needed. Here we compare eleven different approaches for quantitating persistent HIV-1 in 30 patients on HAART, using the original viral outgrowth assay for resting CD4+ T cells carrying inducible, replication-competent viral genomes as a standard for comparison. PCR-based assays for cells containing HIV-1 DNA gave infected cell frequencies at least 2 logs higher than the viral outgrowth assay, even in subjects who started HAART during acute/early infection. This difference may reflect defective viral genomes. The ratio of infected cell frequencies determined by viral outgrowth and PCR-based assays varied dramatically between patients. Although strong correlations with the viral outgrowth assay could not be formally excluded for most assays, correlations achieved statistical significance only for integrated HIV-1 DNA in peripheral blood mononuclear cells and HIV-1 RNA/DNA ratio in rectal CD4+ T cells. Residual viremia was below the limit of detection in many subjects and did not correlate with the viral outgrowth assays. The dramatic differences in infected cell frequencies and the lack of a precise correlation between culture and PCR-based assays raise the possibility that the successful clearance of latently infected cells may be masked by a larger and variable pool of cells with defective proviruses. These defective proviruses are detected by PCR but may not be affected by reactivation strategies and may not require eradication to accomplish an effective cure. A molecular understanding of the discrepancy between infected cell frequencies measured by viral outgrowth versus PCR assays is an urgent priority in HIV-1 cure research. PMID:23459007

Cytidine deamination induced HIV-1 drug resistance

PubMed Central

Mulder, Lubbertus C. F.; Harari, Ariana; Simon, Viviana

2008-01-01

The HIV-1 Vif protein is essential for overcoming the antiviral activity of DNA-editing apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) cytidine deaminases. We show that naturally occurring HIV-1 Vif point mutants with suboptimal anti-APOBEC3G activity induce the appearance of proviruses with lamivudine (3TC) drug resistance-associated mutations before any drug exposure. These mutations, ensuing from cytidine deamination events, were detected in >40% of proviruses with partially defective Vif mutants. Transfer of drug resistance from hypermutated proviruses via recombination allowed for 3TC escape under culture conditions prohibitive for any WT viral growth. These results demonstrate that defective hypermutated genomes can shape the phenotype of the circulating viral population. Partially active Vif alleles resulting in incomplete neutralization of cytoplasmic APOBEC3 molecules are directly responsible for the generation of a highly diverse, yet G-to-A biased, proviral reservoir, which can be exploited by HIV-1 to generate viable and drug-resistant progenies. PMID:18391217

Genome-wide Determinants of Proviral Targeting, Clonal Abundance and Expression in Natural HTLV-1 Infection

PubMed Central

Melamed, Anat; Laydon, Daniel J.; Gillet, Nicolas A.; Tanaka, Yuetsu; Taylor, Graham P.; Bangham, Charles R. M.

2013-01-01

The regulation of proviral latency is a central problem in retrovirology. We postulate that the genomic integration site of human T lymphotropic virus type 1 (HTLV-1) determines the pattern of expression of the provirus, which in turn determines the abundance and pathogenic potential of infected T cell clones in vivo. We recently developed a high-throughput method for the genome-wide amplification, identification and quantification of proviral integration sites. Here, we used this protocol to test two hypotheses. First, that binding sites for transcription factors and chromatin remodelling factors in the genome flanking the proviral integration site of HTLV-1 are associated with integration targeting, spontaneous proviral expression, and in vivo clonal abundance. Second, that the transcriptional orientation of the HTLV-1 provirus relative to that of the nearest host gene determines spontaneous proviral expression and in vivo clonal abundance. Integration targeting was strongly associated with the presence of a binding site for specific host transcription factors, especially STAT1 and p53. The presence of the chromatin remodelling factors BRG1 and INI1 and certain host transcription factors either upstream or downstream of the provirus was associated respectively with silencing or spontaneous expression of the provirus. Cells expressing HTLV-1 Tax protein were significantly more frequent in clones of low abundance in vivo. We conclude that transcriptional interference and chromatin remodelling are critical determinants of proviral latency in natural HTLV-1 infection. PMID:23555266

Introducing a frameshift mutation to the POL sequence of HIV-1 provirus and evaluation of the immunogenic characteristics of the mutated virions (RINNL4-3).

PubMed

Zabihollahi, Rezvan; Sadat, Seyed Mehdi; Vahabpour, Rouhollah; Salehi, Mansoor; Azadmanesh, Kayhan; Siadat, Seyed Davar; Saraji, Ali Reza Azizi; Pouriavali, Mohamamd Hassan; Momen, Seyed Bahman; Aghasadeghi, Mohamad Reza

2012-01-01

Inactivation of the reverse transcriptase (RT) and integrase (IN) enzymes can abolish the replication of the human immunodeficiency virus (HIV) and, thus, its infectivity. Here, inactivated HIV particles convenient for designing virus-like particle (VLP) based vaccines have been produced. Inactivated HIV-provirus was created by introducing a frame shift mutation. HIV provirus DNA was cut in the pol region by Age I restriction enzyme, followed by filling of sticky ends using the Klenow fragment before ligation. The resulting plasmid was named as pRINNL4-3. HEK-293T cells were used as producer, after being transfected with the modified plasmid. Viral particle production and biological activity were assayed by virus capsid protein (p24) quantification and syncytium formation in MT2 cells, respectively. The immunogenicity of the RINNL4-3 virions was investigated in a mouse model. The mutation was expected to inactivate the virus RT and IN enzymes. The results showed that the VLPs were assembled, as measured by the p24 load of the culture supernatant, and contained functional envelope proteins (Env) as monitored by the syncytium formation. However, these VLPs had no ability to infect target MT2 cells, as well as their VSVG (vesicular stomatitis virus-glycoprotein) pseudotyped counterparts infected HEK-293T cells. A high level of antibody response was observed in immunized mice. Since RINNL4-3 virions are replication incompetent, they are convenient for production and use in biomedical studies. Also, RINNL4-3 is a candidate for a vaccine development due to it contains envelope and structural virus proteins which are crucial for triggering neutralizing antibodies and the cellular immune response.

Association between latent proviral characteristics and immune activation in antiretrovirus-treated human immunodeficiency virus type 1-infected adults.

PubMed

Liang, Emily C; Sceats, Lindsay; Bayless, Nicholas L; Strauss-Albee, Dara M; Kubo, Jessica; Grant, Philip M; Furman, David; Desai, Manisha; Katzenstein, David A; Davis, Mark M; Zolopa, Andrew R; Blish, Catherine A

2014-08-01

Generalized immune activation during HIV infection is associated with an increased risk of cardiovascular disease, neurocognitive disease, osteoporosis, metabolic disorders, and physical frailty. The mechanisms driving this immune activation are poorly understood, particularly for individuals effectively treated with antiretroviral medications. We hypothesized that viral characteristics such as sequence diversity may play a role in driving HIV-associated immune activation. We therefore sequenced proviral DNA isolated from peripheral blood mononuclear cells from HIV-infected individuals on fully suppressive antiretroviral therapy. We performed phylogenetic analyses, calculated viral diversity and divergence in the env and pol genes, and determined coreceptor tropism and the frequency of drug resistance mutations. Comprehensive immune profiling included quantification of immune cell subsets, plasma cytokine levels, and intracellular signaling responses in T cells, B cells, and monocytes. These antiretroviral therapy-treated HIV-infected individuals exhibited a wide range of diversity and divergence in both env and pol genes. However, proviral diversity and divergence in env and pol, coreceptor tropism, and the level of drug resistance did not significantly correlate with markers of immune activation. A clinical history of virologic failure was also not significantly associated with levels of immune activation, indicating that a history of virologic failure does not inexorably lead to increased immune activation as long as suppressive antiretroviral medications are provided. Overall, this study demonstrates that latent viral diversity is unlikely to be a major driver of persistent HIV-associated immune activation. Chronic immune activation, which is associated with cardiovascular disease, neurologic disease, and early aging, is likely to be a major driver of morbidity and mortality in HIV-infected individuals. Although treatment of HIV with antiretroviral medications decreases the level of immune activation, levels do not return to normal. The factors driving this persistent immune activation, particularly during effective treatment, are poorly understood. In this study, we investigated whether characteristics of the latent, integrated HIV provirus that persists during treatment are associated with immune activation. We found no relationship between latent viral characteristics and immune activation in treated individuals, indicating that qualities of the provirus are unlikely to be a major driver of persistent inflammation. We also found that individuals who had previously failed treatment but were currently effectively treated did not have significantly increased levels of immune activation, providing hope that past treatment failures do not have a lifelong "legacy" impact. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The retrovirus HTLV-1 inserts an ectopic CTCF-binding site into the human genome.

PubMed

Satou, Yorifumi; Miyazato, Paola; Ishihara, Ko; Yaguchi, Hiroko; Melamed, Anat; Miura, Michi; Fukuda, Asami; Nosaka, Kisato; Watanabe, Takehisa; Rowan, Aileen G; Nakao, Mitsuyoshi; Bangham, Charles R M

2016-03-15

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes malignant and inflammatory diseases in ∼10% of infected people. A typical host has between 10(4) and 10(5) clones of HTLV-1-infected T lymphocytes, each clone distinguished by the genomic integration site of the single-copy HTLV-1 provirus. The HTLV-1 bZIP (HBZ) factor gene is constitutively expressed from the minus strand of the provirus, whereas plus-strand expression, required for viral propagation to uninfected cells, is suppressed or intermittent in vivo, allowing escape from host immune surveillance. It remains unknown what regulates this pattern of proviral transcription and latency. Here, we show that CTCF, a key regulator of chromatin structure and function, binds to the provirus at a sharp border in epigenetic modifications in the pX region of the HTLV-1 provirus in T cells naturally infected with HTLV-1. CTCF is a zinc-finger protein that binds to an insulator region in genomic DNA and plays a fundamental role in controlling higher order chromatin structure and gene expression in vertebrate cells. We show that CTCF bound to HTLV-1 acts as an enhancer blocker, regulates HTLV-1 mRNA splicing, and forms long-distance interactions with flanking host chromatin. CTCF-binding sites (CTCF-BSs) have been propagated throughout the genome by transposons in certain primate lineages, but CTCF binding has not previously been described in present-day exogenous retroviruses. The presence of an ectopic CTCF-BS introduced by the retrovirus in tens of thousands of genomic locations has the potential to cause widespread abnormalities in host cell chromatin structure and gene expression.

Exposure of cats to low doses of FeLV: seroconversion as the sole parameter of infection

PubMed Central

Major, Andrea; Cattori, Valentino; Boenzli, Eva; Riond, Barbara; Ossent, Peter; Meli, Marina Luisa; Hofmann-Lehmann, Regina; Lutz, Hans

2009-01-01

In felids, feline leukemia virus (FeLV) infection results in a variety of outcomes that range from abortive (virus readily eliminated and never detectable) to progressive infection (persistent viremia and viral shedding). Recently, a novel outcome was postulated for low FeLV infectious doses. Naïve cats exposed to faeces of persistently infected cats seroconverted, indicating infection, but remained negative for provirus and p27 antigen in blood. FeLV provirus was found in some tissues but not in the bone marrow, infection of which is usually considered a necessary stage for disease progression. To investigate the impact of low FeLV doses on young cats and to test the hypothesis that low dose exposure may lead to an unknown pathogenesis of infection without involvement of the bone marrow, 21 cats were infected oronasally with variable viral doses. Blood p27, proviral and viral loads were followed until week 20 post-infection. Tissue proviral loads were determined as well. The immune response was monitored by measuring FeLV whole virus and p45 antibodies; and feline oncornavirus-associated cell membrane antigen (FOCMA) assay. One cat showed regressive infection (transient antigenemia, persistent provirus-positivity, and seroconversion) with provirus only found in some organs at sacrifice. In 7 of the 20 remaining cats FOCMA assay positivity was the only sign of infection, while all other tests were negative. Overall, the results show that FeLV low dose exposure can result in seroconversion during a presumed abortive infection. Therefore, commonly used detection methods do not detect all FeLV-infected animals, possibly leading to an underestimation of the prevalence of infection. PMID:19861115

Beyond the replication-competent HIV reservoir: transcription and translation-competent reservoirs.

PubMed

Baxter, Amy E; O'Doherty, Una; Kaufmann, Daniel E

2018-02-02

Recent years have seen a substantial increase in the number of tools available to monitor and study HIV reservoirs. Here, we discuss recent technological advances that enable an understanding of reservoir dynamics beyond classical assays to measure the frequency of cells containing provirus able to propagate a spreading infection (replication-competent reservoir). Specifically, we focus on the characterization of cellular reservoirs containing proviruses able to transcribe viral mRNAs (so called transcription-competent) and translate viral proteins (translation-competent). We suggest that the study of these alternative reservoirs provides complementary information to classical approaches, crucially at a single-cell level. This enables an in-depth characterization of the cellular reservoir, both following reactivation from latency and, importantly, directly ex vivo at baseline. Furthermore, we propose that the study of cellular reservoirs that may not contain fully replication-competent virus, but are able to produce HIV mRNAs and proteins, is of biological importance. Lastly, we detail some of the key contributions that the study of these transcription and translation-competent reservoirs has made thus far to investigations into HIV persistence, and outline where these approaches may take the field next.

Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.

2008-05-10

Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-{gamma} enzyme-linked immunospot responses of low magnitude were observed after immunizationmore » with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus.« less

In vitro modeling of HIV proviral activity in microglia.

PubMed

Campbell, Lee A; Richie, Christopher T; Zhang, Yajun; Heathward, Emily J; Coke, Lamarque M; Park, Emily Y; Harvey, Brandon K

2017-12-01

Microglia, the resident macrophages of the brain, play a key role in the pathogenesis of HIV-associated neurocognitive disorders (HAND) due to their productive infection by HIV. This results in the release of neurotoxic viral proteins and pro-inflammatory compounds which negatively affect the functionality of surrounding neurons. Because models of HIV infection within the brain are limited, we aimed to create a novel microglia cell line with an integrated HIV provirus capable of recreating several hallmarks of HIV infection. We utilized clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing technology and integrated a modified HIV provirus into CHME-5 immortalized microglia to create HIV-NanoLuc CHME-5. In the modified provirus, the Gag-Pol region is replaced with the coding region for NanoLuciferase (NanoLuc), which allows for the rapid assay of HIV long terminal repeat activity using a luminescent substrate, while still containing the necessary genetic material to produce established neurotoxic viral proteins (e.g. tat, nef, gp120). We confirmed that HIV-NanoLuc CHME-5 microglia express NanoLuc, along with the HIV viral protein Nef. We subsequently exposed these cells to a battery of experiments to modulate the activity of the provirus. Proviral activity was enhanced by treating the cells with pro-inflammatory factors lipopolysaccharide (LPS) and tumor necrosis factor alpha and by overexpressing the viral regulatory protein Tat. Conversely, genetic modification of the toll-like receptor-4 gene by CRISPR/Cas9 reduced LPS-mediated proviral activation, and pharmacological application of NF-κB inhibitor sulfasalazine similarly diminished proviral activity. Overall, these data suggest that HIV-NanoLuc CHME-5 may be a useful tool in the study of HIV-mediated neuropathology and proviral regulation. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

T-cell receptor signaling enhances transcriptional elongation from latent HIV proviruses by activating P-TEFb through an ERK-dependent pathway.

PubMed

Kim, Young Kyeung; Mbonye, Uri; Hokello, Joseph; Karn, Jonathan

2011-07-29

Latent human immunodeficiency virus (HIV) proviruses are thought to be primarily reactivated in vivo through stimulation of the T-cell receptor (TCR). Activation of the TCR induces multiple signal transduction pathways, leading to the ordered nuclear migration of the HIV transcription initiation factors NF-κB (nuclear factor κB) and NFAT (nuclear factor of activated T-cells), as well as potential effects on HIV transcriptional elongation. We have monitored the kinetics of proviral reactivation using chromatin immunoprecipitation assays to measure changes in the distribution of RNA polymerase II in the HIV provirus. Surprisingly, in contrast to TNF-α (tumor necrosis factor α) activation, where early transcription elongation is highly restricted due to rate-limiting concentrations of Tat, efficient and sustained HIV elongation and positive transcription elongation factor b (P-TEFb) recruitment are detected immediately after the activation of latent proviruses through the TCR. Inhibition of NFAT activation by cyclosporine had no effect on either HIV transcription initiation or elongation. However, examination of P-TEFb complexes by gel-filtration chromatography showed that TCR signaling led to the rapid dissociation of the large inactive P-TEFb:7SK RNP (small nuclear RNA 7SK ribonucleoprotein) complex and the release of active low-molecular-weight P-TEFb complexes. Both P-TEFb recruitment to the HIV long terminal repeat and enhanced HIV processivity were blocked by the ERK (extracellular-signal-regulated kinase) inhibitor U0126, but not by AKT (serine/threonine protein kinase Akt) and PI3K (phosphatidylinositol 3-kinase) inhibitors. In contrast to treatment with HMBA (hexamethylene bisacetamide) and DRB (5,6-dichlorobenzimidazole 1-β-ribofuranoside), which disrupt the large 7SK RNP complex but do not stimulate early HIV elongation, TCR signaling provides the first example of a physiological pathway that can shift the balance between the inactive P-TEFb pool and the active P-TEFb pool and thereby stimulate proviral reactivation. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Paradigm for Virus–Host Coevolution: Sequential Counter-Adaptations between Endogenous and Exogenous Retroviruses

PubMed Central

Arnaud, Frederick; Caporale, Marco; Varela, Mariana; Biek, Roman; Chessa, Bernardo; Alberti, Alberto; Golder, Matthew; Mura, Manuela; Zhang, Ya-ping; Yu, Li; Pereira, Filipe; DeMartini, James C; Leymaster, Kreg; Spencer, Thomas E; Palmarini, Massimo

2007-01-01

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections of the host germline transmitted vertically from generation to generation. It is hypothesized that some ERVs are used by the host as restriction factors to block the infection of pathogenic retroviruses. Indeed, some ERVs efficiently interfere with the replication of related exogenous retroviruses. However, data suggesting that these mechanisms have influenced the coevolution of endogenous and/or exogenous retroviruses and their hosts have been more difficult to obtain. Sheep are an interesting model system to study retrovirus-host coevolution because of the coexistence in this animal species of two exogenous (i.e., horizontally transmitted) oncogenic retroviruses, Jaagsiekte sheep retrovirus and Enzootic nasal tumor virus, with highly related and biologically active endogenous retroviruses (enJSRVs). Here, we isolated and characterized the evolutionary history and molecular virology of 27 enJSRV proviruses. enJSRVs have been integrating in the host genome for the last 5–7 million y. Two enJSRV proviruses (enJS56A1 and enJSRV-20), which entered the host genome within the last 3 million y (before and during speciation within the genus Ovis), acquired in two temporally distinct events a defective Gag polyprotein resulting in a transdominant phenotype able to block late replication steps of related exogenous retroviruses. Both transdominant proviruses became fixed in the host genome before or around sheep domestication (∼ 9,000 y ago). Interestingly, a provirus escaping the transdominant enJSRVs has emerged very recently, most likely within the last 200 y. Thus, we determined sequentially distinct events during evolution that are indicative of an evolutionary antagonism between endogenous and exogenous retroviruses. This study strongly suggests that endogenization and selection of ERVs acting as restriction factors is a mechanism used by the host to fight retroviral infections. PMID:17997604

Quantitative Analysis of HIV-1 Preintegration Complexes

PubMed Central

Engelman, Alan; Oztop, Ilker; Vandegraaff, Nick; Raghavendra, Nidhanapati K.

2009-01-01

Retroviral replication proceeds through the formation of a provirus, an integrated DNA copy of the viral RNA genome. The linear cDNA product of reverse transcription is the integration substrate and two different integrase activities, 3′ processing and DNA strand transfer, are required for provirus formation. Integrase nicks the cDNA ends adjacent to phylogenetically-conserved CA dinucleotides during 3′ processing. After nuclear entry and locating a suitable chromatin acceptor site, integrase joins the recessed 3′-OHs to the 5′-phosphates of a double-stranded staggered cut in the DNA target. Integrase functions in the context of a large nucleoprotein complex, called the preintegration complex (PIC), and PICs are analyzed to determine levels of integrase 3′ processing and DNA strand transfer activities that occur during acute virus infection. Denatured cDNA end regions are monitored by indirect end-labeling to measure the extent of 3′ processing. Native PICs can efficiently integrate their viral cDNA into exogenously added target DNA in vitro, and Southern blotting or nested PCR assays are used to quantify the resultant DNA strand transfer activity. This study details HIV-1 infection, PIC extraction, partial purification, and quantitative analyses of integrase 3′ processing and DNA strand transfer activities. PMID:19233280

Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konnai, Satoru; Usui, Tatsufumi; Ikeda, Manabu

2005-09-01

Previously, we found an up-regulation of tumor necrosis factor alpha (TNF)-{alpha} and an imbalance of TNF receptors in sheep experimentally infected with bovine leukemia virus (BLV). In order to investigate the different TNF-{alpha}-induced responses, in this study we examined the TNF-{alpha}-induced proliferative response and the expression levels of two distinct TNF receptors on peripheral blood mononuclear cells (PBMC) derived from BLV-uninfected cattle and BLV-infected cattle that were aleukemic (AL) or had persistent lymphocytosis (PL). The proliferative response of PBMC isolated from those cattle with PL in the presence of recombinant bovine TNF-{alpha} (rTNF-{alpha}) was significantly higher than those from ALmore » cattle and uninfected cattle and the cells from PL cattle expressed significantly higher mRNA levels of TNF receptor type II (TNF-RII) than those from AL and BLV-uninfected cattle. No difference was found in TNF-RI mRNA levels. Most cells expressing TNF-RII in PL cattle were CD5{sup +} or sIgM{sup +} cells and these cells showed resistance to TNF-{alpha}-induced apoptosis. Additionally, there were significant positive correlations between the changes in provirus load and TNF-RII mRNA levels, and TNF-{alpha}-induced proliferation and TNF-RII mRNA levels. These data suggest that imbalance in the expression of TNF receptors could at least in part contribute to the progression of lymphocytosis in BLV infection.« less

Induction of infectious petunia vein clearing (pararetro) virus from endogenous provirus in petunia

PubMed Central

Richert-Pöggeler, Katja R.; Noreen, Faiza; Schwarzacher, Trude; Harper, Glyn; Hohn, Thomas

2003-01-01

Infection by an endogenous pararetrovirus using forms of both episomal and chromosomal origin has been demonstrated and characterized, together with evidence that petunia vein clearing virus (PVCV) is a constituent of the Petunia hybrida genome. Our findings allow comparative and direct analysis of horizontally and vertically transmitted virus forms and demonstrate their infectivity using biolistic transformation of a provirus-free petunia species. Some integrants within the genome of P.hybrida are arranged in tandem, allowing direct release of virus by transcription. In addition to known inducers of endogenous pararetroviruses, such as genome hybridization, tissue culture and abiotic stresses, we observed activation of PVCV after wounding. Our data also support the hypothesis that the host plant uses DNA methylation to control the endogenous pararetrovirus. PMID:12970195

Comparison of porcine endogenous retroviruses infectious potential in supernatants of producer cells and in cocultures.

PubMed

Costa, Michael Rodrigues; Fischer, Nicole; Gulich, Barbara; Tönjes, Ralf R

2014-01-01

Porcine endogenous retroviruses (PERV) pose a zoonotic risk potential in pig-to-human xenotransplantation given that PERV capacity to infect different human cell lines in vitro has been clearly shown in the past. However, PERV infectious potential for human peripheral blood mononuclear cells (huPBMC) has been also demonstrated, albeit with controversial results. As productive PERV infection of huPBMC involves immune suppression that may attract opportunistic pathogens as shown for other retroviruses, it is crucial to ascertain unequivocally huPBMC susceptibility for PERV. To address this question, we first investigated in vitro infectivity of PERV for huPBMC using supernatants containing highly infectious PERV-A/C. Second, huPBMC were cocultivated with PERV-A/C producer cells to come a step closer to the in vivo situation of xenotransplantation. In addition, cocultivation of huPBMC with porcine PBMC (poPBMC) isolated from German landrace pigs was performed to distinguish PERV replication competence when they were constitutively produced by immortalized cells or by primary poPBMC. Supernatants containing recombinant highly infectious PERV-A/C were used to infect PHA-activated huPBMC in the presence or absence of polybrene. Next, PERV-producing cell lines such as human 293/5° and primary mitogenically activated poPBMC of three German landrace pigs were cocultivated with huPBMC as well as with susceptible human and porcine cell lines as controls. PERV infection was monitored by using three test approaches. The presence of provirus DNA in putatively infected cells was detected via sensitive nested PCR. Viral expression was determined by screening for the activity of gammaretroviral reverse transcriptase (RT) in cell-free supernatants of infected cells. Virus release was monitored by counting the number of packaged RNA particles in supernatants via PERV-specific quantitative one-step real-time reverse transcriptase PCR. Porcine endogenous retroviruses-A/C in supernatants of human producer 293/5° cells was not able to infect huPBMC. Neither RT activity nor PERV copies were detected. Even provirus could not be detected displaying the inability of PERV-A/C to induce a productive infection in huPBMC. In cocultivation experiments only non-productive infection of huPBMC with PERV derived from 293/5° cell line and from PHA-activated poPBMC was observed by detection of provirus DNA in infected cells. Recombinant PERV-A/C in supernatants of producer cells failed to infect huPBMC, whereas coculture experiments with producer cell lines lead to non-productive infection of huPBMC. PERV in supernatants seem to have not sufficient infectious potential for huPBMC. However, extensive PERV exposure to huPBMC via cocultivation enabled at least virus cell entry as provirus was detected by nested PCR. Furthermore, results presented support previous data showing German landrace pigs as low producers with negligible infectious potential due to the absence of replication-competent PERV in the genome. The low PERV expression profile and the lack of significant replication competence of German landrace pigs raise hope for considering these animals as putative donor animals in future pig-to-human xenotransplantation. Nonetheless, data imply that PERV still represent a virological risk in the course of xenotransplantation, as the presence of PERV provirus in host cells may lead to a provirus integration resulting in insertional mutagenesis and chromosomal rearrangements. © 2014 John Wiley & Sons A/S.

Poorly expressed endogenous ecotropic provirus of DBA/2 mice encodes a mutant Pr65gag protein that is not myristylated.

PubMed Central

Copeland, N G; Jenkins, N A; Nexø, B; Schultz, A M; Rein, A; Mikkelsen, T; Jørgensen, P

1988-01-01

DBA/2 mice carry a single endogenous ecotropic murine leukemia provirus designated Emv-3. Although this provirus appears to be nondefective by genomic restriction enzyme mapping, weanling mice do not produce virus and only about one-third of adult mice ever express virus. 5-Iododeoxyuridine and 5-azacytidine, two potent inducers of ecotropic virus expression, are relatively ineffective at inducing Emv-3 expression. However, the chemical carcinogen 7,12-dimethylbenz(a)anthracene can induce ecotropic virus expression in approximately 95% of treated DBA/2 mice. Previous experiments involving DNA transfection and marker rescue analysis of molecularly cloned Emv-3 DNA suggested that Emv-3 carries a small defect(s) in the gag gene, not detectable by restriction enzyme mapping, that inhibits virus expression in vivo and in vitro. Using a combination of approaches, including DNA sequencing, peptide mapping, and metabolic labeling of cells with [3H]myristate, we have demonstrated that the defect in Emv-3 most likely results from a single nucleotide substitution within the gene for p15gag that inhibits myristylation of the Pr65gag N terminus. Myristylation of Pr65gag is thought to be required for this protein to associate with the plasma membrane and is essential for virus particle formation. These results provide a conceptual framework for understanding how Emv-3 expression is regulated during development and after chemical induction. Images PMID:2826810

The Wnt-1 (int-1) oncogene promoter and its mechanism of activation by insertion of proviral DNA of the mouse mammary tumor virus.

PubMed Central

Nusse, R; Theunissen, H; Wagenaar, E; Rijsewijk, F; Gennissen, A; Otte, A; Schuuring, E; van Ooyen, A

1990-01-01

Wnt-1 (int-1) is a cellular oncogene often activated by insertion of proviral DNA of the mouse mammary tumor virus. We have mapped the 5' end and the promoter area of the Wnt-1 gene by nuclease protection and primer extension assays. In differentiating P19 embryonal carcinoma cells, in which Wnt-1 is naturally expressed, two start sites of transcription were found, one preceded by two TATA boxes and one preceded by several GC boxes. In P19 cells, a 1-kilobase upstream sequence of Wnt-1 was able to confer differentiation-specific expression on a heterologous gene. We have investigated how Wnt-1 transcription was affected by mouse mammary tumor virus proviral integrations in various configurations near the promoters of the gene. One provirus has been inserted in the 5' nontranslated part of Wnt-1, in the same transcriptional orientation, and has functionally replaced the Wnt-1 promoters. Wnt-1 transcription in this tumor starts in the right long terminal repeat of the provirus, with considerable readthrough transcription from the left long terminal repeat. Another provirus has been inserted in the orientation opposite that of Wnt-1 into a GC box, disrupting the first Wnt-1 transcription start site but not the downstream start site. Most insertions have not structurally altered the Wnt-1 transcripts and have enhanced the activity of the normal two promoters. Images PMID:1695322

Noninfectious virus-like particles produced by Moloney murine leukemia virus-based retrovirus packaging cells deficient in viral envelope become infectious in the presence of lipofection reagents

PubMed Central

Sharma, Sanjai; Murai, Fukashi; Miyanohara, Atsushi; Friedmann, Theodore

1997-01-01

Retrovirus packaging cell lines expressing the Moloney murine leukemia virus gag and pol genes but lacking virus envelope genes produce virus-like particles constitutively, whether or not they express a transcript from an integrated retroviral provirus. In the absence of a proviral transcript, the assembled particles contain processed gag and reverse transcriptase, and particles made by cells expressing an integrated lacZ provirus also contain viral RNA. The virus-like particles from both cell types are enveloped and are secreted/budded into the extracellular space but are noninfectious. Their physicochemical properties are similar to those of mature retroviral particles. The noninfectious gag pol RNA particles can readily be made infectious by the addition of lipofection reagents to produce preparations with titers of up to 105 colony-forming units per ml. PMID:9380714

Modes of Human T Cell Leukemia Virus Type 1 Transmission, Replication and Persistence

PubMed Central

Carpentier, Alexandre; Barez, Pierre-Yves; Hamaidia, Malik; Gazon, Hélène; de Brogniez, Alix; Perike, Srikanth; Gillet, Nicolas; Willems, Luc

2015-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes cancer (Adult T cell Leukemia, ATL) and a spectrum of inflammatory diseases (mainly HTLV-associated myelopathy—tropical spastic paraparesis, HAM/TSP). Since virions are particularly unstable, HTLV-1 transmission primarily occurs by transfer of a cell carrying an integrated provirus. After transcription, the viral genomic RNA undergoes reverse transcription and integration into the chromosomal DNA of a cell from the newly infected host. The virus then replicates by either one of two modes: (i) an infectious cycle by virus budding and infection of new targets and (ii) mitotic division of cells harboring an integrated provirus. HTLV-1 replication initiates a series of mechanisms in the host including antiviral immunity and checkpoint control of cell proliferation. HTLV-1 has elaborated strategies to counteract these defense mechanisms allowing continuous persistence in humans. PMID:26198240

Proviral Features of Human T Cell Leukemia Virus Type 1 in Carriers with Indeterminate Western Blot Analysis Results

PubMed Central

Sekizuka, Tsuyoshi; Yamochi, Tadanori; Firouzi, Sanaz; Sato, Tomoo; Umeki, Kazumi; Sasaki, Daisuke; Hasegawa, Hiroo; Kubota, Ryuji; Sobata, Rieko; Matsumoto, Chieko; Kaneko, Noriaki; Momose, Haruka; Araki, Kumiko; Saito, Masumichi; Nosaka, Kisato; Utsunomiya, Atae; Koh, Ki-Ryang; Ogata, Masao; Uchimaru, Kaoru; Iwanaga, Masako; Sagara, Yasuko; Yamano, Yoshihisa; Okayama, Akihiko; Miura, Kiyonori; Satake, Masahiro; Saito, Shigeru; Itabashi, Kazuo; Yamaguchi, Kazunari; Kuroda, Makoto; Watanabe, Toshiki; Okuma, Kazu

2017-01-01

ABSTRACT Western blotting (WB) for human T cell leukemia virus type 1 (HTLV-1) is performed to confirm anti-HTLV-1 antibodies detected at the initial screening of blood donors and in pregnant women. However, the frequent occurrence of indeterminate results is a problem with this test. We therefore assessed the cause of indeterminate WB results by analyzing HTLV-1 provirus genomic sequences. A quantitative PCR assay measuring HTLV-1 provirus in WB-indeterminate samples revealed that the median proviral load was approximately 100-fold lower than that of WB-positive samples (0.01 versus 0.71 copy/100 cells). Phylogenic analysis of the complete HTLV-1 genomes of WB-indeterminate samples did not identify any specific phylogenetic groups. When we analyzed the nucleotide changes in 19 HTLV-1 isolates from WB-indeterminate samples, we identified 135 single nucleotide substitutions, composed of four types, G to A (29%), C to T (19%), T to C (19%), and A to G (16%). In the most frequent G-to-A substitution, 64% occurred at GG dinucleotides, indicating that APOBEC3G is responsible for mutagenesis in WB-indeterminate samples. Moreover, interestingly, five WB-indeterminate isolates had nonsense mutations in Pol and/or Tax, Env, p12, and p30. These findings suggest that WB-indeterminate carriers have low production of viral antigens because of a combination of a low proviral load and mutations in the provirus, which may interfere with host recognition of HTLV-1 antigens. PMID:28701419

Proviral Features of Human T Cell Leukemia Virus Type 1 in Carriers with Indeterminate Western Blot Analysis Results.

PubMed

Kuramitsu, Madoka; Sekizuka, Tsuyoshi; Yamochi, Tadanori; Firouzi, Sanaz; Sato, Tomoo; Umeki, Kazumi; Sasaki, Daisuke; Hasegawa, Hiroo; Kubota, Ryuji; Sobata, Rieko; Matsumoto, Chieko; Kaneko, Noriaki; Momose, Haruka; Araki, Kumiko; Saito, Masumichi; Nosaka, Kisato; Utsunomiya, Atae; Koh, Ki-Ryang; Ogata, Masao; Uchimaru, Kaoru; Iwanaga, Masako; Sagara, Yasuko; Yamano, Yoshihisa; Okayama, Akihiko; Miura, Kiyonori; Satake, Masahiro; Saito, Shigeru; Itabashi, Kazuo; Yamaguchi, Kazunari; Kuroda, Makoto; Watanabe, Toshiki; Okuma, Kazu; Hamaguchi, Isao

2017-09-01

Western blotting (WB) for human T cell leukemia virus type 1 (HTLV-1) is performed to confirm anti-HTLV-1 antibodies detected at the initial screening of blood donors and in pregnant women. However, the frequent occurrence of indeterminate results is a problem with this test. We therefore assessed the cause of indeterminate WB results by analyzing HTLV-1 provirus genomic sequences. A quantitative PCR assay measuring HTLV-1 provirus in WB-indeterminate samples revealed that the median proviral load was approximately 100-fold lower than that of WB-positive samples (0.01 versus 0.71 copy/100 cells). Phylogenic analysis of the complete HTLV-1 genomes of WB-indeterminate samples did not identify any specific phylogenetic groups. When we analyzed the nucleotide changes in 19 HTLV-1 isolates from WB-indeterminate samples, we identified 135 single nucleotide substitutions, composed of four types, G to A (29%), C to T (19%), T to C (19%), and A to G (16%). In the most frequent G-to-A substitution, 64% occurred at GG dinucleotides, indicating that APOBEC3G is responsible for mutagenesis in WB-indeterminate samples. Moreover, interestingly, five WB-indeterminate isolates had nonsense mutations in Pol and/or Tax, Env, p12, and p30. These findings suggest that WB-indeterminate carriers have low production of viral antigens because of a combination of a low proviral load and mutations in the provirus, which may interfere with host recognition of HTLV-1 antigens. Copyright © 2017 American Society for Microbiology.

Reactivation of latent HIV-1 by a wide variety of butyric acid-producing bacteria.

PubMed

Imai, Kenichi; Yamada, Kiyoshi; Tamura, Muneaki; Ochiai, Kuniyasu; Okamoto, Takashi

2012-08-01

Latently infected cells harbor human immunodeficiency virus type 1 (HIV-1) proviral DNA copies integrated in heterochromatin, allowing persistence of transcriptionally silent proviruses. It is widely accepted that hypoacetylation of histone proteins by histone deacetylases (HDACs) is involved in maintaining the HIV-1 latency by repressing viral transcription. HIV-1 replication can be induced from latently infected cells by environmental factors, such as inflammation and co-infection with other microbes. It is known that a bacterial metabolite butyric acid inhibits catalytic action of HDAC and induces transcription of silenced genes including HIV-1 provirus. There are a number of such bacteria in gut, vaginal, and oral cavities that produce butyric acid during their anaerobic glycolysis. Since these organs are known to be the major site of HIV-1 transmission and its replication, we explored a possibility that explosive viral replication in these organs could be ascribable to butyric acid produced from anaerobic resident bacteria. In this study, we demonstrate that the culture supernatant of various bacteria producing butyric acid could greatly reactivate the latently-infected HIV-1. These bacteria include Fusobacterium nucleatum (commonly present in oral cavity, and gut), Clostridium cochlearium, Eubacterium multiforme (gut), and Anaerococcus tetradius (vagina). We also clarified that butyric acid in these culture supernatants could induce histone acetylation and HIV-1 replication by inhibiting HDAC. Our observations indicate that butyric acid-producing bacteria could be involved in AIDS progression by reactivating the latent HIV provirus and, subsequently, by eliminating such bacterial infection may contribute to the prevention of the AIDS development and transmission.

The molecular epidemiological study of bovine leukemia virus infection in Myanmar cattle.

PubMed

Polat, Meripet; Moe, Hla Hla; Shimogiri, Takeshi; Moe, Kyaw Kyaw; Takeshima, Shin-Nosuke; Aida, Yoko

2017-02-01

Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis, which is the most common neoplastic disease of cattle. BLV infects cattle worldwide and affects both health status and productivity. However, no studies have examined the distribution of BLV in Myanmar, and the genetic characteristics of Myanmar BLV strains are unknown. Therefore, the aim of this study was to detect BLV infection in Myanmar and examine genetic variability. Blood samples were obtained from 66 cattle from different farms in four townships of the Nay Pyi Taw Union Territory of central Myanmar. BLV provirus was detected by nested PCR and real-time PCR targeting BLV long terminal repeats. Results were confirmed by nested PCR targeting the BLV env-gp51 gene and real-time PCR targeting the BLV tax gene. Out of 66 samples, six (9.1 %) were positive for BLV provirus. A phylogenetic tree, constructed using five distinct partial and complete env-gp51 sequences from BLV strains isolated from three different townships, indicated that Myanmar strains were genotype-10. A phylogenetic tree constructed from whole genome sequences obtained by sequencing cloned, overlapping PCR products from two Myanmar strains confirmed the existence of genotype-10 in Myanmar. Comparative analysis of complete genome sequences identified genotype-10-specific amino acid substitutions in both structural and non-structural genes, thereby distinguishing genotype-10 strains from other known genotypes. This study provides information regarding BLV infection levels in Myanmar and confirms that genotype-10 is circulating in Myanmar.

Nucleotide sequence analysis establishes the role of endogenous murine leukemia virus DNA segments in formation of recombinant mink cell focus-forming murine leukemia viruses.

PubMed Central

Khan, A S

1984-01-01

The sequence of 363 nucleotides near the 3' end of the pol gene and 564 nucleotides from the 5' terminus of the env gene in an endogenous murine leukemia viral (MuLV) DNA segment, cloned from AKR/J mouse DNA and designated as A-12, was obtained. For comparison, the nucleotide sequence in an analogous portion of AKR mink cell focus-forming (MCF) 247 MuLV provirus was also determined. Sequence features unique to MCF247 MuLV DNA in the 3' pol and 5' env regions were identified by comparison with nucleotide sequences in analogous regions of NFS -Th-1 xenotropic and AKR ecotropic MuLV proviruses. These included (i) an insertion of 12 base pairs encoding four amino acids located 60 base pairs from the 3' terminus of the pol gene and immediately preceding the env gene, (ii) the deletion of 12 base pairs (encoding four amino acids) and the insertion of 3 base pairs (encoding one amino acid) in the 5' portion of the env gene, and (iii) single base substitutions resulting in 2 MCF247 -specific amino acids in the 3' pol and 23 in the 5' env regions. Nucleotide sequence comparison involving the 3' pol and 5' env regions of AKR MCF247 , NFS xenotropic, and AKR ecotropic MuLV proviruses with the cloned endogenous MuLV DNA indicated that MCF247 proviral DNA sequences were conserved in the cloned endogenous MuLV proviral segment. In fact, total nucleotide sequence identity existed between the endogenous MuLV DNA and the MCF247 MuLV provirus in the 3' portion of the pol gene. In the 5' env region, only 4 of 564 nucleotides were different, resulting in three amino acid changes between AKR MCF247 MuLV DNA and the endogenous MuLV DNA present in clone A-12. In addition, nucleotide sequence comparison indicated that Moloney-and Friend-MCF MuLVs were also highly related in the 3' pol and 5' env regions to the cloned endogenous MuLV DNA. These results establish the role of endogenous MuLV DNA segments in generation of recombinant MCF viruses. PMID:6328017

Loss of retrovirus production in JB/RH melanoma cells transfected with H-2Kb and TAP-1 genes.

PubMed

Li, M; Xu, F; Muller, J; Huang, X; Hearing, V J; Gorelik, E

1999-01-20

JB/RH1 melanoma cells, as well as other melanomas of C57BL/6 mice (B16 and JB/MS), express a common melanoma-associated antigen (MAA) encoded by an ecotropic melanoma-associated retrovirus (MelARV). JB/RH1 cells do not express the H-2Kb molecules due to down-regulation of the H-2Kb and TAP-1 genes. When JB/RH1 cells were transfected with the H-2Kb and cotransfected with the TAP-1 gene, it resulted in the appearance of H-2Kb molecules and an increase in their immunogenicity, albeit they lost expression of retrovirus-encoded MAA recognized by MM2-9B6 mAb. Loss of MAA was found to result from a complete and stable elimination of ecotropic MelARV production in the H-2Kb/TAP-1-transfected JB/RH1 cells. Northern blot analysis showed no differences in ecotropic retroviral messages in MelARV-producing and -nonproducing melanoma cells, suggesting that loss of MelARV production was not due to down-regulation of MelARV transcription. Southern blot analysis revealed several rearrangements in the proviral DNA of H-2Kb-positive JB/RH1 melanoma cells. Sequence analysis of the ecotropic proviral DNA from these cells showed numerous nucleotide substitutions, some of which resulted in the appearance of a novel intraviral PstI restriction site and the loss of a HindIII restriction site in the pol region. PCR amplification of the proviral DNAs indicates that an ecotropic provirus found in the H-2Kb-positive cells is novel and does not preexist in the parental H-2Kb-negative melanoma cells. Conversely, the ecotropic provirus of the parental JB/RH1 cells was not amplifable from the H-2Kb-positive cells. Our data indicate that stable loss of retroviral production in the H-2Kb/TAP-1-transfected melanoma cells is probably due to the induction of recombination between a productive ecotropic MelARV and a defective nonecotropic provirus leading to the generation of a defective ecotropic provirus and the loss of MelARV production and expression of the retrovirus-encoded MAA. Copyright 1999 Academic Press.

Characterization of proviruses cloned from mink cell focus-forming virus-infected cellular DNA.

PubMed Central

Khan, A S; Repaske, R; Garon, C F; Chan, H W; Rowe, W P; Martin, M A

1982-01-01

Two proviruses were cloned from EcoRI-digested DNA extracted from mink cells chronically infected with AKR mink cell focus-forming (MCF) 247 murine leukemia virus (MuLV), using a lambda phage host vector system. One cloned MuLV DNA fragment (designated MCF 1) contained sequences extending 6.8 kilobases from an EcoRI restriction site in the 5' long terminal repeat (LTR) to an EcoRI site located in the envelope (env) region and was indistinguishable by restriction endonuclease mapping for 5.1 kilobases (except for the EcoRI site in the LTR) from the 5' end of AKR ecotropic proviral DNA. The DNA segment extending from 5.1 to 6.8 kilobases contained several restriction sites that were not present in the AKR ecotropic provirus. A 0.5-kilobase DNA segment located at the 3' end of MCF 1 DNA contained sequences which hybridized to a xenotropic env-specific DNA probe but not to labeled ecotropic env-specific DNA. This dual character of MCF 1 proviral DNA was also confirmed by analyzing heteroduplex molecules by electron microscopy. The second cloned proviral DNA (designated MCF 2) was a 6.9-kilobase EcoRI DNA fragment which contained LTR sequences at each end and a 2.0-kilobase deletion encompassing most of the env region. The MCF 2 proviral DNA proved to be a useful reagent for detecting LTRs electron microscopically due to the presence of nonoverlapping, terminally located LTR sequences which effected its circularization with DNAs containing homologous LTR sequences. Nucleotide sequence analysis demonstrated the presence of a 104-base-pair direct repeat in the LTR of MCF 2 DNA. In contrast, only a single copy of the reiterated component of the direct repeat was present in MCF 1 DNA. Images PMID:6281459

Dominance of highly divergent feline leukemia virus A progeny variants in a cat with recurrent viremia and fatal lymphoma.

PubMed

Helfer-Hungerbuehler, A Katrin; Cattori, Valentino; Boretti, Felicitas S; Ossent, Pete; Grest, Paula; Reinacher, Manfred; Henrich, Manfred; Bauer, Eva; Bauer-Pham, Kim; Niederer, Eva; Holznagel, Edgar; Lutz, Hans; Hofmann-Lehmann, Regina

2010-02-19

In a cat that had ostensibly recovered from feline leukemia virus (FeLV) infection, we observed the reappearance of the virus and the development of fatal lymphoma 8.5 years after the initial experimental exposure to FeLV-A/Glasgow-1. The goals of the present study were to investigate this FeLV reoccurrence and molecularly characterize the progeny viruses. The FeLV reoccurrence was detected by the presence of FeLV antigen and RNA in the blood and saliva. The cat was feline immunodeficiency virus positive and showed CD4+ T-cell depletion, severe leukopenia, anemia and a multicentric monoclonal B-cell lymphoma. FeLV-A, but not -B or -C, was detectable. Sequencing of the envelope gene revealed three FeLV variants that were highly divergent from the virus that was originally inoculated (89-91% identity to FeLV-A/Glasgow-1). In the long terminal repeat 31 point mutations, some previously described in cats with lymphomas, were detected. The FeLV variant tissue provirus and viral RNA loads were significantly higher than the FeLV-A/Glasgow-1 loads. Moreover, the variant loads were significantly higher in lymphoma positive compared to lymphoma negative tissues. An increase in the variant provirus blood load was observed at the time of FeLV reoccurrence. Our results demonstrate that ostensibly recovered FeLV provirus-positive cats may act as a source of infection following FeLV reactivation. The virus variants that had largely replaced the inoculation strain had unusually heavily mutated envelopes. The mutations may have led to increased viral fitness and/or changed the mutagenic characteristics of the virus.

Identification of TL-Om1, an Adult T-Cell Leukemia (ATL) Cell Line, as Reference Material for Quantitative PCR for Human T-Lymphotropic Virus 1

PubMed Central

Okuma, Kazu; Yamagishi, Makoto; Yamochi, Tadanori; Firouzi, Sanaz; Momose, Haruka; Mizukami, Takuo; Takizawa, Kazuya; Araki, Kumiko; Sugamura, Kazuo; Yamaguchi, Kazunari; Watanabe, Toshiki

2014-01-01

Quantitative PCR (qPCR) for human T-lymphotropic virus 1 (HTLV-1) is useful for measuring the amount of integrated HTLV-1 proviral DNA in peripheral blood mononuclear cells. Many laboratories in Japan have developed different HTLV-1 qPCR methods. However, when six independent laboratories analyzed the proviral load of the same samples, there was a 5-fold difference in their results. To standardize HTLV-1 qPCR, preparation of a well-defined reference material is needed. We analyzed the integrated HTLV-1 genome and the internal control (IC) genes of TL-Om1, a cell line derived from adult T-cell leukemia, to confirm its suitability as a reference material for HTLV-1 qPCR. Fluorescent in situ hybridization (FISH) showed that HTLV-1 provirus was monoclonally integrated in chromosome 1 at the site of 1p13 in the TL-Om1 genome. HTLV-1 proviral genome was not transferred from TL-Om1 to an uninfected T-cell line, suggesting that the HTLV-1 proviral copy number in TL-Om1 cells is stable. To determine the copy number of HTLV-1 provirus and IC genes in TL-Om1 cells, we used FISH, digital PCR, and qPCR. HTLV-1 copy numbers obtained by these three methods were similar, suggesting that their results were accurate. Also, the ratio of the copy number of HTLV-1 provirus to one of the IC genes, RNase P, was consistent for all three methods. These findings indicate that TL-Om1 cells are an appropriate reference material for HTLV-1 qPCR. PMID:25502533

Effects of Homology Length in the Repeat Region on Minus-Strand DNA Transfer and Retroviral Replication

PubMed Central

Dang, Que; Hu, Wei-Shau

2001-01-01

Homology between the two repeat (R) regions in the retroviral genome mediates minus-strand DNA transfer during reverse transcription. We sought to define the effects of R homology lengths on minus-strand DNA transfer. We generated five murine leukemia virus (MLV)-based vectors that contained identical sequences but different lengths of the 3′ R (3, 6, 12, 24 and 69 nucleotides [nt]); 69 nt is the full-length MLV R. After one round of replication, viral titers from the vector with a full-length downstream R were compared with viral titers generated from the other four vectors with reduced R lengths. Viral titers generated from vectors with R lengths reduced to one-third (24 nt) or one-sixth (12 nt) that of the wild type were not significantly affected; however, viral titers generated from vectors with only 3- or 6-nt homology in the R region were significantly lower. Because expression and packaging of the RNA were similar among all the vectors, the differences in the viral titers most likely reflected the impact of the homology lengths on the efficiency of minus-strand DNA transfer. The molecular nature of minus-strand DNA transfer was characterized in 63 proviruses. Precise R-to-R transfer was observed in most proviruses generated from vectors with 12-, 24-, or 69-nt homology in R, whereas aberrant transfers were predominantly used to generate proviruses from vectors with 3- or 6-nt homology. Reverse transcription using RNA transcribed from an upstream promoter, termed read-in RNA transcripts, resulted in most of the aberrant transfers. These data demonstrate that minus-strand DNA transfer is homology driven and a minimum homology length is required for accurate and efficient minus-strand DNA transfer. PMID:11134294

The remarkable frequency of human immunodeficiency virus type 1 genetic recombination.

PubMed

Onafuwa-Nuga, Adewunmi; Telesnitsky, Alice

2009-09-01

The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination--a copy choice mechanism involving the migration of reverse transcriptase between viral RNA templates--occurs several times on average during every round of HIV-1 DNA synthesis. Key biological factors that lead to high recombination rates for all retroviruses are the recombination-prone nature of their reverse transcription machinery and their pseudodiploid RNA genomes. However, HIV-1 genes recombine even more frequently than do those of many other retroviruses. This reflects the way in which HIV-1 selects genomic RNAs for coencapsidation as well as cell-to-cell transmission properties that lead to unusually frequent associations between distinct viral genotypes. HIV-1 faces strong and changeable selective conditions during replication within patients. The mode of HIV-1 persistence as integrated proviruses and strong selection for defective proviruses in vivo provide conditions for archiving alleles, which can be resuscitated years after initial provirus establishment. Recombination can facilitate drug resistance and may allow superinfecting HIV-1 strains to evade preexisting immune responses, thus adding to challenges in vaccine development. These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV-1 eradication.

Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2) group of human endogenous retroviruses

PubMed Central

2011-01-01

Background Integration of retroviral DNA into a germ cell may lead to a provirus that is transmitted vertically to that host's offspring as an endogenous retrovirus (ERV). In humans, ERVs (HERVs) comprise about 8% of the genome, the vast majority of which are truncated and/or highly mutated and no longer encode functional genes. The most recently active retroviruses that integrated into the human germ line are members of the Betaretrovirus-like HERV-K (HML-2) group, many of which contain intact open reading frames (ORFs) in some or all genes, sometimes encoding functional proteins that are expressed in various tissues. Interestingly, this expression is upregulated in many tumors ranging from breast and ovarian tissues to lymphomas and melanomas, as well as schizophrenia, rheumatoid arthritis, and other disorders. Results No study to date has characterized all HML-2 elements in the genome, an essential step towards determining a possible functional role of HML-2 expression in disease. We present here the most comprehensive and accurate catalog of all full-length and partial HML-2 proviruses, as well as solo LTR elements, within the published human genome to date. Furthermore, we provide evidence for preferential maintenance of proviruses and solo LTR elements on gene-rich chromosomes of the human genome and in proximity to gene regions. Conclusions Our analysis has found and corrected several errors in the annotation of HML-2 elements in the human genome, including mislabeling of a newly identified group called HML-11. HML-elements have been implicated in a wide array of diseases, and characterization of these elements will play a fundamental role to understand the relationship between endogenous retrovirus expression and disease. PMID:22067224

Genomically Intact Endogenous Feline Leukemia Viruses of Recent Origin

PubMed Central

Roca, Alfred L.; Pecon-Slattery, Jill; O'Brien, Stephen J.

2004-01-01

We isolated and sequenced two complete endogenous feline leukemia viruses (enFeLVs), designated enFeLV-AGTT and enFeLV-GGAG. In enFeLV-AGTT, the open reading frames are reminiscent of a functioning FeLV genome, and the 5′ and 3′ long terminal repeat sequences are identical. Neither endogenous provirus is genetically fixed in cats but polymorphic, with 8.9 and 15.2% prevalence for enFeLV-AGTT and enFeLV-GGAG, respectively, among a survey of domestic cats. Neither provirus was found in the genomes of related species of the Felis genus, previously shown to harbor enFeLVs. The absence of mutational divergence, polymorphic incidence in cats, and absence in related species suggest that these enFeLVs may have entered the germ line more recently than previously believed, perhaps coincident with domestication, and reopens the question of whether some enFeLVs might be replication competent. PMID:15047851

HIV-1 integration landscape during latent and active infection

PubMed Central

Cohn, Lillian; Silva, Israel T.; Oliveira, Thiago Y.; Rosales, Rafael A.; Parrish, Erica H.; Learn, Gerald H.; Hahn, Beatrice H.; Czartoski, Julie L.; McElrath, M. Juliana; Lehmann, Clara; Klein, Florian; Caskey, Marina; Walker, Bruce D.; Siliciano, Janet D.; Siliciano, Robert F.; Jankovic, Mila; Nussenzweig, Michel C.

2015-01-01

SUMMARY The barrier to curing HIV-1 is thought to reside primarily in CD4+ T cells containing silent proviruses. To characterize these latently infected cells, we studied the integration profile of HIV-1 in viremic progressors, individuals receiving antiretroviral therapy, and viremic controllers. Clonally expanded T cells represented the majority of all integrations and increased during therapy. However, none of the 75 expanded T cell clones assayed contained intact virus. In contrast, the cells bearing single integration events decreased in frequency over time on therapy, and the surviving cells were enriched for HIV-1 integration in silent regions of the genome. Finally, there was a strong preference for integration into, or in close proximity to Alu repeats, which were also enriched in local hotspots for integration. The data indicate that dividing clonally expanded T cells contain defective proviruses, and that the replication competent reservoir is primarily found in CD4+ T cells that remain relatively quiescent. PMID:25635456

Selective targeting of the repressive transcription factors YY1 and cMyc to disrupt quiescent human immunodeficiency viruses.

PubMed

Barton, Kirston; Margolis, David

2013-02-01

Quiescent HIV-1 infection of resting CD4(+) T cells is an obstacle to eradication of HIV-1 infection. These reservoirs are maintained, in part, by repressive complexes that bind to the HIV-1 long terminal repeat (LTR) and recruit histone deacetylases (HDACs). cMyc and YY1 are two transcription factors that are recruited as part of well-described, distinct complexes to the HIV-1 LTR and in turn recruit HDACs. In prior studies, depletion of single factors that recruit HDAC1 in various cell lines was sufficient to upregulate LTR activity. We used short hairpin RNAs (shRNAs) to test the effect of targeted disruption of a single transcription factor on quiescent proviruses in T cell lines. In this study, we found that depletion of YY1 significantly increases mRNA and protein expression from the HIV-1 promoter in some contexts, but does not affect HDAC1, HDAC2, HDAC3, or acetylated histone 3 occupancy of the HIV-1 LTR. Conversely, depletion of cMyc or cMyc and YY1 does not significantly alter the level of transcription from the LTR or affect recruitment of HDACs to the HIV-1 LTR. Furthermore, global inhibition of HDACs with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) enhanced the increase in LTR transcription in cells that were depleted of YY1.These findings show that despite prior isolated findings, redundancy in repressors of HIV-1 LTR expression will require selective targeting of multiple restrictive mechanisms to comprehensively induce the escape of quiescent proviruses from latency.

Draft genome sequences of Actinomyces timonensis strain 7400942T and its prophage.

PubMed

Gorlas, Aurore; Gimenez, Grégory; Raoult, Didier; Roux, Véronique

2012-12-01

A draft genome sequence of Actinomyces timonensis, an anaerobic bacterium isolated from a human clinical osteoarticular sample, is described here. CRISPR-associated proteins, insertion sequence, and toxin-antitoxin loci were found on the genome. A new virus or provirus, AT-1, was characterized.

Chromosomal localization of Emv-16 and Emv-17, two closely linked ecotropic proviruses of RF/J mice.

PubMed Central

Buchberg, A M; Taylor, B A; Jenkins, N A; Copeland, N G

1986-01-01

Emv-16 and Emv-17, the two closely linked ecotropic proviral loci of RF/J mice, have been mapped to chromosome 1 between leaden, ln, and the mouse engrailed homeo-box locus, En-1, by using recombinant inbred strains and conventional backcross analysis. Images PMID:2878091

HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal

PubMed Central

Wu, Guoxin; Swanson, Michael; Talla, Aarthi; Graham, Donald; Strizki, Julie; Gorman, Daniel; Barnard, Richard J.O.; Blair, Wade; Søgaard, Ole S.; Tolstrup, Martin; Østergaard, Lars; Rasmussen, Thomas A.; Sekaly, Rafick-Pierre; Archin, Nancie M.; Hazuda, Daria J.; Howell, Bonnie J.

2017-01-01

Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs. Importantly, we demonstrate that clinical administration of histone deacetylase inhibitors (HDACis; vorinostat and panobinostat) induced HIV gag p24, and ex vivo stimulation produced sufficient viral antigen to elicit immune-mediated cell killing using anti-gp120/CD3 bispecific antibody. These findings extend beyond classical nucleic acid endpoints, which are confounded by the predominance of mutated, defective proviruses and, of paramount importance, enable assessment of cells making HIV protein that can now be targeted by immunological approaches. PMID:28814661

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review.

PubMed

Eckstrand, Chrissy D; Sparger, Ellen E; Murphy, Brian G

2017-08-01

Infection with feline immunodeficiency virus (FIV), a lentivirus similar to human immunodeficiency virus (HIV), results in lifelong viral persistence and progressive immunopathology in the cat. FIV has the ability to infect and produce infectious virus in a number of different cell types. FIV provirus can also be maintained in a replication-competent but transcriptionally quiescent state, facilitating viral persistence over time. Immediately after the initial infection, FIV infection quickly disseminates to many anatomical compartments within the host including lymphoid organs, gastrointestinal tract and brain. Collectively, the anatomic and cellular compartments that harbour FIV provirus constitute the viral reservoir and contain foci of both ongoing viral replication and transcriptionally restricted virus that may persist over time. The relative importance of the different phenotypes observed for infected cells, anatomic compartment, replication status and size of the reservoir represent crucial areas of investigation for developing effective viral suppression and eradication therapies. In this review, we discuss what is currently known about FIV reservoirs, and emphasize the utility of the FIV-infected cat as a model for the HIV-infected human.

Markers of feline leukaemia virus infection or exposure in cats from a region of low seroprevalence.

PubMed

Beatty, Julia A; Tasker, Séverine; Jarrett, Oswald; Lam, Amy; Gibson, Stephanie; Noe-Nordberg, Alice; Phillips, Angela; Fawcett, Anne; Barrs, Vanessa R

2011-12-01

Molecular techniques have demonstrated that cats may harbour feline leukaemia virus (FeLV) provirus in the absence of antigenaemia. Using quantitative real-time polymerase chain reaction (qPCR), p27 enzyme-linked immunosorbent assay (ELISA), anti-feline oncornavirus-associated cell-membrane-antigen (FOCMA) antibody testing and virus isolation (VI) we investigated three groups of cats. Among cats with cytopenias or lymphoma, 2/75 were transiently positive for provirus and anti-FOCMA antibodies were the only evidence of exposure in another. In 169 young, healthy cats, all tests were negative. In contrast, 3/4 cats from a closed household where FeLV was confirmed by isolation, had evidence of infection. Our results support a role for factors other than FeLV in the pathogenesis of cytopenias and lymphoma. There was no evidence of exposure in young cats. In regions of low prevalence, where the positive predictive value of antigen testing is low, qPCR may assist with diagnosis. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

The Population History of Endogenous Retroviruses in Mule Deer (Odocoileus hemionus)

PubMed Central

2014-01-01

Mobile elements are powerful agents of genomic evolution and can be exceptionally informative markers for investigating species and population-level evolutionary history. While several studies have utilized retrotransposon-based insertional polymorphisms to resolve phylogenies, few population studies exist outside of humans. Endogenous retroviruses are LTR-retrotransposons derived from retroviruses that have become stably integrated in the host genome during past infections and transmitted vertically to subsequent generations. They offer valuable insight into host-virus co-evolution and a unique perspective on host evolutionary history because they integrate into the genome at a discrete point in time. We examined the evolutionary history of a cervid endogenous gammaretrovirus (CrERVγ) in mule deer (Odocoileus hemionus). We sequenced 14 CrERV proviruses (CrERV-in1 to -in14), and examined the prevalence and distribution of 13 proviruses in 262 deer among 15 populations from Montana, Wyoming, and Utah. CrERV absence in white-tailed deer (O. virginianus), identical 5′ and 3′ long terminal repeat (LTR) sequences, insertional polymorphism, and CrERV divergence time estimates indicated that most endogenization events occurred within the last 200000 years. Population structure inferred from CrERVs (F ST = 0.008) and microsatellites (θ = 0.01) was low, but significant, with Utah, northwestern Montana, and a Helena herd being particularly differentiated. Clustering analyses indicated regional structuring, and non-contiguous clustering could often be explained by known translocations. Cluster ensemble results indicated spatial localization of viruses, specifically in deer from northeastern and western Montana. This study demonstrates the utility of endogenous retroviruses to elucidate and provide novel insight into both ERV evolutionary history and the history of contemporary host populations. PMID:24336966

The population history of endogenous retroviruses in mule deer (Odocoileus heminous)

USGS Publications Warehouse

Kamath, Pauline L.; Elleder, Daniel; Bao, Le; Cross, Paul C.; Powell, John H.; Poss, Mary

2013-01-01

Mobile elements are powerful agents of genomic evolution and can be exceptionally informative markers for investigating species and population-level evolutionary history. While several studies have utilized retrotransposon-based insertional polymorphisms to resolve phylogenies, few population studies exist outside of humans. Endogenous retroviruses are LTR-retrotransposons derived from retroviruses that have become stably integrated in the host genome during past infections and transmitted vertically to subsequent generations. They offer valuable insight into host-virus co-evolution and a unique perspective on host evolutionary history because they integrate into the genome at a discrete point in time. We examined the evolutionary history of a cervid endogenous gammaretrovirus (CrERVγ) in mule deer (Odocoileus hemionus). We sequenced 14 CrERV proviruses (CrERV-in1 to -in14), and examined the prevalence and distribution of 13 proviruses in 262 deer among 15 populations from Montana, Wyoming, and Utah. CrERV absence in white-tailed deer (O. virginianus), identical 5′ and 3′ long terminal repeat (LTR) sequences, insertional polymorphism, and CrERV divergence time estimates indicated that most endogenization events occurred within the last 200000 years. Population structure inferred from CrERVs (F ST = 0.008) and microsatellites (θ = 0.01) was low, but significant, with Utah, northwestern Montana, and a Helena herd being particularly differentiated. Clustering analyses indicated regional structuring, and non-contiguous clustering could often be explained by known translocations. Cluster ensemble results indicated spatial localization of viruses, specifically in deer from northeastern and western Montana. This study demonstrates the utility of endogenous retroviruses to elucidate and provide novel insight into both ERV evolutionary history and the history of contemporary host populations.

Walleye dermal sarcoma virus: expression of a full-length clone or the rv-cyclin (orf a) gene is cytopathic to the host and human tumor cells.

PubMed

Xu, Kun; Zhang, Ting Ting; Wang, Ling; Zhang, Cun Fang; Zhang, Long; Ma, Li Xia; Xin, Ying; Ren, Chong Hua; Zhang, Zhi Qiang; Yan, Qiang; Martineau, Daniel; Zhang, Zhi Ying

2013-02-01

Walleye dermal sarcoma virus (WDSV) is etiologically associated with a skin tumor, walleye dermal sarcoma (WDS), which develops in the fall and regresses in the spring. WDSV genome contains, in addition to gag, pol and env, three open reading frames (orfs) designated orf a (rv-cyclin), orf b and orf c. Unintegrated linear WDSV provirus DNA isolated from infected tumor cells was used to construct a full-length WDSV provirus clone pWDSV, while orf a was cloned into pSVK3 to construct the expression vector porfA. Stable co-transfection of a walleye cell line (W12) with pWDSV and pcDNA3 generated fewer and smaller G418-resistant colonies compared to the control. By Northern blot analysis, several small transcripts (2.8, 1.8, 1.2, and 0.8 kb) were detected using a WDSV LTR-specific probe. By RT-PCR and Southern blot analysis, three cDNAs (2.4, 1.6 and 0.8 kb) were identified, including both orf a and orf b messenger. Furthermore stable co-transfection of both a human lung adenocarcinoma cell line (SPC-A-1) and a cervical cancer cell line (HeLa) with pcDNA3 and ether porfA or pWDSV also generated fewer and smaller G418-resistant colonies. We conclude that expression of the full-length WDSV clone or the orf a gene inhibits the host fish and human tumor cell growth, and Orf A protein maybe a potential factor which contributes to the seasonal tumor development and regression. This is the first fish provirus clone that has been expressed in cell culture system, which will provide a new in vitro model for tumor research and oncotherapy study.

Retroviral integration: Site matters

PubMed Central

Demeulemeester, Jonas; De Rijck, Jan

2015-01-01

Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success. PMID:26293289

Future technologies for monitoring HIV drug resistance and cure.

PubMed

Parikh, Urvi M; McCormick, Kevin; van Zyl, Gert; Mellors, John W

2017-03-01

Sensitive, scalable and affordable assays are critically needed for monitoring the success of interventions for preventing, treating and attempting to cure HIV infection. This review evaluates current and emerging technologies that are applicable for both surveillance of HIV drug resistance (HIVDR) and characterization of HIV reservoirs that persist despite antiretroviral therapy and are obstacles to curing HIV infection. Next-generation sequencing (NGS) has the potential to be adapted into high-throughput, cost-efficient approaches for HIVDR surveillance and monitoring during continued scale-up of antiretroviral therapy and rollout of preexposure prophylaxis. Similarly, improvements in PCR and NGS are resulting in higher throughput single genome sequencing to detect intact proviruses and to characterize HIV integration sites and clonal expansions of infected cells. Current population genotyping methods for resistance monitoring are high cost and low throughput. NGS, combined with simpler sample collection and storage matrices (e.g. dried blood spots), has considerable potential to broaden global surveillance and patient monitoring for HIVDR. Recent adaptions of NGS to identify integration sites of HIV in the human genome and to characterize the integrated HIV proviruses are likely to facilitate investigations of the impact of experimental 'curative' interventions on HIV reservoirs.

Reporter gene expression in fish following cutaneous infection with pantropic retroviral vectors.

PubMed

Paul, T A; Burns, J C; Shike, H; Getchell, R; Bowser, P R; Whitlock, K E; Casey, J W

2001-06-01

A central issue in gene delivery systems is choosing promoters that will direct defined and sustainable levels of gene expression. Pantropic retroviral vectors provide a means to insert genes into either somatic or germline cells. In this study, we focused on somatic cell infection by evaluating the activity of 3 promoters inserted by vectors into fish cell lines and fish skin using pantropic retroviruses. In bluegill and zebrafish cell lines, the highest levels of luciferase expression were observed from the 5' murine leukemia virus long terminal repeat of the retroviral vector. The Rous sarcoma virus long terminal repeat and cytomegalovirus early promoter, as internal promoters, generated lower levels of luciferase. Luciferase reporter vectors infected zebrafish skin, as measured by the presence of viral DNA, and expressed luciferase. We infected developing walleye dermal sarcomas with retroviral vectors to provide an environment with enhanced cell proliferation, a condition necessary for integration of the provirus into the host genome. We demonstrated a 4-fold to 7-fold increase in luciferase gene expression in tumor tissue over infections in normal walleye skin.

Direct non-productive HIV-1 infection in a T-cell line is driven by cellular activation state and NFκB

PubMed Central

2014-01-01

Background Molecular latency allows HIV-1 to persist in resting memory CD4+ T-cells as transcriptionally silent provirus integrated into host chromosomal DNA. Multiple transcriptional regulatory mechanisms for HIV-1 latency have been described in the context of progressive epigenetic silencing and maintenance. However, our understanding of the determinants critical for the establishment of latency in newly infected cells is limited. Results In this study, we used a recently described, doubly fluorescent HIV-1 latency model to dissect the role of proviral integration sites and cellular activation state on direct non-productive infections at the single cell level. Proviral integration site mapping of infected Jurkat T-cells revealed that productively and non-productively infected cells are indistinguishable in terms of genomic landmarks, surrounding epigenetic landscapes, and proviral orientation relative to host genes. However, direct non-productive infections were inversely correlated with both cellular activation state and NFκB activity. Furthermore, modulating NFκB with either small molecules or by conditional overexpression of NFκB subunits was sufficient to alter the propensity of HIV-1 to directly enter a non-productive latent state in newly infected cells. Importantly, this modulatory effect was limited to a short time window post-infection. Conclusions Taken together, our data suggest that cellular activation state and NFκB activity during the time of infection, but not the site of proviral integration, are important regulators of direct HIV-1 non-productive infections. PMID:24502247

Insertional Polymorphisms of Endogenous Feline Leukemia Viruses

PubMed Central

Roca, Alfred L.; Nash, William G.; Menninger, Joan C.; Murphy, William J.; O'Brien, Stephen J.

2005-01-01

The number, chromosomal distribution, and insertional polymorphisms of endogenous feline leukemia viruses (enFeLVs) were determined in four domestic cats (Burmese, Egyptian Mau, Persian, and nonbreed) using fluorescent in situ hybridization and radiation hybrid mapping. Twenty-nine distinct enFeLV loci were detected across 12 of the 18 autosomes. Each cat carried enFeLV at only 9 to 16 of the loci, and many loci were heterozygous for presence of the provirus. Thus, an average of 19 autosomal copies of enFeLV were present per cat diploid genome. Only five of the autosomal enFeLV sites were present in all four cats, and at only one autosomal locus, B4q15, was enFeLV present in both homologues of all four cats. A single enFeLV occurred in the X chromosome of the Burmese cat, while three to five enFeLV proviruses occurred in each Y chromosome. The X chromosome and nine autosomal enFeLV loci were telomeric, suggesting that ectopic recombination between nonhomologous subtelomeres may contribute to enFeLV distribution. Since endogenous FeLVs may affect the infectiousness or pathogenicity of exogenous FeLVs, genomic variation in enFeLVs represents a candidate for genetic influences on FeLV leukemogenesis in cats. PMID:15767400

Zinc finger nuclease: a new approach for excising HIV-1 proviral DNA from infected human T cells.

PubMed

Qu, Xiying; Wang, Pengfei; Ding, Donglin; Wang, Xiaohui; Zhang, Gongmin; Zhou, Xin; Liu, Lin; Zhu, Xiaoli; Zeng, Hanxian; Zhu, Huanzhang

2014-09-01

A major reason that Acquired Immune Deficiency Syndrome (AIDS) cannot be completely cured is the human immunodeficiency virus 1 (HIV-1) provirus integrated into the human genome. Though existing therapies can inhibit replication of HIV-1, they cannot eradicate it. A molecular therapy gains popularity due to its specifically targeting to HIV-1 infected cells and effectively removing the HIV-1, regardless of viral genes being active or dormant. Now, we propose a new method which can excellently delete the HIV provirus from the infected human T cell genome. First, we designed zinc-finger nucleases (ZFNs) that target a sequence within the long terminal repeat (LTR) U3 region that is highly conserved in whole clade. Then, we screened out one pair of ZFN and named it as ZFN-U3. We discovered that ZFN-U3 can exactly target and eliminate the full-length HIV-1 proviral DNA after the infected human cell lines treated with it, and the frequency of its excision was about 30 % without cytotoxicity. These results prove that ZFN-U3 can efficiently excise integrated HIV-1 from the human genome in infected cells. This method to delete full length HIV-1 in human genome can therefore provide a novel approach to cure HIV-infected individuals in the future.

HIV Integration at Certain Sites in Host DNA Is Linked to the Expansion and Persistence of Infected Cells | Poster

Cancer.gov

Editor’s note: This article was originally published on the Center for Cancer Research website. When the Human Immunodeficiency Virus (HIV) infects a cell, the virus inserts a copy of its genetic material into the host cell’s DNA. The inserted genetic material, which is also called a provirus, is used to produce new viruses. Because the viral DNA can be inserted at many sites

Replacement of Murine Leukemia Virus Readthrough Mechanism by Human Immunodeficiency Virus Frameshift Allows Synthesis of Viral Proteins and Virus Replication

PubMed Central

Brunelle, Marie-Noëlle; Brakier-Gingras, Léa; Lemay, Guy

2003-01-01

Retroviruses use unusual recoding strategies to synthesize the Gag-Pol polyprotein precursor of viral enzymes. In human immunodeficiency virus, ribosomes translating full-length viral RNA can shift back by 1 nucleotide at a specific site defined by the presence of both a slippery sequence and a downstream stimulatory element made of an extensive secondary structure. This so-called frameshift mechanism could become a target for the development of novel antiviral strategies. A different recoding strategy is used by other retroviruses, such as murine leukemia viruses, to synthesize the Gag-Pol precursor; in this case, a stop codon is suppressed in a readthrough process, again due to the presence of a specific structure adopted by the mRNA. Development of antiframeshift agents will greatly benefit from the availability of a simple animal and virus model. For this purpose, the murine leukemia virus readthrough region was rendered inactive by mutagenesis and the frameshift region of human immunodeficiency virus was inserted to generate a chimeric provirus. This substitution of readthrough by frameshift allows the synthesis of viral proteins, and the chimeric provirus sequence was found to generate infectious viruses. This system could be a most interesting alternative to study ribosomal frameshift in the context of a virus amenable to the use of a simple animal model. PMID:12584361

The presence of ancient human T-cell lymphotropic virus type I provirus DNA in an Andean mummy.

PubMed

Li, H C; Fujiyoshi, T; Lou, H; Yashiki, S; Sonoda, S; Cartier, L; Nunez, L; Munoz, I; Horai, S; Tajima, K

1999-12-01

The worldwide geographic and ethnic clustering of patients with diseases related to human T-cell lymphotropic virus type I (HTLV-I) may be explained by the natural history of HTLV-I infection. The genetic characteristics of indigenous people in the Andes are similar to those of the Japanese, and HTLV-I is generally detected in both groups. To clarify the common origin of HTLV-I in Asia and the Andes, we analyzed HTLV-I provirus DNA from Andean mummies about 1,500 years old. Two of 104 mummy bone marrow specimens yielded a band of human beta-globin gene DNA 110 base pairs in length, and one of these two produced bands of HTLV-I-pX (open reading frame encoding p40x, p27x) and HTLV-I-LTR (long terminal repeat) gene DNA 159 base pairs and 157 base pairs in length, respectively. The nucleotide sequences of ancient HTLV-I-pX and HTLV-I-LTR clones isolated from mummy bone marrow were similar to those in contemporary Andeans and Japanese, although there was microheterogeneity in the sequences of some mummy DNA clones. This result provides evidence that HTLV-I was carried with ancient Mongoloids to the Andes before the Colonial era. Analysis of ancient HTLV-I sequences could be a useful tool for studying the history of human retroviral infection as well as human prehistoric migration.

Ancient HTLV type 1 provirus DNA of Andean mummy.

PubMed

Sonoda, S; Li, H C; Cartier, L; Nunez, L; Tajima, K

2000-11-01

The worldwide geographic and ethnic clustering of patients with diseases related to human T cell lymphotropic virus type 1 (HTLV-1) may be explained by the natural history of HTLV-1 infection. The genetic characteristics of indigenous people in the Andes are similar to those of the Japanese, and HTLV-1 is generally detected in both groups. To clarify the common origin of HTLV-1 in Asia and the Andes, we analyzed HTLV-1 provirus DNA from Andean mummies about 1500 years old. Two of 104 mummy bone marrow specimens yielded a band of human beta-globin gene DNA 110 base pairs in length, and one of these two produced bands of HTLV-1-pX (open reading frame encoding p(40x), p(27x)) and HTLV-1-LTR (long terminal repeat) gene DNA 159 base pairs and 157 base pairs in length, respectively. The nucleotide sequences of ancient HTLV-1-pX and HTLV-1-LTR clones isolated from mummy bone marrow were similar to those in contemporary Andeans and Japanese, although there was microheterogeneity in the sequences of some mummy DNA clones. This result provides evidence that HTLV-1 was carried with ancient Mongoloids to the Andes before the Colonial era. Analysis of ancient HTLV-1 sequences could be a useful tool for studying the history of human retroviral infection as well as human prehistoric migration.

HIV Integration at Certain Sites in Host DNA is Linked to the Expansion and Persistence of Infected Cells | Center for Cancer Research

Cancer.gov

When the Human Immunodeficiency Virus (HIV) infects a cell, the virus inserts a copy of its genetic material into the host cell’s DNA. The inserted genetic material, which is also called a provirus, is used to produce new viruses. Because the viral DNA can be inserted at many sites in the host cell DNA, the site of integration marks each infected cell. Patients infected with

Discordance between bovine leukemia virus tax immortalization in vitro and oncogenicity in vivo.

PubMed

Twizere, J C; Kerkhofs, P; Burny, A; Portetelle, D; Kettmann, R; Willems, L

2000-11-01

Bovine leukemia virus (BLV) Tax protein, a transcriptional activator of viral expression, is essential for viral replication in vivo. Tax is believed to be involved in leukemogenesis because of its second function, immortalization of primary cells in vitro. These activities of Tax can be dissociated on the basis of point mutations within specific regions of the protein. For example, mutation of the phosphorylation sites at serines 106 and 293 abrogates immortalization potential in vitro but maintains transcriptional activity. This type of mutant is thus particularly useful for unraveling the role of Tax immortalization activity during leukemogenesis independently of viral replication. In this report, we describe the biological properties of BLV recombinant proviruses mutated in the Tax phosphorylation sites (BLVTax106+293). Titration of the proviral loads by semiquantitative PCR revealed that the BLV mutants propagated at wild-type levels in vivo. Furthermore, two animals (sheep 480 and 296) infected with BLVTax106+293 developed leukemia or lymphosarcoma after 16 and 36 months, respectively. These periods of time are within the normal range of latencies preceding the onset of pathogenesis induced by wild-type viruses. The phenotype of the mutant-infected cells was characteristic of a B lymphocyte (immunoglobulin M positive) expressing CD11b and CD5 (except at the final stage for the latter marker), a pattern that is typical of wild-type virus-infected target cells. Interestingly, the transformed B lymphocytes from sheep 480 also coexpressed the CD8 marker, a phenotype rarely observed in tumor biopsies from chronic lymphocytic leukemia patients. Finally, direct sequencing of the tax gene demonstrated that the leukemic cells did not harbor revertant proviruses. We conclude that viruses expressing a Tax mutant unable to transform primary cells in culture are still pathogenic in the sheep animal model. Our data thus provide a clear example of the discordant conclusions that can be drawn from in vitro immortalization assays and in vivo experiments. These observations could be of interest for other systems, such as the related human T-cell leukemia virus type 1, which currently lack animal models allowing the study of the leukemogenic process.

HIV integration sites and implications for maintenance of the reservoir.

PubMed

Symons, Jori; Cameron, Paul U; Lewin, Sharon R

2018-03-01

To provide an overview of recent research of how HIV integration relates to productive and latent infection and implications for cure strategies. How and where HIV integrates provides new insights into how HIV persists on antiretroviral therapy (ART). Clonal expansion of infected cells with the same integration site demonstrates that T-cell proliferation is an important factor in HIV persistence, however, the driver of proliferation remains unclear. Clones with identical integration sites harbouring defective provirus can accumulate in HIV-infected individuals on ART and defective proviruses can express RNA and produce protein. HIV integration sites differ in clonally expanded and nonexpanded cells and in latently and productively infected cells and this influences basal and inducible transcription. There is a growing number of cellular proteins that can alter the pattern of integration to favour latency. Understanding these pathways may identify new interventions to eliminate latently infected cells. Using advances in analysing HIV integration sites, T-cell proliferation of latently infected cells is thought to play a major role in HIV persistence. Clonal expansion has been demonstrated with both defective and intact viruses. Production of viral RNA and protein from defective viruses may play a role in driving chronic immune activation. The site of integration may determine the likelihood of proliferation and the degree of basal and induced transcription. Finally, host factors and gene expression at the time of infection may determine the integration site. Together these new insights may lead to novel approaches to elimination of latently infected cells.

Chromosomal Distribution of Endogenous Jaagsiekte Sheep Retrovirus Proviral Sequences in the Sheep Genome

PubMed Central

Carlson, Jonathan; Lyon, Monique; Bishop, Jeanette; Vaiman, Anne; Cribiu, Edmond; Mornex, Jean-François; Brown, Susan; Knudson, Dennis; DeMartini, James; Leroux, Caroline

2003-01-01

A family of endogenous retroviruses (enJSRV) closely related to Jaagsiekte sheep retrovirus (JSRV) is ubiquitous in domestic and wild sheep and goats. Southern blot hybridization studies indicate that there is little active replication or movement of the enJSRV proviruses in these species. Two approaches were used to investigate the distribution of proviral loci in the sheep genome. Fluorescence in situ hybridization (FISH) to metaphase chromosome spreads using viral DNA probes was used to detect loci on chromosomes. Hybridization signals were reproducibly detected on seven sheep chromosomes and eight goat chromosomes in seven cell lines. In addition, a panel of 30 sheep-hamster hybrid cell lines, each of which carries one or more sheep chromosomes and which collectively contain the whole sheep genome, was examined for enJSRV sequences. DNA from each of the lines was used as a template for PCR with JSRV gag-specific primers. A PCR product was amplified from 27 of the hybrid lines, indicating that JSRV gag sequences are found on at least 15 of the 28 sheep chromosomes, including those identified by FISH. Thus, enJSRV proviruses are essentially randomly distributed among the chromosomes of sheep and goats. FISH and/or Southern blot hybridization on DNA from several of the sheep-hamster hybrid cell lines suggests that loci containing multiple copies of enJSRV are present on chromosomes 6 and 9. The origin and functional significance of these arrays is not known. PMID:12915578

A New Approach to Establish a Cell Line with Reduced Risk of Endogenous Retroviruses

PubMed Central

Fukuma, Aiko; Yoshikawa, Rokusuke; Miyazawa, Takayuki; Yasuda, Jiro

2013-01-01

Endogenous retroviruses (ERVs) are integrated as DNA proviruses in the genomes of all mammalian species. Several ERVs are replication-competent and produced as fully infectious viruses from host cell. Thus, live-attenuated vaccines and biological substances have been prepared using the cell lines which may produce ERV. Indeed, we recently reported that several commercial live-attenuated vaccines for pets were contaminated with the infectious feline endogenous retrovirus, RD-114. In this study, to establish a cell line for vaccine manufacture with reduced risk of ERVs, we generated a cell line stably expressing human tetherin (Teth-CRFK cells). The release of infectious ERV from Teth-CRFK cells was suppressed to undetectable levels, while the production of parvovirus in Teth-CRFK cells was similar to that in parental CRFK cells. These observations suggest that Teth-CRFK cells will be useful as a cell line for the manufacture of live-attenuated vaccines or biological substances with reduced risk of ERV. PMID:23585909

A new approach to establish a cell line with reduced risk of endogenous retroviruses.

PubMed

Fukuma, Aiko; Yoshikawa, Rokusuke; Miyazawa, Takayuki; Yasuda, Jiro

2013-01-01

Endogenous retroviruses (ERVs) are integrated as DNA proviruses in the genomes of all mammalian species. Several ERVs are replication-competent and produced as fully infectious viruses from host cell. Thus, live-attenuated vaccines and biological substances have been prepared using the cell lines which may produce ERV. Indeed, we recently reported that several commercial live-attenuated vaccines for pets were contaminated with the infectious feline endogenous retrovirus, RD-114. In this study, to establish a cell line for vaccine manufacture with reduced risk of ERVs, we generated a cell line stably expressing human tetherin (Teth-CRFK cells). The release of infectious ERV from Teth-CRFK cells was suppressed to undetectable levels, while the production of parvovirus in Teth-CRFK cells was similar to that in parental CRFK cells. These observations suggest that Teth-CRFK cells will be useful as a cell line for the manufacture of live-attenuated vaccines or biological substances with reduced risk of ERV.

Hot News: Gene Therapy with CRISPR/Cas9 Coming to Age for HIV Cure.

PubMed

Soriano, Vicente

2017-01-01

The huge success of current antiretroviral therapy is mediated by a triple effect: (i) Halting progression to AIDS in infected persons; (ii) reducing the risk of transmission to contacts (treatment as prevention); and (iii) minimizing the risk of HIV acquisition treating uninfected persons at risk (pre-exposure prophylaxis). However, UNAIDS has estimated that only 70% of infected people globally are diagnosed, only 53% are treated, and overall 44% have undetectable viral load, which is the necessary request for ensuring any antiretroviral benefit. Thus, with 37 million people currently living with HIV worldwide and more than 2 million new infections per year, the prospects for global HIV eradication are far on the horizon. Over the past couple of years, rapid development has been seen for technologies enabling modification of gene expression, either by direct inhibition by RNA interference (RNAi) or by genomic modification at DNA level. In particular, genome-editing endonucleases have significantly improved our ability to make precise changes in the DNA of eukaryotic cells. Notably, firstgeneration genome-editing technologies (i.e., ZFNs and TALENs) have been replaced by clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), which work with a short guide RNA (gRNA) to hybridize to a target DNA site and recruit the Cas9 endonuclease. Once integrated into the host genome, HIV gene expression is regulated by the LTR promoter. Hypothetically, gene editing of the HIV promoter might have the potential to deactivate viral transcription by the introduction of mutations or fragment excision. HIV gene therapy progressed very slowly until recent breakthroughs in gene-editing methods using CRISPR/Cas9 (Liao et al. Nat Commun 2015;6:6413). Using a shorter version of the Cas9 endonuclease ensembled into an adenoviral vector, critical segments of thAQ!e viral DNA genome spanning between the LTR and gag regions were successfully removed in HIV transgenic mice. Excision was confirmed in all examined tissues as well as in circulating lymphocytes and resulted in a drastic reduction of HIV-RNA (Kaminski et al. Gene Ther 2016;23:690-5). Moreover, using latently infected CD4+ T lymphocytes from HIV-infected persons, lentiviral-delivered CRISPR/Cas9 precisely removed the entire HIV genome spanning between the 50 and 30 LTRs of integrated HIV proviral DNA (Kaminski et al., Sci Rep 2016;6:22555), providing a proof of concept of the high potential of genome-editing technologies. Before moving to the clinic, the CRISPR/Cas9 technology must solve several major issues in the HIV scenario. First, generation of resistance is a major concern. Mutations may occur surrounding the targeted site and result in the selection of strains that are no longer recognized nor cleaved by CRISPR (Badia et al. Curr Opin Virol 2017;24:46-54). The efficacy of the anti-HIV CRISPR/Cas9 strategy is highly dependent on the gRNA sequence, yet some mutant viral strains show poor or no cleavage at all. Higher CRISPR/Cas9 pressure could delay but not eliminate viral replication when using a combination of distinct gRNAs targeting distinct HIV proviral genes. In this case, although the reading frame may remain unaltered, an accumulation of insertions and/or deletions may occur in the target sequence, rendering new viral strains insensitive to CRISPR/Cas9 cleavage. Finally, double-strand breaks resulting from CRISPR/Cas9 activity and subsequent cellular non-homologous end joining machinery may introduce mutations in sequences that are no longer recognized by the gRNA, and therefore not susceptible to Cas9 cleavage. A second consideration is a need for developing safe and effective mechanisms of delivery. Adenoviral vectors have long been studied in gene therapy and represent an ideal viral vector for transduction at different tissues. However, the packaging size of adenoviral vectors is a limiting factor, especially for CRIPSR/Cas9. Third, HIV has a genome of about 10 kb while a gRNA generally only targets 20 bp of the DNA molecule, which means that there are thousands available targeting sites for the provirus in latently infected cells. To date, there is no platform established solely for gRNA candidate evaluation in HIV provirus eradication. A final consideration is an access to all tissues and cells potentially harboring the HIV provirus, including reservoirs as the central nervous system. In this regard, efforts are being focused in the development of Cas9/gRNA nanoparticle formulations. To overcome these problems, a group in Florida recently developed human transgenic cells that may be used for gene-editing studies and as platform for high-throughput screen of HIV provirus disrupters (Huang et al. Sci Rep 2017;7:5955). Of note, Cas9 protein instead of a Cas9 plasmid was used. Compared to a plasmid introduction, Cas9 protein agents could be easily quantitatively applied and standardized, mimicking better real clinic scenarios. In summary, RNAi-based technologies have widely dominated gene therapy research during the past decade, with overall slow progress. However, the advent of new gene-editing technologies, and especially the CRISPR/Cas9 system, has revolutionized the field. In the HIV context, CRISPR/Cas9 applications might go further than those of RNAi, for example, enabling excision of segments of integrated proviral DNA from latently infected cells and allowing complete provirus elimination, or it may be used to reverse HIV latency. Although important challenges still need to be overcome, a promising pathway to HIV cure seems to have been found.

HIV-1 transcription and latency: an update

PubMed Central

2013-01-01

Combination antiretroviral therapy, despite being potent and life-prolonging, is not curative and does not eradicate HIV-1 infection since interruption of treatment inevitably results in a rapid rebound of viremia. Reactivation of latently infected cells harboring transcriptionally silent but replication-competent proviruses is a potential source of persistent residual viremia in cART-treated patients. Although multiple reservoirs may exist, the persistence of resting CD4+ T cells carrying a latent infection represents a major barrier to eradication. In this review, we will discuss the latest reports on the molecular mechanisms that may regulate HIV-1 latency at the transcriptional level, including transcriptional interference, the role of cellular factors, chromatin organization and epigenetic modifications, the viral Tat trans-activator and its cellular cofactors. Since latency mechanisms may also operate at the post-transcriptional level, we will consider inhibition of nuclear RNA export and inhibition of translation by microRNAs as potential barriers to HIV-1 gene expression. Finally, we will review the therapeutic approaches and clinical studies aimed at achieving either a sterilizing cure or a functional cure of HIV-1 infection, with a special emphasis on the most recent pharmacological strategies to reactivate the latent viruses and decrease the pool of viral reservoirs. PMID:23803414

Sequence of retrovirus provirus resembles that of bacterial transposable elements

NASA Astrophysics Data System (ADS)

Shimotohno, Kunitada; Mizutani, Satoshi; Temin, Howard M.

1980-06-01

The nucleotide sequences of the terminal regions of an infectious integrated retrovirus cloned in the modified λ phage cloning vector Charon 4A have been elucidated. There is a 569-base pair direct repeat at both ends of the viral DNA. The cell-virus junctions at each end consist of a 5-base pair direct repeat of cell DNA next to a 3-base pair inverted repeat of viral DNA. This structure resembles that of a transposable element and is consistent with the protovirus hypothesis that retroviruses evolved from the cell genome.

Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

PubMed Central

Wei, Datsen George; Chiang, Vicki; Fyne, Elizabeth; Balakrishnan, Mini; Barnes, Tiffany; Graupe, Michael; Hesselgesser, Joseph; Irrinki, Alivelu; Murry, Jeffrey P.; Stepan, George; Stray, Kirsten M.; Tsai, Angela; Yu, Helen; Spindler, Jonathan; Kearney, Mary; Spina, Celsa A.; McMahon, Deborah; Lalezari, Jacob; Sloan, Derek; Mellors, John; Geleziunas, Romas; Cihlar, Tomas

2014-01-01

Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 µM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART. PMID:24722454

Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors.

PubMed Central

Groner, B; Hynes, N E

1980-01-01

The Southern DNA filter transfer technique was used to characterize the genomic location of the mouse mammary tumor proviral DNA in different inbred strains of mice. Two of the strains (C3H and CBA) arose from a cross of a Bagg albino (BALB/c) mouse and a DBA mouse. The mouse mammary tumor virus-containing restriction enzyme DNA fragments of these strains had similar patterns, suggesting that the proviruses of these mice are in similar genomic locations. Conversely, the pattern arising from the DNA of the GR mouse, a strain genetically unrelated to the others, appeared different, suggesting that its mouse mammary tumor proviruses are located in different genomic sites. The structure of another gene, that coding for beta-globin, was also compared. The mice strains which we studied can be categorized into two classes, expressing either one or two beta-globin proteins. The macroenvironment of the beta-globin gene appeared similar among the mice strains belonging to one genetic class. Female mice of the C3H strain exogenously transmit mouse mammary tumor virus via the milk, and their offspring have a high incidence of mammary tumor occurrence. DNA isolated from individual mammary tumors taken from C3H mice or from BALB/c mice foster nursed on C3H mothers was analyzed by the DNA filter transfer technique. Additional mouse mammary tumor virus-containing fragments were found in the DNA isolated from each mammary tumor. These proviral sequences were integrated into different genomic sites in each tumor. Images PMID:6245257

Molecular characterization of a novel gammaretrovirus in killer whales (Orcinus orca).

PubMed

Lamere, Sarah A; St Leger, Judy A; Schrenzel, Mark D; Anthony, Simon J; Rideout, Bruce A; Salomon, Daniel R

2009-12-01

There are currently no published data documenting the presence of retroviruses in cetaceans, though the occurrences of cancers and immunodeficiency states suggest the potential. We examined tissues from adult killer whales and detected a novel gammaretrovirus by degenerate PCR. Reverse transcription-PCR also demonstrated tissue and serum expression of retroviral mRNA. The full-length sequence of the provirus was obtained by PCR, and a TaqMan-based copy number assay did not demonstrate evidence of productive infection. PCR on blood samples from 11 healthy captive killer whales and tissues from 3 free-ranging animals detected the proviral DNA in all tissues examined from all animals. A survey of multiple cetacean species by PCR for gag, pol, and env sequences showed homologs of this virus in the DNA of eight species of delphinids, pygmy and dwarf sperm whales, and harbor porpoises, but not in beluga or fin whales. Analysis of the bottlenose dolphin genome revealed two full-length proviral sequences with 97.4% and 96.9% nucleotide identity to the killer whale gammaretrovirus. The results of single-cell PCR on killer whale sperm and Southern blotting are also consistent with the conclusion that the provirus is endogenous. We suggest that this gammaretrovirus entered the delphinoid ancestor's genome before the divergence of modern dolphins or that an exogenous variant existed following divergence that was ultimately endogenized. However, the transcriptional activity demonstrated in tissues and the nearly intact viral genome suggest a more recent integration into the killer whale genome, favoring the latter hypothesis. The proposed name for this retrovirus is killer whale endogenous retrovirus.

Evidence for a Stable Intermediate in Leukemia Virus Activation in AKR Mouse Embryo Cells

PubMed Central

Ihle, James N.; Kenney, Francis T.; Tennant, Raymond W.

1974-01-01

Analysis of the requirement for serum in the activation of the endogenous leukemia virus expression in AKR mouse embryo cells by 5-iododeoxyuridine shows that activation can be dissociated into two discrete serum-dependent events. The first involves incorporation of 5-iododeoxyuridine into DNA and results in the formation of a stable “activation intermediate” resembling the provirus formed during infection of stationary mouse embryo cells with exogenous leukemia virus. The second event, resulting in expression of the activation intermediate as synthesis of virus proteins, requires DNA replication but not 5-iododeoxyuridine. PMID:4604455

Preparation of a cell line persistently infected with maedi/visna virus and production of viral antigens.

PubMed

Suzuki, Kazuya; Oguma, Keisuke; Sentsui, Hiroshi

2017-01-20

We attempted to prepare a cell line that produces maedi/visna virus (MVV) and is free of contamination by other viruses and mycoplasmas. Three cell lines, which originated from a sheep, goat and bat, were infected with MVV and passaged approximately every 5 days. The cultured cells were then subjected to polymerase chain reaction analysis for MVV provirus. As a result, a cell line persistently infected with MVV was established from ZZ-R cells, which originated from the fetal goat tongue. The 50-fold concentrated culture fluid formed a precipitation line against reference antiserum.

The grafting of universal T-helper epitopes enhances immunogenicity of HIV-1 Tat concurrently improving its safety profile.

PubMed

Kashi, Venkatesh P; Jacob, Rajesh A; Shamanna, Raghavendra A; Menon, Malini; Balasiddaiah, Anangi; Varghese, Rebu K; Bachu, Mahesh; Ranga, Udaykumar

2014-01-01

Extracellular Tat (eTat) plays an important role in HIV-1 pathogenesis. The presence of anti-Tat antibodies is negatively correlated with disease progression, hence making Tat a potential vaccine candidate. The cytotoxicity and moderate immunogenicity of Tat however remain impediments for developing Tat-based vaccines. Here, we report a novel strategy to concurrently enhance the immunogenicity and safety profile of Tat. The grafting of universal helper T-lymphocyte (HTL) epitopes, Pan DR Epitope (PADRE) and Pol711 into the cysteine rich domain (CRD) and the basic domain (BD) abolished the transactivation potential of the Tat protein. The HTL-Tat proteins elicited a significantly higher titer of antibodies as compared to the wild-type Tat in BALB/c mice. While the N-terminal epitope remained immunodominant in HTL-Tat immunizations, an additional epitope in exon-2 was recognized with comparable magnitude suggesting a broader immune recognition. Additionally, the HTL-Tat proteins induced cross-reactive antibodies of high avidity that efficiently neutralized exogenous Tat, thus blocking the activation of a Tat-defective provirus. With advantages such as presentation of multiple B-cell epitopes, enhanced antibody response and importantly, transactivation-deficient Tat protein, this approach has potential application for the generation of Tat-based HIV/AIDS vaccines.

Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fink, J.K.; Correll, P.H.; Perry, L.K.

1990-03-01

Retroviral gene transfer has been used successfully to correct the glucocerebrosidase (GCase) deficiency in primary hematopoietic cells from patients with Gaucher disease. For this model of somatic gene therapy, the authors developed a high-titer, amphotropic retroviral vector designated NTG in which the human GCase gene was driven by the mutant polyoma virus enhancer/herpesvirus thymidine kinase gene (tk) promoter (Py{sup +}/Htk). NTG normalized GCase activity in transduced Gaucher fibroblasts and efficiently infected human monocytic and erythroleukemic cell lines. RNA blot-hybridization (Northern blot) analysis of these hemaptopoietic cell lines showed unexpectedly high-level expression from the Moloney murine leukemia virus long terminal repeatmore » (Mo-MLV LTR) and levels of Py{sup +}/Htk enhancer/promoter-initiated human GCase RNA that approximated endogenous GCase RNA levels. Furthermore, NTG efficiently infected human hematopoietic progenitor cells. Detection of the provirus in approximately one-third of NTG-infected progenitor colonies that had not been selected in G418-containing medium indicates that relative resistance to G418 underestimated the actual gene transfer efficiency. Northern blot analysis of NTG-infected, progenitor-derived cells showed expression from both the Mo-MLV LTR and the Py{sup +}/Htk enhancer/promoter. NTG-transduced hematopoietic progenitor cells from patients with Gaucher disease generated progeny in which GCase activity has been normalized.« less

Broad spectrum antiretroviral activity of 2',3'-dideoxynucleosides.

PubMed Central

Dahlberg, J E; Mitsuya, H; Blam, S B; Broder, S; Aaronson, S A

1987-01-01

Certain dideoxynucleosides have been shown to markedly inhibit the infectivity of human T-lymphotropic virus type III/lymphadenopathy-associated virus, the causative agent of acquired immunodeficiency syndrome (AIDS). Our present studies demonstrate that these drugs are broad spectrum antiretroviral agents capable of inhibiting the infectivity of evolutionarily divergent mammalian type C and animal lentiviruses. Under some conditions, virus infectivity could be inhibited by more than six orders of magnitude. However, the potency of these agents was shown to be greatly influenced by cell-specified determinants. Drug exposure during the initial 24 hr was almost as effective as prolonged treatment on the inhibition of a single cycle of virus infection and expression. Moreover, virus infection was shown directly to be inhibited at the level of proviral DNA synthesis. Thus the time period during which reverse transcription and provirus integration occur is the critical period required for drug action. Our findings have implications concerning strategies to be considered in attempts to utilize 2',3'-dideoxynucleosides in control and treatment of retrovirus-induced diseases of animals and humans. Images PMID:3470806

[A new variant of the simian T-lymphotropic retrovirus type I (STLV-IF) in the Sukhumi colony of hamadryas baboons].

PubMed

Chikobaeva, M G; Schatzl, H; Rose, D; Bush, U; Iakovleva, L A; Deinhardt, F; Helm, K; Lapin, B A

1993-01-01

Polymerase chain reaction (PCR) was developed for the detection of simian T-lymphotropic virus type 1 (STLV-1) infection of P. hamadryas and direct sequencing using oligo-nucleotide primer pairs specific for the tax and env regions of the related human T-lymphotropic virus type 1 (HTLV-1). Excellent specificity was shown in the detection of STLV-1 provirus in infected baboons by PCR using HTLV-1-derived primers. The nucleotide sequences of env 467bp and tax 159bp of the proviral genome (env position 5700-6137, tax position 7373-7498 HTLV-1, according to Seiki et al., 1983) derived from STLV-1-infected P. hamadryas were analysed using PCR and direct sequencing techniques. Two STLV-1 isolates from different sources (Sukhumi main-SuTLV-1 and forest stocks-STLV-1F) were compared. Two variants of STLV-1 among P. hamadryas with different level of homology to HTLV-1 were wound (83.8% and 95.2%, respectively). A possible role of nucleotide changes in env and tax sequenced fragments and oncogenicity of STLV-1 variants is discussed.

Analysis of HTLV-1 proviral load (PVL) and antibody detected with various kinds of tests in Japanese blood donors to understand the relationship between PVL and antibody level and to gain insights toward better antibody testing.

PubMed

Matsumoto, Chieko; Sagara, Yasuko; Sobata, Rieko; Inoue, Yukiko; Morita, Maiko; Uchida, Shigeharu; Kiyokawa, Hiroyuki; Satake, Masahiro; Tadokoro, Kenji

2017-08-01

Adult T-cell leukemia/lymphoma (ATL) occurs in approximately 5% of individuals infected with human T-cell leukemia virus type 1 (HTLV-1). A high proviral load (PVL; more than four copies per 100 peripheral blood mononuclear cells (PBMCs) or 1.6 copies per 100 blood leukocytes) and being male are risk factors for ATL development. Whether anti-HTLV-1 antibody level is related to such risk is unknown. Here, PVL and antibody levels were examined using real-time PCR and other tests in 600 HTLV-1 positive screened Japanese blood donors to understand the relationship between PVL and antibody level in asymptomatic carriers and to gain insights toward better antibody testing for HTLV-1 infection. The 430 donors in whom proviral DNA was detected were considered as true positives for HTLV-1 infection. Among donors aged 40 years or older, more males than females had a PVL corresponding to more than 1.6% infected leukocytes, and an antibody titer below the median (P = 0.0018). In antibody tests using an HTLV-1 positive cell line or Env antigens there was a large discrepancy in antibody titer among 13 provirus-positive samples, probably suggesting that antibody-based screening tests should incorporate multiple HTLV-1 antigens, such as Gag and Env antigens. © 2017 Wiley Periodicals, Inc.

Expression and regulation of human endogenous retrovirus W elements.

PubMed

Li, Fang; Karlsson, Håkan

2016-01-01

Human endogenous retroviruses (HERV) comprise 8% of the human genome and can be classified into at least 31 families. A typical HERV provirus consists of internal gag, pol and env genes, flanked by two long terminal repeats (LTRs). No single provirus is capable of engendering infectious particles. HERV are by nature repetitive and have with few notable exceptions lost their protein-coding capacity. Therefore, HERV have consistently been excluded from array-based expression studies and hence little is known of their expression, regulation, and potential functional significance. An increasing number of studies have, however, observed expression of the W family of HERV in various human tissues and cells, predominantly in placenta. HERV-W LTRs act as promoters in directing transcription of HERV-W members, contribute to their tissue-specific and highly diversified expression pattern. Furthermore, leaky transcription originating from adjacent genes plays a role in the transcription initiation of HERV-W psudoelements. It has been reported that HERV-W elements, including ERVWE1 (the so far only known HERV-W locus harboring a gene (env) functionally adopted by the human host to critically participate in placenta biogenesis), can become transactivated in a range of human non-placental cell-lines during exogenous virus infections. Aberrant expression of HERV-W has been associated with human diseases, such as cancer, multiple sclerosis, and schizophrenia. Based on published reports, transcriptional activities of HERV-W appear to be influenced by several mechanisms; binding of transcription factors to LTR promoters and enhancers outside of LTRs, genetic variation and alteration in DNA methylation and histone modification. Emerging mechanistic studies support the notion that HERV-W represents a potential marker or mediator of environmental exposures (e.g., virus infection) in the development of chronic complex diseases. © 2016 APMIS. Published by John Wiley & Sons Ltd.

[Feline leukemia virus infection: importance and current situation in Switzerland].

PubMed

Hofmann-Lehmann, R; Gönczi, E; Riond, B; Meli, M; Willi, B; Howard, J; Schaarschmidt-Kiener, D; Regli, W; Gilli, U; Boretti, F

2018-02-01

Feline leukemia virus (FeLV) leads to fatal disease in cats with progressive infection. The aim of this study was to determine the importance of FeLV infection in Switzerland and make a comparison with previous studies. Of 881 blood samples taken from cats living in Switzerland (minimum of 20 samples per Canton), 47 samples were provirus-positive (5.3%; 95% confidence interval (CI) 3.9-7.0%) and 18 samples were antigen-positive (2%; 95% CI 1.2-3.2%). Together with data previously collected in similar studies, these findings demonstrated a decrease in prevalence between 1997 and 2003 followed by a relative constant low prevalence thereafter. Young cats (=2 years) were more frequently infected than older cats, but FeLV-positive cats were up to 15 (antigen-positive) and 19 (provirus-positive) years old. Sexually intact cats were more frequently viremic than neutered cats; purebred cats were somewhat less frequently FeLV-positive than non-purebred cats. In a second study, in which 300 saliva samples were analyzed, samples from 5 cats were FeLV-RNA positive (1.7%; 95% CI, 0.5-3.8%), although one young feral cat had been falsely assumed to be FeLV-negative based on a point-of-care test. Of the 300 cats, only 50% were FeLV tested or vaccinated, although 90% of the cats were at risk of exposure to FeLV. Testing and vaccination of all cats with exposure risk may help further decrease the prevalence of FeLV infection. Moreover, characteristics of FeLV tests should be considered, such as the risk of false negative results in the early phase of infection when performing antigen testing.

Prevalence of koala retrovirus in geographically diverse populations in Australia.

PubMed

Simmons, G S; Young, P R; Hanger, J J; Jones, K; Clarke, D; McKee, J J; Meers, J

2012-10-01

To determine the prevalence of koala retrovirus (KoRV) in selected koala populations and to estimate proviral copy number in a subset of koalas. Blood or tissue samples from 708 koalas in Queensland, New South Wales, Victoria and South Australia were tested for KoRV pol provirus gene using standard polymerase chain reaction (PCR), nested PCR and real-time PCR (qPCR). Prevalence of KoRV provirus-positive koalas was 100% in four regions of Queensland and New South Wales, 72.2% in mainland Victoria, 26.6% on four Victorian islands and 14.8% on Kangaroo Island, South Australia. Estimated proviral copy number per cell in four groups of koalas from Queensland and Victoria showed marked variation, ranging from a mean of 165 copies per cell in the Queensland group to 1.29 × 10(-4) copies per cell in one group of Victorian koalas. The higher prevalence of KoRV-positive koalas in the north of Australia and high proviral loads in Queensland koalas may indicate KoRV entered and became endogenous in the north and is spreading southwards. It is also possible there are genetic differences between koalas in northern and southern Australia that affect susceptibility to KoRV infection or endogenisation, or that environmental factors affecting transmission in northern states are absent or uncommon in southern regions. Although further studies are required, the finding of proviral copy numbers orders of magnitude lower than what would be expected for the presence of a single copy in every cell for many Victorian animals suggests that KoRV is not endogenous in these animals and likely reflects ongoing exogenous infection. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

Koala retrovirus genotyping analyses reveal a low prevalence of KoRV-A in Victorian koalas and an association with clinical disease.

PubMed

Legione, Alistair R; Patterson, Jade L S; Whiteley, Pam; Firestone, Simon M; Curnick, Megan; Bodley, Kate; Lynch, Michael; Gilkerson, James R; Sansom, Fiona M; Devlin, Joanne M

2017-02-01

Koala retrovirus (KoRV) is undergoing endogenization into the genome of koalas in Australia, providing an opportunity to assess the effect of retrovirus infection on the health of a population. The prevalence of KoRV in north-eastern Australia (Queensland and New South Wales) is 100 %, whereas previous preliminary investigations in south-eastern Australia (Victoria) suggested KoRV is present at a lower prevalence, although the values have varied widely. Here, we describe a large study of free-ranging koalas in Victoria to estimate the prevalence of KoRV and assess the clinical significance of KoRV infection in wild koalas. Blood or spleen samples from 648 koalas where tested for KoRV provirus, and subsequently genotyped, using PCRs to detect the pol and env genes respectively. Clinical data was also recorded where possible and analysed in comparison to infection status. The prevalence of KoRV was 24.7 % (160/648). KoRV-A was detected in 141/160 cases, but KoRV-B, a genotype associated with neoplasia in captive koalas, was not detected. The genotype in 19 cases could not be determined. Genomic differences between KoRV in Victoria and type strains may have impacted genotyping. Factors associated with KoRV infection, based on multivariable analysis, were low body condition score, region sampled, and 'wet bottom' (a staining of the fur around the rump associated with chronic urinary incontinence). Koalas with wet bottom were nearly twice as likely to have KoRV provirus detected than those without wet bottom (odds ratio=1.90, 95 % confidence interval 1.21, 2.98). Our findings have important implications for the conservation of this iconic species, particularly regarding translocation potential of Victorian koalas.

The antiretrovirus drug 3'-azido-3'-deoxythymidine increases the retrovirus mutation rate.

PubMed Central

Julias, J G; Kim, T; Arnold, G; Pathak, V K

1997-01-01

It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis virus (SNV) mutation rate 13-fold in one cycle of retrovirus replication (V. K. Pathak and H. M. Temin, J. Virol. 66:3093-3100, 1992). Based on this observation, we hypothesized that nucleoside analogs used as antiviral drugs may also increase retrovirus mutation rates. We sought to determine if 3'-azido-3'-deoxythymidine (AZT), the primary treatment for human immunodeficiency virus type 1 (HIV-1) infection, increases the retrovirus mutation rate. Two assays were used to determine the effects of AZT on retrovirus mutation rates. The strategy of the first assay involved measuring the in vivo rate of inactivation of the lacZ gene in one replication cycle of SNV- and murine leukemia virus-based retroviral vectors. We observed 7- and 10-fold increases in the SNV mutant frequency following treatment of target cells with 0.1 and 0.5 microM AZT, respectively. The murine leukemia virus mutant frequency increased two- and threefold following treatment of target cells with 0.5 and 1.0 microM AZT, respectively. The second assay used an SNV-based shuttle vector containing the lacZ alpha gene. Proviruses were recovered as plasmids in Escherichia coli, and the rate of inactivation of lacZ alpha was measured. The results indicated that treatment of target cells increased the overall mutation rate two- to threefold. DNA sequence analysis of mutant proviruses indicated that AZT increased both the deletion and substitution rates. These results suggest that AZT treatment of HIV-1 infection may increase the degree of viral variation and alter virus evolution or pathogenesis. PMID:9151812

Retroviral mutation rates and A-to-G hypermutations during different stages of retroviral replication.

PubMed Central

Kim, T; Mudry, R A; Rexrode, C A; Pathak, V K

1996-01-01

Retroviruses mutate at a high rate in vivo during viral replication. Mutations may occur during proviral transcription by RNA polymerase II, during minus-strand DNA synthesis (RNA template) by viral reverse transcriptase, or during plus-strand DNA synthesis (DNA template) by reverse transcriptase. To determine the contributions of different stages of replication to the retroviral mutation rates, we developed a spleen necrosis virus-based in vivo system to selectively identify mutations occurring during the early stage (RNA transcription plus minus-strand synthesis) and the late stage (plus-strand synthesis plus DNA repair). A lacZalpha reporter gene was inserted into the long terminal repeat (LTR) of a spleen necrosis virus shuttle vector, and proviruses were recovered from infected cells as plasmids containing either one or both LTRs. Plasmids containing both LTRs generated a mutant phenotype only if the lacZalpha genes in both LTRs were mutated, which is most likely to occur during the early stage. Mutant phenotypes were identified from plasmids containing one LTR regardless of the stage at which the mutations occurred. Thus, mutant frequencies obtained after recovery of plasmids containing both LTRs or one LTR provided early-stage and total mutation rates, respectively. Analysis of 56,409 proviruses suggested that the retroviral mutation rates during the early and late stages of replication were equal or within twofold of each other. In addition, two mutants with A-to-G hypermutations were discovered, suggesting a role for mammalian double-stranded RNA adenosine deaminase enzyme in retroviral mutations. These experiments provide a system to selectively identify mutations in the early stage of retroviral replication and to provide upper and lower limits to the in vivo mutation rates during minus-strand and plus-strand synthesis, respectively. PMID:8892879

Standardization of Quantitative PCR for Human T-Cell Leukemia Virus Type 1 in Japan: a Collaborative Study

PubMed Central

Okuma, Kazu; Yamochi, Tadanori; Sato, Tomoo; Sasaki, Daisuke; Hasegawa, Hiroo; Umeki, Kazumi; Kubota, Ryuji; Sobata, Rieko; Matsumoto, Chieko; Kaneko, Noriaki; Naruse, Isao; Yamagishi, Makoto; Nakashima, Makoto; Momose, Haruka; Araki, Kumiko; Mizukami, Takuo; Mizusawa, Saeko; Okada, Yoshiaki; Ochiai, Masaki; Utsunomiya, Atae; Koh, Ki-Ryang; Ogata, Masao; Nosaka, Kisato; Uchimaru, Kaoru; Iwanaga, Masako; Sagara, Yasuko; Yamano, Yoshihisa; Satake, Masahiro; Okayama, Akihiko; Mochizuki, Manabu; Izumo, Shuji; Saito, Shigeru; Itabashi, Kazuo; Kamihira, Shimeru; Yamaguchi, Kazunari; Watanabe, Toshiki

2015-01-01

Quantitative PCR (qPCR) analysis of human T-cell leukemia virus type 1 (HTLV-1) was used to assess the amount of HTLV-1 provirus DNA integrated into the genomic DNA of host blood cells. Accumulating evidence indicates that a high proviral load is one of the risk factors for the development of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, interlaboratory variability in qPCR results makes it difficult to assess the differences in reported proviral loads between laboratories. To remedy this situation, we attempted to minimize discrepancies between laboratories through standardization of HTLV-1 qPCR in a collaborative study. TL-Om1 cells that harbor the HTLV-1 provirus were serially diluted with peripheral blood mononuclear cells to prepare a candidate standard. By statistically evaluating the proviral loads of the standard and those determined using in-house qPCR methods at each laboratory, we determined the relative ratios of the measured values in the laboratories to the theoretical values of the TL-Om1 standard. The relative ratios of the laboratories ranged from 0.84 to 4.45. Next, we corrected the proviral loads of the clinical samples from HTLV-1 carriers using the relative ratio. As expected, the overall differences between the laboratories were reduced by half, from 7.4-fold to 3.8-fold on average, after applying the correction. HTLV-1 qPCR can be standardized using TL-Om1 cells as a standard and by determining the relative ratio of the measured to the theoretical standard values in each laboratory. PMID:26292315

Standardization of Quantitative PCR for Human T-Cell Leukemia Virus Type 1 in Japan: a Collaborative Study.

PubMed

Kuramitsu, Madoka; Okuma, Kazu; Yamochi, Tadanori; Sato, Tomoo; Sasaki, Daisuke; Hasegawa, Hiroo; Umeki, Kazumi; Kubota, Ryuji; Sobata, Rieko; Matsumoto, Chieko; Kaneko, Noriaki; Naruse, Isao; Yamagishi, Makoto; Nakashima, Makoto; Momose, Haruka; Araki, Kumiko; Mizukami, Takuo; Mizusawa, Saeko; Okada, Yoshiaki; Ochiai, Masaki; Utsunomiya, Atae; Koh, Ki-Ryang; Ogata, Masao; Nosaka, Kisato; Uchimaru, Kaoru; Iwanaga, Masako; Sagara, Yasuko; Yamano, Yoshihisa; Satake, Masahiro; Okayama, Akihiko; Mochizuki, Manabu; Izumo, Shuji; Saito, Shigeru; Itabashi, Kazuo; Kamihira, Shimeru; Yamaguchi, Kazunari; Watanabe, Toshiki; Hamaguchi, Isao

2015-11-01

Quantitative PCR (qPCR) analysis of human T-cell leukemia virus type 1 (HTLV-1) was used to assess the amount of HTLV-1 provirus DNA integrated into the genomic DNA of host blood cells. Accumulating evidence indicates that a high proviral load is one of the risk factors for the development of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, interlaboratory variability in qPCR results makes it difficult to assess the differences in reported proviral loads between laboratories. To remedy this situation, we attempted to minimize discrepancies between laboratories through standardization of HTLV-1 qPCR in a collaborative study. TL-Om1 cells that harbor the HTLV-1 provirus were serially diluted with peripheral blood mononuclear cells to prepare a candidate standard. By statistically evaluating the proviral loads of the standard and those determined using in-house qPCR methods at each laboratory, we determined the relative ratios of the measured values in the laboratories to the theoretical values of the TL-Om1 standard. The relative ratios of the laboratories ranged from 0.84 to 4.45. Next, we corrected the proviral loads of the clinical samples from HTLV-1 carriers using the relative ratio. As expected, the overall differences between the laboratories were reduced by half, from 7.4-fold to 3.8-fold on average, after applying the correction. HTLV-1 qPCR can be standardized using TL-Om1 cells as a standard and by determining the relative ratio of the measured to the theoretical standard values in each laboratory. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Diagnosis of feline leukaemia virus infection by semi-quantitative real-time polymerase chain reaction.

PubMed

Pinches, Mark D G; Helps, Christopher R; Gruffydd-Jones, Tim J; Egan, Kathy; Jarrett, Oswald; Tasker, Séverine

2007-02-01

In this paper the design and use of a semi-quantitative real-time polymerase chain reaction assay (RT-PCR) for feline leukaemia virus (FeLV) provirus is described. Its performance is evaluated against established methods of FeLV diagnosis, including virus isolation and enzyme-linked immunoassay (ELISA) in a population of naturally infected cats. The RT-PCR assay is found to have both a high sensitivity (0.92) and specificity (0.99) when examined by expectation maximisation methods and is also able to detect a large number of cats with low FeLV proviral loads that were negative by other conventional test methods.

A Temporospatial Map That Defines Specific Steps at Which Critical Surfaces in the Gag MA and CA Domains Act during Immature HIV-1 Capsid Assembly in Cells

PubMed Central

Robinson, Bridget A.; Reed, Jonathan C.; Geary, Clair D.; Swain, J. Victor

2014-01-01

ABSTRACT During HIV-1 assembly, Gag polypeptides target to the plasma membrane, where they multimerize to form immature capsids that undergo budding and maturation. Previous mutational analyses identified residues within the Gag matrix (MA) and capsid (CA) domains that are required for immature capsid assembly, and structural studies showed that these residues are clustered on four exposed surfaces in Gag. Exactly when and where the three critical surfaces in CA function during assembly are not known. Here, we analyzed how mutations in these four critical surfaces affect the formation and stability of assembly intermediates in cells expressing the HIV-1 provirus. The resulting temporospatial map reveals that critical MA residues act during membrane targeting, residues in the C-terminal CA subdomain (CA-CTD) dimer interface are needed for the stability of the first membrane-bound assembly intermediate, CA-CTD base residues are necessary for progression past the first membrane-bound intermediate, and residues in the N-terminal CA subdomain (CA-NTD) stabilize the last membrane-bound intermediate. Importantly, we found that all four critical surfaces act while Gag is associated with the cellular facilitators of assembly ABCE1 and DDX6. When correlated with existing structural data, our findings suggest the following model: Gag dimerizes via the CA-CTD dimer interface just before or during membrane targeting, individual CA-CTD hexamers form soon after membrane targeting, and the CA-NTD hexameric lattice forms just prior to capsid release. This model adds an important new dimension to current structural models by proposing the potential order in which key contacts within the immature capsid lattice are made during assembly in cells. IMPORTANCE While much is known about the structure of the completed HIV-1 immature capsid and domains of its component Gag proteins, less is known about the sequence of events leading to formation of the HIV-1 immature capsid. Here we used biochemical and ultrastructural analyses to generate a temporospatial map showing the precise order in which four critical surfaces in Gag act during immature capsid formation in provirus-expressing cells. Because three of these surfaces make important contacts in the hexameric lattices that are found in the completed immature capsid, these data allow us to propose a model for the sequence of events leading to formation of the hexameric lattices. By providing a dynamic view of when and where critical Gag-Gag contacts form during the assembly process and how those contacts function in the nascent capsid, our study provides novel insights into how an immature capsid is built in infected cells. PMID:24623418

T-cell tropism of simian T-cell leukaemia virus type 1 and cytokine profiles in relation to proviral load and immunological changes during chronic infection of naturally infected mandrills (Mandrillus sphinx).

PubMed

Souquière, Sandrine; Mouinga-Ondeme, Augustin; Makuwa, Maria; Beggio, Paola; Radaelli, Antonia; De Giuli Morghen, Carlo; Mortreux, Franck; Kazanji, Mirdad

2009-08-01

Although a wide variety of non-human primates are susceptible to simian T-cell leukaemia virus type 1 (STLV-1), little is known about the virological or molecular determinants of natural STLV-1 infection. We determined STLV-1 virus tropism in vivo and its relation to the immune response by evaluating cytokine production and T-cell subsets in naturally infected and uninfected mandrills. With real-time PCR methods, we found that STLV-1 in mandrills infects both CD4(+) and CD8(+) T cells; however, proviral loads were significantly higher (P = 0.01) in CD4(+) than in CD8(+) cells (mean STLV-1 copies number per 100 cells (+/- SD) was 7.8 +/- 8 in CD4(+) T cells and 3.9 +/- 4.5 in CD8(+) T cells). After culture, STLV-1 provirus was detected in enriched CD4(+) but not in enriched CD8(+) T cells. After 6 months of culture, STLV-1-transformed cell lines expressing CD3(+), CD4(+) and HLADR(+) were established, and STLV-1 proteins and tax/rex mRNA were detected. In STLV-1 infected monkeys, there was a correlation between high proviral load and elevated levels of interleukin (IL)-2, IL-6, IL-10, interferon-gamma and tumour necrosis factor-alpha. The two monkeys with the highest STLV-1 proviral load had activated CD4(+)HLADR(+) and CD8(+)HLADR(+) T-cell subsets and a high percentage of CD25(+) in CD4(+) and CD8(+) T cells. Our study provides the first cellular, immunological and virological characterization of natural STLV-1 infection in mandrills and shows that they are an appropriate animal model for further physiopathological studies of the natural history of human T-cell leukaemia viruses.

Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression.

PubMed

Tso, For Yue; Abrahamyan, Levon; Hu, Shiu-Lok; Ruprecht, Ruth M; Wood, Charles

2013-01-01

A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice.

PubMed

Pérès, Eléonore; Blin, Juliana; Ricci, Emiliano P; Artesi, Maria; Hahaut, Vincent; Van den Broeke, Anne; Corbin, Antoine; Gazzolo, Louis; Ratner, Lee; Jalinot, Pierre; Duc Dodon, Madeleine

2018-03-01

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive malignant proliferation of activated CD4+ T lymphocytes. The viral Tax oncoprotein is critically involved in both HTLV-1-replication and T-cell proliferation, a prerequisite to the development of ATLL. In this study, we investigated the in vivo contribution of the Tax PDZ domain-binding motif (PBM) to the lymphoproliferative process. To that aim, we examined T-cell proliferation in humanized mice (hu-mice) carrying a human hemato-lymphoid system infected with either a wild type (WT) or a Tax PBM-deleted (ΔPBM) provirus. We observed that the frequency of CD4+ activated T-cells in the peripheral blood and in the spleen was significantly higher in WT than in ΔPBM hu-mice. Likewise, human T-cells collected from WT hu-mice and cultivated in vitro in presence of interleukin-2 were proliferating at a higher level than those from ΔPBM animals. We next examined the association of Tax with the Scribble PDZ protein, a prominent regulator of T-cell polarity, in human T-cells analyzed either after ex vivo isolation or after in vitro culture. We confirmed the interaction of Tax with Scribble only in T-cells from the WT hu-mice. This association correlated with the presence of both proteins in aggregates at the leading edge of the cells and with the formation of long actin filopods. Finally, data from a comparative genome-wide transcriptomic analysis suggested that the PBM-PDZ association is implicated in the expression of genes regulating proliferation, apoptosis and cytoskeletal organization. Collectively, our findings suggest that the Tax PBM is an auxiliary motif that contributes to the sustained growth of HTLV-1 infected T-cells in vivo and in vitro and is essential to T-cell immortalization.

PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice

PubMed Central

Artesi, Maria; Jalinot, Pierre

2018-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive malignant proliferation of activated CD4+ T lymphocytes. The viral Tax oncoprotein is critically involved in both HTLV-1-replication and T-cell proliferation, a prerequisite to the development of ATLL. In this study, we investigated the in vivo contribution of the Tax PDZ domain-binding motif (PBM) to the lymphoproliferative process. To that aim, we examined T-cell proliferation in humanized mice (hu-mice) carrying a human hemato-lymphoid system infected with either a wild type (WT) or a Tax PBM-deleted (ΔPBM) provirus. We observed that the frequency of CD4+ activated T-cells in the peripheral blood and in the spleen was significantly higher in WT than in ΔPBM hu-mice. Likewise, human T-cells collected from WT hu-mice and cultivated in vitro in presence of interleukin-2 were proliferating at a higher level than those from ΔPBM animals. We next examined the association of Tax with the Scribble PDZ protein, a prominent regulator of T-cell polarity, in human T-cells analyzed either after ex vivo isolation or after in vitro culture. We confirmed the interaction of Tax with Scribble only in T-cells from the WT hu-mice. This association correlated with the presence of both proteins in aggregates at the leading edge of the cells and with the formation of long actin filopods. Finally, data from a comparative genome-wide transcriptomic analysis suggested that the PBM-PDZ association is implicated in the expression of genes regulating proliferation, apoptosis and cytoskeletal organization. Collectively, our findings suggest that the Tax PBM is an auxiliary motif that contributes to the sustained growth of HTLV-1 infected T-cells in vivo and in vitro and is essential to T-cell immortalization. PMID:29566098

The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes

PubMed Central

Shmakov, Sergey A.; Sitnik, Vassilii; Makarova, Kira S.; Wolf, Yuri I.; Severinov, Konstantin V.

2017-01-01

ABSTRACT Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein (CRISPR-Cas) systems store the memory of past encounters with foreign DNA in unique spacers that are inserted between direct repeats in CRISPR arrays. For only a small fraction of the spacers, homologous sequences, called protospacers, are detectable in viral, plasmid, and microbial genomes. The rest of the spacers remain the CRISPR “dark matter.” We performed a comprehensive analysis of the spacers from all CRISPR-cas loci identified in bacterial and archaeal genomes, and we found that, depending on the CRISPR-Cas subtype and the prokaryotic phylum, protospacers were detectable for 1% to about 19% of the spacers (~7% global average). Among the detected protospacers, the majority, typically 80 to 90%, originated from viral genomes, including proviruses, and among the rest, the most common source was genes that are integrated into microbial chromosomes but are involved in plasmid conjugation or replication. Thus, almost all spacers with identifiable protospacers target mobile genetic elements (MGE). The GC content, as well as dinucleotide and tetranucleotide compositions, of microbial genomes, their spacer complements, and the cognate viral genomes showed a nearly perfect correlation and were almost identical. Given the near absence of self-targeting spacers, these findings are most compatible with the possibility that the spacers, including the dark matter, are derived almost completely from the species-specific microbial mobilomes. PMID:28928211

Cloning of a long HIV-1 readthrough transcript and detection of an increased level of early growth response protein-1 (Egr-1) mRNA in chronically infected U937 cells.

PubMed

Dron, M; Hameau, L; Benboudjema, L; Guymarho, J; Cajean-Feroldi, C; Rizza, P; Godard, C; Jasmin, C; Tovey, M G; Lang, M C

1999-01-01

To identify the pathways involved in HIV-1 modification of cellular gene expression, chronically infected U937 cells were screened by mRNA differential display. A chimeric transcript consisting of the 3' end of the LTR of a HIV-1 provirus, followed by 3.7 kb of cellular RNA was identified suggesting that long readthrough transcription might be one of the mechanisms by which gene expression could be modified in individual infected cells. Such a phenomenon may also be the first step towards the potential transduction of cellular sequences. Furthermore, the mRNA encoding for the transcription factor Egr-1 was detected as an over-represented transcript in infected cells. Northern blot analysis confirmed the increase of Egr-1 mRNA content in both HIV-1 infected promonocytic U937 cells and T cell lines such as Jurkat and CEM. Interestingly a similar increase of Egr-1 mRNA has previously been reported to occur in HTLV-1 and HTLV-2 infected T cell lines. Despite the consistent increase in the level of Egr-1 mRNA, the amount of the encoded protein did not appear to be modified in HIV-1 infected cells, suggesting an increased turn over of the protein in chronically infected cells.

CRISPR/Cas9 Inhibits Multiple Steps of HIV-1 Infection.

PubMed

Yin, Lijuan; Hu, Siqi; Mei, Shan; Sun, Hong; Xu, Fengwen; Li, Jian; Zhu, Weijun; Liu, Xiaoman; Zhao, Fei; Zhang, Di; Cen, Shan; Liang, Chen; Guo, Fei

2018-05-09

CRISPR/Cas9 is an adaptive immune system where bacteria and archaea have evolved to resist the invading viruses and plasmid DNA by creating site-specific double-strand breaks in DNA. This study tested this gene editing system in inhibiting human immunodeficiency virus type 1 (HIV-1) infection by targeting the viral long terminal repeat and the gene coding sequences. Strong inhibition of HIV-1 infection by Cas9/gRNA was observed, which resulted not only from insertions and deletions (indels) that were introduced into viral DNA due to Cas9 cleavage, but also from the marked decrease in the levels of the late viral DNA products and the integrated viral DNA. This latter defect might have reflected the degradation of viral DNA that has not been immediately repaired after Cas9 cleavage. It was further observed that Cas9, when solely located in the cytoplasm, inhibits HIV-1 as strongly as the nuclear Cas9, except that the cytoplasmic Cas9 does not act on the integrated HIV-1 DNA and thus cannot be used to excise the latent provirus. Together, the results suggest that Cas9/gRNA is able to target and edit HIV-1 DNA both in the cytoplasm and in the nucleus. The inhibitory effect of Cas9 on HIV-1 is attributed to both the indels in viral DNA and the reduction in the levels of viral DNA.

Human Immunodeficiency Virus (HIV) Latency: The Major Hurdle in HIV Eradication

PubMed Central

Tyagi, Mudit; Bukrinsky, Michael

2012-01-01

Failure of highly active antiretroviral therapy to eradicate the human immunodeficiency virus (HIV), even in patients who suppress the virus to undetectable levels for many years, underscores the problems associated with fighting this infection. The existence of persistent infection in certain cellular and anatomical reservoirs appears to be the major hurdle in HIV eradication. The development of therapeutic interventions that eliminate or limit the latent viral pools or prevent the reemergence of the viruses from producing cells will therefore be required to enhance the effectiveness of current antiretroviral strategies. To achieve this goal, there is a pressing need to understand HIV latency at the molecular level to design novel and improved therapies to either eradicate HIV or find a functional cure in which patients could maintain a manageable viral pool without AIDS in the absence of antiretroviral therapy. The integrated proviral genome remains transcriptionally silent for a long period in certain subsets of T cells. This ability to infect cells latently helps HIV to establish a persistent infection despite strong humoral and cellular immune responses against the viral proteins. The main purpose of this report is to provide a general overview of the HIV latency. We will describe the hurdles being faced in eradicating latent HIV proviruses. We will also briefly discuss the ongoing strategies aimed toward curing HIV infection. PMID:22692576

A majority of mice show long-term expression of a human. beta. -globin gene after retrovirus transfer into hematopoietic stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bender, M.A.; Gelinas, R.E.; Miller

1989-04-01

Murine bone marrow was infected with a high-titer retrovirus vector containing the human {beta}-globin and neomycin phosphotransferase genes. Anemic W/W/sup v/ mice were transplanted with infected marrow which in some cases had been exposed to the selective agent G418. Human {beta}-globin expression was monitored in transplanted animals by using a monoclonal antibody specific for human {beta}-globin polypeptide, and hematopoietic reconstitution was monitored by using donor and recipient mice which differed in hemoglobin type. In some experiments all transplanted mice expressed the human {beta}-globin polypeptide for over 4 months, and up to 50% of peripheral erythrocytes contained detectable levels of polypeptide.more » DNA analysis of transplanted animals revealed that virtually every myeloid cell contained a provirus. Integration site analysis and reconstitution of secondary marrow recipients suggested that every mouse was reconstituted with at least one infected stem cell which had extensive repopulation capability. The ability to consistently transfer an active {beta}-globin gene into mouse hematopoietic cells improves the feasibility of using these techniques for somatic cell gene therapy in humans.« less

Role of TAR RNA splicing in translational regulation of simian immunodeficiency virus from rhesus macaques.

PubMed Central

Viglianti, G A; Rubinstein, E P; Graves, K L

1992-01-01

The untranslated leader sequences of rhesus macaque simian immunodeficiency virus mRNAs form a stable secondary structure, TAR. This structure can be modified by RNA splicing. In this study, the role of TAR splicing in virus replication was investigated. The proportion of viral RNAs containing a spliced TAR structure is high early after infection and decreases at later times. Moreover, proviruses containing mutations which prevent TAR splicing are significantly delayed in replication. These mutant viruses require approximately 20 days to achieve half-maximal virus production, in contrast to wild-type viruses, which require approximately 8 days. We attribute this delay to the inefficient translation of unspliced-TAR-containing mRNAs. The molecular basis for this translational effect was examined in in vitro assays. We found that spliced-TAR-containing mRNAs were translated up to 8.5 times more efficiently than were similar mRNAs containing an unspliced TAR leader. Furthermore, these spliced-TAR-containing mRNAs were more efficiently associated with ribosomes. We postulate that the level of TAR splicing provides a balance for the optimal expression of both viral proteins and genomic RNA and therefore ultimately controls the production of infectious virions. Images PMID:1629957

Towards HIV-1 remission: potential roles for broadly neutralizing antibodies.

PubMed

Halper-Stromberg, Ariel; Nussenzweig, Michel C

2016-02-01

Current antiretroviral drug therapies do not cure HIV-1 because they do not eliminate a pool of long-lived cells harboring immunologically silent but replication-competent proviruses - termed the latent reservoir. Eliminating this reservoir and stimulating the immune response to control infection in the absence of therapy remain important but unsolved goals of HIV-1 cure research. Recently discovered broadly neutralizing antibodies (bNAbs) exhibit remarkable breadth and potency in their ability to neutralize HIV-1 in vitro, and recent studies have demonstrated new therapeutic applications for passively administered bNAbs in vivo. This Review discusses the roles bNAbs might play in HIV-1 treatment regimens, including prevention, therapy, and cure.

Human Foamy Virus Capsid Formation Requires an Interaction Domain in the N Terminus of Gag

PubMed Central

Tobaly-Tapiero, Joelle; Bittoun, Patricia; Giron, Marie-Lou; Neves, Manuel; Koken, Marcel; Saïb, Ali; de Thé, Hugues

2001-01-01

Retroviral Gag expression is sufficient for capsid assembly, which occurs through interaction between distinct Gag domains. Human foamy virus (HFV) capsids assemble within the cytoplasm, although their budding, which mainly occurs in the endoplasmic reticulum, requires the presence of homologous Env. Yet little is known about the molecular basis of HFV Gag precursor assembly. Using fusions between HFV Gag and a nuclear reporter protein, we have identified a strong interaction domain in the N terminus of HFV Gag which is predicted to contain a conserved coiled-coil motif. Deletion within this region in an HFV provirus abolishes viral production through inhibition of capsid assembly. PMID:11287585

In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1) rat-bovine chimeric antibody against bovine leukemia virus infection.

PubMed

Nishimori, Asami; Konnai, Satoru; Okagawa, Tomohiro; Maekawa, Naoya; Ikebuchi, Ryoyo; Goto, Shinya; Sajiki, Yamato; Suzuki, Yasuhiko; Kohara, Junko; Ogasawara, Satoshi; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

2017-01-01

Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV) and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow. However, this did not induce T-cell proliferation or reduction of BLV provirus loads during the test period, and only bound to circulating IgM+ B cells until one week post-inoculation. We hypothesized that this lack of in vivo effects was due to its lower stability in cattle and so established an anti-PD-L1 rat-bovine chimeric antibody (Boch4G12). Boch4G12 was able to bind specifically with bovine PD-L1, interrupt the PD-1/PD-L1 interaction, and activate the immune response in both healthy and BLV-infected cattle in vitro. Therefore, we experimentally infected a healthy calf with BLV and inoculated it intravenously with 1 mg/kg of Boch4G12 once it reached the aleukemic (AL) stage. Cultivation of peripheral blood mononuclear cells (PBMCs) isolated from the tested calf indicated that the proliferation of CD4+ T cells was increased by Boch4G12 inoculation, while BLV provirus loads were significantly reduced, clearly demonstrating that this treatment induced antivirus activities. Therefore, further studies using a large number of animals are required to support its efficacy for clinical application.

Human T-Cell Lymphotropic Virus Type 1 Open Reading Frame II-Encoded p30II Is Required for In Vivo Replication: Evidence of In Vivo Reversion

PubMed Central

Silverman, Lee R.; Phipps, Andrew J.; Montgomery, Andrew; Ratner, Lee; Lairmore, Michael D.

2004-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma and exhibits high genetic stability in vivo. HTLV-1 contains four open reading frames (ORFs) in its pX region. ORF II encodes two proteins, p30II and p13II, both of which are incompletely characterized. p30II localizes to the nucleus or nucleolus and has distant homology to the transcription factors Oct-1, Pit-1, and POU-M1. In vitro studies have demonstrated that at low concentrations, p30II differentially regulates cellular and viral promoters through an interaction with CREB binding protein/p300. To determine the in vivo significance of p30II, we inoculated rabbits with cell lines expressing either a wild-type clone of HTLV-1 (ACH.1) or a clone containing a mutation in ORF II, which eliminated wild-type p30II expression (ACH.30.1). ACH.1-inoculated rabbits maintained higher HTLV-1-specific antibody titers than ACH.30.1-inoculated rabbits, and all ACH.1-inoculated rabbits were seropositive for HTLV-1, whereas only two of six ACH.30.1-inoculated rabbits were seropositive. Provirus could be consistently PCR amplified from peripheral blood mononuclear cell (PBMC) DNA in all ACH.1-inoculated rabbits but in only three of six ACH.30.1-inoculated rabbits. Quantitative competitive PCR indicated higher PBMC proviral loads in ACH.1-inoculated rabbits. Interestingly, sequencing of ORF II from PBMC of provirus-positive ACH.30.1-inoculated rabbits revealed a reversion to wild-type sequence with evidence of early coexistence of mutant and wild-type sequence. Our data provide evidence that HTLV-1 must maintain its key accessory genes to survive in vivo and that in vivo pressures select for maintenance of wild-type ORF II gene products during the early course of infection. PMID:15047799

Human T-cell lymphotropic virus type 1 provirus and phylogenetic analysis in patients with mycosis fungoides and their family relatives.

PubMed

Shohat, M; Shohat, B; Mimouni, D; Pauli, G; Ellerbrok, H; David, M; Hodak, E

2006-08-01

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma of unknown aetiology. A pathogenic role of human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. To determine whether MF is linked to HTLV-1. Blood samples were collected from 60 patients, 15 family relatives of patients with MF (MFRs), 20 healthy controls and 10 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The presence of HTLV-1 antibodies in serum was tested by the Western blot rp21e-enhanced test. DNA was extracted from the blood with the Qiagen blood kit. We used 500 ng of DNA either in conventional HTLV-1-specific polymerase chain reaction (PCR) or in real-time PCR using primers sk43 and sk44 together with a tax-specific fluorescent probe. In Western blot, antibodies against three to four HTLV-1 antigens were detected in 52% of patients with MF. All of the patients with HAM/TSP were positive, while only 7% of the MFRs and none of the 20 healthy controls reacted with HTLV-1 antigens in Western blot. One of 60 patients with MF and one of 15 MFRs were positive in HTLV-1 PCR. These two PCR-positive samples which were quantified in real-time PCR showed that fewer than five in 10(6) cells were HTLV-1 infected. We succeeded in amplifying and sequencing the 5' end of the provirus from the blood of the PCR-positive MFR by seminested PCR. A positive result was also obtained in this test. Phylogenetic tree analyses revealed a high homology of this sequence with other HTLV-1 sequences from the Middle East. The above PCR-positive MFR was the brother of a PCR-negative patient with MF. These findings demonstrate that HTLV-1 is probably not the aetiological agent of MF. However, it may play a role in immunosuppression and in the spreading of the disease.

In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1) rat-bovine chimeric antibody against bovine leukemia virus infection

PubMed Central

Nishimori, Asami; Okagawa, Tomohiro; Maekawa, Naoya; Ikebuchi, Ryoyo; Goto, Shinya; Sajiki, Yamato; Suzuki, Yasuhiko; Kohara, Junko; Ogasawara, Satoshi; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

2017-01-01

Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV) and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow. However, this did not induce T-cell proliferation or reduction of BLV provirus loads during the test period, and only bound to circulating IgM+ B cells until one week post-inoculation. We hypothesized that this lack of in vivo effects was due to its lower stability in cattle and so established an anti-PD-L1 rat-bovine chimeric antibody (Boch4G12). Boch4G12 was able to bind specifically with bovine PD-L1, interrupt the PD-1/PD-L1 interaction, and activate the immune response in both healthy and BLV-infected cattle in vitro. Therefore, we experimentally infected a healthy calf with BLV and inoculated it intravenously with 1 mg/kg of Boch4G12 once it reached the aleukemic (AL) stage. Cultivation of peripheral blood mononuclear cells (PBMCs) isolated from the tested calf indicated that the proliferation of CD4+ T cells was increased by Boch4G12 inoculation, while BLV provirus loads were significantly reduced, clearly demonstrating that this treatment induced antivirus activities. Therefore, further studies using a large number of animals are required to support its efficacy for clinical application. PMID:28445479

HIV-1 activation of innate immunity depends strongly on the intracellular level of TREX1 and sensing of incomplete reverse transcription products.

PubMed

Kumar, Swati; Morrison, James H; Dingli, David; Poeschla, Eric

2018-05-16

TREX1 has been reported to degrade cytosolic immune-stimulatory DNA, including viral DNA generated during HIV-1 infection, but the dynamic range of its capacity to suppress innate immune stimulation is unknown and its full role in the viral life cycle remains unclear. A main purpose of our study was to determine how the intracellular level of TREX1 affects HIV-1 activation and avoidance of innate immunity. Using stable over-expression and CRISPR-mediated gene disruption, we engineered a range of TREX1 levels in human THP-1 monocytes. Increasing the level of TREX1 dramatically suppressed HIV-1 induction of interferon-stimulated genes (ISGs). Productive infection and integrated proviruses were equal to increased. Knocking out TREX1 impaired viral infectivity, increased early viral cDNA and caused ten-fold or greater increases in HIV-1 ISG induction. Knockout of cyclic GMP-AMP synthase (cGAS) abrogated all ISG induction. Moreover, cGAS knockout produced no increase in single cycle infection, establishing that HIV-1 DNA-triggered signaling is not rapid enough to impair the initial ISG-triggering infection cycle. Disruption of the HIV-1 capsid by PF74 also induced ISGs and this was TREX1 level-dependent, required reverse transcriptase catalysis, and was eliminated by cGAS gene knockout. Thus, the intracellular level of TREX1 pivotally modulates innate immune induction by HIV-1. Partial HIV-1 genomes are the TREX1 target and are sensed by cGAS. The nearly complete lack of innate immune induction despite equal to increased viral integration observed when the TREX1 protein level is experimentally elevated indicates that integration-competent genomes are shielded from cytosolic sensor-effectors during uncoating and transit to the nucleus. IMPORTANCE Much remains unknown about how TREX1 influences HIV-1 replication, whether it targets full-length viral DNA versus partial intermediates, how intracellular TREX1 protein levels correlate with ISG induction, and whether TREX1 digestion of cytoplasmic DNA and subsequent cGAS pathway activation affects both initial and subsequent cycles of infection. To answer these questions, we experimentally varied the intracellular level of TREX1 and show that this strongly determines the innate immunogenicity of HIV-1. In addition, several lines of evidence including time of addition experiments with drugs that impair reverse transcription or capsid integrity showed that the pathogen-associated molecular patterns sensed after viral entry contain DNA, are TREX1 and cGAS substrates, and are derived from incomplete RT products. In contrast, the experiments demonstrate that full-length integration competent viral DNA is immune to TREX1. Treatment approaches that reduce TREX1 levels or facilitate release of DNA intermediates may advantageously combine enhanced innate immunity with antiviral effects. Copyright © 2018 American Society for Microbiology.

APOBEC3G-Induced Hypermutation of Human Immunodeficiency Virus Type-1 Is Typically a Discrete “All or Nothing” Phenomenon

PubMed Central

Armitage, Andrew E.; Deforche, Koen; Chang, Chih-hao; Wee, Edmund; Kramer, Beatrice; Welch, John J.; Gerstoft, Jan; Fugger, Lars; McMichael, Andrew; Rambaut, Andrew; Iversen, Astrid K. N.

2012-01-01

The rapid evolution of Human Immunodeficiency Virus (HIV-1) allows studies of ongoing host–pathogen interactions. One key selective host factor is APOBEC3G (hA3G) that can cause extensive and inactivating Guanosine-to-Adenosine (G-to-A) mutation on HIV plus-strand DNA (termed hypermutation). HIV can inhibit this innate anti-viral defense through binding of the viral protein Vif to hA3G, but binding efficiency varies and hypermutation frequencies fluctuate in patients. A pivotal question is whether hA3G-induced G-to-A mutation is always lethal to the virus or if it may occur at sub-lethal frequencies that could increase viral diversification. We show in vitro that limiting-levels of hA3G-activity (i.e. when only a single hA3G-unit is likely to act on HIV) produce hypermutation frequencies similar to those in patients and demonstrate in silico that potentially non-lethal G-to-A mutation rates are ∼10-fold lower than the lowest observed hypermutation levels in vitro and in vivo. Our results suggest that even a single incorporated hA3G-unit is likely to cause extensive and inactivating levels of HIV hypermutation and that hypermutation therefore is typically a discrete “all or nothing” phenomenon. Thus, therapeutic measures that inhibit the interaction between Vif and hA3G will likely not increase virus diversification but expand the fraction of hypermutated proviruses within the infected host. PMID:22457633

Advancements in Developing Strategies for Sterilizing and Functional HIV Cures

PubMed Central

Li, Haoyang; Hua, Chen; Zhang, Hanzhen

2017-01-01

Combined antiretroviral therapy (cART) has been successful in prolonging lifespan and reducing mortality of patients infected with human immunodeficiency virus (HIV). However, the eradication of latent HIV reservoirs remains a challenge for curing HIV infection (HIV cure) because of HIV latency in primary memory CD4+ T cells. Currently, two types of HIV cures are in development: a “sterilizing cure” and a “functional cure.” A sterilizing cure refers to the complete elimination of replication-competent proviruses in the body, while a functional cure refers to the long-term control of HIV replication without treatment. Based on these concepts, significant progress has been made in different areas. This review focuses on recent advancements and future prospects for HIV cures. PMID:28529952

Recent advances in the identification of Tat-mediated transactivation inhibitors: progressing toward a functional cure of HIV.

PubMed

Tabarrini, Oriana; Desantis, Jenny; Massari, Serena

2016-01-01

The current anti-HIV combination therapy does not eradicate the virus that persists mainly in quiescent infected CD4(+) T cells as a latent integrated provirus that resumes after therapy interruption. The Tat-mediated transactivation (TMT) is a critical step in the HIV replication cycle that could give the opportunity to reduce the size of latent reservoirs. More than two decades of research led to the identification of various TMT inhibitors. While none of them met the criteria to reach the market, the search for a suitable TMT inhibitor is still actively pursued. Really promising compounds, including one in a Phase III clinical trial, have been recently identified, thus warranting an update.

Mouse chromosomal mapping of a murine leukemia virus integration region (Mis-1) first identified in rat thymic leukemia.

PubMed Central

Jolicoeur, P; Villeneuve, L; Rassart, E; Kozak, C

1985-01-01

We have previously identified a region of genomic DNA which constitutes the site of frequent provirus integration in rat thymomas induced by Moloney murine leukemia virus (Lemay and Jolicoeur, Proc. Natl. Acad. Sci. USA 81:38-42, 1984). This genetic locus is now designated Mis-1 (Moloney integration site). Cellular sequences homologous to Mis-1 are present in mouse DNA. Using a series of hamster-mouse somatic cell hybrids, we mapped the Mis-1 locus to mouse chromosome 15. Frequent chromosome 15 aberrations have been described in mouse thymomas. Mis-1 represents a putative new oncogene which might be involved in the initiation or maintenance or both of these neoplasms. Images PMID:4068142

TCF1 and LEF1 act as T-cell intrinsic HTLV-1 antagonists by targeting Tax.

PubMed

Ma, Guangyong; Yasunaga, Jun-ichirou; Akari, Hirofumi; Matsuoka, Masao

2015-02-17

Human T-cell leukemia virus type 1 (HTLV-1) is a delta-type retrovirus that induces malignant and inflammatory diseases during its long persistence in vivo. HTLV-1 can infect various kinds of cells; however, HTLV-1 provirus is predominantly found in peripheral CD4 T cells in vivo. Here we find that TCF1 and LEF1, two Wnt transcription factors that are specifically expressed in T cells, inhibit viral replication through antagonizing Tax functions. TCF1 and LEF1 can each interact with Tax and inhibit Tax-dependent viral expression and activation of NF-κB and AP-1. As a result, HTLV-1 replication is suppressed in the presence of either TCF1 or LEF1. On the other hand, T-cell activation suppresses the expression of both TCF1 and LEF1, and this suppression enables Tax to function as an activator. We analyzed the thymus of a simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaque, and found a negative correlation between proviral load and TCF1/LEF1 expression in various T-cell subsets, supporting the idea that TCF1 and LEF1 negatively regulate HTLV-1 replication and the proliferation of infected cells. Thus, this study identified TCF1 and LEF1 as Tax antagonistic factors in vivo, a fact which may critically influence the peripheral T-cell tropism of this virus.

Genome-wide scan for commons SNPs affecting bovine leukemia virus infection level in dairy cattle.

PubMed

Carignano, Hugo A; Roldan, Dana L; Beribe, María J; Raschia, María A; Amadio, Ariel; Nani, Juan P; Gutierrez, Gerónimo; Alvarez, Irene; Trono, Karina; Poli, Mario A; Miretti, Marcos M

2018-02-13

Bovine leukemia virus (BLV) infection is omnipresent in dairy herds causing direct economic losses due to trade restrictions and lymphosarcoma-related deaths. Milk production drops and increase in the culling rate are also relevant and usually neglected. The BLV provirus persists throughout a lifetime and an inter-individual variation is observed in the level of infection (LI) in vivo. High LI is strongly correlated with disease progression and BLV transmission among herd mates. In a context of high prevalence, classical control strategies are economically prohibitive. Alternatively, host genomics studies aiming to dissect loci associated with LI are potentially useful tools for genetic selection programs tending to abrogate the viral spreading. The LI was measured through the proviral load (PVL) set-point and white blood cells (WBC) counts. The goals of this work were to gain insight into the contribution of SNPs (bovine 50KSNP panel) on LI variability and to identify genomics regions underlying this trait. We quantified anti-p24 response and total leukocytes count in peripheral blood from 1800 cows and used these to select 800 individuals with extreme phenotypes in WBCs and PVL. Two case-control genomic association studies using linear mixed models (LMMs) considering population stratification were performed. The proportion of the variance captured by all QC-passed SNPs represented 0.63 (SE ± 0.14) of the phenotypic variance for PVL and 0.56 (SE ± 0.15) for WBCs. Overall, significant associations (Bonferroni's corrected -log 10 p > 5.94) were shared for both phenotypes by 24 SNPs within the Bovine MHC. Founder haplotypes were used to measure the linkage disequilibrium (LD) extent (r 2  = 0.22 ± 0.27 at inter-SNP distance of 25-50 kb). The SNPs and LD blocks indicated genes potentially associated with LI in infected cows: i.e. relevant immune response related genes (DQA1, DRB3, BOLA-A, LTA, LTB, TNF, IER3, GRP111, CRISP1), several genes involved in cell cytoskeletal reorganization (CD2AP, PKHD1, FLOT1, TUBB5) and modelling of the extracellular matrix (TRAM2, TNXB). Host transcription factors (TFs) were also highlighted (TFAP2D; ABT1, GCM1, PRRC2A). Data obtained represent a step forward to understand the biology of BLV-bovine interaction, and provide genetic information potentially applicable to selective breeding programs.

Advances and hope for perinatal HIV remission and cure in children and adolescents.

PubMed

Rainwater-Lovett, Kaitlin; Uprety, Priyanka; Persaud, Deborah

2016-02-01

The known timing of HIV infection in perinatal transmission, combined with the capacity for early antiretroviral therapy (ART) initiation and immune reconstitution, can provide unique insights into HIV persistence. The scientific basis for a pediatric-specific research agenda aimed at HIV remission and cure is discussed. Accumulating evidence supports a favorable biomarker profile for immunotherapeutic interventions in early treated, perinatally infected individuals. HIV DNA concentrations in infected cells of early treated infants decrease over the first few years of life and, after more than 10 years of ART, the overwhelming majority of noninduced proviral genomes are replication-deficient. With early ART initiation, approximately half of perinatally infected individuals become seronegative. Studies of untreated infants and vaccine trials indicate that infected infants can generate HIV-specific humoral responses. Taken together, this evidence suggests that early treatment results in low levels of replication-competent provirus, an absence of HIV-specific immunity, and the capacity to generate immune responses to potential immunotherapeutic interventions. Perinatally HIV-infected individuals require lifelong ART because of the prompt establishment of viral latency in long-lived resting memory CD4 T cells that rekindle viremia upon treatment cessation. However, intense research efforts are ongoing to perturb HIV latency toward reservoir clearance for virologic remission and cure in which perinatally infected individuals can discontinue ART.

Virus-Host and CRISPR Dynamics in Archaea-Dominated Hypersaline Lake Tyrrell, Victoria, Australia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emerson, Joanne B.; Andrade, Karen; Thomas, Brian C.

The study of natural archaeal assemblages requires community context, namely, a concurrent assessment of the dynamics of archaeal, bacterial, and viral populations. Here, we use filter size-resolved metagenomic analyses to report the dynamics of 101 archaeal and bacterial OTUs and 140 viral populations across 17 samples collected over different timescales from 2007–2010 from Australian hypersaline Lake Tyrrell (LT). All samples were dominated by Archaea (75–95%). Archaeal, bacterial, and viral populations were found to be dynamic on timescales of months to years, and different viral assemblages were present in planktonic, relative to host-associated (active and provirus) size fractions. Analyses of clusteredmore » regularly interspaced short palindromic repeat (CRISPR) regions indicate that both rare and abundant viruses were targeted, primarily by lower abundance hosts. Although very few spacers had hits to the NCBI nr database or to the 140 LT viral populations, 21% had hits to unassembled LT viral concentrate reads. This suggests local adaptation to LT-specific viruses and/or undersampling of haloviral assemblages in public databases, along with successful CRISPR-mediated maintenance of viral populations at abundances low enough to preclude genomic assembly. This is the first metagenomic report evaluating widespread archaeal dynamics at the population level on short timescales in a hypersaline system.« less

Virus-Host and CRISPR Dynamics in Archaea-Dominated Hypersaline Lake Tyrrell, Victoria, Australia

DOE PAGES

Emerson, Joanne B.; Andrade, Karen; Thomas, Brian C.; ...

2013-01-01

The study of natural archaeal assemblages requires community context, namely, a concurrent assessment of the dynamics of archaeal, bacterial, and viral populations. Here, we use filter size-resolved metagenomic analyses to report the dynamics of 101 archaeal and bacterial OTUs and 140 viral populations across 17 samples collected over different timescales from 2007–2010 from Australian hypersaline Lake Tyrrell (LT). All samples were dominated by Archaea (75–95%). Archaeal, bacterial, and viral populations were found to be dynamic on timescales of months to years, and different viral assemblages were present in planktonic, relative to host-associated (active and provirus) size fractions. Analyses of clusteredmore » regularly interspaced short palindromic repeat (CRISPR) regions indicate that both rare and abundant viruses were targeted, primarily by lower abundance hosts. Although very few spacers had hits to the NCBI nr database or to the 140 LT viral populations, 21% had hits to unassembled LT viral concentrate reads. This suggests local adaptation to LT-specific viruses and/or undersampling of haloviral assemblages in public databases, along with successful CRISPR-mediated maintenance of viral populations at abundances low enough to preclude genomic assembly. This is the first metagenomic report evaluating widespread archaeal dynamics at the population level on short timescales in a hypersaline system.« less

HIV-1 Infection of Primary CD4+ T Cells Regulates the Expression of Specific Human Endogenous Retrovirus HERV-K (HML-2) Elements.

PubMed

Young, George R; Terry, Sandra N; Manganaro, Lara; Cuesta-Dominguez, Alvaro; Deikus, Gintaras; Bernal-Rubio, Dabeiba; Campisi, Laura; Fernandez-Sesma, Ana; Sebra, Robert; Simon, Viviana; Mulder, Lubbertus C F

2018-01-01

Endogenous retroviruses (ERVs) occupy extensive regions of the human genome. Although many of these retroviral elements have lost their ability to replicate, those whose insertion took place more recently, such as the HML-2 group of HERV-K elements, still retain intact open reading frames and the capacity to produce certain viral RNA and/or proteins. Transcription of these ERVs is, however, tightly regulated by dedicated epigenetic control mechanisms. Nonetheless, it has been reported that some pathological states, such as viral infections and certain cancers, coincide with ERV expression, suggesting that transcriptional reawakening is possible. HML-2 elements are reportedly induced during HIV-1 infection, but the conserved nature of these elements has, until recently, rendered their expression profiling problematic. Here, we provide comprehensive HERV-K HML-2 expression profiles specific for productively HIV-1-infected primary human CD4 + T cells. We combined enrichment of HIV-1 infected cells using a reporter virus expressing a surface reporter for gentle and efficient purification with long-read single-molecule real-time sequencing. We show that three HML-2 proviruses-6q25.1, 8q24.3, and 19q13.42-are upregulated on average between 3- and 5-fold in HIV-1-infected CD4 + T cells. One provirus, HML-2 12q24.33, in contrast, was repressed in the presence of active HIV replication. In conclusion, this report identifies the HERV-K HML-2 loci whose expression profiles differ upon HIV-1 infection in primary human CD4 + T cells. These data will help pave the way for further studies on the influence of endogenous retroviruses on HIV-1 replication. IMPORTANCE Endogenous retroviruses inhabit big portions of our genome. Moreover, although they are mainly inert, some of the evolutionarily younger members maintain the ability to express both RNA and proteins. We have developed an approach using long-read single-molecule real-time (SMRT) sequencing that produces long reads that allow us to obtain detailed and accurate HERV-K HML-2 expression profiles. We applied this approach to study HERV-K expression in the presence or absence of productive HIV-1 infection of primary human CD4 + T cells. In addition to using SMRT sequencing, our strategy also includes the magnetic selection of the infected cells so that levels of background expression due to uninfected cells are kept at a minimum. The results presented here provide a blueprint for in-depth studies of the interactions of the authentic upregulated HERV-K HML-2 elements and HIV-1. Copyright © 2017 American Society for Microbiology.

Natural history of the ERVWE1 endogenous retroviral locus

PubMed Central

Bonnaud, Bertrand; Beliaeff, Jean; Bouton, Olivier; Oriol, Guy; Duret, Laurent; Mallet, François

2005-01-01

Background The human HERV-W multicopy family includes a unique proviral locus, termed ERVWE1, whose full-length envelope ORF was preserved through evolution by the action of a selective pressure. The encoded Env protein (Syncytin) is involved in hominoid placental physiology. Results In order to infer the natural history of this domestication process, a comparative genomic analysis of the human 7q21.2 syntenic regions in eutherians was performed. In primates, this region was progressively colonized by LTR-elements, leading to two different evolutionary pathways in Cercopithecidae and Hominidae, a genetic drift versus a domestication, respectively. Conclusion The preservation in Hominoids of a genomic structure consisting in the juxtaposition of a retrotransposon-derived MaLR LTR and the ERVWE1 provirus suggests a functional link between both elements. PMID:16176588

The Discovery of Reverse Transcriptase.

PubMed

Coffin, John M; Fan, Hung

2016-09-29

In 1970 the independent and simultaneous discovery of reverse transcriptase in retroviruses (then RNA tumor viruses) by David Baltimore and Howard Temin revolutionized molecular biology and laid the foundations for retrovirology and cancer biology. In this historical review we describe the formulation of the controversial provirus hypothesis by Temin, which ultimately was proven by his discovery of reverse transcriptase in Rous sarcoma virus virions. Baltimore arrived at the same discovery through his studies on replication of RNA-containing viruses, starting with poliovirus and then moving to vesicular stomatitis virus, where he discovered a virion RNA polymerase. Subsequent studies of reverse transcriptase led to the elucidation of the mechanism of retrovirus replication, the discovery of oncogenes, the advent of molecular cloning, the search for human cancer viruses, and the discovery and treatment of HIV/AIDS.

Remembering Jan Svoboda: A Personal Reflection.

PubMed

Weiss, Robin A

2018-04-18

The Czech scientist Jan Svoboda was a pioneer of Rous sarcoma virus (RSV). In the 1960s, before the discovery of reverse transcriptase, he demonstrated the long-term persistence of the viral genome in non-productive mammalian cells, and he supported the DNA provirus hypothesis of Howard Temin. He showed how the virus can be rescued in the infectious form and elucidated the replication-competent nature of the Prague strain of RSV later used for the identification of the src oncogene. His studies straddled molecular oncology and virology, and he remained an active contributor to the field until his death last year. Throughout the 50 years that I was privileged to know Svoboda as my mentor and friend, I admired his depth of scientific inquiry and his steadfast integrity in the face of political oppression.

Remembering Jan Svoboda: A Personal Reflection

PubMed Central

Weiss, Robin A.

2018-01-01

The Czech scientist Jan Svoboda was a pioneer of Rous sarcoma virus (RSV). In the 1960s, before the discovery of reverse transcriptase, he demonstrated the long-term persistence of the viral genome in non-productive mammalian cells, and he supported the DNA provirus hypothesis of Howard Temin. He showed how the virus can be rescued in the infectious form and elucidated the replication-competent nature of the Prague strain of RSV later used for the identification of the src oncogene. His studies straddled molecular oncology and virology, and he remained an active contributor to the field until his death last year. Throughout the 50 years that I was privileged to know Svoboda as my mentor and friend, I admired his depth of scientific inquiry and his steadfast integrity in the face of political oppression. PMID:29670049

Characterization of simian T-cell leukemia virus type 1 in naturally infected Japanese macaques as a model of HTLV-1 infection

PubMed Central

2013-01-01

Background Human T-cell leukemia virus type 1 (HTLV-1) causes chronic infection leading to development of adult T-cell leukemia (ATL) and inflammatory diseases. Non-human primates infected with simian T-cell leukemia virus type 1 (STLV-1) are considered to constitute a suitable animal model for HTLV-1 research. However, the function of the regulatory and accessory genes of STLV-1 has not been analyzed in detail. In this study, STLV-1 in naturally infected Japanese macaques was analyzed. Results We identified spliced transcripts of STLV-1 corresponding to HTLV-1 tax and HTLV-1 bZIP factor (HBZ). STLV-1 Tax activated the NFAT, AP-1 and NF-κB signaling pathways, whereas STLV-1 bZIP factor (SBZ) suppressed them. Conversely, SBZ enhanced TGF-β signaling and induced Foxp3 expression. Furthermore, STLV-1 Tax activated the canonical Wnt pathway while SBZ suppressed it. STLV-1 Tax enhanced the viral promoter activity while SBZ suppressed its activation. Then we addressed the clonal proliferation of STLV-1+ cells by massively sequencing the provirus integration sites. Some clones proliferated distinctively in monkeys with higher STLV-1 proviral loads. Notably, one of the monkeys surveyed in this study developed T-cell lymphoma in the brain; STLV-1 provirus was integrated in the lymphoma cell genome. When anti-CCR4 antibody, mogamulizumab, was administered into STLV-1-infected monkeys, the proviral load decreased dramatically within 2 weeks. We observed that some abundant clones recovered after discontinuation of mogamulizumab administration. Conclusions STLV-1 Tax and SBZ have functions similar to those of their counterparts in HTLV-1. This study demonstrates that Japanese macaques naturally infected with STLV-1 resemble HTLV-1 carriers and are a suitable model for the investigation of persistent HTLV-1 infection and asymptomatic HTLV-1 carrier state. Using these animals, we verified that mogamulizumab, which is currently used as a drug for relapsed ATL, is also effective in reducing the proviral load in asymptomatic individuals. PMID:24156738

New acute transforming feline retovirus with fms homology specifies a C-terminally truncated version of the c-fms protein that is different from SM-feline sarcoma virus v-fms protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Besmer, P.; Lader, E.; George, P.C.

1986-10-01

The HZ5-feline sarcoma virus (FeSV) is a new acute transforming feline retrovirus which was isolated from a multicentric fibrosarcoma of a domestic cat. The HZ5-FeSV transforms fibroblasts in vitro and is replication defective. A biologically active integrated HZ5-FeSV provirus was molecularly cloned from cellular DNA of HZ5-FeSV-infected FRE-3A rat cells. The HZ5-FeSV has oncogene homology with the fms sequences of the SM-FeSV. The genome organization of the 8.6-kilobase HZ5-FeSV provirus is 5' ..delta..gag-fms-..delta..pol-..delta..env 3'. The HZ5- and SM-FeSVs display indistinguishable in vitro transformation characteristics, and the structures of the gag-fms transforming genes in the two viruses are very similar. Inmore » the HZ5-FeSV and the SM-FeSV, identical c-fms and feline leukemia virus p10 sequences form the 5' gag-fms junction. With regard to v-fms the two viruses are homologous up to 11 amino acids before the C terminus of the SM-FeSV v-fms protein. In HZ5-FeSV a segment of 362 nucleotides then follows before the 3' recombination site with feline leukemia virus pol. The new 3' v-fms sequence encodes 27 amino acids before reaching a TGA termination signal. The relationship of this sequence with the recently characterized human c-fms sequence has been examined. The 3' HZ5-FeSV v-fms sequence is homologous with 3' c-fms sequences. A frameshift mutation (11-base-pair deletion) was found in the C-terminal fms coding sequence of the HZ5-FeSV. As a result, the HZ5-FeSV v-fms protein is predicted to be a C-terminally truncated version of c-fms. This frameshift mutation may determine the oncogenic properties of v-fms in the HZ5-FeSV.« less

Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy.

PubMed

Kearney, Mary F; Anderson, Elizabeth M; Coomer, Charles; Smith, Luke; Shao, Wei; Johnson, Nicholas; Kline, Christopher; Spindler, Jonathan; Mellors, John W; Coffin, John M; Ambrose, Zandrea

2015-11-11

Determining the anatomic compartments that contribute to plasma HIV-1 is critical to understanding the sources of residual viremia during combination antiretroviral therapy (ART). We analyzed viral DNA and RNA populations in the plasma and tissues from macaques infected with SIV containing HIV-1 RT (RT-SHIV) to identify possible sources of persistent viremia and to investigate the effect of ART on viral replication in tissues. Tissues were collected at necropsy from four pigtailed macaques infected for 30 weeks with a diverse population of RT-SHIV. Two animals (6760 and 8232) were untreated and two animals (8030 and 8272) were treated with efavirenz, tenofovir, and emtricitabine for 20 weeks. A total of 1800 single-genome RT-SHIV pol and env DNA and RNA sequences were analyzed from the plasma, PBMCs, axillary and mesenteric lymph nodes, spleen, thymus, small intestine, bone marrow, lung, and brain. Analyses of intracellular DNA and RNA populations revealed that the majority of proviruses in tissues from untreated animal 8232 were not expressed, whereas a greater proportion of proviruses in tissues were expressed from 6760. Few intracellular RNA sequences were detected in treated animals and most contained inactivating mutations, such as frame shifts or large deletions. Phylogenetics showed that RT-SHIV DNA populations in tissues were not different from virus in contemporary plasma samples in the treated or untreated animals, demonstrating a lack of anatomic compartmentalization and suggesting that plasma viremia is derived from multiple tissue sources. No sequence divergence was detected in the plasma or between tissues in the treated animals after 20 weeks of ART indicating a lack of ongoing replication in tissues during treatment. Virus populations in plasma and tissues did not differ significantly in either treated or untreated macaques, suggesting frequent exchange of virus or infected cells between tissues and plasma, consistent with non-compartmentalized and widely disseminated infection. There was no genetic evidence of ongoing replication in tissues during suppressive ART.

A new acute transforming feline retrovirus with fms homology specifies a C-terminally truncated version of the c-fms protein that is different from SM-feline sarcoma virus v-fms protein.

PubMed Central

Besmer, P; Lader, E; George, P C; Bergold, P J; Qiu, F H; Zuckerman, E E; Hardy, W D

1986-01-01

The HZ5-feline sarcoma virus (FeSV) is a new acute transforming feline retrovirus which was isolated from a multicentric fibrosarcoma of a domestic cat. The HZ5-FeSV transforms fibroblasts in vitro and is replication defective. A biologically active integrated HZ5-FeSV provirus was molecularly cloned from cellular DNA of HZ5-FeSV-infected FRE-3A rat cells. The HZ5-FeSV has oncogene homology with the fms sequences of the SM-FeSV. The genome organization of the 8.6-kilobase HZ5-FeSV provirus is 5' delta gag-fms-delta pol-delta env 3'. The HZ5-and SM-FeSVs display indistinguishable in vitro transformation characteristics, and the structures of the gag-fms transforming genes in the two viruses are very similar. In the HZ5-FeSV and the SM-FeSV, identical c-fms and feline leukemia virus p10 sequences form the 5' gag-fms junction. With regard to v-fms the two viruses are homologous up to 11 amino acids before the C terminus of the SM-FeSV v-fms protein. In HZ5-FeSV a segment of 362 nucleotides then follows before the 3' recombination site with feline leukemia virus pol. The new 3' v-fms sequence encodes 27 amino acids before reaching a TGA termination signal. The relationship of this sequence with the recently characterized human c-fms sequence has been examined. The 3' HZ5-FeSV v-fms sequence is homologous with 3' c-fms sequences. A frameshift mutation (11-base-pair deletion) was found in the C-terminal fms coding sequence of the HZ5-FeSV. As a result, the HZ5-FeSV v-fms protein is predicted to be a C-terminally truncated version of c-fms. This frameshift mutation may determine the oncogenic properties of v-fms in the HZ5-FeSV. Images PMID:3018286

Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus)

PubMed Central

Meli, Marina L.; Cattori, Valentino; Martínez, Fernando; López, Guillermo; Vargas, Astrid; Simón, Miguel A.; Zorrilla, Irene; Muñoz, Alvaro; Palomares, Francisco; López-Bao, Jose V.; Pastor, Josep; Tandon, Ravi; Willi, Barbara; Hofmann-Lehmann, Regina; Lutz, Hans

2009-01-01

Background The Iberian lynx (Lynx pardinus) is considered the most endangered felid species in the world. In order to save this species, the Spanish authorities implemented a captive breeding program recruiting lynxes from the wild. In this context, a retrospective survey on prevalence of selected feline pathogens in free-ranging lynxes was initiated. Methodology/ Principal Findings We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. With the exception of feline immunodeficiency virus (FIV), evidence of infection by all tested feline pathogens was found in Iberian lynxes. Fourteen lynxes were feline leukemia virus (FeLV) provirus-positive; eleven of these were antigenemic (FeLV p27 positive). All 14 animals tested negative for other viral infections. During a six-month period in 2007, six of the provirus-positive antigenemic lynxes died. Infection with FeLV but not with other infectious agents was associated with mortality (p<0.001). Sequencing of the FeLV surface glycoprotein gene revealed a common origin for ten of the eleven samples. The ten sequences were closely related to FeLV-A/61E, originally isolated from cats in the USA. Endogenous FeLV sequences were not detected. Conclusions/Significance It was concluded that the FeLV infection most likely originated from domestic cats invading the lynx's habitats. Data available regarding the time frame, co-infections, and outcome of FeLV-infections suggest that, in contrast to the domestic cat, the FeLV strain affecting the lynxes in 2007 is highly virulent to this species. Our data argue strongly for vaccination of lynxes and domestic cats in and around lynx's habitats in order to prevent further spread of the virus as well as reduction the domestic cat population if the lynx population is to be maintained. PMID:19270739

VISA--Vector Integration Site Analysis server: a web-based server to rapidly identify retroviral integration sites from next-generation sequencing.

PubMed

Hocum, Jonah D; Battrell, Logan R; Maynard, Ryan; Adair, Jennifer E; Beard, Brian C; Rawlings, David J; Kiem, Hans-Peter; Miller, Daniel G; Trobridge, Grant D

2015-07-07

Analyzing the integration profile of retroviral vectors is a vital step in determining their potential genotoxic effects and developing safer vectors for therapeutic use. Identifying retroviral vector integration sites is also important for retroviral mutagenesis screens. We developed VISA, a vector integration site analysis server, to analyze next-generation sequencing data for retroviral vector integration sites. Sequence reads that contain a provirus are mapped to the human genome, sequence reads that cannot be localized to a unique location in the genome are filtered out, and then unique retroviral vector integration sites are determined based on the alignment scores of the remaining sequence reads. VISA offers a simple web interface to upload sequence files and results are returned in a concise tabular format to allow rapid analysis of retroviral vector integration sites.

RNA helicase A modulates translation of HIV-1 and infectivity of progeny virions

PubMed Central

Bolinger, Cheryl; Sharma, Amit; Singh, Deepali; Yu, Lianbo; Boris-Lawrie, Kathleen

2010-01-01

Retroviruses rely on host RNA-binding proteins to modulate various steps in their replication. Previously several animal retroviruses were determined to mediate Dhx9/RNA helicase A (RHA) interaction with a 5′ terminal post-transcriptional control element (PCE) for efficient translation. Herein PCE reporter assays determined HTLV-1 and HIV-1 RU5 confer orientation-dependent PCE activity. The effect of Dhx9/RHA down-regulation and rescue with siRNA-resistant RHA on expression of HIV-1NL4–3 provirus determined that RHA is necessary for efficient HIV-1 RNA translation and requires ATPase-dependent helicase function. Quantitative analysis determined HIV-1 RNA steady-state and cytoplasmic accumulation were not reduced; rather the translational activity of viral RNA was reduced. Western blotting determined that RHA-deficient virions assemble with Lys-tRNA synthetase, exhibit processed reverse transcriptase and contain similar level of viral RNA, but they are poorly infectious on primary lymphocytes and HeLa cells. The results demonstrate RHA is an important host factor within the virus-producer cell and within the viral particle. The identification of RHA-dependent PCE activity in cellular junD RNA and in six of seven genera of Retroviridae suggests conservation of this translational control mechanism among vertebrates, and convergent evolution of Retroviridae to utilize this host mechanism. PMID:20007598

A systematic evaluation of expression of HERV-W elements; influence of genomic context, viral structure and orientation

PubMed Central

2011-01-01

Background One member of the W family of human endogenous retroviruses (HERV) appears to have been functionally adopted by the human host. Nevertheless, a highly diversified and regulated transcription from a range of HERV-W elements has been observed in human tissues and cells. Aberrant expression of members of this family has also been associated with human disease such as multiple sclerosis (MS) and schizophrenia. It is not known whether this broad expression of HERV-W elements represents transcriptional leakage or specific transcription initiated from the retroviral promoter in the long terminal repeat (LTR) region. Therefore, potential influences of genomic context, structure and orientation on the expression levels of individual HERV-W elements in normal human tissues were systematically investigated. Results Whereas intronic HERV-W elements with a pseudogene structure exhibited a strong anti-sense orientation bias, intronic elements with a proviral structure and solo LTRs did not. Although a highly variable expression across tissues and elements was observed, systematic effects of context, structure and orientation were also observed. Elements located in intronic regions appeared to be expressed at higher levels than elements located in intergenic regions. Intronic elements with proviral structures were expressed at higher levels than those elements bearing hallmarks of processed pseudogenes or solo LTRs. Relative to their corresponding genes, intronic elements integrated on the sense strand appeared to be transcribed at higher levels than those integrated on the anti-sense strand. Moreover, the expression of proviral elements appeared to be independent from that of their corresponding genes. Conclusions Intronic HERV-W provirus integrations on the sense strand appear to have elicited a weaker negative selection than pseudogene integrations of transcripts from such elements. Our current findings suggest that the previously observed diversified and tissue-specific expression of elements in the HERV-W family is the result of both directed transcription (involving both the LTR and internal sequence) and leaky transcription of HERV-W elements in normal human tissues. PMID:21226900

Digital detection of endonuclease mediated gene disruption in the HIV provirus

PubMed Central

Sedlak, Ruth Hall; Liang, Shu; Niyonzima, Nixon; De Silva Feelixge, Harshana S.; Roychoudhury, Pavitra; Greninger, Alexander L.; Weber, Nicholas D.; Boissel, Sandrine; Scharenberg, Andrew M.; Cheng, Anqi; Magaret, Amalia; Bumgarner, Roger; Stone, Daniel; Jerome, Keith R.

2016-01-01

Genome editing by designer nucleases is a rapidly evolving technology utilized in a highly diverse set of research fields. Among all fields, the T7 endonuclease mismatch cleavage assay, or Surveyor assay, is the most commonly used tool to assess genomic editing by designer nucleases. This assay, while relatively easy to perform, provides only a semi-quantitative measure of mutation efficiency that lacks sensitivity and accuracy. We demonstrate a simple droplet digital PCR assay that quickly quantitates a range of indel mutations with detection as low as 0.02% mutant in a wild type background and precision (≤6%CV) and accuracy superior to either mismatch cleavage assay or clonal sequencing when compared to next-generation sequencing. The precision and simplicity of this assay will facilitate comparison of gene editing approaches and their optimization, accelerating progress in this rapidly-moving field. PMID:26829887

Extended Minus-Strand DNA as Template for R-U5-Mediated Second-Strand Transfer in Recombinational Rescue of Primer Binding Site-Modified Retroviral Vectors

PubMed Central

Mikkelsen, Jacob Giehm; Lund, Anders H.; Dybkær, Karen; Duch, Mogens; Pedersen, Finn Skou

1998-01-01

We have previously demonstrated recombinational rescue of primer binding site (PBS)-impaired Akv murine leukemia virus-based vectors involving initial priming on endogenous viral sequences and template switching during cDNA synthesis to obtain PBS complementarity in second-strand transfer of reverse transcription (Mikkelsen et al., J. Virol. 70:1439–1447, 1996). By use of the same forced recombination system, we have now found recombinant proviruses of different structures, suggesting that PBS knockout vectors may be rescued through initial priming on endogenous virus RNA, read-through of the mutated PBS during minus-strand synthesis, and subsequent second-strand transfer mediated by the R-U5 complementarity of the plus strand and the extended minus-strand DNA acceptor template. Mechanisms for R-U5-mediated second-strand transfer and its possible role in retrovirus replication and evolution are discussed. PMID:9499117

Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen?

PubMed Central

Allison, Andrew B.; Keel, M. Kevin; Philips, Jamie E.; Cartoceti, Andrew N.; Munk, Brandon A.; Nemeth, Nicole M.; Welsh, Trista I.; Thomas, Jesse M.; Crum, James M.; Lichtenwalner, Anne B.; Fadly, Aly M.; Zavala, Guillermo; Holmes, Edward C.; Brown, Justin D.

2014-01-01

Lymphoproliferative disease virus (LPDV) is an exogenous oncogenic retrovirus that induces lymphoid tumors in some galliform species of birds. Historically, outbreaks of LPDV have been reported from Europe and Israel. Although the virus has previously never been detected in North America, herein we describe the widespread distribution, genetic diversity, pathogenesis, and evolution of LPDV in the United States. Characterization of the provirus genome of the index LPDV case from North America demonstrated an 88% nucleotide identity to the Israeli prototype strain. Although phylogenetic analysis indicated that the majority of viruses fell into a single North American lineage, a small subset of viruses from South Carolina were most closely related to the Israeli prototype. These results suggest that LPDV was transferred between continents to initiate outbreaks of disease. However, the direction (New World to Old World or vice versa), mechanism, and time frame of the transcontinental spread currently remain unknown. PMID:24503062

Generation of neutralising antibodies against porcine endogenous retroviruses (PERVs)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaulitz, Danny; Fiebig, Uwe; Eschricht, Magdalena

2011-03-01

Antibodies neutralising porcine endogenous retroviruses (PERVs) were induced in different animal species by immunisation with the transmembrane envelope protein p15E. These antibodies recognised epitopes, designated E1, in the fusion peptide proximal region (FPPR) of p15E, and E2 in the membrane proximal external region (MPER). E2 is localised in a position similar to that of an epitope in the transmembrane envelope protein gp41 of the human immunodeficiency virus-1 (HIV-1), recognised by the monoclonal antibody 4E10 that is broadly neutralising. To detect neutralising antibodies specific for PERV, a novel assay was developed, which is based on quantification of provirus integration by real-timemore » PCR. In addition, for the first time, highly effective neutralising antibodies were obtained by immunisation with the surface envelope protein of PERV. These data indicate that neutralising antibodies can be induced by immunisation with both envelope proteins.« less

HIV Integration at Certain Sites in Host DNA is Linked to the Expansion and Persistence of Infected Cells | Center for Cancer Research

Cancer.gov

When the Human Immunodeficiency Virus (HIV) infects a cell, the virus inserts a copy of its genetic material into the host cell’s DNA. The inserted genetic material, which is also called a provirus, is used to produce new viruses. Because the viral DNA can be inserted at many sites in the host cell DNA, the site of integration marks each infected cell. Patients infected with HIV are currently treated with combined antiretroviral therapy (cART), which prevents viral replication in the majority of treated patients. When cART is initiated, most HIV-infected cells die in one or two days, and more of the infected cells die over a period of weeks to months. However there are some long-lived infected cells that do not die, which prevents patients from being cured.

HIV Integration at Certain Sites in Host DNA Is Linked to the Expansion and Persistence of Infected Cells | Poster

Cancer.gov

Editor’s note: This article was originally published on the Center for Cancer Research website. When the Human Immunodeficiency Virus (HIV) infects a cell, the virus inserts a copy of its genetic material into the host cell’s DNA. The inserted genetic material, which is also called a provirus, is used to produce new viruses. Because the viral DNA can be inserted at many sites in the host cell DNA, the site of integration marks each infected cell. Patients infected with HIV are currently treated with combined antiretroviral therapy (cART), which prevents viral replication in the majority of treated patients. When cART is initiated, most HIV-infected cells die in one or two days, and more of the infected cells die over a period of weeks to months. However there are some long-lived infected cells that do not die, which prevents patients from being cured.

[The detection and sequence analysis of the simian T-lymphotrophic retrovirus (STLV-1 Papio) by using the polymerase chain reaction].

PubMed

D'iachenko, A G; Dzhalagoniia, B E; Kapanadze, B I

1993-01-01

The gene amplification technique was used for detection and sequence analysis of STLV-1 Papio proviral DNA. The polymerase chain reaction was performed with a primer pair at tax region of HTLV-1, 7336-7354, sense strand, and 7516-7494, antisense strand. One microgram of DNAs isolated from LUG-4 cells and autopsies was used in a reaction volume of 50 microliters involving 30 cycles of amplifications. The reaction product was blunt-end cloned into pUC19 cut with Smal. The sequence was done with T7-polymerase using 32P-dATR as a label. Our results indicate that STLV-1 Papio provirus is actually present in the cells of a lymphoid cell line and tumor cells of lymphomatous monkeys. There are some differences between STLV-1 Papio and reported sequences of HTLV-1 and STLV-1.

Partial regulatory T cell depletion prior to acute feline immunodeficiency virus infection does not alter disease pathogenesis.

PubMed

Mikkelsen, S Rochelle; Long, Julie M; Zhang, Lin; Galemore, Erin R; VandeWoude, Sue; Dean, Gregg A

2011-02-25

Feline immunodeficiency virus (FIV) infection in cats follows a disease course similar to HIV-1, including a short acute phase characterized by high viremia, and a prolonged asymptomatic phase characterized by low viremia and generalized immune dysfunction. CD4(+)CD25(hi)FoxP3(+) immunosuppressive regulatory T (Treg) cells have been implicated as a possible cause of immune dysfunction during FIV and HIV-1 infection, as they are capable of modulating virus-specific and inflammatory immune responses. Additionally, the immunosuppressive capacity of feline Treg cells has been shown to be increased during FIV infection. We have previously shown that transient in vivo Treg cell depletion during asymptomatic FIV infection reveals FIV-specific immune responses suppressed by Treg cells. In this study, we sought to determine the immunological influence of Treg cells during acute FIV infection. We asked whether Treg cell depletion prior to infection with the highly pathogenic molecular clone FIV-C36 in cats could alter FIV pathogenesis. We report here that partial Treg cell depletion prior to FIV infection does not significantly change provirus, viremia, or CD4(+) T cell levels in blood and lymphoid tissues during the acute phase of disease. The effects of anti-CD25 mAb treatment are truncated in cats acutely infected with FIV-C36 as compared to chronically infected cats or FIV-naïve cats, as Treg cell levels were heightened in all treatment groups included in the study within two weeks post-FIV infection. Our findings suggest that the influence of Treg cell suppression during FIV pathogenesis is most prominent after Treg cells are activated in the environment of established FIV infection.

The Alphabet Soup of HIV Reservoir Markers.

PubMed

Sharaf, Radwa R; Li, Jonathan Z

2017-04-01

Despite the success of antiretroviral therapy in suppressing HIV, life-long therapy is required to avoid HIV reactivation from long-lived viral reservoirs. Currently, there is intense interest in searching for therapeutic interventions that can purge the viral reservoir to achieve complete remission in HIV patients off antiretroviral therapy. The evaluation of such interventions relies on our ability to accurately and precisely measure the true size of the viral reservoir. In this review, we assess the most commonly used HIV reservoir assays, as a clear understanding of the strengths and weaknesses of each is vital for the accurate interpretation of results and for the development of improved assays. The quantification of intracellular or plasma HIV RNA or DNA levels remains the most commonly used tests for the characterization of the viral reservoir. While cost-effective and high-throughput, these assays are not able to differentiate between replication-competent or defective fractions or quantify the number of infected cells. Viral outgrowth assays provide a lower bound for the fraction of cells that can produce infectious virus, but these assays are laborious, expensive and substantially underestimate the potential reservoir of replication-competent provirus. Newer assays are now available that seek to overcome some of these problems, including full-length proviral sequencing, inducible HIV RNA assays, ultrasensitive p24 assays and murine adoptive transfer techniques. The development and evaluation of strategies for HIV remission rely upon our ability to accurately and precisely quantify the size of the remaining viral reservoir. At this time, all current HIV reservoir assays have drawbacks such that combinations of assays are generally needed to gain a more comprehensive view of the viral reservoir. The development of novel, rapid, high-throughput assays that can sensitively quantify the levels of the replication-competent HIV reservoir is still needed.

Analysis of single-nucleotide polymorphisms in the APOBEC3H gene of domestic cats (Felis catus) and their association with the susceptibility to feline immunodeficiency virus and feline leukemia virus infections.

PubMed

de Castro, Fernanda Luz; Junqueira, Dennis Maletich; de Medeiros, Rúbia Marília; da Silva, Tailene Rabello; Costenaro, Jamile Girardi; Knak, Marcus Braga; de Matos Almeida, Sabrina Esteves; Campos, Fabrício Souza; Roehe, Paulo Michel; Franco, Ana Cláudia

2014-10-01

Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are widely distributed retroviruses that infect domestic cats (Felis catus). Restriction factors are proteins that have the ability to hamper retroviruses' replication and are part of the conserved mechanisms of anti-viral immunity of mammals. The APOBEC3 protein family is the most studied class of restriction factors; they are cytidine deaminases that generate hypermutations in provirus DNA during reverse transcription, thus causing hypermutations in the viral genome, hindering virus replication. One of the feline APOBEC3 genes, named APOBEC3H, encodes two proteins (APOBEC3H and APOBEC3CH). In other mammals, APOBEC3H single-nucleotide polymorphisms (SNPs) can alter the stability and cellular localization of the encoded protein, thus influencing its subcellular localization and reducing its anti-viral effect. In cats, the association of APOBEC3H SNPs with susceptibility to retroviral infections was not yet demonstrated. Therefore, this study aimed the investigation on the variability of APOBEC3H and the possible association with FIV/FeLV infections. DNA obtained from whole blood of fifty FIV- and/or FeLV-infected cats and fifty-nine FIV- and/or FeLV-uninfected cats were used as templates to amplify two different regions of the APOBEC3H, with subsequent sequencing and analysis. The first region was highly conserved among all samples, while in the second, six single-nucleotide variation points were identified. One of the SNPs, A65S (A65I), was significantly correlated with the susceptibility to FIV and/or FeLV infections. On the other hand, the haplotype analysis showed that the combination "GGGGCC" was positively correlated with the lack of FIV and/or FeLV infections. Our results indicate that, as previously shown in other mammals, variability of restriction factors may contribute to susceptibility of domestic cats to retroviral infections; however, these results should be confirmed by more extensive analysis and in vitro experiments. Copyright © 2014 Elsevier B.V. All rights reserved.

Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers

PubMed Central

Policicchio, Benjamin B.; Xu, Cuiling; Brocca-Cofano, Egidio; Raehtz, Kevin D.; He, Tianyu; Ma, Dongzhu; Li, Hui; Haret-Richter, George S.; Dunsmore, Tammy; Trichel, Anita; Mellors, John W.; Hahn, Beatrice H.; Shaw, George M.; Ribeiro, Ruy M.; Pandrea, Ivona; Apetrei, Cristian

2016-01-01

Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the “shock and kill” strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD) to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35–50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml) peaking at 5–12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml) that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control. Comparison of the patterns of virus rebound after RMD administration and CD8+ cell depletion suggested that RMD impact on T cells is only transient and does not irreversibly alter the ability of SIV-specific T cells to control the reactivated virus. PMID:27632364

Increased expression of activated pSTAT3 and PIM-1 in the pulmonary vasculature of experimental congenital diaphragmatic hernia.

PubMed

Hofmann, Alejandro D; Takahashi, Toshiaki; Duess, Johannes; Gosemann, Jan-Hendrik; Puri, Prem

2015-06-01

Signal transducer and activator of transcription (STAT) protein family (STAT1-6) regulates diverse cellular processes. Recently, the isoform STAT3 has been implicated to play a central role in the pathogenesis of pulmonary hypertension (PH). In human PH activated STAT3 (pSTAT3) was shown to directly trigger expression of the provirus integration site for Moloney murine leukemia virus (Pim-1), which promotes proliferation and resistance to apoptosis in SMCs. We designed this study to investigate the hypothesis that pSTAT3 and Pim-1 pulmonary vascular expression is increased in nitrofen-induced CDH. Pregnant rats were exposed to nitrofen or vehicle on D9.5. Fetuses were sacrificed on D21 and divided into nitrofen (n=16) and control group (n=16). QRT-PCR, western blotting, and confocal-immunofluorescence were performed to determine pulmonary gene and protein expression levels of pSTAT3 and Pim-1. Pulmonary Pim-1 gene expression was significantly increased in the CDH group compared to controls. Western blotting and confocal-microscopy confirmed increased pulmonary protein expression of Pim-1 and increased activation of pSTAT3 in CDH lungs compared to controls. Markedly increased gene and protein expression of Pim-1 and activated pSTAT3 in the pulmonary vasculature of nitrofen-induced CDH lungs suggest that pSTAT3 and Pim-1 are important mediators of PH in nitrofen-induced CDH. Copyright © 2015. Published by Elsevier Inc.

MicroRNA-101-3p suppresses cell proliferation, invasion and enhances chemotherapeutic sensitivity in salivary gland adenoid cystic carcinoma by targeting Pim-1

PubMed Central

Liu, Xiao-Yu; Liu, Zhi-Jian; He, Hong; Zhang, Chen; Wang, Yun-Long

2015-01-01

MicroRNAs (miRNAs) play critical roles in carcinogenesis and tumor progression. Recent research has revealed miR-101-3p as an important regulator in several cancers. Nevertheless, its function in salivary gland Adenoid cystic carcinoma (ACC), a relatively rare malignance with poor long-term survival rate arisen in head and neck region, remain unknown. In this study, down-regulated miR-101-3p expression was detected in ACC tissues and ACC cell lines with high potential for metastasis. Ectopic expression of miR-101-3p significantly repressed the invasion, proliferation, colony formation, and formation of nude mice xenografts and induced potent apoptosis in ACC cell lines. The provirus integration site for Moloney murine leukemia virus 1 (Pim-1) oncogene was subsequently confirmed as a direct target gene of miR-101-3p in ACC. Functional restoration assays revealed that miR-101-3p inhibits cell growth and invasion by directly decreasing Pim-1 expression. Protein levels of Survivin, Cyclin D1 and β-catenin were also down-regulated by miR-101-3p. miR-101-3p enhanced the sensitivity of cisplatin in ACC cell lines. Taken together, our results demonstrate that the novel miR-101-3p/Pim-1 axis provides excellent insights into the carcinogenesis and tumor progression of ACC and may be a promising therapeutic target for this type of cancer. PMID:26693056

Exogenous JH and ecdysteroid applications alter initiation of polydnaviral replication in an endoparasitoid wasp, Cotesia plutellae (Braconidae: Hymenoptera).

PubMed

Park, Bokri; Kim, Yonggyun

2011-06-01

Polydnaviruses are a group of double-stranded DNA viruses and are symbiotically associated with some ichneumonoid wasps. As proviruses, the replication of polydnaviruses occurs in the female reproductive organ at the pupal stage. This study analyzed the effects of two developmental hormones, juvenile hormone (JH) and ecdysteroid, on the viral replication of Cotesia plutellae bracovirus (CpBV). All 23 CpBV segments identified contained a conserved excision/rejoining site ('AGCTTT') from their proviral segments. Using quantitative real-time PCR based on this excision/rejoining site marker, initiation of CpBV replication was determined to have occurred on day 4 on the pupal stage. Pyriproxyfen, a JH agonist, significantly inhibited adult emergence of C. plutellae, whereas RH5992, an ecdysteroid agonist, had no inhibitory effect. Although RH5992 had no effect dose on adult development, it significantly accelerated viral replication. The results of immunoblotting assays against viral coat proteins support the effects of the hormone agonists on viral replication.

von Hippel–Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step

PubMed Central

Mousnier, Aurélie; Kubat, Nicole; Massias-Simon, Aurélie; Ségéral, Emmanuel; Rain, Jean-Christophe; Benarous, Richard; Emiliani, Stéphane; Dargemont, Catherine

2007-01-01

HIV-1 integrase, the viral enzyme responsible for provirus integration into the host genome, can be actively degraded by the ubiquitin–proteasome pathway. Here, we identify von Hippel–Lindau binding protein 1(VBP1), a subunit of the prefoldin chaperone, as an integrase cellular binding protein that bridges interaction between integrase and the cullin2 (Cul2)-based von Hippel–Lindau (VHL) ubiquitin ligase. We demonstrate that VBP1 and Cul2/VHL are required for proper HIV-1 expression at a step between integrase-dependent proviral integration into the host genome and transcription of viral genes. Using both an siRNA approach and Cul2/VHL mutant cells, we show that VBP1 and the Cul2/VHL ligase cooperate in the efficient polyubiquitylation of integrase and its subsequent proteasome-mediated degradation. Results presented here support a role for integrase degradation by the prefoldin–VHL–proteasome pathway in the integration–transcription transition of the viral replication cycle. PMID:17698809

Establishment of a novel feline leukemia virus (FeLV)-negative B-cell cell line from a cat with B-cell lymphoma.

PubMed

Mochizuki, Hiroyuki; Takahashi, Masashi; Nishigaki, Kazuo; Ide, Tetsuya; Goto-Koshino, Yuko; Watanabe, Shinya; Sato, Hirofumi; Sato, Masahiko; Kotera, Yukiko; Fujino, Yasuhito; Ohno, Koichi; Uchida, Kazuyuki; Tsujimoto, Hajime

2011-04-15

We established a novel feline B-cell line, MS4, from the neoplastic pleural effusion of a cat with cutaneous B-cell lymphoma. Immunophenotype staining of the MS4 cells was positive for CD20, CD79α, and IgA and negative for CD3, CD4, CD5, CD8α, CD18, CD21, CD22, IgM, IgG, Ig light chain, and MHC class II. PCR analysis for immunoglobulin heavy chain gene rearrangements revealed a monoclonal rearrangement, whereas no clonal rearrangement of the T-cell receptor γ gene was detected. Southern blotting with an exogenous feline leukemia virus (FeLV) U3 probe revealed no integration of exogenous FeLV provirus. The MS4 cell line is the first FeLV-negative feline B-cell lymphoma cell line, and may be used to investigate the pathogenesis of spontaneously occurring feline lymphoma and the development of new therapies. Copyright © 2011 Elsevier B.V. All rights reserved.

Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen?

PubMed

Allison, Andrew B; Kevin Keel, M; Philips, Jamie E; Cartoceti, Andrew N; Munk, Brandon A; Nemeth, Nicole M; Welsh, Trista I; Thomas, Jesse M; Crum, James M; Lichtenwalner, Anne B; Fadly, Aly M; Zavala, Guillermo; Holmes, Edward C; Brown, Justin D

2014-02-01

Lymphoproliferative disease virus (LPDV) is an exogenous oncogenic retrovirus that induces lymphoid tumors in some galliform species of birds. Historically, outbreaks of LPDV have been reported from Europe and Israel. Although the virus has previously never been detected in North America, herein we describe the widespread distribution, genetic diversity, pathogenesis, and evolution of LPDV in the United States. Characterization of the provirus genome of the index LPDV case from North America demonstrated an 88% nucleotide identity to the Israeli prototype strain. Although phylogenetic analysis indicated that the majority of viruses fell into a single North American lineage, a small subset of viruses from South Carolina were most closely related to the Israeli prototype. These results suggest that LPDV was transferred between continents to initiate outbreaks of disease. However, the direction (New World to Old World or vice versa), mechanism, and time frame of the transcontinental spread currently remain unknown. © 2013 Published by Elsevier Inc.

Retrovirus Integration Database (RID): a public database for retroviral insertion sites into host genomes.

PubMed

Shao, Wei; Shan, Jigui; Kearney, Mary F; Wu, Xiaolin; Maldarelli, Frank; Mellors, John W; Luke, Brian; Coffin, John M; Hughes, Stephen H

2016-07-04

The NCI Retrovirus Integration Database is a MySql-based relational database created for storing and retrieving comprehensive information about retroviral integration sites, primarily, but not exclusively, HIV-1. The database is accessible to the public for submission or extraction of data originating from experiments aimed at collecting information related to retroviral integration sites including: the site of integration into the host genome, the virus family and subtype, the origin of the sample, gene exons/introns associated with integration, and proviral orientation. Information about the references from which the data were collected is also stored in the database. Tools are built into the website that can be used to map the integration sites to UCSC genome browser, to plot the integration site patterns on a chromosome, and to display provirus LTRs in their inserted genome sequence. The website is robust, user friendly, and allows users to query the database and analyze the data dynamically. https://rid.ncifcrf.gov ; or http://home.ncifcrf.gov/hivdrp/resources.htm .

Humoral and Innate Antiviral Immunity as Tools to Clear Persistent HIV Infection.

PubMed

Ferrari, Guido; Pollara, Justin; Tomaras, Georgia D; Haynes, Barton F

2017-03-15

Human immunodeficiency virus (HIV) type 1 uses the CD4 molecule as its principal receptor to infect T cells. HIV-1 integrates its viral genome into the host cell, leading to persistent infection wherein HIV-1 can remain transcriptionally silent in latently infected CD4+ T cells. On reactivation of replication-competent provirus, HIV-1 envelope glycoproteins (Env) are expressed and accumulate on the cell surface, allowing infected cells to be detected and targeted by endogenous immune responses or immune interventions. HIV-1 Env-specific antibodies have the potential to bind HIV-1 cell surface Env and promote elimination of infected CD4+ T cells by recruiting cytotoxic effector cells, such as natural killer cells, monocytes, and polymorphonuclear cells. Harnessing humoral and innate cellular responses has become one focus of research to develop innovative strategies to recruit and redirect cytotoxic effector cells to eliminate the HIV-1 latently infected CD4+ T-cell reservoir. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Viral discovery in the invasive Australian cane toad (Rhinella marina) using metatranscriptomic and genomic approaches.

PubMed

Russo, Alice G; Eden, John-Sebastian; Enosi Tuipulotu, Daniel; Shi, Mang; Selechnik, Daniel; Shine, Richard; Rollins, Lee Ann; Holmes, Edward C; White, Peter A

2018-06-13

Cane toads are a notorious invasive species, inhabiting over 1.2 million km 2 of Australia and threatening native biodiversity. Release of pathogenic cane toad viruses is one possible biocontrol strategy yet is currently hindered by the poorly-described cane toad virome. Metatranscriptomic analysis of 16 cane toad livers revealed the presence of a novel and full-length picornavirus, Rhimavirus A (RhiV-A), a member of a reptile and amphibian specific-cluster of the Picornaviridae basal to the Kobuvirus -like group. In the combined liver transcriptome, we also identified a complete genome sequence of a distinct epsilonretrovirus, R. marina endogenous retrovirus (RMERV). The recently sequenced cane toad genome contains eight complete RMERV proviruses, as well as 21 additional truncated insertions. The oldest full length RMERV provirus was estimated to have inserted 1.9 MYA. To screen for these viral sequences in additional toads, we analysed publicly available transcriptomes from six diverse Australian locations. RhiV-A transcripts were identified in toads sampled from three locations across 1,000 km of Australia, stretching to the current Western Australia (WA) invasion front, whilst RMERV transcripts were observed at all six sites. Lastly, we scanned the cane toad genome for non-retroviral endogenous viral elements, finding three sequences related to small DNA viruses in the family Circoviridae This shows ancestral circoviral infection with subsequent genomic integration. The identification of these current and past viral infections enriches our knowledge of the cane toad virome, an understanding of which will facilitate future work on infection and disease in this important invasive species. Importance Cane toads are poisonous amphibians which were introduced to Australia in 1935 for insect control. Since then, their population has increased dramatically, and they now threat many native Australian species. One potential method to control the population is to release a cane toad virus with high mortality, yet few cane toad viruses have been characterised. This study samples cane toads from different Australian locations and uses an RNA sequencing and computational approach to find new viruses. We report novel complete picornavirus and retrovirus sequences which were genetically similar to viruses infecting frogs, reptiles and fish. Using data generated in other studies, we show that these viral sequences are present in cane toads from distinct Australian locations. Three sequences related to circoviruses were also found in the toad genome. The identification of new viral sequences will aid future studies which investigate their prevalence and potential as agents for biocontrol. Copyright © 2018 American Society for Microbiology.

Myelodysplastic syndromes and acute myeloid leukemia in cats infected with feline leukemia virus clone33 containing a unique long terminal repeat.

PubMed

Hisasue, Masaharu; Nagashima, Naho; Nishigaki, Kazuo; Fukuzawa, Isao; Ura, Shigeyoshi; Katae, Hiromi; Tsuchiya, Ryo; Yamada, Takatsugu; Hasegawa, Atsuhiko; Tsujimoto, Hajime

2009-03-01

Feline leukemia virus (FeLV) clone33 was obtained from a domestic cat with acute myeloid leukemia (AML). The long terminal repeat (LTR) of this virus, like the LTRs present in FeLV from other cats with AML, differs from the LTRs of other known FeLV in that it has 3 tandem direct 47-bp repeats in the upstream region of the enhancer (URE). Here, we injected cats with FeLV clone33 and found 41% developed myelodysplastic syndromes (MDS) characterized by peripheral blood cytopenias and dysplastic changes in the bone marrow. Some of the cats with MDS eventually developed AML. The bone marrow of the majority of cats with FeLV clone33 induced MDS produced fewer erythroid and myeloid colonies upon being cultured with erythropoietin or granulocyte-macrophage colony-stimulating factor (GM-SCF) than bone marrow from normal control cats. Furthermore, the bone marrow of some of the cats expressed high-levels of the apoptosis-related genes TNF-alpha and survivin. Analysis of the proviral sequences obtained from 13 cats with naturally occurring MDS reveal they also bear the characteristic URE repeats seen in the LTR of FeLV clone33 and other proviruses from cats with AML. Deletions and mutations within the enhancer elements are frequently observed in naturally occurring MDS as well as AML. These results suggest that FeLV variants that bear URE repeats in their LTR strongly associate with the induction of both MDS and AML in cats.

Molecular and epidemiological characterization of HIV-1 subtypes among Libyan patients.

PubMed

Daw, Mohamed A; El-Bouzedi, Abdallah; Ahmed, Mohamed O; Dau, Aghnyia A

2017-04-28

The epidemiological and clinical aspects of human immunodeficiency virus subtypes are of great interest worldwide. These subtypes are rarely studied in North African countries. Libya is a large country with the longest coast on the Mediterranean Sea, facing the Southern European countries. Studies on the characterization of HIV-1 subtypes are limited in Libya. This study aimed to determine the magnitude of the HIV problem among the Libyan population and to better understand the genetic diversity and the epidemiologic dynamics of HIV 1, as well as to correlate that with the risk factors involved. A total of 159 HIV-1 strains were collected from 814 HIV positive patients from the four Libyan regions during a 16-year period (1995-2010). To determine the HIV-1 subtypes, genetic analysis and molecular sequencing were carried out using provirus polygene. Epidemiologic and demographic information was obtained from each participant and correlated with HIV-1 subtypes using logistic regression. The overall prevalence of HIV among Libyans ranged from 5 to 10 per 100,000 during the study period. It was higher among intravenous drug users (IVDUs) (53.9%), blood recipients (25.9%) and heterosexuals (17.6%) than by vertical transmission (2.6%). Prevalence was higher among males aged 20-40 years (M:F 1:6, P > 0.001). Among the 159 strains of HIV-1 available for typing, 117 strains (73.6%) were subtype B, 29 (18.2%) were CRF02_AG, and 13 (8.2%) were subtype A. HIV-1 subtype B was the most prevalent all over the country, and it was more prevalent in the Northern region, particularly among IVDUs (P < 0.001). GRF02_AG was common in the Eastern region, particularly among blood recipients while subtype A emerged in the Western region, particularly among IVDUs. HIV-1 infection is emerging in Libya with a shifting prevalence of subtypes associated with the changing epidemiology of HIV-1 among risk groups. A genetic analysis of HIV-1 strains demonstrated low subtype heterogeneity with the evolution of subtype B, and CRF_20 AG, as well as HIV-1 subtype A. Our study highlights the importance of expanded surveillance programs to control HIV infection and the necessity of introducing public health strategies to target the risk groups, particularly IVDUs.

Different thresholds of T cell activation regulate FIV infection of CD4{sup +}CD25{sup +} and CD4{sup +}CD25{sup -} cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joshi, Anjali; Garg, Himanshu; Tompkins, Mary B.

2005-05-10

Cellular activation plays an important role in retroviral replication. Previously, we have shown that CD4{sup +}CD25{sup +} T cells by the virtue of their partially activated phenotype represent ideal candidates for a productive feline immunodeficiency virus (FIV) infection. In the present study, we extended our previous observations with regard to FIV replication in CD4{sup +}CD25{sup +} and CD4{sup +}CD25{sup -} cells under different stimulation conditions. Both CD4{sup +}CD25{sup +} and CD4{sup +}CD25{sup -} cells remain latently infected in the absence of IL-2 or concanvalinA (ConA), respectively; harboring a replication competent provirus capable of reactivation several days post-infection. While CD4{sup +}CD25{supmore » +} cells require low levels of exogenous IL-2 and virus inputs for an efficient FIV replication, CD4{sup +}CD25{sup -} T cells can only be productively infected in the presence of either high concentrations of IL-2 or high virus titers, even in the absence of mitogenic stimulation. Interestingly, while high virus input activates CD4{sup +}CD25{sup -} cells to replicate FIV, it induces apoptosis in a high percentage of CD4{sup +}CD25{sup +} T cells. High IL-2 concentrations but not high virus inputs lead to surface upregulation of CD25 and significant cellular proliferation in CD4{sup +}CD25{sup -} cells. These results suggest that CD4{sup +}CD25{sup +} and CD4{sup +}CD25{sup -} T cells have different activation requirements which can be modulated by both viral and cytokine stimuli to reach threshold activation levels in order to harbor a productive FIV infection. This holds implications in vivo for CD4{sup +}CD25{sup +} and CD4{sup +}CD25{sup -} cells to serve as potential reservoirs of a productive and latent FIV infection.« less

Prevalence and phylogenetic analysis of HTLV-1 in a segregated population in Iran.

PubMed

Rafatpanah, Houshang; Torkamani, Mahmood; Valizadeh, Narges; Vakili, Rosita; Meshkani, Baratali; Khademi, Hassan; Gerayli, Sina; Mozhgani, Sayed Hamid Reza; Rezaee, Seyed Abdolrahim

2016-07-01

Human T-lymphotropic virus type 1 (HTLV-1) infection is an important health issue that affects a variety of endemic areas. The Khorasan province, mainly its capital Mashhad in northeastern Iran, was reported to be as one of these endemic regions. Torbat-e Heydarieh, a large city Southwest border to Mashhad with a segregated population was investigated for the prevalence and associated risk factors of HTLV-1 infection in 400 randomly selected individuals. Blood samples were tested for the presence of HTLV-1 antibodies via the ELISA method and then were confirmed by an Immunoblot test. For the presence of HTLV-1 in lymphocytes of infected subjects, PCR was performed on LTR and TAX regions. DNA sequencing of LTR fragment was also carried out to determine the phylogenetic of HTLV-1, using the Maximum likelihood method. HTLV-1 sero-reactivity (sero-prevalence) among the study population was 2% (8/400), of which 1.25% had HTLV-1 provirus in lymphocytes (actual prevalence). HTLV-1 infection was significantly associated with the age, marital status, and history of blood transfusion (P < 0.05). However, there were no statistical differences between HTLV-1 infection, and gender, surgery, and hospitalization. In regression analysis, age showed the most significant correlation with the infection (P = 0.006, OR = 4.33). Based on our phylogenetic study, the HTLV-1 prevalent sequence type of Torbat-e Heydarieh belongs to the cosmopolitan subtype A. HTLV-1 prevalence in Torbat-e Heydarieh (1.25%) is low comparing to those of both Mashhad (2-3%) and Neishabour (3.5-5%) in the province of Khorasan. Thus, traveling mobility and population mixing such as marriage, bureaucratic affairs, occupation, and economic activities could be the usual routs of HTLV-1 new wave of spreading in this segregated city. © 2015 Wiley Periodicals, Inc.

PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread

NASA Astrophysics Data System (ADS)

Tang, Xiaolong; Liang, Yong; Liu, Xinkuang; Zhou, Shuping; Liu, Liang; Zhang, Fujina; Xie, Chunmei; Cai, Shuyu; Wei, Jia; Zhu, Yongqiang; Hou, Wei

2015-10-01

Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA- and SAHA + Nel-loaded nanoparticles can target latently infected CD4+ T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.

First Molecular Characterization of Feline Immunodeficiency Virus in Domestic Cats from Mainland China.

PubMed

Zhang, Jilei; Wang, Liang; Li, Jing; Kelly, Patrick; Price, Stuart; Wang, Chengming

2017-01-01

The feline immunodeficiency virus (FIV) is a retrovirus of the Lentivirus genus that was initially isolated from a colony of domestic cats in California in 1986 and has now been recognized as a common feline pathogen worldwide. To date, there is only one recent serology-based report on FIV in mainland China which was published in 2016. We designed this study to investigate the molecular prevalence and diversity of feline immunodeficiency virus (FIV) in domestic cats from mainland China. We studied the prevalence of FIV in whole blood samples of 615 domestic cats in five cities (Beijing, Guangzhou, Nanjing, Shanghai and Yangzhou) of mainland China and examined them using FRET-PCR (Fluorescence Resonance Energy Transfer-Polymerase Chain Reaction) and regular PCRs for the gag and env genes. Overall, 1.3% (8/615) of the cats were positive for provirus DNA with nucleotide analysis using PCRs for the gag and env sequences showing the cats were infected with FIV subtype A. This is the first molecular characterization of FIV in mainland China and the first description of subtype A in continental Asia.

Incidence of persistent viraemia and latent feline leukaemia virus infection in cats with lymphoma.

PubMed

Stützer, Bianca; Simon, Karin; Lutz, Hans; Majzoub, Monir; Hermanns, Walter; Hirschberger, Johannes; Sauter-Louis, Carola; Hartmann, Katrin

2011-02-01

In the past, feline leukaemia virus (FeLV) infection, and also latent FeLV infection, were commonly associated with lymphoma and leukaemia. In this study, the prevalence of FeLV provirus in tumour tissue and bone marrow in FeLV antigen-negative cats with these tumours was assessed. Seventy-seven diseased cats were surveyed (61 antigen-negative, 16 antigen-positive). Blood, bone marrow, and tumour samples were investigated by two polymerase chain reaction (PCR) assays detecting deoxyribonucleic acid (DNA) sequences of the long terminal repeats (LTR) and the envelope (env) region of the FeLV genome. Immunohistochemistry (IHC) was performed in bone marrow and tumour tissue. None of the antigen-negative cats with lymphoma was detectably infected with latent FeLV. The prevalence of FeLV viraemia in cats with lymphoma was 20.8%. This suggests that causes other than FeLV play a role in tumorigenesis, and that latent FeLV infection is unlikely to be responsible for most feline lymphomas and leukaemias. Copyright © 2010. Published by Elsevier Ltd.

Genotoxicity of retroviral hematopoietic stem cell gene therapy

PubMed Central

Trobridge, Grant D

2012-01-01

Introduction Retroviral vectors have been developed for hematopoietic stem cell (HSC) gene therapy and have successfully cured X-linked severe combined immunodeficiency (SCID-X1), adenosine deaminase deficiency (ADA-SCID), adrenoleukodystrophy, and Wiskott-Aldrich syndrome. However, in HSC gene therapy clinical trials, genotoxicity mediated by integrated vector proviruses has led to clonal expansion, and in some cases frank leukemia. Numerous studies have been performed to understand the molecular basis of vector-mediated genotoxicity with the aim of developing safer vectors and safer gene therapy protocols. These genotoxicity studies are critical to advancing HSC gene therapy. Areas covered This review provides an introduction to the mechanisms of retroviral vector genotoxicity. It also covers advances over the last 20 years in designing safer gene therapy vectors, and in integration site analysis in clinical trials and large animal models. Mechanisms of retroviral-mediated genotoxicity, and the risk factors that contribute to clonal expansion and leukemia in HSC gene therapy are introduced. Expert opinion Continued research on virus–host interactions and next-generation vectors should further improve the safety of future HSC gene therapy vectors and protocols. PMID:21375467

Psi- vectors: murine leukemia virus-based self-inactivating and self-activating retroviral vectors.

PubMed Central

Delviks, K A; Hu, W S; Pathak, V K

1997-01-01

We have developed murine leukemia virus (MLV)-based self-inactivating and self-activating vectors to show that the previously demonstrated high-frequency direct repeat deletions are not unique to spleen necrosis virus (SNV) or the neomycin drug resistance gene. Retroviral vectors pKD-HTTK and pKD-HTpTK containing direct repeats composed of segments of the herpes simplex virus type 1 thymidine kinase (HTK) gene were constructed; in pKD-HTpTK, the direct repeat flanked the MLV packaging signal. The generation of hypoxanthine-aminopterin-thymidine-resistant colonies after one cycle of retroviral replication demonstrated functional reconstitution of the HTK gene. Quantitative Southern analysis indicated that direct repeat deletions occurred in 57 and 91% of the KD-HTTK and KD-HTpTK proviruses, respectively. These results demonstrate that (i) deletion of direct repeats occurs at similar high frequencies in SNV and MLV vectors, (ii) MLV psi can be efficiently deleted by using direct repeats, (iii) suicide genes can be functionally reconstituted during reverse transcription, and (iv) the psi region may be a hot spot for reverse transcriptase template switching events. PMID:9223521

Integration Site and Clonal Expansion in Human Chronic Retroviral Infection and Gene Therapy

PubMed Central

Niederer, Heather A.; Bangham, Charles R. M.

2014-01-01

Retroviral vectors have been successfully used therapeutically to restore expression of genes in a range of single-gene diseases, including several primary immunodeficiency disorders. Although clinical trials have shown remarkable results, there have also been a number of severe adverse events involving malignant outgrowth of a transformed clonal population. This clonal expansion is influenced by the integration site profile of the viral integrase, the transgene expressed, and the effect of the viral promoters on the neighbouring host genome. Infection with the pathogenic human retrovirus HTLV-1 also causes clonal expansion of cells containing an integrated HTLV-1 provirus. Although the majority of HTLV-1-infected people remain asymptomatic, up to 5% develop an aggressive T cell malignancy. In this review we discuss recent findings on the role of the genomic integration site in determining the clonality and the potential for malignant transformation of cells carrying integrated HTLV-1 or gene therapy vectors, and how these results have contributed to the understanding of HTLV-1 pathogenesis and to improvements in gene therapy vector safety. PMID:25365582

Functional analysis of human foamy virus accessory reading frames.

PubMed Central

Baunach, G; Maurer, B; Hahn, H; Kranz, M; Rethwilm, A

1993-01-01

Foamy viruses belong to the retroviruses which possess a complex genome structure. The human foamy virus (HFV) isolate bears three open reading frames (the so-called bel genes) in the 3' region of the genome which have been reported to give rise to possibly six different proteins via alternative splicing (W. Muranyi and R. M. Flügel, J. Virol. 65:727-735, 1991). In order to analyze the requirements of these proteins for HFV replication in vitro, we constructed a set of single and combinatory bel gene mutants of an infectious molecular clone of HFV. The mutant which lacked the transacting activator, bel-1, was found to be replication incompetent. All other mutants replicated equally well and gave rise to comparable titers of infectious cell-free virus. When HFV proviruses were put under the control of a heterologous promoter (simian virus 40), none of the accessory gene products was found to be required for expression of structural (gag) proteins. There was no evidence for a posttranscriptional regulatory protein that is present in other complex retroviruses. Images PMID:8394455

Domestic chickens activate a piRNA defense against avian leukosis virus

PubMed Central

Sun, Yu Huining; Xie, Li Huitong; Zhuo, Xiaoyu; Chen, Qiang; Ghoneim, Dalia; Zhang, Bin; Jagne, Jarra; Yang, Chengbo; Li, Xin Zhiguo

2017-01-01

PIWI-interacting RNAs (piRNAs) protect the germ line by targeting transposable elements (TEs) through the base-pair complementarity. We do not know how piRNAs co-evolve with TEs in chickens. Here we reported that all active TEs in the chicken germ line are targeted by piRNAs, and as TEs lose their activity, the corresponding piRNAs erode away. We observed de novo piRNA birth as host responds to a recent retroviral invasion. Avian leukosis virus (ALV) has endogenized prior to chicken domestication, remains infectious, and threatens poultry industry. Domestic fowl produce piRNAs targeting ALV from one ALV provirus that was known to render its host ALV resistant. This proviral locus does not produce piRNAs in undomesticated wild chickens. Our findings uncover rapid piRNA evolution reflecting contemporary TE activity, identify a new piRNA acquisition modality by activating a pre-existing genomic locus, and extend piRNA defense roles to include the period when endogenous retroviruses are still infectious. DOI: http://dx.doi.org/10.7554/eLife.24695.001 PMID:28384097

Characterization of human MMTV-like (HML) elements similar to a sequence that was highly expressed in a human breast cancer: further definition of the HML-6 group.

PubMed

Yin, H; Medstrand, P; Kristofferson, A; Dietrich, U; Aman, P; Blomberg, J

1999-03-30

Previously, we found a retroviral sequence, HML-6.2BC1, to be expressed at high levels in a multifocal ductal breast cancer from a 41-year-old woman who also developed ovarian carcinoma. The sequence of a human genomic clone (HML-6.28) selected by high-stringency hybridization with HML-6.2BC1 is reported here. It was 99% identical to HML-6.2BC1 and gave the same restriction fragments as total DNA. HML-6.28 is a 4.7-kb provirus with a 5'LTR, truncated in RT. Data from two similar genomic clones and sequences found in GenBank are also reported. Overlaps between them gave a rather complete picture of the HML-6.2BC1-like human endogenous retroviral elements. Work with somatic cell hybrids and FISH localized HML-6.28 to chromosome 6, band p21, close to the MHC region. The causal role of HML-6.28 in breast cancer remains unclear. Nevertheless, the ca. 20 Myr old HML-6 sequences enabled the definition of common and unique features of type A, B, and D (ABD) retroviruses. In Gag, HML-6 has no intervening sequences between matrix and capsid proteins, unlike extant exogenous ABD viruses, possibly an ancestral feature. Alignment of the dUTPase showed it to be present in all ABD viruses, but gave a phylogenetic tree different from trees made from other ABD genes, indicating a distinct phylogeny of dUTPase. A conserved 24-mer sequence in the amino terminus of some ABD envelope genes suggested a conserved function. Copyright 1999 Academic Press.

Permissive Sense and Antisense Transcription from the 5′ and 3′ Long Terminal Repeats of Human T-Cell Leukemia Virus Type 1

PubMed Central

Polakowski, Nicholas; Hoang, Kimson

2016-01-01

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus, and, as such, its genome becomes chromosomally integrated following infection. The resulting provirus contains identical 5′ and 3′ peripheral long terminal repeats (LTRs) containing bidirectional promoters. Antisense transcription from the 3′ LTR regulates expression of a single gene, hbz, while sense transcription from the 5′ LTR controls expression of all other viral genes, including tax. Both the HBZ and Tax proteins are implicated in the development of adult T-cell leukemia (ATL), a T-cell malignancy caused by HTLV-1 infection. However, these proteins appear to harbor opposing molecular functions, indicating that they may act independently and at different time points prior to leukemogenesis. Here, we used bidirectional reporter constructs to test whether transcriptional interference serves as a mechanism that inhibits simultaneous expression of Tax and HBZ. We found that sense transcription did not interfere with antisense transcription from the 3′ LTR and vice versa, even with strong transcription emanating from the opposing direction. Therefore, bidirectional transcription across the provirus might not restrict hbz or tax expression. Single-cell analyses revealed that antisense transcription predominates in the absence of Tax, which transactivates viral sense transcription. Interestingly, a population of Tax-expressing cells exhibited antisense but not activated sense transcription. Consistent with the ability of Tax to induce cell cycle arrest, this population was arrested in G0/G1 phase. These results imply that cell cycle arrest inhibits Tax-mediated activation of sense transcription without affecting antisense transcription, which may be important for long-term viral latency. IMPORTANCE The chromosomally integrated form of the retrovirus human T-cell leukemia virus type 1 (HTLV-1) contains identical DNA sequences, known as long terminal repeats (LTRs), at its 5′ and 3′ ends. The LTRs modulate transcription in both forward (sense) and reverse (antisense) directions. We found that sense transcription from the 5′ LTR does not interfere with antisense transcription from the 3′ LTR, allowing viral genes encoded on opposite DNA strands to be simultaneously transcribed. Two such genes are tax and hbz, and while they are thought to function at different times during the course of infection to promote leukemogenesis of infected T cells, our results indicate that they can be simultaneously transcribed. We also found that the ability of Tax to induce cell cycle arrest inhibits its fundamental function of activating viral sense transcription but does not affect antisense transcription. This regulatory mechanism may be important for long-term HTLV-1 infection. PMID:26792732

Immunological alterations and associated diseases in mandrills (Mandrillus sphinx) naturally co-infected with SIV and STLV.

PubMed

Souquière, Sandrine; Makuwa, Maria; Sallé, Bettina; Lepelletier, Yves; Mortreux, Franck; Hermine, Olivier; Kazanji, Mirdad

2014-04-01

Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4(+) and CD8(+) T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4(+) and CD8(+) T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates. Copyright © 2014 Elsevier Inc. All rights reserved.

Transcriptional regulation of latent feline immunodeficiency virus in peripheral CD4+ T-lymphocytes.

PubMed

McDonnel, Samantha J; Sparger, Ellen E; Luciw, Paul A; Murphy, Brian G

2012-05-01

Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 10(3) CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.

Significant differences in genotoxicity induced by retrovirus integration in human T cells and induced pluripotent stem cells.

PubMed

Zheng, Weiyan; Wang, Yingjia; Chang, Tammy; Huang, He; Yee, Jiing-Kuan

2013-04-25

Retrovirus is frequently used in the genetic modification of mammalian cells and the establishment of induced pluripotent stem cells (iPSCs) via cell reprogramming. Vector-induced genotoxicity could induce profound effect on the physiology and function of these stem cells and their differentiated progeny. We analyzed retrovirus-induced genotoxicity in somatic cell Jurkat and two iPSC lines. In Jurkat cells, retrovirus frequently activated host gene expression and gene activation was not dependent on the distance between the integration site and the transcription start site of the host gene. In contrast, retrovirus frequently down-regulated host gene expression in iPSCs, possibly due to the action of chromatin silencing that spreads from the provirus to the nearby host gene promoter. Our data raises the issue that some of the phenotypic variability observed among iPSC clones derived from the same parental cell line may be caused by retrovirus-induced gene expression changes rather than by the reprogramming process itself. It also underscores the importance of characterizing retrovirus integration and carrying out risk assessment of iPSCs before they can be applied in basic research and clinics. Copyright © 2013 Elsevier B.V. All rights reserved.

Generation of fibrosarcomas in vivo by a retrovirus that expresses the normal B chain of platelet-derived growth factor and mimics the alternative splice pattern of the v-sis oncogene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pech, M.; Gazit, A.; Arnstein, P.

1989-04-01

A retrovirus containing the entire human platelet-derived growth factor B-chain (PDGF-B) gene was constructed in order to investigate the in vivo biological activity of its encoded growth factor. When this virus was introduced into newborn mice, it reproducibly generated fibrosarcomas at the site of inoculation. Proviruses in each fibrosarcoma analyzed had lost 149 nucleotides downstream of the PDGF-B coding region. This deletion originated from an alternative or aberrant splice event that occurred within exon 7 of the PDGF-B gene and mimicked the v-sis oncogene. Thus, deletion of this region may be necessary for efficient retrovirus replication or for more potentmore » transforming function. Evidence that the normal growth factor coding sequence was unaltered derived from RNase protection studies and immunoprecipitation analysis. Tumors were generally polyclonal but demonstrated clonal subpopulations. Moreover, tumor-derived cell lines became monoclonal within a few tissue culture passages and rapidly formed tumors in vivo. These findings argue that overexpression of the normal human PDGF-B gene product under retrovirus control can induce the fully malignant phenotype.« less

HMBA Enhances Prostratin-Induced Activation of Latent HIV-1 via Suppressing the Expression of Negative Feedback Regulator A20/TNFAIP3 in NF-κB Signaling.

PubMed

Chen, Duchu; Wang, Huiping; Aweya, Jude Juventus; Chen, Yanheng; Chen, Meihua; Wu, Xiaomeng; Chen, Xiaonan; Lu, Jing; Chen, Ruichuan; Liu, Min

2016-01-01

In the past decade, much emphasis has been put on the transcriptional activation of HIV-1, which is proposed as a promised strategy for eradicating latent HIV-1 provirus. Two drugs, prostratin and hexamethylene bisacetamide (HMBA), have shown potent effects as inducers for releasing HIV-1 latency when used alone or in combination, although their cellular target(s) are currently not well understood, especially under drug combination. Here, we have shown that HMBA and prostratin synergistically release HIV-1 latency via different mechanisms. While prostratin strongly stimulates HMBA-induced HIV-1 transcription via improved P-TEFb activation, HMBA is capable of boosting NF-κB-dependent transcription initiation by suppressing prostratin-induced expression of the deubiquitinase A20, a negative feedback regulator in the NF-κB signaling pathway. In addition, HMBA was able to increase prostratin-induced phosphorylation and degradation of NF-κB inhibitor IκBα, thereby enhancing and prolonging prostratin-induced nuclear translocation of NF-κB, a prerequisite for stimulation of transcription initiation. Thus, by blocking the negative feedback circuit, HMBA functions as a signaling enhancer of the NF-κB signaling pathway.

Detection of fowl poxvirus integrated with reticuloendotheliosis virus sequences from an outbreak in backyard chickens in India.

PubMed

Biswas, Sanchay K; Jana, Chandrakanta; Chand, Karam; Rehman, Waseem; Mondal, Bimalendu

2011-01-01

Fowl poxvirus (FPV) infection was observed in unvaccinated backyard chickens. A total of 15 birds were affected in a flock of 37. Pock lesions were observed on the comb, eyelids, beak and wattles. The birds appeared sick with roughened feathers and stunted growth. No mortality was recorded. DNA was isolated from scabs and polymerase chain reaction (PCR) was performed to amplify the 4b core protein gene of FPV, the envelope (env) gene of reticuloendotheliosis virus (REV) and the region of FPV flanking REV 5´ long terminal repeat (LTR). Correct-size PCR products of 578 bp, 807 bp and 370 bp, respectively, were observed in agarose gel electrophoresis. Sequence analysis of these products suggests that the virus was an FPV with a genome containing an integrated near full-length REV provirus. Given the fact that REV has been associated with immunosuppression, its presence in the genome of FPV appears to play an important role in the pathogenesis of fowl pox and presumably prolongs persistence of FPV in bird populations. In the present case, fowl pox has been observed to have persisted for about three years in fowl that were reared in backyard systems in villages.

Endogenous avian leukosis viral loci in the Red Jungle Fowl genome assembly.

PubMed

Benkel, Bernhard; Rutherford, Katherine

2014-12-01

The current build (galGal4) of the genome of the ancestor of the modern chicken, the Red Jungle Fowl, contains a single endogenous avian leukosis viral element (ALVE) on chromosome 1 (designated RSV-LTR; family ERVK). The assembly shows the ALVE provirus juxtaposed with a member of a second family of avian endogenous retroviruses (designated GGERV20; family ERVL); however, the status of the 3' end of the ALVE element as well as its flanking region remain unclear due to a gap in the reference genome sequence. In this study, we filled the gap in the assembly using a combination of long-range PCR (LR-PCR) and a short contig present in the unassembled portion of the reference genome database. Our results demonstrate that the ALVE element (ALVE-JFevB) is inserted into the putative envelope region of a GGERV20 element, roughly 1 kbp from its 3' end, and that ALVE-JFevB is complete, and depending on its expression status, potentially capable of directing the production of virus. Moreover, the unassembled portion of the genome database contains junction fragments for a second, previously characterized endogenous proviral element, ALVE-6. ©2014 Poultry Science Association Inc.

Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a herpesvirus saimiri vector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grassmann, R.; Dengler, C.; Mueller-Fleckenstein, I.

1989-05-01

The role of the X region of the genome of the human T-cell leukemia virus type I (HTLV-I) in the immortalization of lymphocytes has been difficult to distinguish from its role in viral replication as this region encodes at least two genes, tax and rex, required for replication and the expression of viral proteins. To determine whether the X region does encode immortalizing functions, a fragment of the HTLV-I provirus capable of expressing known X-region proteins was inserted into the genome of a transformation-defective, replication-competent Herpesvirus saimiri. Infection of fresh mitogen-activated human cord blood and thymocytes yielded immortal T-cell linesmore » that had the same phenotype (CD4{sup +}, Cd5{sup +}, HLA class II{sup +}, interleukin 2 receptor {alpha}-chain +) as lymphocytes transformed by cocultivation with HTLV-I. These experiments demonstrate that the X region encodes the functions of HTLV-I that immortalize a distinct subpopulation of human T cells. The experiments also demonstrate the utility of the H. saimiri vector for the transduction of heterologous genes into human T cells.« less

Evolutionary Strategies of Viruses, Bacteria and Archaea in Hydrothermal Vent Ecosystems Revealed through Metagenomics

PubMed Central

Anderson, Rika E.; Sogin, Mitchell L.; Baross, John A.

2014-01-01

The deep-sea hydrothermal vent habitat hosts a diverse community of archaea and bacteria that withstand extreme fluctuations in environmental conditions. Abundant viruses in these systems, a high proportion of which are lysogenic, must also withstand these environmental extremes. Here, we explore the evolutionary strategies of both microorganisms and viruses in hydrothermal systems through comparative analysis of a cellular and viral metagenome, collected by size fractionation of high temperature fluids from a diffuse flow hydrothermal vent. We detected a high enrichment of mobile elements and proviruses in the cellular fraction relative to microorganisms in other environments. We observed a relatively high abundance of genes related to energy metabolism as well as cofactors and vitamins in the viral fraction compared to the cellular fraction, which suggest encoding of auxiliary metabolic genes on viral genomes. Moreover, the observation of stronger purifying selection in the viral versus cellular gene pool suggests viral strategies that promote prolonged host integration. Our results demonstrate that there is great potential for hydrothermal vent viruses to integrate into hosts, facilitate horizontal gene transfer, and express or transfer genes that manipulate the hosts’ functional capabilities. PMID:25279954

Comparison of HTLV-I Proviral Load in Adult T Cell Leukemia/Lymphoma (ATL), HTLV-I-Associated Myelopathy (HAM-TSP) and Healthy Carriers.

PubMed

Akbarin, Mohammad Mehdi; Rahimi, Hossein; Hassannia, Tahereh; Shoja Razavi, Ghazaleh; Sabet, Faezeh; Shirdel, Abbas

2013-03-01

Human T Lymphocyte Virus Type one (HTLV-I) is a retrovirus that infects about 10-20 million people worldwide. Khorasan province in Iran is an endemic area. The majority of HTLV-I-infected individuals sustain healthy carriers but small proportion of infected population developed two progressive diseases: HAM/TSP and ATL. The proviral load could be a virological marker for disease monitoring, therefore in the present study HTLV-I proviral load has been evaluated in ATL and compared to HAM/TSP and healthy carriers. In this case series study, 47 HTLV-I infected individuals including 13 ATL, 23 HAM/TSP and 11 asymptomatic subjects were studied. Peripheral blood mononuclear cells (PBMCs) were investigated for presence of HTLV-I DNA provirus by PCR using LTR and Tax fragments. Then in infected subjects, HTLV-I proviral load was measured using real time PCR TaqMan method. The average age of patients in ATL was 52±8, in HAM/TSP 45.52±15.17 and in carrier's 38.65±14.9 years which differences were not statistically significant. The analysis of data showed a significant difference in mean WBC among study groups (ATL vs HAM/TSP and carriers P=0.0001). Moreover, mean HTLV-I proviral load was 11967.2 ± 5078, 409 ± 71.3 and 373.6 ± 143.3 in ATL, HAM/TSP and Healthy Carriers, respectively. The highest HTLV-I proviral load was measured in ATL group that had a significant correlation with WBC count (R=0.495, P=0.001). The proviral load variations between study groups was strongly significant (ATL vs carrier P=0.0001; ATL vs HAM/TSP P= 0.0001 and HAM/TSP vs carriers P< 0.05). Conclusion : The present study demonstrated that HTLV-I proviral load was higher in ATL group in comparison with HAM/TSP and healthy carriers. Therefore, HTLV-I proviral load is a prognostic factor for development of HTLV-I associated diseases and can be used as a monitoring marker for the efficiency of therapeutic regime.

Presence of a Shared 5'-Leader Sequence in Ancestral Human and Mammalian Retroviruses and Its Transduction into Feline Leukemia Virus.

PubMed

Kawasaki, Junna; Kawamura, Maki; Ohsato, Yoshiharu; Ito, Jumpei; Nishigaki, Kazuo

2017-10-15

Recombination events induce significant genetic changes, and this process can result in virus genetic diversity or in the generation of novel pathogenicity. We discovered a new recombinant feline leukemia virus (FeLV) gag gene harboring an unrelated insertion, termed the X region, which was derived from Felis catus endogenous gammaretrovirus 4 (FcERV-gamma4). The identified FcERV-gamma4 proviruses have lost their coding capabilities, but some can express their viral RNA in feline tissues. Although the X-region-carrying recombinant FeLVs appeared to be replication-defective viruses, they were detected in 6.4% of tested FeLV-infected cats. All isolated recombinant FeLV clones commonly incorporated a middle part of the FcERV-gamma4 5'-leader region as an X region. Surprisingly, a sequence corresponding to the portion contained in all X regions is also present in at least 13 endogenous retroviruses (ERVs) observed in the cat, human, primate, and pig genomes. We termed this shared genetic feature the commonly shared (CS) sequence. Despite our phylogenetic analysis indicating that all CS-sequence-carrying ERVs are classified as gammaretroviruses, no obvious closeness was revealed among these ERVs. However, the Shannon entropy in the CS sequence was lower than that in other parts of the provirus genome. Notably, the CS sequence of human endogenous retrovirus T had 73.8% similarity with that of FcERV-gamma4, and specific signals were detected in the human genome by Southern blot analysis using a probe for the FcERV-gamma4 CS sequence. Our results provide an interesting evolutionary history for CS-sequence circulation among several distinct ancestral viruses and a novel recombined virus over a prolonged period. IMPORTANCE Recombination among ERVs or modern viral genomes causes a rapid evolution of retroviruses, and this phenomenon can result in the serious situation of viral disease reemergence. We identified a novel recombinant FeLV gag gene that contains an unrelated sequence, termed the X region. This region originated from the 5' leader of FcERV-gamma4, a replication-incompetent feline ERV. Surprisingly, a sequence corresponding to the X region is also present in the 5' portion of other ERVs, including human endogenous retroviruses. Scattered copies of the ERVs carrying the unique genetic feature, here named the commonly shared (CS) sequence, were found in each host genome, suggesting that ancestral viruses may have captured and maintained the CS sequence. More recently, a novel recombinant FeLV hijacked the CS sequence from inactivated FcERV-gamma4 as the X region. Therefore, tracing the CS sequences can provide unique models for not only the modern reservoir of new recombinant viruses but also the genetic features shared among ancient retroviruses. Copyright © 2017 American Society for Microbiology.

Correlation between normal glucose-6-phosphate dehydrogenase level and haematological parameters.

PubMed

Ajlaan, S K; al-Naama, L M; al-Naama, M M

2000-01-01

The study involved 143 individuals and aimed to correlate normal glucose-6-phosphate dehydrogenase (G6PD) level with haematological parameters. A statistically significant negative correlation was found between G6PD level and haemoglobin, packed cell volume, red blood cell count, mean corpuscular haemoglobin and mean corpuscular volume. A statistically significant positive correlation was found between G6PD level and white blood cell count and reticulocyte count, but no significant correlation was found between G6PD level and mean corpuscular haemoglobin concentration. The negative correlation between G6PD level and haemoglobin suggests that anaemic people have higher G6PD levels than normal individuals. The positive correlation between G6PD level and white blood cell count indicates that white blood cells may play an important role in contributing to G6PD level.

EBNA3C Augments Pim-1 Mediated Phosphorylation and Degradation of p21 to Promote B-Cell Proliferation

PubMed Central

Banerjee, Shuvomoy; Lu, Jie; Cai, Qiliang; Sun, Zhiguo; Jha, Hem Chandra; Robertson, Erle S.

2014-01-01

Epstein–Barr virus (EBV), a ubiquitous human herpesvirus, can latently infect the human population. EBV is associated with several types of malignancies originating from lymphoid and epithelial cell types. EBV latent antigen 3C (EBNA3C) is essential for EBV-induced immortalization of B-cells. The Moloney murine leukemia provirus integration site (PIM-1), which encodes an oncogenic serine/threonine kinase, is linked to several cellular functions involving cell survival, proliferation, differentiation, and apoptosis. Notably, enhanced expression of Pim-1 kinase is associated with numerous hematological and non-hematological malignancies. A higher expression level of Pim-1 kinase is associated with EBV infection, suggesting a crucial role for Pim-1 in EBV-induced tumorigenesis. We now demonstrate a molecular mechanism which reveals a direct role for EBNA3C in enhancing Pim-1 expression in EBV-infected primary B-cells. We also showed that EBNA3C is physically associated with Pim-1 through its amino-terminal domain, and also forms a molecular complex in B-cells. EBNA3C can stabilize Pim-1 through abrogation of the proteasome/Ubiquitin pathway. Our results demonstrate that EBNA3C enhances Pim-1 mediated phosphorylation of p21 at the Thr145 residue. EBNA3C also facilitated the nuclear localization of Pim-1, and promoted EBV transformed cell proliferation by altering Pim-1 mediated regulation of the activity of the cell-cycle inhibitor p21/WAF1. Our study demonstrated that EBNA3C significantly induces Pim-1 mediated proteosomal degradation of p21. A significant reduction in cell proliferation of EBV-transformed LCLs was observed upon stable knockdown of Pim-1. This study describes a critical role for the oncoprotein Pim-1 in EBV-mediated oncogenesis, as well as provides novel insights into oncogenic kinase-targeted therapeutic intervention of EBV-associated cancers. PMID:25121590

Comparison of three blood transfusion guidelines applied to 31 feline donors to minimise the risk of transfusion-transmissible infections.

PubMed

Marenzoni, Maria Luisa; Lauzi, Stefania; Miglio, Arianna; Coletti, Mauro; Arbia, Andrea; Paltrinieri, Saverio; Antognoni, Maria Teresa

2017-08-01

Objectives The increased demand for animal blood transfusions creates the need for an adequate number of donors. At the same time, a high level of blood safety must be guaranteed and different guidelines (GLs) deal with this topic. The aim of this study was to evaluate the appropriateness of different GLs in preventing transfusion-transmissible infections (TTI) in Italian feline blood donors. Methods Blood samples were collected from 31 cats enrolled as blood donors by the owners' voluntary choice over a period of approximately 1 year. Possible risk factors for TTI were recorded. Based on Italian, European and American GLs, specific TTI, including haemoplasmas, feline leukaemia virus (FeLV), feline immunodeficiency virus (FIV), Anaplasma phagocytophilum, Ehrlichia species, Bartonella species, Babesia species, Theileria species, Cytauxzoon species, Leishmania donovani sensu lato and feline coronavirus (FCoV) were screened. Rapid antigen and serological tests and biomolecular investigations (PCR) were used. Several PCR protocols for haemoplasma and FeLV DNA were compared. Results The presence of at least one recognised risk factor for TTI was reported in all cats. Results for FIV and FeLV infections were negative using rapid tests, whereas five (16.1%) cats were positive for FCoV antibodies. Four (12.9%) cats were PCR positive for haemoplasma DNA and one (3.2%) for FeLV provirus, the latter being positive only using the most sensitive PCR protocol applied. Other TTI were not detected using PCR. Conclusions and relevance Blood safety increases by combining the recommendations of different GLs. To reduce the risk of TTI, sensitive tests are needed and the choice of the best protocol is a critical step in improving blood safety. The cost and time of the screening procedures may be reduced if appropriate tests are selected. To this end, the GLs should include appropriate recruitment protocols and questionnaire-based risk profiles to identify suitable donors.

Replication-Competent Foamy Virus Vaccine Vectors as Novel Epitope Scaffolds for Immunotherapy

PubMed Central

Lei, Janet; Osen, Wolfram; Gardyan, Adriane; Hotz-Wagenblatt, Agnes; Wei, Guochao; Gissmann, Lutz; Eichmüller, Stefan; Löchelt, Martin

2015-01-01

The use of whole viruses as antigen scaffolds is a recent development in vaccination that improves immunogenicity without the need for additional adjuvants. Previous studies highlighted the potential of foamy viruses (FVs) in prophylactic vaccination and gene therapy. Replication-competent FVs can trigger immune signaling and integrate into the host genome, resulting in persistent antigen expression and a robust immune response. Here, we explored feline foamy virus (FFV) proteins as scaffolds for therapeutic B and T cell epitope delivery in vitro. Infection- and cancer-related B and T cell epitopes were grafted into FFV Gag, Env, or Bet by residue replacement, either at sites of high local sequence homology between the epitope and the host protein or in regions known to tolerate sequence alterations. Modified proviruses were evaluated in vitro for protein steady state levels, particle release, and virus titer in permissive cells. Modification of Gag and Env was mostly detrimental to their function. As anticipated, modification of Bet had no impact on virion release and affected virus titers of only some recombinants. Further evaluation of Bet as an epitope carrier was performed using T cell epitopes from the model antigen chicken ovalbumin (OVA), human tyrosinase-related protein 2 (TRP-2), and oncoprotein E7 of human papillomavirus type 16 (HPV16E7). Transfection of murine cells with constructs encoding Bet-epitope chimeric proteins led to efficient MHC-I-restricted epitope presentation as confirmed by interferon-gamma enzyme-linked immunospot assays using epitope-specific cytotoxic T lymphocyte (CTL) lines. FFV infection-mediated transduction of cells with epitope-carrying Bet also induced T-cell responses, albeit with reduced efficacy, in a process independent from the presence of free peptides. We show that primate FV Bet is also a promising T cell epitope carrier for clinical translation. The data demonstrate the utility of replication-competent and -attenuated FVs as antigen carriers in immunotherapy. PMID:26397953

Job stress and agentic-communal personality traits related to serum cortisol levels of male workers in a Japanese medium-sized company: a cross-sectional study.

PubMed

Hirokawa, Kumi; Taniguchi, Toshiyo; Fujii, Yasuhito

2015-02-01

Although serum cortisol is a widely accepted index of stress levels, associations between job stress and cortisol levels have been inconsistent. Individual differences in personality traits were discussed as one compelling explanation for this discrepancy. Agentic-communal personality traits have been examined as possible predictive factors for psychological stress. This study investigated correlations among agentic-communal personality traits and serum cortisol levels. It was also investigated whether job stress levels modified correlations between agentic-communal personality and cortisol levels. Participants were 198 male workers (mean age = 52.2 years) employed by a shipbuilding company in Japan. Questionnaire data and blood samples were collected during an annual health checkup. Participants completed a self-report questionnaire that included the Job Content Questionnaire (JCQ) that assesses job control as job stress levels the Communion-Agency scale (CAS) and questions regarding health behaviors. Communion positively correlated with serum cortisol levels and unmitigated agency negatively correlated with serum cortisol levels. Stratified by job control, communion positively correlated with serum cortisol levels and agency negatively correlated with serum cortisol levels in participants with low levels of job control. Unmitigated agency negatively correlated with serum cortisol levels in participants with high levels of job control. Levels of job control may modify correlations of gender-related personality with serum cortisol levels. Especially with exposure to high job stress, male workers with high femininity (i.e., high communion and low agency) were more likely to have a high stress response as measured by serum cortisol levels.

Frequent Infection of Human Cancer Xenografts with Murine Endogenous Retroviruses in Vivo

PubMed Central

Naseer, Asif; Terry, Anne; Gilroy, Kathryn; Kilbey, Anna; Watts, Ciorsdaidh; Mackay, Nancy; Bell, Margaret; Mason, Susan; Blyth, Karen; Cameron, Ewan; Neil, James C.

2015-01-01

Infection of human cancer xenografts in mice with murine leukemia viruses (MLVs) is a long-standing observation, but the likelihood of infection in vivo and its biological consequences are poorly understood. We therefore conducted a prospective study in commonly used xenograft recipient strains. From BALB/c nude mice engrafted with MCF7 human mammary carcinoma cells, we isolated a virus that was virtually identical to Bxv1, a locus encoding replication-competent xenotropic MLV (XMLV). XMLV was detected in 9/17 (53%) independently isolated explants. XMLV was not found in primary leukemias or in THP1 leukemia cells grown in Bxv1-negative NSG (NOD/SCID/γCnull) mice, although MCF7 explants harbored replication-defective MLV proviruses. To assess the significance of infection for xenograft behavior in vivo, we examined changes in growth and global transcription in MCF7 and the highly susceptible Raji Burkitt lymphoma cell line chronically infected with XMLV. Raji cells showed a stronger transcriptional response that included up-regulation of chemokines and effectors of innate antiviral immunity. In conclusion, the risk of de novo XMLV infection of xenografts is high in Bxv1 positive mice, while infection can have positive or negative effects on xenograft growth potential with significant consequences for interpretation of many xenograft studies. PMID:25912714

Adenosine Deaminase Acting on RNA-1 (ADAR1) Inhibits HIV-1 Replication in Human Alveolar Macrophages

PubMed Central

Levy, David N.; Li, Yonghua; Kumar, Rajnish; Burke, Sean A.; Dawson, Rodney; Hioe, Catarina E.; Borkowsky, William; Rom, William N.; Hoshino, Yoshihiko

2014-01-01

While exploring the effects of aerosol IFN-γ treatment in HIV-1/tuberculosis co-infected patients, we observed A to G mutations in HIV-1 envelope sequences derived from bronchoalveolar lavage (BAL) of aerosol IFN-γ-treated patients and induction of adenosine deaminase acting on RNA 1 (ADAR1) in the BAL cells. IFN-γ induced ADAR1 expression in monocyte-derived macrophages (MDM) but not T cells. ADAR1 siRNA knockdown induced HIV-1 expression in BAL cells of four HIV-1 infected patients on antiretroviral therapy. Similar results were obtained in MDM that were HIV-1 infected in vitro. Over-expression of ADAR1 in transformed macrophages inhibited HIV-1 viral replication but not viral transcription measured by nuclear run-on, suggesting that ADAR1 acts post-transcriptionally. The A to G hyper-mutation pattern observed in ADAR1 over-expressing cells in vitro was similar to that found in the lungs of HIV-1 infected patients treated with aerosol IFN-γ suggesting the model accurately represented alveolar macrophages. Together, these results indicate that ADAR1 restricts HIV-1 replication post-transcriptionally in macrophages harboring HIV-1 provirus. ADAR1 may therefore contribute to viral latency in macrophages. PMID:25272020

An Evolutionarily Young Polar Bear (Ursus maritimus) Endogenous Retrovirus Identified from Next Generation Sequence Data.

PubMed

Tsangaras, Kyriakos; Mayer, Jens; Alquezar-Planas, David E; Greenwood, Alex D

2015-11-24

Transcriptome analysis of polar bear (Ursus maritimus) tissues identified sequences with similarity to Porcine Endogenous Retroviruses (PERV). Based on these sequences, four proviral copies and 15 solo long terminal repeats (LTRs) of a newly described endogenous retrovirus were characterized from the polar bear draft genome sequence. Closely related sequences were identified by PCR analysis of brown bear (Ursus arctos) and black bear (Ursus americanus) but were absent in non-Ursinae bear species. The virus was therefore designated UrsusERV. Two distinct groups of LTRs were observed including a recombinant ERV that contained one LTR belonging to each group indicating that genomic invasions by at least two UrsusERV variants have recently occurred. Age estimates based on proviral LTR divergence and conservation of integration sites among ursids suggest the viral group is only a few million years old. The youngest provirus was polar bear specific, had intact open reading frames (ORFs) and could potentially encode functional proteins. Phylogenetic analyses of UrsusERV consensus protein sequences suggest that it is part of a pig, gibbon and koala retrovirus clade. The young age estimates and lineage specificity of the virus suggests UrsusERV is a recent cross species transmission from an unknown reservoir and places the viral group among the youngest of ERVs identified in mammals.

In vitro excision of adeno-associated virus DNA from recombinant plasmids: Isolation of an enzyme fraction from HeLa cells that cleaves DNA at poly(G) sequences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gottlieb, J.; Muzyczka, N.

1988-06-01

When circular recombinant plasmids containing adeno-associated virus (AAV) DNA sequences are transfected into human cells, the AAV provirus is rescued. Using these circular AAV plasmids as substrates, the authors isolated an enzyme fraction from HeLa cell nuclear extracts that excises intact AAV DNA in vitro from vector DNA and produces linear DNA products. The recognition signal for the enzyme is a polypurine-polypyrimidine sequence which is at least 9 residues long and rich in G . C base pairs. Such sequences are present in AAV recombinant plasmids as part of the first 15 base pairs of the AAV terminal repeat andmore » in some cases as the result of cloning the AAV genome by G . C tailing. The isolated enzyme fraction does not have significant endonucleolytic activity on single-stranded or double-stranded DNA. Plasmid DNA that is transfected into tissue culture cells is cleaved in vivo to produce a pattern of DNA fragments similar to that seen with purified enzyme in vitro. The activity has been called endo R for rescue, and its behavior suggests that it may have a role in recombination of cellular chromosomes.« less

Proviral Latency, Persistent Human Immunodeficiency Virus Infection, and the Development of Latency Reversing Agents

PubMed Central

Archin, Nancie M.

2017-01-01

Abstract Quiescent proviral genomes that persist during human immunodeficiency virus type 1 (HIV-1) infection despite effective antiretroviral therapy (ART) can fuel rebound viremia after ART interruption and is a central obstacle to the cure of HIV infection. The induction of quiescent provirus is the goal of a new class of potential therapeutics, latency reversing agents (LRAs). The discovery, development, and testing of HIV LRAs is a key part of current efforts to develop latency reversal and viral clearance strategies to eradicate established HIV infection. The development of LRAs is burdened by many uncertainties that make drug discovery difficult. The biology of HIV latency is complex and incompletely understood. Potential targets for LRAs are host factors, and the potential toxicities of host-directed therapies in individuals that are otherwise clinically stable may be unacceptable. Assays to measure latency reversal and assess the effectiveness of potential therapeutics are complex and incompletely validated. Despite these obstacles, novel LRAs are under development and beginning to enter combination testing with viral clearance strategies. It is hoped that the steady advances in the development of LRAs now being paired with emerging immunotherapeutics to clear persistently infected cells will soon allow measurable clinical advances toward an HIV cure. PMID:28520964

Insight into HIV-2 latency may disclose strategies for a cure for HIV-1 infection.

PubMed

Saleh, Suha; Vranckx, Lenard; Gijsbers, Rik; Christ, Frauke; Debyser, Zeger

2017-01-01

HIV-1 and HIV-2 originate from two distinct zoonotic transmissions of simian immunodeficiency viruses from primate to human. Although both share similar modes of transmission and can result in the development of AIDS with similar clinical manifestations, HIV-2 infection is generally milder and less likely to progress to AIDS. HIV is currently incurable due to the presence of HIV provirus integrated into the host DNA of long-lived memory cells of the immune system without active replication. As such, the latent virus is immunologically inert and remains insensitive to the administered antiviral drugs targeting active viral replication steps. Recent evidence suggests that persistent HIV replication may occur in anatomical sanctuaries such as the lymphoid tissue due to low drug penetration. At present, different strategies are being evaluated either to completely eradicate the virus from the patient (sterilising cure) or to allow treatment interruption without viral rebound (functional cure). Because HIV-2 is naturally less pathogenic and displays a more latent phenotype than HIV-1, it may represent a valuable model that provides elementary information to cure HIV-1 infection. Insight into the viral and cellular determinants of HIV-2 replication may therefore pave the way for alternative strategies to eradicate HIV-1 or promote viral remission.

The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology

PubMed Central

Mallet, François; Bouton, Olivier; Prudhomme, Sarah; Cheynet, Valérie; Oriol, Guy; Bonnaud, Bertrand; Lucotte, Gérard; Duret, Laurent; Mandrand, Bernard

2004-01-01

The definitive demonstration of a role for a recently acquired gene is a difficult task, requiring exhaustive genetic investigations and functional analysis. The situation is indeed much more complicated when facing multicopy gene families, because most or portions of the gene are conserved among the hundred copies of the family. This is the case for the ERVWE1 locus of the human endogenous retrovirus W family (HERV-W), which encodes an envelope glycoprotein (syncytin) likely involved in trophoblast differentiation. Here we describe, in 155 individuals, the positional conservation of this locus and the preservation of the envelope ORF. Sequencing of the critical elements of the ERVWE1 provirus showed a striking conservation among the 48 alleles of 24 individuals, including the LTR elements involved in the transcriptional machinery, the splice sites involved in the maturation of subgenomic Env mRNA, and the Env ORF. The functionality and tissue specificity of the 5′ LTR were demonstrated, as well as the fusogenic activity of the envelope polymorphic variants. Such functions were also shown to be preserved in the orthologous loci isolated from chimpanzee, gorilla, orangutan, and gibbon. This functional preservation among humans and during evolution strongly argued for the involvement of this recently acquired retroviral envelope glycoprotein in hominoid placental physiology. PMID:14757826

Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors

PubMed Central

Bii, Victor M.; Trobridge, Grant D.

2016-01-01

Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations. They can also be used for almost any human cancer due to the broad tropism of the vectors. Replication-incompetent retroviral vectors have the ability to dysregulate nearby cancer genes via several mechanisms including enhancer-mediated activation of gene promoters. The integrated provirus acts as a unique molecular tag for nearby candidate driver genes which can be rapidly identified using well established methods that utilize next generation sequencing and bioinformatics programs. Recently, retroviral vector screens have been used to efficiently identify candidate driver genes in prostate, breast, liver and pancreatic cancers. Validated driver genes can be potential therapeutic targets and biomarkers. In this review, we describe the emergence of retroviral insertional mutagenesis screens using replication-incompetent retroviral vectors as a novel tool to identify cancer driver genes in different cancer types. PMID:27792127

HCIV-1 and Other Tailless Icosahedral Internal Membrane-Containing Viruses of the Family Sphaerolipoviridae.

PubMed

Demina, Tatiana A; Pietilä, Maija K; Svirskaitė, Julija; Ravantti, Janne J; Atanasova, Nina S; Bamford, Dennis H; Oksanen, Hanna M

2017-02-18

Members of the virus family Sphaerolipoviridae include both archaeal viruses and bacteriophages that possess a tailless icosahedral capsid with an internal membrane. The genera Alpha- and Betasphaerolipovirus comprise viruses that infect halophilic euryarchaea, whereas viruses of thermophilic Thermus bacteria belong to the genus Gammasphaerolipovirus . Both sequence-based and structural clustering of the major capsid proteins and ATPases of sphaerolipoviruses yield three distinct clades corresponding to these three genera. Conserved virion architectural principles observed in sphaerolipoviruses suggest that these viruses belong to the PRD1-adenovirus structural lineage. Here we focus on archaeal alphasphaerolipoviruses and their related putative proviruses. The highest sequence similarities among alphasphaerolipoviruses are observed in the core structural elements of their virions: the two major capsid proteins, the major membrane protein, and a putative packaging ATPase. A recently described tailless icosahedral haloarchaeal virus, Haloarcula californiae icosahedral virus 1 (HCIV-1), has a double-stranded DNA genome and an internal membrane lining the capsid. HCIV-1 shares significant similarities with the other tailless icosahedral internal membrane-containing haloarchaeal viruses of the family Sphaerolipoviridae . The proposal to include a new virus species, Haloarcula virus HCIV1 , into the genus Alphasphaerolipovirus was submitted to the International Committee on Taxonomy of Viruses (ICTV) in 2016.

Homologous recombination occurs in a distinct retroviral subpopulation and exhibits high negative interference.

PubMed Central

Hu, W S; Bowman, E H; Delviks, K A; Pathak, V K

1997-01-01

Homologous recombination and deletions occur during retroviral replication when reverse transcriptase switches templates. While recombination occurs solely by intermolecular template switching (between copackaged RNAs), deletions can occur by an intermolecular or an intramolecular template switch (within the same RNA). To directly compare the rates of intramolecular and intermolecular template switching, two spleen necrosis virus-based vectors were constructed. Each vector contained a 110-bp direct repeat that was previously shown to delete at a high rate. The 110-bp direct repeat was flanked by two different sets of restriction site markers. These vectors were used to form heterozygotic virions containing RNAs of each parental vector, from which recombinant viruses were generated. By analyses of the markers flanking the direct repeats in recombinant and nonrecombinant proviruses, the rates of intramolecular and intermolecular template switching were determined. The results of these analyses indicate that intramolecular template switching is much more efficient than intermolecular template switching and that direct repeat deletions occur primarily through intramolecular template switching events. These studies also indicate that retroviral recombination occurs within a distinct viral subpopulation and exhibits high negative interference, whereby the selection of one recombination event increases the probability that a second recombination event will be observed. PMID:9223494

Molecular mechanisms of retroviral integration site selection

PubMed Central

Kvaratskhelia, Mamuka; Sharma, Amit; Larue, Ross C.; Serrao, Erik; Engelman, Alan

2014-01-01

Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic. PMID:25147212

An Evolutionarily Young Polar Bear (Ursus maritimus) Endogenous Retrovirus Identified from Next Generation Sequence Data

PubMed Central

Tsangaras, Kyriakos; Mayer, Jens; Alquezar-Planas, David E.; Greenwood, Alex D.

2015-01-01

Transcriptome analysis of polar bear (Ursus maritimus) tissues identified sequences with similarity to Porcine Endogenous Retroviruses (PERV). Based on these sequences, four proviral copies and 15 solo long terminal repeats (LTRs) of a newly described endogenous retrovirus were characterized from the polar bear draft genome sequence. Closely related sequences were identified by PCR analysis of brown bear (Ursus arctos) and black bear (Ursus americanus) but were absent in non-Ursinae bear species. The virus was therefore designated UrsusERV. Two distinct groups of LTRs were observed including a recombinant ERV that contained one LTR belonging to each group indicating that genomic invasions by at least two UrsusERV variants have recently occurred. Age estimates based on proviral LTR divergence and conservation of integration sites among ursids suggest the viral group is only a few million years old. The youngest provirus was polar bear specific, had intact open reading frames (ORFs) and could potentially encode functional proteins. Phylogenetic analyses of UrsusERV consensus protein sequences suggest that it is part of a pig, gibbon and koala retrovirus clade. The young age estimates and lineage specificity of the virus suggests UrsusERV is a recent cross species transmission from an unknown reservoir and places the viral group among the youngest of ERVs identified in mammals. PMID:26610552

Molecular Studies of HTLV-1 Replication: An Update

PubMed Central

Martin, Jessica L.; Maldonado, José O.; Mueller, Joachim D.; Zhang, Wei; Mansky, Louis M.

2016-01-01

Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus discovered. Studies on HTLV-1 have been instrumental for our understanding of the molecular pathology of virus-induced cancers. HTLV-1 is the etiological agent of an adult T-cell leukemia (ATL) and can lead to a variety of neurological pathologies, including HTLV-1-associated-myelopathy/tropical spastic paraparesis (HAM/TSP). The ability to treat the aggressive ATL subtypes remains inadequate. HTLV-1 replicates by (1) an infectious cycle involving virus budding and infection of new permissive target cells and (2) mitotic division of cells harboring an integrated provirus. Virus replication initiates host antiviral immunity and the checkpoint control of cell proliferation, but HTLV-1 has evolved elegant strategies to counteract these host defense mechanisms to allow for virus persistence. The study of the molecular biology of HTLV-1 replication has provided crucial information for understanding HTLV-1 replication as well as aspects of viral replication that are shared between HTLV-1 and human immunodeficiency virus type 1 (HIV-1). Here in this review, we discuss the various stages of the virus replication cycle—both foundational knowledge as well as current updates of ongoing research that is important for understanding HTLV-1 molecular pathogenesis as well as in developing novel therapeutic strategies. PMID:26828513

The therapeutic application of CRISPR/Cas9 technologies for HIV

PubMed Central

Saayman, Sheena; Ali, Stuart A.; Morris, Kevin V.; Weinberg, Marc S.

2015-01-01

Introduction The use of antiretroviral therapy (ART) has led to a significant decrease in morbidity and mortality in HIV-infected individuals. Nevertheless gene-based therapies represent a promising therapeutic paradigm for HIV-1, as they have the potential for sustained viral inhibition and reduced treatment interventions. One new method amendable to a gene-based therapy is the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 gene editing system. Areas covered CRISPR/Cas9 can be engineered to successfully modulate an array of disease-causing genetic elements. We discuss the diverse roles that CRISPR/Cas9 may play in targeting HIV and eradicating infection. The Cas9 nuclease coupled with one or more small guide RNAs (sgRNAs) can target the provirus to mediate excision of the integrated viral genome. Moreover, a modified nuclease deficient Cas9 fused to transcription activating domains may induce targeted activation of proviral gene expression allowing for the purging of the latent reservoirs. These technologies can also be exploited to target host dependency factors such as the co-receptor CCR5, thus preventing cellular entry of the virus. Expert opinion The diversity of the CRISPR/Cas9 technologies hold great promise for targeting different stages of the viral life cycle, and have the capacity for mediating an effective and sustained genetic therapy against HIV. PMID:25865334

HTLV-1 basic leucine zipper factor downregulates cyclin D1 expression via interactions with NF-κB.

PubMed

Ma, Yunyun; Zhang, Bo; Wang, Dong; Qian, Lili; Song, Xianmei; Wang, Xueyin; Yang, Chaokuan; Zhao, Guoqiang

2017-03-01

Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus. It can cause adult T cell leukemia (ATL) and other diseases. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ), which is encoded by the minus-strand of the provirus, is expressed in all cases of ATL and involved in T cell proliferation. However, the exact mechanism underlying its growth-promoting activity is poorly understood. Herein, we demonstrated that HBZ suppressed cyclin D1 expression by inhibiting the nuclear factor (NF)-κB signaling pathway. Among the potential mechanisms of cyclin D1 inhibition mediated by HBZ, we found that HBZ suppressed cyclin D1 promoter activity. Luciferase assay analysis revealed that HBZ repressed cyclin D1 promoter activity by suppressing NF-κB‑driven transcription mediated by the p65 subunit. Using an immunoprecipitation assay, we found that HBZ could bind to p65, but not p50. Finally, we showed that HBZ selectively interacted with p65 via its AD+bZIP domains. By suppressing cyclin D1 expression, HBZ can alter cell cycle progression of HTLV-1-infected cells, which may be critical for oncogenesis.

A curative regimen would decrease HIV prevalence but not HIV incidence unless targeted to an ART-naïve population.

PubMed

Dimitrov, Dobromir T; Kiem, Hans-Peter; Jerome, Keith R; Johnston, Christine; Schiffer, Joshua T

2016-02-24

HIV curative strategies currently under development aim to eradicate latent provirus, or prevent viral replication, progression to AIDS, and transmission. The impact of implementing curative programs on HIV epidemics has not been considered. We developed a mathematical model of heterosexual HIV transmission to evaluate the independent and synergistic impact of ART, HIV prevention interventions and cure on HIV prevalence and incidence. The basic reproduction number was calculated to study the potential for the epidemic to be eliminated. We explored scenarios with and without the assumption that patients enrolled into HIV cure programs need to be on antiretroviral treatment (ART). In our simulations, curative regimes had limited impact on HIV incidence if only ART patients were eligible for cure. Cure implementation had a significant impact on HIV incidence if ART-untreated patients were enrolled directly into cure programs. Concurrent HIV prevention programs moderately decreased the percent of ART treated or cured patients needed to achieve elimination. We project that widespread implementation of HIV cure would decrease HIV prevalence under all scenarios but would only lower rate of new infections if ART-untreated patients were targeted. Current efforts to identify untreated HIV patients will gain even further relevance upon availability of an HIV cure.

Promoter Targeting RNAs: Unexpected Contributors to the Control of HIV-1 Transcription.

PubMed

Suzuki, Kazuo; Ahlenstiel, Chantelle; Marks, Katherine; Kelleher, Anthony D

2015-01-27

In spite of prolonged and intensive treatment with combined antiretroviral therapy (cART), which efficiently suppresses plasma viremia, the integrated provirus of HIV-1 persists in resting memory CD4(+) T cells as latent infection. Treatment with cART does not substantially reduce the burden of latent infection. Once cART is ceased, HIV-1 replication recrudesces from these reservoirs in the overwhelming majority of patients. There is increasing evidence supporting a role for noncoding RNAs (ncRNA), including microRNAs (miRNAs), antisense (as)RNAs, and short interfering (si)RNA in the regulation of HIV-1 transcription. This appears to be mediated by interaction with the HIV-1 promoter region. Viral miRNAs have the potential to act as positive or negative regulators of HIV transcription. Moreover, inhibition of virally encoded long-asRNA can induce positive transcriptional regulation, while antisense strands of siRNA targeting the NF-κB region suppress viral transcription. An in-depth understanding of the interaction between ncRNAs and the HIV-1 U3 promoter region may lead to new approaches for the control of HIV reservoirs. This review focuses on promoter associated ncRNAs, with particular emphasis on their role in determining whether HIV-1 establishes active or latent infection.

Promoter Targeting RNAs: Unexpected Contributors to the Control of HIV-1 Transcription

PubMed Central

Suzuki, Kazuo; Ahlenstiel, Chantelle; Marks, Katherine; Kelleher, Anthony D

2015-01-01

In spite of prolonged and intensive treatment with combined antiretroviral therapy (cART), which efficiently suppresses plasma viremia, the integrated provirus of HIV-1 persists in resting memory CD4+ T cells as latent infection. Treatment with cART does not substantially reduce the burden of latent infection. Once cART is ceased, HIV-1 replication recrudesces from these reservoirs in the overwhelming majority of patients. There is increasing evidence supporting a role for noncoding RNAs (ncRNA), including microRNAs (miRNAs), antisense (as)RNAs, and short interfering (si)RNA in the regulation of HIV-1 transcription. This appears to be mediated by interaction with the HIV-1 promoter region. Viral miRNAs have the potential to act as positive or negative regulators of HIV transcription. Moreover, inhibition of virally encoded long-asRNA can induce positive transcriptional regulation, while antisense strands of siRNA targeting the NF-κB region suppress viral transcription. An in-depth understanding of the interaction between ncRNAs and the HIV-1 U3 promoter region may lead to new approaches for the control of HIV reservoirs. This review focuses on promoter associated ncRNAs, with particular emphasis on their role in determining whether HIV-1 establishes active or latent infection. PMID:25625613

Correlation of serum intercellular adhesion molecule 1 and vascular endothelial growth factor with tumor grading and staging in breast cancer patients.

PubMed

Haghi, Alireza Rastgoo; Vahedi, Amir; Shekarchi, Ali Akbar; Kamran, Aziz

2017-01-01

Breast cancer is the most common cancer among women. There are several prognostic factors for this disease. The aim of this article is to explore the correlation of serum level of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM1) with tumor, node, metastasis staging and grading of breast cancer. Serum samples of 51 patients with breast cancer were assessed with enzyme-linked immunosorbent assay for the level of VEGF and ICAM1 preoperatively. After the operation, histopathologic specimens stained with hematoxylin and eosin were evaluated for tumor size, histopathologic subtype, grade, lymph node, vascular and lymphatic involvement. Then, the correlation of tumor stage and grade and serum level of markers was analyzed. There was no significant correlation between serum level of markers with vascular invasions, lymph node involvement, and menstruation. There was a weak correlation between tumor size and serum level of ICAM1 with Pearson score correlation, but there was no significant correlation with VEGF. There was no significant correlation between tumor grading and staging with the level of markers. There was a significant correlation between the level of VEGF and ICAM1 and histologic type of tumors in invasive through in situ tumors. Levels of VEGF and ICAM1 can be used as a predictor of tumor invasion and also for target therapy.

Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer's disease, and related to neuropathological disease stage.

PubMed

Naylor, Jennifer C; Hulette, Christine M; Steffens, David C; Shampine, Lawrence J; Ervin, John F; Payne, Victoria M; Massing, Mark W; Kilts, Jason D; Strauss, Jennifer L; Calhoun, Patrick S; Calnaido, Rohana P; Blazer, Daniel G; Lieberman, Jeffrey A; Madison, Roger D; Marx, Christine E

2008-08-01

It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer's disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex. DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer's Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses. CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects. These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.

Serum human chorionic gonadotropin levels on the day before oocyte retrieval do not correlate with oocyte maturity.

PubMed

Levy, Gary; Hill, Micah J; Ramirez, Christina; Plowden, Torrie; Pilgrim, Justin; Howard, Robin S; Segars, James H; Csokmay, John

2013-05-01

To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. Retrospective cohort study. Military assisted reproductive technology (ART) program. Fresh autologous ART cycles. Serum hCG level the day before oocyte retrieval. Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful. Copyright © 2013. Published by Elsevier Inc.

Correlation of Body Mass Index (BMI) with Thyroid Function in Euthyroid Pregnant Women in Manipur, India.

PubMed

Kumar, Sumit; Chiinngaihlun, T; Singh, M Rameswar; Punyabati, O

2017-04-01

Body Mass Index (BMI) is significantly increased during pregnancy due to gain of weight with normal progression of pregnancy. The exact influence of thyroid function on BMI are ill defined in euthyroid pregnant women. To correlate serum levels of Free Triiodothyronine (FT3), Free Thyroxine (FT4) and Thyroid Stimulating Hormone (TSH) level with BMI of participant normal pregnant women in all the three trimesters. In this cross-sectional comparative study, total of 210 healthy pregnant women comprising of 70 participants in each trimester, attending Obstetrics Outpatient Department (OPD) for antenatal check-up were consecutively selected. Estimation of serum FT3, FT4 and TSH level was done by ELISA based methods. The correlation of BMI with serum levels of FT3, FT4 and TSH was done using Pearson correlation test (r) by SPSS version 21.0 software. TSH level of participant normal pregnant women showed significant positive correlation with BMI during first (r=0.254 and p=0.034) and second trimester (r=0.263 and p=0.028) of pregnancy. FT4 level showed significant negative correlation in second (r= -0.454 and p<0.001) and third trimester (r= -0.351 and p=0.003) of pregnancy. Correlation between BMI and FT3 level showed no significant association in any of the trimesters. BMI correlates positively with TSH level in first and second trimesters while it correlates negatively with FT4 level in second and third trimesters, but, failed to demonstrate significant association with FT3 level in any of trimesters in euthyroid pregnant women. Serum TSH along with FT4 level appears more useful modality compared to serum TSH alone for targeted thyroid screening particularly in obese pregnant women.

Genomic Flexibility of Human Endogenous Retrovirus Type K

PubMed Central

Dube, Derek; Contreras-Galindo, Rafael; He, Shirley; King, Steven R.; Gonzalez-Hernandez, Marta J.; Gitlin, Scott D.; Kaplan, Mark H.

2014-01-01

ABSTRACT Human endogenous retrovirus type K (HERV-K) proviruses are scattered throughout the human genome, but as no infectious HERV-K virus has been detected to date, the mechanism by which these viruses replicated and populated the genome remains unresolved. Here, we provide evidence that, in addition to the RNA genomes that canonical retroviruses package, modern HERV-K viruses can contain reverse-transcribed DNA (RT-DNA) genomes. Indeed, reverse transcription of genomic HERV-K RNA into the DNA form is able to occur in three distinct times and locations: (i) in the virus-producing cell prior to viral release, yielding a DNA-containing extracellular virus particle similar to the spumaviruses; (ii) within the extracellular virus particle itself, transitioning from an RNA-containing particle to a DNA-containing particle; and (iii) after entry of the RNA-containing virus into the target cell, similar to canonical retroviruses, such as murine leukemia virus and HIV. Moreover, using a resuscitated HERV-K virus construct, we show that both viruses with RNA genomes and viruses with DNA genomes are capable of infecting target cells. This high level of genomic flexibility historically could have permitted these viruses to replicate in various host cell environments, potentially assisting in their many integration events and resulting in their high prevalence in the human genome. Moreover, the ability of modern HERV-K viruses to proceed through reverse transcription and package RT-DNA genomes suggests a higher level of replication competency than was previously understood, and it may be relevant in HERV-K-associated human diseases. IMPORTANCE Retroviral elements comprise at least 8% of the human genome. Of all the endogenous retroviruses, HERV-K viruses are the most intact and biologically active. While a modern infectious HERV-K has yet to be found, HERV-K activation has been associated with cancers, autoimmune diseases, and HIV-1 infection. Thus, determining how this virus family became such a prevalent member of our genome and what it is capable of in its current form are of the utmost importance. Here, we provide evidence that HERV-K viruses currently found in the human genome are able to proceed through reverse transcription and historically utilized a life cycle with a surprising degree of genomic flexibility in which both RNA- and DNA-containing viruses were capable of mediating infection. PMID:24920813

An In-Depth Comparison of Latency-Reversing Agent Combinations in Various In Vitro and Ex Vivo HIV-1 Latency Models Identified Bryostatin-1+JQ1 and Ingenol-B+JQ1 to Potently Reactivate Viral Gene Expression.

PubMed

Darcis, Gilles; Kula, Anna; Bouchat, Sophie; Fujinaga, Koh; Corazza, Francis; Ait-Ammar, Amina; Delacourt, Nadège; Melard, Adeline; Kabeya, Kabamba; Vanhulle, Caroline; Van Driessche, Benoit; Gatot, Jean-Stéphane; Cherrier, Thomas; Pianowski, Luiz F; Gama, Lucio; Schwartz, Christian; Vila, Jorge; Burny, Arsène; Clumeck, Nathan; Moutschen, Michel; De Wit, Stéphane; Peterlin, B Matija; Rouzioux, Christine; Rohr, Olivier; Van Lint, Carine

2015-07-01

The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART) is a major hurdle to HIV-1 eradication. Strategies to purge these reservoirs are needed and activation of viral gene expression in latently infected cells is one promising strategy. Bromodomain and Extraterminal (BET) bromodomain inhibitors (BETi) are compounds able to reactivate latent proviruses in a positive transcription elongation factor b (P-TEFb)-dependent manner. In this study, we tested the reactivation potential of protein kinase C (PKC) agonists (prostratin, bryostatin-1 and ingenol-B), which are known to activate NF-κB signaling pathway as well as P-TEFb, used alone or in combination with P-TEFb-releasing agents (HMBA and BETi (JQ1, I-BET, I-BET151)). Using in vitro HIV-1 post-integration latency model cell lines of T-lymphoid and myeloid lineages, we demonstrated that PKC agonists and P-TEFb-releasing agents alone acted as potent latency-reversing agents (LRAs) and that their combinations led to synergistic activation of HIV-1 expression at the viral mRNA and protein levels. Mechanistically, combined treatments led to higher activations of P-TEFb and NF-κB than the corresponding individual drug treatments. Importantly, we observed in ex vivo cultures of CD8+-depleted PBMCs from 35 cART-treated HIV-1+ aviremic patients that the percentage of reactivated cultures following combinatory bryostatin-1+JQ1 treatment was identical to the percentage observed with anti-CD3+anti-CD28 antibodies positive control stimulation. Remarkably, in ex vivo cultures of resting CD4+ T cells isolated from 15 HIV-1+ cART-treated aviremic patients, the combinations bryostatin-1+JQ1 and ingenol-B+JQ1 released infectious viruses to levels similar to that obtained with the positive control stimulation. The potent effects of these two combination treatments were already detected 24 hours post-stimulation. These results constitute the first demonstration of LRA combinations exhibiting such a potent effect and represent a proof-of-concept for the co-administration of two different types of LRAs as a potential strategy to reduce the size of the latent HIV-1 reservoirs.

An In-Depth Comparison of Latency-Reversing Agent Combinations in Various In Vitro and Ex Vivo HIV-1 Latency Models Identified Bryostatin-1+JQ1 and Ingenol-B+JQ1 to Potently Reactivate Viral Gene Expression

PubMed Central

Bouchat, Sophie; Fujinaga, Koh; Corazza, Francis; Ait-Ammar, Amina; Delacourt, Nadège; Melard, Adeline; Kabeya, Kabamba; Vanhulle, Caroline; Van Driessche, Benoit; Gatot, Jean-Stéphane; Cherrier, Thomas; Pianowski, Luiz F.; Gama, Lucio; Schwartz, Christian; Vila, Jorge; Burny, Arsène; Clumeck, Nathan; Moutschen, Michel; De Wit, Stéphane; Peterlin, B. Matija; Rouzioux, Christine; Rohr, Olivier; Van Lint, Carine

2015-01-01

The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART) is a major hurdle to HIV-1 eradication. Strategies to purge these reservoirs are needed and activation of viral gene expression in latently infected cells is one promising strategy. Bromodomain and Extraterminal (BET) bromodomain inhibitors (BETi) are compounds able to reactivate latent proviruses in a positive transcription elongation factor b (P-TEFb)-dependent manner. In this study, we tested the reactivation potential of protein kinase C (PKC) agonists (prostratin, bryostatin-1 and ingenol-B), which are known to activate NF-κB signaling pathway as well as P-TEFb, used alone or in combination with P-TEFb-releasing agents (HMBA and BETi (JQ1, I-BET, I-BET151)). Using in vitro HIV-1 post-integration latency model cell lines of T-lymphoid and myeloid lineages, we demonstrated that PKC agonists and P-TEFb-releasing agents alone acted as potent latency-reversing agents (LRAs) and that their combinations led to synergistic activation of HIV-1 expression at the viral mRNA and protein levels. Mechanistically, combined treatments led to higher activations of P-TEFb and NF-κB than the corresponding individual drug treatments. Importantly, we observed in ex vivo cultures of CD8+-depleted PBMCs from 35 cART-treated HIV-1+ aviremic patients that the percentage of reactivated cultures following combinatory bryostatin-1+JQ1 treatment was identical to the percentage observed with anti-CD3+anti-CD28 antibodies positive control stimulation. Remarkably, in ex vivo cultures of resting CD4+ T cells isolated from 15 HIV-1+ cART-treated aviremic patients, the combinations bryostatin-1+JQ1 and ingenol-B+JQ1 released infectious viruses to levels similar to that obtained with the positive control stimulation. The potent effects of these two combination treatments were already detected 24 hours post-stimulation. These results constitute the first demonstration of LRA combinations exhibiting such a potent effect and represent a proof-of-concept for the co-administration of two different types of LRAs as a potential strategy to reduce the size of the latent HIV-1 reservoirs. PMID:26225566

Contribution of fasting and postprandial hyperglycemia to hemoglobin A1c in insulin-treated Japanese diabetic patients.

PubMed

Shimizu, Hiroyuki; Uehara, Yutaka; Okada, Shuichi; Mori, Masatomo

2008-08-01

The contribution of fasting and postprandial glucose to hemoglobin A(1c) (HbA(1c)) levels was evaluated in insulin-treated patients. In 57 insulin-treated, diabetic out-patients, fasting glucose (before breakfast (B-FG), lunch (L-FG) and dinner (D-FG)) and postprandial glucose (B-PPG, L-PPG and D-PPG) levels were determined by the patients themselves at home using glucose self-monitoring apparatus over the course of one week. The correlation between HbA(1c) levels and self monitored blood glucose levels were calculated. In the conventionally treated group, there was a significant correlation between HbA(1c) and fasting glucose (FG) levels only before lunch, but at 2 hr after (PPG) all meals. In the intensively treated group, a significant correlation between HbA(1c) levels and FG levels was found before lunch and at 2 hr after breakfast and dinner. In all subjects, only FG levels before lunch correlated significantly with HbA(1c) levels, although PPG levels were significantly correlated with HbA(1c) at all points. The correlation was highest with PPG after breakfast and dinner. The sum of all FG, PPG and FG + PPG levels was significantly correlated with HbA(1c) levels. Postprandial hyperglycemia after breakfast and dinner should be regarded as most important for improving HbA(1c) levels in insulin treated diabetic patients.

[Correlation analysis of hearing level and soft palate movement after palatoplasty].

PubMed

Lou, Qun; Ma, Xiaoran; Ma, Lian; Luo, Yi; Zhu, Hongping; Zhou, Zhibo

2015-10-01

To explore the relationship between hearing level and soft palate movement after palatoplasty and to verify the importance of recovery of soft palate movement function for improving the middle ear function as well as reducing the hearing loss. A total of 64 non-syndromic cleft palate patients were selected and the lateral cephalometric radiographs were taken. The patients hearing level was evaluated by the pure tone hearing threshold examination. This study also analyzed the correlation between hearing threshold of the patients after palatoplasty and the soft palate elevation angle and velopharyngeal rate respectively. Kendall correlation analysis revealed that the correlation coefficient between hearing threshold and the soft palate elevation angle after palatoplasty was -0.339 (r = -0.339, P < 0.01).The correlation showed a negative correlation. The hearing threshold decreased as the soft palate elevation angle increased. After palatoplasty, the correlation coefficient between the hearing threshold and the rate of velopharyngeal closure was -0.277 (r = -0.277, P < 0.01). The correlation showed a negative correlation. While, The hearing threshold decreased with the increase of velopharyngeal closure rate. The hearing threshold was correlated with soft palate elevation angle and velpharyngeal closure rate. The movement of soft palate and velopharyngeal closure function after palatoplasty both have impact on patient hearing level. In terms of the influence level, the movement of soft palate has a higher level of impact on patient hearing level than velopharygeal closure function.

Historical groundwater trends in northern New England and relations with streamflow and climatic variables

USGS Publications Warehouse

Dudley, Robert W.; Hodgkins, Glenn A.

2013-01-01

Water-level trends spanning 20, 30, 40, and 50 years were tested using month-end groundwater levels in 26, 12, 10, and 3 wells in northern New England (Maine, New Hampshire, and Vermont), respectively. Groundwater levels for 77 wells were used in interannual correlations with meteorological and hydrologic variables related to groundwater. Trends in the contemporary groundwater record (20 and 30 years) indicate increases (rises) or no substantial change in groundwater levels in all months for most wells throughout northern New England. The highest percentage of increasing 20-year trends was in February through March, May through August, and October through November. Forty-year trend results were mixed, whereas 50-year trends indicated increasing groundwater levels. Whereas most monthly groundwater levels correlate strongly with the previous month's level, monthly levels also correlate strongly with monthly streamflows in the same month; correlations of levels with monthly precipitation are less frequent and weaker than those with streamflow. Groundwater levels in May through August correlate strongly with annual (water year) streamflow. Correlations of groundwater levels with streamflow data and the relative richness of 50- to 100-year historical streamflow data suggest useful proxies for quantifying historical groundwater levels in light of the relatively short and fragmented groundwater data records presently available.

Serum human chorionic gonadotropin levels on the day before oocyte retrieval do not correlate with oocyte maturity

PubMed Central

Levy, Gary; Hill, Micah J.; Ramirez, Christina; Plowden, Torrie; Pilgrim, Justin; Howard, Robin S.; Segars, James H.; Csokmay, John

2014-01-01

Objective To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. Design Retrospective cohort study. Setting Military assisted reproductive technology (ART) program. Patient(s) Fresh autologous ART cycles. Intervention(s) Serum hCG level the day before oocyte retrieval. Main Outcome Measure(s) Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥ 75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. Result(s) A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥ 75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. Conclusion(s) Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful. PMID:23375205

Correlations of chemokine CXCL16 and TNF-α with coronary atherosclerotic heart disease.

PubMed

Xing, Jieyong; Liu, Yanshao; Chen, Tao

2018-01-01

This study determined the correlations of CXC ligand 16 (CXCL16) and tumor necrosis factor-α (TNF-α) levels with coronary atherosclerotic heart disease (CAHD) and screened for new clinical markers for the prognosis and treatment of the disease. Eighty patients with coronary heart disease and 50 healthy subjects were enrolled into a CAHD or healthy control group, respectively. Computed tomography (CT) coronary angiography and Gensini integral were used to classify plaques and evaluate patients with coronary heart disease. The serum levels of CXCL16 and TNF-α of subjects in each group were detected by enzyme-linked immunosorbent assays (ELISA), and the correlation between levels and clinical markers (such as blood pressure, glucose, lipid and heart rate) and the severity of disease were analyzed. Our results showed the serum levels of CXCL16 and TNF-α were significantly higher in the CAHD group than those in the CK group. The serum CXCL16 levels of the CAHD group patients with plaques were distinctly higher than those of the CADH group patients without plaques, but there were no significant difference in serum TNF-α levels between these two groups of patients. The level of CXCL16 had a significantly positive correlation with the severity of disease, but there was no significant correlation between TNF-α level and the severity of disease. Also, there was no significant correlation between the CXCL16 levels and blood pressure, blood glucose, heart rate, total cholesterol, triglyceride or high-density lipoprotein cholesterol, but there was a clear correlation with the low-density lipoprotein cholesterol. Finally no significant correlations were found between TNF-α levels and each of the clinical markers studied. Based on our findings, the levels of CXCL16 and TNF-α in the patients with coronary heart disease were abnormally increased and the level of CXCL16 correlated closely with the severity of disease. These markers seem to be reliable biological markers for prognosis and disease evaluation in coronary heart disease patients.

Pro-Brain Natriuretic Peptide and Troponin T-Hypersensitivity Levels Correlate With the Severity of Liver Dysfunction in Liver Cirrhosis.

PubMed

Zhao, Jiancheng; Li, Sai; Ren, Linan; Guo, Xiaozhong; Qi, Xingshun

2017-08-01

Increased pro-brain natriuretic peptide (pro-BNP) or troponin T-hypersensitivity (TnT-HSST) levels are common in liver cirrhosis. We conducted a retrospective observational study aimed to evaluate the correlation of pro-BNP and TnT-HSST levels with the clinical characteristics, laboratory data and in-hospital outcomes of patients with liver cirrhosis. We selected cirrhotic patients admitted to our hospital between January 2011 and June 2014. All eligible patients had pro-BNP or TnT-HSST data, or both. The pro-BNP and TnT-HSST data were further divided according to the presence of cardiac diseases. The prevalence of pro-BNP level >900pg/mL was 41.72% (63 of 151 patients). The prevalence of TnT-HSST level >0.05ng/mL was 11.22% (45 of 401 patients). In the overall analysis, pro-BNP level significantly correlated with red blood cell (RBC), platelet, ascites, blood urea nitrogen (BUN), creatinine (Cr), Child-Pugh score, model for end-stage liver disease (MELD) score and in-hospital death; TnT-HSST level significantly correlated with white blood cell, ascites, albumin (ALB), BUN, Cr, Child-Pugh score, MELD score and in-hospital death. In patients with cardiac diseases, pro-BNP level significantly correlated with RBC, ascites, BUN, Cr, Child-Pugh score and MELD score; TnT-HSST level significantly correlated with sex, ascites, white blood cell, ALB, BUN, Cr, Child-Pugh score, MELD score and in-hospital death. In patients without cardiac diseases, pro-BNP level significantly correlated with ascites, RBC, platelet, BUN, Cr, MELD score and in-hospital death; TnT-HSST level significantly correlated with age, ascites, RBC, ALB, BUN, Cr, Child-Pugh score, MELD score and in-hospital death. Pro-BNP and TnT-HSST levels significantly correlated with the severity of liver dysfunction and in-hospital mortality in cirrhosis. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes.

PubMed

Shmakov, Sergey A; Sitnik, Vassilii; Makarova, Kira S; Wolf, Yuri I; Severinov, Konstantin V; Koonin, Eugene V

2017-09-19

Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein (CRISPR-Cas) systems store the memory of past encounters with foreign DNA in unique spacers that are inserted between direct repeats in CRISPR arrays. For only a small fraction of the spacers, homologous sequences, called protospacers, are detectable in viral, plasmid, and microbial genomes. The rest of the spacers remain the CRISPR "dark matter." We performed a comprehensive analysis of the spacers from all CRISPR- cas loci identified in bacterial and archaeal genomes, and we found that, depending on the CRISPR-Cas subtype and the prokaryotic phylum, protospacers were detectable for 1% to about 19% of the spacers (~7% global average). Among the detected protospacers, the majority, typically 80 to 90%, originated from viral genomes, including proviruses, and among the rest, the most common source was genes that are integrated into microbial chromosomes but are involved in plasmid conjugation or replication. Thus, almost all spacers with identifiable protospacers target mobile genetic elements (MGE). The GC content, as well as dinucleotide and tetranucleotide compositions, of microbial genomes, their spacer complements, and the cognate viral genomes showed a nearly perfect correlation and were almost identical. Given the near absence of self-targeting spacers, these findings are most compatible with the possibility that the spacers, including the dark matter, are derived almost completely from the species-specific microbial mobilomes. IMPORTANCE The principal function of CRISPR-Cas systems is thought to be protection of bacteria and archaea against viruses and other parasitic genetic elements. The CRISPR defense function is mediated by sequences from parasitic elements, known as spacers, that are inserted into CRISPR arrays and then transcribed and employed as guides to identify and inactivate the cognate parasitic genomes. However, only a small fraction of the CRISPR spacers match any sequences in the current databases, and of these, only a minority correspond to known parasitic elements. We show that nearly all spacers with matches originate from viral or plasmid genomes that are either free or have been integrated into the host genome. We further demonstrate that spacers with no matches have the same properties as those of identifiable origins, strongly suggesting that all spacers originate from mobile elements.

Highly efficient focus formation by Rous sarcoma virus on adenovirus type 12 E1A-transformed rat 3Y1 cells.

PubMed Central

Shiroki, K; Hamaguchi, M; Kawai, S

1992-01-01

When rat 3Y1 cells were infected with Rous sarcoma virus (RSV) variant SR-RSV-D(H), many 3Y1 cells acquired a stable provirus but only few of them formed transformed foci. In contrast, 12E1AY cells (3Y1 cells expressing the adenovirus type 12 [Ad12] E1A protein) formed transformed foci upon RSV infection with the same high frequency as did chicken embryo fibroblast cells. This enhancement of focus-forming efficiency was specifically observed in 3Y1 cells expressing Ad12 E1A protein but was not observed in 3Y1 cells expressing simian virus 40 T, c-myc, p53, c-fos, or v-fos protein. This enhancement was not evident in 5E1AY cells (3Y1 cells expressing the Ad5 E1A protein). Judging from the experiment using Ad12-Ad5 hybird E1A DNAs, the N-terminal half of the Ad12 E1A protein was responsible for this enhancement. The promoter activity of the RSV long terminal repeat measured by pLTR-CAT did not correlate to the efficiency of focus formation by RSV in these 3Y1 cells. Moreover, RSV containing the neo gene instead of the src gene produced G418-resistant cells equally efficiently among 3Y1, E1AY, and chicken embryo fibroblast cells. These results suggest that the enhancement of focus formation by RSV is not due to the increased expression of the src gene by the E1A protein. src mRNA and src protein were lower in RSV-transformed E1AY (RSVE1AY) cells than in RSV-transformed 3Y1 (RSV3Y1) cells. The phosphotyrosine-containing proteins were also less abundant in RSVE1AY cells than in RSV3Y1 cells, suggesting that E1AY cells require a lower threshold dose of p60v-src for transformation than do 3Y1 cells. E1AY cells were found to be more sensitive to lysis by detergents. The results suggest that the enhancement is due to changes in membrane structures in E1AY cells. Images PMID:1310757

Low Offset AC Correlator.

DTIC Science & Technology

This patent describes a low offset AC correlator avoids DC offset and low frequency noise by frequency operating the correlation signal so that low...noise, low level AC amplification can be substituted for DC amplification. Subsequently, the high level AC signal is demodulated to a DC level. (Author)

Serum HDL-C levels, log (TG/HDL-C) values and serum total cholesterol/HDL-C ratios significantly correlate with radiological extent of disease in patients with community-acquired pneumonia.

PubMed

Deniz, Omer; Tozkoparan, Ergun; Yaman, Halil; Cakir, Erdinc; Gumus, Seyfettin; Ozcan, Omer; Bozlar, Ugur; Bilgi, Cumhur; Bilgic, Hayati; Ekiz, Kudret

2006-03-01

In several studies, it was shown that there was a marked decrease in serum levels of HDL-C during infection and inflammation in general. In particular, a decrease in the level of serum HDL-C was also shown in pneumonia. Correlations between inflammatory markers such as acute phase proteins, cytokines and serum HDL-C levels were shown. However, there are no studies indicating a correlation between serum HDL-C levels and the radiological extent of the disease (RED) in community-acquired pneumonia (CAP). We hypothesized that there could be a relationship between serum HDL-C levels and RED in CAP. A case-controlled study, including 97 patients with CAP and 45 healthy subjects, was performed. Chest X-rays of CAP patients were scored for RED, and correlations were investigated between RED scores, serum lipid parameters, the erythrocyte sedimentation rate (ESR) and serum albumin levels. The mean serum HDL-C level was lower in CAP patients than in controls. A significant and negative correlation between RED scores (REDS) and serum HDL-C levels was detected (r = -0.64, P = 0.0001). There were also significant correlations between REDS and other lipid parameters. Significant correlations between ESR and serum HDL-C levels and between ESR and other serum lipid parameters were also found. It appears that serum HDL-C levels are generally lower in CAP cases than in healthy controls. Serum HDL-C levels and serum albumin levels might decrease and serum total cholesterol/HDL-C ratios and log (TG/HDL-C) values might increase proportionally with RED in CAP patients. These results might have some significance for individuals having long-standing and/or recurrent pneumonia and other cardiovascular risk factors.

Serum calprotectin levels correlate with biochemical and histological markers of disease activity in TNBS colitis

PubMed Central

Cury, Didia Bismara; Mizsputen, Sender Jankiel; Versolato, Clara; Miiji, Luciana Odashiro; Pereira, Edson; Delboni, Maria Aparecida; Schor, Nestor; Moss, Alan C.

2014-01-01

Background and aim Serum calprotectin is elevated in patients with inflammatory bowel disease (IBD). Whether it correlates other markers of disease activity is unknown. The aim of this study was to correlate serum calprotectin with biochemical and histological measures of intestinal inflammation. Materials and methods TNBS colitis was induced in wistar rats, and serial blood samples were collected at 0, 3, and 12 days. Animals were subsequently sacrificed for pathological evaluation at day 12. Serum calprotectin and cytokines were measured by ELISA. Pathologic changes were classified at the macroscopic and microscopic levels. Results TNBS colitis induced elevated serum calprotectin, TNF and IL-6 within 24 h. Levels of serum calprotectin remained elevated in parallel to persistence of loose stool and weight loss to day 12. Serum calprotectin levels correlated with serum levels of TNF-α and IL6 (p < 0.001), but not CRP. Animals with liquid stool had significantly higher levels of serum calprotectin than control animals. There was a correlation between macroscopic colitis scores, and levels of serum calprotectin. Conclusion Serum calprotectin levels correlate with biochemical and histological markers of inflammation in TNBS colitis. This biomarker may have potential for diagnostic use in patients with IBD. PMID:23685388

Circulating leptin level in rheumatoid arthritis and its correlation with disease activity: a meta-analysis.

PubMed

Lee, Y H; Bae, S-C

2016-12-01

This study aimed to evaluate the relationship between the circulating serum leptin level and rheumatoid arthritis (RA) and to establish a correlation between serum leptin levels and RA activity. We searched the PUBMED, EMBASE, and Cochrane databases. A meta-analysis was performed, comparing the serum/plasma leptin levels in patients with RA and healthy controls. Correlation coefficients between serum leptin level and either disease activity score 28 (DAS28) or C‑reactive protein (CRP) in RA patients were also examined. Thirteen studies with a total of 648 RA patients and 426 controls were included in this meta-analysis. Circulating leptin level was significantly higher in the RA group than in the control group (SMD = 1.056, 95 % CI = 0.647-1.465, p = 4.2 × 10 -7 ). In addition, stratification by ethnicity showed a significantly elevated leptin level in the RA group in Caucasian, Turkish, and Arab populations (SMD = 0.813, 95 % CI = 0.137-1.490, p = 0.018, SMD = 0.981, 95 % CI = 0.307-1.655, p = 0.004, and SMD = 1.469, 95 % CI = 0.443-2.495, p = 0.005 respectively). A meta-analysis of correlation coefficients showed a small but significantly positive correlation between the circulating leptin level and either DAS28 (correlation coefficient = 0.275, 95 % CI = 0.076-0.452, p = 0.007) or CRP (correlation coefficient = 0.274, 95 % CI = 0.068-0.458, p = 0.010). Our meta-analysis demonstrated that the circulating leptin level is significantly higher in patients with RA and that a small but significantly positive correlation exists between leptin levels and RA activity.

Plasma RANTES and eotaxin levels are correlated with the severity of chronic rhinosinusitis.

PubMed

Chao, Pin-Zhir; Chou, Chi-Ming; Chen, Chen-Ho

2012-11-01

Eosinophilia occurs in up to 75-90% of nasal polyps in Caucasians. The chemokines eotaxin and RANTES increase eosinophil recruitment, activation, and survival, and these chemokines are significantly expressed in nasal polyps. We hypothesized that eotaxin and RANTES plasma levels might be correlated with disease severity. We compared the eotaxin and RANTES plasma levels in 20 Taiwanese patients with chronic rhinosinusitis and nasal polyps and 20 Taiwanese healthy controls. Eotaxin and RANTES plasma levels were measured by ELISA and disease severity was scored by CT scans. Compared to controls, patients with nasal polyps had significantly elevated plasma levels of eotaxin and RANTES and increased peripheral blood eosinophils (p < 0.001). Eotaxin plasma levels were significantly correlated with disease severity in patients with chronic rhinosinusitis to a greater extent than were RANTES levels. RANTES and eotaxin levels were also positively correlated with the percentages of peripheral blood eosinophils. Eotaxin plasma levels are significantly correlated with disease severity in Taiwanese patients with nasal polyposis to a greater degree than are RANTES levels. Additional studies are needed to assess whether eotaxin plasma levels can be used to monitor disease progression and attenuation.

Archaeal Viruses, Not Archaeal Phages: An Archaeological Dig

PubMed Central

Abedon, Stephen T.; Murray, Kelly L.

2013-01-01

Viruses infect members of domains Bacteria, Eukarya, and Archaea. While those infecting domain Eukarya are nearly universally described as “Viruses”, those of domain Bacteria, to a substantial extent, instead are called “Bacteriophages,” or “Phages.” Should the viruses of domain Archaea therefore be dubbed “Archaeal phages,” “Archaeal viruses,” or some other construct? Here we provide documentation of published, general descriptors of the viruses of domain Archaea. Though at first the term “Phage” or equivalent was used almost exclusively in the archaeal virus literature, there has been a nearly 30-year trend away from this usage, with some persistence of “Phage” to describe “Head-and-tail” archaeal viruses, “Halophage” to describe viruses of halophilic Archaea, use of “Prophage” rather than “Provirus,” and so forth. We speculate on the root of the early 1980's transition from “Phage” to “Virus” to describe these infectious agents, consider the timing of introduction of “Archaeal virus” (which can be viewed as analogous to “Bacterial virus”), identify numerous proposed alternatives to “Archaeal virus,” and also provide discussion of the general merits of the term, “Phage.” Altogether we identify in excess of one dozen variations on how the viruses of domain Archaea are described, and document the timing of both their introduction and use. PMID:23653528

Production of transgenic chickens using an avian retroviral vector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kopchick, J.; Mills, E.; Rosenblum C.

1987-05-01

The authors efforts to insert genes into the chicken germ line are dependent upon the ability of exogenous avian retroviruses to infect chicken germ cells. They have used a transformation defective Schmidt Ruppin A strain of Rous Sarcoma Virus (RSV-SRA) in their initial experiments. The general protocol involved generating RSV-SRA viremic female chickens (Go), which shed exogenous virus via the oviduct. As the fertilized egg passes through the oviduct, embryonic cells are exposed to the virus. If the germ cell precursors are infected by the virus, offspring (G1) should be generated which are capable of passing the viral DNA tomore » the next generation (G2). Fifteen viremic G1 males were selected for breeding and progeny testing. Since male chickens do not congenitally pass retroviruses through semen, production of viremic G2 offspring indicates germ line DNA transmission. This is confirmed by DNA analysis of the experimental chickens. Using a specific probe for exogenous retrovirus, they have detected the presence of RSV-SRA DNA in viremic chickens. Southern DNA analysis revealed junction fragments for RSV-SRA DNA in viremic G2 chickens, but not in non-viremic siblings. Furthermore, DNA isolated from various tissues of a viremic G2 chicken showed an identical DNA junction fragment pattern, indicating all tissues were derived from the same embryonic cell which contained integrated provirus. To date they have generated 50 transgenic chickens.« less

Provirus Integration at the 3 Region of N‐myc in Cell Lines Established from Thymic Lymphomas Spontaneously Formed in AKR Mice and a [(BALB/c × B6)F1AKR] Bone Marrow Chimera

PubMed Central

Yano, Yoko; Kobayashi, Seiichi; Yasumizu, Ryoji; Tamaki, Junko; Kubo, Mitsumasa; Sasaki, Akio; Hasan, Shahid; Okuyama, Harue; Inaba, Muneo; Ikehara, Susumu; Hiai, Hiroshi; Kakinuma, Mitsuaki

1991-01-01

Among 18 thymic leukemia cell lines which have been established from spontaneous thymic lym‐phomas in AKR mice as well as in bone marrow chimeras which were constructed by transplanting allogeneic bone marrow cells into irradiated AKR mice, three proviral integration sites were identified; near c‐myc, N‐myc and pim‐l loci. No integration site specific for chimeric leukemia cell lines was found. In three thymic leukemia cell lines which contained rearranged N‐myc, genes, insertions of long terminal repeats (LTRs) of murine leukemia viruses were detected at 18 or 20 bp downstream of the translational termination codon. These results demonstrate that the 3’region of the N‐myc gene is one of the integration targets for murine leukemia viruses in spontaneous thymic lymphomas. In these three cell lines, N‐myc mRNA was stably transcribed and transcription of c‐myc mRNA was down‐regulated. The integrated murine leukemia viruses in AKR thymic leukemia were most likely AKV, though the DNA sequence of the LTR inserted in the genome of a leukemic cell line from [(BALB/c × B6)F1‐AKR], CAK20, was different from LTRs of murine leukemia viruses so far reported. PMID:1900822

Multiple invasions of an infectious retrovirus in cat genomes

PubMed Central

Shimode, Sayumi; Nakagawa, So; Miyazawa, Takayuki

2015-01-01

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections of host germ-line cells. While most ERVs are defective, some are active and express viral proteins. The RD-114 virus is a replication-competent feline ERV, and several feline cell lines produce infectious RD-114 viral particles. All domestic cats are considered to have an ERV locus encoding a replication-competent RD-114 virus in their genomes; however, the locus has not been identified. In this study, we investigated RD-114 virus-related proviral loci in genomes of domestic cats, and found that none were capable of producing infectious viruses. We also found that all domestic cats have an RD-114 virus-related sequence on chromosome C2, termed RDRS C2a, but populations of the other RDRSs are different depending on the regions where cats live or breed. Our results indicate that RDRS C2a, the oldest RD-114-related provirus, entered the host genome before an ancestor of domestic cats started diverging and the other new RDRSs might have integrated into migrating cats in Europe. We also show that infectious RD-114 virus can be resurrected by the recombination between two non-infectious RDRSs. From these data, we conclude that cats do not harbor infectious RD-114 viral loci in their genomes and RD-114-related viruses invaded cat genomes multiple times. PMID:25641657

APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles.

PubMed

Dussart, Sylvie; Douaisi, Marc; Courcoul, Marianne; Bessou, Gilles; Vigne, Robert; Decroly, Etienne

2005-01-21

APOBEC3G is a cytidine deaminase that limits the replication of many retroviruses. This antiviral host factor is packaged into retrovirus particles, where it targets single-stranded DNA generated during reverse transcription and induces up to 2% of G-to-A mutations, which are lethal for the HIV-1 provirus. Vif protein counteracts this antiviral factor by decreasing its packaging into lentivirus particles. Here, we demonstrate that Nedd4-1, an HECT E3 ubiquitin ligase, interacts with APOBEC3G, through its WW2 and WW3 domains. As a result of this interaction, APOBEC3G undergoes post-translational modification by addition of ubiquitin moieties. Accordingly, we demonstrate that the dominant negative Nedd4-1 C/S form prevents APOBEC3G ubiquitination. Moreover, the packaging of APOBEC3G into Pr55 Gag virus-like particles and into HIV-1 virions is reduced when Nedd4-1 C/S is expressed. During HIV-1 viral production in the presence of APOBEC3G, Nedd4-1 C/S restores partially the infectivity of Deltavif HIV-1. We conclude that the ubiquitination of APOBEC3G by Nedd4-1 favors its targeting to the virus assembly site where APOBEC3G interacts with Gag and is packaged into HIV-1 particles in the absence of Vif.

Prevalence of Drug-Resistance Mutations and Non–Subtype B Strains Among HIV-Infected Infants From New York State

PubMed Central

Karchava, Marine; Pulver, Wendy; Smith, Lou; Philpott, Sean; Sullivan, Timothy J.; Wethers, Judith; Parker, Monica M.

2010-01-01

Summary Prevalence studies indicate that transmission of drug-resistant HIV has been rising in the adult population, but data from the perinatally infected pediatric population are limited. In this retrospective study, we sequenced the pol region of HIV from perinatally infected infants diagnosed in New York State in 2001–2002. Analyses of drug resistance, subtype diversity, and perinatal antiretroviral exposure were conducted, and the results were compared with those from a previous study of HIV-infected infants identified in 1998–1999. Eight of 42 infants (19.1%) had provirus carrying at least 1 drug-resistance mutation, an increase of 58% over the 1998–1999 results. Mutations conferring resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors were detected in 7.1%, 11.9%, and 2.4% of specimens, respectively. Consistent with previous results, perinatal antiretroviral exposure was not associated with drug resistance (P = 0.70). Phylogenetic analysis indicated that 16.7% of infants were infected with a non–subtype B strain of HIV. It seems that drug-resistant and non–subtype B strains of HIV are becoming increasingly common in the perinatally infected population. Our results highlight the value of resistance testing for all HIV-infected infants upon diagnosis and the need to consider subtype diversity in diagnostic and treatment strategies. PMID:16868498

Seroprevalence of bovine immunodeficiency virus and bovine leukemia virus in draught animals in Cambodia.

PubMed

Meas, S; Ohashi, K; Tum, S; Chhin, M; Te, K; Miura, K; Sugimoto, C; Onuma, M

2000-07-01

Since bovine immunodeficiency virus (BIV), known as bovine lentivirus, has been detected in dairy and beef cattle in various countries around the world, a prevalence study of antibodies to BIV and bovine leukemia virus (BLV) was conducted in draught animals in five provinces in Cambodia, where protozoan parasite infections were suspected in some animals. To clarify the status of draught animals including Haryana, Brahman, mixed-breed, local breed cattle and muscle water buffaloes, a total of 544 cattle and 42 buffaloes were tested, and 26.3 and 16.7%, respectively, were found positive for anti-BIV p26 antibodies determined by Western blotting. There were 5.3% positive for anti-BLV antibodies detected by immunodiffusion test among the cattle, but no reactors among buffaloes and no dual infection for both BIV and BLV was determined in this study. Peripheral blood mononuclear cells from BIV-seropositive cattle were found to have BIV-provirus DNA, as detected by polymerase chain reaction and subsequent Southern blot hybridization. This is the first evidence for the presence of BIV and BLV infections in draught animals in tropical countries such as Cambodia. This wide distribution of BIV suggests its association with problems in animal health as reported worldwide, and that a primary BIV infection can predispose death of affected animals by other aggressive pathogens or stresses.

Evolution of plant virus movement proteins from the 30K superfamily and of their homologs integrated in plant genomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mushegian, Arcady R., E-mail: mushegian2@gmail.com; Elena, Santiago F., E-mail: sfelena@ibmcp.upv.es; The Santa Fe Institute, Santa Fe, NM 87501

Homologs of Tobacco mosaic virus 30K cell-to-cell movement protein are encoded by diverse plant viruses. Mechanisms of action and evolutionary origins of these proteins remain obscure. We expand the picture of conservation and evolution of the 30K proteins, producing sequence alignment of the 30K superfamily with the broadest phylogenetic coverage thus far and illuminating structural features of the core all-beta fold of these proteins. Integrated copies of pararetrovirus 30K movement genes are prevalent in euphyllophytes, with at least one copy intact in nearly every examined species, and mRNAs detected for most of them. Sequence analysis suggests repeated integrations, pseudogenizations, andmore » positive selection in those provirus genes. An unannotated 30K-superfamily gene in Arabidopsis thaliana genome is likely expressed as a fusion with the At1g37113 transcript. This molecular background of endopararetrovirus gene products in plants may change our view of virus infection and pathogenesis, and perhaps of cellular homeostasis in the hosts. - Highlights: • Sequence region shared by plant virus “30K” movement proteins has an all-beta fold. • Most euphyllophyte genomes contain integrated copies of pararetroviruses. • These integrated virus genomes often include intact movement protein genes. • Molecular evidence suggests that these “30K” genes may be selected for function.« less

A novel gammaretroviral shuttle vector insertional mutagenesis screen identifies SHARPIN as a breast cancer metastasis gene and prognostic biomarker.

PubMed

Bii, Victor M; Rae, Dustin T; Trobridge, Grant D

2015-11-24

Breast cancer (BC) is the second leading cause of malignancy among U.S. women. Metastasis results in a poor prognosis and increased mortality, but the molecular mechanisms by which metastatic tumors occur are not well understood. Identifying the genes that drive the metastatic process could provide targets for improved therapy and biomarkers to improve BC patient outcomes. Using a forward mutagenesis screen, BC cells mutagenized with a replication-incompetent gammaretroviral vector (γRV) were xenotransplanted into the mammary fat pad of immunodeficient mice. In this approach the vector provirus dysregulates nearby genes, providing a selective advantage to transduced cells to form metastases. Metastatic tumors were analyzed for proviral integration sites to identify nearby candidate metastasis genes. The γRV has a transgene cassette that allows for rescue in bacteria and rapid identification of vector integration sites. Using this approach, we identified the previously described metastasis gene WWTR1 (TAZ), and three other novel candidate metastasis genes including SHARPIN. SHARPIN was independently validated in vivo as a BC metastasis gene. Analysis of patient data showed that SHARPIN expression predicts metastasis-free survival after adjuvant therapy. Our approach has broad potential to identify genes involved in oncogenic processes for BC and other cancers. We show here it can identify both known (WWTR1) and novel (SHARPIN) BC metastasis genes.

Association between blood cholesterol level with periodontal status of coronary heart disease patients

NASA Astrophysics Data System (ADS)

Valensia, Rosy; Masulili, Sri Lelyati C.; Lessang, Robert; Radi, Basuni

2017-02-01

Coronary heart disease (CHD) is an abnormal narrowing of heart arteries associated with local accumulation of lipids, in the form of cholesterol and triglycerides. Periodontal disease is a chronic inflammatory that suggests link to the development of CHD. In periodontitis have been reported changes in lipid profile, include increased of cholesterol levels of blood. Objective: to analyse correlation between blood cholesterol level with periodontal status of CHD and non CHD subjects. Methods: Periodontal status and blood cholesterol level of 60 CHD and 40 non CHD subjects was measured. Result: Blood cholesterol level in CHD subjects differs from non CHD subjects (p=0.032). Blood cholesterol level correlates with pocket depth (p=0.003) and clinical attachment loss (CAL) (p=0.000) in CHD subjects. Blood cholesterol level correlates with pocket depth (p=0.010) in non CHD subjects. There is no significant correlation between blood cholesterol level and bleeding on probing (BOP) in CHD subjects. There is no significant correlation between blood cholesterol level with BOP and CAL in non CHD subjects. Conclusion: Blood cholesterol level in control group is higher than CHD patients. Blood cholesterol level positively associated with pocket depth (r=0.375) and CAL (r=0.450) in CHD patients. Blood cholesterol level is positively associated with pocket depth (r=0.404) in control group.

Correlates of vitamin D in psychotic disorders: A comprehensive systematic review.

PubMed

Adamson, James; Lally, John; Gaughran, Fiona; Krivoy, Amir; Allen, Lauren; Stubbs, Brendon

2017-03-01

People with psychosis have high prevalence of low vitamin D levels but the correlates and relevance of this deficiency are unclear. A systematic search of major databases from inception to 03/2016 was undertaken investigating correlates of vitamin D in people with psychosis. Data was summarised with a best evidence synthesis. Across 23 included studies (n=1770 psychosis, n=8171 controls) a mean difference in vitamin D levels between both groups of -11.14ng/ml±0.59 was found. 53 unique correlations between vitamin D and outcomes in people with psychosis were identified. The evidence base was broadly equivocal although season of blood sampling (67% of studies found a positive correlation with warmer seasons) and parathyroid hormone (100% of studies found a negative correlation) were associated with vitamin D levels. The most commonly non-correlated variables were: BMI (83% found no correlation), age (73%), gender (86%), smoking (100%), duration of illness (100%) and general assessment of functioning score (100%). In conclusion, whilst many unique correlates have been investigated, there is weak and inconclusive evidence regarding the consistency and meaning of the correlates of vitamin D levels in people with psychosis. Future longitudinal studies should consider the correlates of vitamin D in people with psychosis. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Correlation between benzene and testosterone in workers exposed to urban pollution.

PubMed

Rosati, M V; Sancini, A; Tomei, F; Sacco, C; Traversini, V; De Vita, A; De Cesare, D P; Giammichele, G; De Marco, F; Pagliara, F; Massoni, F; Ricci, L; Tomei, G; Ricci, S

2017-01-01

Many studies have examined the effects of benzene on testosterone. The purpose of this study was to evaluate the possible correlation between the blood levels of benzene and the levels of testosterone. The study involved a group of 148 subjects. For every worker have been made out a blood sample for the evaluation of benzene and testosterone levels and an urine analysis for the evaluation of the levels of trans, trans-muconic acid and S-phenylmercapturic acid. We estimated the Pearson correlation coefficient between the variables in the sample and the urinary metabolites, age, length of service, gender, BMI. For the analysis of the major confounding factors it was performed a multiple linear regression. The Pearson correlation coefficiet showed: 1. a significant inverse correlation between the S-phenyl mercapturic acid and free testosterone; 2. a significant direct correlation between trans-trans muconic acid and BMI. After dividing the sample according to the median of blood benzene (161.0 ng / L), Pearson correlation coefficient showed a significant inverse correlation between the S-phenyl mercapturic acid and free testosterone in the group with values below this median. Our results, to be considered preliminary, suggest that occupational exposure to low levels of benzene, present in urban pollution, affect the blood levels of testosterone. These results need to be confirmed in future studies, with the eventual possibility of including more specific fertility tests.

High Avidity dsDNA Autoantibodies in Brazilian Women with Systemic Lupus Erythematosus: Correlation with Active Disease and Renal Dysfunction

PubMed Central

Oliveira, Rodrigo C.; Oliveira, Isabela S.; Santiago, Mittermayer B.; Sousa Atta, Maria L. B.; Atta, Ajax M.

2015-01-01

We investigated in Brazilian women with SLE the prevalence and levels of high avidity (HA) dsDNA antibodies and tested their correlation with lupus activity and biomarkers of renal disease. We also compared these correlations to those observed with total dsDNA antibodies and antibodies against nucleosome (ANuA). Autoantibodies were detected by ELISA, while C3 and C4 levels were determined by nephelometry. Urine protein/creatinine ratio was determined, and lupus activity was measured by SLEDAI-2K. The prevalence of total and HA dsDNA antibodies was similar to but lower than that verified for ANuA. The levels of the three types of antibodies were correlated, but the correlation was more significant between HA dsDNA antibodies and ANuA. High avidity dsDNA antibodies correlated positively with ESR and SLEDAI and inversely with C3 and C4. Similar correlations were observed for ANuA levels, whereas total dsDNA antibodies only correlated with SLEDAI and C3. The levels of HA dsDNA antibodies were higher in patients with proteinuria, but their levels of total dsDNA antibodies and ANuA were unaltered. High avidity dsDNA antibodies can be found in high prevalence in Brazilian women with SLE and are important biomarkers of active disease and kidney dysfunction. PMID:26583157

High Avidity dsDNA Autoantibodies in Brazilian Women with Systemic Lupus Erythematosus: Correlation with Active Disease and Renal Dysfunction.

PubMed

Oliveira, Rodrigo C; Oliveira, Isabela S; Santiago, Mittermayer B; Sousa Atta, Maria L B; Atta, Ajax M

2015-01-01

We investigated in Brazilian women with SLE the prevalence and levels of high avidity (HA) dsDNA antibodies and tested their correlation with lupus activity and biomarkers of renal disease. We also compared these correlations to those observed with total dsDNA antibodies and antibodies against nucleosome (ANuA). Autoantibodies were detected by ELISA, while C3 and C4 levels were determined by nephelometry. Urine protein/creatinine ratio was determined, and lupus activity was measured by SLEDAI-2K. The prevalence of total and HA dsDNA antibodies was similar to but lower than that verified for ANuA. The levels of the three types of antibodies were correlated, but the correlation was more significant between HA dsDNA antibodies and ANuA. High avidity dsDNA antibodies correlated positively with ESR and SLEDAI and inversely with C3 and C4. Similar correlations were observed for ANuA levels, whereas total dsDNA antibodies only correlated with SLEDAI and C3. The levels of HA dsDNA antibodies were higher in patients with proteinuria, but their levels of total dsDNA antibodies and ANuA were unaltered. High avidity dsDNA antibodies can be found in high prevalence in Brazilian women with SLE and are important biomarkers of active disease and kidney dysfunction.

Possible correlation between gut microbiota and immunity among healthy middle-aged and elderly people in southwest China.

PubMed

Shen, Xi; Miao, Junjie; Wan, Qun; Wang, Shuyue; Li, Ming; Pu, Fangfang; Wang, Guoqing; Qian, Wei; Yu, Qian; Marotta, Francesco; He, Fang

2018-01-01

The present study was conducted to investigate the possible association between gut microbes and immunity among healthy middle-aged and elderly individuals in southwest China. A total of 148 healthy adults aged ≥ 50 years were divided into two age groups: middle-aged group (50-59 years; n = 67, 54.13 ± 3.32) and elderly group (≥ 60 years; n = 81, 64.70 ± 3.93). Blood samples were collected to measure serum immune and biochemical indices. Gut microbiota compositions of the groups were characterized on the basis of faecal DNA using 16S rRNA gene sequencing. Among the detected gut microbes, the presence of Alistipes was negatively correlated with age in both groups. In the middle-aged group, age was negatively correlated with the presence of Desulfovibrio and Faecalibacterium . In the elderly group, Coprococcus was present at significantly higher levels; age was negatively correlated with the presence of Lachnobacterium , Oxalobacter and the Chao index, whereas positively correlated with the presence of Sutterella. In the middle-aged group, the presence of Bacteroidetes was positively correlated with serum immunoglobulin G (IgG) levels and the percent of CD8 + T cells and negatively correlated with the CD4 + /CD8 + ratio; the presence of Firmicutes was negatively correlated with IgM levels; Bacteroidetes/Firmicutes ratio was positively correlated with IgG and IgM levels and Simpson index was negatively correlated with the percent of CD8 + T cells and positively correlated with CD4 + /CD8 + ratio. In the elderly group, the presence of Verrucomicrobia (identified as genus Akkermansia ) was positively correlated with IgA levels and the percent of CD8 + T cells and negatively correlated with the percent of CD4 + T cells and CD4 + /CD8 + ratio; the Chao index and observed species were positively correlated with IgA levels. These results indicated that ageing could significantly correlate with the composition of gut microbiota in terms of quantity and quality. Changes in gut microbiota caused by ageing, characterized by decreased Bacteroidetes levels, might be associated with immunosenescence among healthy middle-aged and elderly people in southwest China.

Neural Correlates of Decision-Making Under Ambiguity and Conflict.

PubMed

Pushkarskaya, Helen; Smithson, Michael; Joseph, Jane E; Corbly, Christine; Levy, Ifat

2015-01-01

HIGHLIGHTS We use a simple gambles design in an fMRI study to compare two conditions: ambiguity and conflict.Participants were more conflict averse than ambiguity averse.Ambiguity aversion did not correlate with conflict aversion.Activation in the medial prefrontal cortex correlated with ambiguity level and ambiguity aversion.Activation in the ventral striatum correlated with conflict level and conflict aversion. Studies of decision making under uncertainty generally focus on imprecise information about outcome probabilities ("ambiguity"). It is not clear, however, whether conflicting information about outcome probabilities affects decision making in the same manner as ambiguity does. Here we combine functional magnetic resonance imaging (fMRI) and a simple gamble design to study this question. In this design the levels of ambiguity and conflict are parametrically varied, and ambiguity and conflict gambles are matched on expected value. Behaviorally, participants avoided conflict more than ambiguity, and attitudes toward ambiguity and conflict did not correlate across participants. Neurally, regional brain activation was differentially modulated by ambiguity level and aversion to ambiguity and by conflict level and aversion to conflict. Activation in the medial prefrontal cortex was correlated with the level of ambiguity and with ambiguity aversion, whereas activation in the ventral striatum was correlated with the level of conflict and with conflict aversion. These novel results indicate that decision makers process imprecise and conflicting information differently, a finding that has important implications for basic and clinical research.

Neural Correlates of Decision-Making Under Ambiguity and Conflict

PubMed Central

Pushkarskaya, Helen; Smithson, Michael; Joseph, Jane E.; Corbly, Christine; Levy, Ifat

2015-01-01

HIGHLIGHTS We use a simple gambles design in an fMRI study to compare two conditions: ambiguity and conflict.Participants were more conflict averse than ambiguity averse.Ambiguity aversion did not correlate with conflict aversion.Activation in the medial prefrontal cortex correlated with ambiguity level and ambiguity aversion.Activation in the ventral striatum correlated with conflict level and conflict aversion. Studies of decision making under uncertainty generally focus on imprecise information about outcome probabilities (“ambiguity”). It is not clear, however, whether conflicting information about outcome probabilities affects decision making in the same manner as ambiguity does. Here we combine functional magnetic resonance imaging (fMRI) and a simple gamble design to study this question. In this design the levels of ambiguity and conflict are parametrically varied, and ambiguity and conflict gambles are matched on expected value. Behaviorally, participants avoided conflict more than ambiguity, and attitudes toward ambiguity and conflict did not correlate across participants. Neurally, regional brain activation was differentially modulated by ambiguity level and aversion to ambiguity and by conflict level and aversion to conflict. Activation in the medial prefrontal cortex was correlated with the level of ambiguity and with ambiguity aversion, whereas activation in the ventral striatum was correlated with the level of conflict and with conflict aversion. These novel results indicate that decision makers process imprecise and conflicting information differently, a finding that has important implications for basic and clinical research. PMID:26640434

[Immune status in infantile autism. Correlation between the immune status, autistic symptoms and levels of serotonin].

PubMed

Ferrari, P; Marescot, M R; Moulias, R; Bursztejn, C; Deville Chabrolle, A; Thiollet, M; Lesourd, B; Braconnier, A; Dreux, C; Zarifian, E

1988-01-01

In sixteen autistic children high values of IgG and a high level of lymphocyte stimulation with PHA were observed. Principal component analysis showed: 1) a significant correlation between basic lymphocyte mitogenic activity and the clinical symptoms opposition and hyperactivity, 2) a significant correlation between high Ig levels, high PHA stimulation responses and the main autistic symptoms (withdrawal, inaffectivity, hypoactivity, mannerism, stereotypy and negatively echolalia), 3) a significant correlation with serotonin uptake by platelets and high immunological responses. Such correlations are strongly in favor of an immunologic component in autistic disease.

Increased serum APRIL differentially correlates with distinct cytokine profiles and disease activity in systemic lupus erythematosus patients.

PubMed

Boghdadi, Ghada; Elewa, Enass A

2014-09-01

Cytokines play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Among the cytokines that regulate B cell homeostasis is a proliferation-inducing ligand (APRIL). This study aimed to determine whether serum levels of APRIL are raised in patients with SLE and correlate with disease activity or proinflammatory cytokines production, or both. Serum APRIL, interleukin-17 (IL-17), IL-4 and interferon gamma (IFN-γ) levels were measured in forty patients with SLE and 30 healthy controls. Disease activity was assessed by SLE disease activity index (SLEDAI), and results were correlated with serum APRIL levels. Serum APRIL levels were significantly higher in patients with SLE than in healthy controls. Positive correlation was found between serum APRIL levels and total SLEDAI score and anti-dsDNA antibody titers. Moreover, serum APRIL levels was significantly higher in patients with arthritis, mucocutaneous manifestations and proteinuria. APRIL is increased in patients with active SLE accompanying the increase of IL-17 and IFN-γ. Significant positive correlations between serum levels of APRIL and IL-17 and IFN-γ and a negative correlation between serum levels of APRIL and IL-4 were found. The results suggest that APRIL may be an important marker of disease activity in patients with SLE. We provide the analyses of APRIL levels in patients with SLE, suggesting new tools for the diagnosis, prognosis and possible therapeutic management of SLE.

Assessing bicycle-related trauma using the biomarker S100B reveals a correlation with total injury severity.

PubMed

Thelin, E P; Zibung, E; Riddez, L; Nordenvall, C

2016-10-01

Worldwide, the use of bicycles, for both recreation and commuting, is increasing. S100B, a suggested protein biomarker for cerebral injury, has been shown to correlate to extracranial injury as well. Using serum levels of S100B, we aimed to investigate how S100B could be used when assessing injuries in patients suffering from bicycle trauma injury. As a secondary aim, we investigated how hospital length of stay and injury severity score (ISS) were correlated to S100B levels. We performed a retrospective, database study including all patients admitted for bicycle trauma to a level 1 trauma center over a four-year period with admission samples of S100B (n = 127). Computerized tomography (CT) scans were reviewed and remaining data were collected from case records. Univariate- and multivariate regression analyses, linear regressions and comparative statistics (Mann-Whitney) were used where appropriate. Both intra- and extracranial injuries were correlated with S100B levels. Stockholm CT score presented the best correlation of an intracranial parameter with S100B levels (p < 0.0001), while the presences of extremity injury, thoracic injury, and non-cervical spinal injury were also significantly correlated (all p < 0.0001, respectively). A multivariate linear regression revealed that Stockholm CT score, non-cervical spinal injury, and abdominal injury all independently correlated with levels of S100B. Patients with a ISS > 15 had higher S100 levels than patients with ISS < 16 (p < 0.0001). Patients with extracranial, as well as intracranial- and extracranial injuries, had significantly higher levels of S100B than patients without injuries (p < 0.05 and p < 0.01, respectively). The admission serum levels of S100B (log, µg/L) were correlated with ISS (log) (r = 0.53) and length of stay (log, days) (r = 0.45). S100B levels were independently correlated with intracranial pathology, but also with the extent of extracranial injury. Length of stay and ISS were both correlated with the admission levels of S100B in bicycle trauma, suggesting S100B to be a good marker of aggregated injury severity. Further studies are warranted to confirm our findings.

Serum vaspin levels and vaspin mRNA expression in subcutaneous adipose tissue in women with gestational diabetes mellitus.

PubMed

Mm, Wei Qian; Fan, Jianxia; Khor, Shuzin; Song, Mengfan; Hong, Wei; Dai, Xiaobei

2014-11-01

To compare serum vaspin level and mRNA and protein levels of vaspin in adipose tissue in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGR), along with the correlation between serum vaspin level with fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and birth-weight. Thirty-seven women with GDM and 36 with NGR were enrolled. Total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), FINS and vaspin levels were measured. The mRNA and protein levels were detected using RT-PCR and Western blot. Pearson correlation analysis (PCA) was performed to reveal the correlation between serum vaspin level and FINS, HOMA-IR. Spearman correlation analysis (SCA) was conducted to examine the association between serum vaspin level and birth-weight. HDL-C level in GDM was lower than NGR group (P<0.05), and there were no statistical differences in TC, TG, LDL-C, FPG, FINS and HOMA-IR between the two groups. Serum vaspin level, mRNA and protein expression levels of vaspin in GDM were higher than NGR group (P<0.05). Serum vaspin level was not significantly correlated with FINS and HOMA-IR, but had a positive correlation with birth-weight (P=0.023). Serum vaspin level cannot serve as an independent predictor of IR. The increased serum vaspin level and increased vaspin mRNA and protein expression in adipose tissues in GDM women indicate that vaspin may be involved in the pathogenesis of GDM, but its exact mechanism needs further study. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Gama-aminobutyric acid accumulation in Elsholtzia splendens in response to copper toxicity*

PubMed Central

Yang, Xiao-e; Peng, Hong-yun; Tian, Sheng-ke

2005-01-01

A solution with different Cu supply levels was cultured to investigate gama-aminobutyric acid (GABA) accumulation in Elsholtzia splendens, a native Chinese Cu-tolerant and accumulating plant species. Increasing Cu from 0.25 to 500 μmol/L significantly enhanced levels of GABA and histidine (His), but considerably decreased levels of aspartate (Asp) and glutamate (Glu) in the leaves. The leaf Asp level negatively correlated with leaf Cu level, while leaf GABA level positively correlated with leaf Cu level. The leaf Glu level negatively correlated with leaf GABA level in Elsholtzia splendens. The depletion of leaf Glu may be related to the enhanced synthesis of leaf GABA under Cu stress. PMID:15633244

The correlation between serum amyloid A and reactive oxygen metabolites in a young Mongolian population.

PubMed

Kotani, Kazuhiko; Yamada, Toshiyuki; Uurtuya, Shuumarjav; Taniguchi, Nobuyuki

2012-01-01

Chronic inflammation and oxidative stress are associated with lifestyle-related diseases. Research into the pathophysiology of lifestyle-related diseases is important for Mongolian people. Our study investigated the correlation among the d-ROMs test (a measure of the total oxidant capacity of blood), serum amyloid A (SAA) and high-sensitivity C-reactive protein (hs-CRP) levels in a young Mongolian population. The data, including anthropometric and biochemical markers, were collected from 78 Mongolian volunteers (male/female = 27/ 51, mean age 21 years). The correlation between the SAA and d-ROMs levels was examined, as well as the correlation between the hs-CRP and d-ROMs levels. The SAA levels were 3.2 microg/mL (median), hs-CRP .04 mg/dL (median) and d-ROMs 309 CARR U, respectively. There was a significant and positive correlation between the SAA and d-ROMs levels (r=.40, P<.01), in addition to a significant and positive correlation between the hs-CRP and d-ROMs levels (r = .32, P < .01). These significant correlations remained independent in a multiple linear regression analysis. A subgroup analysis by sex revealed the positive correlation between the SAA and d-ROMs levels to be greater, relative to that between the hs-CRP and d-ROMs levels, particularly in the female group. The coexistence of chronic inflammation and oxidative stress can be present even in young Mongolian people, suggesting that their coexistence may be a target of early prevention of lifestyle-related diseases. In addition, not only hs-CRP, but also SAA can be used to evaluate the relationship of oxidative stress in this population. Further studies are necessary to confirm the observed relationship.

Correlation Between Personality Traits and Testosterone Concentrations in Healthy Population.

PubMed

Tajima-Pozo, Kazuhiro; Bayón, Camila; Díaz-Marsá, Marina; Carrasco, Jose Luis

2015-01-01

High plasma testosterone levels have been associated with aggression, sexual behaviour and social status. The aim of this paper was to study the correlation between basal plasma testosterone levels and personality variables in healthy participants. Fifty-four participants were randomly enrolled into this study. Basal plasma testosterone levels were measured between 8:30 am and 10 am. After 24 hours of blood drawing, each subject completed personality questionnaires. Positive correlation between basal plasma testosterone levels and anti-social personality traits in both genders was observed (r = 0.336 and P < 0.018). Also, a positive correlation was observed between basal plasmatestosterone levels and criminal thinking traits (r = 0. 376, P < 0.05) and Millon compulsive (r = 0.386, P < 0.010) in both genders. In female participants, a positive correlation between basal plasmatestosterone levels and psychoticism (r = 0. 25, P < 0.019) and Cloninger AUTO TCI (r = 0.507, P < 0.004) was observed. In males participants positive correlation between baseline plasmatic Testosterone levels and Millon Antisocial trait (r = 0. 544, P < 0.19) and Millon Hypomania trait (r = 0. 485, P < 0.41) and Millon Drug Abuse trait (r = 0.632, P < 0.05) was reported. Our results suggest gender differences in clinical and personality variables related with basal plasma testosterone level. In men, high plasma testosterone levels were associated with clinical traits, substance abuse and hypomania. Women with higher basal testosterone levels showed higher scores on personality self-direction traits.

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

PubMed

Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

2004-01-01

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

Correlation of Zn2+ content with aflatoxin content of corn.

PubMed Central

Failla, L J; Lynn, D; Niehaus, W G

1986-01-01

Forty-nine samples from the 1983 Virginia corn harvest were analyzed for aflatoxin, zinc, copper, iron, and manganese content. Values (mean +/- standard deviation) were as follows: aflatoxin, 117 +/- 360 micrograms/kg; zinc, 22.5 +/- 3.4 mg/kg; copper, 2.27 +/- 0.56 mg/kg; iron, 40.8 +/- 18.7 mg/kg; and manganese, 5.1 +/- 1.1 mg/kg. Aflatoxin levels positively correlated with zinc (Spearman correlation coefficient, 0.385; P less than 0.006) and copper levels (Spearman correlation coefficient, 0.573; P less than 0.0001). Based on biochemical data in the literature, we believe that the correlation with zinc is important and that there may be a cause-and-effect relationship between zinc levels in corn and aflatoxin levels which are produced upon infection with Aspergillus flavus or A. parasiticus. Control of aflatoxin contamination in field corn by decreasing the zinc levels may be feasible, but no methods to decrease zinc levels are currently available. PMID:3729406

Pseudocholinesterase levels in patients under electroconvulsive therapy

PubMed Central

Küçükosman, Gamze; Pişkin, Özcan; Hancı, Volkan; Okyay, Rahşan D.; Ayoğlu, Hilal; Yurtlu, Bülent S.; Akın, Mehmet; Turan, Işıl

2018-01-01

Objectives: In this study, we aimed to retrospectively assess the correlation of pseudocholinesterase (PChE) levels with age, gender, body weight and diagnosed psychiatric diseases in electroconvulsive therapy (ECT) cases. Methods: This retrospective study was conducted at Bülent Ecevit University Hospital, Zonguldak, Turkey, between 2007 and 2011. In the study, 193 ECT case files were retrospectively scanned to evaluate PChE values before ECT and other file information. Results: There was no difference between gender in terms of PChE levels. Correlation analysis determined a weakly positive correlation between age (p=0.013; correlation coefficient [cc]: 0.178) and body weight (p<0.001; cc: 0.273) and PChE levels. No correlation was found between age, gender, weight or psychiatric diagnosis, and PChE levels. Conclusion: Neuromuscular blockage is a significant factor that increases patient safety, while increasing the efficacy of ECT. In choosing muscle relaxant agents, both patient factors and the pharmacological properties of the neuromuscular blocker should be considered. We think that in situations with delayed recovery of ECT cases without identified PChE levels, low PChE levels must be considered. PMID:29332117

Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs.

PubMed

Marsella, Rosanna; Ahrens, Kim; Sanford, Rachel

2018-02-01

IL-31 is a cytokine that is believed to play an important role in atopic dermatitis (AD). IL-31 levels positively correlate with disease severity in children with AD. Currently, there is no study that has investigated such a correlation in atopic dogs. The purpose of this study was to evaluate the correlation between IL-31 serum levels and severity of dermatitis. It was hypothesized that a positive correlation exists between severity of AD and circulating levels of IL-31. Sixteen atopic beagles experimentally sensitized to house dust mites. Atopic beagles were exposed to dust mites epicutaneously twice weekly for four weeks. Severity of dermatitis was scored by the Canine Atopic Dermatitis and Extent Severity Index, 3 rd iteration (CADESI-03) on days 0 and 28. Blood samples were taken on days 0 and 28 to measure serum IL-31 using a commercially available ELISA. Correlation between CADESI-03 scores and serum IL-31 levels was not detected on day 0 (Pearson, r = -0.2609, P = 0.3291). After flare-up of dermatitis was induced with allergen exposure, a significant positive correlation was detected between serum IL-31 and CADESI-03 on Day 28 (r = 0.6738, P = 0.004). Positive correlation was detected in active disease between severity of dermatitis and circulating levels of IL-31. Additional studies are needed to investigate this correlation in other breeds of dogs and to test whether circulating levels of IL-31 may predict clinical response to biological agents aimed at IL-31. © 2017 ESVD and ACVD.

Surgical management of congenital heart disease: correlation between hospital costs and the Aristotle complexity score.

PubMed

Sinzobahamvya, N; Kopp, T; Photiadis, J; Arenz, C; Schindler, E; Haun, C; Hraska, V; Asfour, B

2010-09-01

Hospital costs are expected to correlate with clinical complexity. Do costs for congenital heart surgery correlate with Aristotle complexity scores? 442 inpatient stays in 2008 were evaluated. Aristotle scores and levels were determined. Costs were estimated according to the German Institute for Hospital Reimbursement system. Pearson and Spearman R correlation coefficients and corresponding goodness-of-fit regression coefficients R2 were calculated. Mean basic and comprehensive Aristotle scores were 7.60 +/- 2.74 and 9.23 +/- 2.94 points, respectively. Mean expenses per hospital stay amounted to 29,369 +/- 30,823 Euros. Aristotle basic and comprehensive scores and levels were positively correlated with hospital costs. With a Spearman R of 1 and related R2 of 0.9436, scores of the 6 Aristotle comprehensive levels correlated best. Mean hospital reimbursement was 26,412 +/- 17,962 Euros. Compensation was higher than expenses for patients in comprehensive levels 1 to 3, but much lower for those in levels 4 to 6. Aristotle comprehensive complexity scores were highly correlated with hospital costs. The Aristotle score could be used as a scale to establish the correct reimbursement after congenital heart surgery. Georg Thieme Verlag KG Stuttgart, New York.

Interactions between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly.

PubMed

Dilley, Kari A; Nikolaitchik, Olga A; Galli, Andrea; Burdick, Ryan C; Levine, Louis; Li, Kelvin; Rein, Alan; Pathak, Vinay K; Hu, Wei-Shau

2017-08-15

Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious viruslike particles, and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus. However, such enhancement is diminished when Gag is overexpressed, suggesting that the effects of viral RNA can be replaced by increased Gag concentration in cells. We also showed that the specific interactions between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA-Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged into each nascent virion. These studies shed light on the mechanism by which HIV-1 achieves efficient genome packaging during virus assembly. IMPORTANCE Retrovirus assembly is a well-choreographed event, during which many viral and cellular components come together to generate infectious virions. The viral RNA genome carries the genetic information to new host cells, providing instructions to generate new virions, and therefore is essential for virion infectivity. In this report, we show that the specific interaction of the viral RNA genome with the structural protein Gag facilitates virion assembly and particle production. These findings resolve the conundrum that HIV-1 RNA is selectively packaged into virions with high efficiency despite being dispensable for virion assembly. Understanding the mechanism used by HIV-1 to ensure genome packaging provides significant insights into viral assembly and replication. Copyright © 2017 American Society for Microbiology.

Ethical decision-making and professional behaviour among nurses: a correlational study.

PubMed

Cerit, Birgül; Dinç, Leyla

2013-03-01

This study examined the relationship between nurses' ethical decision-making levels and their professional behaviours. Data were collected from 225 nurses who were recruited from university hospitals in Ankara using proportionate sampling. Data were analysed using descriptive statistics and Pearson correlations. Most of the nurses were familiar with ethical dilemmas in nursing practice. The Nursing Principled Thinking level was above average, while the Practical Consideration level was average. Nurses' professionalism level was low. There was a positive but weak correlation between professional behaviours of the nurses and their ethical decision-making levels. Increasing nurses' professionalism level can provide a positive contribution to the ethical decision-making level.

Powering Up Mitichondrial Functions to Treat Mitochondrial Disease

DTIC Science & Technology

2017-10-01

derived hormone whose serum level correlates positively with the severity of mitochondrial cardiomyopathy (recently published with DOD grant support...derived hormone that regulates body growth. Circulating GDF15 level correlates positively with the severity of mitochondrial cardiomyopathy and can...Pei lab recently discovered that GDF15 is a heart-derived hormone that regulates body growth. Circulating GDF15 level correlates positively with the

Spectral correlations in Anderson insulating wires

NASA Astrophysics Data System (ADS)

Marinho, M.; Micklitz, T.

2018-01-01

We calculate the spectral level-level correlation function of Anderson insulating wires for all three Wigner-Dyson classes. A measurement of its Fourier transform, the spectral form factor, is within reach of state-of-the-art cold atom quantum quench experiments, and we find good agreement with recent numerical simulations of the latter. Our derivation builds on a representation of the level-level correlation function in terms of a local generating function which may prove useful in other contexts.

IGF-1 levels are significantly correlated with patient-reported measures of sexual function.

PubMed

Pastuszak, A W; Liu, J S; Vij, A; Mohamed, O; Sathyamoorthy, K; Lipshultz, L I; Khera, M

2011-01-01

Growth hormone (GH) supplementation may help to preserve erectile function. We assessed whether serum insulin-like growth factor 1 (IGF-1) levels, a surrogate for GH levels, correlate with sexual function scores in 65 men who completed the Sexual Health Inventory for Men (SHIM) and Expanded Prostate Cancer Index Composite (EPIC) questionnaires, and had serum IGF-1 and testosterone levels determined. Median±s.d. IGF-1 level, SHIM and EPIC scores were 235.0±86.4, 19.5±8.7 and 56.4±28.3 mg ml(-1), respectively. IGF-1 levels and total SHIM score correlate significantly (r=0.31, P=0.02), as do IGF-1 levels and all individual SHIM question scores, and IGF-1 levels and the sexual domain of the EPIC questionnaire (r=0.30, P=0.02). No correlation was observed between IGF-1 levels and Gleason score, IGF-1 and testosterone level or SHIM score and testosterone level. These data support a potential role for the GH axis in erectile function.

Omentin, an adipokine with insulin-sensitizing properties, is negatively associated with insulin resistance in normal gestation.

PubMed

Brandt, Benny; Mazaki-Tovi, Shali; Hemi, Rina; Yinon, Yoav; Schiff, Eyal; Mashiach, Roy; Kanety, Hannah; Sivan, Eyal

2015-05-01

Omentin, a newly identified adipokine, enhances insulin mediated glucose uptake in human adipocytes, thus, inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with insulin resistance indices and to assess which compartment, maternal, fetal, or placental, is the source of omentin in maternal circulation. Fasting serum glucose, insulin, and omentin were determined in 25 healthy pregnant women at the third trimester, before and 3 days after elective cesarean section. Cord blood omentin was measured in the 25 term neonates. Homeostasis model assessment (HOMA) was used to evaluate insulin sensitivity before and after delivery. Antepartum maternal omentin levels were negatively correlated with insulin levels (r=-0.41, P=0.04) and positively correlated with insulin sensitivity (HOMA%S; r=0.4, P=0.04). Postpartum omentin levels were negatively correlated with maternal body mass index (r=-0.44, P=0.02). Median maternal omentin levels was comparable before and after delivery (57.2, inter-quartile range: 38.2-76.2 ng/mL vs. 53.4, 39.8-69.4 ng/mL, respectively, P=0.25) and highly correlated (r=0.83, P<0.001). Antepartum maternal and neonatal omentin levels did not differ significantly (fetal: 62.2, 44.3-74.2 ng/mL, P=0.77) and did not correlate (P=0.6). Circulating maternal omentin levels are correlated with insulin resistance indices, suggesting that this adipokine may play a role in metabolic adaptations of normal gestation. The strong correlation between anteparum and postpartum maternal omentin levels, as well as the lack of association between maternal and neonatal omentin levels, suggest that placental or fetal compartments are unlikely as the main source of circulating maternal omentin.

Natriuretic Peptide and High-Sensitive Troponin T Concentrations Correlate with Effectiveness of Short-Term CPAP in Patients with Obstructive Sleep Apnea and Coronary Artery Disease.

PubMed

Strehmel, Ralf; Valo, Misa; Teupe, Claudius

2016-01-01

The risk of cardiovascular complications is increased in patients with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) is the most effective way to treat clinically significant OSA. We hypothesized that the concentrations of the cardiac risk markers N-terminal brain natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TropT) correlate with the effectiveness of CPAP therapy in patients with OSA and coexisting coronary artery disease (CAD). Twenty-one patients with severe OSA and coexisting CAD (group 1) and 20 control patients with severe OSA alone (group 2) were treated with CPAP and monitored by laboratory-based polysomnography. NT-proBNP and hs-TropT levels were measured before and after CPAP. Apnea-hypopnea index (AHI) and oxygen desaturation were similar in both groups. In group 1, hs-TropT levels correlated with AHI and oxygen desaturation upon CPAP. Elevated NT-proBNP levels in group 1 were significantly reduced by CPAP. NT-proBNP levels correlated with AHI and showed negative correlation with ST-segment depression. No such correlations were found in group 2. CPAP has the potential to normalize elevated NT-proBNP serum levels in patients with severe OSA and coexisting CAD. Levels of NT-proBNP and hs-TropT correlated with AHI and oxygen desaturation.

Relationships between serum brain-derived neurotrophic factor, plasma catecholamine metabolites, cytokines, cognitive function and clinical symptoms in Japanese patients with chronic schizophrenia treated with atypical antipsychotic monotherapy.

PubMed

Hori, Hikaru; Yoshimura, Reiji; Katsuki, Asuka; Atake, Kiyokazu; Igata, Ryohei; Konishi, Yuki; Nakamura, Jun

2017-08-01

Catecholamines, brain-derived neurotrophic factor (BDNF) and cytokines may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations between serum BDNF levels, plasma catecholamine metablolites, cytokines and the cognitive functions of patients with schizophrenia treated with atypical antipsychotic monotherapy. One hundred and forty-six patients with schizophrenia and 51 age- and sex-matched healthy controls were examined for peripheral biological markers and neurocognitive test. There were positive correlations between serum BDNF levels and scores for verbal memory and attention and processing speed as well as between serum BDNF levels and negative symptoms. Furthermore, there was a negative correlation between the plasma homovanillic acid (HVA) level and motor function and a positive correlation between the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) level and attention and processing speed. There were no significant correlations between interleukin-6 or tumour necrosis factor alpha and cognitive function. Moreover, there were no significant correlations between the plasma levels of HVA, MHPG, cytokines and clinical symptoms. Serum BDNF levels are positively related to the impairment of verbal memory and attention, plasma HVA levels are positively related to motor function, and plasma MHPG levels are positively related to attention in patients with schizophrenia.

Bayesian Correlation Analysis for Sequence Count Data

PubMed Central

Lau, Nelson; Perkins, Theodore J.

2016-01-01

Evaluating the similarity of different measured variables is a fundamental task of statistics, and a key part of many bioinformatics algorithms. Here we propose a Bayesian scheme for estimating the correlation between different entities’ measurements based on high-throughput sequencing data. These entities could be different genes or miRNAs whose expression is measured by RNA-seq, different transcription factors or histone marks whose expression is measured by ChIP-seq, or even combinations of different types of entities. Our Bayesian formulation accounts for both measured signal levels and uncertainty in those levels, due to varying sequencing depth in different experiments and to varying absolute levels of individual entities, both of which affect the precision of the measurements. In comparison with a traditional Pearson correlation analysis, we show that our Bayesian correlation analysis retains high correlations when measurement confidence is high, but suppresses correlations when measurement confidence is low—especially for entities with low signal levels. In addition, we consider the influence of priors on the Bayesian correlation estimate. Perhaps surprisingly, we show that naive, uniform priors on entities’ signal levels can lead to highly biased correlation estimates, particularly when different experiments have widely varying sequencing depths. However, we propose two alternative priors that provably mitigate this problem. We also prove that, like traditional Pearson correlation, our Bayesian correlation calculation constitutes a kernel in the machine learning sense, and thus can be used as a similarity measure in any kernel-based machine learning algorithm. We demonstrate our approach on two RNA-seq datasets and one miRNA-seq dataset. PMID:27701449

[Evaluation of leptin levels in plasma and their reliance on other hormonal factors affecting tissue fat levels in people with various levels of endogenous cotisol].

PubMed

Robaczyk, Maciej G

2002-01-01

The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk when compared to OTY subjects. Absolute LEP levels were correlated with trunk BF in CUS patients whereas in KON and AD groups these levels were correlated only with limb fat. Absolute LEP levels in CUS and OTY groups were comparable, whereas LEP/BFM and LEP/%BF indices were higher in the CUS group (Table 1) reflecting upregulation of LEP levels (Figs. 1, 2). BFM-corrected LEP levels were comparable in groups with normal cortisolemia, i.e. in OTY and KON groups, whereas in the AD group both absolute and BFM-corrected LEP levels were lower than in controls. No correlation was found between plasma levels of F and LEP in CUS and AD groups. This correlation was negative in KON (Fig. 3) and positive in OTY groups (Fig. 4). Moreover, KON and AD groups demonstrated a negative correlation between plasma ACTH and LEP levels. CUS patients showed positive, BFM-independent correlations between LEP levels, FIRI and G values, and a positive, BFM-dependent correlation between IRI and LEP levels. OTY patients exhibited a BFM-dependent positive correlation between FIRI and LEP levels. In these and in AD patients, a positive, BFM-independent correlation between IRI and LEP levels was found. Moreover, a negative, BFM-dependent correlation between GH and LEP levels was found in OTY patients. In this group, B-EP levels were positively correlated with LEP/BFM and LEP/%BF indices (Fig. 5). A negative correlation between LEP levels, LEP/BFM and LEP/%BF indices was ascertained in the AD group. In CUS, OTY, and KON groups, but not in the AD group, a midnight increase in leptin levels was observed. In conclusion, upregulation of leptin levels in relation to body fat in Cushing's syndrome is independent of the source of hypercortisolism. Apparently, it results from insulin resistance and hyperglycaemia and contributes to coexisting metabolic abnormalities. In Addison's disease, downregulation of leptin may reflect an adaptation mechanism to cortisol deficiency and result from low insulin and extremely high adrenocorticotrophin levels. In women with normal cortisol levels, irrespectively of nutritional status; leptin levels reflect body fat content. In obese subjects, leptin levels may be influenced by cortisol levels, high levels of insulin, IGF-1, and beta-endorphin as well as low levels of growth hormone. Disturbed function of hypothalamic-pituitary-adrenal axis (CUS, AD) does not directly influence diurnal variation in plasma leptin levels. In Cushing's syndrome, visceral fat may be a predominant source of leptin, whereas in women with normal or low cortisol levels peripherally accumulated fat may determine leptin secretion.

Powering Up Mitochondrial Functions to Treat Mitochondrial Disease

DTIC Science & Technology

2017-10-01

derived hormone whose serum level correlates positively with the severity of mitochondrial cardiomyopathy (recently published with DOD grant support...o Pei lab has recently discovered that GDF15 is a heart-derived hormone that regulates body growth. Circulating GDF15 level correlates positively...Circulating GDF15 level correlates positively with the severity of mitochondrial cardiomyopathy and can be used as a serum biomarker for our 5

Puberty timing and fluid intelligence: a study of correlations between testosterone and intelligence in 8- to 12-year-old Chinese boys.

PubMed

Shangguan, Fangfang; Shi, Jiannong

2009-08-01

Sex hormone such as testosterone was recently recognized as an important contributor of spatial cognition and intelligence during development, but the relationship between puberty timing and intelligence especially in children is largely unknown. Here in this study, we investigated the potential relationship between the level of sex hormones in saliva and fluid intelligence in 8- to 12-year-old Chinese boys. Fluid intelligence was measured by the Cattell's Culture Fair Intelligence Test. 1600 children aged 8-12 years were included in the Cattell's Culture Fair Intelligence Test and saliva samples were collected thereafter from 166 boys with normal intelligence distribution, composed of 49, 54 and 63 boys in 8-, 10- and 12-year-old group respectively. The level of salivary testosterone and estradiol was measured with enzyme-immunoassay technique. Data of BMI and age were collected. The relationship between the level of salivary sex hormones and fluid intelligence was analysed by correlation test. There was no significant correlation between salivary testosterone level and fluid intelligence in 8-year-old boys, whereas there was a significant positive correlation in 10-year-old boys and a significant negative correlation in 12-year-old boys between those two variable. To verify the correlation, we performed stepwise multivariate linear regression and discriminant analysis, with both the age and BMI of the boys and their parents, and salivary estradiol level considered. The results showed that the level of testosterone and intelligence was correlated, and the correlation was much stronger when the level of salivary testosterone was higher than 14 pg/ml. In summary, the study suggests that the relationship of testosterone and intelligence varies from late childhood to early adolescence, and the puberty timing is closely related with fluid intelligence.

Dynamical manifestations of quantum chaos

NASA Astrophysics Data System (ADS)

Torres Herrera, Eduardo Jonathan; Santos, Lea

2017-04-01

A main feature of a chaotic quantum system is a rigid spectrum, where the levels do not cross. Dynamical quantities, such as the von Neumann entanglement entropy, Shannon information entropy, and out-of-time correlators can differentiate the ergodic from the nonergodic phase in disordered interacting systems, but not level repulsion from level crossing in the delocalized phase of disordered and clean models. This is in contrast with the long-time evolution of the survival probability of the initial state. The onset of correlated energy levels is manifested by a drop, referred to as correlation hole, below the asymptotic value of the survival probability. The correlation hole is an unambiguous indicator of the presence of level repulsion. EJTH is grateful to VIEP, BUAP for financial support through the VIEP projects program.

Serum leptin levels, hormone levels, and hot flashes in midlife women.

PubMed

Alexander, Carolyn; Cochran, Chrissy J; Gallicchio, Lisa; Miller, Susan R; Flaws, Jodi A; Zacur, Howard

2010-08-01

To examine the associations between serum leptin levels, sex steroid hormone levels, and hot flashes in normal weight and obese midlife women. Cross-sectional study. University clinic. 201 Caucasian, nonsmoking women aged 45 to 54 years with a body mass index of <25 kg/m2 or >or=30 kg/m2. Questionnaire, fasting blood samples. Serum leptin and sex steroid hormone levels. Correlation and regression models were performed to examine associations between leptin levels, hormone levels, and hot flashes. Leptin levels were associated with BMI, with "ever experiencing hot flashes" (questionnaire), with hot flashes within the last 30 days, and with duration of hot flashes (>1 year, P=.03). Leptin was positively correlated with testosterone, free testosterone index, and free estrogen index and inversely associated with levels of sex hormone-binding globulin. In women with a body mass index>or=30 kg/m2, leptin levels no longer correlated with testosterone levels. Serum leptin levels are associated with the occurrence and duration of hot flashes in midlife women; however, no correlation was found between leptin and serum estradiol. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

C-reactive protein and reactive oxygen metabolites in subjects with metabolic syndrome.

PubMed

Kotani, K; Sakane, N

2012-01-01

This cross-sectional study investigated the correlation between diacron reactive oxygen metabolites (d-ROMs) and high-sensitivity C-reactive protein (hs-CRP) in subjects with or without metabolic syndrome. Cardiometabolic risk factors, d-ROMs and hs-CRP were determined in 457 women: 123 with metabolic syndrome and 334 without metabolic syndrome. The correlation between d-ROMs and hs-CRP levels was compared between the two groups. The group with metabolic syndrome had significantly higher d-ROMs and hs-CRP levels than the group without metabolic syndrome. While the d-ROMs level was significantly and positively correlated with the hs-CRP level in both groups, the correlation level between the two groups was significantly different. Multiple linear regression analysis adjusted for other cardiometabolic risk factors also showed significant positive correlation between dROMs and hs-CRP levels in both groups. Subjects with metabolic syndrome may have a closer relationship between inflammation and oxidative stress than subjects without metabolic syndrome, possibly reflecting their increased predisposition to atherosclerosis. Further studies are necessary to confirm the observed relationship.

Correlations Between MMPs and TIMPs Levels in Aqueous Humor from High Myopia and Cataract Patients.

PubMed

Jia, Yan; Hu, Dan-Ning; Sun, Jing; Zhou, Jibo

2017-04-01

To study the relationships between matrix metalloproteinases (MMP)-2, MMP-3, and tissue inhibitors of matrix metalloproteinases (TIMP)-1, TIMP-2, and TIMP-3 aqueous humor levels in patients with high myopia or cataract. MMPs and TIMPs protein levels in 65 aqueous humor samples collected from patients with high myopia or cataract during cataract or clear lens extraction surgery were measured with the Luminex xMAP Technology. The relationship between MMPs and TIMPs levels was analyzed with Spearman's correlation test. MMP-2 levels, but not MMP-3 levels, were increased in the aqueous humor from high-myopia patients. Levels of TIMP-1, -2, and -3 were positively and very significantly correlated with the MMP-2 levels (TIMP-1: r=0.626, p < 0.001; TIMP-2: r = 0.545, p < 0.001; TIMP-3: r = 0.439, p < 0.001). TIMP-2 and-3 levels did not significantly correlate with MMP-3 levels (TIMP-2: r = 0.175, p > 0.05; TIMP-3: r = 0.127, p > 0.05) and TIMP-1 levels only marginally correlated with MMP-3 levels (r = 0.278, 0.01< P < 0.05). Compared to the present findings with the relationship of MMPs and TIMPs in other fields of medicine, our results are consistent with the homeostasis hypothesis that the increase of TIMPs serves as a compensation reaction to inhibit the excessive degradation caused by the increase of MMPs and limits the development of myopia.

Congruence and functions of personal and cultural values: do my values reflect my culture's values?

PubMed

Fischer, Ronald

2006-11-01

Two studies are described examining the correlation between self- and culture-referenced values at a culture level (Study 1) and correlation between self- and culture-referenced values and self-reported behavior at an individual level (Study 2). It is found that values related to individual-group relationships (embeddedness) and expression and experience of affective feelings and emotions (affective autonomy) are significantly correlated at a culture level. In Study 2, culture-referenced values are shown to correlate with behaviors attached to social norms, whereas self-rated values are found to correlate with behaviors that are not norm-governed. Implications for measurement of cultural values and cultural and cross-cultural research designs are discussed.

Jaw Dysfunction Is Associated with Neck Disability and Muscle Tenderness in Subjects with and without Chronic Temporomandibular Disorders

PubMed Central

Silveira, A.; Gadotti, I. C.; Armijo-Olivo, S.; Biasotto-Gonzalez, D. A.; Magee, D.

2015-01-01

Purpose. Tender points in the neck are common in patients with temporomandibular disorders (TMD). However, the correlation among neck disability, jaw dysfunction, and muscle tenderness in subjects with TMD still needs further investigation. This study investigated the correlation among neck disability, jaw dysfunction, and muscle tenderness in subjects with and without chronic TMD. Participants. Forty females between 19 and 49 years old were included in this study. There were 20 healthy controls and 20 subjects who had chronic TMD and neck disability. Methods. Subjects completed the neck disability index and the limitations of daily functions in TMD questionnaires. Tenderness of the masticatory and cervical muscles was measured using an algometer. Results. The correlation between jaw disability and neck disability was significantly high (r = 0.915, P < 0.05). The correlation between level of muscle tenderness in the masticatory and cervical muscles with jaw dysfunction and neck disability showed fair to moderate correlations (r = 0.32–0.65). Conclusion. High levels of muscle tenderness in upper trapezius and temporalis muscles correlated with high levels of jaw and neck dysfunction. Moreover, high levels of neck disability correlated with high levels of jaw disability. These findings emphasize the importance of considering the neck and its structures when evaluating and treating patients with TMD. PMID:25883963

Jaw dysfunction is associated with neck disability and muscle tenderness in subjects with and without chronic temporomandibular disorders.

PubMed

Silveira, A; Gadotti, I C; Armijo-Olivo, S; Biasotto-Gonzalez, D A; Magee, D

2015-01-01

Tender points in the neck are common in patients with temporomandibular disorders (TMD). However, the correlation among neck disability, jaw dysfunction, and muscle tenderness in subjects with TMD still needs further investigation. This study investigated the correlation among neck disability, jaw dysfunction, and muscle tenderness in subjects with and without chronic TMD. Participants. Forty females between 19 and 49 years old were included in this study. There were 20 healthy controls and 20 subjects who had chronic TMD and neck disability. Subjects completed the neck disability index and the limitations of daily functions in TMD questionnaires. Tenderness of the masticatory and cervical muscles was measured using an algometer. The correlation between jaw disability and neck disability was significantly high (r = 0.915, P < 0.05). The correlation between level of muscle tenderness in the masticatory and cervical muscles with jaw dysfunction and neck disability showed fair to moderate correlations (r = 0.32-0.65). High levels of muscle tenderness in upper trapezius and temporalis muscles correlated with high levels of jaw and neck dysfunction. Moreover, high levels of neck disability correlated with high levels of jaw disability. These findings emphasize the importance of considering the neck and its structures when evaluating and treating patients with TMD.

Heavy metals in fish from the Red Sea, Arabian Sea, and Indian Ocean: effect of origin, fish species and size and correlation among the metals.

PubMed

Obaidat, Mohammad M; Massadeh, Adnan M; Al-Athamneh, Ahmad M; Jaradat, Qasem M

2015-04-01

This study determined the levels of As, Cu, Pb, and Cd in fish from Red Sea, Arabian Sea, and Indian Ocean by graphite furnace atomic absorption spectrophotometry. Metal levels were compared with international standards. The levels among fish types and origin, the relationship among metals, and the correlation between the levels and fish size were statistically tested. Fish type and origin significantly affected the levels. None of the fish contained As, Cu, and Pb above the FAO and EU codes. However, Cd exceeded the Jordanian, FAO, and EC codes from the three origins. As and Cd positively correlated with each other in Arabian Sea fish. As and Pb correlated negatively, but Cu and Cd did not correlate with fish size. This study indicates that Cd is common in fish from the three origins regardless the fish size. This warrants continuous monitoring for heavy metals, especially Cd, in internationally traded fish.

Undercarboxylated osteocalcin is associated with insulin resistance, but not adiponectin, during pregnancy.

PubMed

Srichomkwun, Panudda; Houngngam, Natnicha; Pasatrat, Sophitsachi; Tharavanij, Thipaporn; Wattanachanya, Lalita; Khovidhunkit, Weerapan

2016-07-01

In mice, undercarboxylated osteocalcin (ucOC) improves beta-cell function and insulin sensitivity through adiponectin. In humans, levels of total osteocalcin (OC) and ucOC were negatively correlated with insulin resistance (IR) indices in patients with type 2 diabetes. Whether ucOC plays a role in glucose homeostasis and whether its effect is mediated through adiponectin during pregnancy is unclear. Serum levels of total OC, ucOC, and adiponectin were measured in 130 pregnant women with varying degrees of IR [gestational diabetes mellitus (GDM), n = 74 and non-GDM, n = 56]. In all participants, total OC and ucOC levels were positively correlated with HOMA-IR and HOMA-%B, and negatively correlated with QUICKI. In contrast, adiponectin levels were negatively correlated with HOMA-IR and positively correlated with QUICKI (P < 0.01, both). However, neither total OC nor ucOC was associated with adiponectin. Although none of these markers could help distinguish women with and without GDM, total OC and ucOC levels were significantly higher in non-GDM women who had 1 abnormal OGTT value than those who had all normal OGTT values. Total OC and ucOC levels were significantly correlated with insulin secretion and IR indices, but not adiponectin levels, in pregnant women. Changes in OC might be a sensitive response to increased IR during pregnancy, which was not mediated through adiponectin.

The Correlation Between Schizophrenic Patients' Level of Internalized Stigma and Their Level of Hope.

PubMed

Olçun, Zeynep; Şahin Altun, Özlem

2017-08-01

The aim of this study is to determine the correlation between schizophrenic patients' level of internalized stigma and their level of hope. The population of the study consisted of patients who had been diagnosed with schizophrenia and also met the study inclusion criteria. The study sample selection from the population was not further divided; the study was conducted with 76 patients. The data of the study were collected using a personal information form, the Internalized Stigma of Mental Illness (ISMI) Scale, and Herth Hope Scale. The patients' mean score on the Internalized Stigma Scale was 72.78±16.05. Their score on the Hope Scale is 50.36±11.91. A significant negative correlation was found between the total mean scores of ISMI and the Herth Hope Scale (r=-0.360, p<0.01). A significant positive correlation was found between the stigma resistance subscale mean score of ISMI and the total mean score of the Herth Hope Scale (r=0.510, p<0.01). The internalized stigma levels of schizophrenic patients were found to be high, whereas their hope levels were found to be moderate. A significant negative correlation was found between internalized stigma and hope. This study also found a significant positive correlation between the stigma resistance of patients and their hope levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Positive correlation between retinol binding protein 4 (RBP4) and triglyceride level in central obesity

NASA Astrophysics Data System (ADS)

Oktaria, S.; Sari, D. K.; Dalimunthe, D.; Eyanoer, P. C.

2018-03-01

Obesity has become an epidemic in both developed and developing countries. Central obesity considered a risk factor that is closely related to several chronic diseases. Central obesity is associated with elevated triglyceride levels and associated with RBP4 which can lead to insulin resistance. Increased level of RBP4 can cause lipid metabolism disorders and can become a marker for insulin resistance and metabolic syndrome. This study aims to find the correlation of RBP4 with triglycerides and Apo B100 in central obesity. It was a cross- sectional study on 46 subjects with central obesity, aged 20-50 years old. Blood samples were taken in cubital vein and examined for RBP4 and triglyceride levels. Data analysis was performed using Spearman correlation test. The results showed that gender frequency distribution showed little difference between men and women, i. e., men 43.5% and women 56.5%. RBP4 level was positively correlated with triglyceride (r = 0.48) and statistically significant (p = 0.001). The rbp4 level was positively correlated with triglyceride, indicating the role of RBP4 on high triglyceride level in central obesity.

Pseudocholinesterase levels in patients under electroconvulsive therapy.

PubMed

Küçükosman, Gamze; Pişkin, Özcan; Hancı, Volkan; Okyay, Rahşan D; Ayoğlu, Hilal; Yurtlu, Bülent S; Akın, Mehmet; Turan, Işıl Ö

2018-01-01

In this study, we aimed to retrospectively assess the correlation of pseudocholinesterase (PChE) levels with age, gender, body weight and diagnosed psychiatric diseases in electroconvulsive therapy (ECT) cases. Methods: This retrospective study was conducted at Bülent Ecevit University Hospital, Zonguldak, Turkey, between 2007 and 2011. In the study, 193 ECT case files were retrospectively scanned to evaluate PChE values before ECT and other file information.  Results: There was no difference between gender in terms of PChE levels. Correlation analysis determined a weakly positive correlation between age (p=0.013; correlation coefficient [cc]: 0.178) and body weight (p less than 0.001; cc: 0.273) and PChE levels. No correlation was found between age, gender, weight or psychiatric diagnosis, and PChE levels.  Conclusion: Neuromuscular blockage is a significant factor that increases patient safety, while increasing the efficacy of ECT. In choosing muscle relaxant agents, both patient factors and the pharmacological properties of the neuromuscular blocker should be considered. We think that in situations with delayed recovery of ECT cases without identified PChE levels, low PChE levels must be considered.

Salivary cortisol and alpha-amylase levels during an assessment procedure correlate differently with risk-taking measures in male and female police recruits

PubMed Central

van den Bos, Ruud; Taris, Ruben; Scheppink, Bianca; de Haan, Lydia; Verster, Joris C.

2013-01-01

Recent laboratory studies have shown that men display more risk-taking behavior in decision-making tasks following stress, whilst women are more risk-aversive or become more task-focused. In addition, these studies have shown that sex differences are related to levels of the stress hormone cortisol (indicative of activation of the hypothalamus-pituitary-adrenocortical-axis): the higher the levels of cortisol the more risk-taking behavior is shown by men, whereas women generally display more risk-aversive or task-focused behavior following higher levels of cortisol. Here, we assessed whether such relationships hold outside the laboratory, correlating levels of cortisol obtained during a job-related assessment procedure with decision-making parameters in the Cambridge Gambling Task (CGT) in male and female police recruits. The CGT allows for discriminating different aspects of reward-based decision-making. In addition, we correlated levels of alpha-amylase [indicative of activation of the sympatho-adrenomedullary-axis (SAM)] and decision-making parameters. In line with earlier studies men and women only differed in risk-adjustment in the CGT. Salivary cortisol levels correlated positively and strongly with risk-taking measures in men, which was significantly different from the weak negative correlation in women. In contrast, and less strongly so, salivary alpha-amylase levels correlated positively with risk-taking in women, which was significantly different from the weak negative correlation with risk-taking in men. Collectively, these data support and extend data of earlier studies indicating that risky decision-making in men and women is differently affected by stress hormones. The data are briefly discussed in relation to the effects of stress on gambling. PMID:24474909

Correlation analysis of Standardized Precipitation Index (SPI) for the water debit and level of the Cisadane River during El Niño and La Niña years

NASA Astrophysics Data System (ADS)

Khoir, A. N.; Rohmah, M.; Nuryadi

2018-03-01

Hydrometeorological factor causes most disaster in Indonesia, and two of them are drought and flood. This study aims to correlate Standardized Precipitation Index (SPI) 3-monthly to water debit and water level in the Cisadane River. The monthly rainfall data from Serpong and Pasar Baru rain station from 2009 to 2011 when moderate El Niño and moderate La Niña happened. The correlation analysis between debit and water level to SPI 3-monthly used rain post of Serpong to represent the condition of the upstream area and rain post of Pasar Baru to represent the condition of the downstream area. The results showed that during La Niña year, the rainfall on the upstream area of the Cisadane River influenced the increase and the decrease in water debit and water level. Meanwhile, the rainfall on the downstream area of the river has an opposite effect on the increase and the decrease of debit and water level of the Pasar Baru. On the upstream area, the correlation between rainfall and water debit is 0.8, and the correlation between rainfall and water level is also 0.8. During El Niño year, the correlation was less than 0.5.

Implementation of Biplot Analysis for Mapping Elementary and Junior High Schools in West Sumatra Based on National Examination Results 2016

NASA Astrophysics Data System (ADS)

Amalita, N.; Fitria, D.; Distian, V.

2018-04-01

National examination is an assessment of learning outcomes that aims to assess the achievement of graduate competence nationally. The result of the national examination is used as a mapping of educational issues in order to arrange the national education policy. Therefore the results of National Examination are used, also, as a reference for the admission of new students to continue their education to a higher level. The results of National Examination in West Sumatra in 2016 decreased from the previous year, both elementary schools (SD) and Junior High School level (SMP). This paper aims to determine the characteristics of the National Examination results in each regency / city in West Sumatra for elementary and junior levels by using Bi-plot analysis. The result of Bi-plot Analysis provides the information that the results of the National Examination of Regency / City in West Sumatra Province are quite diverse. At Junior High School level there are 9 of Regencies / Cities which have similar characteristics. English subjects are the greatest diversity among all of subjects. The calculation results of the correlation of each variable in junior high school level are positively correlated. The variables with positive correlation are mathematics that correlates with English. Based on the mark of National Examination for elementary school level in West Sumatra, there are 8 Regencies / Cities have similar characteristics. The correlations of each variable at the elementary level are positively correlated. The variables that have positive correlation are Sciences (IPA) with Language.

1H-MR spectroscopy metabolite levels correlate with executive function in vascular cognitive impairment

PubMed Central

Gasparovic, Charles; Prestopnik, Jillian; Thompson, Jeffrey; Taheri, Saeid; Huisa, Branko; Schrader, Ronald; Adair, John C; Rosenberg, Gary A

2013-01-01

Background White matter hyperintensities (WMHs) are associated with vascular cognitive impairment (VCI) but fail to correlate with neuropsychological measures. As proton MR spectroscopy (1H-MRS) can identify ischaemic tissue, we hypothesised that MRS detectable brain metabolites would be superior to WMHs in predicting performance on neuropsychological tests. Methods 60 patients with suspected VCI underwent clinical, neuropsychological, MRI and CSF studies. They were diagnosed as having subcortical ischaemic vascular disease (SIVD), multiple infarcts, mixed dementia and leukoaraiosis. We measured brain metabolites in a white matter region above the lateral ventricles with 1H-MRS and WMH volume in this region and throughout the brain. Results We found a significant correlation between both total creatine (Cr) and N-acetylaspartyl compounds (NAA) and standardised neuropsychological test scores. Cr levels in white matter correlated significantly with executive function (p=0.001), attention (p=0.03) and overall T score (p=0.007). When lesion volume was added as a covariate, NAA also showed a significant correlation with executive function (p=0.003) and overall T score (p=0.015). Furthermore, while metabolite levels also correlated with total white matter lesion volume, adjusting the Cr levels for lesion volume did not diminish the strength of the association between Cr levels and neuropsychological scores. The lowest metabolite levels and neuropsychological scores were found in the SIVD group. Finally, lesion volume alone did not correlate significantly with any neuropsychological test score. Conclusion These results suggest that estimates of neurometabolite levels provide additional and useful information concerning cognitive function in VCI not obtainable by measurements of lesion load. PMID:23418212

Correlation between serum E-selectin levels and panoramic nailfold capillaroscopy in systemic sclerosis.

PubMed

Valim, V; Assis, L S S; Simões, M F J; Trevisani, V F M; Pucinelli, M L C; Andrade, L E C

2004-09-01

E-selectin is expressed by the activated endothelium and its plasma levels are increased in patients with systemic sclerosis. Eighteen patients fulfilling the American Rheumatism Association criteria for systemic sclerosis, 15 females and 3 males, 42-70 years old, 9 with diffuse and 9 with limited forms, were sequentially recruited for this study. Serum E-selectin levels were determined by commercially available ELISA and their association with nailfold capillaroscopic abnormalities was investigated. Nailfold capillaries were analyzed by 16X magnification wide-field capillaroscopy. Two parameters on capillaroscopy were used to correlate to serum E-selectin: deletion and ectasia. Data were analyzed statistically by the Student t-test and Spearman correlation. Two-tailed P values below 0.05 were considered significant. E-selectin range was 38 to 200 ng/ml (80 +/- 39.94). There was a correlation between serum E-selectin levels and the deletion capillaroscopic score (r = 0.50, P < 0.035). This correlation was even stronger within the first 48 months of diagnosis (r = 0.63, P < 0.048). On the other hand, no association was observed between selectin and ectasia. Patients with diffuse disease presented higher serum E-selectin levels than patients with limited disease, although the difference was not statistically significant (96.44 +/- 48.04 vs 63.56 +/- 21.77 ng/dl; P = 0.08). The present study is the first showing a correlation between soluble serum E-selectin levels and alterations in capillaroscopy. The stronger correlation of deletion score in capillaroscopy in early disease suggests that serum E-selectin levels might be a useful biochemical marker of disease activity in systemic sclerosis.

Direct correlation between serum homocysteine level and insulin resistance index in patients with subclinical hypothyroidism: Does subclinical hypothyroidism increase the risk of diabetes and cardio vascular disease together?

PubMed

Ebrahimpour, Anahita; Vaghari-Tabari, Mostafa; Qujeq, Durdi; Moein, Soheila; Moazezi, Zoleikha

2018-05-05

Subclinical hypothyroidism known as mild thyroid disorder without significant sign and symptoms. The correlation between subclinical hypothyroidism and some of cardiovascular disease risk factors such as serum lipids, homocysteine levels and also insulin resistance index is not well established and the current study was conducted to clarify this issue. Seventy four patients with mild elevation in levels of thyroid stimulating hormone (TSH) along with normal levels of T3 and T4 were selected as patients group and 74 age and sex matched individuals were selected as healthy control group. Serum insulin, triglyceride, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and homocysteine levels were measured. Obtained data compared between groups with independent sample t-test. For evaluation of the correlation between mentioned parameters Pearson correlation coefficient method was used. Serum levels of LDL-C and total cholesterol significantly increased in SCH group compared to healthy control group. Homeostatic Model Assessment of Insulin Resistance (HOM-IR) and serum homocysteine level significantly elevated in patients with SCH compared to control group. There was a significant direct correlation between HOM-IR and serum homocysteine levels in SCH patients. Subclinical hypothyroidism likely have significant effect on insulin resistance as major diabetes risk factors and also cardiovascular disease risk factors such as homocysteine. The direct correlation between HOM-IR with serum homocysteine level indicate the possible role of insulin resistance in elevation of serum homocysteine in SCH patient group. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Glial Cell Line-Derived Neurotrophic Factor (GDNF) serum level in women with schizophrenia and depression, correlation with clinical and metabolic parameters.

PubMed

Skibinska, Maria; Kapelski, Pawel; Pawlak, Joanna; Rajewska-Rager, Aleksandra; Dmitrzak-Weglarz, Monika; Szczepankiewicz, Aleksandra; Czerski, Piotr; Twarowska-Hauser, Joanna

2017-10-01

Neurotrophic factors have been implicated in neuropsychiatric disorders, including schizophrenia and depression. Glial Cell Line-Derived Neurotrophic Factor (GDNF) promotes development, differentiation, and protection of dopaminergic, serotonergic, GABAergic and noradrenergic neurons as well as glial cells in different brain regions. This study examined serum levels of GDNF in schizophrenia and depression and its correlation with metabolic parameters during 8 weeks of treatment. Serum GDNF level, fasting serum glucose and lipid profile were measured at baseline and week 8 in 133 women: 55 with schizophrenia, 30 with a first episode depression and 48 healthy controls. The severity of the symptoms was evaluated using Positive and Negative Syndrome Scale (PANSS), 17-item Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). There was statistically significant higher GDNF level in schizophrenia at baseline when compared with week 8. Correlations of GDNF with PANSS in schizophrenia and cholesterol level in depression have also been detected. To our knowledge, this is the first study which correlates GDNF levels with metabolic parameters. Our results show no differences in GDNF serum level between schizophrenia, a first depressive episode, and healthy controls. GDNF serum level did not correlate with metabolic parameters except for total cholesterol in depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Serum PTHrP level as a biomarker in assessing skeletal maturation during circumpubertal development.

PubMed

Hussain, Mohammed Zahid; Talapaneni, Ashok Kumar; Prasad, Mandava; Krishnan, Ramalingam

2013-04-01

Many investigators have studied the cellular organization and the local and systemic factors regulating endochondral bone growth in the growth plate and condylar cartilage. Parathyroid hormone-related protein (PTHrP) and Indian hedgehog protein have been reported to regulate multiple steps during such skeletal morphogenesis. The aims of this study were to quantify serum PTHrP levels at 6 cervical vertebral stages and to correlate serum PTHrP levels to the 6 skeletal maturation stages for use as a biologic indicator of skeletal maturation. Mean serum PTHrP levels were measured in 90 subjects categorized into 6 cervical vertebral stages. Mean serum PTHrP levels were significantly higher in the late pubertal stages than in the early pubertal stages. Pearson correlation showed that serum PTHrP levels had a positive correlation with cervical vertebral maturation stages from the prepubertal to the late pubertal stages, and a negative correlation from the late pubertal to the postpubertal stages. Peak serum PTHrP levels do not correlate with early pubertal stages characterized by maximum growth increments. Hence, the validity of using serum PTHrP levels to predict peak growth velocity is questionable. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Serum klotho protein levels and their correlations with the progression of type 2 diabetes mellitus.

PubMed

Nie, Fang; Wu, Dongming; Du, Hongfei; Yang, Xianggui; Yang, Min; Pang, Xueli; Xu, Ying

2017-03-01

To investigate the associations of serum α-Klotho and β-Klotho levels with type 2 diabetes mellitus (T2DM) progression. We evaluated 106 healthy controls and 261 cases of T2DM with or without diabetic complications (range: 45-84years). Serum α-Klotho and β-Klotho levels were analyzed using enzyme-linked immunosorbent assays. Compared to the healthy controls, α-Klotho and β-Klotho levels were significantly lower among patients with T2DM and with or without diabetic complications (P<0.05). Furthermore, α-Klotho levels were lower in the microalbuminuric and macroalbuminuric groups, compared to the normoalbuminuric group. However, β-Klotho levels were only lower in the macroalbuminuric group (P<0.05). Multiple linear regression analyses revealed that α-Klotho and β-Klotho levels were positively correlated with the creatinine clearance rate, and negatively correlated with the urinary albumin to creatinine ratio and randomly sampled serum levels of creatinine, blood urea nitrogen, and blood glucose. Moreover, α-Klotho and β-Klotho levels were positively correlated among patients with T2DM (r=0.693, P<0.001). Serum levels of α-Klotho and β-Klotho are down-regulated in patients with T2DM. Thus, these proteins may participate in the pathological mechanism of diabetes, and the positive correlation of α-Klotho and β-Klotho levels indicates that they might have similar mechanisms in T2DM. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebrospinal fluid neural cell adhesion molecule levels and their correlation with clinical variables in patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hidese, Shinsuke; Hattori, Kotaro; Sasayama, Daimei; Miyakawa, Tomoko; Matsumura, Ryo; Yokota, Yuuki; Ishida, Ikki; Matsuo, Junko; Noda, Takamasa; Yoshida, Sumiko; Teraishi, Toshiya; Hori, Hiroaki; Ota, Miho; Kunugi, Hiroshi

2017-06-02

Neural cell adhesion molecule (NCAM) plays an important role in neural plasticity, and its altered function has been implicated in psychiatric disorders. However, previous studies have yielded inconsistent results on cerebrospinal fluid (CSF) NCAM levels in psychiatric disorders. The aim of our study was to examine CSF NCAM levels in patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD), and their possible relationship with clinical variables. The participants comprised 85 patients with schizophrenia, 57 patients with BD, 83 patients with MDD and 111 healthy controls, all matched for age, sex, and Japanese ethnicity. The CSF samples were drawn using a lumbar puncture and NCAM levels were quantified by an enzyme-linked immunosorbent assay. Analysis of covariance controlling for age and sex revealed that CSF NCAM levels were lower in all patients (p=0.033), and in those with BD (p=0.039), than in the controls. NCAM levels positively correlated with age in patients with BD (p<0.01), MDD (p<0.01), and the controls (p<0.01). NCAM levels negatively correlated with depressive symptom scores in patients with BD (p=0.040). In patients with schizophrenia, NCAM levels correlated negatively with negative symptom scores (p=0.029), and correlated positively with scores for cognitive functions such as category fluency (p=0.011) and letter fluency (p=0.023) scores. We showed that CSF NCAM levels were lower in psychiatric patients, particularly bipolar patients than in the controls. Furthermore, we found correlations of NCAM levels with clinical symptoms in patients with BD and in those with schizophrenia, suggesting the involvement of central NCAM in the symptom formation of severe psychiatric disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Electricity supply efficiency and organizational growth and profitability in Lagos, Nigeria

NASA Astrophysics Data System (ADS)

Adeleke, Adedeji Tajudeen

A modern and efficient infrastructure is a basic necessity for economic development and integration into the global economy. The specific problem was the inadequate and unreliable supply of electricity to manufacturing corporations in Lagos, Nigeria. The purpose of the current quantitative correlational research study was to examine if there was a correlation between electricity supply efficiency and organizational growth and profitability in manufacturing corporations in Lagos, Nigeria. The population of the current correlational research study involved 28 out of 34 manufacturing corporations from various industrial sectors in Lagos, Nigeria, that are listed and traded on the Nigerian Stock Exchange. Spearman rho correlations were used to assess the relationships between independent variables of electricity supply efficiency levels and the dependent variables of organizational growth and profitability. The result of the correlational analysis of the data revealed that there was a statistically significant, strong positive correlation between the Average Gross Income (1998-2007) and Average Actual Electricity supply efficiency level (1998-2007), rho = 0.57; p = 0.002. A statistically significant, strong positive correlation was found between the Average Balance Sheet Size (1998-2007) and Average Actual Electricity Supply Efficiency Level (1998-2007), rho = 0.54; p = 0.003. A statistically significant, strong positive correlation between the Average Profit After Tax (1998-2007) and Average Actual Electricity Supply Efficiency Level (1998-2007), rho = 0.60; p = 0.001, was found. No statistically significant correlation between the Average Return on Investment (1998-2007) and Average Actual Electricity supply efficiency level (1998-2007), rho = 0.19; p = 0.33, was discovered.

American College of Surgeons Level I trauma centers outcomes do not correlate with patients' perception of hospital experience.

PubMed

Joseph, Bellal; Azim, Asad; O'Keeffe, Terence; Ibraheem, Kareem; Kulvatunyou, Narong; Tang, Andrew; Vercruysse, Gary; Friese, Randall; Latifi, Rifat; Rhee, Peter

2017-04-01

The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is a data collection methodology for measuring a patient's perception of his/her hospital experience, and it has been selected by the Centers of Medicare and Medicaid Services as the validated and transparent national survey tool with publicly available results. Since 2012, hospital reimbursements rates have been linked to HCAHPS data based on patient satisfaction scores. The aim of this study was, therefore, to assess whether HCAHPS scores of Level I trauma centers correlate with actual hospital performance. Retrospective analysis of the latest publicly available HCAHPS data (2014-2015) was performed. American College of Surgeons (ACS) verified Level I trauma centers for each state were identified from the ACS registry and then the following data points were collected for each hospital: HCAHPS linear mean scores regarding cleanliness of the hospital, doctor and nurse communication with the patient, staff responsiveness, pain management, overall hospital rating, and patient willingness to recommend the hospital. Our outcome measure were serious complication scores, failure-to-rescue (FTR) scores and readmission-after-discharge scores. Spearman correlation analysis was performed. A total of 119 ACS verified Level I trauma centers across 46 states were included. The median [IQR] overall hospital rating score for Level I trauma centers was 89 (87-90). The mean ± SD score for serious complication was 0.96 ± 0.266, FTR was 123.06 ± 22.5, and readmission after discharge was 15.71 ± 1.07. The Spearman correlation analysis showed that overall HCAHP-based hospital rating scores did not correlate with serious complications (correlation coefficient = 0.14 p = 0.125), FTR (correlation coefficient = -0.15 p = 0.073), or readmission after discharge (correlation coefficient = -0.18 p = 0.053). The findings of our study suggest that no correlation exists between HCAHPS patient satisfaction scores and hospital performance for Level I trauma centers. Consequently, the Centers of Medicare and Medicaid Services should reconsider hospital reimbursement decisions based on HCAHP patient satisfaction scores. Prognostic/epidemiologic study, level III; therapeutic study, level IV.

Clinical and metabolic abnormalities associated with occupational exposure to polychlorinated biphenyls (PCBs)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chase, K.H.; Wong, O.; Thomas, D.

1982-02-01

A cross-sectional study of 120 male workers was conducted to determine the prevalence of increased polychlorinated biphenyl (PCB) absorption as well as the presence of potentially related clinical and metabolic abnormalities. Three exposure categories (''exposed'', ''nominally exposed'', ''nonexposed'') were defined. Complete work histories, clinical histories, physical examinations and laboratory tests, including plasma PCB determinations were obtained. In addition, fat PCB levels were determined in randomly selected subjects in each exposed group. Evidence of dermatotoxicity was observed and elevated PCB levels were noted more frequently in the exposed group (p < .00001), correlating well with age and duration of employment. Thesemore » correlations were stronger for fat (p < .001) than for plasma (p < .01) PCB levels. In the exposed group, significant correlations were found between plasma PCB and serum triglyceride (p < .00001) and serum glutamic oxaloacetic transaminase (SGOT) levels (p < .01). These correlations remained significant after controlling for either age or length of employment. No significant correlations were found between PCB levels and levels of cholesterol, high-density lipoprotein cholesterol or levels studied on liver function tests other than SGOT. Further analyses relating frequency of reported direct contact with PCB levels suggested a dermal route of exposure. An analysis by union affiliation demonstrated that those in crafts involving greater direct exposure had correspondingly higher elevations of PCB levels.« less

Clinical and metabolic abnormalities associated with occupational exposure to polychlorinated biphenyls (PCBs)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chase, K.H.; Wong, O.; Thomas, D.

1982-02-01

A cross-sectional study of 120 male workers was conducted to determine the prevalence of increased polychlorinated biphenyl (PCB) absorption as well as the presence of potentially related clinical and metabolic abnormalities. Three exposure categories (''exposed'', ''nominally exposed'', ''nonexposed'') were defined. Complete work histories, clinical histories, physical examinations and laboratory tests, including plasma PCB determinations were obtained. In addition, fat PCB levels were determined in randomly selected subjects in each exposed group. Evidence of dermatotoxicity was observed and elevated PCB levels were noted more frequently in the exposed group (p less than .0001), correlating well with age and duration of employment.more » These correlations were stronger for fat (p less than .001) than for plasma (p less than .01) PCB levels. In the exposed group, significant correlations were found between plasma PCB and serum triglyceride (p less than .0001) and serum glutamic oxaloacetic transaminase (SGOT) levels (p less than .01). These correlations remained significant after controlling for either age or length of employment. No significant correlations were found between PCB levels and levels of cholesterol, high-density lipoprotein cholesterol or levels studied on liver function tests other than SGOT. Further analyses relating frequency of reported direct contact with PCB levels suggested a dermal route of exposure. An analysis by union affiliation demonstrated that those in crafts involving greater direct exposure had correspondingly higher elevations of PCB levels.« less

Circulating prolactin level in systemic lupus erythematosus and its correlation with disease activity: a meta-analysis.

PubMed

Song, G G; Lee, Y H

2017-10-01

Objective This study aimed to evaluate the relationship between circulating prolactin level and systemic lupus erythematosus (SLE), and to establish a correlation between plasma/serum prolactin levels and SLE activity. Methods We performed a meta-analysis comparing the plasma/serum prolactin levels in patients with SLE to controls, and examined correlation coefficients between circulating prolactin level and SLE disease activity. Results Twenty-five studies with a total of 1056 SLE patients and 426 controls were included. Prolactin levels were significantly higher overall in the SLE group than in the control group (standardized mean difference (SMD) = 0.987, 95% CI = 0.512-1.463, p = 4.7 × 10 -5 ). Stratification by ethnicity showed significantly elevated prolactin levels in the SLE group in Asian, Latin American, and mixed populations (SMD = 0.813, 95% CI = 0.137-1.490, p = 0.018; SMD = 0.981, 95% CI = 0.307-1.655, p = 0.004; SMD = 1.469, 95% CI = 0.443-2.495, p = 0.005, respectively), but not in the European population. Subgroup analysis by sample size showed significantly higher prolactin levels in the SLE group by small ( n < 30) and large sample numbers ( n > 30). Meta-analysis of correlation coefficients showed a significantly positive correlation between circulating prolactin level and SLE activity (correlation coefficient = 0.379, 95% CI = 0.026-0.487, p = 4.0 × 10 -9 ). Circulating prolactin levels were positively associated with SLE activity in European, Asian, and mixed populations (SMD = 0.532, 95% CI = 0.443-0.609  p < 1.0 × 10 -8 ; SMD = 0.427, 95% CI = 0.240-0.583, p = 2.4 × 10 -5 ; SMD = 0.433, 95% CI = 0.212-0.591, p = 2.7 × 10 -5 , respectively). Conclusions Our meta-analysis demonstrated that circulating prolactin levels are higher in patients with SLE, and that a significantly positive correlation exists between prolactin levels and SLE activity.

Handling Correlations between Covariates and Random Slopes in Multilevel Models

ERIC Educational Resources Information Center

Bates, Michael David; Castellano, Katherine E.; Rabe-Hesketh, Sophia; Skrondal, Anders

2014-01-01

This article discusses estimation of multilevel/hierarchical linear models that include cluster-level random intercepts and random slopes. Viewing the models as structural, the random intercepts and slopes represent the effects of omitted cluster-level covariates that may be correlated with included covariates. The resulting correlations between…

Low 25-OH vitamin D serum levels correlate with severe fibrosis in HIV-HCV co-infected patients with chronic hepatitis.

PubMed

Terrier, Benjamin; Carrat, Fabrice; Geri, Guillaume; Pol, Stanislas; Piroth, Lionel; Halfon, Philippe; Poynard, Thierry; Souberbielle, Jean-Claude; Cacoub, Patrice

2011-10-01

Recent findings in hepatitis C virus (HCV)-monoinfected patients have shown a correlation between low serum levels of 25-OH vitamin D3 [25(OH)D3] and severe liver fibrosis and low sustained virologic response to therapy. Data are lacking in HIV-HCV coinfected patients. One hundred and eighty nine HIV-HCV coinfected patients, who received ≥80% of interferon (IFN) plus ribavirin therapy, were analyzed for baseline serum 25(OH)D3 levels. Correlations between serum 25(OH)D3 levels, chronic hepatitis C features, HCV virologic response to antiviral therapy, and HIV infection characteristics were analyzed. Mean serum 25(OH)D3 level was 18.5 ± 9.8 ng/ml, including 162 (85%) patients with level ≤30 ng/ml. Serum 25(OH)D3 levels were significantly correlated with the histological Metavir fibrosis score (r = -0.16; p = 0.027). Patients with severe fibrosis (Metavir F3/F4) had lower serum 25(OH)D3 levels compared to F2 and F1 patients (16.2 ± 10.0 vs. 18.9 ± 8.5 and 20.9 ± 11.1 ng/ml, respectively; p = 0.06). In multivariate analysis, low serum 25(OH)D levels were independently associated with severe liver fibrosis (p = 0.04) and cold season (p = 0.0002). Serum levels of 25(OH)D3 were also significantly correlated with liver fibrosis as assessed by FibroTest® (r = -0.22; p = 0.008) and serum α2-macroglobulin levels (r = -0.23; p = 0.006). In contrast, no correlation was found between 25(OH)D3 levels and HCV sustained virologic response to IFN-based therapy [OR 0.98 (0.95-1.01); p = 0.22]. No association was found between 25(OH)D3 levels and markers of HIV-related immunodeficiency. In HIV-HCV coinfected patients, low serum 25(OH)D3 levels correlate with severe liver fibrosis. In contrast, serum 25(OH)D3 levels are not linked to HCV virologic response to therapy or severity of immunodeficiency. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Relationship between the {sup 137}Cs whole-body counting results and soil and food contamination in farms near Chernobyl

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takatsuji, Toshihiro; Sato, Hitoshi; Takada, Jun

The authors measured the radioactivity in the soil and child food samples from farms near Mogilev (56--270 GBq km{sup {minus}2} {sup 137}Cs), Gomel (36--810 GBq km{sup {minus}2} {sup 137}Cs), and Klincy (59--270 GBq km{sup {minus}2} {sup 137}Cs), who had whole-body {sup 137}Cs counting results measured as part of a health examination in the Chernobyl Sasakawa Health and Medical Cooperation Project. Soil contamination on the family farm seems to be the main source of human contamination because most of the people in the area live on small farms and they and their domestic animals eat crops from the farms. A clearmore » correlation was found between the children's whole-body {sup 137}Cs counting results and the radioactivity in their food (correlation coefficient: 0.76; confidence level of correlation: 3.2 x 10{sup {minus}9}). There were also significant correlations between the whole-body {sup 137}Cs counting results and both the radioactivity of the soil samples (correlation coefficient: 0.22; confidence level of correlation: 0.0107) and the average contamination level of their current residence (correlation coefficient: 0.20; confidence level of correlation: 0.0174).« less

Pathology and polymerase chain reaction detection of ovine progressive pneumonia (maedi) cases in slaughtered sheep in India

PubMed Central

Singh, Rahul; Kumar, Pawan; Singh, Rajendra; Dhama, Kuldeep; Kumari, Swati; Yadav, Jay Prakash; Kashyap, Gayatri; Singh, Karam Pal; Singh, Vidya; Sahoo, Monalisa

2017-01-01

Aim: The small ruminant lentiviruses are known to cause maedi-visna (MV) and caprine arthritis - encephalitis in sheep and goats, typically affecting joints, udder, lungs, and the central nervous system. The diagnosis usually involves serology, clinical signs, immunohistochemistry, and polymerase chain reaction (PCR). In the present study, the histopathologically positive pneumonia cases of MV were confirmed by PCR in lung tissue probably for the first time in India. Materials and Methods: A total of 888 lungs of adult sheep, aged between 2 and 5 years, were screened during slaughter, of which 121 were found to have pneumonic lesions. The tissues from each pneumonic lung including associated lymph nodes were collected in 10% neutral buffered formalin for histopathology. The frozen tissues of the same were also collected and stored at −20°C for PCR confirmation. Results: Three of 121 cases of pneumonic lungs of sheep revealed gross and histopathological lesions suggestive of maedi or ovine progressive pneumonia infection. These 3 cases were further confirmed by PCR technique that amplified 291-base pair DNA in the long terminal repeat sequence of MV provirus. Conclusion: This study suggests the low occurrence of MV virus (MVV) infection in India in naturally affected sheep based on pathomorphological lesions and using the molecular tool of PCR detection of the virus in tissues. Further, a combination of pathomorphology or/and PCR testing might be optimal for detecting the animals infected with MVV. PMID:29263606

Characteristics of lentiviral vectors harboring the proximal promoter of the vav proto-oncogene: a weak and efficient promoter for gene therapy.

PubMed

Almarza, Elena; Río, Paula; Meza, Nestor W; Aldea, Montserrat; Agirre, Xabier; Guenechea, Guillermo; Segovia, José C; Bueren, Juan A

2007-08-01

Recent published data have shown the efficacy of gene therapy treatments of certain monogenic diseases. Risks of insertional oncogenesis, however, indicate the necessity of developing new vectors with weaker or cell-restricted promoters to minimize the trans-activation activity of integrated proviruses. We have inserted the proximal promoter of the vav proto-oncogene into self-inactivating lentiviral vectors (vav-LVs) and investigated the expression pattern and therapeutic efficacy of these vectors. Compared with other LVs frequently used in gene therapy, vav-LVs mediated a weak, though homogeneous and stable, expression in in vitro-cultured cells. Transplantation experiments using transduced mouse bone marrow and human CD34(+) cells confirmed the stable activity of the promoter in vivo. To investigate whether the weak activity of this promoter was compatible with a therapeutic effect, a LV expressing the Fanconi anemia A (FANCA) gene was constructed (vav-FANCA LV). Although this vector induced a low expression of FANCA, compared to the expression induced by a LV harboring the spleen focus-forming virus (SFFV) promoter, the two vectors corrected the phenotype of cells from a patient with FA-A with the same efficacy. We propose that self-inactivating vectors harboring weak promoters, such as the vav promoter, will improve the safety of gene therapy and will be of particular interest for the treatment of diseases where a high expression of the transgene is not required.

Comparative Methylation of ERVWE1/Syncytin-1 and Other Human Endogenous Retrovirus LTRs in Placenta Tissues

PubMed Central

Gimenez, Juliette; Montgiraud, Cécile; Oriol, Guy; Pichon, Jean-Philippe; Ruel, Karine; Tsatsaris, Vassilis; Gerbaud, Pascale; Frendo, Jean-Louis; Evain-Brion, Danièle; Mallet, François

2009-01-01

Human endogenous retroviruses (HERVs) are globally silent in somatic cells. However, some HERVs display high transcription in physiological conditions. In particular, ERVWE1, ERVFRDE1 and ERV3, three proviruses of distinct families, are highly transcribed in placenta and produce envelope proteins associated with placenta development. As silencing of repeated elements is thought to occur mainly by DNA methylation, we compared the methylation of ERVWE1 and related HERVs to appreciate whether HERV methylation relies upon the family, the integration site, the tissue, the long terminal repeat (LTR) function or the associated gene function. CpG methylation of HERV-W LTRs in placenta-associated tissues was heterogeneous but a joint epigenetic control was found for ERVWE1 5′LTR and its juxtaposed enhancer, a mammalian apparent LTR retrotransposon. Additionally, ERVWE1, ERVFRDE1 and ERV3 5′LTRs were all essentially hypomethylated in cytotrophoblasts during pregnancy, but showed distinct and stage-dependent methylation profiles. In non-cytotrophoblastic cells, they also exhibited different methylation profiles, compatible with their respective transcriptional activities. Comparative analyses of transcriptional activity and LTR methylation in cell lines further sustained a role for methylation in the control of functional LTRs. These results suggest that HERV methylation might not be family related but copy-specific, and related to the LTR function and the tissue. In particular, ERVWE1 and ERV3 could be developmentally epigenetically regulated HERVs. PMID:19561344

HIV-1 resistance dynamics in patients failing dolutegravir maintenance monotherapy.

PubMed

Wijting, Ingeborg E A; Lungu, Cynthia; Rijnders, Bart J A; van der Ende, Marchina E; Pham, Hanh T; Mesplede, Thibault; Pas, Suzan D; Voermans, Jolanda J C; Schuurman, Rob; van de Vijver, David A M C; Boers, Patrick H M; Gruters, Rob A; Boucher, Charles A B; van Kampen, Jeroen J A

2018-03-29

A high genetic resistance barrier to the integrase-strand-transfer-inhibitor (INSTI) dolutegravir has been reported in vitro and in vivo. We describe the dynamics of INSTI-resistance-associated-mutations (INSTI-RAMs) and mutations in the 3'-polypurine tract (3'-PPT) in relation to virological failure (VF) observed in the randomized dolutegravir maintenance monotherapy study (DOMONO, NCT02401828). From ten patients with VF plasma samples prior to start cART and during VF were used to generate Sanger sequences of integrase, the 5' terminal bases of the 3'- LTR, and the 3'-PPT. Median HIV-RNA (IQR) at VF was 3,490 (1,440-4,990) c/mL. INSTI-RAMs were detected in 4/10 patients (S230R, R263K, N155H, E92Q+N155H) and in 4/10 patients no INSTI-RAMs were detected (2/10 patients integrase sequencing was unsuccessful). The time-to-VF ranged from 4 weeks to 72 weeks. In one patient, mutations developed in the highly conserved 3'-PPT. No changes in the terminal bases of the 3'-LTR were observed. The genetic barrier to resistance is too low to justify dolutegravir maintenance monotherapy as single INSTI-RAMs are sufficient to cause VF. The large variation in time-to-VF suggests that stochastic reactivation of a pre-existing provirus containing a single INSTI-RAM is the mechanism for failure. Changes in the 3'-PPT point to a new dolutegravir resistance mechanism in vivo.

Candidatus Nitrosocaldus cavascurensis, an Ammonia Oxidizing, Extremely Thermophilic Archaeon with a Highly Mobile Genome

PubMed Central

Abby, Sophie S.; Melcher, Michael; Kerou, Melina; Krupovic, Mart; Stieglmeier, Michaela; Rossel, Claudia; Pfeifer, Kevin; Schleper, Christa

2018-01-01

Ammonia oxidizing archaea (AOA) of the phylum Thaumarchaeota are widespread in moderate environments but their occurrence and activity has also been demonstrated in hot springs. Here we present the first enrichment of a thermophilic representative with a sequenced genome, which facilitates the search for adaptive strategies and for traits that shape the evolution of Thaumarchaeota. Candidatus Nitrosocaldus cavascurensis has been enriched from a hot spring in Ischia, Italy. It grows optimally at 68°C under chemolithoautotrophic conditions on ammonia or urea converting ammonia stoichiometrically into nitrite with a generation time of approximately 23 h. Phylogenetic analyses based on ribosomal proteins place the organism as a sister group to all known mesophilic AOA. The 1.58 Mb genome of Ca. N. cavascurensis harbors an amoAXCB gene cluster encoding ammonia monooxygenase and genes for a 3-hydroxypropionate/4-hydroxybutyrate pathway for autotrophic carbon fixation, but also genes that indicate potential alternative energy metabolisms. Although a bona fide gene for nitrite reductase is missing, the organism is sensitive to NO-scavenging, underlining the potential importance of this compound for AOA metabolism. Ca. N. cavascurensis is distinct from all other AOA in its gene repertoire for replication, cell division and repair. Its genome has an impressive array of mobile genetic elements and other recently acquired gene sets, including conjugative systems, a provirus, transposons and cell appendages. Some of these elements indicate recent exchange with the environment, whereas others seem to have been domesticated and might convey crucial metabolic traits. PMID:29434576

Human T-cell leukemia virus type-1-encoded protein HBZ represses p53 function by inhibiting the acetyltransferase activity of p300/CBP and HBO1

PubMed Central

Hoang, Kimson; Ankney, John A.; Nguyen, Stephanie T.; Rushing, Amanda W.; Polakowski, Nicholas; Miotto, Benoit; Lemasson, Isabelle

2016-01-01

Adult T-cell leukemia (ATL) is an often fatal malignancy caused by infection with the complex retrovirus, human T-cell Leukemia Virus, type 1 (HTLV-1). In ATL patient samples, the tumor suppressor, p53, is infrequently mutated; however, it has been shown to be inactivated by the viral protein, Tax. Here, we show that another HTLV-1 protein, HBZ, represses p53 activity. In HCT116 p53+/+ cells treated with the DNA-damaging agent, etoposide, HBZ reduced p53-mediated activation of p21/CDKN1A and GADD45A expression, which was associated with a delay in G2 phase-arrest. These effects were attributed to direct inhibition of the histone acetyltransferase (HAT) activity of p300/CBP by HBZ, causing a reduction in p53 acetylation, which has be linked to decreased p53 activity. In addition, HBZ bound to, and inhibited the HAT activity of HBO1. Although HBO1 did not acetylate p53, it acted as a coactivator for p53 at the p21/CDKN1A promoter. Therefore, through interactions with two separate HAT proteins, HBZ impairs the ability of p53 to activate transcription. This mechanism may explain how p53 activity is restricted in ATL cells that do not express Tax due to modifications of the HTLV-1 provirus, which accounts for a majority of patient samples. PMID:26625199

Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells

PubMed Central

Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z.; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung’u, Thumbi; Walker, Bruce D.; Rosenberg, Eric S.; Yu, Xu G.

2017-01-01

HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells. PMID:28628034

Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells.

PubMed

Lee, Guinevere Q; Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung'u, Thumbi; Walker, Bruce D; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

2017-06-30

HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells.

Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes.

PubMed

Labenski, Verena; Suerth, Julia D; Barczak, Elke; Heckl, Dirk; Levy, Camille; Bernadin, Ornellie; Charpentier, Emmanuelle; Williams, David A; Fehse, Boris; Verhoeyen, Els; Schambach, Axel

2016-08-01

Primary human T lymphocytes represent an important cell population for adoptive immunotherapies, including chimeric-antigen and T-cell receptor applications, as they have the capability to eliminate non-self, virus-infected and tumor cells. Given the increasing numbers of clinical immunotherapy applications, the development of an optimal vector platform for genetic T lymphocyte engineering, which allows cost-effective high-quality vector productions, remains a critical goal. Alpharetroviral self-inactivating vectors (ARV) have several advantages compared to other vector platforms, including a more random genomic integration pattern and reduced likelihood for inducing aberrant splicing of integrated proviruses. We developed an ARV platform for the transduction of primary human T lymphocytes. We demonstrated functional transgene transfer using the clinically relevant herpes-simplex-virus thymidine kinase variant TK.007. Proof-of-concept of alpharetroviral-mediated T-lymphocyte engineering was shown in vitro and in a humanized transplantation model in vivo. Furthermore, we established a stable, human alpharetroviral packaging cell line in which we deleted the entry receptor (SLC1A5) for RD114/TR-pseudotyped ARVs to prevent superinfection and enhance genomic integrity of the packaging cell line and viral particles. We showed that superinfection can be entirely prevented, while maintaining high recombinant virus titers. Taken together, this resulted in an improved production platform representing an economic strategy for translating the promising features of ARVs for therapeutic T-lymphocyte engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

Viral load, tissue distribution and histopathological lesions in goats naturally and experimentally infected with the Small Ruminant Lentivirus Genotype E (subtype E1 Roccaverano strain).

PubMed

Grego, E; Reina, R; Lanfredini, S; Tursi, M; Favole, A; Profiti, M; Lungu, M M; Perona, G; Gay, L; Stella, M C; DeMeneghi, D

2018-06-01

Small Ruminant Lentivirus (SRLV) subtype E1, also known as Roccaverano strain, is considered a low pathogenic virus on the basis of natural genetic deletions, in vitro properties and on-farm observations. In order to gain more knowledge on this atypical lentivirus we investigated the in vivo tropism of Roccaverano strain in both, experimentally and naturally infected goats. Antibody responses were monitored as well as tissue distribution and viral load, evaluated by real time PCR on single spliced (gag/env) and multiple spliced (rev) RNA targets respectively, that were compared to histopathological lesions. Lymph nodes, spleen, alveolar macrophages and mammary gland turned out to be the main tissue reservoirs of genotype E1-provirus. Moreover, mammary gland and/or mammary lymph nodes acted as active replication sites in dairy goats, supporting the lactogenic transmission of this virus. Notably, a direct association between viral load and concomitant infection or inflammatory processes was evident within organs such as spleen, lung and testis. Our results validate the low pathogenicity designation of SRLV genotype E1 in vivo, and confirm the monocyte-macrophage cell lineage as the main virus reservoir of this genotype. Accordingly, SRLV genotype E displays a tropism towards all tissues characterized by an abundant presence of these cells, either for their own anatomical structure or for an occasional infectious/inflammatory status. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genital herpes simplex virus type 2 infection in humanized HIV-transgenic mice triggers HIV shedding and is associated with greater neurological disease.

PubMed

Nixon, Briana; Fakioglu, Esra; Stefanidou, Martha; Wang, Yanhua; Dutta, Monica; Goldstein, Harris; Herold, Betsy C

2014-02-15

Epidemiological studies consistently demonstrate synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). Higher HIV-1 loads are observed in coinfected individuals, and conversely, HIV-1 is associated with more-severe herpetic disease. A small animal model of coinfection would facilitate identification of the biological mechanisms underlying this synergy and provide the opportunity to evaluate interventions. Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4 promoter (JR-CSF/hu-cycT1) were intravaginally infected with HSV-2 and evaluated for disease progression, HIV shedding, and mucosal immune responses. HSV-2 infection resulted in higher vaginal HIV loads and genital tissue expression of HIV RNA, compared with HSV-uninfected JR-CSF/hu-cycT1 mice. There was an increase in genital tract inflammatory cells, cytokines, chemokines, and interferons in response to HSV-2, although the kinetics of the response were delayed in HIV-transgenic, compared with control mice. Moreover, the JR-CSF/hu-cycT1 mice exhibited earlier and more-severe neurological disease. The latter was associated with downregulation of secretory leukocyte protease inhibitor expression in neuronal tissue, a molecule with antiinflammatory, antiviral, and neuroprotective properties. JR-CSF/hu-cycT1 mice provide a valuable model to study HIV/HSV-2 coinfection and identify potential mechanisms by which HSV-2 facilitates HIV-1 transmission and HIV modulates HSV-2-mediated disease.

Restriction by APOBEC3 proteins of endogenous retroviruses with an extracellular life cycle: ex vivo effects and in vivo "traces" on the murine IAPE and human HERV-K elements

PubMed Central

Esnault, Cécile; Priet, Stéphane; Ribet, David; Heidmann, Odile; Heidmann, Thierry

2008-01-01

Background APOBEC3 cytosine deaminases have been demonstrated to restrict infectivity of a series of retroviruses, with different efficiencies depending on the retrovirus. In addition, APOBEC3 proteins can severely restrict the intracellular transposition of a series of retroelements with a strictly intracellular life cycle, including the murine IAP and MusD LTR-retrotransposons. Results Here we show that the IAPE element, which is the infectious progenitor of the strictly intracellular IAP elements, and the infectious human endogenous retrovirus HERV-K are restricted by both murine and human APOBEC3 proteins in an ex vivo assay for infectivity, with evidence in most cases of strand-specific G-to-A editing of the proviruses, with the expected signatures. In silico analysis of the naturally occurring genomic copies of the corresponding endogenous elements performed on the mouse and human genomes discloses "traces" of APOBEC3-editing, with the specific signature of the murine APOBEC3 and human APOBEC3G enzymes, respectively, and to a variable extent depending on the family member. Conclusion These results indicate that the IAPE and HERV-K elements, which can only replicate via an extracellular infection cycle, have been restricted at the time of their entry, amplification and integration into their target host genomes by definite APOBEC3 proteins, most probably acting in evolution to limit the mutagenic effect of these endogenized extracellular parasites. PMID:18702815

Relation of indoor and outdoor airborne fungal spore levels in the Kansas City metropolitan area.

PubMed

Jara, David; Portnoy, Jay; Dhar, Minati; Barnes, Charles

2017-03-01

Environmental control is an important component of asthma management for persons with asthma. A damp indoor environment and elevated airborne spore levels are factors in housing environmental control. We investigated if indoor airborne fungal spore levels correlated with outdoor ground-level airborne fungal spores or outdoor centrally collected spore levels as to types and abundance. Air collections were taken from home interiors, outdoor areas adjacent to the homes, and at a central location in the metropolitan area at the approximate same time. All air collections were examined and enumerated microscopically, and airborne spore estimates per cubic meter of air were reported for total fungal spores and for 11 identifiable spore groups. The 244 homes in the study were typical of the North American Midwest. The overall mean total spore counts in spores per cubic meter of air was indoors (4076 spores/m3), outdoors at ground level (8899 spores/m3), and outdoor metropolitan area (8342 spores/m3). All of the major indoor taxa were strongly correlated with the mean total spores present in the home. Total outdoor ground spore levels were highly correlated with levels of major outdoor taxa, such as ascospores and Cladosporium. Correlations of indoor spore levels with outdoor spore levels are strong for most major outdoor taxa. Indoor Aspergillus-Penicillium and Chaetomium are significantly correlated between indoor and local ground-level outdoor air. Although conditions may exist where indoor or outdoor spore levels were not well aligned, in most circumstances, the outdoor airborne spore community was reflected in the indoor airborne spore community.

Impact of parents’ physical activity on preschool children’s physical activity: a cross-sectional study

PubMed Central

Quan, Minghui; Zhang, Hanbin; Zhou, Chenglin

2018-01-01

Purpose This study examined the associations of physical activity levels between parents and their pre-school children based on gender and weekday/weekend. Method A total of 247 parent-preschool child triads from Shanghai, China were analyzed. The children had a mean age of 57.5 ± 5.2 months. Both sedentary behavior and physical activity were measured in all participants using an ActiGraph GT3X+ accelerometer over seven consecutive days from Monday through the following Sunday. A multivariate regression model was derived to identify significant relationships between parental and child physical activity according to gender and weekday/weekend. Results There was a significant correlation between mothers’ and girls’ moderate-to-vigorous physical activity (MVPA) and total physical activity (TPA) on weekdays. Fathers’ MPVA levels correlated significantly with those of boys and girls, with paternal influence appearing to be stronger than maternal influence. However, there was not a significant correlation between fathers’ and children’s TPA. TPA levels of both mothers and fathers correlated with those of girls, but not with those of boys. Parental sedentary levels on the weekend correlated significantly with girls’ levels, but not with boys’ levels. Children’s physical activity levels on weekends were influenced more by fathers’ activity levels than by mothers’, while the opposite was observed on weekdays. Conclusion Sedentary behavior and physical activity levels of parents can strongly influence those of their preschool children, with maternal influence stronger during the weekdays and paternal influence stronger on the weekends. Parents’ activity levels influence girls’ levels more strongly than they influence boys’ levels. PMID:29503768

Correlated environmental corrections in TOPEX/POSEIDON, with a note on ionospheric accuracy

NASA Technical Reports Server (NTRS)

Zlotnicki, V.

1994-01-01

Estimates of the effectiveness of an altimetric correction, and interpretation of sea level variability as a response to atmospheric forcing, both depend upon assuming that residual errors in altimetric corrections are uncorrelated among themselves and with residual sea level, or knowing the correlations. Not surprisingly, many corrections are highly correlated since they involve atmospheric properties and the ocean surface's response to them. The full corrections (including their geographically varying time mean values), show correlations between electromagnetic bias (mostly the height of wind waves) and either atmospheric pressure or water vapor of -40%, and between atmospheric pressure and water vapor of 28%. In the more commonly used collinear differences (after removal of the geographically varying time mean), atmospheric pressure and wave height show a -30% correlation, atmospheric pressure and water vapor a -10% correlation, both pressure and water vapor a 7% correlation with residual sea level, and a bit surprisingly, ionospheric electron content and wave height a 15% correlation. Only the ocean tide is totally uncorrelated with other corrections or residual sea level. The effectiveness of three ionospheric corrections (TOPEX dual-frequency, a smoothed version of the TOPEX dual-frequency, and Doppler orbitography and radiopositioning integrated by satellite (DORIS) is also evaluated in terms of their reduction in variance of residual sea level. Smooth (90-200 km along-track) versions of the dual-frequency altimeter ionosphere perform best both globally and within 20 deg in latitude from the equator. The noise variance in the 1/s TOPEX inospheric samples is approximately (11 mm) squared, about the same as noise in the DORIS-based correction; however, the latter has its error over scales of order 10(exp 3) km. Within 20 deg of the equator, the DORIS-based correction adds (14 mm) squared to the residual sea level variance.

Evaluation of Serum S100A8/S100A9 Levels in Patients with Autoimmune Thyroid Diseases.

PubMed

Korkmaz, Hakan; Tabur, Suzan; Savaş, Esen; Özkaya, Mesut; Aksoy, Şefika Nur; Aksoy, Nurten; Akarsu, Ersin

2016-09-01

The correlation of S100A8/S100A9 with various inflammatory conditions, including autoimmune diseases have been reported. There is no study investigating the levels of S100A8/S100A9 in autoimmune thyroid diseases (AITD). We aimed to evaluate the level of serum S100A8/S100A9 in AITD. Case control study. Fifty patients with AITD (25 Hashimoto's thyroiditis (HT) and 25 Graves' disease (GD)) were included in the study. Twenty seven healthy subjects participated as a control group. Blood samples were obtained in the 3 months after the initiation of medical treatment. Serum levels of total antioxidant status (TAS), total oxidative status (TOS), total free sulfhydryl (SH), lipid hydroperoxide (LOOH) and S100A8/S100A9 were analyzed. The patients with AITD had significantly higher S100A8/S100A9, OSI, LOOH and TOS levels than the healthy control group. There was no significant difference between GD and HT patients in terms of S100A8/S100A9, TOS and OSI levels. S100A8/S100A9 level was positively correlated with LOOH, TOS and OSI levels but negatively correlated with -SH level in the patients with AITD. Serum S100A8/S100A9 levels were increased in patients with AITD and positively correlated with LOOH, TOS and OSI whereas negatively correlated with SH.

Phenotype of postural instability/gait difficulty in Parkinson disease: relevance to cognitive impairment and mechanism relating pathological proteins and neurotransmitters

PubMed Central

Zuo, Li-Jun; Piao, Ying-Shan; Li, Li-Xia; Yu, Shu-Yang; Guo, Peng; Hu, Yang; Lian, Teng-Hong; Wang, Rui-Dan; Yu, Qiu-Jin; Jin, Zhao; Wang, Ya-Jie; Wang, Xiao-Min; Chan, Piu; Chen, Sheng-Di; Wang, Yong-Jun; Zhang, Wei

2017-01-01

Parkinson disease (PD) is identified as tremor-dominant (TD) and postural instability and gait difficulty (PIGD) phenotypes. The relationships between motor phenotypes and cognitive impairment and the underlying mechanisms relating pathological proteins and neurotransmitters in cerebrospinal fluid (CSF) are unknown. We evaluated the motor symptoms and cognitive function by scales, and detected the levels of pathological proteins and neurotransmitters in CSF. TD group and PIGD group had significantly higher levels of total tau, tau phosphorylated at the position of threonine 181(P-tau181t), threonine 231, serine 396, serine 199 and lower β amyloid (Aβ)1–42 level in CSF than those in control group; PIGD group had significantly higher P-tau181t level and lower Aβ1–42 level than those in TD group. In PD group, PIGD severity was negatively correlated with MoCA score and Aβ1–42 level in CSF, and positively correlated with Hoehn-Yahr stage and P-tau181t level in CSF. In PIGD group, PIGD severity was negatively correlated with homovanillic acid (HVA) level in CSF, and HVA level was positively correlated with Aβ1–42 level in CSF. PIGD was significantly correlated with cognitive impairment, which underlying mechanism might be involved in Aβ1–42 aggregation in brain and relevant neurochemical disturbance featured by the depletion of HVA in CSF. PMID:28332604

Correlates of anxiety and depression among patients with type 2 diabetes mellitus.

PubMed

Balhara, Yatan Pal Singh; Sagar, Rajesh

2011-07-01

Research has established the relation between diabetes and depression. Both diabetes and anxiety/depression are independently associated with increased morbidity and mortality. The present study aims at assessing the prevalence of anxiety/depression among outpatients receiving treatment for type 2 diabetes. The study was conducted in the endocrinology outpatient department of an urban tertiary care center. The instruments used included a semi-structured questionnaire, HbA1c levels, fasting blood glucose and postprandial blood glucose, Brief Patient Health Questionnaire, and Hospital Anxiety and Depression Scale (HADS). Analysis was carried out using the SPSS version 16.0. Pearson's correlation coefficient was calculated to find out the correlations. ANOVA was carried out for the in between group comparisons. There was a significant correlation between the HADS-Anxiety scale and Body Mass Index (BMI) with a correlation coefficient of 0.34 (P = 0.008). Also, a significant correlation existed between HADS-Depression scale and BMI (correlation coefficient, 0.36; P = 0.004). Significant correlation were observed between the duration of daily physical exercise and HADS-Anxiety (coefficient of correlation, -0.25; P = 0.04) scores. HADS-Anxiety scores were found to be related to HbA1c levels (correlation-coefficient, 0.41; P = 0.03) and postprandial blood glucose levels (correlation-coefficient, 0.51; P = 0.02). Monitoring of biochemical parameters like HbA1c and postprandial blood glucose levels and BMI could be a guide to development of anxiety in these patients. Also, physical exercise seems to have a protective effect on anxiety in those with type 2 diabetes mellitus.

Correlations of carotenoid content and transcript abundances for fibrillin and carotenogenic enzymes in Capsicum annum fruit pericarp.

PubMed

Kilcrease, James; Rodriguez-Uribe, Laura; Richins, Richard D; Arcos, Juan Manuel Garcia; Victorino, Jesus; O'Connell, Mary A

2015-03-01

The fruits of Capsicum spp. are especially rich sites for carotenoid synthesis and accumulation, with cultivar-specific carotenoid accumulation profiles. Differences in chromoplast structure as well as carotenoid biosynthesis are correlated with distinct carotenoid accumulations and fruit color. In the present study, the inheritance of chromoplast shape, carotenoid accumulation profiles, and transcript levels of four genes were measured. Comparisons of these traits were conducted using fruit from contrasting variants, Costeño Amarillo versus Costeño Red, and from F1 hybrids; crosses between parental lines with novel versions of these traits. Intermediate chromoplast shapes were observed in the F1, but no association between specific carotenoid accumulation and chromoplast shape was detected. Increased total carotenoid content was associated with increased β-carotene and violaxanthin content. Transcript levels for phytoene synthase (Psy) and β-carotene hydroxylase (CrtZ-2) were positively correlated with increased levels of specific carotenoids. No correlation was detected between transcript levels of capsanthin/capsorubin synthase (Ccs) and carotenoid composition or chromoplast shape. Transcript levels of fibrillin, were differentially correlated with specific carotenoids, negatively correlated with accumulation of capsanthin, and positively correlated with violaxanthin. The regulation of carotenoid accumulation in chromoplasts in Capsicum fruit continues to be a complex process with multiple steps for control. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Do End-of-Rotation and End-of-Shift Assessments Inform Clinical Competency Committees’ (CCC) Decisions?

PubMed Central

Regan, Linda; Cope, Leslie; Omron, Rodney; Bright, Leah; Bayram, Jamil D.

2018-01-01

Introduction Clinical Competency Committees (CCC) require reliable, objective data to inform decisions regarding assignment of milestone proficiency levels, which must be reported to the Accreditation Council for Graduate Medical Education. After the development of two new assessment methods, the end-of-shift (EOS) assessment and the end-of-rotation (EOR) assessment, we sought to evaluate their performance. We report data on the concordance between these assessments, as well as how each informs the final proficiency level determined in biannual CCC meetings. We hypothesized that there would be a high concordance level between the two assessment methods, including concordance of both the EOS and EOR with the final proficiency level designation by the CCC. Methods The residency program is an urban academic four-year emergency medicine residency with 48 residents. After their shifts in the emergency department (ED), residents handed out EOS assessment forms asking about individual milestones from 15 subcompetencies to supervising physicians, as well as triggered electronic EOR-doctor (EORd) assessments to supervising doctors and EOR-nurse (EORn) to nurses they had worked with after each two-week ED block. EORd assessments contained the full proficiency level scale from 16 subcompetencies, while EORn assessments contained four subcompetencies. Data reports were generated after each six-month assessment period and data was aggregated. We calculated Spearman’s rank order correlations for correlations between assessment types and between assessments and final CCC proficiency levels. Results Over 24 months, 5,234 assessments were completed. The strongest correlations with CCC proficiency levels were the EORd for the immediate six-month assessment period prior (rs 0.71–0.84), and the CCC proficiency levels from the previous six-months (rs 0.83–0.92). EOS assessments had weaker correlations (rs 0.49 to 0.62), as did EORn (rs 0.4 to 0.73). Conclusion End-of-rotation assessments completed by supervising doctors are most highly correlated with final CCC proficiency level designations, while end-of-shift assessments and end-of-rotation assessments by nurses did not correlate strongly with final CCC proficiency levels, both with overestimation of levels noted. Every level of proficiency the CCC assigned appears to be highly correlated with the designated level in the immediate six-month period, perhaps implying CCC members are biased by previous level assignments. PMID:29383066

Do End-of-Rotation and End-of-Shift Assessments Inform Clinical Competency Committees' (CCC) Decisions?

PubMed

Regan, Linda; Cope, Leslie; Omron, Rodney; Bright, Leah; Bayram, Jamil D

2018-01-01

Clinical Competency Committees (CCC) require reliable, objective data to inform decisions regarding assignment of milestone proficiency levels, which must be reported to the Accreditation Council for Graduate Medical Education. After the development of two new assessment methods, the end-of-shift (EOS) assessment and the end-of-rotation (EOR) assessment, we sought to evaluate their performance. We report data on the concordance between these assessments, as well as how each informs the final proficiency level determined in biannual CCC meetings. We hypothesized that there would be a high concordance level between the two assessment methods, including concordance of both the EOS and EOR with the final proficiency level designation by the CCC. The residency program is an urban academic four-year emergency medicine residency with 48 residents. After their shifts in the emergency department (ED), residents handed out EOS assessment forms asking about individual milestones from 15 subcompetencies to supervising physicians, as well as triggered electronic EOR-doctor (EORd) assessments to supervising doctors and EOR-nurse (EORn) to nurses they had worked with after each two-week ED block. EORd assessments contained the full proficiency level scale from 16 subcompetencies, while EORn assessments contained four subcompetencies. Data reports were generated after each six-month assessment period and data was aggregated. We calculated Spearman's rank order correlations for correlations between assessment types and between assessments and final CCC proficiency levels. Over 24 months, 5,234 assessments were completed. The strongest correlations with CCC proficiency levels were the EORd for the immediate six-month assessment period prior (r s 0.71-0.84), and the CCC proficiency levels from the previous six-months (r s 0.83-0.92). EOS assessments had weaker correlations (r s 0.49 to 0.62), as did EORn (r s 0.4 to 0.73). End-of-rotation assessments completed by supervising doctors are most highly correlated with final CCC proficiency level designations, while end-of-shift assessments and end-of-rotation assessments by nurses did not correlate strongly with final CCC proficiency levels, both with overestimation of levels noted. Every level of proficiency the CCC assigned appears to be highly correlated with the designated level in the immediate six-month period, perhaps implying CCC members are biased by previous level assignments.

Accounting for correlation in network meta-analysis with multi-arm trials.

PubMed

Franchini, A J; Dias, S; Ades, A E; Jansen, J P; Welton, N J

2012-06-01

Multi-arm trials (trials with more than two arms) are particularly valuable forms of evidence for network meta-analysis (NMA). Trial results are available either as arm-level summaries, where effect measures are reported for each arm, or as contrast-level summaries, where the differences in effect between arms compare with the control arm chosen for the trial. We show that likelihood-based inference in both contrast-level and arm-level formats is identical if there are only two-arm trials, but that if there are multi-arm trials, results from the contrast-level format will be incorrect unless correlations are accounted for in the likelihood. We review Bayesian and frequentist software for NMA with multi-arm trials that can account for this correlation and give an illustrative example of the difference in estimates that can be introduced if the correlations are not incorporated. We discuss methods of imputing correlations when they cannot be derived from the reported results and urge trialists to report the standard error for the control arm even if only contrast-level summaries are reported. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd.

Correlation Between Stress and Quality of Life Experienced by Caregivers: Perception of a Group of Healthcare Professionals.

PubMed

Silva, Bhárbara Karolline Rodrigues; Quaresma, Fernando Rodrigues Peixoto; Maciel, Erika da Silva; Figueiredo, Francisco Winter Dos Santos; Sarraf, Jonathan Souza; Adami, Fernando

2017-01-01

This study aims to evaluate the relationship between perceived level of stress and quality of life of professionals working in Prompt Service Units in the city of Palmas, Tocantins. A cross-sectional study was performed among 164 professionals from Prompt Service Units. Stress levels were evaluated using the Perceived Stress Scale. The WHOQOL-bref was used to evaluate the perception of quality of life. Quantitative variables distribution was evaluated using Shapiro-Wilk's test. For the analyses of correlations among perceived level of stress, total quality of life score, and the physical health domain of the WHOQOL-bref, Pearson's correlation test was applied. The significance level adopted for this trial was 95%. The study was approved by the Committee of Ethics in Research with Human Beings. When assessing the perceived level of stress with the total quality of life score, there was no significant correlation between those variables. However, there was an association between the perceived level of stress and the physical health domain of quality of life. Perceived quality of life was correlated with the physical health domain, and this result reinforces the importance of the facets that make up this area.

The Use of Breast Magnetic Resonance Imaging Parameters to Identify Possible Signaling Pathways of a Serum Biomarker, HE4.

PubMed

Durur-Karakaya, Afak; Durur-Subasi, Irmak; Karaman, Adem; Akcay, Mufide Nuran; Palabiyik, Saziye Sezin; Erdemci, Burak; Alper, Fatih; Acemoglu, Hamit

2016-01-01

This study aimed to investigate the relationship between breast magnetic resonance imaging (MRI) parameters; clinical features such as age, tumor diameter, N, T, and TNM stages; and serum human epididymis protein 4 (HE4) levels in patients with breast carcinoma and use this as a means of estimating possible signaling pathways of the biomarker, HE4. Thirty-seven patients with breast cancer were evaluated by breast MRI and serum HE4 levels before therapy. Correlations between parameters including age, tumor diameter T and N, dynamic curve type, enhancement ratio (ER), slope washin (S-WI), time to peak (TTP), slope washout (S-WO), and the serum level of HE4 were investigated statistically. Human epididymis protein 4 levels of early and advanced stage of disease were also compared statistically. Breast MRI parameters showed correlation to serum HE4 levels and correlations were statistically significant. Of these MRI parameters, S-WI had higher correlation coefficient than the others. Human epididymis protein 4 levels were not statistically different in early and advanced stage of disease. High correlation with MRI parameters related to neoangiogenesis may indicate signaling pathway of HE4.

The skin of Commerson's dolphins (Cephalorhynchus commersonii) as a biomonitor of mercury and selenium in Subantarctic waters.

PubMed

Cáceres-Saez, Iris; Goodall, R Natalie P; Dellabianca, Natalia A; Cappozzo, H Luis; Ribeiro Guevara, Sergio

2015-11-01

The skin of bycaught Commerson's dolphins was tested for mercury (Hg) and selenium (Se) biomonitoring in Subantarctic environments. The correlation of levels detected in the skin with those found in internal tissues - lung, liver, kidney and muscle - was assessed to evaluate how skin represents internal Hg and Se distribution for monitoring purposes. Mercury in skin had a concentration range of 0.68-3.11 μg g(-1) dry weight (DW), while Se had a higher concentration range of 74.3-124.5 μg g(-1) DW. There was no significant correlation between selenium levels in any of the analyzed tissues. Thus, the skin selenium concentration did not reflect the tissular Se levels and did not provide information for biomonitoring. The lack of correlation is explained by the biological role of Se, provided that each tissue regulates Se levels according to physiological needs. However, the skin Hg level had significant positive correlation with the levels in internal tissues (ANOVA p<0.05), particularly with that of muscle (R(2)=0.79; ANOVA p=0.0008). Thus, this correlation permits the estimation of Hg content in muscle based on the multiplication of skin biopsy levels by a factor of 1.85. Mercury bioindication using skin biopsies is a non-lethal approach that allows screening of a large number of specimens with little disturbance and makes possible an adequate sampling strategy that produces statistically valid results in populations and study areas. The correlation between Hg levels in the skin and internal tissues supports the use of the epidermis of Commerson's dolphins for Hg biomonitoring in the waters of the Subantarctic, which is a poorly studied region regarding Hg levels, sources and processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Maternal serum nitric oxide levels associated with biochemical and clinical parameters in hypertension in pregnancy.

PubMed

Bartha, J L; Comino-Delgado, R; Bedoya, F J; Barahona, M; Lubian, D; Garcia-Benasach, F

1999-02-01

To measure maternal serum concentrations of total nitrites, as an index of nitric oxide synthesis, in normal and hypertensive pregnant women, and to examine the correlation between these concentrations and several variables of clinical interest. A total of 60 women in four different groups were studied: 10 normotensive pregnant women, 17 pregnant women with preeclampsia, 18 pregnant women with gestational hypertension and 15 pregnant women with chronic hypertension. Serum nitrite levels were determined using the Griess reaction after reduction with nitrate reductase. Serum nitrite levels were higher in preeclamptic women (34.11+/-14 micromol/l, P=0.04), lower in chronic hypertensive women (19.56+/-6.46 micromol/l, P=0.04) and similar in women with gestational hypertension (26.97+/-9.44 micromol/l) in comparison to the control group (25.37+/-7.24 micromol/l). Serum nitrite levels in preeclamptic women had significant positive correlations with hematocrit, fasting insulinemia, and apolipoprotein B and negative correlations with platelet count, serum phosphorus and glucose:insulin ratio. In pregnant women with chronic hypertension a negative correlation was found between serum nitrite levels and active partial thromboplastin time. In pregnant women with gestational hypertension, serum nitrite levels had negative correlations with birthweight and 24-h urine calcium, and positive correlations with mean corspuscular hemoglobin, 24-h urine sodium and maternal age. We suggest that in women with preeclampsia, a higher maternal nitric oxide level may act as a compensatory mechanism against hemoconcentration and platelet aggregation and that nitric oxide production may be related to some metabolic events. In women with gestational hypertension, higher serum nitrite levels may be related to clinical and biochemical findings common in preeclampsia. In chronic hypertension, a lower maternal nitric oxide level is related to the status of coagulation.

Anisotropy of stress correlation in two-dimensional liquids and a pseudospin model

DOE PAGES

Wu, Bin; Iwashita, Takuya; Egami, Takeshi

2015-11-04

Liquids are condensed matter in which atoms are strongly correlated in position and momentum. The atomic pair density function (PDF) is used often in describing such correlation. However, elucidation of many properties requires higher degrees of correlation than the pair correlation. For instance, viscosity depends upon the stress correlations in space and time. We examine the cross correlation between the stress correlation at the atomic level and the PDF for two-dimensional liquids. We introduce the concept of the stress-resolved pair distribution function (SRPDF) that uses the sign of atomic-level stress as a selection rule to include particles from density correlations.more » The connection between SRPDFs and stress correlation function is explained through an approximation in which the shear stress is replaced by a pseudospin. Lastly, we further assess the possibility of interpreting the long-range stress correlation as a consequence of short-range Ising-like pseudospin interactions.« less

Correlation of combustor acoustic power levels inferred from internal fluctuating pressure measurements

NASA Technical Reports Server (NTRS)

Vonglahn, U. H.

1978-01-01

Combustion chamber acoustic power levels inferred from internal fluctuating pressure measurements are correlated with operating conditions and chamber geometries over a wide range. The variables include considerations of chamber design (can, annular, and reverse-flow annular) and size, number of fuel nozzles, burner staging and fuel split, airflow and heat release rates, and chamber inlet pressure and temperature levels. The correlated data include those obtained with combustion component development rigs as well as engines.

Correlation of transforming growth factor-β1 and tumour necrosis factor levels with left ventricular function in Chagas disease.

PubMed

Curvo, Eduardo Ov; Ferreira, Roberto R; Madeira, Fabiana S; Alves, Gabriel F; Chambela, Mayara C; Mendes, Veronica G; Sangenis, Luiz Henrique C; Waghabi, Mariana C; Saraiva, Roberto M

2018-02-19

Transforming growth factor β1 (TGF-β1) and tumour necrosis factor (TNF) have been implicated in Chagas disease pathophysiology and may correlate with left ventricular (LV) function. We determined whether TGF-β1 and TNF serum levels correlate with LV systolic and diastolic functions and brain natriuretic peptide (BNP) serum levels in chronic Chagas disease. This cross-sectional study included 152 patients with Chagas disease (43% men; 57 ± 12 years old), classified as 53 patients with indeterminate form and 99 patients with cardiac form (stage A: 24, stage B: 25, stage C: 44, stage D: 6). TGF-β1, TNF, and BNP were determined by enzyme-linked immunosorbent assay ELISA. Echocardiogram was used to determine left atrial and LV diameters, as well as LV ejection fraction and diastolic function. TGF-b1 serum levels were lower in stages B, C, and D, while TNF serum levels were higher in stages C and D of the cardiac form. TGF-β1 presented a weak correlation with LV diastolic function and LV ejection fraction. TNF presented a weak correlation with left atrial and LV diameters and LV ejection fraction. TNF is increased, while TGF-β1 is decreased in the cardiac form of chronic Chagas disease. TNF and TGF-β1 serum levels present a weak correlation with LV systolic and diastolic function in Chagas disease patients.

Can anti-Mullerian hormone (AMH) predict the outcome of intrauterine insemination with controlled ovarian stimulation?

PubMed

Bakas, Panagiotis; Boutas, Ioannis; Creatsa, Maria; Vlahos, Nicos; Gregoriou, Odysseas; Creatsas, George; Hassiakos, Dimitrios

2015-10-01

To assess whether the levels of anti-Mullerian hormone (AMH) are related to outcome of intrauterine insemination (IUI) in patients treated with gonadotropins. A total of 195 patients underwent controlled ovarian stimulation (COS) with recombinant follicle stimulating hormone (rFSH) (50-150 IU/d). All patients were submitted upto three cycles of IUI. Primary outcome was the ability of AMH levels to predict clinical pregnancy at first attempt and the cumulative clinical pregnancy probability of upto three IUI cycles. Secondary outcomes were the relation of AMH, LH, FSH, BMI, age, parity and basic estradiol levels with each other and the outcome of IUI. The area under the receiver operating characteristic (ROC) curve in predicting clinical pregnancy for AMH at first attempt was 0.53 and for cumulative clinical pregnancy was 0.76. AMH levels were positively correlated with clinical pregnancy rate at first attempt and with cumulative clinical pregnancy rate, but negatively correlated with patient's age and FSH levels. Patient's FSH, LH levels were negatively correlated with cumulative clinical pregnancy rate. AMH levels seem to have a positive correlation and patient's age and LH levels had a negative correlation with the outcome of IUI and COS with gonadotropins. AMH concentration was significantly higher and LH was significantly lower in patients with a clinical pregnancy after three cycles of IUI treatment compared with those who did not achieve pregnancy.

The correlational research among serum CXCL13 levels, circulating plasmablasts and memory B cells in patients with systemic lupus erythematosus: A STROBE-compliant article.

PubMed

Fang, Chenglong; Luo, Tingting; Lin, Ling

2017-12-01

We investigated whether serum CXC ligand 13 protein (CXCL13) levels correlate with the circulating plasmablasts and memory B-cells alteration in systemic lupus erythematosus (SLE) patients. The diagnostic use of CXCL13 concentrations in active lupus was also analyzed.A total of 36 SLE patients and 18 healthy controls were included. Serum CXCL13 levels were examined by enzyme-linked immunosorbent assay. The frequency and absolute count of circulating plasmablasts and memory B cells were analyzed by flow cytometry. Receiver operating characteristic curves (ROC curves) were generated to analyze the utility of serum CXCL13 level and plasmablasts frequency as tools for the recognition of active SLE.Elevation of serum CXCL13 levels, higher plasmablasts frequency, and reduction of memory B-cells count were observed in SLE patients, compared with healthy controls. Interestingly, correlational analyses showed not only significantly positive association between CXCL13 levels and SLE Disease Activity Index (SLEDAI) or plasmablasts frequency, but an inverse correlation between CXCL13 concentration and memory B-cell count. ROC curves showed that serum CXCL13 level and plasmablasts frequency were practical in identifying active disease from overall SLE patients, with considerable accuracy.Serum CXCL13 levels correlate with the alteration of plasmablasts and memory B cells in SLE. CXCL13 may be used as a practical tool in judgment of active SLE.

Correlation of low levels of nitrite and high levels of fetal hemoglobin in patients with sickle cell disease at baseline

PubMed Central

Elias, Darcielle Bruna Dias; Rocha, Lilianne Brito da Silva; Cavalcante, Maritza Barbosa; Pedrosa, Alano Martins; Justino, Izabel Cristina Bandeira; Gonçalves, Romélia Pinheiro

2012-01-01

Background Sickle cell disease is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and recurrent vaso-occlusive crises that reduces the quality of life of sufferers. Objective To evaluate the correlation of the levels of lactate dehydrogenase, malonaldehyde and nitrite to fetal hemoglobin in patients with sickle cell disease not under treatment with hydroxyurea in outpatients at a university hospital in Fortaleza, Ceará, Brazil. Methods Forty-four patients diagnosed with sickle cell disease were enrolled at baseline. Diagnosis was confirmed by evaluating the beta globin gene using polymerase chain reaction-restriction fragment length polymorphism. The concentration of fetal hemoglobin was obtained by high-performance liquid chromatography. Serum levels of nitrite, malonaldehyde and lactate dehydrogenase were measured by biochemical methods. Results Significantly higher levels of lactate dehydrogenase, nitrite and malonaldehyde were observed in patients with sickle cell disease compared to a control group. The study of the correlation between fetal hemoglobin levels and these variables showed a negative correlation with nitrite levels. No correlation was found between fetal hemoglobin and malonaldehyde or lactate dehydrogenase. When the study population was stratified according to fetal hemoglobin levels, a decrease in the levels of nitrite was observed with higher levels of fetal hemoglobin (p-value = 0.0415). Conclusion The results show that, similar to fetal hemoglobin levels, the concentration of nitrite can predict the clinical course of the disease, but should not be used alone as a modulator of prognosis in patients with sickle cell disease. PMID:23049438

Correlation of serum metal ion levels with pathological changes of ARMD in failed metal-on-metal-hip-resurfacing arthroplasties.

PubMed

Grammatopoulos, George; Munemoto, Mitsuru; Pollalis, Athanasios; Athanasou, Nicholas A

2017-08-01

Metal-on-metal-hip-resurfacing arthroplasties (MoMHRAs) have been associated with an increased failure rates due to an adverse-response-to-metal-debris (ARMD) associated with a spectrum of pathological features. Serum levels of cobalt (Co) and chromium (Cr) are used to assess MoMHRAs, with regard to ARMD, but it is not certain whether ion levels correlate with pathological changes in periprosthetic tissues. Serum Co and Cr levels were correlated with histological findings in 38 revised MoMHRAs (29 pseudotumour cases and 9 non-pseudotumour cases revised for pain). The extent of necrosis and macrophage infiltrate as well as the aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response was assessed semi-quantitatively; the prosthesis linear wear rate (PLWR) was also determined in ten cases. Cr levels were elevated in 82% and Co levels elevated in 53% of cases; the PLWR correlated with Cr level (rho = 0.8, p = 0.006). Tissue necrosis and macrophage infiltration were noted in all, most of which also exhibited significant ALVAL. Although a discrete correlation was not seen between Co and/or Cr ion levels and the extent of necrosis, degree of macrophage infiltration, or ALVAL score, it was noted that cases with acceptable metal ions levels had high ALVAL score. Histological features of both innate and adaptive immune response to metal wear are seen in periprosthetic tissues in cases with both elevated and non-elevated metal ion levels. MoMHRA failures with acceptable ion levels exhibited a pronounced ALVAL response. Although metal ion levels are elevated in most cases of MoMHRA failure due to ARMD, the finding of a normal metal ion level does not exclude this diagnosis.

Temperature properties in the tropical tropopause layer and their correlations with Outgoing Longwave Radiation: FORMOSAT-3/COSMIC observations

NASA Astrophysics Data System (ADS)

Wang, Kaiti; Wu, Yi-chao; Lin, Jia-Ting; Tan, Pei-Hua

2018-06-01

The properties of temperature at the level of lapse rate minimum (LRM) in the tropical tropopause layer between 20°S and 20°N are investigated using 3-year radio occultation observations based on the FORMOSAT-3/COSMIC mission from November of 2006 to October of 2009. The correlations between this LRM temperature and Outgoing Longwave Radiation (OLR) are analyzed by 5° × 5° grids in longitude and latitude. Two primary regions, one from 60°E to 180°E and the other from 90°W to 30°E, are found to have higher correlations and can be associated with regions of lower OLR values. The patterns of this spatial distributions of regions with higher correlations begin to change more obviously when the altitude ascends to the level of Cold Point Tropopause (CPT). This correlation at the LRM altitude in annual and seasonal scales also shows spatial distributions associated with OLR intensities. The altitudinal dependence of the correlations between temperature and OLR is further analyzed based on grids of high correlations with significance at LRM altitude, for the two primary regions. The results show that for the different time scales in this analysis (3-year, annual, and seasonal), the correlations all gradually decrease above the LRM levels but maintain a significant level to as high as 2.5-3.5 km. Below the LRM level, the correlation decreases with a slower rate as the altitude descends and still keeps significant at the deep 5 km level. These suggest that the vertical temperature profiles could be affected by the convection mechanism for a wide range of altitudes in the troposphere even above LRM altitude. Applying the same analysis on one complete La Niña event during the survey period also reveals similar features.

Evaluation of Correlation of Blood Glucose and Salivary Glucose Level in Known Diabetic Patients.

PubMed

Gupta, Anjali; Singh, Siddharth Kumar; Padmavathi, B N; Rajan, S Y; Mamatha, G P; Kumar, Sandeep; Roy, Sayak; Sareen, Mohit

2015-05-01

Diabetes mellitus is a chronic heterogenous disease in which there is dysregulation of carbohydrates, protein and lipid metabolism; leading to elevated blood glucose levels. The present study was conducted to evaluate the correlation between blood glucose and salivary glucose levels in known diabetic patients and control group and also to evaluate salivary glucose level as a diagnostic tool in diabetic patients. A total number of 250 patients were studied, out of which 212 formed the study group and 38 formed the control group. Among 250 patients, correlation was evaluated between blood glucose and salivary glucose values which on analysis revealed Pearson correlation of 0.073. The p-value was 0.247, which was statistically non significant. Salivary glucose values cannot be considered as a diagnostic tool for diabetic individuals.

Increased serum level of homocysteine correlates with retinal nerve fiber layer thinning in diabetic retinopathy

PubMed Central

Srivastav, Khushboo; Mahdi, Abbas A.; Shukla, Rajendra K.; Meyer, Carsten H.; Akduman, Levent; Khanna, Vinay K.

2016-01-01

Purpose To study the correlation between serum levels of vitamin B12, folic acid, and homocysteine and the severity of diabetic retinopathy and the correlation with retinal nerve fiber layer (RNFL) thinning on spectral domain optical coherence tomography (SD-OCT). Methods In a tertiary care center–based prospective cross-sectional study, 60 consecutive cases and 20 healthy controls in the age group of 40–65 years were included. The eyes of the cases were divided into three groups according to Early Treatment Diabetic Retinopathy Study (ETDRS) classification: diabetes mellitus without retinopathy (n = 20), non-proliferative diabetic retinopathy with macular edema (n = 20), and proliferative diabetic retinopathy with macular edema (n = 20). The serum levels of vitamin B12 and folic acid were measured using a standard protocol. The serum homocysteine assay was performed using an enzyme-linked immunosorbent assay (ELISA) kit. Average RNFL thickness was measured using SD-OCT. Statistical analysis was used to assess the correlations between the study variables. Results Increased severity of diabetic retinopathy was found to correlate with an increase in the serum levels of homocysteine (F = 53.79; p<0.001). The mean serum levels of vitamin B12 and folic acid were found to be within the normal reference range. A positive correlation was found between retinal nerve fiber layer thinning and serum levels of homocysteine (p<0.001). Conclusions This study, for the first time, demonstrated a correlation between increased homocysteine with a decrease in RNFL thickness and increased severity of diabetic retinopathy. PMID:27994434

Changes with aging in gastric biomarkers levels and in biochemical factors associated with Helicobacter pylori infection in asymptomatic Chinese population

PubMed Central

Shan, Jin-Hua; Bai, Xiao-Juan; Han, Lu-Lu; Yuan, Yuan; Sun, Xue-Feng

2017-01-01

AIM To observe changes in gastric biomarker levels with age and effects of Helicobacter pylori (H. pylori) infection in a healthy population, and explore factors associated with gastric biomarkers. METHODS Three hundred and ninety-five subjects were selected and underwent physical examinations, biochemical tests, and measurement of serum pepsinogen (PG) I and II, gastrin-17 (G-17) and H. pylori antibody levels. Analyses were made by Student’s t-test, ANOVA, Pearson’s correlation and multiple linear regressions. RESULTS PGII levels were higher in the ≥ 65-years-old age group (P < 0.05) and PGI/PGII were lower in the ≥ 75-years-old age group (P = 0.035) compared to the 35-44-years-old age group. Levels of low-density lipoprotein cholesterol (LDL-C) were higher (P = 0.009) in H. pylori-infected subjects that were male. LDL-C levels were higher in 55-74-years-old age group (P < 0.05) for H. pylori-infected subjects and 45-64-years-old age group (P < 0.05) for non-infected subjects compared to 35-44-years-old age group. Hp-IgG level positively correlated with PGI, PGII and G-17 (P < 0.001, P < 0.001, P = 0.006), and negatively correlated with PGI/PGII (P < 0.001). Creatinine positively correlated with PGI, PGII and G-17 (P < 0.001, P < 0.001, P < 0.001). Fasting blood glucose (FBG) positively correlated with PGI/PGII and G-17 (P < 0.001, P = 0.037). Age positively correlated with PGII and G-17 (P = 0.005, P = 0.026). CONCLUSION PGII levels increased while PGI/PGII declined with age in a healthy population. H. pylori infection had an effect on raising LDL-C levels to increase the risk of atherosclerosis in males, especially those of elderly age. Age, H. pylori infection, levels of renal function and FBG were associated with levels of pepsinogens and gastrin. PMID:28932086

Changes with aging in gastric biomarkers levels and in biochemical factors associated with Helicobacter pylori infection in asymptomatic Chinese population.

PubMed

Shan, Jin-Hua; Bai, Xiao-Juan; Han, Lu-Lu; Yuan, Yuan; Sun, Xue-Feng

2017-08-28

To observe changes in gastric biomarker levels with age and effects of Helicobacter pylori ( H. pylori ) infection in a healthy population, and explore factors associated with gastric biomarkers. Three hundred and ninety-five subjects were selected and underwent physical examinations, biochemical tests, and measurement of serum pepsinogen (PG) I and II, gastrin-17 (G-17) and H. pylori antibody levels. Analyses were made by Student's t -test, ANOVA, Pearson's correlation and multiple linear regressions. PGII levels were higher in the ≥ 65-years-old age group ( P < 0.05) and PGI/PGII were lower in the ≥ 75-years-old age group ( P = 0.035) compared to the 35-44-years-old age group. Levels of low-density lipoprotein cholesterol (LDL-C) were higher ( P = 0.009) in H. pylori -infected subjects that were male. LDL-C levels were higher in 55-74-years-old age group ( P < 0.05) for H. pylori -infected subjects and 45-64-years-old age group ( P < 0.05) for non-infected subjects compared to 35-44-years-old age group. Hp-IgG level positively correlated with PGI, PGII and G-17 ( P < 0.001, P < 0.001, P = 0.006), and negatively correlated with PGI/PGII ( P < 0.001). Creatinine positively correlated with PGI, PGII and G-17 ( P < 0.001, P < 0.001, P < 0.001). Fasting blood glucose (FBG) positively correlated with PGI/PGII and G-17 ( P < 0.001, P = 0.037). Age positively correlated with PGII and G-17 ( P = 0.005, P = 0.026). PGII levels increased while PGI/PGII declined with age in a healthy population. H. pylori infection had an effect on raising LDL-C levels to increase the risk of atherosclerosis in males, especially those of elderly age. Age, H. pylori infection, levels of renal function and FBG were associated with levels of pepsinogens and gastrin.

Cytokines profile and its correlation with endothelial damage and oxidative stress in patients with type 1 diabetes mellitus and nephropathy.

PubMed

Pestana, Rodrigo M C; Domingueti, Caroline P; Duarte, Rita C F; Fóscolo, Rodrigo B; Reis, Janice S; Rodrigues, Ana Maria S; Martins, Laís B; Sousa, Lirlândia P; Lage, Daniela P; Ferreira, Cláudia N; Ferreira, Adaliene V M; Fernandes, Ana P; Gomes, Karina B

2016-08-01

The aim of the present study was to investigate the association between the presence of albuminuria and cytokines profile with biomarkers of endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 63 DM1 patients with normoalbuminuria (<30 mg of albumin/g of creatinine) and 62 DM1 patients with micro- and macroalbuminuria (≥30 mg of albumin/g of creatinine). Plasma and urinary cytokines (TNF-α, IL-6 and IL-10) and thrombomodulin levels were determined by ELISA. Oxidative status was evaluated using the TBARS and MTT assays. Diabetic patients were characterized by elevated levels of urinary cytokines TNF-α, IL-6 and IL-10. Those with macroalbuminuria presented significantly higher TNF-α and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-α were positively correlated with plasma levels of cystatin C, creatinine, urea and albuminuria, while they were negatively correlated with estimated glomerular filtration rate. Urinary IL-10 levels proved positive correlation with fasting glucose, HbA1c, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Only urinary TNF-α levels were associated with the presence and severity of macroalbuminuria, after logistic regression analysis. This finding suggests that measurement of urinary TNF-α level may be helpful to evaluate progression to nephropathy in DM1 patients.

Effects of environmental lead pollution on blood lead and sex hormone levels among occupationally exposed group in an E-waste dismantling area.

PubMed

Yang, Yan; Lu, Xiao Song; Li, Ding Long; Yu, Yun Jiang

2013-06-01

To study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels. An E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied. The blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 μg/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks. There was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Plasma BDNF levels are correlated with aggressiveness in patients with amnestic mild cognitive impairment or Alzheimer disease.

PubMed

Nagata, Tomoyuki; Kobayashi, Nobuyuki; Shinagawa, Shunichiro; Yamada, Hisashi; Kondo, Kazuhiro; Nakayama, Kazuhiko

2014-04-01

In the present study, we examined whether neuropsychiatric symptoms were correlated with plasma brain-derived neurotrophic factor (BDNF) levels as a state marker or were associated with the BDNF polymorphism Val66Met in patients with amnestic mild cognitive impairment (A-MCI) or Alzheimer disease (AD). One hundred and seventy-six outpatients with AD (n = 129) or A-MCI (n = 47) were selected and their plasma BDNF concentrations measured. Next, we investigated the correlation between the plasma BDNF level and the Behavioral Pathology in Alzheimer Disease (Behave-AD) subscale scores, which reflect neuropsychiatric symptoms. We also compared the plasma BDNF level and the Behave-AD subscale scores among the BDNF Val66Met genotypic groups. Among the seven Behave-AD subscale scores, aggressiveness was positively correlated with the plasma BDNF level (ρ = 0.237, P < 0.005), but did not differ significantly among the three BDNF Val66Met genotypic groups. The Behave-AD total and other subscale scores did not differ significantly among the BDNF Val66Met genotypic groups and were not associated with the plasma BDNF level. Moreover, the plasma BDNF level did not differ significantly among the three BDNF Val66Met genotypic groups or between patients with A-MCI and those with AD. The plasma BDNF level was robustly correlated with aggressiveness, implying that the plasma BDNF level might be useful as a behavioral state marker in patients with AD or A-MCI.

Airborne electromagnetic data levelling using principal component analysis based on flight line difference

NASA Astrophysics Data System (ADS)

Zhang, Qiong; Peng, Cong; Lu, Yiming; Wang, Hao; Zhu, Kaiguang

2018-04-01

A novel technique is developed to level airborne geophysical data using principal component analysis based on flight line difference. In the paper, flight line difference is introduced to enhance the features of levelling error for airborne electromagnetic (AEM) data and improve the correlation between pseudo tie lines. Thus we conduct levelling to the flight line difference data instead of to the original AEM data directly. Pseudo tie lines are selected distributively cross profile direction, avoiding the anomalous regions. Since the levelling errors of selective pseudo tie lines show high correlations, principal component analysis is applied to extract the local levelling errors by low-order principal components reconstruction. Furthermore, we can obtain the levelling errors of original AEM data through inverse difference after spatial interpolation. This levelling method does not need to fly tie lines and design the levelling fitting function. The effectiveness of this method is demonstrated by the levelling results of survey data, comparing with the results from tie-line levelling and flight-line correlation levelling.

Comparative Performance of Ground vs. Aerially Assessed RGB and Multispectral Indices for Early-Growth Evaluation of Maize Performance under Phosphorus Fertilization

PubMed Central

Gracia-Romero, Adrian; Kefauver, Shawn C.; Vergara-Díaz, Omar; Zaman-Allah, Mainassara A.; Prasanna, Boddupalli M.; Cairns, Jill E.; Araus, José L.

2017-01-01

Low soil fertility is one of the factors most limiting agricultural production, with phosphorus deficiency being among the main factors, particularly in developing countries. To deal with such environmental constraints, remote sensing measurements can be used to rapidly assess crop performance and to phenotype a large number of plots in a rapid and cost-effective way. We evaluated the performance of a set of remote sensing indices derived from Red-Green-Blue (RGB) images and multispectral (visible and infrared) data as phenotypic traits and crop monitoring tools for early assessment of maize performance under phosphorus fertilization. Thus, a set of 26 maize hybrids grown under field conditions in Zimbabwe was assayed under contrasting phosphorus fertilization conditions. Remote sensing measurements were conducted in seedlings at two different levels: at the ground and from an aerial platform. Within a particular phosphorus level, some of the RGB indices strongly correlated with grain yield. In general, RGB indices assessed at both ground and aerial levels correlated in a comparable way with grain yield except for indices a* and u*, which correlated better when assessed at the aerial level than at ground level and Greener Area (GGA) which had the opposite correlation. The Normalized Difference Vegetation Index (NDVI) evaluated at ground level with an active sensor also correlated better with grain yield than the NDVI derived from the multispectral camera mounted in the aerial platform. Other multispectral indices like the Soil Adjusted Vegetation Index (SAVI) performed very similarly to NDVI assessed at the aerial level but overall, they correlated in a weaker manner with grain yield than the best RGB indices. This study clearly illustrates the advantage of RGB-derived indices over the more costly and time-consuming multispectral indices. Moreover, the indices best correlated with GY were in general those best correlated with leaf phosphorous content. However, these correlations were clearly weaker than against grain yield and only under low phosphorous conditions. This work reinforces the effectiveness of canopy remote sensing for plant phenotyping and crop management of maize under different phosphorus nutrient conditions and suggests that the RGB indices are the best option. PMID:29230230

Association between tumour infiltrating lymphocytes, histotype and clinical outcome in epithelial ovarian cancer.

PubMed

James, Fiona R; Jiminez-Linan, Mercedes; Alsop, Jennifer; Mack, Marie; Song, Honglin; Brenton, James D; Pharoah, Paul D P; Ali, H Raza

2017-09-20

There is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised method for their H&E visual evaluation has been validated in breast cancer. We sought to investigate the prognostic significance of TILs in a study of 953 invasive epithelial ovarian cancer tumour samples, both primary and metastatic, from 707 patients from the prospective population-based SEARCH study. TILs were analysed using a standardised method based on H&E staining producing a percentage score for stromal and intratumoral compartments. We used Cox regression to estimate hazard ratios of the association between TILs and survival. The extent of stromal and intra-tumoral TILs were correlated in the primary tumours (n = 679, Spearman's rank correlation = 0.60, P < 0.001) with a similar correlation in secondary tumours (n = 224, Spearman's rank correlation = 0.62, P < 0.001). There was a weak correlation between stromal TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.29, P < 0.001) and intra-tumoral TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.19, P = 0.0094). The extent of stromal TILs differed between histotypes (Pearson chi2 (12d.f.) 54.1, P < 0.0001) with higher levels of stromal infiltration in the high-grade serous and endometriod cases. A significant association was observed for higher intratumoral TIL levels and a favourable prognosis (HR 0.74 95% CI 0.55-1.00 p = 0.047). This study is the largest collection of epithelial ovarian tumour samples evaluated for TILs. We have shown that stromal and intratumoral TIL levels are correlated and that their levels correlate with clinical variables such as tumour histological subtype. We have also shown that increased levels of both intratumoral and stromal TILs are associated with a better prognosis; however, this is only statistically significant for intratumoral TILs. This study suggests that a clinically useful immune prognostic indicator in epithelial ovarian cancer could be developed using this technique.

Correlation Between Quality of Evidence and Number of Citations in Top 50 Cited Articles on Elbow Medial Ulnar Collateral Ligament Surgery.

PubMed

Jack, Robert A; Sochacki, Kyle R; Morehouse, Hannah A; McCulloch, Patrick C; Lintner, David M; Harris, Joshua D

2018-04-01

Several studies have analyzed the most cited articles in shoulder, elbow, pediatrics, and foot and ankle surgery. However, no study has analyzed the quality of the most cited articles in elbow medial ulnar collateral ligament (UCL) surgery. To (1) identify the top 50 most cited articles related to UCL surgery, (2) determine whether there was a correlation between the top cited articles and level of evidence, and (3) determine whether there was a correlation between study methodological quality and the top cited articles. Systematic review. Web of Science and Scopus online databases were searched to identify the top 50 cited articles in UCL surgery. Level of evidence, number of times cited, year of publication, name of journal, country of origin, and study type were recorded for each study. Study methodological quality was analyzed for each article with the Modified Coleman Methodology Score (MCMS) and the Methodological Index for Non-randomized Studies (MINORS). Correlation coefficients were calculated. The 50 most cited articles were published between 1981 and 2015. The number of citations per article ranged from 20 to 301 (mean ± SD, 71 ± 62 citations). Most articles (92%) were from the United States and were level 3 (16%), level 4 (58%), or unclassified (16%) evidence. There were no articles of level 1 evidence quality. The mean MCMS and MINORS scores were 28.1 ± 13.4 (range, 3-52) and 9.2 ± 3.6 (range, 2-19), respectively. There was no significant correlation between the mean number of citations and level of evidence or quality ( r s = -0.01, P = .917), MCMS ( r s = 0.09, P = .571), or MINORS ( r s = -0.26, P = .089). The top 50 cited articles in UCL surgery constitute a low level of evidence and low methodological quality, including no level 1 articles. There was no significant correlation between the mean number of citations and level of evidence or study methodological quality. However, weak correlations were observed for later publication date and improved level of evidence and methodological quality.

Correlation Between Quality of Evidence and Number of Citations in Top 50 Cited Articles on Elbow Medial Ulnar Collateral Ligament Surgery

PubMed Central

Jack, Robert A.; Sochacki, Kyle R.; Morehouse, Hannah A.; McCulloch, Patrick C.; Lintner, David M.; Harris, Joshua D.

2018-01-01

Background: Several studies have analyzed the most cited articles in shoulder, elbow, pediatrics, and foot and ankle surgery. However, no study has analyzed the quality of the most cited articles in elbow medial ulnar collateral ligament (UCL) surgery. Purpose: To (1) identify the top 50 most cited articles related to UCL surgery, (2) determine whether there was a correlation between the top cited articles and level of evidence, and (3) determine whether there was a correlation between study methodological quality and the top cited articles. Study Design: Systematic review. Methods: Web of Science and Scopus online databases were searched to identify the top 50 cited articles in UCL surgery. Level of evidence, number of times cited, year of publication, name of journal, country of origin, and study type were recorded for each study. Study methodological quality was analyzed for each article with the Modified Coleman Methodology Score (MCMS) and the Methodological Index for Non-randomized Studies (MINORS). Correlation coefficients were calculated. Results: The 50 most cited articles were published between 1981 and 2015. The number of citations per article ranged from 20 to 301 (mean ± SD, 71 ± 62 citations). Most articles (92%) were from the United States and were level 3 (16%), level 4 (58%), or unclassified (16%) evidence. There were no articles of level 1 evidence quality. The mean MCMS and MINORS scores were 28.1 ± 13.4 (range, 3-52) and 9.2 ± 3.6 (range, 2-19), respectively. There was no significant correlation between the mean number of citations and level of evidence or quality (rs = –0.01, P = .917), MCMS (rs = 0.09, P = .571), or MINORS (rs = –0.26, P = .089). Conclusion: The top 50 cited articles in UCL surgery constitute a low level of evidence and low methodological quality, including no level 1 articles. There was no significant correlation between the mean number of citations and level of evidence or study methodological quality. However, weak correlations were observed for later publication date and improved level of evidence and methodological quality. PMID:29780841

Serum osteopontin concentration is decreased by exercise-induced fat loss but is not correlated with body fat percentage in obese humans.

PubMed

You, Jeong Soon; Ji, Hye-In; Chang, Kyung Ja; Yoo, Myung Chul; Yang, Hyung-In; Jeong, In-Kyung; Kim, Kyoung Soo

2013-08-01

To evaluate the extent to which fat mass contributes to serum osteopontin (OPN) concentration, we investigated whether serum OPN levels are decreased by exercise-induced fat mass loss and whether they are associated with body fat percentage in obese humans. Twenty‑three female college students were recruited to participate in an 8‑week body weight control program. Body composition [body weight, soft lean mass, body fat mass, body fat percentage, waist-hip ratio and body mass index (BMI)] were assessed prior to and following the program. Serum lipid profiles and serum adiponectin, leptin and osteopontin levels were measured from serum collected prior to and following the program. To understand the effect of fat mass loss on the serum levels of adipokine, which is mainly produced in adipose tissue, the leptin and adiponectin levels were also measured prior to and following the program. Serum leptin levels (mean ± standard error of the mean) decreased significantly following the program (from 9.82±0.98 to 7.23±0.67 ng/ml) and were closely correlated with body fat percentage. In addition, serum adiponectin levels were negatively correlated with body fat percentage, while serum adiponectin levels were not significantly altered. By contrast, serum OPN levels decreased significantly following the program (from 16.03±2.34 to 10.65±1.22 ng/ml). However, serum OPN levels were not correlated with body fat percentage, suggesting that serum OPN levels are controlled by several other factors in humans. In conclusion, a high expression of OPN in adipose tissues may not be correlated with serum OPN levels in obese humans. Thus, tissues or physiological factors other than fat mass may have a greater contribution to the serum OPN levels.

Does lymphopenia or macrocytosis reflect 6-thioguanine levels in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine?

PubMed

Heerasing, N M; Ng, J F; Dowling, D

2016-04-01

The thiopurine drugs, 6-mercaptopurine and azathioprine, remain the mainstay of immunomodulator therapy for inflammatory bowel disease (IBD). Optimal management depends on achieving therapeutic levels of 6-thioguanine (6-TGN), but measuring thiopurine metabolites is associated with significant cost. Thiopurines cause lymphopenia and an increase in mean corpuscular volume (MCV). It is unclear whether any clinically useful correlation exists between 6-TGN levels and lymphocyte count or MCV. The aim of this study is to investigate the correlation between 6-TGN levels and lymphocyte count and MCV in thiopurine-treated patients with IBD. We analysed a prospectively acquired database of 67 patients with IBD treated with thiopurine therapy. The data were analysed looking at the relationship between 6-TGN levels and both lymphocyte count and MCV by using the Spearman's rank correlation coefficient. Twenty-seven (40%) patients had therapeutic 6-TGN levels. Thirty-three (49%) patients had sub-therapeutic 6-TGN levels. A weak positive correlation between 6-TGN levels and lymphocyte count was demonstrated, but this was not statistically significant (Spearman's R = 0.14, P = 0.23). Spearman's rank correlation coefficient between 6-TGN levels and MCV was statistically significant (R = 0.42, P = 0.0005). MCV >101 fL excluded a subtherapeutic 6-TGN level with positive predictive value of 92%. There is no specific lymphopenia that can be assumed to indicate a therapeutic 6-TGN level. The relationship between 6-TGN levels and MCV is likely to be clinically relevant. If MCV is elevated, 6-TGN is unlikely to be sub-therapeutic. MCV is a potential surrogate marker which can rule out sub-therapeutic thiopurine metabolites in patients with IBD treated with azathioprine or 6-mercaptopurine. © 2016 Royal Australasian College of Physicians.

Stochastic analyses to identify wellfield withdrawal effects on surface-water and groundwater in Miami-Dade County, Florida.

PubMed

Swain, Eric

2012-12-30

Several stochastic analyses were conducted in Miami-Dade County, Florida, to evaluate the effects of wellfield withdrawal on aquifer water levels, canal stage, and canal flow. Multiyear data for withdrawals at four water-supply wellfields, water levels at the S-121 canal control structure and groundwater head at a nearby monitoring well were used to determine the interrelation between wellfield withdrawals and water levels in the canal and aquifer. A spectral analysis was performed first on the wellfield withdrawals, showing similar patterns of fluctuations, but no well-defined seasonality. In order to compare water-level response with withdrawals at each wellfield, the intercorrelation effects between wellfields was removed through a 'causal chain' approach where the inter-wellfield correlation is used to isolate the wellfield/water-level correlation. Most computed correlations have magnitudes less than 5 percent, but with statistical significance above 90 percent. Results indicate that withdrawals from the wellfields most distant from the canal had no significant correlation to the canal levels. However the highest correlation was not at the wellfield closest to the canal, but at the two wellfields at the intermediate distance that have higher withdrawal rates. The hydraulic interconnectivity of the canal with the rest of the canal network, covering the study area, allows the canal equalizes with all connected canals. This explains why proximity to a particular canal location does not appear to be as important a factor as the withdrawal rate. Groundwater levels are more highly correlated to a wellfield on the same side of the canal, and to pumping wells in the same wellfield on the same side of the canal. This indicates that canals are an effective barrier and source/sink for the groundwater. Further nonlinear correlation analysis indicates that high withdrawal rates disproportionally affect water levels and are the predominant effect on the canal. Published by Elsevier Ltd.

Level of Discipline among University Academic Staff as a Correlate of University Development in Nigeria

ERIC Educational Resources Information Center

Uhoman, Anyi Mary

2017-01-01

This study entitled "Level of Discipline Among University Academic Staff as a Correlate of University Development in Nigeria" adopted the correlation design with a population of 2,301 academic staff purposively selected from four Universities in the North-Central Geo-Political zone of Nigeria. The Stratified Random Sampling Method was…

Correlation analysis of a ground-water level monitoring network, Miami-Dade County, Florida

USGS Publications Warehouse

Prinos, Scott T.

2005-01-01

The U.S. Geological Survey cooperative ground-water monitoring program in Miami-Dade County, Florida, expanded from 4 to 98 continuously recording water-level monitoring wells during the 1939-2001 period. Network design was based on area specific assessments; however, no countywide statistical assessments of network coverage had been performed for the purpose of assessing network redundancy. To aid in the assessment of network redundancy, correlation analyses were performed using S-PLUS 2000 statistical analysis software for daily maximum water-level data from 98 monitoring wells for the November 1, 1973, to October 31, 2000 period. Because of the complexities of the hydrologic, water-supply, and water-management systems in Miami-Dade County and the changes that have occurred to these systems through time, spatial and temporal variations in the degree of correlation had to be considered. To assess temporal variation in correlation, water-level data from each well were subdivided by year and by wet and dry seasons. For each well, year, and season, correlation analyses were performed on the data from those wells that had available data. For selected wells, the resulting correlation coefficients from each year and season were plotted with respect to time. To assess spatial variation in correlation, the coefficients determined from the correlation analysis were averaged. These average wet- and dry-season correlation coefficients were plotted spatially using geographic information system software. Wells with water-level data that correlated with a coefficient of 0.95 or greater were almost always located in relatively close proximity to each other. Five areas were identified where the water-level data from wells within the area remained correlated with that of other wells in the area during the wet and dry seasons. These areas are located in or near the C-1 and C-102 basins (2 wells), in or near the C-6 and C-7 basins (2 wells), near the Florida Keys Aqueduct Authority Well Field (2 wells), near the Hialeah-Miami Springs Well Field (6 wells), and near the West Well Field (21 wells). Data from the remaining 65 wells (most of the wells in the network) generally were not correlated with those of other wells during both the wet and dry seasons with an average coefficient of 0.95 or greater for the comparison. Because many of the wells near the West Well Field and some near the Hialeah-Miami Springs Well Field had not been in operation for very long (most having been installed in 1994), the averaged correlation coefficients for these wells were often determined using only a few seasons of data. For the few instances where water-level data were found to be well correlated on average for a lengthy period of record, short-term declines in correlation were often identified. In general, it would be beneficial to compare data for longer periods of record than currently available.

[Plasma orexin-A level in patients with obstructive apnea-hypopnea syndrome].

PubMed

Yao, Xingqi; Yang, Hui; Zhang, Guifeng; Tang, Ying

2006-06-01

To investigate the effect of uvulopalatopharyngoplasty (UPPP) on changes of plasma orexin-A levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Fifty-four cases with OSAHS diagnosed by polysomnography were treated with uvulopalatopharyngoplasty and hyoid suspension. Plasma orexin-A levels in patients with OSAHS before and after surgical procedure 6 months, and in 20 healthy people with age,sex and BMI matched controls were measured by radioimmunoassay. The plasma was deproteinized by chromatography. Correlations between orexin-A levels and AHI, MAI and SaO2 min were analyzed. The plasma orexin-A levels in the OSAHS group was significantly higher than those in the control group (P < 0.01). Plasma orexin A levels in the patients with OSAHS correlated positively with the AHI (r < 0.658, P < 0.05) and MAI. (r = 0.464, P < 0.05) but correlated negatively with the SaO2 min. The plasma orexin-A levels of 54 responders after 6 months were significantly decreased (P < 0.01) than that of pre-operation, and there is no correlation between plasma orexin-A levels and BMI. The plasma orexin-A levels in the OSAHS patients are increased which may be caused by repeated nocturnal apnoea and hypoxia due to OSAHS. Surgical procedures may decreased the plasma orexin-A levels.

Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab.

PubMed

Scaldaferri, Franco; D'Ambrosio, Daria; Holleran, Grainne; Poscia, Andrea; Petito, Valentina; Lopetuso, Loris; Graziani, Cristina; Laterza, Lucrezia; Pistone, Maria Teresa; Pecere, Silvia; Currò, Diego; Gaetani, Eleonora; Armuzzi, Alessandro; Papa, Alfredo; Cammarota, Giovanni; Gasbarrini, Antonio

2017-01-01

Infliximab is an effective treatment for inflammatory bowel disease (IBD). Studies differ regarding the influence of body mass index (BMI) on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported. Examine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α) and anti-drug antibodies(ATI), and determine if these factors can predict future response. We collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed. We confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%). Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion. This study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.

Right ventricular function and N-terminal pro-brain natriuretic peptide levels in adult patients with simple dextro-transposition of the great arteries.

PubMed

Martínez-Quintana, Efrén; Marrero-Negrín, Natalia; Gopar-Gopar, Silvia; Rodríguez-González, Fayna

2017-06-01

Dextro-transposition of the great arteries (d-TGA) patients is at high risk of developing right ventricular dysfunction and tricuspid regurgitation in adulthood. Determining the relation between echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the New York Heart Association (NYHA) functional class may help determining the best time to operate them. Patients with simple d-TGA operated in infancy with an atrial switch procedure (Mustard or Senning operation) were followed up in our Adult Congenital Heart Disease Unit. Analytical, echocardiographic, and clinical parameters were determined to evaluate the correlation between right echocardiographic ventricular function, NT-pro-BNP levels, and NYHA functional class. Twenty-four patients with d-TGA were operated in infancy of whom 17 alive patients had simple d-TGA. Nine patients had NT-pro-BNP levels lower than 200 pg/mL and eight patients were above 200 pg/mL. Patients with lower hemoglobin concentration, higher right ventricular diameter or under diuretic treatment showed significant higher NT-pro-BNP levels (above 200 pg/dL). The Spearman test showed a positive correlation between basal right ventricular diameter and tricuspid regurgitation with pro NT BNP levels (correlation coefficient of .624; P=.017 and .490; P=.046, respectively) and a negative correlation with the right ventricle fractional area change (-.508, P=.045). No correlation was seen between NT-pro-BNP levels and the rest of echocardiographic parameters or the NYHA functional class. NT-pro-BNP levels showed a positive correlation with basal right ventricular diameter and tricuspid regurgitation but not with NYHA association functional class in d-TGA patients. © 2017, Wiley Periodicals, Inc.

Systematic evaluation of environmental factors: persistent pollutants and nutrients correlated with serum lipid levels

PubMed Central

Patel, Chirag J; Cullen, Mark R; Ioannidis, John PA; Butte, Atul J

2012-01-01

Background Both genetic and environmental factors contribute to triglyceride, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) levels. Although genome-wide association studies are currently testing the genetic factors systematically, testing and reporting one or a few factors at a time can lead to fragmented literature for environmental chemical factors. We screened for correlation between environmental factors and lipid levels, utilizing four independent surveys with information on 188 environmental factors from the Centers of Disease Control, National Health and Nutrition Examination Survey, collected between 1999 and 2006. Methods We used linear regression to correlate each environmental chemical factor to triglycerides, LDL-C and HDL-C adjusting for age, age2, sex, ethnicity, socio-economic status and body mass index. Final estimates were adjusted for waist circumference, diabetes status, blood pressure and survey. Multiple comparisons were controlled for by estimating the false discovery rate and significant findings were tentatively validated in an independent survey. Results We identified and validated 29, 9 and 17 environmental factors correlated with triglycerides, LDL-C and HDL-C levels, respectively. Findings include hydrocarbons and nicotine associated with lower HDL-C and vitamin E (γ-tocopherol) associated with unfavourable lipid levels. Higher triglycerides and lower HDL-C were correlated with higher levels of fat-soluble contaminants (e.g. polychlorinated biphenyls and dibenzofurans). Nutrients and vitamin markers (e.g. vitamins B, D and carotenes), were associated with favourable triglyceride and HDL-C levels. Conclusions Our systematic association study has enabled us to postulate about broad environmental correlation to lipid levels. Although subject to confounding and reverse causality bias, these findings merit evaluation in additional cohorts. PMID:22421054

Hyposecretion of adrenal androgens and the relation of serum adrenal steroids, serotonin and insulin-like growth factor-1 to clinical features in women with fibromyalgia.

PubMed

Dessein, P H; Shipton, E A; Joffe, B I; Hadebe, D P; Stanwix, A E; Van der Merwe, B A

1999-11-01

Neuroendocrine deficiencies have been implicated in fibromyalgia (FM). In the present study, adrenal androgen metabolites and their relationship with health status in FM were investigated. For comparison, serum levels of other implicated neuroendocrine mediators were correlated with health status. Fifty-seven consecutive women with FM completed the Fibromyalgia Impact Questionnaire (FIQ). Fasting blood samples were taken for measurement of dehydroepiandrosterone sulphate (DHEAS), free testosterone (T), cortisol, serotonin and insulin-like growth factor-1. Normal value for DHEAS and T were obtained from 114 controls. DHEAS levels were decreased significantly in pre- and postmenopausal patients (P<0.0001 and P<0.0005, respectively). T levels were decreased significantly in premenopausal and insignificantly in postmenopausal patients (P<0.0001 and P=0.06, respectively). The following correlations between neurohormonal levels and FIQ scores were found: DHEAS (after adjustment for age) vs. pain (P<0.001) and T (after adjustment for age) versus physical functioning (P=0.002). None of the other neurohormonal levels correlated significantly with any of the FIQ scores. IGF-1 levels were lower in the obese patients as compared to those who were non-obese (P=0.03). The BMI correlated positively with pain (P<0. 001) and inversely with DHEAS levels (P=0.006). After further adjustment for BMI, the correlation between age adjusted DHEAS and pain was no longer significant. Hyposecretion of adrenal androgens was documented in FM. This was more pronounced in obese patients. Low serum androgen levels correlated with poor health status in FM. Longitudinal studies are needed to elucidate whether these are cause and/or effect relationships.

Country-Level Correlates of Educational Achievement: Evidence from Large-Scale Surveys

ERIC Educational Resources Information Center

He, Jia; Van de Vijver, Fons J. R.; Kulikova, Alena

2017-01-01

Linking country-level educational achievement with other country-level indicators has the potential to drive systemic educational changes, as these correlates may reflect characteristics relevant for policy-making decisions to improve educational effectiveness. This study establishes a nomological network of educational achievement at the country…

Subclinical herpesvirus shedding among HIV-1-infected men on antiretroviral therapy.

PubMed

Agudelo-Hernandez, Arcadio; Chen, Yue; Bullotta, Arlene; Buchanan, William G; Klamar-Blain, Cynthia R; Borowski, Luann; Riddler, Sharon A; Rinaldo, Charles R; Macatangay, Bernard J C

2017-09-24

We evaluated the subclinical shedding of six different herpesviruses in antiretroviral drug-treated HIV-positive [HIV(+)] MSM, and determined how this is associated with markers of inflammation and immune activation. We obtained blood, semen, throat washing, urine, and stool from 15 antiretroviral-treated HIV-1-infected MSM with CD4 T-cell reconstitution, and 12 age-matched HIV-negative [HIV (-)] MSM from the Multicenter AIDS Cohort Study at four timepoints over 24 weeks to measure DNA levels of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 and 2, human herpesvirus 6 (HHV6), and HHV8. T-cell activation and plasma levels of soluble markers of inflammation and activation were also measured at the corresponding timepoints. HIV(+) participants had a trend for higher total herpesvirus shedding rate. HIV(+) participants also had a significantly higher rate of shedding EBV and CMV compared with the HIV(-) group. Herpesvirus shedding was mostly seen in throat washings. In the HIV(+) group, herpesvirus shedding rate inversely correlated with plasma levels of interferon γ-induced protein 10 and soluble CD163. CMV DNA levels negatively correlated with levels of T-cell activation. There was a trend for a positive correlation between EBV shedding rate and plasma soluble CD14. HHV6 shedding rate negatively correlated with plasma levels of interleukin-6, soluble CD163, and interferon gamma-induced protein 10. Correlations were not observed among HIV(-) individuals. Among treated HIV-infected MSM, there are higher subclinical shedding rates of some herpesviruses that occur in different body compartments and negatively correlate with levels of inflammation and immune activation.

The impact of the haemoglobin level on the response to radiotherapy.

PubMed

Haydaroğlu, A; Yürüt, V; Arican, A; Yalman, D; Bülent Aras, A; Esassolak, M; Ozkök, S

2002-01-01

To define the impact of preradiotherapy haemoglobin (Hb) levels on the response rate of radiotherapy in patients with head and neck, uterine cervix and lung cancer. One hundred thirteen patients- 38 with head and neck cancer, 43 with carcinona of the uterine cervix and 32 with lung cancer- were retrospectively evaluated to determine the correlation between tumor response and preradiotherapy Hb levels. Hb level of 11 g/dl was taken as cut-off value for anemia. Patients were divided in two groups according to their objective response to radiotherapy. Histologically 30 of the head and neck cancers, 36 of the cervical cancers and 17 of the lung cancers were squamous-cell carcinomas. Tumor response of the epidermoid carcinomas were significantly correlated with preradiotherapy Hb levels (p < 0.001). Tumor response in patients with head and neck and cervical cancers was significantly correlated with pretreatment Hb levels while in patients with lung cancer this correlation did not reach statistical significance (p=0.059). Preradiotherapy Hb level is an important factor in determining the efficacy of radiotherapy. Raising the Hb level before radiotherapy may have a beneficial impact on the response to radiotherapy.

Utility of the Measurement of Carboxyhemoglobin Level at the Site of Acute Carbon Monoxide Poisoning in Rural Areas.

PubMed

Onodera, Makoto; Fujino, Yasuhisa; Kikuchi, Satoshi; Sato, Masayuki; Mori, Kiyofumi; Beppu, Takaaki; Inoue, Yoshihiro

2016-01-01

Objective. This study examined the hypothesis that correlations exist between the carbon monoxide exposure time and the carboxyhemoglobin concentration at the site of carbon monoxide poisoning, using a pulse carbon monoxide oximeter in rural areas or the carboxyhemoglobin concentration measured at a given medical institution. Background. In previous studies, no definitive relationships between the arterial blood carboxyhemoglobin level and the severity of carbon monoxide poisoning have been observed. Method. The subjects included patients treated for acute carbon monoxide poisoning in whom a medical emergency team was able to measure the carboxyhemoglobin level at the site of poisoning. We examined the relationship between the carboxyhemoglobin level at the site of poisoning and carbon monoxide exposure time and the relationships between the arterial blood carboxyhemoglobin level and carbon monoxide exposure time. Results. A total of 10 patients met the above criteria. The carboxyhemoglobin levels at the site of poisoning were significantly and positively correlated with the exposure time (rs = 0.710, p = 0.021), but the arterial blood carboxyhemoglobin levels were not correlated with the exposure time. Conclusion. In rural areas, the carboxyhemoglobin level measured at the site of carbon monoxide poisoning correlated with the exposure time.

Individual-and Setting-Level Correlates of Secondary Traumatic Stress in Rape Crisis Center Staff.

PubMed

Dworkin, Emily R; Sorell, Nicole R; Allen, Nicole E

2016-02-01

Secondary traumatic stress (STS) is an issue of significant concern among providers who work with survivors of sexual assault. Although STS has been studied in relation to individual-level characteristics of a variety of types of trauma responders, less research has focused specifically on rape crisis centers as environments that might convey risk or protection from STS, and no research to knowledge has modeled setting-level variation in correlates of STS. The current study uses a sample of 164 staff members representing 40 rape crisis centers across a single Midwestern state to investigate the staff member-and agency-level correlates of STS. Results suggest that correlates exist at both levels of analysis. Younger age and greater severity of sexual assault history were statistically significant individual-level predictors of increased STS. Greater frequency of supervision was more strongly related to secondary stress for non-advocates than for advocates. At the setting level, lower levels of supervision and higher client loads agency-wide accounted for unique variance in staff members' STS. These findings suggest that characteristics of both providers and their settings are important to consider when understanding their STS. © The Author(s) 2014.

Noise correlation in CBCT projection data and its application for noise reduction in low-dose CBCT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hua; Ouyang, Luo; Wang, Jing, E-mail: jhma@smu.edu.cn, E-mail: jing.wang@utsouthwestern.edu

2014-03-15

Purpose: To study the noise correlation properties of cone-beam CT (CBCT) projection data and to incorporate the noise correlation information to a statistics-based projection restoration algorithm for noise reduction in low-dose CBCT. Methods: In this study, the authors systematically investigated the noise correlation properties among detector bins of CBCT projection data by analyzing repeated projection measurements. The measurements were performed on a TrueBeam onboard CBCT imaging system with a 4030CB flat panel detector. An anthropomorphic male pelvis phantom was used to acquire 500 repeated projection data at six different dose levels from 0.1 to 1.6 mAs per projection at threemore » fixed angles. To minimize the influence of the lag effect, lag correction was performed on the consecutively acquired projection data. The noise correlation coefficient between detector bin pairs was calculated from the corrected projection data. The noise correlation among CBCT projection data was then incorporated into the covariance matrix of the penalized weighted least-squares (PWLS) criterion for noise reduction of low-dose CBCT. Results: The analyses of the repeated measurements show that noise correlation coefficients are nonzero between the nearest neighboring bins of CBCT projection data. The average noise correlation coefficients for the first- and second-order neighbors are 0.20 and 0.06, respectively. The noise correlation coefficients are independent of the dose level. Reconstruction of the pelvis phantom shows that the PWLS criterion with consideration of noise correlation (PWLS-Cor) results in a lower noise level as compared to the PWLS criterion without considering the noise correlation (PWLS-Dia) at the matched resolution. At the 2.0 mm resolution level in the axial-plane noise resolution tradeoff analysis, the noise level of the PWLS-Cor reconstruction is 6.3% lower than that of the PWLS-Dia reconstruction. Conclusions: Noise is correlated among nearest neighboring detector bins of CBCT projection data. An accurate noise model of CBCT projection data can improve the performance of the statistics-based projection restoration algorithm for low-dose CBCT.« less

Correlation between root respiration and the levels of biomass and glycyrrhizic acid in Glycyrrhiza uralensis

PubMed Central

Liu, Wenlan; Sun, Zhirong; Qu, Jixu; Yang, Chunning; Zhang, Xiaomin; Wei, Xinxin

2017-01-01

The aim of the present study was to investigate the correlation between root respiration and the levels of biomass and glycyrrhizic acid in Glycyrrhiza uralensis. Root respiration was determined using a biological oxygen analyzer. Respiration-related enzymes including glucose-6-phosphate dehydrogenase plus 6-phosphogluconate dehydrogenase, phosphohexose isomerase and succinate dehydrogenase, and respiratory pathways were evaluated. Biomass was determined by a drying-weighing method. In addition, the percentage of glycyrrhizic acid was detected using high-performance liquid chromatography. The association between root respiration and the levels of biomass and glycyrrhizic acid was investigated. The glycolysis pathway (EMP), tricarboxylic acid cycle (TCA) and pentose phosphate (PPP) pathway acted concurrently in the roots of G. uralensis. Grey correlation analysis showed that TCA had the strongest correlation (correlation coefficient, 0.8003) with biomass. Starch and acetyl coenzyme A had the closest association with above-ground biomass, while soluble sugar correlated less strongly with above-ground biomass. Grey correlation analysis between biochemical pathways and the intermediates showed that pyruvic acid had the strongest correlation with EMP, while acetyl coenzyme A correlated most strongly with TCA. Among the intermediates and pathways, pyruvic acid and EMP exhibited the greatest correlation with glycyrrhizic acid, while acetyl coenzyme A and TCA correlated with glycyrrhizic acid less closely. The results of this study may aid the cultivation of G. uralensis. However, these results require verification in further studies. PMID:28962162

Correlation between root respiration and the levels of biomass and glycyrrhizic acid in Glycyrrhiza uralensis.

PubMed

Liu, Wenlan; Sun, Zhirong; Qu, Jixu; Yang, Chunning; Zhang, Xiaomin; Wei, Xinxin

2017-09-01

The aim of the present study was to investigate the correlation between root respiration and the levels of biomass and glycyrrhizic acid in Glycyrrhiza uralensis . Root respiration was determined using a biological oxygen analyzer. Respiration-related enzymes including glucose-6-phosphate dehydrogenase plus 6-phosphogluconate dehydrogenase, phosphohexose isomerase and succinate dehydrogenase, and respiratory pathways were evaluated. Biomass was determined by a drying-weighing method. In addition, the percentage of glycyrrhizic acid was detected using high-performance liquid chromatography. The association between root respiration and the levels of biomass and glycyrrhizic acid was investigated. The glycolysis pathway (EMP), tricarboxylic acid cycle (TCA) and pentose phosphate (PPP) pathway acted concurrently in the roots of G. uralensis . Grey correlation analysis showed that TCA had the strongest correlation (correlation coefficient, 0.8003) with biomass. Starch and acetyl coenzyme A had the closest association with above-ground biomass, while soluble sugar correlated less strongly with above-ground biomass. Grey correlation analysis between biochemical pathways and the intermediates showed that pyruvic acid had the strongest correlation with EMP, while acetyl coenzyme A correlated most strongly with TCA. Among the intermediates and pathways, pyruvic acid and EMP exhibited the greatest correlation with glycyrrhizic acid, while acetyl coenzyme A and TCA correlated with glycyrrhizic acid less closely. The results of this study may aid the cultivation of G. uralensis . However, these results require verification in further studies.

Correlation of transforming growth factor-β1 and tumour necrosis factor levels with left ventricular function in Chagas disease

PubMed Central

Curvo, Eduardo OV; Ferreira, Roberto R; Madeira, Fabiana S; Alves, Gabriel F; Chambela, Mayara C; Mendes, Veronica G; Sangenis, Luiz Henrique C; Waghabi, Mariana C; Saraiva, Roberto M

2018-01-01

BACKGROUND Transforming growth factor β1 (TGF-β1) and tumour necrosis factor (TNF) have been implicated in Chagas disease pathophysiology and may correlate with left ventricular (LV) function. OBJECTIVES We determined whether TGF-β1 and TNF serum levels correlate with LV systolic and diastolic functions and brain natriuretic peptide (BNP) serum levels in chronic Chagas disease. METHODS This cross-sectional study included 152 patients with Chagas disease (43% men; 57 ± 12 years old), classified as 53 patients with indeterminate form and 99 patients with cardiac form (stage A: 24, stage B: 25, stage C: 44, stage D: 6). TGF-β1, TNF, and BNP were determined by enzyme-linked immunosorbent assay ELISA. Echocardiogram was used to determine left atrial and LV diameters, as well as LV ejection fraction and diastolic function. FINDINGS TGF-b1 serum levels were lower in stages B, C, and D, while TNF serum levels were higher in stages C and D of the cardiac form. TGF-β1 presented a weak correlation with LV diastolic function and LV ejection fraction. TNF presented a weak correlation with left atrial and LV diameters and LV ejection fraction. CONCLUSIONS TNF is increased, while TGF-β1 is decreased in the cardiac form of chronic Chagas disease. TNF and TGF-β1 serum levels present a weak correlation with LV systolic and diastolic function in Chagas disease patients. PMID:29513876

Quantitation of Vascular Endothelial Growth Factor and Interleukin-6 in Different Stages of Breast Cancer.

PubMed

Raghunathachar Sahana, Kabbathi; Akila, Prashant; Prashant, Vishwanath; Sharath Chandra, Bellekere; Nataraj Suma, Maduvanahalli

2017-10-01

Determination of the impact of angiogenesis on tumor development and progression is essential. This study aimed to determine the serum levels of Vascular endothelial growth factor (VEGF) and Interleukin 6 (IL-6) in breast carcinoma, and to correlate them with tumor size, lymph node involvement, and cancer stage. Under aseptic precautions 5 ml of venous blood was collected from 37 breast cancer patients and 20 healthy females after obtaining due consent and ethical committee clearance. Serum levels of VEGF and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA). Serum IL-6 and VEGF levels were both significantly greater in patients than controls (P = 0.001, P = 0.001, respectively). The serum IL-6 and VEGF levels also significantly correlated with TNM staging (P = 0.001, P = 0.001). Serum IL-6 and VEGF positively correlated with each other (r 2 = 0.668, P = 0.01). Serum IL-6 and VEGF levels did not correlate with tumor size (P = 0.45, P = 0.17) or lymph node metastasis (P = 0.95, P = 0.68). Serum IL-6 and VEGF were greater in breast cancer patients than controls. The levels increased with advanced tumor, nodes, metastasis (TNM) staging, thus correlating with the patients' prognoses. Serum IL-6 and VEGF levels can be used as diagnostic tools and prognostic factors in breast cancer.

Prediction of short-term changes in symptom severity by baseline plasma homovanillic acid levels in schizophrenic patients receiving clozapine.

PubMed

Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

1997-03-24

The relationship between pretreatment levels of plasma homovanillic acid (pHVA) and the outcome of clozapine treatment was studied in 18 male patients with schizophrenia who were resistant to treatment with conventional neuroleptics. After 6 months of clozapine treatment, 7 patients demonstrated > or = 20% decrease in the Brief Psychiatric Rating Scale (BPRS) (responders), while 11 patients did not (non-responders). Responders and non-responders did not differ with respect to the baseline pHVA level. The BPRS Positive Symptom scores at 6 weeks and 3 months, but not those at baseline and 6 months, following initiation of clozapine treatment negatively correlated with pHVA levels for all patients. The correlations became stronger when only responders were included. No significant correlation between Positive Symptom scores and pHVA levels was observed for non-responders. The BPRS Total and Negative Symptom scores did not correlate with pHVA for all patients, responders or non-responders at any time. The percent decrease in the BPRS Positive Symptom scores from baseline at 6 weeks following clozapine treatment correlated significantly with pHVA levels in responders. These results suggest that pretreatment levels of pHVA can be used to predict relatively short-term changes in the positive symptoms of patients with schizophrenia receiving clozapine treatment, particularly for clozapine responders.

HBsAg level and hepatitis B viral load correlation with focus on pregnancy

PubMed Central

Belopolskaya, Maria; Avrutin, Viktor; Firsov, Sergey; Yakovlev, Alexey

2015-01-01

Background Viral load measurement is necessary to estimate mother-to-child transmission risk for women with chronic hepatitis B (CHB), however, it is expensive. The present study aimed to investigate the relationship between HBsAg and hepatitis B virus (HBV) DNA levels, and to determine potential applications of HBsAg level monitoring for estimating viral load. Methods 85 patients with CHB (31 pregnant women, 26 non-pregnant women, 28 men) were included in the study. HBV DNA level was measured by real-time PCR, and HBsAg level by chemiluminescent immunoassay method. Dependency between viral load and HBsAg level was determined by Spearman correlation coefficient ρ. Results The correlation between HBsAg and HBV DNA levels was significant for all patients [ρ=0.3762 (P<0.0005; n=85)]. In the group of pregnant women, a low (unmeasurable) HBV DNA level led to a decrease in the Spearman coefficient ρ. In almost all cases a low level of the HBsAg corresponded to a low HBV DNA level. Only 2 patients had a low level of HBsAg and a relatively high viral load. By contrast, a high HBsAg level was observed in patients both with high and low viral load. Conclusions Correlation between HBsAg and HBV DNA levels is significant. In most cases, a low level of HBsAg indicates a low HBV DNA level, whereas a high HBsAg level does not always correspond to a high viral load. The measurement of HBV DNA level is necessary for pregnant women with a high HBsAg level. PMID:26127004

Protein disorder is positively correlated with gene expression in E. coli

PubMed Central

Paliy, Oleg; Gargac, Shawn M.; Cheng, Yugong; Uversky, Vladimir N.; Dunker, A. Keith

2009-01-01

We considered on a global scale the relationship between the predicted fraction of protein disorder and RNA and protein expression in E. coli. Fraction of protein disorder correlated positively with both measured RNA expression levels of E. coli genes in three different growth media and with predicted abundance levels of E. coli proteins. Though weak, the correlation was highly significant. Correlation of protein disorder with RNA expression did not depend on the growth rate of E. coli cultures and was not caused by a small subset of genes showing exceptionally high concordance in their disorder and expression levels. Global analysis was complemented by detailed consideration of several groups of proteins. PMID:18465893

Heavy Metals' Effect on Susceptibility to Attention-Deficit/Hyperactivity Disorder: Implication of Lead, Cadmium, and Antimony.

PubMed

Lee, Min-Jing; Chou, Miao-Chun; Chou, Wen-Jiun; Huang, Chien-Wei; Kuo, Ho-Chang; Lee, Sheng-Yu; Wang, Liang-Jen

2018-06-10

Background: Heavy metals are known to be harmful for neurodevelopment and they may correlate to attention deficit/hyperactivity disorder (ADHD). In this study, we aim to explore the relationships between multiple heavy metals (manganese, lead, cadmium, mercury, antimony, and bismuth), neurocognitive function, and ADHD symptoms. Methods: We recruited 29 patients with ADHD inattentive type (ADHD-I), 47 patients with ADHD hyperactivity/impulsivity type (ADHD-H/I), and 46 healthy control children. Urine samples were obtained to measure the levels of the aforementioned heavy metals in each child. Participants’ cognitive function and clinical symptoms were assessed, respectively. Results: We found ADHD-H/I patients demonstrated the highest antimony levels ( p = 0.028), and ADHD-I patients demonstrated the highest cadmium levels ( p = 0.034). Antimony levels were positively correlated with the severity of ADHD symptoms that were rated by teachers, and cadmium levels were negatively correlated with the Full Scale Intelligence Quotient. Lead levels were negatively correlated with most indices of the Wechsler Intelligence Scale for Children⁻Fourth Edition (WISC-IV), but positively correlated with inattention and hyperactivity/impulsivity symptoms ( p < 0.05). Conclusion: Lead, cadmium and antimony were associated with susceptibility to ADHD and symptom severity in school-age children. Eliminating exposure to heavy metals may help to prevent neurodevelopmental disorders in children.

The correlation between highly sensitive C-reactive protein levels and erectile function among men with late-onset hypogonadism.

PubMed

Shigehara, Kazuyoshi; Konaka, Hiroyuki; Ijima, Masashi; Nohara, Takahiro; Narimoto, Kazutaka; Izumi, Koji; Kadono, Yoshifumi; Kitagawa, Yasuhide; Mizokami, Atsushi; Namiki, Mikio

2016-12-01

We investigated the correlation between highly sensitive C-reactive protein (hs-CRP) levels and erectile function, and assessed the clinical role of hs-CRP levels in men with late-onset hypogonadism (LOH) syndrome. For 77 participants, we assessed Sexual Health Inventory for men (SHIM) score, Aging Male Symptoms (AMS) score and International Prostate Symptom Score (IPSS). We also evaluated free testosterone (FT), hs-CRP, total cholesterol, triglyceride levels, high density lipoprotein cholesterol, hemoglobin A1c, body mass index, waist size and blood pressure. We attempted to identify parameters correlated with SHIM score and to determine the factors affecting cardiovascular risk based on hs-CRP levels. A Spearman rank correlation test revealed that age, AMS score, IPSS and hs-CRP levels were significantly correlated with SHIM score. Age-adjusted analysis revealed that hs-CRP and IPSS were the independent factors affecting SHIM score (r= -0.304 and -0.322, respectively). Seventeen patients belonged to the moderate to high risk group for cardiovascular disease, whereas the remaining 60 belonged to the low risk group. Age, FT value and SHIM score showed significant differences between the two groups. A multivariate regression analysis demonstrated that SHIM score was an independent factor affecting cardiovascular risk (OR: 0.796; 95%CI: 0.637-0.995).

Systems effects on family planning innovativeness.

PubMed

Lee, S B

1983-12-01

Data from Korea were used to explore the importance of community level variables in explaining family planning adoption at the individual level. An open system concept was applied, assuming that individual family planning behavior is influenced by both environmental and individual factors. The environmental factors were measured at the village level and designated as community characteristics. The dimension of communication network variables was introduced. Each individual was characterized in terms of the degree of her involvement in family planning communication with others in her village. It was assumed that the nature of the communication network linking individuals with each other effects family planning adoption at the individual level. Specific objectives were to determine 1) the relative importance of the specific independent variables in explaining family planning adoption and 2) the relative importance of the community level variables in comparison with the individual level variables in explaining family planning adoption at the individual level. The data were originally gathered in a 1973 research project on Korea's mothers' clubs. 1047 respondents were interviewed, comprising all married women in 25 sample villages having mothers' clubs. The dependent variable was family planning adoption behavior, defined as current use of any of the modern methods of family planning. The independent variables were defined at 3 levels: individual, community, and at a level intermediate between them involving communication links between individuals. More of the individual level independent variables were significantly correlated with the dependent variables than the community level variables. Among those variables with statistically significant correlations, the correlation coefficients were consistently higher for the individual level than for the community level variables. More of the variance in the dependent variable was explained by individual level than by community level variables. Community level variables accounted for only about 2.5% of the total variance in the dependent variable, in marked contrast to the result showing individual level variables accounting for as much as 19% of the total variance. When both individual and community level variables were entered into a multiple correlation analysis, a multiple correlation coefficient of .4714 was obtained together they explained about 20% of the total variance. The 2 communication network variables--connectedness and integrativeness--were correlated with the dependent variable at much higher levels than most of the individual or community level variables. Connectedness accounted for the greatest amount of the total variance. The communication network variables as a group explained as much of the total variance in the dependent variable as the individual level variables and greatly more that the community level variables.

First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia.

PubMed

Saxena, Aditi R; Seely, Ellen W; Rich-Edwards, Janet W; Wilkins-Haug, Louise E; Karumanchi, S Ananth; McElrath, Thomas F

2013-04-04

First trimester Pregnancy Associated Plasma Protein A (PAPP-A) levels, routinely measured for aneuploidy screening, may predict development of preeclampsia. This study tests the hypothesis that first trimester PAPP-A levels correlate with soluble fms-like tyrosine kinase-1 (sFlt-1) levels, an angiogenic marker associated with preeclampsia, throughout pregnancy. sFlt-1 levels were measured longitudinally in 427 women with singleton pregnancies in all three trimesters. First trimester PAPP-A and PAPP-A Multiples of Median (MOM) were measured. Student's T and Wilcoxon tests compared preeclamptic and normal pregnancies. A linear mixed model assessed the relationship between log PAPP-A and serial log sFlt-1 levels. PAPP-A and PAPP-A MOM levels were significantly lower in preeclamptic (n = 19), versus normal pregnancies (p = 0.02). Although mean third trimester sFlt-1 levels were significantly higher in preeclampsia (p = 0.002), first trimester sFlt-1 levels were lower in women who developed preeclampsia, compared with normal pregnancies (p = 0.03). PAPP-A levels correlated significantly with serial sFlt-1 levels. Importantly, low first trimester PAPP-A MOM predicted decreased odds of normal pregnancy (OR 0.2, p = 0.002). Low first trimester PAPP-A levels suggests increased future risk of preeclampsia and correlate with serial sFlt-1 levels throughout pregnancy. Furthermore, low first trimester PAPP-A status significantly predicted decreased odds of normal pregnancy.

Profiling signaling proteins in human spermatozoa: biomarker identification for sperm quality evaluation.

PubMed

Silva, Joana Vieira; Freitas, Maria João; Correia, Bárbara Regadas; Korrodi-Gregório, Luís; Patrício, António; Pelech, Steven; Fardilha, Margarida

2015-10-01

To determine the correlation between semen basic parameters and the expression and activity of signaling proteins. In vitro studies with human spermatozoa. Academic research institute. Thirty-seven men provided semen samples for routine analysis. None. Basic semen parameters tracked included sperm DNA fragmentation (SDF), the expression levels of 75 protein kinases, and the phosphorylation/cleavage patterns of 18 signaling proteins in human spermatozoa. The results indicated that the phosphorylated levels of several proteins (Bad, GSK-3β, HSP27, JNK/SAPK, mTOR, p38 MAPK, and p53), as well as cleavage of PARP (at D214) and Caspase-3 (at D175), were significantly correlated with motility parameters. Additionally, the percentage of morphologically normal spermatozoa demonstrated a significant positive correlation with the phosphorylated levels of p70 S6 kinase and, in turn, head defects and the teratozoospermia index (TZI) showed a significant negative correlation with the phosphorylated levels of Stat3. There was a significant positive correlation between SDF and the teratozoospermia index, as well as the presence of head defects. In contrast, SDF negatively correlated with the percentage of morphologically normal spermatozoa and the phosphorylation of Akt and p70 S6 kinase. Subjects with varicocele demonstrated a significant negative correlation between head morphological defects and the phosphorylated levels of Akt, GSK3β, p38 MAPK, and Stat1. Additionally, 34 protein kinases were identified as expressed in their total protein levels in normozoospermic samples. This study contributed toward establishing a biomarker "fingerprint" to assess sperm quality on the basis of molecular parameters. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Exposure assessment in epidemiologic studies of adverse pregnancy outcomes and disinfection byproducts.

PubMed

King, Will D; Dodds, Linda; Armson, B Anthony; Allen, Alexander C; Fell, Deshayne B; Nimrod, Carl

2004-11-01

A major challenge in studies that examine the association between disinfection byproducts in drinking water and pregnancy outcomes is the accurate representation of a subject's exposure. We used household water samples and questionnaire information on water-use behavior to examine several aspects of exposure assessment: (i) the distribution and correlation of specific disinfection byproducts, (ii) spatial distribution system and temporal variation in byproduct levels, and (iii) the contribution of individual water-use behavior. The level of specific trihalomethanes (THMs) and haloacetic acids (HAAs) was determined for 360 household water samples in Eastern Ontario and Nova Scotia. Subjects were interviewed regarding tap water ingestion and showering and bathing practices. In both provinces, total THMs correlated highly with chloroform (correlation coefficient (r) >0.95) and less so with total HAAs (r = 0.74 in Nova Scotia and r = 0.52 in Ontario). The correlation between total THMs and bromodichloromethane was high in Nova Scotia (r = 0.63), but low in Ontario (r = 0.26). The correlation was between THM level in individual household samples, and the mean THM level during the same time period from several distribution system samples was 0.63, while a higher correlation in THM level was observed for samples taken at the same location 1 year apart (r = 0.87). A correlation of 0.73 was found between household THM level and a total exposure measure incorporating ingestion, showering, and bathing behaviors. These results point to the importance of: measurement of different classes of byproducts; household rather than distribution system sampling; and, incorporation of subject behaviors in exposure assessment in epidemiologic studies of disinfection byproducts and adverse pregnancy outcomes.

Analysis of spatial correlations in a model two-dimensional liquid through eigenvalues and eigenvectors of atomic-level stress matrices.

PubMed

Levashov, V A; Stepanov, M G

2016-01-01

Considerations of local atomic-level stresses associated with each atom represent a particular approach to address structures of disordered materials at the atomic level. We studied structural correlations in a two-dimensional model liquid using molecular dynamics simulations in the following way. We diagonalized the atomic-level stress tensor of every atom and investigated correlations between the eigenvalues and orientations of the eigenvectors of different atoms as a function of distance between them. It is demonstrated that the suggested approach can be used to characterize structural correlations in disordered materials. In particular, we found that changes in the stress correlation functions on decrease of temperature are the most pronounced for the pairs of atoms with separation distance that corresponds to the first minimum in the pair density function. We also show that the angular dependencies of the stress correlation functions previously reported by Wu et al. [Phys. Rev. E 91, 032301 (2015)10.1103/PhysRevE.91.032301] do not represent the anisotropic Eshelby's stress fields, as it is suggested, but originate in the rotational properties of the stress tensors.

Fear and/or anxiety of children and parents associated with the dental environment.

PubMed

Leal, A M; Serra, K G; Queiroz, R C; Araújo, M A; Maia Filho, E M

2013-12-01

To assess levels of anxiety in children concerning different dental instruments and equipment and to relate them with parents' anxiety levels moments before the appointment. Fifty children from 4 to 12 years of age (average of 10±3.07) and their respective parents were evaluated. A facial scale was used to assess children's anxiety levels, while the Dental Anxiety Scale (DAS) was used to assess parents. Friedman test was applied to check any differences in children's anxiety levels relative to the equipment/instruments, and this was complemented by the use of the Wilcoxon test for two-by-two comparison. In order to assess correlation between parents' and their children's anxiety levels, the study used Spearman correlation coefficient. With regard to parents' anxiety levels, 4% resulted as null, 18% were low, 56% were moderate, and 22% were exacerbated; children's anxiety level results were: 52% light, 44% intermediate, and 4% intense. Anxiety levels related to instruments/equipment were, in descending order: carpule syringe > paediatric forceps > dental explorer > x-ray machine > rubber dam punch > high speed handpiece > rubber dam forceps > mouth mirror > clinical tweezers > dental chair. No correlation was found between parents' anxiety levels and those of their children (p=0.546). The instruments/equipment used in the assessment generated different anxiety levels in the children. No correlation was found between parents' anxiety levels and those of their children.

Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis

PubMed Central

2012-01-01

Introduction The current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA. Methods This study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerr's criteria, disease extent index-Takayasu, physician's global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay. Results Unacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity. Conclusions This study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity. PMID:23259466

Effects of delivery on maternal & neonatal irisin levels in normal and preeclamptic pregnant women.

PubMed

Foda, Ashraf A; Foda, Engy A

2017-10-01

The aim of this work was to measure the irisin levels in maternal and umbilical cord serums at cesarean section and vaginal delivery. This is a case-control study conducted at the Obstetric Department of the Mansoura University Hospital, Mansoura University, Egypt. The 150 nulliparous cases were divided into three groups. Serum irisin concentrations were assayed by enzyme-linked immunosorbent assay (ELISA) method. Unpaired t-test and correlation were done by using the Statistical Package for Social Scientists (SPSS). The maternal irisin levels in cases with mild preeclampsia were found to be significantly lower than that of the normal cases. In cases with mild preeclampsia, the maternal irisin levels early in labor for vaginal deliveries were significantly higher than that during cesarean section. The maternal irisin levels after vaginal deliveries were significantly higher than the levels early in labor. The maternal serum irisin was a significantly correlated with the duration of the first stage. The umbilical cord serum irisin levels were significantly correlated with the neonatal weight and with the duration of the first stage of labor. Labor is a strong stimulus to the release of irisin into the maternal and fetal circulations. Neonatal serum irisin levels are positively correlated with the birth weight and with the duration of the first stage. The neonatal birth weight and the duration of the first stage of labor are positively correlated with the umbilical cord serum irisin levels. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

County level incidence rates of chronic lymphocytic leukemia are associated with residential radon levels.

PubMed

Oancea, S Cristina; Rundquist, Bradley C; Simon, Isaac; Swartz, Sami; Zheng, Yun; Zhou, Xudong; Sens, Mary Ann; Schwartz, Gary G

2017-09-01

We previously reported that incidence rates for chronic lymphocytic leukemia (CLL) among US states are significantly correlated with levels of residential radon (RR). Because these correlations could be influenced by confounding and/or misclassification among large geographic units, we reinvestigated them using smaller geographic units that better reflect exposure and disease at the individual level. We examined the relationships between CLL and RR per county in 478 counties with publicly-available data. After adjustment for ultraviolet radiation, a possible risk factor for CLL, county rates for CLL and RR were significantly correlated among males and females both together and separately (p < 0.0001). CLL is significantly associated with RR at the county level.

A clinical study of electrophysiological correlates of behavioural comfort levels in cochlear implantees.

PubMed

Raghunandhan, S; Ravikumar, A; Kameswaran, Mohan; Mandke, Kalyani; Ranjith, R

2014-05-01

Indications for cochlear implantation have expanded today to include very young children and those with syndromes/multiple handicaps. Programming the implant based on behavioural responses may be tedious for audiologists in such cases, wherein matching an effective Measurable Auditory Percept (MAP) and appropriate MAP becomes the key issue in the habilitation program. In 'Difficult to MAP' scenarios, objective measures become paramount to predict optimal current levels to be set in the MAP. We aimed to (a) study the trends in multi-modal electrophysiological tests and behavioural responses sequentially over the first year of implant use; (b) generate normative data from the above; (c) correlate the multi-modal electrophysiological thresholds levels with behavioural comfort levels; and (d) create predictive formulae for deriving optimal comfort levels (if unknown), using linear and multiple regression analysis. This prospective study included 10 profoundly hearing impaired children aged between 2 and 7 years with normal inner ear anatomy and no additional handicaps. They received the Advanced Bionics HiRes 90 K Implant with Harmony Speech processor and used HiRes-P with Fidelity 120 strategy. They underwent, impedance telemetry, neural response imaging, electrically evoked stapedial response telemetry (ESRT), and electrically evoked auditory brainstem response (EABR) tests at 1, 4, 8, and 12 months of implant use, in conjunction with behavioural mapping. Trends in electrophysiological and behavioural responses were analyzed using paired t-test. By Karl Pearson's correlation method, electrode-wise correlations were derived for neural response imaging (NRI) thresholds versus most comfortable level (M-levels) and offset based (apical, mid-array, and basal array) correlations for EABR and ESRT thresholds versus M-levels were calculated over time. These were used to derive predictive formulae by linear and multiple regression analysis. Such statistically predicted M-levels were compared with the behaviourally recorded M-levels among the cohort, using Cronbach's alpha reliability test method for confirming the efficacy of this method. NRI, ESRT, and EABR thresholds showed statistically significant positive correlations with behavioural M-levels, which improved with implant use over time. These correlations were used to derive predicted M-levels using regression analysis. On an average, predicted M-levels were found to be statistically reliable and they were a fair match to the actual behavioural M-levels. When applied in clinical practice, the predicted values were found to be useful for programming members of the study group. However, individuals showed considerable deviations in behavioural M-levels, above and below the electrophysiologically predicted values, due to various factors. While the current method appears helpful as a reference to predict initial maps in 'difficult to Map' subjects, it is recommended that behavioural measures are mandatory to further optimize the maps for these individuals. The study explores the trends, correlations and individual variabilities that occur between electrophysiological tests and behavioural responses, recorded over time among a cohort of cochlear implantees. The statistical method shown may be used as a guideline to predict optimal behavioural levels in difficult situations among future implantees, bearing in mind that optimal M-levels for individuals can vary from predicted values. In 'Difficult to MAP' scenarios, following a protocol of sequential behavioural programming, in conjunction with electrophysiological correlates will provide the best outcomes.

Physical activity, sedentary behavior and their correlates in children with Autism Spectrum Disorder: A systematic review

PubMed Central

Downing, Katherine; Rinehart, Nicole J.; Barnett, Lisa M.; May, Tamara; McGillivray, Jane A.; Papadopoulos, Nicole V.; Skouteris, Helen; Timperio, Anna

2017-01-01

Autism Spectrum Disorder affects up to 2.5% of children and is associated with harmful health outcomes (e.g. obesity). Low levels of physical activity and high levels of sedentary behaviors may contribute to harmful health outcomes. To systematically review the prevalence and correlates of physical activity and sedentary behaviors in children with Autism Spectrum Disorder, electronic databases (PsycINFO, SPORTDiscus, EMBASE, Medline) were searched from inception to November 2015. The review was registered with PROSPERO (CRD42014013849). Peer-reviewed, English language studies were included. Two reviewers screened potentially relevant articles. Outcomes of interest were physical activity and sedentary behaviour levels and their potential correlates. Data were collected and analysed in 2015. Of 35 included studies, 15 reported physical activity prevalence, 10 reported physical activity correlates, 18 reported sedentary behavior prevalence, and 10 reported sedentary behavior correlates. Estimates of children’s physical activity (34–166 mins/day, average 86 mins/day) and sedentary behavior (126–558 mins/day in screen time, average 271 mins/day; 428–750 mins/day in total sedentary behavior, average 479 mins/day) varied across studies. Age was consistently inversely associated, and sex inconsistently associated with physical activity. Age and sex were inconsistently associated with sedentary behavior. Sample sizes were small. All but one of the studies were classified as having high risk of bias. Few correlates have been reported in sufficient studies to provide overall estimates of associations. Potential correlates in the physical environment remain largely unexamined. This review highlights varying levels of physical activity and sedentary behavior in children with Autism Spectrum Disorder. Research is needed to consistently identify the correlates of these behaviors. There is a critical need for interventions to support healthy levels of these behaviors. PMID:28245224

The Potentials of Fas Receptors and Ligands in Monitoring HIV-1 Disease in Children in Yaoundé, Cameroon.

PubMed

Ikomey, G; Assoumou, M-C Okomo; Atashili, J; Mesembe, M; Mukwele, B; Lyonga, E; Eyoh, A; Kafando, A; Ndumbe, P M

2016-09-01

Difficulties in systematically monitoring HIV viral load in resource-limited settings prompt the search for alternate approaches. The authors aimed at assessing the correlation between the plasma levels of soluble forms of Fas receptors (Fas) and Fas ligands (FasL) with standard indicators of HIV disease progression in children. Twenty-two HIV-1-positive children were enrolled in Yaounde. CD4 counts, CD4% counts, plasma levels of Fas, FasL, and HIV-1 RNA levels were assayed. The correlation coefficients (P values) between FasL levels and each of HIV-1 viral load, CD4 counts, and CD4% were, respectively, .56 (.01), -.29 (.18), and .30 (.18). On the other hand, the respective correlation coefficients (P values) with Fas levels were .12 (.60), -.30 (.18), and -.29 (.19). The significant correlation between levels of HIV-1 viral load and FasL suggests that the latter needs to be further studied as a potential biomarker to monitor HIV-1 disease progression in children in resource-limited setting. © The Author(s) 2013.

Leptin levels in patients with systemic lupus erythematosus inversely correlate with regulatory T cell frequency.

PubMed

Wang, X; Qiao, Y; Yang, L; Song, S; Han, Y; Tian, Y; Ding, M; Jin, H; Shao, F; Liu, A

2017-11-01

Leptin levels are increased in patients with systemic lupus erythematosus (SLE) but little is known on how this correlates with several disease characteristics including the frequency of regulatory T cells (Tregs). Here we compared serum leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25 healthy matched controls. Correlations with lupus disease activity were also analyzed, as well as Treg proliferation potential. It was found that leptin was remarkably increased in SLE patients as compared to controls, particularly in SLE patients with moderate and severe active SLE, and the increase correlated with disease activity. Importantly, increased leptin in lupus patients inversely correlated with the frequency of Tregs but not in controls, and leptin neutralization resulted in the expansion of Tregs ex vivo. Thus, hyperleptinemia in lupus patients correlates directly with disease activity and inversely with Treg frequency. The finding that leptin inhibition expands Tregs in SLE suggests possible inhibition of this molecule for an enhanced Treg function in the disease.

Relationships among cardiovascular, muscular, and oxytocin responses during human sexual activity.

PubMed

Carmichael, M S; Warburton, V L; Dixen, J; Davidson, J M

1994-02-01

To determine the psychophysiological correlates of hormonal response during sexual activity, systolic blood pressure (SBP), anal electromyography (EMG), and anal photoplethysmography (APG) were monitored continuously throughout testing in 13 women and 10 men. Each subject completed two or more tests of self-stimulation to 5 min beyond orgasm. Blood samples were obtained continuously for measurement of oxytocin (OT) levels. In both men and women, very high positive correlations were observed between the percentage change in levels from baseline through orgasm of: OT and SBP; OT and EMG intensity prior to and during orgasm; APG and EMG. The number of anal contractions and duration of orgasm were also highly correlated. Two patterns of orgasm were defined by the presence or absence of a quiescent period between orgasmic contractions. EMG and APG amplitudes correlated with the pattern of orgasm. Subjective orgasm intensity correlated significantly with increased levels of OT in multiorgasmic women only. The positive correlations between measures are consistent with a possible functional role for OT in human sexual response.

Improved estimation of subject-level functional connectivity using full and partial correlation with empirical Bayes shrinkage.

PubMed

Mejia, Amanda F; Nebel, Mary Beth; Barber, Anita D; Choe, Ann S; Pekar, James J; Caffo, Brian S; Lindquist, Martin A

2018-05-15

Reliability of subject-level resting-state functional connectivity (FC) is determined in part by the statistical techniques employed in its estimation. Methods that pool information across subjects to inform estimation of subject-level effects (e.g., Bayesian approaches) have been shown to enhance reliability of subject-level FC. However, fully Bayesian approaches are computationally demanding, while empirical Bayesian approaches typically rely on using repeated measures to estimate the variance components in the model. Here, we avoid the need for repeated measures by proposing a novel measurement error model for FC describing the different sources of variance and error, which we use to perform empirical Bayes shrinkage of subject-level FC towards the group average. In addition, since the traditional intra-class correlation coefficient (ICC) is inappropriate for biased estimates, we propose a new reliability measure denoted the mean squared error intra-class correlation coefficient (ICC MSE ) to properly assess the reliability of the resulting (biased) estimates. We apply the proposed techniques to test-retest resting-state fMRI data on 461 subjects from the Human Connectome Project to estimate connectivity between 100 regions identified through independent components analysis (ICA). We consider both correlation and partial correlation as the measure of FC and assess the benefit of shrinkage for each measure, as well as the effects of scan duration. We find that shrinkage estimates of subject-level FC exhibit substantially greater reliability than traditional estimates across various scan durations, even for the most reliable connections and regardless of connectivity measure. Additionally, we find partial correlation reliability to be highly sensitive to the choice of penalty term, and to be generally worse than that of full correlations except for certain connections and a narrow range of penalty values. This suggests that the penalty needs to be chosen carefully when using partial correlations. Copyright © 2018. Published by Elsevier Inc.

Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

PubMed Central

Orlander, Philip R.

2011-01-01

Background: There is a renewed interest in adrenal function during severe sepsis. Most studies have used total serum cortisol levels; however, only free serum cortisol is biologically active. The aim of this study was to determine the validity of salivary cortisol levels as a surrogate for free serum cortisol levels during septic shock. Methods: Fifty-seven patients with septic shock were studied to determine the correlation between total serum cortisol and salivary cortisol to free serum cortisol levels. Thirty-eight patients were included in the salivary to free serum cortisol correlation. Salivary cortisol level was tested by enzyme immunoassay. Serum total cortisol, free cortisol, and cortisol-binding globulin (CBG) levels were determined by liquid chromatography-mass spectrometry, equilibrium analysis, and radioimmunoassay, respectively. Results: The mean ± SD age was 56.6 ± 18.5 years. Fifty-seven percent were women. APACHE (Acute Physiology and Chronic Health Evaluation) II score median was 26, Simplified Acute Physiology Score II median was 61, and Sequential Organ Failure Assessment median was 13. The correlation between salivary and free serum cortisol levels was 0.79 (95% CI, 0.63-0.89; P < .0001). The correlation between free serum cortisol and total serum cortisol levels was 0.86 (95% CI, 0.78-0.92; P < .0001). The mean ± SD free serum cortisol level was 2.27 ± 1.64 μg/dL. The mean ± SD salivary cortisol level was 2.60 ± 2.69 μg/dL. The mean ± SD total serum cortisol level was 21.56 ± 8.71 μg/dL. The mean ± SD CBG level was 23.54 ± 8.33 mg/dL. Conclusions: Salivary cortisol level can be used as a surrogate of free serum cortisol level in patients with septic shock with very good correlation. Salivary cortisol testing is noninvasive, easy to perform, and can be conducted daily. Trial registry: ClinicalTrials.gov; No.: NCT00523198; URL: www.clinicaltrials.gov PMID:21816912

The relation of cortisol and sex hormone levels to results of psychological, performance, IQ and memory tests in military men and women.

PubMed

Flegr, Jaroslav; Hampl, Richard; Černochová, Dana; Preiss, Marek; Bičíková, Marie; Sieger, Ladislav; Příplatová, Lenka; Kaňková, Šárka; Klose, Jiří

2012-01-01

Cortisol, along with other hormones of hypothalamo-pituitary-adrenal axis, belongs to one of the main factors influencing psychological and pathognomic factors, intelligence, and memory. The aim of our study was to review a large battery of psychological, performance, IQ and memory tests as to their relation with cortisol, testosterone and estrogen levels in groups of 100 men and 93 women who attended the Central Military Hospital in Prague for regular entrance psychological examinations for military personnel. In men, we detected positive correlations between cortisol and emotional lability, and negative correlations with impulsivity, while in women hypochondria and psychopathology were negatively correlated, and aggression measured with the Meili selective memory test had a positive relation to cortisol level. Testosterone correlated positively with emotional liability and negatively with impulsivity in men, and negatively with hypochondria and psychasteny, indirect aggression, irritability and paranoia in women. Estradiol correlated positively with psychopathology in men, and negatively with phobia. It was positively correlated with negativism in women. No clear correlation was observed between the concentration of steroid hormones and psychomotor performance or intelligence. Concentrations of steroid hormones correlate with results of several psychological tests, the sign and magnitude of these correlations, however, very often differ in military men and women.

Correlations between Prenatal Exposure to Perfluorinated Chemicals and Reduced Fetal Growth

PubMed Central

Washino, Noriaki; Saijo, Yasuaki; Sasaki, Seiko; Kato, Shizue; Ban, Susumu; Konishi, Kanae; Ito, Rie; Nakata, Ayako; Iwasaki, Yusuke; Saito, Koichi; Nakazawa, Hiroyuki; Kishi, Reiko

2009-01-01

Background Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are man-made, ubiquitous, and persistent contaminants in the environment, wildlife, and humans. Although recent studies have shown that these chemicals interfere with fetal growth in humans, the results are inconsistent. Objectives Our goal was to investigate the correlation between relatively low levels of PFOS and PFOA in maternal serum and birth weight and birth size. Methods We conducted a hospital-based prospective cohort study between July 2002 and October 2005 in Sapporo, Japan. A total of 428 women and their infants were involved in the study. We obtained characteristics of the mothers and infants from self-administered questionnaire surveys and from medical records. We analyzed maternal serum samples for PFOS and PFOA by liquid chromatography–tandem mass spectrometry (LC/MS/MS). Results After adjusting for confounding factors, PFOS levels negatively correlated with birth weight [per log10 unit: β = −148.8 g; 95% confidence interval (CI), −297.0 to −0.5 g]. In addition, analyses stratified by sex revealed that PFOS levels negatively correlated with birth weight only in female infants (per log10 unit: β = −269.4 g; 95% CI, −465.7 to −73.0 g). However, we observed no correlation between PFOA levels and birth weight. Conclusion Our results indicate that in utero exposure to relatively low levels of PFOS was negatively correlated with birth weight. PMID:19440508

Appetite suppression through smelling of dark chocolate correlates with changes in ghrelin in young women.

PubMed

Massolt, Elske T; van Haard, Paul M; Rehfeld, Jens F; Posthuma, Eduardus F; van der Veer, Eveline; Schweitzer, Dave H

2010-04-09

Cephalic effects on appetite are mediated by vagal tone and altered gastrointestinal hormones. The objective of this study is to explore the relationship between appetite and levels of gastrointestinal hormones after smelling chocolate and after melt-and-swallow 30 g chocolate (1.059 oz, 85% cocoa, 12.5 g of sugar per 100g product). Twelve female residents (BMI between 18 and 25 kg/m(2)) all participated in two 60-minute study sessions. In the first session, all 12 women ate chocolate; for the second session, they were randomized either to smell chocolate (n=6) or to serve as a control (no eating or smelling; n=6). At the start of the sessions, levels of insulin, glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK), but not glucose, correlated with appetite scored on a visual analogue scale (VAS). In contrast, ghrelin levels correlated inversely with scored appetite. Chocolate eating and smelling both induced a similar appetite suppression with a disappearance of correlations between VAS scores and insulin, GLP-1 and CCK levels. However, while the correlation between VAS score and ghrelin disappeared completely after chocolate eating, it reversed after chocolate smelling, that is, olfactory stimulation with dark chocolate (85%) resulted in a satiation response that correlated inversely with ghrelin levels. Copyright 2010 Elsevier B.V. All rights reserved.

Quantum correlations and violation of the Bell inequality induced by an external field in a two-photon radiative cascade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan Luqi; Das, Sumanta

2011-06-15

We study the polarization-dependent second-order correlation of a pair of photons emitted in a four-level radiative cascade driven by an external field. It is found that the quantum correlations of the emitted photons, degraded by the energy splitting of the intermediate levels in the radiative cascade, can be efficiently revived by a far-detuned external field. The physics of this revival is linked to an induced Stark shift and the formation of dressed states in the system by the nonresonant external field. Furthermore, we investigated the competition between the effect of the coherent external field and incoherent dephasing of the intermediatemore » levels. We find that the degradation of quantum correlations due to the incoherent dephasing can be contained for small dephasing with the external field. We also studied the nonlocality of the correlations by evaluating the Bell inequality in the linear polarization basis for the radiative cascade. We find that the Bell parameter decreases rapidly with increase in the intermediate-level energy splitting or incoherent dephasing rate to the extent that there is no violation. However, the presence of an external field leads to control over the degrading mechanisms and preservation of nonlocal correlation among the photons. This in turn can induce a violation of Bell's inequality in the radiative cascade for arbitrary intermediate-level splitting and small incoherent dephasing.« less

Intraday LeBaron effects

PubMed Central

Bianco, Simone; Corsi, Fulvio; Renò, Roberto

2009-01-01

We study the relation at intraday level between serial correlation and volatility of the Standard and Poor (S&P) 500 stock index futures returns. At daily and weekly levels, serial correlation and volatility forecasts have been found to be negatively correlated (LeBaron effect). After finding a significant attenuation of the original effect over time, we show that a similar but more pronounced effect holds by using intraday measures, by such as realized volatility and variance ratio. We also test the impact of unexpected volatility, defined as the part of volatility which cannot be forecasted, on the presence of intraday serial correlation in the time series by employing a model for realized volatility based on the heterogeneous market hypothesis. We find that intraday serial correlation is negatively correlated to volatility forecasts, whereas it is positively correlated to unexpected volatility.

Correlation of serum levels of fibroblast growth factor 23 and Klotho protein levels with bone mineral density in maintenance hemodialysis patients.

PubMed

Zheng, Shubei; Chen, Yan; Zheng, Yu; Zhou, Zhihong; Li, Zhanyuan

2018-04-17

The correlation of serum fibroblast growth factor 23 (FGF-23) and Klotho protein levels with bone mineral density (BMD) in maintenance hemodialysis (MHD) patients was analyzed. Between January 2015 and November 2015, 125 MHD patients in our hospital were enrolled. Dual-energy X-ray absorptiometry was used to examine the BMD in the femoral neck and lumbar spine of MHD patients. The patients were divided into three groups: a normal bone mass group, an osteopenia group, and an osteoporosis group. An ELISA was performed to measure serum FGF-23, Klotho protein, and 1,25(OH) 2 VitD 3 levels. Other parameters, including calcium (Ca), phosphorus (P), and parathyroid hormone, were also measured. Of the 125 MHD patients, 82.40% of patients had femoral neck osteopenia, and 56.00% of patients had lumbar spinal osteopenia. The serum FGF-23 level was highest in the osteoporosis group. However, there was no significant difference in serum FGF-23 levels among the three groups, depending on femoral neck and lumbar spinal BMD (P > 0.05). Spearman's correlation analysis also pointed to a lack of correlation between serum FGF-23 levels and BMD. Among the three groups, there were significant differences in serum Klotho protein levels and femoral neck BMD (P < 0.05). Serum Klotho protein levels in the osteoporosis group were clearly lower than those in the normal bone mass group and osteopenia group (P < 0.05). Similarly, serum Klotho protein levels were significantly lower in those with lumbar spinal osteopenia as compared with those in the normal group. There was a positive correlation between serum Klotho protein levels and BMD and T values for the femoral neck and lumbar spine. The results of a multiple linear regression analysis revealed that the serum Klotho protein level was one of the main factors affecting BMD in MHD patients. The serum level of FGF-23 was not correlated with a change in BMD of MHD patients, whereas the serum Klotho protein level was associated with the degree of BMD. A high Klotho protein level may decrease the severity of chronic kidney disease and mineral bone disorder (CKD-MBD) in MHD patients with low BMD.

Correlation of MLH1 and MGMT methylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients.

PubMed

Li, Xia; Wang, Yibaina; Zhang, Zuoming; Yao, Xiaoping; Ge, Jie; Zhao, Yashuang

2013-11-01

CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 ( MLH1 ) and DNA repair gene O 6 -methylguanine-DNA methyltransferase ( MGMT ) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels of MGMT and MLH1 gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels of MGMT and MLH1 were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on the MLH1 and MGMT gene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman's rank test. Agreement was determined by generalized κ-statistics. Spearman's rank correlation coefficients (r) for the methylation levels of the MGMT and MLH1 genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of the MGMT and MLH1 gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (κ=0.299 and 0.126, respectively). The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation.

Vitamin D status in Egyptian euthyroid multinodular non-toxic goiter patients and its correlation with TSH levels.

PubMed

Aboelnaga, Mohamed M; Elshafei, Maha M; Elsayed, Eman

2016-10-01

Although the prevalence of MNG is widespread throughout the world, its pathogenesis is poorly understood, and the complex interactions of both genetic predisposition and the individuals' environment are likely. However, to the best of our knowledge, it remains unknown whether there is a relationship between vitamin D status and prevalence or pathogenesis of euthyroid MNG. Therefore, the goal of the present study was determination of vitamin D status in euthyroid MNG as well as exploration of the correlation between vitamin D status & TSH levels. A total of 77 patients diagnosed with euthyroid MNG and 50 subjects without goiter were matched according to age, weight and BMI as control group in this case control study. We found that patients with euthyroid MNG had statistically significant lower mean of [25(OH)D] (24.21±8.68ng/mL) in comparison with its mean in control subjects (28.37±10.91ng/mL, P value=0.019). The 28 sufficient vitamin D MNG patients had statistically significant lower level of TSH than 49 insufficient vitamin D MNG patients. Vitamin D and TSH levels correlate with vitamin D levels in MNG patients in Pearson correlation. Also 25 OH vitamin D was a significant independent predictor for TSH levels among euthyroid MNG patients in regression analysis. Patients with euthyroid MNG have lower levels of vitamin D and TSH levels correlate with vitamin D levels in euthyroid MNG patients. In addition, 25 OH vitamin D was a significant independent predictor for TSH levels among euthyroid MNG patients. We recommend hypovitaminosis D evaluation and correction in patients with MNG. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Relations between serum reactive oxygen metabolites (ROMs) and various inflammatory and metabolic parameters in a Japanese population.

PubMed

Hirose, Hiroshi; Kawabe, Hiroshi; Komiya, Naoko; Saito, Ikuo

2009-04-01

Both oxidative stress and inflammation are known to play roles in the pathogenesis of cardiovascular disease. We investigated the relations between reactive oxygen metabolites (ROMs) and various inflammatory and metabolic parameters in a Japanese population. We analyzed 48 male and 69 female subjects, aged 25 to 65 years, who underwent an annual health checkup in our university. Serum ROM level was assayed using a free radical elective evaluator. We also measured serum concentrations of high-sensitivity C-reactive protein (hsCRP), insulin, and high molecular weight (HMW) adiponectin. Although the serum ROM level in females (347+/-83 Carr U) was slightly higher than in males (333+/-53 Carr U), this was not statistically significant. In the 48 male subjects, the ROM level negatively correlated with age (r=-0.344, p=0.0161), and positively correlated with the hsCRP level (r=0.306, p=0.0338). In the 69 female subjects, the ROM level negatively correlated with serum creatinine (r=-0.293, p=0.0141), and positively correlated with insulin (r=0.278, p=0.0202), the insulin resistance index (r=0.286, p=0.0170) and hsCRP levels (r=0.487, p<0.0001). Stepwise multiple regression analysis revealed that serum hsCRP, creatinine, and age were independently correlated with the serum ROMs level (R2=0.365; F value highest for hsCRP). When the study subjects were divided into tertiles according to the ROM level, serum hsCRP was significantly different among the three groups: its level was highest in the highest tertile of ROMs (p<0.001). These results suggest that the serum ROM level is closely associated with serum hsCRP in Japanese adult subjects.

Serum Leptin and Ghrelin Levels in Women with Polycystic Ovary Syndrome: Correlation with Anthropometric, Metabolic, and Endocrine Parameters

PubMed Central

Houjeghani, Shiva; Pourghassem Gargari, Bahram; Farzadi, Laya

2012-01-01

Background Polycystic ovary syndrome (PCOS) patients are more prone to abnormal production of some regulatory peptides. In these patients, studies on the serum levels of leptin and ghrelin are controversial. This study aims to investigate serum levels of leptin and ghrelin and their correlation with metabolic and endocrine indices in PCOS. Materials and Methods This case-control study was conducted on 60 women; 30 with PCOS and 30 healthy women whose age and body mass index (BMI) were matched and who were referred to Alzahra Hospital, Tabriz, Iran. Serum levels of leptin, ghrelin, insulin, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and testosterone were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Descriptive statistics and correlations were performed using SPSS 12.0 for Windows. Results In PCOS women, serum levels of leptin, insulin, HOMA-IR, testosterone, LH, and LH/FSH were significantly higher, while SHBG was lower than in healthy women. Ghrelin and FSH were similar in both groups. Serum levels of leptin correlated with BMI (r=0.85, p<0.001), waist to hip ratio (WHR) (r=0.55, p<0.01), insulin levels (r=0.85, p<0.001) and HOMA-IR (r=0.67, p<0.01), while ghrelin levels had an inverse association with testosterone (r=-0.32, p=0.04). Conclusion The results showed increased leptin levels while ghrelin remained unchanged in PCOS patients. In PCOS patients, leptin positively correlated with BMI, WHR, insulin, and insulin resistance, while ghrelin was only associated with serum testosterone levels. PMID:25493169

Hippuric Acid Levels in Paint Workers at Steel Furniture Manufacturers in Thailand

PubMed Central

Decharat, Somsiri

2014-01-01

Background The aims of this study were to determine hippuric acid levels in urine samples, airborne toluene levels, acute and chronic neurological symptoms, and to describe any correlation between urinary hippuric acid and airborne toluene. Methods The hippuric acid concentration in the urine of 87 paint workers exposed to toluene at work (exposed group), and 87 nonexposed people (control group) was studied. Study participants were selected from similar factories in the same region. Urine samples were collected at the end of a shift and analyzed for hippuric acid by high performance liquid chromatography. Air samples for the estimation of toluene exposure were collected with diffusive personal samplers and the toluene quantified using gas–liquid chromatography. The two groups were also interviewed and observed about their work practices and health. Results The median of the 87 airborne toluene levels was 55 ppm (range, 12–198 ppm). The median urinary hippuric acid level was 800 mg/g creatinine (range, 90–2547 mg/g creatinine). A statistically significant positive correlation was found between airborne toluene exposure and urine hippuric acid levels (r = 0.548, p < 0.01). Workers with acute symptoms had significantly higher hippuric acid levels than those who did not (p < 0.05). It was concluded that there was a significant correlation between toluene exposure, hippuric acid levels, and health (p < 0.001). Conclusion There appears to be a significant correlation between workers exposure to toluene at work, their urine hippuric acid levels, and resulting symptoms of poor health. Improvements in working conditions and occupational health education are required at these workplaces. There was good correlation between urinary hippuric acid and airborne toluene levels. PMID:25516817

ROS production, intracellular HSP70 levels and their relationship in human neutrophils: effects of age.

PubMed

Kovalenko, Elena I; Boyko, Anna A; Semenkov, Victor F; Lutsenko, Gennady V; Grechikhina, Maria V; Kanevskiy, Leonid M; Azhikina, Tatyana L; Telford, William G; Sapozhnikov, Alexander M

2014-12-15

ROS production and intracellular HSP70 levels were measured in human neutrophils for three age groups: young (20-59 years), elders (60-89 years) and nonagenarians (90 years and older). Elders showed higher levels of spontaneous intracellular ROS content compared with young and nonagenarian groups, which had similar intracellular ROS levels. Zymosan-induced (non-spontaneous) extracellular ROS levels were also similar for young and nonagenarians but were lower in elders. However, spontaneous extracellular ROS production increased continuously with age. Correlation analysis revealed positive relationships between HSP70 levels and zymosan-stimulated ROS production in the elder group. This was consistent with a promoting role for HSP70 in ROS-associated neutrophils response to pathogens. No positive correlation between ROS production and intracellular HSP70 levels was found for groups of young people and nonagenarians. In contrast, significant negative correlations of some ROS and HSP70 characteriscics were found for neutrophils from young people and nonagenarians. The observed difference in ROS and HSP70 correlations in elders and nonagenarians might be associated with an increased risk of mortality in older individuals less than 90 years old.

Leptin levels are negatively correlated with 2-arachidonoylglycerol in the cerebrospinal fluid of patients with osteoarthritis.

PubMed

Nicholson, James; Azim, Syed; Rebecchi, Mario J; Galbavy, William; Feng, Tian; Reinsel, Ruth; Rizwan, Sabeen; Fowler, Christopher J; Benveniste, Helene; Kaczocha, Martin

2015-01-01

There is compelling evidence in humans that peripheral endocannabinoid signaling is disrupted in obesity. However, little is known about the corresponding central signaling. Here, we have investigated the relationship between gender, leptin, body mass index (BMI) and levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the serum and cerebrospinal fluid (CSF) of primarily overweight to obese patients with osteoarthritis. Patients (20 females, 15 males, age range 44-78 years, BMI range 24-42) undergoing total knee arthroplasty for end-stage osteoarthritis were recruited for the study. Endocannabinoids were quantified by liquid chromatography - mass spectrometry. AEA and 2-AG levels in the serum and CSF did not correlate with either age or BMI. However, 2-AG levels in the CSF, but not serum, correlated negatively with CSF leptin levels (Spearman's ρ -0.48, P=0.0076, n=30). No such correlations were observed for AEA and leptin. In the patient sample investigated, there is a negative association between 2-AG and leptin levels in the CSF. This is consistent with pre-clinical studies in animals, demonstrating that leptin controls the levels of hypothalamic endocannabinoids that regulate feeding behavior.

Lipid profile of women qualifying for hypolipidaemic treatment.

PubMed

Kolovou, Genovefa D; Anagnostopoulou, Katherine K; Salpea, Klelia D; Damaskos, Dimitris S; Hoursalas, Ioannis S; Petropoulos, Ilias; Bilianou, Helen I; Cokkinos, Dennis V

2006-08-01

Death rates from coronary heart disease continue to rise in women despite a marked decrease in men for the past two decades. Our study aimed to evaluate essential risk factors in high-risk adult women. Lipid profiles of 547 dyslipidaemic adult women aged 57.5 +/- 10.6 years (mean +/- standard deviation) were evaluated and stratified according to fasting plasma lipid levels. Classification of the cohort was performed based on triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) levels and correlations between TG and HDL-C were estimated. Patients with TG > or =150 mg/dl had lower HDL-C levels compared to those with TG <150 mg/dl (p < 0.001). Patients with HDL-C <40 mg/dl had lower TC levels and higher TG levels compared to those with HDL-C > or =40 mg/dl (p = 0.012 and p < 0.001, respectively). In the cohort and the subgroups an inverse correlation between TG and HDL-C was observed (r = -0.428, slope = -0.048, p < 0.001). The expected inverse correlation between fasting high TG and low HDL levels was confirmed. The novelty of the study is that this correlation persists even in the case of low fasting TG levels.

Human aqueous humor levels of transforming growth factor-β2: Association with matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases

PubMed Central

Jia, Yan; Yue, Yu; Hu, Dan-Ning; Chen, Ji-Li; Zhou, Ji-Bo

2017-01-01

The present study aims to investigate the association of transforming growth factor-β2 (TGF-β2) and matrix metalloproteinases (MMPs), MMP-2 and MMP-3, and tissue inhibitors of matrix metalloproteinases (TIMPs), TIMP-1, TIMP-2 and TIMP-3 in the aqueous humor of patients with high myopia or cataracts. The levels of TGF-β2 and MMPs/TIMPs were measured with the Luminex xMAP Technology using commercially available Milliplex xMAP kits. The association between TGF-β2 and MMPs/TIMPs levels was analyzed using the Spearmans correlation test. The levels of TGF-β2 were identified to be positively correlated with the levels of TIMP-1 and TIMP-3 (TIMP-1: r=0.334; P=0.007; TIMP-3: r=0.309; P=0.012). The levels of MMP-2, MMP-3 and TIMP-2 did not significantly correlate with TGF-β2 levels (P>0.05). A positive correlation was identified between TGF-β2 and TIMPs in the aqueous humor of human eyes with elongated axial length. It appears that TGF-β2 stimulates the expression of TIMPs as a compensatory reaction to the development of high myopia. PMID:29188062

Plasma apelin levels, blood pressure and cardiovascular risk factors in a coastal Chinese population.

PubMed

Zhu, Pengli; Huang, Feng; Lin, Fan; Yuan, Yin; Chen, Falin; Li, Qiaowei

2013-11-01

To describe the relationship of plasma apelin levels with blood pressure in a coastal Chinese population. This cross-sectional study included a total of 1031 subjects from the coastal areas of China. One-way analysis of variance (ANOVA) and linear trend test, Pearson's correlation analysis, as well as multivariate linear regression analysis were used to evaluate the association between plasma apelin levels and blood pressure. Plasma apelin levels dropped with increasing quartiles of systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MABP) (all P<0.001). SBP, DBP, and MABP values decreased as the apelin levels increased within the quartiles. After adjusting for age and gender, the significant differences in SBP, DBP, and MABP between the groups within the apelin quartiles remained (all P<0.05). A significant negative correlation between SBP, DBP, as well as MABP and apelin levels was observed (all P<0.01); even after adjusting for cardiovascular confounding factors, this negative correlation remained (all P<0.001). A negative correlation between plasma apelin levels and blood pressure was found in this 1000-population-based epidemiological study. Apelin may become a potential therapeutic target of anti-hypertensive treatment.

Study on the relationship between the expression of IGF-1 in umbilical cord blood and abnormal glucose metabolism during pregnancy.

PubMed

Liu, K; Wu, H-Y; Xu, Y-H

2017-02-01

To explore the relationship between the expression of insulin-like growth factor-1 (IGF-1) in neonatal umbilical cord blood and abnormal glucose metabolism during pregnancy. We have selected 63 cases of delivery randomly, term birth and maternal from January 2015 to January 2016 in our hospital, gestational diabetes mellitus for Group A, abnormal gestational glucose tolerance for Group B and normal for Group C with 21 cases in each group. The venous blood samples were collected from all the pregnant females 2 weeks before delivery, and the levels of HbA1c in serum were detected by Elisa method. During the delivery, the umbilical cord blood was collected and the levels of IGF-1 were measured by double site immune enzyme analysis. The neonatal weight was recorded and the correlation analysis was made in respect of the measurement results. The level of HbA1c in Group A was significantly higher than that in Group C (p < 0.05); IGF-1 level and neonatal weight of Group B were significantly higher than that of Group C (p < 0.05), IGF-1 has a significant correlation with neonatal weight in Group C, and HbA1c and IGF-1 were positively correlated (p < 0.05); IGF-1 was positively correlated with neonatal weight in Group A and Group B (p < 0.05). There was a significant positive correlation between the IGF-1 level of neonatal umbilical cord blood and the neonatal weight (p < 0.05). Also, the level of HbA1c was positively correlated with the level of IGF-1 in neonatal umbilical cord blood at the end of pregnancy (p < 0.05). The expression level of IGF-1 in the final stage of pregnant females can be detected to predict the expression level of IGF-1 in newborn infants and then the growth status of the fetus can be obtained.

Relationships among plasma granzyme B level, pruritus and dermatitis in patients with atopic dermatitis.

PubMed

Kamata, Yayoi; Kimura, Utako; Matsuda, Hironori; Tengara, Suhandy; Kamo, Atsuko; Umehara, Yoshie; Iizumi, Kyoichi; Kawasaki, Hiroaki; Suga, Yasushi; Ogawa, Hideoki; Tominaga, Mitsutoshi; Takamori, Kenji

2016-12-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H 1 -antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear. This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients. Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays. Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD. Plasma GzmB levels may reflect the degree of pruritus and dermatitis in patients with AD. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Quantifying the range of cross-correlated fluctuations using a q- L dependent AHXA coefficient

NASA Astrophysics Data System (ADS)

Wang, Fang; Wang, Lin; Chen, Yuming

2018-03-01

Recently, based on analogous height cross-correlation analysis (AHXA), a cross-correlation coefficient ρ×(L) has been proposed to quantify the levels of cross-correlation on different temporal scales for bivariate series. A limitation of this coefficient is that it cannot capture the full information of cross-correlations on amplitude of fluctuations. In fact, it only detects the cross-correlation at a specific order fluctuation, which might neglect some important information inherited from other order fluctuations. To overcome this disadvantage, in this work, based on the scaling of the qth order covariance and time delay L, we define a two-parameter dependent cross-correlation coefficient ρq(L) to detect and quantify the range and level of cross-correlations. This new version of ρq(L) coefficient leads to the formation of a ρq(L) surface, which not only is able to quantify the level of cross-correlations, but also allows us to identify the range of fluctuation amplitudes that are correlated in two given signals. Applications to the classical ARFIMA models and the binomial multifractal series illustrate the feasibility of this new coefficient ρq(L) . In addition, a statistical test is proposed to quantify the existence of cross-correlations between two given series. Applying our method to the real life empirical data from the 1999-2000 California electricity market, we find that the California power crisis in 2000 destroys the cross-correlation between the price and the load series but does not affect the correlation of the load series during and before the crisis.

Relationship of antioxidant and oxidative stress markers in different organs following copper toxicity in a rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Vijay; Kalita, Jayantee, E-mail: jayanteek@yahoo.com; Bora, Himangsu K.

Copper (Cu) at a higher level becomes toxic and it can catalyze the formation of highly reactive hydroxyl radical. We report the vulnerability of liver, kidney and brain to different dose of copper sulfate (CuSO{sub 4}) induced oxidative stress at different time duration. Fifty-four male Wistar rats (weight range = 205 ± 10 g) were equally divided into three groups. CuSO{sub 4} was administered orally to the experimental groups (Group-II and III) up to 90 days in a dose of 100 and 200 mg/Kg body weight per day. Saline water was given to the control group (Group-I). At the endmore » of 30, 60 and 90 days of administration, neurobehavioral studies were done and six rats from each group were sacrificed. Their liver, kidney and brain tissues were subjected for Cu, glutathione (GSH), malondialdehyde (MDA) and total antioxidant capacity (TAC) assay. Blood urea nitrogen (BUN), serum creatinine, bilirubin and transaminases were measured. GSH, TAC and MDA levels were correlated with the markers of respective organ dysfunction. Administration of CuSO{sub 4} resulted in increased free Cu and MDA level, and decrease GSH and TAC levels in group-II and III compared with group-I. In experimental groups, the reduction in TAC and GSH levels was maximum in liver tissue followed by brain and kidney; whereas increase in MDA level was highest in liver followed by brain and kidney at 30, 60 and 90 days. TAC and GSH levels in the liver inversely correlated with serum transaminases and bilirubin, and tissue free Cu, and positively correlated with MDA levels. Free Cu level in kidney tissue and BUN inversely correlated with TAC and GSH, and positively with MDA level. Grip-strength, rotarod and Y-maze findings were inversely correlated with brain free Cu and MDA levels and positively with GSH and TAC levels. The oxidative stress was highest in liver followed by brain and kidney after oral CuSO{sub 4} exposure in a rat model. These levels correlated with the respective organ dysfunction and tissue free Cu concentration. - Highlights: • Oral dosing of CuSO{sub 4} leads to oxidative stress in liver, brain and kidney. • Liver has maximum oxidative stress followed by brain and kidney. • Oxidative stress correlated with the respective organ dysfunction and tissue Cu concentration.« less

Integrated Analysis of the Effects of Cold and Dehydration on Rice Metabolites, Phytohormones, and Gene Transcripts1[W][OPEN

PubMed Central

Maruyama, Kyonoshin; Urano, Kaoru; Yoshiwara, Kyouko; Morishita, Yoshihiko; Sakurai, Nozomu; Suzuki, Hideyuki; Kojima, Mikiko; Sakakibara, Hitoshi; Shibata, Daisuke; Saito, Kazuki; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2014-01-01

Correlations between gene expression and metabolite/phytohormone levels under abiotic stress conditions have been reported for Arabidopsis (Arabidopsis thaliana). However, little is known about these correlations in rice (Oryza sativa ‘Nipponbare’), despite its importance as a model monocot. We performed an integrated analysis to clarify the relationships among cold- and dehydration-responsive metabolites, phytohormones, and gene transcription in rice. An integrated analysis of metabolites and gene expression indicated that several genes encoding enzymes involved in starch degradation, sucrose metabolism, and the glyoxylate cycle are up-regulated in rice plants exposed to cold or dehydration and that these changes are correlated with the accumulation of glucose (Glc), fructose, and sucrose. In particular, high expression levels of genes encoding isocitrate lyase and malate synthase in the glyoxylate cycle correlate with increased Glc levels in rice, but not in Arabidopsis, under dehydration conditions, indicating that the regulation of the glyoxylate cycle may be involved in Glc accumulation under dehydration conditions in rice but not Arabidopsis. An integrated analysis of phytohormones and gene transcripts revealed an inverse relationship between abscisic acid (ABA) signaling and cytokinin (CK) signaling under cold and dehydration stresses; these stresses increase ABA signaling and decrease CK signaling. High levels of Oryza sativa 9-cis-epoxycarotenoid dioxygenase transcripts correlate with ABA accumulation, and low levels of Cytochrome P450 (CYP) 735A transcripts correlate with decreased levels of a CK precursor in rice. This reduced expression of CYP735As occurs in rice but not Arabidopsis. Therefore, transcriptional regulation of CYP735As might be involved in regulating CK levels under cold and dehydration conditions in rice but not Arabidopsis. PMID:24515831

Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

PubMed Central

López-Mejías, Raquel; Rueda-Gotor, Javier; Miranda-Filloy, José A.; Ubilla, Begoña; Carnero-López, Beatriz; Palmou-Fontana, Natalia; Gómez-Acebo, Inés; Blanco, Ricardo; Pina, Trinitario; Ochoa, Rodrigo; González-Juanatey, Carlos; González-Gay, Miguel A.

2014-01-01

Objective. TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients. PMID:24976690

[Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis].

PubMed

Ren, Xingfei; Wu, Chunlei; Yu, Qinnan; Zhu, Feng; Liu, Pei; Zhang, Huiqing

2016-01-01

To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (P<0.05). The patients with prostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (P<0.001). Multiple linear regression analysis showed that IL-8 and IL-6 levels and white blood cell count in the prostatic fluid were all positively correlated with serum PSA level. Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level.

A Disposable Tear Glucose Biosensor—Part 4

PubMed Central

Engelschall, Erica; Lan, Kenneth; Shah, Pankti; Saez, Neil; Maxwell, Stephanie; Adamson, Teagan; Abou-Eid, Michelle; McAferty, Kenyon; Patel, Dharmendra R.; Cook, Curtiss B.

2014-01-01

Objective: A prototype tear glucose (TG) sensor was tested in New Zealand white rabbits to assess eye irritation, blood glucose (BG) and TG lag time, and correlation with BG. Methods: A total of 4 animals were used. Eye irritation was monitored by Lissamine green dye and analyzed using image analysis software. Lag time was correlated with an oral glucose load while recording TG and BG readings. Correlation between TG and BG were plotted against one another to form a correlation diagram, using a Yellow Springs Instrument (YSI) and self-monitoring of blood glucose as the reference measurements. Finally, TG levels were calculated using analytically derived expressions. Results: From repeated testing carried over the course of 12 months, little to no eye irritation was detected. TG fluctuations over time visually appeared to trace the same pattern as BG with an average lag times of 13 minutes. TG levels calculated from the device current measurements ranged from 4 to 20 mg/dL and correlated linearly with BG levels of 75-160 mg/dL (TG = 0.1723 BG = 7.9448 mg/dL; R2 = .7544). Conclusion: The first steps were taken toward preliminary development of a sensor for self-monitoring of tear glucose (SMTG). No conjunctival irritation in any of the animals was noted. Lag time between TG and BG was found to be noticeable, but a quantitative modeling to correlate lag time in this study is unnecessary. Measured currents from the sensors and the calculated TG showed promising correlation to BG levels. Previous analytical bench marking showed BG and TG levels consistent with other literature. PMID:24876546

Tree-level correlations in the strong field regime

NASA Astrophysics Data System (ADS)

Gelis, François

2017-09-01

We consider the correlation function of an arbitrary number of local observables in quantum field theory, in situations where the field amplitude is large. Using a quasi-classical approximation (valid for a highly occupied initial mixed state, or for a coherent initial state if the classical dynamics has instabilities), we show that at tree level these correlations are dominated by fluctuations at the initial time. We obtain a general expression of the correlation functions in terms of the classical solution of the field equation of motion and its derivatives with respect to its initial conditions, that can be arranged graphically as the sum of labeled trees where the nodes are the individual observables, and the links are pairs of derivatives acting on them. For 3-point (and higher) correlation functions, there are additional tree-level terms beyond the quasi-classical approximation, generated by fluctuations in the bulk.

The Examination of the Correlation between Social Physique Anxiety Levels and Narcissism Levels of the Students Who Studied at the SPES

ERIC Educational Resources Information Center

Gezer, Engin

2014-01-01

The aim of the study was to discover the correlation between social physique anxiety levels and narcissism levels of the students of the school of the physical education and sports. A total of 308 students who studied at different academic departments of the school of the physical education and sports of Mustafa Kemal University participated in…

The Impact of Intraclass Correlation on the Effectiveness of Level-Specific Fit Indices in Multilevel Structural Equation Modeling: A Monte Carlo Study

ERIC Educational Resources Information Center

Hsu, Hsien-Yuan; Lin, Jr-Hung; Kwok, Oi-Man; Acosta, Sandra; Willson, Victor

2017-01-01

Several researchers have recommended that level-specific fit indices should be applied to detect the lack of model fit at any level in multilevel structural equation models. Although we concur with their view, we note that these studies did not sufficiently consider the impact of intraclass correlation (ICC) on the performance of level-specific…

Designing a neurofeedback device to quantify attention levels using coffee as a reward system.

PubMed

Cheng, Kok Suen; Lee, Jun Xiang; Lee, Poh Foong

2018-05-09

Work performance is closely related to one's attention level. In this study, a brain-computer interface (BCI) device suitable for office usage was chosen to quantify the individual's attention levels. A BCI system was adopted to interface brainwave signals to a coffee maker via three ascending levels of laser detectors. The preliminary test with this prototype was to characterize the attention level through the collected coffee amount. Here, the preliminary testing was comparing the correlation between the attention level and the participants' cumulative grade point average (CGPA) and scores from the 21-item depression, anxiety, and stress scale (DASS-21) and the attentional control scale (ACS) using ordinal regression. It was assumed that a greater CGPA would generate a greater attention level. The generated coffee amount from the BCI system had a significant positive correlation with the CGPA (p = 0.004), mild depression (p = 0.019) and mild and extremely severe anxiety (p = 0.044 and p = 0.019, respectively) and a negative correlation with the ACS score (p = 0.042). This simple and cost-effective prototype has the potential to enable everyone to know their immediate attention level and predict the possible correlation to their mental state.

Correlation of BDNF blood levels with interoceptive awareness and maturity fears in anorexia and bulimia nervosa patients.

PubMed

Mercader, J M; Fernández-Aranda, F; Gratacòs, Mònica; Aguera, Zaida; Forcano, Laura; Ribasés, Marta; Villarejo, Cynthia; Estivill, Xavier

2010-04-01

Association studies and rodent models suggest a major role for BDNF (brain-derived neurotrophic factor) in feeding regulation. Altered BDNF blood levels have been associated with eating disorders (ED) and their related psychopathological traits. Since the influence of BDNF on self-reported eating disorder inventory scores (EDI) has not been tested, we investigated the correlation of EDI scales with BDNF plasma levels. BDNF levels were measured by (ELISA), and the EDI questionnaire was administered in a total of 81 ED patients. The relationship between BDNF levels and EDI scores was calculated using a general linear model. After correcting for multiple testing, BDNF plasma levels negatively correlated with the EDI total score (R (2) = 0.26; p = 4.09 x 10(-4)), interoceptive awareness (R (2) = 0.26; p = 1.96 x 10(-4)), and maturity fears (R (2) = 0.13; p = 6.92 x 10(-4)). When subdividing according to the main diagnoses, interoceptive awareness presented significant correlations with BDNF blood levels in both the anorexia nervosa (R (2) = 0.33, p = 0.0026) and bulimia nervosa groups (R (2) = 0.10; p = 0.008). Our data suggest that BDNF levels may influence the severity of the ED by modulating the associated psychopathology, in particular through the impairment of interoceptive awareness.

Parental selection of hybrid breeding based on maternal and paternal inheritance of traits in rapeseed (Brassica napus L.).

PubMed

Xing, Nailin; Fan, Chuchuan; Zhou, Yongming

2014-01-01

Parental selection is crucial for hybrid breeding, but the methods available for such a selection are not very effective. In this study, a 6×6 incomplete diallel cross was designed using 12 rapeseed germplasms, and a total of 36 hybrids together with their parental lines were planted in 4 environments. Four yield-related traits and seed oil content (OC) were evaluated. Genetic distance (GD) was estimated with 359 simple sequence repeats (SSRs) markers. Heterosis levels, general combining ability (GCA) and specific combining ability (SCA) were evaluated. GD was found to have a significant correlation with better-parent heterosis (BPH) of thousand seed weight (TSW), SCA of seeds per silique (SS), TSW, and seed yield per plant (SY), while SCA showed a statistically significant correlation with heterosis levels of all traits at 1% significance level. Statistically significant correlations were also observed between GCA of maternal or paternal parents and heterosis levels of different traits except for SS. Interestingly, maternal (TSW, SS, and OC) and paternal (siliques per plant (SP) and SY) inheritance of traits was detected using contribution ratio of maternal and paternal GCA variance as well as correlations between GCA and heterosis levels. Phenotype and heterosis levels of all the traits except TSW of hybrids were significantly correlated with the average performance of parents. The correlations between SS and SP, SP and OC, and SY and OC were statistically significant in hybrids but not in parents. Potential applications of parental selection in hybrid breeding were discussed.

Correlation between calcium and phosphate levels to calculus accumulation on coronary heart disease patients

NASA Astrophysics Data System (ADS)

Cahaya, Cindy; Masulili, Sri Lelyati C.; Lessang, Robert; Radi, Basuni

2017-02-01

Coronary Artery Disease (CAD) or Coronary Heart Disease (CHD) is a disease that happened because of blood flow being blocked by atherosclerosis. Atherosclerosis is a process of hardening of the arteries which characterized by thickening and loss of elasticity of the intimal layer of vascular wall, by lipid deposit. Periodontitis is a chronic multifactorial inflammatory disease caused by microorganism and characterized by progressive destruction of the tooth supporting apparatus leading to tooth loss. Many studies use saliva as a valuable source for clinically information, as an asset for early diagnosis, prognostic and reviewer for pascatherapy status. Dental calculus had happened as a consequence of saliva supersaturation by calcium and phosphate. Salivary flow rate and its composition influence the formation of calculus. Increasing salivary calcium levels is characteristic of periodontitis patients. An important hipotesis in Cardiology is chronic infections contribute in atherosclerosis. Objective: To analyse the correlation between calcium and phosphate levels in saliva to calculus accumulation on CHD patients. Result: Correlation analysis between salivary calcium levels with calculus accumulation in patients with CHD and non-CHD showed no significant p value, p=0.59 and p=0.518. Correlation analysis between salivary phosphate levels and calculus accumulation showed no significant p value, p=0.836 for CHD patients and p=0.484 for non-CHD patients. Conclusion: There are no correlation between calcium levels and phosphate levels with calculus accumulation in CHD patients. Further research need to be done.

Mercury levels, reproduction, and hematology in western grebes from three California Lakes, USA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elbert, R.A.; Anderson, D.W.

1998-02-01

Twenty-three healthy adult western and Clark`s grebes (Aechmorphorus occidentalis and Aechmorphorus clarkii) were collected at three study sites in California, USA, in 1992: Clear Lake, Lake County; Eagle Lake, Lassen County; and Tule Lake, Siskiyou County. Liver, kidney, breast muscle, and brain were analyzed for total mercury (Hg) concentration (ppm wet weight), and blood was analyzed for various blood parameters. Clear Lake birds had greater Hg concentrations in kidney, breast muscle, and brain than birds from the other two lakes whereas liver concentrations were not statistically different. Average concentrations for Clear Lake birds were 2.74 ppm for liver, 2.06 ppmmore » for kidney, 1.06 ppm for breast muscle, and 0.28 ppm for brain. The tissue levels of kidney, breast muscle, and brain at the other two study sites were one half the levels found at Clear Lake. These mean tissue levels were near, but below, those known to cause adverse effects. When data from all sites were merged, kidney, breast muscle, and brain concentrations are positively correlated to each other. Liver concentrations were not correlated to any other value. Brain Hg concentrations were also negatively correlated to blood potassium and blood phosphorus levels. Kidney Hg levels were positively correlated to percent blood heterophils and negatively correlated to percent eosinophils, suggesting that mercury levels might be affecting immune function. These biomarkers could not be related to any obvious ecological effects.« less

Nature of the endogenous pyrogen (EP) induced by influenza viruses: lack of correlation between EP levels and content of the known pyrogenic cytokines, interleukin 1, interleukin 6 and tumour necrosis factor.

PubMed

Jakeman, K J; Bird, C R; Thorpe, R; Smith, H; Sweet, C

1991-03-01

Fever in influenza results from the release of endogenous pyrogen (EP) following virus-phagocyte interaction and its level correlates with the differing virulence of virus strains. However, the different levels of fever produced in ferrets by intracardial inoculation of EP obtained from the interaction of different virus strains with ferret of human phagocytes did not correlate with the levels of interleukin 1 (IL-1), IL-6 or tumour necrosis factor in the same samples as assayed by conventional in vitro methods. Hence, the EP produced by influenza virus appears to be different to these cytokines.

Analytic tools for investigating the structure of network reliability measures with regard to observation correlations

NASA Astrophysics Data System (ADS)

Prószyński, W.; Kwaśniak, M.

2018-03-01

A global measure of observation correlations in a network is proposed, together with the auxiliary indices related to non-diagonal elements of the correlation matrix. Based on the above global measure, a specific representation of the correlation matrix is presented, being the result of rigorously proven theorem formulated within the present research. According to the theorem, each positive definite correlation matrix can be expressed by a scale factor and a so-called internal weight matrix. Such a representation made it possible to investigate the structure of the basic reliability measures with regard to observation correlations. Numerical examples carried out for two test networks illustrate the structure of those measures that proved to be dependent on global correlation index. Also, the levels of global correlation are proposed. It is shown that one can readily find an approximate value of the global correlation index, and hence the correlation level, for the expected values of auxiliary indices being the only knowledge about a correlation matrix of interest. The paper is an extended continuation of the previous study of authors that was confined to the elementary case termed uniform correlation. The extension covers arbitrary correlation matrices and a structure of correlation effect.

Chronic atrophic gastritis in association with hair mercury level.

PubMed

Xue, Zeyun; Xue, Huiping; Jiang, Jianlan; Lin, Bing; Zeng, Si; Huang, Xiaoyun; An, Jianfu

2014-11-01

The objective of this study was to explore hair mercury level in association with chronic atrophic gastritis, a precancerous stage of gastric cancer (GC), and thus provide a brand new angle of view on the timely intervention of precancerous stage of GC. We recruited 149 healthy volunteers as controls and 152 patients suffering from chronic gastritis as cases. The controls denied upper gastrointestinal discomforts, and the cases were diagnosed as chronic superficial gastritis (n=68) or chronic atrophic gastritis (n=84). We utilized Mercury Automated Analyzer (NIC MA-3000) to detect hair mercury level of both healthy controls and cases of chronic gastritis. The statistic of measurement data was expressed as mean ± standard deviation, which was analyzed using Levene variance equality test and t test. Pearson correlation analysis was employed to determine associated factors affecting hair mercury levels, and multiple stepwise regression analysis was performed to deduce regression equations. Statistical significance is considered if p value is less than 0.05. The overall hair mercury level was 0.908949 ± 0.8844490 ng/g [mean ± standard deviation (SD)] in gastritis cases and 0.460198 ± 0.2712187 ng/g (mean±SD) in healthy controls; the former level was significantly higher than the latter one (p=0.000<0.01). The hair mercury level in chronic atrophic gastritis subgroup was 1.155220 ± 0.9470246 ng/g (mean ± SD) and that in chronic superficial gastritis subgroup was 0.604732 ± 0.6942509 ng/g (mean ± SD); the former level was significantly higher than the latter level (p<0.01). The hair mercury level in chronic superficial gastritis cases was significantly higher than that in healthy controls (p<0.05). The hair mercury level in chronic atrophic gastritis cases was significantly higher than that in healthy controls (p<0.01). Stratified analysis indicated that the hair mercury level in healthy controls with eating seafood was significantly higher than that in healthy controls without eating seafood (p<0.01) and that the hair mercury level in chronic atrophic gastritis cases was significantly higher than that in chronic superficial gastritis cases (p<0.01). Pearson correlation analysis indicated that eating seafood was most correlated with hair mercury level and positively correlated in the healthy controls and that the severity of gastritis was most correlated with hair mercury level and positively correlated in the gastritis cases. Multiple stepwise regression analysis indicated that the regression equation of hair mercury level in controls could be expressed as 0.262 multiplied the value of eating seafood plus 0.434, the model that was statistically significant (p<0.01). Multiple stepwise regression analysis also indicated that the regression equation of hair mercury level in gastritis cases could be expressed as 0.305 multiplied the severity of gastritis, the model that was also statistically significant (p<0.01). The graphs of regression standardized residual for both controls and cases conformed to normal distribution. The main positively correlated factor affecting the hair mercury level is eating seafood in healthy people whereas the predominant positively correlated factor affecting the hair mercury level is the severity of gastritis in chronic gastritis patients. That is to say, the severity of chronic gastritis is positively correlated with the level of hair mercury. The incessantly increased level of hair mercury possibly reflects the development of gastritis from normal stomach to superficial gastritis and to atrophic gastritis. The detection of hair mercury is potentially a means to predict the severity of chronic gastritis and possibly to insinuate the environmental mercury threat to human health in terms of gastritis or even carcinogenesis.

Blood coagulation, fibrinolytic activity and lipid profile in subclinical thyroid disease: subclinical hyperthyroidism increases plasma factor X activity.

PubMed

Erem, Cihangir

2006-03-01

Various abnormalities of coagulation and fibrinolysis occur in patients with thyroid diseases, and may range from subclinical laboratory abnormalities to clinically significant disorders of coagulation and, rarely, major haemorrhage or thromboembolism. The influence of subclinical hypothyroidism (SHypo) on haemostasis is controversial, both hypercoagulable and hypocoagulable states have been reported. A hypercoagulable state might be a risk factor for thromboembolic disease in SHypo. On the other hand, subclinical hyperthyroidism (SCHyper) is associated with enhanced cardiovascular risk. In the English literature, there are no studies on changes in coagulation and fibriolytic status in subjects with SCHyper. Therefore, the aim of the present study was to investigate the markers of endogenous coagulation and fibrinolysis, and to evaluate the relationships between serum lipid profile and thyroid hormones and these haemostatic parameters in subclinical thyroid patients. Various haemostatic parameters were investigated in 30 patients with SHypo and 20 patients with SCHyper and compared to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these haemostatic parameters were examined. Compared with the control subjects, only FX activity was significantly increased in patients with SCHyper (P < 0.01). Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in patients with SHypo compared with the control group (P < 0.001 and P < 0.01, respectively). TC levels were significantly higher in patients with SCHyper than in controls (P < 0.05). No differences could be found in coagulation/fibrinolysis parameters between subclinical hypothyroid patients and control subjects. In patients with SCHyper, serum TSH level was positively correlated with FX activity (r: 0.58, P < 0.01) and inversely correlated with PAI-1 (r: -0.55. P < 0.05). Serum TG levels were inversely correlated with plasma activities of factors V, VII, VIII, IX, X and vWF (r: -0.83, P < 0.001; r: -0.68, P < 0.05; r: -0.61, P < 0.05; r: -0.77, P < 0.01; r: -0.63, P < 0.05; r: -0.60, P < 0.05, respectively). Serum TC levels were positively correlated with plasma fibrinogen levels (r: 0.72, P < 0.05). Serum HDL-C levels were positively correlated with protein S activity (r: 0.68, P < 0.05) and negatively correlated with F VII activity (r: -0.69, P < 0.05). Also, in patients with SHypo, serum TG levels were positively correlated with serum TSH levels (r: 0.42, P < 0.05), plasma activities of factors V, VII and X (r: 0.42, P < 0.05; r: 0.54, P < 0.01; r: 0.57, P < 0.01, respectively) and negatively correlated with plasma fibrinogen levels (r: -0.41, P < 0.05). Serum TC levels were positively correlated with factors V and X (r: 0.42, P < 0.05; r: 0.58, P < 0.01, respectively) and negatively correlated with t-PA Ag levels (r: -0.44, P < 0.05). Serum HDL-C levels were inversely correlated with F VII activity (r: -0.48, P < 0.05). Some differences were found in the haemostatic parameters and lipid profile between the subclinical thyroid patients and healthy controls. Increased factor X activity in patients with subclinical hyperthyroidism represent a potential hypercoagulable state, which might augment the already existing risk for atheroscleroic complications. Also, subclinical hypothyroid patients exhibit a more atherogenic lipid profile compared with healthy individuals. Therefore, subclinical hypothyroidism is also associated with an increased risk of cardiovascular disease. However, thyroid hormones may play a role at different levels of the complex haemostatic system in subclinical thyroid disease.

Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer.

PubMed

Wang, Xijuan; An, Peng; Zeng, Jiling; Liu, Xiaoyan; Wang, Bo; Fang, Xuexian; Wang, Fudi; Ren, Guoping; Min, Junxia

2017-03-14

Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13-1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores (p < 0.001). Notably, serum PSA values had even higher predictive accuracy among prostate cancer patients with serum ferritin levels > 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher (p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls (n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity (r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

Calprotectin in gingival crevicular fluid correlates with clinical and biochemical markers of periodontal disease.

PubMed

Kido, J; Nakamura, T; Kido, R; Ohishi, K; Yamauchi, N; Kataoka, M; Nagata, T

1999-10-01

Clinical and biochemical markers of periodontal disease have been used for precise objective diagnosis of periodontal inflammation. Interleukin 1beta (IL-1beta) and prostaglandin E2 (PGE2), inflammatory factors, levels in gingival crevicular fluid (GCF) of patients with periodontal disease are elevated and have been studied as biochemical markers. The levels of calprotectin, a leukocyte protein, in body fluids of patients with some inflammatory diseases are raised. Recently, we detected calprotectin in GCF and its concentrations in periodontal pockets were higher than those in healthy gingival crevices. In this study, we investigated the correlations between GCF calprotectin levels and clinical indicators (probing depth and bleeding on probing, BOP), and the IL-1beta or PGE2 levels in GCE Probing depth and BOP at 130 sites of 110 subjects with periodontal or other oral diseases were examined, then GCF samples were collected and their calprotectin, IL-1beta and PGE2 were determined by ELISA. The calprotectin level correlated positively with the probing depth and was significantly higher at BOP-positive than BOP-negative sites. There were significant, positive correlations between the calprotectin and IL-1beta or PGE2 concentrations. These results indicate that the calprotectin level in GCF correlates well with clinical and biochemical markers of periodontal disease and suggest that calprotectin may be useful for evaluating the extent of periodontal inflammation.

Judging in Rhythmic Gymnastics at Different Levels of Performance.

PubMed

Leandro, Catarina; Ávila-Carvalho, Lurdes; Sierra-Palmeiro, Elena; Bobo-Arce, Marta

2017-12-01

This study aimed to analyse the quality of difficulty judging in rhythmic gymnastics, at different levels of performance. The sample consisted of 1152 difficulty scores concerning 288 individual routines, performed in the World Championships in 2013. The data were analysed using the mean absolute judge deviation from the final difficulty score, a Cronbach's alpha coefficient and intra-class correlations, for consistency and reliability assessment. For validity assessment, mean deviations of judges' difficulty scores, the Kendall's coefficient of concordance W and ANOVA eta-squared values were calculated. Overall, the results in terms of consistency (Cronbach's alpha mostly above 0.90) and reliability (intra-class correlations for single and average measures above 0.70 and 0.90, respectively) were satisfactory, in the first and third parts of the ranking on all apparatus. The medium level gymnasts, those in the second part of the ranking, had inferior reliability indices and highest score dispersion. In this part, the minimum of corrected item-total correlation of individual judges was 0.55, with most values well below, and the matrix for between-judge correlations identified remarkable inferior correlations. These findings suggest that the quality of difficulty judging in rhythmic gymnastics may be compromised at certain levels of performance. In future, special attention should be paid to the judging analysis of the medium level gymnasts, as well as the Code of Points applicability at this level.

Nuclear anxiety: a test-construction study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braunstein, A.L.

1986-01-01

The Nuclear Anxiety Scale was administered to 263 undergraduate and graduate studies (on eight occasions in December, 1985 and January, 1986). (1) The obtained alpha coefficient was .91. This was significant at the .01 level, and demonstrated that the scale was internally homogeneous and consistent. (2) Item discrimination indices (point biserial correlation coefficients) computered for the thirty (30) items yielded a range of .25 to .64. All coefficients were significant at the .01 level, and all 30 items were retained as demonstrating significant discriminability. (3) The correlation between two administrations of the scale (with a 48-hour interval) was .83. Thismore » was significant at the .01 level, and demonstrated test-retest reliability and stability over time. (4) The point-biserial correlation coefficient between scores on the Nuclear Anxiety Scale, and the students' self-report of nuclear anxiety as being either a high or low ranked stressor, was .59. This was significant at the .01 level, and demonstrated concurrent validity. (5) The correlation coefficient between scores on the Nuclear Anxiety Scale and the Spielberger State-Trait Anxiety Inventory, A-Trait, (1970), was .41. This was significant at the .01 level, and demonstrated convergent validity. (6) The correlation coefficient between positively stated and negatively stated items (with scoring reversed) was .76. This was significant at the .01 level, and demonstrated freedom from response set bias.« less

Judging in Rhythmic Gymnastics at Different Levels of Performance

PubMed Central

Ávila-Carvalho, Lurdes; Sierra-Palmeiro, Elena; Bobo-Arce, Marta

2017-01-01

Abstract This study aimed to analyse the quality of difficulty judging in rhythmic gymnastics, at different levels of performance. The sample consisted of 1152 difficulty scores concerning 288 individual routines, performed in the World Championships in 2013. The data were analysed using the mean absolute judge deviation from the final difficulty score, a Cronbach’s alpha coefficient and intra-class correlations, for consistency and reliability assessment. For validity assessment, mean deviations of judges’ difficulty scores, the Kendall’s coefficient of concordance W and ANOVA eta-squared values were calculated. Overall, the results in terms of consistency (Cronbach’s alpha mostly above 0.90) and reliability (intra-class correlations for single and average measures above 0.70 and 0.90, respectively) were satisfactory, in the first and third parts of the ranking on all apparatus. The medium level gymnasts, those in the second part of the ranking, had inferior reliability indices and highest score dispersion. In this part, the minimum of corrected item-total correlation of individual judges was 0.55, with most values well below, and the matrix for between-judge correlations identified remarkable inferior correlations. These findings suggest that the quality of difficulty judging in rhythmic gymnastics may be compromised at certain levels of performance. In future, special attention should be paid to the judging analysis of the medium level gymnasts, as well as the Code of Points applicability at this level. PMID:29339996

The correlation of leptin/leptin receptor gene polymorphism and insulin-like growth factor-1 and their impact on childhood growth hormone deficiency.

PubMed

He, J-S; Lian, C-W; Zhou, H-W; Lin, X-F; Yang, H-C; Ye, X-L; Zhu, S-B

2016-09-01

Growth hormone deficiency (GHD) is the most common cause for childhood dwarfism. Currently, the significance of insulin-like growth factor-1 (IGF-1) in diagnosis of GHD is still debatable. Due to the possible correlation between leptin (LEP) and GHD pathogenesis, this study investigated the gene polymorphism of LEP and its receptor (LEPR) genes, along with serum IGF-1 and LEP levels in GHD patients. This study attempted to illustrate the correlation between gene polymorphism and GHD pathogenesis. A case-control study was performed using 180 GHD children in addition to 160 healthy controls. PCR-DNA sequencing method was employed for genotyping various polymorphism loci of LEP and LEPR genes in both GHD and healthy individuals. Serum IGF-1 and LEP levels were also determined. Results revealed a statistically significant difference between the levels of IGF-1 and LEP in the serum samples collected from patients in the GHD and the control groups. Both IGF-1 and LEP levels were found to be correlated with polymorphism at rs7799039 loci of LEP gene, in which GG and GA genotypes carriers had higher serum IGF-1 levels when compared to AA genotype carriers. GHD pathogenesis is well correlated with the LEP and IGF-1 levels in the both of which were mediated by the gene polymorphism at rs7799039 loci of LEP gene.

Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis.

PubMed Central

Balogh, Z; El-Ghobarey, A F; Fell, G S; Brown, D H; Dunlop, J; Dick, W C

1980-01-01

Total plasma zinc levels in patients with rheumatoid arthritis on different therapeutic treatments were determined in conjunction with total serum proteins, serum albumin and globulin, and articular index of joint tenderness, erythrocyte sedimentation rate, rheumatoid factor, serum copper, and serum iron. There were significantly lower zinc levels in patients with rheumatoid arthritis on nonsteroidal anti-inflammatory drugs than in patients on levamisole and penicillamine. Zinc levels correlated positively with serum albumin, and there was an inverse correlation between zinc levels and both ESR and globulin concentration in all rheumatoid patients. However, the correlation coefficient varied in the different treatment groups. The results of this study support the hypothesis that low plasma zinc level in rheumatoid arthritis is one of the nonspecific features of inflammation. PMID:7436558

Correlation between fecal calprotectin levels, disease severity and the hypervirulent ribotype 027 strain in patients with Clostridium difficile infection.

PubMed

Peretz, Avi; Tkhawkho, Linda; Pastukh, Nina; Brodsky, Diana; Halevi, Chen Namimi; Nitzan, Orna

2016-06-22

Clostridium difficile is the most common infectious etiology of nosocomial diarrhea. Fecal calprotectin (fc) is a sensitive marker of intestinal inflammation, found to be associated with enteric bacterial infections and inflammatory bowel disease. We evaluated fc levels using a Chemiluminescent immunoassay method, in hospitalized patients with C. difficile infection (CDI) diagnosed by molecular stool examination and assessed correlation with virulent ribotype 027 strain infection, antibiotic susceptibility by gradient Etest strip performed on C. difficile colonies and clinical and laboratory measures of disease severity. Statistical analysis was performed for correlation of fc levels with clinical and laboratory parameters, disease severity and patient outcomes. Overall 29 patients with CDI were admitted at the Poria medical center in northern Israel, during June 2014-May 2015. Resistance to metronidazole was found in 3 (10.3 %) isolates and to vancomycin in 5 (17.2 %) isolates. Regarding patient outcomes, within 30 days of CDI diagnosis, recurrence of disease occurred in 10 (34.5 %) patients and 2 patients (6.9 %) died. Seven (24.1 %) isolates were C. difficile ribotype 027. Mean fc level was 331.4 μg/g (21-932). Higher fc levels were found in patients with C. difficile ribotype 027 (p < 0.0005). Fc levels were also correlated with elevated peripheral blood white cell count (p = 0.0007). A trend for higher fc levels was found in patients with a higher clostridium severity score index (p = 0.0633). No correlation was found between fecal calprotectin levels and age, sex, functional status, community versus hospital acquired CDI, antibiotic susceptibility, fever, and creatinine levels. Our study highlights the fact that fc has a potential role as a biomarker of disease severity and binary toxin producing ribotype associated disease.

Global variations in the level of cancer-related research activity and correlation to cancer-specific mortality: Proposal for a global curriculum.

PubMed

Are, C; Caniglia, A; Malik, Mohammed; Smith, L; Cummings, Charmaine; Lecoq, Carine; Berman, R; Audisio, R; Wyld, L

2018-01-01

The aim of this study was to analyze global variations in the level of cancer-related research activity and correlate this with cancer-specific mortality. The SCOPUS database was explored to obtain data relating to the number of cancer-related publications per country. Cancer-specific mortality rates were obtained from the World Health Organization. Global variations in the level of scholarly activity were analyzed and correlated with variations in cancer-specific mortality. Data for 142 countries were obtained and significant variations in the level of research activity was noted. The level of research activity increased with rising socio-economic status. The United States was the most prolific country with 222,300 publications followed by Japan and Germany. Several countries in different regions of the world had a low level of research activity. An inverse relationship between the level of research activity and cancer-specific mortality was noted. This relationship persisted even in countries with a low level of research activity. The socioeconomic status of a nation and geographic location (continent) had a mixed influence with an overall apparent correlation with cancer-related research activity. This study demonstrates significant global variation in the level of cancer-related research activity and a correlation with cancer-specific mortality. The presence of a minimum set of standards for research literacy, as proposed by the European Society of Surgical Oncology and the Society of Surgical Oncology may contribute to enhanced research activity and improve outcomes for cancer patients worldwide. Copyright © 2017 Society of Surgical Oncology, European Society of Surgical Oncology. Published by Elsevier Ltd.. All rights reserved.

The Eating and Drinking Ability Classification System: concurrent validity and reliability in children with cerebral palsy.

PubMed

Tschirren, Lea; Bauer, Susanne; Hanser, Chiara; Marsico, Petra; Sellers, Diane; van Hedel, Hubertus J A

2018-06-01

As there is little evidence for concurrent validity of the Eating and Drinking Ability Classification System (EDACS), this study aimed to determine its concurrent validity and reliability in children and adolescents with cerebral palsy (CP). After an extensive translation procedure, we applied the German language version to 52 participants with CP (30 males, 22 females, mean age 9y 7mo [SD 4y 2mo]). We correlated (Kendall's tau or K τ ) the EDACS levels with the Bogenhausener Dysphagiescore (BODS), and the EDACS level of assistance with the Manual Ability Classification System (MACS) and the item 'eating' of the Functional Independence Measure for Children (WeeFIM). We further quantified the interrater reliability between speech and language therapists (SaLTs) and between SaLTs and parents with Kappa (κ). The EDACS levels correlated highly with the BODS (K τ =0.79), and the EDACS level of assistance correlated highly with the MACS (K τ =0.73) and WeeFIM eating item (K τ =-0.80). Interrater reliability proved almost perfect between SaLTs (EDACS: κ=0.94; EDACS level of assistance: κ=0.89) and SaLTs and parents (EDACS: κ=0.82; EDACS level of assistance: κ=0.89). The EDACS levels and level of assistance seem valid and showed almost perfect interrater reliability when classifying eating and drinking problems in children and adolescents with CP. The Eating and Drinking Ability Classification System (EDACS) correlates well with a dysphagia score. The EDACS level of assistance proves valid. The German version of EDACS is highly reliable. EDACS correlates moderately to highly with other classification systems. © 2018 Mac Keith Press.

Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD

PubMed Central

Hu, Yang; Yu, Shu-Yang; Zuo, Li-Jun; Piao, Ying-Shan; Cao, Chen-Jie; Wang, Fang; Chen, Ze-Jie; Du, Yang; Lian, Teng-Hong; Liu, Gai-Fen; Wang, Ya-Jie; Chan, Piu; Chen, Sheng-Di; Wang, Xiao-Min; Zhang, Wei

2015-01-01

Objective To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD). Methods Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed. Results (1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL–1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL–1β in PD group. Iron level is positively correlated with the levels of NO and IL–1β in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group. Conclusions PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation. PMID:26431210

Physical inactivity post-stroke: a 3-year longitudinal study.

PubMed

Kunkel, Dorit; Fitton, Carolyn; Burnett, Malcolm; Ashburn, Ann

2015-01-01

To explore change in activity levels post-stroke. We measured activity levels using the activPAL™ in hospital and at 1, 2 and 3 years' post-stroke onset. Of the 74 participants (mean age 76 (SD 11), 39 men), 61 were assessed in hospital: 94% of time was spent in sitting/lying, 4% standing and 2% walking. Activity levels improved over time (complete cases n = 15); time spent sitting/lying decreased (p = 0.001); time spent standing, walking and number of steps increased (p = 0.001, p = 0.028 and p = 0.03, respectively). At year 3, 18% of time was spent in standing and 9% walking. Time spent upright correlated significantly with Barthel (r = 0.69 on admission, r = 0.68 on discharge, both p < 0.01) and functional ambulation category scores (r = 0.55 on admission, 0.63 on discharge, both p < 0.05); correlations remained significant at all assessment points. Depression (in hospital), left hemisphere infarction (Years 1-2), visual neglect (Year 2), poor mobility and balance (Years 1-3) correlated with poorer activity levels. People with stroke were inactive for the majority of time. Time spent upright improved significantly by 1 year post-stroke; improvements slowed down thereafter. Poor activity levels correlated with physical and psychological measures. Larger studies are indicated to identify predictors of activity levels. Implications for Rehabilitation Activity levels (measured using activPAL™ activity monitor), increased significantly by 1 year post-stroke but improvements slowed down at 2 and 3 years. People with stroke were inactive for the majority of their day in hospital and in the community. Poor activity levels correlated with physical and psychological measures. Larger studies are indicated to identify the most important predictors of activity levels.

Serum Albumin and Disease Severity of Non-Cystic Fibrosis Bronchiectasis.

PubMed

Lee, Seung Jun; Kim, Hyo-Jung; Kim, Ju-Young; Ju, Sunmi; Lim, Sujin; Yoo, Jung Wan; Nam, Sung-Jin; Lee, Gi Dong; Cho, Hyun Seop; Kim, Rock Bum; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog

2017-08-01

A clinical classification system has been developed to define the severity and predict the prognosis of subjects with non-cystic fibrosis (CF) bronchiectasis. We aimed to identify laboratory parameters that are correlated with the bronchiectasis severity index (BSI) and FACED score. The medical records of 107 subjects with non-CF bronchiectasis for whom BSI and FACED scores could be calculated were retrospectively reviewed. The correlations between the laboratory parameters and BSI or FACED score were assessed, and multiple-linear regression analysis was performed to identify variables independently associated with BSI and FACED score. An additional subgroup analysis was performed according to sex. Among all of the enrolled subjects, 49 (45.8%) were male and 58 (54.2%) were female. The mean BSI and FACED scores were 9.43 ± 3.81 and 1.92 ± 1.59, respectively. The serum albumin level (r = -0.49), bilirubin level (r = -0.31), C-reactive protein level (r = 0.22), hemoglobin level (r = -0.2), and platelet/lymphocyte ratio (r = 0.31) were significantly correlated with BSI. Meanwhile, serum albumin (r = -0.37) and bilirubin level (r = -0.25) showed a significant correlation with the FACED score. Multiple-linear regression analysis showed that the serum bilirubin level was independently associated with BSI, and the serum albumin level was independently associated with both scoring systems. Subgroup analysis revealed that the level of uric acid was also a significant variable independently associated with the BSI in male bronchiectasis subjects. Several laboratory variables were identified as possible prognostic factors for non-CF bronchiectasis. Among them, the serum albumin level exhibited the strongest correlation and was identified as an independent variable associated with the BSI and FACED scores. Copyright © 2017 by Daedalus Enterprises.

Estimating historical groundwater levels based on relations with hydrologic and meteorological variables in the U.S. glacial aquifer system

NASA Astrophysics Data System (ADS)

Dudley, R. W.; Hodgkins, G. A.; Nielsen, M. G.; Qi, S. L.

2018-07-01

A number of previous studies have examined relations between groundwater levels and hydrologic and meteorological variables over parts of the glacial aquifer system, but systematic analyses across the entire U.S. glacial aquifer system are lacking. We tested correlations between monthly groundwater levels measured at 1043 wells in the U.S. glacial aquifer system considered to be minimally influenced by human disturbance and selected hydrologic and meteorological variables with the goal of extending historical groundwater records where there were strong correlations. Groundwater levels in the East region correlated most strongly with short-term (1 and 3 month) averages of hydrologic and meteorological variables, while those in the Central and West Central regions yielded stronger correlations with hydrologic and meteorological variables averaged over longer time intervals (6-12 months). Variables strongly correlated with high and low annual groundwater levels were identified as candidate records for use in statistical linear models as a means to fill in and extend historical high and low groundwater levels respectively. Overall, 37.4% of study wells meeting data criteria had successful models for high and (or) low groundwater levels; these wells shared characteristics of relatively higher local precipitation, higher local land-surface slope, lower amounts of clay within the surficial sediments, and higher base-flow index. Streamflow and base flow served as explanatory variables in about two thirds of both high- and low-groundwater-level models in all three regions, and generally yielded more and better models compared to precipitation and Palmer Drought Severity Index. The use of variables such as streamflow with substantially longer and more complete records than those of groundwater wells provide a means for placing contemporary groundwater levels in a longer historical context and can support site-specific analyses such as groundwater modeling.

Relationship among Glutamine, γ-Aminobutyric Acid, and Social Cognition in Autism Spectrum Disorders

PubMed Central

Sikoglu, Elif M.; Hodge, Steven M.; Edden, Richard A.E.; Foley, Ann; Kennedy, David N.; Moore, Constance M.; Frazier, Jean A.

2015-01-01

Abstract Objective: An imbalance of excitatory and inhibitory neurotransmission in autism spectrum disorder (ASD) has been proposed. We compared glutamate (Glu), glutamine (Gln), and γ-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) of 13 males with ASD and 14 typically developing (TD) males (ages 13–17), and correlated these levels with intelligence quotient (IQ) and measures of social cognition. Methods: Social cognition was evaluated by administration of the Social Responsiveness Scale (SRS) and the Reading the Mind in the Eyes Test (RMET). We acquired proton magnetic resonance spectroscopy (1H-MRS) data from the bilateral ACC using the single voxel point resolved spectroscopy sequence (PRESS) to quantify Glu and Gln, and Mescher–Garwood point-resolved spectroscopy sequence (MEGA-PRESS) to quantify GABA levels referenced to creatine (Cr). Results: There were higher Gln levels (p=0.04), and lower GABA/Cre levels (p=0.09) in the ASD group than in the TD group. There was no difference in Glu levels between groups. Gln was negatively correlated with RMET score (rho=−0.62, p=0.001) and IQ (rho=−0.56, p=0.003), and positively correlated with SRS scores (rho=0.53, p=0.007). GABA/Cre levels were positively correlated with RMET score (rho=0.34, p=0.09) and IQ (rho=0.36, p=0.07), and negatively correlated with SRS score (rho=−0.34, p=0.09). Conclusions: These data suggest an imbalance between glutamatergic neurotransmission and GABA-ergic neurotransmission in ASD. Higher Gln levels and lower GABA/Cre levels were associated with lower IQ and greater impairments in social cognition across groups. PMID:25919578

Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults

PubMed Central

Morris, Martha Clare; Brockman, John; Schneider, Julie A.; Wang, Yamin; Bennett, David A.; Tangney, Christy C.; van de Rest, Ondine

2017-01-01

IMPORTANCE Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern. OBJECTIVE To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004–2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years. EXPOSURES Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death. MAIN OUTCOMES AND MEASURES Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses. RESULTS Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (ρ = 0.16; P = .02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (≥1 meal[s]/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (β = −0.69 score units [95% CI, −1.34 to −0.04]), less severe and widespread neurofibrillary tangles (β = −0.77 score units [95% CI, −1.52 to −0.02]), and lower neuropathologically defined Alzheimer disease (β = −0.53 score units [95% CI, −0.96 to −0.10]) but only among apolipoprotein E (APOE ε4) carriers. Higher intake levels of α-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology. CONCLUSIONS AND RELEVANCE In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology. PMID:26836731

The relationship between hemoglobin level and the type 1 diabetic nephropathy in Anhui Han's patients.

PubMed

Jiang, Jun; Lei, Lan; Zhou, Xiaowan; Li, Peng; Wei, Ren

2018-02-20

Recent studies have shown that low hemoglobin (Hb) level promote the progression of chronic kidney disease. This study assessed the relationship between Hb level and type 1 diabetic nephropathy (DN) in Anhui Han's patients. There were a total of 236 patients diagnosed with type 1 diabetes mellitus and (T1DM) seen between January 2014 and December 2016 in our centre. Hemoglobin levels in patients with DN were compared with those without DN. The relationship between Hb level and the urinary albumin-creatinine ratio (ACR) was examined by Spearman's correlational analysis and multiple stepwise regression analysis. The binary logistic multivariate regression analysis was performed to analyze the correlated factors for type 1 DN, calculate the Odds Ratio (OR) and 95%confidence interval (CI). The predicting value of Hb level for DN was evaluated by area under receiver operation characteristic curve (AUROC) for discrimination and Hosmer-Lemeshow goodness-of-fit test for calibration. The average Hb levels in the DN group (116.1 ± 20.8 g/L) were significantly lower than the non-DN group (131.9 ± 14.4 g/L) , P < 0.001. Hb levels were independently correlated with the urinary ACR in multiple stepwise regression analysis. The logistic multivariate regression analysis showed that the Hb level (OR: 0.936, 95% CI: 0.910 to 0.963, P < 0.001) was inversely correlated with DN in patients with T1DM. In sub-analysis, low Hb level (Hb < 120g/L in female, Hb < 130g/L in male) was still negatively associated with DN in patients with T1DM. The AUROC was 0.721 (95% CI: 0.655 to 0.787) in assessing the discrimination of the Hb level for DN. The value of P was 0.593 in Hosmer-Lemeshow goodness-of-fit test. In Anhui Han's patients with T1DM, the Hb level is inversely correlated with urinary ACR and DN. This article is protected by copyright. All rights reserved.

Serum total bilirubin levels are negatively correlated with metabolic syndrome in aged Chinese women: a community-based study.

PubMed

Zhong, P; Sun, D M; Wu, D H; Li, T M; Liu, X Y; Liu, H Y

2017-01-26

We evaluated serum total bilirubin levels as a predictor for metabolic syndrome (MetS) and investigated the relationship between serum total bilirubin levels and MetS prevalence. This cross-sectional study included 1728 participants over 65 years of age from Eastern China. Anthropometric data, lifestyle information, and previous medical history were collected. We then measured serum levels of fasting blood-glucose, total cholesterol, triglycerides, and total bilirubin, as well as alanine aminotransferase activity. The prevalence of MetS and each of its individual component were calculated per quartile of total bilirubin level. Logistic regression was used to assess the correlation between serum total bilirubin levels and MetS. Total bilirubin level in the women who did not have MetS was significantly higher than in those who had MetS (P<0.001). Serum total bilirubin quartiles were linearly and negatively correlated with MetS prevalence and hypertriglyceridemia (HTG) in females (P<0.005). Logistic regression showed that serum total bilirubin was an independent predictor of MetS for females (OR: 0.910, 95%CI: 0.863-0.960; P=0.001). The present study suggests that physiological levels of serum total bilirubin might be an independent risk factor for aged Chinese women, and the prevalence of MetS and HTG are negatively correlated to serum total bilirubin levels.

Correlation between GH and IGF-1 during treatment for acromegaly.

PubMed

Oldfield, Edward H; Jane, John A; Thorner, Michael O; Pledger, Carrie L; Sheehan, Jason P; Vance, Mary Lee

2017-06-01

OBJECTIVE The relationship between growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly as serial levels drop over time after treatment has not been examined previously. Knowledge of this relationship is important to correlate pretreatment levels that best predict response to treatment. To examine the correlation between GH and IGF-1 and IGF-1 z-scores over a wide range of GH levels, the authors examined serial GH and IGF-1 levels at intervals before and after surgery and radiosurgery for acromegaly. METHODS This retrospective analysis correlates 414 pairs of GH and IGF-1 values in 93 patients with acromegaly. RESULTS Absolute IGF-1 levels increase linearly with GH levels only up to a GH of 4 ng/ml, and with IGF-1 z-scores only to a GH level of 1 ng/ml. Between GH levels of 1 and 10 ng/ml, increases in IGF-1 z-scores relative to changes in GH diminish and then plateau at GH concentrations of about 10 ng/ml. From patient to patient there is a wide range of threshold GH levels beyond which IGF-1 increases are no longer linear, GH levels at which the IGF-1 response plateaus, IGF-1 levels at similar GH values after the IGF-1 response plateaus, and of IGF-1 levels at similar GH levels. CONCLUSIONS In acromegaly, although IGF-1 levels represent a combination of the integrated effects of GH secretion and GH action, the tumor produces GH, not IGF-1. Nonlinearity between GH and IGF-1 occurs at GH levels far below those previously recognized. To monitor tumor activity and tumor viability requires measurement of GH levels.

Serum tumour necrosis factor-α and interleukin-6 levels in Alzheimer's disease and mild cognitive impairment.

PubMed

Kim, Yo Sup; Lee, Kang Joon; Kim, Hyun

2017-07-01

Neuroinflammation has been recognized as a feature of Alzheimer's disease (AD), and mild cognitive impairment (MCI) is believed to share several pathological features with AD. The aim of the present study was to compare serum cytokine levels between patients with AD, subjects with MCI, and healthy controls, and to assess the correlation between cytokine levels and cognitive performance in these subjects. Participants included 35 patients with AD, 29 subjects with MCI, and 28 healthy controls from the Department of Psychiatry of IIlsan Paik Hospital in South Korea. Demographic and neuropsychological information were obtained, and peripheral cytokine levels, specifically tumour necrosis factor (TNF)-α and interleukin (IL)-6 levels, were measured for all subjects. After adjustment for age, a significant difference in IL-6 levels (P = 0.045), but not in TNF-α (P = 0.082) levels, was observed among the three groups. IL-6 levels were higher in patients with AD than in subjects with MCI and healthy controls. TNF-α and IL-6 levels negatively and positively correlated with Mini-Mental State Examination and Global Deterioration Scale scores, respectively. TNF-α and IL-6 levels were also positively correlated with each other. The present study suggests that serum IL-6 levels of patients with AD might be higher than those of subjects with MCI and healthy controls. Serum TNF-α and IL-6 levels might be negatively correlated with cognitive function, and we suspect that serum IL-6 levels could be biomarkers for AD. © 2017 Japanese Psychogeriatric Society.

Androgen deficiency and dry eye syndrome in the aging male.

PubMed

Azcarate, Patrick M; Venincasa, Vincent D; Feuer, William; Stanczyk, Frank; Schally, Andrew V; Galor, Anat

2014-07-03

To evaluate the relationship between androgen levels and subjective and objective measures of dry eye syndrome (DES). A total of 263 male patients from the Miami Veterans Affairs Medical Center eye clinic aged ≥50 were recruited for this prospective cross-sectional study. Patients completed Dry Eye Questionnaire 5, underwent tear film evaluation, and had serum androgen levels measured. The correlations between androgen levels, DES composite scores, DES symptoms, and global, lipid, and aqueous tear film parameters were evaluated. Two hundred sixty-three patients with a mean age of 69 (50-95) were examined. There was no linear association between composite DES scores (generated using latent class analysis) and androgen levels. However, eyes with high DES scores (0.95-1.0) had higher levels of sex hormone-binding globulin (P = 0.03) and lower levels of dehydroepiandrosterone sulfate (DHEAS) (P = 0.02), androstenedione (A) (P = 0.02), and androstane-3α,17β-diol glucuronide (P = 0.03) compared to eyes with intermediate (0.05-0.95) or low (0-0.05) scores. There were no strong correlations between tear film measures and androgen levels. Regarding global parameters, a weak inverse correlation was found between corneal staining and A (r = -0.17, P = 0.009). For lipid parameters, a weak correlation existed between tear breakup time (TBUT) and A (r = 0.15, P = 0.02). When considering aqueous and lipid deficiency independently, the association between TBUT and A existed only with aqueous tear deficiency (r = 0.66, P = 0.002). Regarding aqueous parameters, a weak correlation existed between Schirmer test and DHEAS (r = 0.13, P = 0.047) and A (r = 0.21, P = 0.001). There was a weak correlation between higher levels of androstenedione and healthier global, lipid, and aqueous tear film parameters. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Elevated Glutamate Levels in the Left Dorsolateral Prefrontal Cortex Are Associated with Higher Cravings for Alcohol.

PubMed

Frye, Mark A; Hinton, David J; Karpyak, Victor M; Biernacka, Joanna M; Gunderson, Lee J; Geske, Jennifer; Feeder, Scott E; Choi, Doo-Sup; Port, John D

2016-08-01

Quantifying craving longitudinally during the course of withdrawal, early abstinence, and relapse is essential for optimal management of alcohol use disorder (AUD). In an effort to identify biological correlates of craving, we used proton magnetic resonance spectroscopy (1H-MRS) to investigate the correlation between craving and glutamate levels in the left dorsolateral prefrontal cortex (LDLPFC) of patients with AUD. Participants underwent 1H-MRS of the LDLPFC with 2-dimensional J-resolved (2DJ) averaged PRESS. MRS data were processed with LCModel and cerebrospinal fluid (CSF)-corrected to generate metabolite concentrations. The Penn Alcohol Craving Scale (PACS) and the 30-day time line follow-back (TLFB 30) were used to quantify craving for alcohol and drinking patterns, respectively. There was a statistically significant positive correlation between CSF-corrected glutamate ([Glu]) levels and PACS scores (n = 14; p = 0.005). When PACS scores were dichotomized (< or ≥median = 16), [Glu] levels were significantly higher in the high- versus low-craving group (p = 0.007). In addition, there was a significant negative correlation between CSF-corrected N-acetyl aspartic acid ([NAA]) levels and mean number of drinks per drinking day in the past month (n = 13; TLFB 30; p = 0.012). When mean TLFB 30 was dichotomized (< or ≥median = 7.86), [NAA] levels were significantly lower in subjects that consumed more alcoholic beverages. There was no significant correlation between [Glu] and [NAA] levels with other measures of drinking behavior and or depression symptom severity. While limited by small sample size, these data suggest that glutamate levels in LDLPFC are associated with alcohol craving intensity in patients with AUD. Further study with larger sample size is needed to replicate this finding and evaluate the merits of glutamate spectroscopy as a biological correlate of alcohol craving intensity and a guide to treatment interventions. Copyright © 2016 by the Research Society on Alcoholism.

Study of the Disintegration Process and of the Angular Moments of the Excited Levels of Pm-147 Using Spectrographic and Angular Correlation Measurements (thesis); ETUDE DU SCHEMA DE DESINTEGRATION ET DES MOMENTS ANGULAIRES DES NIVEAUX EXCITES DU Pm 147 PAR DES MESURES DE SPECTROGRAPHIE ET DE CORRELATIONS ANGULAIRES (these)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Philis, C.

1963-07-01

The energies and relative intensities of fifteen gamma lines were determined by a direct spectrographic study. A previously unreported level at 77 plus or minus 2 kev was identified. A coincidence study confirmed the positions of the excited levels of Pm/sup 147/. The 77-kev line was laced between the 409 and 490-kev levels. Angular correlation measurements permitted the assignment of angular moments of 5/2, 7/2, and 5/2 to the 92, 409, and 532-kev levels and of 5/2 or 7/2 to the 685-kev level. The associated mixing coefficients were also obtained. (D.C.W.)

Position Between Trunk and Pelvis During Gait Depending on the Gross Motor Function Classification System.

PubMed

Sanz-Mengibar, Jose Manuel; Altschuck, Natalie; Sanchez-de-Muniain, Paloma; Bauer, Christian; Santonja-Medina, Fernando

2017-04-01

To understand whether there is a trunk postural control threshold in the sagittal plane for the transition between the Gross Motor Function Classification System (GMFCS) levels measured with 3-dimensional gait analysis. Kinematics from 97 children with spastic bilateral cerebral palsy from spine angles according to Plug-In Gait model (Vicon) were plotted relative to their GMFCS level. Only average and minimum values of the lumbar spine segment correlated with GMFCS levels. Maximal values at loading response correlated independently with age at all functional levels. Average and minimum values were significant when analyzing age in combination with GMFCS level. There are specific postural control patterns in the average and minimum values for the position between trunk and pelvis in the sagittal plane during gait, for the transition among GMFCS I-III levels. Higher classifications of gross motor skills correlate with more extended spine angles.

Studying the Relative Strengths of Environmental Factors that Influence Echinoderm Body Size Trends

NASA Astrophysics Data System (ADS)

Low, A.; Randhawa, S.; Heim, N. A.; Payne, J.

2013-12-01

Body size is often a useful metric in observing how a clade responds to environmental changes. Previous research has uncovered how environmental factors such as carbon dioxide and oxygen levels influence body size evolution. However, we wanted to look into how these natural factors interact and which factors seem to have a stronger relative influence on echinoderm body size. We analyzed carbon dioxide levels, a proxy for paleotemperature, oxygen levels, and sea level. Our research process involved measuring and calculating the volume of Phanerozoic echinoderm fossils recorded in the Treatise on Invertebrate Paleontology, plotting their mean volumes over various natural factors, and using statistical tools such as correlation tests and the PaleoTS statistical analysis software to compare the relative strengths of these factors. Furthermore, we divided our data into the following three subsets to uncover more specific relationships: 1) A set that included all data of the phylum Echinodermata 2) A set that focused on the two classes with the most recorded data, Echinoidea and Crinoidea 3) A set that focused on the crinoid specimens that originated in the Paleozoic and in the post-Paleozoic. In the first subset, echinoderms had the strongest correlation with carbon dioxide, a proxy for temperature, and possessed a weaker correlation with oxygen. In the second subset, we discovered that the echinoid data also possessed a strong correlation with carbon dioxide and a weaker correlation with oxygen. For crinoids, we found that the class as a whole showed no strong correlation with any measured environmental factors. However, when we divided the crinoids based on age, we found that both Paleozoic and post-Paleozoic crinoids individually correlated strongly with sea level. However, some uncertainty with this correlation arose as the comparison of the environmental correlate models suggested that an unbiased random walk was the best fit for the data. This stands as a sharp contrast to the strong evidence provided by the appropriate graphs and correlation tests that indicate strong, dominant relationships between body size and environmental factors. Thus, though further research is necessary to settle such uncertainty, we were able to identify, observe, and compare the diversity in body size responses to environmental factors within echinoderms.

Dual-induced multifractality in online viewing activity.

PubMed

Qin, Yu-Hao; Zhao, Zhi-Dan; Cai, Shi-Min; Gao, Liang; Stanley, H Eugene

2018-01-01

Although recent studies have found that the long-term correlations relating to the fat-tailed distribution of inter-event times exist in human activity and that these correlations indicate the presence of fractality, the property of fractality and its origin have not been analyzed. We use both detrended fluctuation analysis and multifractal detrended fluctuation analysis to analyze the time series in online viewing activity separating from Movielens and Netflix. We find long-term correlations at both the individual and communal levels and that the extent of correlation at the individual level is determined by the activity level. These long-term correlations also indicate that there is fractality in the pattern of online viewing. We first find a multifractality that results from the combined effect of the fat-tailed distribution of inter-event times (i.e., the times between successive viewing actions of individuals) and the long-term correlations in online viewing activity and verify this finding using three synthesized series. Therefore, it can be concluded that the multifractality in online viewing activity is caused by both the fat-tailed distribution of inter-event times and the long-term correlations and that this enlarges the generic property of human activity to include not just physical space but also cyberspace.

Dual-induced multifractality in online viewing activity

NASA Astrophysics Data System (ADS)

Qin, Yu-Hao; Zhao, Zhi-Dan; Cai, Shi-Min; Gao, Liang; Stanley, H. Eugene

2018-01-01

Although recent studies have found that the long-term correlations relating to the fat-tailed distribution of inter-event times exist in human activity and that these correlations indicate the presence of fractality, the property of fractality and its origin have not been analyzed. We use both detrended fluctuation analysis and multifractal detrended fluctuation analysis to analyze the time series in online viewing activity separating from Movielens and Netflix. We find long-term correlations at both the individual and communal levels and that the extent of correlation at the individual level is determined by the activity level. These long-term correlations also indicate that there is fractality in the pattern of online viewing. We first find a multifractality that results from the combined effect of the fat-tailed distribution of inter-event times (i.e., the times between successive viewing actions of individuals) and the long-term correlations in online viewing activity and verify this finding using three synthesized series. Therefore, it can be concluded that the multifractality in online viewing activity is caused by both the fat-tailed distribution of inter-event times and the long-term correlations and that this enlarges the generic property of human activity to include not just physical space but also cyberspace.

Agreement of arterial sodium and arterial potassium levels with venous sodium and venous potassium in patients admitted to intensive care unit.

PubMed

Nanda, Sunil Kumar; Ray, Lopamudra; Dinakaran, Asha

2015-02-01

Electrolyte abnormalities are one of the common causes of morbidity and mortality in critically ill patients. The turnaround time for electrolyte reporting should be as low as possible. Electrolytes are measured conventionally in serum obtained from venous blood by electrolyte analyser which takes 20 to 30 min. Point of care analysers are now available where in electrolytes can be measured in arterial blood within 5 min. This study was done to study the agreement of arterial sodium and arterial potassium with venous sodium and venous potassium levels. Venous sodium and venous potassium levels and arterial sodium and arterial potassium levels were analysed on 206 patient samples admitted to Intensive Care Unit (ICU). The venous values were compared with the arterial values for correlation. Venous sodium was compared with arterial sodium by spearman correlation. Venous potassium was compared with arterial potassium by pearson correlation. The mean value of arterial sodium was 134 and venous sodium was 137. The mean value of arterial potassium was 3.6 and venous potassium was 4.1. The correlation coefficient obtained for sodium was 0.787 and correlation coefficient obtained for potassium was 0.701. There was positive correlation of arterial sodium and arterial potassium with venous sodium and venous potassium indicating agreement between the parameters. Arterial sodium and arterial potassium can be used instead of venous sodium and venous potassium levels in management of critically ill patients.

Salivary chromogranin A levels correlate with disease severity but do not reflect anxiety or personality of adult patients with atopic dermatitis.

PubMed

Kaneko, Sakae; Liu, Lijuan; Kakamu, Takeyasu; Minami-Hori, Masako; Morita, Eishin

2017-08-01

Stress-induced scratching is an issue in patients with adult atopic dermatitis (AD). Although itching and stress are believed to be intimately related, no objective index is available; therefore, most evaluations are subjective. Using saliva, which is easily collected, we investigated the degree to which AD severity and patient stress levels are reflected in stress proteins in the saliva. Here, we evaluated the severity (Scoring Atopic Dermatitis [SCORAD] score), stress (State-Trait Anxiety Index [STAI] score), personality (Tokyo University Egogram [TEG] II score) and quality of life (Dermatology Life Quality Index [DLQI] score) of 51 patients with AD who were examined in the Department of Dermatology of Shimane University between April and December 2015. We collected saliva and measured salivary chromogranin A (CgA), amylase and cortisol. The amount of salivary CgA per protein in patients with AD was correlated with their SCORAD score (r = 0.458, P < 0.001). There was no correlation between cortisol or amylase levels and SCORAD score. SCORAD score was correlated with DLQI (r = 0.390, P = 0.006). CgA per protein was correlated with DLQI (r = 0.393, P = 0.004). There was no correlation between scores for the anxiety component of the STAI, TEG II or DLQI. Our results suggested that patients with more severe AD may have high stress levels. The personalities of these patients with AD tended to involve elevated anxiety levels. © 2017 Japanese Dermatological Association.

Correlation between anthropometrics measurements, prealbumin level and transferin serum with Child-Pugh classification in evaluating nutritional status of liver cirrhosis patient.

PubMed

Yovita, H; Djumhana, Ali; Abdurachman, S A; Saketi, Juke Roslia

2004-01-01

to evaluate nutritional status by using anthropometrics and biochemistry examination and to determine the correlation between albumin, prealbumin and transferin serum level with anthropometrics measures in liver cirrhosis patient according to Child-Pugh classification. study was conducted on 30 patients with liver cirrhosis Child-Pugh A, B and C. There were 8 patient of Child-Pugh A, 18 Child-Pugh B and 4 Child-Pugh C. Every patient underwent anthropometrics and biochemistry examination including ideal body weight (IBW), body mass index (BMI), triceps skin-fold thickness (TSF), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), albumin, prealbumin and transferin serum. We used statistical analysis Spearman and Pearson correlation test. by IBW and BMI measurement, most of liver cirrhosis patients indicated normal results. By MAMC measurement, there was no liver cirrhosis patient with good nutritional status. Most of them have slight and moderate malnutrition. There was no significant correlation between anthropometrics measurement with Child-Pugh score, with [p > 0.01]. And also, there was no significant relationship between albumin, prealbumin and serum transferin with anthropometrics measures, but there was significant correlation between prealbumin and transferin level with Child-Pugh score, with [p < 0.01]. the conclusion of this study is prealbumin and transferin level may be used to evaluate nutritional status of liver cirrhosis patient, and on the contrary with anthropometrics measures. There was no correlation between anthropometrics measures with albumin, prealbumin and transferin level.

An experimental study on the noise correlation properties of CBCT projection data

NASA Astrophysics Data System (ADS)

Zhang, Hua; Ouyang, Luo; Ma, Jianhua; Huang, Jing; Chen, Wufan; Wang, Jing

2014-03-01

In this study, we systematically investigated the noise correlation properties among detector bins of CBCT projection data by analyzing repeated projection measurements. The measurements were performed on a TrueBeam on-board CBCT imaging system with a 4030CB flat panel detector. An anthropomorphic male pelvis phantom was used to acquire 500 repeated projection data at six different dose levels from 0.1 mAs to 1.6 mAs per projection at three fixed angles. To minimize the influence of the lag effect, lag correction was performed on the consecutively acquired projection data. The noise correlation coefficient between detector bin pairs was calculated from the corrected projection data. The noise correlation among CBCT projection data was then incorporated into the covariance matrix of the penalized weighted least-squares (PWLS) criterion for noise reduction of low-dose CBCT. The analyses of the repeated measurements show that noise correlation coefficients are non-zero between the nearest neighboring bins of CBCT projection data. The average noise correlation coefficients for the first- and second- order neighbors are 0.20 and 0.06, respectively. The noise correlation coefficients are independent of the dose level. Reconstruction of the pelvis phantom shows that the PWLS criterion with consideration of noise correlation results in a lower noise level as compared to the PWLS criterion without considering the noise correlation at the matched resolution.

Molecular analysis of human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) seroindeterminate blood donors from Northeast Iran: evidence of proviral tax, env, and gag sequences.

PubMed

Zanjani, Delaram Sayadpour; Shahabi, Majid; Talaei, Nasim; Afzalaghaee, Monavar; Tehranian, Farahnaz; Bazargani, Reihane

2011-02-01

Human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) Western blot indeterminate results are a problem for blood banks in endemic areas. To determine the prevalence of HTLV-1/2 infection among indeterminate donors, we analyzed 130 cases from Mashhad, an HTLV-1/2 endemic area in Northeast Iran. The most frequent Western blot bands were GD21 alone (37.2%) followed by rgp46-2 alone (32.1%). We further tested 40 available DNA samples of these cases by PCR for viral sequences, tax, gag, and pol, and found five cases (12.5%) to be positive for two or three HTLV-1 genes. There were no significant age, sex, and blood group differences between PCR-positive and PCR-negative cases. Among PCR-positive individuals, the most prevalent Western blot bands were variable combinations of rgp46-1, GD21, and gp21. The mean of the optical density (OD) of the enzyme-linked immunosorbent assay (ELISA) test was significantly higher in PCR-positive individuals. The frequency of the rgp46-1 band was also significantly higher in PCR-positive cases compared to PCR-negative ones. In conclusion, the majority of HTLV-indeterminate donors lack the HTLV provirus and therefore are not considered infected. However, in some cases with higher ODs in the ELISA test and seroreactivity to env proteins, rgp46-1 and GD21 in particular may be indicative of infection and need further evaluation by molecular methods.

Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus.

PubMed Central

Pavelitz, T; Rusché, L; Matera, A G; Scharf, J M; Weiner, A M

1995-01-01

In primates, the tandemly repeated genes encoding U2 small nuclear RNA evolve concertedly, i.e. the sequence of the U2 repeat unit is essentially homogeneous within each species but differs somewhat between species. Using chromosome painting and the NGFR gene as an outside marker, we show that the U2 tandem array (RNU2) has remained at the same chromosomal locus (equivalent to human 17q21) through multiple speciation events over > 35 million years leading to the Old World monkey and hominoid lineages. The data suggest that the U2 tandem repeat, once established in the primate lineage, contained sequence elements favoring perpetuation and concerted evolution of the array in situ, despite a pericentric inversion in chimpanzee, a reciprocal translocation in gorilla and a paracentric inversion in orang utan. Comparison of the 11 kb U2 repeat unit found in baboon and other Old World monkeys with the 6 kb U2 repeat unit in humans and other hominids revealed that an ancestral U2 repeat unit was expanded by insertion of a 5 kb retrovirus bearing 1 kb long terminal repeats (LTRs). Subsequent excision of the provirus by homologous recombination between the LTRs generated a 6 kb U2 repeat unit containing a solo LTR. Remarkably, both junctions between the human U2 tandem array and flanking chromosomal DNA at 17q21 fall within the solo LTR sequence, suggesting a role for the LTR in the origin or maintenance of the primate U2 array. Images PMID:7828589

Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Xiuxiu, E-mail: show-1989@163.com; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000; Yu, Yunfang, E-mail: yyf_8247425@163.com

Provirus integration site for Moloney murine leukemia virus 1 (Pim-1) has proved to be an oncogene and it is known that to depress Pim-1 activity may be a novel oncological treatment strategy. SGI-1776, a small molecule, is the first clinically tested inhibitor of the Pim kinase family. Here, we aimed to explore the effect of SGI-1776 on salivary adenoid cystic carcinoma (SACC). Expression of Pim-1 was confirmed in SACC and control tissues by qRT-PCR. After SGI-1776 treatment, the Pim-1 expressions and Pim-1 kinase activity in both SACC-83 and SACC-LM cell lines were measured. Cell proliferation, cell invasion, cell cycle, apoptosismore » and mitochondrial membrane potential were analyzed. Also, the expression of FOXO3a, p-FOXO3a, RUNX3, Bcl-2, BAD, p-BAD, Bim and p-Bim were detected by Western blot. The results showed that Pim-1 was significantly overexpressed in SACC tissues. SGI-1776 down-regulated the Pim-1 expression, inhibited Pim-1 kinase activity, reduced cell proliferation, decreased invasive ability, increased caspase-3 activity and induced apoptosis, cell cycle arrest and mitochondrial depolarization. Reduced expression was also seen in p-FOXO3a, RUNX3, Bcl-2, p-BAD and p-Bim, whereas no significant changes were observed from FOXO3a, BAD and Bim. These results confirm the pivotal role of Pim-1 in SACC and suggest that targeting Pim-1 kinase signal pathway by SGI-1776 might be a promising therapeutic modality for SACC.« less

Pan-vertebrate comparative genomics unmasks retrovirus macroevolution.

PubMed

Hayward, Alexander; Cornwallis, Charlie K; Jern, Patric

2015-01-13

Although extensive research has demonstrated host-retrovirus microevolutionary dynamics, it has been difficult to gain a deeper understanding of the macroevolutionary patterns of host-retrovirus interactions. Here we use recent technological advances to infer broad patterns in retroviral diversity, evolution, and host-virus relationships by using a large-scale phylogenomic approach using endogenous retroviruses (ERVs). Retroviruses insert a proviral DNA copy into the host cell genome to produce new viruses. ERVs are provirus insertions in germline cells that are inherited down the host lineage and consequently present a record of past host-viral associations. By mining ERVs from 65 host genomes sampled across vertebrate diversity, we uncover a great diversity of ERVs, indicating that retroviral sequences are much more prevalent and widespread across vertebrates than previously appreciated. The majority of ERV clades that we recover do not contain known retroviruses, implying either that retroviral lineages are highly transient over evolutionary time or that a considerable number of retroviruses remain to be identified. By characterizing the distribution of ERVs, we show that no major vertebrate lineage has escaped retroviral activity and that retroviruses are extreme host generalists, having an unprecedented ability for rampant host switching among distantly related vertebrates. In addition, we examine whether the distribution of ERVs can be explained by host factors predicted to influence viral transmission and find that internal fertilization has a pronounced effect on retroviral colonization of host genomes. By capturing the mode and pattern of retroviral evolution and contrasting ERV diversity with known retroviral diversity, our study provides a cohesive framework to understand host-virus coevolution better.

Human endogenous retrovirus HERV-K(HML-2) encodes a stable signal peptide with biological properties distinct from Rec

PubMed Central

Ruggieri, Alessia; Maldener, Esther; Sauter, Marlies; Mueller-Lantzsch, Nikolaus; Meese, Eckart; Fackler, Oliver T; Mayer, Jens

2009-01-01

Background The human endogenous retrovirus HERV-K(HML-2) family is associated with testicular germ cell tumors (GCT). Various HML-2 proviruses encode viral proteins such as Env and Rec. Results We describe here that HML-2 Env gives rise to a 13 kDa signal peptide (SP) that harbors a different C-terminus compared to Rec. Subsequent to guiding Env to the endoplasmatic reticulum (ER), HML-2 SP is released into the cytosol. Biochemical analysis and confocal microscopy demonstrated that similar to Rec, SP efficiently translocates to the granular component of nucleoli. Unlike Rec, SP does not shuttle between nucleus and cytoplasm. SP is less stable than Rec as it is subjected to proteasomal degradation. Moreover, SP lacks export activity towards HML-2 genomic RNA, the main function of Rec in the original viral context, and SP does not interfere with Rec's RNA export activity. Conclusion SP is a previously unrecognized HML-2 protein that, besides targeting and translocation of Env into the ER lumen, may exert biological functions distinct from Rec. HML-2 SP represents another functional similarity with the closely related Mouse Mammary Tumor Virus that encodes an Env-derived SP named p14. Our findings furthermore support the emerging concept of bioactive SPs as a conserved retroviral strategy to modulate their host cell environment, evidenced here by a "retroviral fossil". While the specific role of HML-2 SP remains to be elucidated in the context of human biology, we speculate that it may be involved in immune evasion of GCT cells or tumorigenesis. PMID:19220907

Pan-vertebrate comparative genomics unmasks retrovirus macroevolution

PubMed Central

Hayward, Alexander; Cornwallis, Charlie K.; Jern, Patric

2015-01-01

Although extensive research has demonstrated host-retrovirus microevolutionary dynamics, it has been difficult to gain a deeper understanding of the macroevolutionary patterns of host–retrovirus interactions. Here we use recent technological advances to infer broad patterns in retroviral diversity, evolution, and host–virus relationships by using a large-scale phylogenomic approach using endogenous retroviruses (ERVs). Retroviruses insert a proviral DNA copy into the host cell genome to produce new viruses. ERVs are provirus insertions in germline cells that are inherited down the host lineage and consequently present a record of past host–viral associations. By mining ERVs from 65 host genomes sampled across vertebrate diversity, we uncover a great diversity of ERVs, indicating that retroviral sequences are much more prevalent and widespread across vertebrates than previously appreciated. The majority of ERV clades that we recover do not contain known retroviruses, implying either that retroviral lineages are highly transient over evolutionary time or that a considerable number of retroviruses remain to be identified. By characterizing the distribution of ERVs, we show that no major vertebrate lineage has escaped retroviral activity and that retroviruses are extreme host generalists, having an unprecedented ability for rampant host switching among distantly related vertebrates. In addition, we examine whether the distribution of ERVs can be explained by host factors predicted to influence viral transmission and find that internal fertilization has a pronounced effect on retroviral colonization of host genomes. By capturing the mode and pattern of retroviral evolution and contrasting ERV diversity with known retroviral diversity, our study provides a cohesive framework to understand host–virus coevolution better. PMID:25535393

Residual Expression of the Reprogramming Factors Prevents Differentiation of iPSC Generated from Human Fibroblasts and Cord Blood CD34+ Progenitors

PubMed Central

Ramos-Mejía, Verónica; Montes, Rosa; Bueno, Clara; Ayllón, Verónica; Real, Pedro J.; Rodríguez, René; Menendez, Pablo

2012-01-01

Human induced pluripotent stem cells (hiPSC) have been generated from different tissues, with the age of the donor, tissue source and specific cell type influencing the reprogramming process. Reprogramming hematopoietic progenitors to hiPSC may provide a very useful cellular system for modelling blood diseases. We report the generation and complete characterization of hiPSCs from human neonatal fibroblasts and cord blood (CB)-derived CD34+ hematopoietic progenitors using a single polycistronic lentiviral vector containing an excisable cassette encoding the four reprogramming factors Oct4, Klf4, Sox2 and c-myc (OKSM). The ectopic expression of OKSM was fully silenced upon reprogramming in some hiPSC clones and was not reactivated upon differentiation, whereas other hiPSC clones failed to silence the transgene expression, independently of the cell type/tissue origin. When hiPSC were induced to differentiate towards hematopoietic and neural lineages those hiPSC which had silenced OKSM ectopic expression displayed good hematopoietic and early neuroectoderm differentiation potential. In contrast, those hiPSC which failed to switch off OKSM expression were unable to differentiate towards either lineage, suggesting that the residual expression of the reprogramming factors functions as a developmental brake impairing hiPSC differentiation. Successful adenovirus-based Cre-mediated excision of the provirus OKSM cassette in CB-derived CD34+ hiPSC with residual transgene expression resulted in transgene-free hiPSC clones with significantly improved differentiation capacity. Overall, our findings confirm that residual expression of reprogramming factors impairs hiPSC differentiation. PMID:22545141

Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776.

PubMed

Hou, Xiuxiu; Yu, Yunfang; Feng, Jianguo; Wang, Jiafeng; Zheng, Chuanming; Ling, Zhiqiang; Ge, Minghua; Zhu, Xin

2017-03-15

Provirus integration site for Moloney murine leukemia virus 1 (Pim-1) has proved to be an oncogene and it is known that to depress Pim-1 activity may be a novel oncological treatment strategy. SGI-1776, a small molecule, is the first clinically tested inhibitor of the Pim kinase family. Here, we aimed to explore the effect of SGI-1776 on salivary adenoid cystic carcinoma (SACC). Expression of Pim-1 was confirmed in SACC and control tissues by qRT-PCR. After SGI-1776 treatment, the Pim-1 expressions and Pim-1 kinase activity in both SACC-83 and SACC-LM cell lines were measured. Cell proliferation, cell invasion, cell cycle, apoptosis and mitochondrial membrane potential were analyzed. Also, the expression of FOXO3a, p-FOXO3a, RUNX3, Bcl-2, BAD, p-BAD, Bim and p-Bim were detected by Western blot. The results showed that Pim-1 was significantly overexpressed in SACC tissues. SGI-1776 down-regulated the Pim-1 expression, inhibited Pim-1 kinase activity, reduced cell proliferation, decreased invasive ability, increased caspase-3 activity and induced apoptosis, cell cycle arrest and mitochondrial depolarization. Reduced expression was also seen in p-FOXO3a, RUNX3, Bcl-2, p-BAD and p-Bim, whereas no significant changes were observed from FOXO3a, BAD and Bim. These results confirm the pivotal role of Pim-1 in SACC and suggest that targeting Pim-1 kinase signal pathway by SGI-1776 might be a promising therapeutic modality for SACC. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Platelet Serotonin Levels in Pervasive Developmental Disorders and Mental Retardation: Diagnostic Group Differences, Within-Group Distribution, and Behavioral Correlates.

ERIC Educational Resources Information Center

Mulder, Erik J.; Anderson, George M.; Kema, Ido P.; De Bildt, Annelies; Van Lang, Natasja D.J.; Den Boer, Johan A.; Minderaa Ruud B.

2004-01-01

Objective: To investigate group differences, the within-group distributions, and the clinical correlates of platelet serotonin (5-HT) levels in pervasive developmental disorders (PDD). Method: Platelet 5-HT levels were measured in Dutch children and young adults, recruited from 2001 through 2003, with PDD (autism, Asperger's and PDD-not otherwise…

Correlation between the Physical Activity Level and Grade Point Averages of Faculty of Education Students

ERIC Educational Resources Information Center

Imdat, Yarim

2014-01-01

The aim of the study is to find the correlation that exists between physical activity level and grade point averages of faculty of education students. The subjects consist of 359 (172 females and 187 males) under graduate students To determine the physical activity levels of the students in this research, International Physical Activity…

The correlation between albumin levels with 30 days mortality in community acquired pneumonia patients

NASA Astrophysics Data System (ADS)

Damayanti, N.; Abidin, A.; Keliat, E. N.

2018-03-01

The assessment of level severity ofCommunity-Acquired Pneumonia (CAP) patient at the early admission to the hospital is critical because it will determine the severity of the disease and the subsequent management of the plan. Albumin can be used as a biomarker to assess the severity of CAP. To identify the correlation between albumin level at early admission in hospital with 30-day mortality in patients with CAP. It was a cohort study. We had examined of 50 CAP subject with theCURB-65 score (Confusion, Urea, Respiratory rate, Blood pressure, Age >65years), albumin, sputum culture at the early admission at Emergency Room (ER). Then, albumin levels associated with 30-day mortality was assessed using Chi-Square test. Analysis with chi-square test found a significant correlation between albumin level with 30-day mortality (p=0.001) and Relative Risk was 2.376 (95% CI 1.515-3.723). It means that patients with CAP who has severe hypoalbuminemia have a higher risk ofdying in 30 days with 2,376 times more significant than patients with mild to moderate hypoalbuminemia. In conclusion, albumin levels at early admission in the hospital correlate with 30-day mortality in CAP patients.

Bone mineral density in short bowel syndrome: correlation with BMI and serum vitamins C, E and K.

PubMed

Braga, Camila Bitu Moreno; Bizari, Letícia; Suen, Vivian Miguel Marques; Marchini, Júlio Sérgio; Paula, Francisco José Albuquerque de; Cunha, Selma Freire de Carvalho da

2015-06-01

Bone loss has been established as a major extra-intestinal complication of short bowel syndrome (SBS). The purpose of this study was to correlate bone mineral density (BMD) with body mass index (BMI), serum vitamin and mineral levels in patients with SBS. The study was conducted on 13 patients (8 male and 5 female, 54.7 ± 11.4 years) with SBS (residual small bowel length of 10 to 100 cm). We determined the food ingestion, anthropometry, serum levels of vitamins C, A, D, E and K, as well as serum and urinary levels of phosphorus and calcium. BMD was measured by dual-energy x-ray absorptiometry (DXA). Osteopenia and osteoporosis was diagnosed in all but one SBS patient. Serum levels of vitamin D were low in all volunteers. Sixty-one percent of patients had vitamin E deficiency; hypovitaminosis A and C occurred in one subject. BMI and C, E and K vitamin serum levels correlated with T-score of BMD. Osteopenia and osteoporosis were common in SBS patients. There was a correlation between BMD and the serum levels of vitamins C, E and K, an indicative that such vitamins may influence bone health.

Association of circulating sTRAIL and high-sensitivity CRP with type 2 diabetic nephropathy and foot ulcers

PubMed Central

Arık, Hasan Onur; Yalcin, Arzu Didem; Gumuslu, Saadet; Genç, Gizem Esra; Turan, Adil; Sanlioglu, Ahter Dilsad

2013-01-01

Background Hyperglycemia is among the potent factors that may induce or facilitate apoptosis. TNF-Related Apoptosis-Inducing Factor (TRAIL) is known for its apoptotic and immunomodulatory effects that have recently been correlated with diabetes. We examined serum-soluble TRAIL (sTRAIL) and high-sensitivity CRP (hs-CRP) levels and their association with various distinct parameters in type 2 diabetic nephropathy patients with diabetic foot disease. Material/Methods Twenty-two diabetic nephropathy patients with foot ulcers were enrolled in our study. Patients had been diagnosed with diabetes at age 24±10.58 years. Circulating sTRAIL and Hs-CRP levels were compared with control values, and possible correlations were investigated with parameters such as age, Wagner’s Grade (WG), BMI, HbA1c, and creatinine. Results Serum sTRAIL levels were significantly reduced in the patient group, compared to healthy subjects. High HsCRP levels correlated with age, and WGS correlated with BMI and creatinine levels. Conclusions Significantly suppressed sTRAIL levels in diabetic nephropathy patients with foot ulcers compared to healthy controls suggest a protective role for TRAIL in the disease setting. PMID:23986130

Estimation and correlation of salivary thiocyanate levels in periodontally healthy subjects, smokers, nonsmokers, and gutka-chewers with chronic periodontitis.

PubMed

Hegde, Shashikanth; Chatterjee, Elashri; Rajesh, K S; Kumar, M S Arun

2016-01-01

This study was conducted to estimate and correlate salivary thiocyanate (SCN) levels in periodontally healthy subjects, smokers, nonsmokers, and gutka-chewers with chronic periodontitis. The study population consisted of 40 systemically healthy subjects in the age group of 18-55 years that was further divided into four groups: Control, smokers, nonsmokers, and gutka-chewers with chronic periodontitis. Gingival index (GI) (Loe and Silness-1963), probing depth (PD), clinical attachment loss was assessed. Estimation of SCN was performed by ultraviolet spectrophotometer at 447 nm wavelength. Statistical analysis was performed using the one-way ANOVAs Welch test and Pearson's correlation test using SPSS version 17 software. Results showed statistically significant increase in SCN levels in smokers as compared to gutka-chewers with chronic periodontitis, control, and nonsmokers with chronic periodontitis subjects. Significantly higher PD and loss of attachment were seen in smokers group compared with other groups. A negative correlation observed between the GI and thiocyanate levels. The present study revealed a significant increase in SCN levels in smokers with periodontitis as compared to nonsmokers.

Comparison of two correlated ROC curves at a given specificity or sensitivity level

PubMed Central

Bantis, Leonidas E.; Feng, Ziding

2017-01-01

The receiver operating characteristic (ROC) curve is the most popular statistical tool for evaluating the discriminatory capability of a given continuous biomarker. The need to compare two correlated ROC curves arises when individuals are measured with two biomarkers, which induces paired and thus correlated measurements. Many researchers have focused on comparing two correlated ROC curves in terms of the area under the curve (AUC), which summarizes the overall performance of the marker. However, particular values of specificity may be of interest. We focus on comparing two correlated ROC curves at a given specificity level. We propose parametric approaches, transformations to normality, and nonparametric kernel-based approaches. Our methods can be straightforwardly extended for inference in terms of ROC−1(t). This is of particular interest for comparing the accuracy of two correlated biomarkers at a given sensitivity level. Extensions also involve inference for the AUC and accommodating covariates. We evaluate the robustness of our techniques through simulations, compare to other known approaches and present a real data application involving prostate cancer screening. PMID:27324068

Cerebrospinal fluid and plasma C-reactive protein and aggression in personality-disordered subjects: a pilot study.

PubMed

Coccaro, Emil F; Lee, Royce; Coussons-Read, Mary

2015-02-01

C-reactive protein (CRP), in the plasma, serves as a marker of systemic inflammation and has been shown to correlate with history of actual aggressive behavior, and as a personality trait of aggressive tendency, in human subjects. This pilot study was conducted to determine if plasma CRP levels are correlated with cerebrospinal fluid levels (CSF CRP) and if CSF CRP also correlates with aggression. If so, this would suggest a role for central inflammatory processes in human aggression. Both plasma and basal lumbar CSF samples were obtained from 17 subjects with DSM-5 personality disorder and assayed for CRP. Plasma and CSF CRP levels were correlated (r = 0.65, p = 0.005) and each correlated with aggression (Plasma: r = 0.53, p = 0.029; CSF: r = 0.84, p < 0.001). When considered simultaneously, CSF CRP, but not plasma CRP, uniquely correlated with aggression. No relationship was seen with other measures of psychopathology. These data suggest a positive relationship between central nervous system CRP and aggression in humans.

Comparative assessment of salivary cotinine level and psychological dependence among tobacco users

PubMed Central

Patel, Vrushali D.; Jadhav, Kiran B.; Shah, Vandana S.; Gupta, Nidhi D.

2017-01-01

Background: The aim of the study was to assess the correlation between salivary cotinine level and psychological dependence measured through Fagerstrom test for nicotine dependence (FTND) questionnaire among tobacco users. Materials and Methods: This was a cross-sectional study, conducted on tobacco users. Participants with the present habit of tobacco chewing and smoking above the age of 16 years were included in the study. A standard questionnaire form of FTND revised version for smoking and smokeless form of tobacco were given to each participant. Each participant was asked to answer the questions as per their experience of tobacco consumption and calculate the total point score or FTND score. Salivary cotinine level assessment was done using commercial available NicAlert kit. Results: When salivary cotinine level was correlated with different variables of both groups, it was observed that weak correlation between salivary cotinine level and FTND scoring in smokers group (r = 0.083) and also in smokeless group (r = 0.081). When two groups were compared for salivary cotinine level, statistically significant difference (P = 0.021) was observed, with smokeless group showing high level of salivary cotinine level as compared to smokers group. Conclusion: Salivary cotinine and psychological dependence through FTND scoring are not strongly correlating with each other. This indicates that dependence over tobacco is a separate phenomenon and cannot be assessed by salivary cotinine level. It is well accepted that salivary cotinine level is influenced by age of individual, duration of habit, and type of tobacco consumption. PMID:28584536

Regular aerobic exercise correlates with reduced anxiety and incresed levels of irisin in brain and white adipose tissue.

PubMed

Uysal, Nazan; Yuksel, Oguz; Kizildag, Servet; Yuce, Zeynep; Gumus, Hikmet; Karakilic, Aslı; Guvendi, Guven; Koc, Basar; Kandis, Sevim; Ates, Mehmet

2018-05-29

We have recently shown that regular voluntary aerobic exercised rats have low levels of anxiety. Irisin is an exercise-induced myokine that is produced by many tissues; and the role it plays in anxiolytic behavior is unknown. In this study we aimed to investigate the correlation between anxiety like behavior and irisin levels following regular voluntary aerobic exercise in male mice. We've have shown that anxiety levels decreased in exercised mice, while irisin levels increased in the brain, brown adipose tissue, white adipose tissue, kidney, and pancreas tissues. No significant difference of irisin levels in the liver, muscle and serum were detected in the exercise group, when compared to controls. In addition, there was a strong positive correlation between brain irisin levels and activity in middle area of open field test and in the open arms of elevated plus maze test; both which are indicators of low anxiety levels. Our results suggest that decrease in anxiolytic behavior due to regular voluntary exercise may be associated with locally produced brain irisin. White adipose tissue irisin levels also correlated very strongly with low anxiety. However, no serum irisin increase was detected, ruling out the possibility of increased peripheral irisin levels affecting the brain via the bloodstream. Further research is necessary to explain the mechanisms of which peripheral and central irisin effects anxiety and the brain region affected. Copyright © 2018 Elsevier B.V. All rights reserved.

Subjectively and objectively assessed social and physical environmental correlates of preschoolers' accelerometer-based physical activity.

PubMed

Eichinger, Michael; Schneider, Sven; De Bock, Freia

2017-11-06

Overweight and low levels of physical activity (PA) in preschoolers are major public health concerns. However, to date only few studies have investigated subjective and objective correlates of PA across different socioecological domains in preschoolers. We therefore simultaneously investigate associations between preschoolers' objectively measured leisure-time PA and a comprehensive set of subjective and objective potential PA correlates across the behavioral, social and physical environmental domains on both family- and community-level. In this cross-sectional study time spent in moderate-to-vigorous PA (MVPA) and total PA (TPA) were measured by combined accelerometry and heart rate monitoring in 735 3-6 year-old children from 52 preschools in Southern Germany. Family- and community-level potential correlates of PA from different domains (behavioral, social and physical environmental) were subjectively (i.e. by parent proxy-report) and objectively assessed. Their associations with PA on weekend days and weekday afternoons were tested by covariate-adjusted multilevel regression models. While none of the objective social and physical environmental factors showed associations with PA, subjective parental traffic safety perceptions were positively associated with MVPA and TPA on weekends. Also, preschoolers' participation in organized sports was positively correlated with MVPA (on weekends) and TPA (both on weekends and weekday afternoons). Subjective traffic safety perceptions and participation in organized sports, an indicator and a result of parental support towards PA - i.e. subjective parental perceptions of environmental factors and family-level correlates which are more proximal to preschoolers - might be more central to PA in preschool age than objectively assessed community-level environmental features which tend to be more distal correlates. If replicable, targeting parental perceptions of environmental factors and parental support for PA in preschool age might be powerful leverages for public health policy.

A Disposable Tear Glucose Biosensor-Part 4: Preliminary Animal Model Study Assessing Efficacy, Safety, and Feasibility.

PubMed

La Belle, Jeffrey T; Engelschall, Erica; Lan, Kenneth; Shah, Pankti; Saez, Neil; Maxwell, Stephanie; Adamson, Teagan; Abou-Eid, Michelle; McAferty, Kenyon; Patel, Dharmendra R; Cook, Curtiss B

2014-01-01

A prototype tear glucose (TG) sensor was tested in New Zealand white rabbits to assess eye irritation, blood glucose (BG) and TG lag time, and correlation with BG. A total of 4 animals were used. Eye irritation was monitored by Lissamine green dye and analyzed using image analysis software. Lag time was correlated with an oral glucose load while recording TG and BG readings. Correlation between TG and BG were plotted against one another to form a correlation diagram, using a Yellow Springs Instrument (YSI) and self-monitoring of blood glucose as the reference measurements. Finally, TG levels were calculated using analytically derived expressions. From repeated testing carried over the course of 12 months, little to no eye irritation was detected. TG fluctuations over time visually appeared to trace the same pattern as BG with an average lag times of 13 minutes. TG levels calculated from the device current measurements ranged from 4 to 20 mg/dL and correlated linearly with BG levels of 75-160 mg/dL (TG = 0.1723 BG = 7.9448 mg/dL; R 2 = .7544). The first steps were taken toward preliminary development of a sensor for self-monitoring of tear glucose (SMTG). No conjunctival irritation in any of the animals was noted. Lag time between TG and BG was found to be noticeable, but a quantitative modeling to correlate lag time in this study is unnecessary. Measured currents from the sensors and the calculated TG showed promising correlation to BG levels. Previous analytical bench marking showed BG and TG levels consistent with other literature. © 2014 Diabetes Technology Society.

Contribution of the blood glucose level in perinatal asphyxia.

PubMed

Basu, Pallab; Som, Sabbasachi; Choudhuri, Nabendu; Das, Harendranath

2009-07-01

This is a comparative study between 60 asphyxiated newborns (cases) and 60 normal neonates (controls) in respect of their plasma glucose and uric acid levels and also their clinical and neurological status. The mean plasma glucose level was significantly lower (35.1 +/- 11.4 mg/dl vs. 56.9 +/- 5.5 mg/dl; P < 0.001) and the mean serum uric acid level was higher (8.0 +/- 1.2 mg/dl vs. 4.5 +/- 0.83 mg/dl; P < 0.001) in the asphyxiated group when compared to the controls. Within the perinatal asphyxia group, the plasma glucose level and Apgar scores showed a significant positive linear correlation (r = 0.740, P < 0.001), whereas a significant negative linear correlation was observed between the glucose level and different stages of hypoxic ischemic encephalopathy (HIE) (r = -0.875, P < 0.001). Although a strong positive linear correlation was found between uric acid and HIE stages (r = 0.734, P < or = 0.001), the linear correlation between uric acid and Apgar scores (r = -0.885, P < 0.001) and uric acid and the plasma glucose level (r = -0.725, P < 0.001) were found to be significantly negative among the cases. The severity of encephalopathy and cellular damage varies with the severity of hypoglycemia.

Relationships between oral MUC1 expression and salivary hormones in burning mouth syndrome.

PubMed

Kang, Jeong-Hyun; Kim, Yoon-Young; Chang, Ji-Youn; Kho, Hong-Seop

2017-06-01

To investigate possible relationships among oral mucosal epithelial MUC1 expression, salivary female gonadal hormones and stress markers, and clinical characteristics in patients with burning mouth syndrome (BMS). Thirty post-menopausal female patients with BMS (60.0±5.0 years) were included. Clinical and psychological evaluations were performed and the expression level of oral mucosal epithelial MUC1 was analyzed. The levels of cortisol, dehydroepiandrosterone (DHEA), 17β-estradiol, progesterone, chromogranin A, and blood contamination were determined from unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) samples. Salivary progesterone level had significant positive correlations with oral mucosal epithelial MUC1 expression level and with salivary cortisol and DHEA levels. The salivary level of 17β-estradiol showed significant positive correlations with period of symptom duration, severity of effects of oral complaints on daily life, and results from psychological evaluations. Cortisol level in UWS and cortisol/DHEA ratio in UWS and SWS had negative correlations with severity of oral burning sensation significantly. The severity of taste disturbance had positive correlations with results from psychometry significantly. Dysregulated psychoendocrinological interactions might affect oral mucosal MUC1 expression and severity of oral burning sensation in post-menopausal BMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Plasma Periostin Levels Are Increased in Chinese Subjects with Obesity and Type 2 Diabetes and Are Positively Correlated with Glucose and Lipid Parameters.

PubMed

Luo, Yuanyuan; Qu, Hua; Wang, Hang; Wei, Huili; Wu, Jing; Duan, Yang; Liu, Dan; Deng, Huacong

2016-01-01

The purpose of this study is to examine the relations among plasma periostin, glucose and lipid metabolism, insulin resistance and inflammation in Chinese patients with obesity (OB), and type 2 diabetes mellitus (T2DM). Plasma periostin levels in the T2DM group were significantly higher than the NGT group (P < 0.01). Patients with both OB and T2DM had the highest periostin levels. Correlation analysis showed that plasma periostin levels were positively correlated with weight, waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), fasting plasma glucose (FPG), 2 h postchallenge plasma glucose (2 h PG), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), TNF-α, and IL-6 (P < 0.05 or 0.001) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (P < 0.001). Multiple linear regression analysis showed that TG, TNF-α, and HOMA-IR were independent related factors in influencing the levels of plasma periostin (P < 0.001). These results suggested that Chinese patients with obesity and T2DM had significantly higher plasma periostin levels. Plasma periostin levels were strongly associated with plasma TG, chronic inflammation, and insulin resistance.

The Croton megalobotrys Müll Arg. traditional medicine in HIV/AIDS management: Documentation of patient use, in vitro activation of latent HIV-1 provirus, and isolation of active phorbol esters.

PubMed

Tietjen, Ian; Ngwenya, Barbara N; Fotso, Ghislain; Williams, David E; Simonambango, Sundana; Ngadjui, Bonaventure T; Andersen, Raymond J; Brockman, Mark A; Brumme, Zabrina L; Andrae-Marobela, Kerstin

2018-01-30

Current HIV therapies do not act on latent cellular HIV reservoirs; hence they are not curative. While experimental latency reversal agents (LRAs) can promote HIV expression in these cells, thereby exposing them to immune recognition, existing LRAs exhibit limited clinical efficacy and high toxicity. We previously described a traditional 3-step medicinal plant regimen used for HIV/AIDS management in Northern Botswana that inhibits HIV replication in vitro. Here we describe use of one component of the regimen that additionally contains novel phorbol esters possessing HIV latency-reversal properties. We sought to document experiences of traditional medicine users, assess the ability of traditional medicine components to reverse HIV latency in vitro, and identify pure compounds that conferred these activities. Experiences of two HIV-positive traditional medicine users (patients) were documented using qualitative interview techniques. Latency reversal activity was assessed using a cell-based model (J-Lat, clone 9.2). Crude plant extracts were fractionated by open column chromatography and reverse-phase HPLC. Compound structures were elucidated using NMR spectroscopy and mass spectrometry. Patients using the 3-step regimen reported improved health over several years despite no reported use of standard HIV therapies. Crude extracts from Croton megalobotrys Müll Arg. ("Mukungulu"), the third component of the 3-step regimen, induced HIV expression in J-lat cells to levels comparable to the known LRA prostratin. Co-incubation with known LRAs and pharmacological inhibitors indicated that the active agent(s) in C. megalobotrys were likely to be protein kinase C (PKC) activator(s). Consistent with these results, two novel phorbol esters (Namushen 1 and 2) were isolated as abundant components of C. megalobotrys and were sufficient to confer HIV latency reversal in vitro. We have identified novel LRAs of the phorbol ester class from a medicinal plant used in HIV/AIDS management. These data, combined with self-reported health effects and previously-described in vitro anti-HIV activities of this traditional 3-step regimen, support the utility of longitudinal observational studies of patients undergoing this regimen to quantify its effects on plasma viral loads and HIV reservoir size in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Metals in tissues of migrant semipalmated sandpipers (Calidris pusilla) from Delaware Bay, New Jersey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burger, Joanna, E-mail: burger@biology.rutgers.edu; Environmental and Occupational Health Sciences Institute; Gochfeld, Michael

2014-08-15

There is an abundance of field data on levels of metals for feathers in a variety of birds, but relatively few data for tissues, especially for migrant species from one location. In this paper we examine the levels of arsenic, cadmium, chromium, lead, manganese, mercury and selenium in muscle, liver, brain, fat and breast feathers from migrant semipalmated sandpipers (Calidris pusilla) collected from Delaware Bay, New Jersey. Our primary objectives were to (1) examine variation as a function of tissue, (2) determine the relationship of metal levels among tissues, and (3) determine the selenium:mercury molar ratio in different tissues sincemore » selenium is thought to protect against mercury toxicity. We were also interested in whether the large physiological changes that occur while shorebirds are on Delaware Bay (e.g. large weight gains in 2–3 weeks) affected metal levels, especially in the brain. There were significant differences among tissues for all metals. The brain had the lowest levels of arsenic and cadmium, and was tied for the lowest levels of all other metals except lead and selenium. Correlations among metals in tissues were varied, with mercury levels being positively correlated for muscle and brain, and for liver and breast feathers. Weights vary among individuals at the Delaware Bay stopover, as they arrive light, and gain weight prior to migration north. Bird weight and levels of arsenic, cadmium, and selenium in the brain were negatively correlated, while they were positively correlated for lead. There was no positive correlation for mercury in the brain as a function of body weight. The selenium:mercury molar ratio varied significantly among tissues, with brain (ratio of 141) and fat having the highest ratios, and liver and breast feathers having the lowest. In all cases, the ratio was above 21, suggesting the potential for amelioration of mercury toxicity. - Highlights: • Metal levels were examined for migrant semipalmated sandpipers. • There were differences in metal levels among internal tissues. • Brain had the lowest levels of arsenic and cadmium. • Bird weight and arsenic, cadmium, and selenium levels in brain were negatively correlated. • Selenium:mercury molar ratio varied among tissues (21–141, suggesting protection)« less

Serum levels of natriuretic peptides in children with various types of loading conditions.

PubMed

Eerola, Anneli; Jokinen, Eero; Pihkala, Jaana I

2009-06-01

To evaluate the influence of volume overload of the left (LV) and right ventricle (RV) and pressure overload of LV and restrictive physiology on levels of N-terminal proatriopeptide (ANPN) and N-terminal pro-brain natriuretic peptide (NT-proBNP). We studied 41 children with atrial septal defect (ASD), 35 with patent ductus arteriosus (PDA), 27 with coarctation of the aorta (CoA), 25 with restrictive physiology caused by Mulibrey nanism, and 64 control children. We measured serum concentrations of natriuretic peptides and evaluated ventricular size and function with echocardiography. In patients with ASD, PDA, and Mulibrey nanism, levels of both ANPN and NT-proBNP were higher than in controls but in children with CoA, only ANPN levels were higher. ANPN levels correlated with RV size in ASD and NT-proBNP levels with LV size in PDA. In patients with restriction, NT-proBNP levels correlated negatively with LV size. Correlation between echo measurements and levels of natriuretic peptides varied according to loading condition. Measurement of natriuretic peptide levels provides a supplemental method for non-invasive haemodynamic evaluation of children's heart disease.

The western pond turtle (Clemmys marmorata) in the Mojave River, California, USA: highly adapted survivor or tenuous relict?

USGS Publications Warehouse

Lovich, J.; Meyer, K.

2002-01-01

During Late 1970 and early 1971, 229 woodcock (Philohela minor) were collected from 23 Eastern and Midwestern States. Analyses for chlorinated hydrocarbons and mercury in these migratory birds showed generally low levels which are not considered dangerous to human consumers. In this survey, Louisiana woodcock had lower residues of heptachlor epoxide and DDE than those tested in a 1965 survey. PCB levels, however, may have increased. Mirex levels were greatest in Mississipi and Louisiana woodcock. Pooling of birds and averaging of individually analyzed birds did not provide equivalent estimates of equivalent residues; pool values tended to be larger and more variable. Levels of six chlorinated hydrocarbons and mercury were negatively correlated with the latitude of the collection site. However, this relationship seemed weakest for PCB's. Among eight chemical residues, PCB levels were most often correlated with levels of the other seven. Levels of chlorinated hydrocarbons in wings were correlated with levels in breast muscle and in carcass; however, mean levels of certain residues differed significantly among wing, muscle, and carcass even when compared on a lipid basis.

Assessing skeletal maturity by using blood spot insulin-like growth factor I (IGF-I) testing.

PubMed

Masoud, Mohamed; Masoud, Ibrahim; Kent, Ralph L; Gowharji, Nour; Cohen, Laurie E

2008-08-01

Accurate determination of skeletal maturity and remaining growth is crucial to many orthodontic, orthognathic, and dental-implant timing decisions. Cervical vertebral stages and hand-wrist radiographs are currently used to identify peak mandibular bone growth. These are highly subjective techniques that not only involve radiographic exposure but also lack the ability to determine the intensity of the growth spurt and the end of growth. Insulin-like growth factor I (IGF-I) is a circulating growth hormone-dependent factor whose level correlates with sexual maturity; it is used to diagnose growth hormone deficiency and excess. We hypothesized that IGF-I levels would also correlate with cervical skeletal maturity and would be highest at the cervical stages that correspond to the greatest amount of facial growth. We measured mean blood spot IGF-I levels in a cross-sectional study of 83 patients (44 female, 39 male) on recall to begin orthodontic treatment, in active treatment, or in posttreatment follow-up. Mean blood spot IGF-I levels were significantly higher in the late pubertal stages than in the prepubertal, early pubertal, and postpubertal stages. Linear correlation showed that IGF-I levels had a significant positive correlation with cervical skeletal maturity from the prepubertal to the late pubertal stages, and a significant negative correlation from the late pubertal to the postpubertal stages. In the postpubertal stage, IGF-I levels had a negative linear correlation with increasing time since the onset of puberty and with chronological age. Blood spot IGF-I could be used as a skeletal maturity indicator and might be useful in detecting residual mandibular growth in young adults.

An fMRI study of joint action–varying levels of cooperation correlates with activity in control networks

PubMed Central

Chaminade, Thierry; Marchant, Jennifer L.; Kilner, James; Frith, Christopher D.

2012-01-01

As social agents, humans continually interact with the people around them. Here, motor cooperation was investigated using a paradigm in which pairs of participants, one being scanned with fMRI, jointly controlled a visually presented object with joystick movements. The object oscillated dynamically along two dimensions, color and width of gratings, corresponding to the two cardinal directions of joystick movements. While the overall control of each participant on the object was kept constant, the amount of cooperation along the two dimensions varied along four levels, from no (each participant controlled one dimension exclusively) to full (each participant controlled half of each dimension) cooperation. Increasing cooperation correlated with BOLD signal in the left parietal operculum and anterior cingulate cortex (ACC), while decreasing cooperation correlated with activity in the right inferior frontal and superior temporal gyri, the intraparietal sulci and inferior temporal gyri bilaterally, and the dorsomedial prefrontal cortex. As joint performance improved with the level of cooperation, we assessed the brain responses correlating with behavior, and found that activity in most of the areas associated with levels of cooperation also correlated with the joint performance. The only brain area found exclusively in the negative correlation with cooperation was in the dorso medial frontal cortex, involved in monitoring action outcome. Given the cluster location and condition-related signal change, we propose that this region monitored actions to extract the level of cooperation in order to optimize the joint response. Our results, therefore, indicate that, in the current experimental paradigm involving joint control of a visually presented object with joystick movements, the level of cooperation affected brain networks involved in action control, but not mentalizing. PMID:22715326

Effect of Flunarizine on Serum Glutamate Levels and its Correlation with Headache Intensity in Chronic Tension-Type Headache Patients.

PubMed

Surbakti, Khairul Putra; Sjahrir, Hasan; Juwita-Sembiring, Rosita; Mutiara, Erna

2017-10-15

Some of the excitatory neurotransmitters including glutamate have been suggested to be involved in headache pathophysiology. To our knowledge, there is a lack of publication about flunarizine efficacy in chronic tension-type headache (CTTH) treatments and the roles of glutamate in CTTH pathophysiology. This study aimed to investigate the flunarizine effect on serum levels of glutamate and its correlation with headache intensity based on the Numeric Rating Scale for pain (NRS) scores in CTTH patients. In a prospective randomised, double-blind study with pre and post-test design, seventy-three CTTH patients were randomly allocated with flunarizine 5 mg, flunarizine 10 mg and amitriptyline 12.5 mg groups. The serum levels of glutamate and NRS scores were measured before and after 15-day treatment. Flunarizine 5 mg was more effective than flunarizine 10 mg and amitriptyline 12.5 mg in reducing serum glutamate levels, whereas amitriptyline 12.5 mg was the most effective in reducing headache intensity. There was found nonsignificant, but very weak negative correlation between headache intensity and serum glutamate levels after flunarizine 5 mg administration (r = -0.062; P = 0.385), nonsignificant very weak negative correlation after flunarizine 10 mg administration (r = -0.007; P = 0.488) and there was found a significant moderate positive correlation (r = 0.508; P = 0.007) between headache intensity and serum glutamate levels after amitriptyline 12.5 mg administration. Since there was no significant correlation found between serum glutamate and headache intensity after treatment with flunarizine, it is suggested that decreasing of headache intensity after flunarizine treatment occurred not through glutamate pathways in CTTH patients.

Decreased Serum Hepcidin Concentration Correlates with Brain Iron Deposition in Patients with HBV-Related Cirrhosis

PubMed Central

Liu, Jian-Ying; He, Yi-Feng; Dai, Zhi; Chen, Cai-Zhong; Cheng, Wei-Zhong; Zhou, Jian; Wang, Xin

2013-01-01

Purpose Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level. Methods Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters. Results Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients. Conclusions Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential. PMID:23776499

Advanced glycation end products (AGEs) and its receptors in the pathogenesis of hyperthyroidism.

PubMed

Caspar-Bell, Gudrun; Dhar, Indu; Prasad, Kailash

2016-03-01

Oxidative stress has been implicated in the pathogenesis of hyperthyroidism and its complications. Interaction of advanced glycation end products (AGEs) with receptor RAGE (receptor for AGEs) generates reactive oxygen species. Soluble receptor for AGEs (sRAGE) competes with RAGE for binding with AGEs and attenuates the generation of ROS. Low levels sRAGE and high levels AGEs would generate more ROS leading to hyperthyroidism and its complications. The objectives are to determine if levels of serum sRAGE are low and the levels of AGEs and AGEs/sRAGE are high in patients with hyperthyroidism. The study subjects comprised of 33 patients with hyperthyroidism and 20 controls. Levels of serum sRAGE were lower, while that of AGEs and AGEs/sRAGE were higher in patients compared to controls, being significant only for sRAGE and AGEs/sRAGE. When the levels of sRAGE, AGEs, and AGEs/sRAGE were assessed for hyperthyroidism associated with different diseases, the levels of sRAGE were lower in Hashimoto disease, and levels of AGEs were higher in patients with Graves' disease compared to control. The levels of AGEs/sRAGE were elevated in an all except patients with Hashimoto disease. The levels of AGEs, sRAGE, or AGEs/RAGE were not correlated with age, weight, and blood pressures except systolic pressure which was inversely correlated with sRAGE. The levels of sRAGE were negatively correlated with AGEs and AGEs/sRAGE. The levels of AGEs/sRAGE were positively correlated with AGEs. In conclusion, low levels of sRAGE, and high levels of AGEs and AGEs/sRAGE are risk biomarkers in the pathogenesis hyperthyroidism and its complications.

Phenytoin intoxication with no symptoms correlated with serum drug level: a case study.

PubMed

Avcil, Mucahit; Duman, Ali; Turkdogan, Kenan Ahmet; Kapci, Mucahit; Akoz, Ayhan; Canakci, Selcuk Eren; Ozluer, Yunus Emre

2015-01-01

In high-dose intake of phenytoin, which is used frequently to treat epilepsy, nystagmus, diplopia, nausea-vomiting, lethargy, confusion, seizure, and coma can be observed. In recent studies on phenytoin intoxication, in which seizure and coma were observed in drug levels greater than 50 ug/mL. The serum phenytoin level of a patient, who consumed approximately 100 pcs of 100 mg phenytoin tablets in an effort to commit suicide, and who had no pathological finding in her neurologic examination, was 124 ug/mL. High drug level and the absence of toxic effect (or the absence of toxic effect correlated with the drug level) indicates that cytochrome P450 is functioning, but there can be a mutation in the MDR1 gene. In our case study, we report on phenytoin intoxication in a patient having a high level of phenytoin but no symptoms correlated with serum drug level, as supported by the findings in the literature.

An empirical test of Rogers' original and revised theory of correlates in adolescents.

PubMed

Yarcheski, A; Mahon, N E

1991-12-01

The purpose of this study was to examine Rogers' original and revised theory of correlates in adolescents. The correlates were measured by Perceived Field Motion, Human Field Rhythms, Creativity, Sentience, Fast Tempo, and Waking Periods. The original theory was tested with data obtained from samples of early (n = 116), middle (n = 116), and late (n = 116) adolescents. The revised theory was tested in a fourth selectively combined sample of adolescents, aged 12 to 21 (n = 89). Data were collected in classroom settings. Although the findings did not support either theory, they did indicate that: (1) four of the six correlates studied performed as correlates when examined in three discrete phases of adolescence, as determined by chronological age, (2) the means of the individual correlates increased slightly in frequency levels developmentally, and (3) the correlates emerged at different frequency levels when examined in adolescents, aged 12 to 21.

Elevated lead levels from e-waste exposure are linked to decreased olfactory memory in children.

PubMed

Zhang, Bo; Huo, Xia; Xu, Long; Cheng, Zhiheng; Cong, Xiaowei; Lu, Xueling; Xu, Xijin

2017-12-01

Lead (Pb) is a developmental neurotoxicant and can cause abnormal development of the nervous system in children. Hence, the aim of this study was to investigate the effect of Pb exposure on child olfactory memory by correlating the blood Pb levels of children in Guiyu with olfactory memory tests. We recruited 61 preschool children, 4- to 7-years of age, from Guiyu and 57 children from Haojiang. The mean blood Pb level of Guiyu children was 9.40 μg/dL, significantly higher than the 5.04 μg/dL mean blood Pb level of Haojiang children. In addition, approximately 23% of Guiyu children had blood Pb levels exceeding 10.00 μg/dL. The correlation analysis showed that blood Pb levels in children highly correlated with e-waste contact (r s  = 0.393). Moreover, the mean concentration of serum BDNF in Guiyu children (35.91 ng/ml) was higher than for Haojiang (28.10 ng/ml) and was positively correlated with blood Pb levels. Both item and source olfactory memory tests at 15 min, 5 h and 24 h after odor exposure showed that scores were lower in Guiyu children indicative of reduced olfactory memory in Guiyu children. Olfactory memory tests scores negatively correlated with blood Pb and serum BDNF levels, but were positively associated with parental education levels. At the same time, scores of both tests on children in the high blood Pb level group (blood Pb levels > 5.00 μg/dL) were lower than those in the low blood Pb level group (blood Pb levels ≤ 5.00 μg/dL), implying that Pb exposure decreases olfactory memory in children. Our findings suggest that Pb exposure in e-waste recycling and dismantling areas could result in an increase in serum BDNF level and a decrease in child olfactory memory, in addition, BDNF might be involved in olfactory memory impairment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of body mass index on the growth hormone response to provocative testing in short children without growth hormone deficiency.

PubMed

Lee, Jieun; Yoon, Juyoung; Kang, Min Jae; Lee, Young Ah; Lee, Seong Yong; Shin, Choong Ho; Yang, Sei Won

2013-09-01

Obesity and its related factors are known to suppress the secretion of growth hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the peak GH response to provocative testing in short children without GH deficiency. We conducted a retrospective review of medical records of 88 children (2-15 yr old) whose height was less than 3 percentile for one's age and sex, with normal results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF-1 level were measured. Univariate analysis showed that the BMI standard deviation score (SDS) correlated negatively with the natural log (ln) of the peak stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with ln peak GH level induced by clonidine but not by dopamine. In stepwise multivariate regression analysis, BMI SDS was the only significant predictor of ln peak GH level in the combination of tests and the clonidine test, but not in the dopamine test. In children without GH deficiency, BMI SDS correlates negatively with the peak GH level. BMI SDS should be included in the analysis of the results of GH provocation tests, especially tests with clonidine.