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Laser Microdissection Unravels Cell-Type-Specific Transcription in Arbuscular Mycorrhizal Roots, Including CAAT-Box Transcription Factor Gene Expression Correlating with Fungal Contact and Spread1[W  

PubMed Central

Arbuscular mycorrhizae (AM) are the most widespread symbioses on Earth, promoting nutrient supply of most terrestrial plant species. To unravel gene expression in defined stages of Medicago truncatula root colonization by AM fungi, we here combined genome-wide transcriptome profiling based on whole mycorrhizal roots with real-time reverse transcription-PCR experiments that relied on characteristic cell types obtained via laser microdissection. Our genome-wide approach delivered a core set of 512 genes significantly activated by the two mycorrhizal fungi Glomus intraradices and Glomus mossae. Focusing on 62 of these genes being related to membrane transport, signaling, and transcriptional regulation, we distinguished whether they are activated in arbuscule-containing or the neighboring cortical cells harboring fungal hyphae. In addition, cortical cells from nonmycorrhizal roots served as a reference for gene expression under noncolonized conditions. Our analysis identified 25 novel arbuscule-specific genes and 37 genes expressed both in the arbuscule-containing and the adjacent cortical cells colonized by fungal hyphae. Among the AM-induced genes specifying transcriptional regulators were two members encoding CAAT-box binding transcription factors (CBFs), designated MtCbf1 and MtCbf2. Promoter analyses demonstrated that both genes were already activated by the first physical contact between the symbionts. Subsequently, and corresponding to our cell-type expression patterns, they were progressively up-regulated in those cortical areas colonized by fungal hyphae, including the arbuscule-containing cells. The encoded CBFs thus represent excellent candidates for regulators that mediate a sequential reprogramming of root tissues during the establishment of an AM symbiosis.

Hogekamp, Claudia; Arndt, Damaris; Pereira, Patricia A.; Becker, Jorg D.; Hohnjec, Natalija; Kuster, Helge



Laser microdissection unravels cell-type-specific transcription in arbuscular mycorrhizal roots, including CAAT-box transcription factor gene expression correlating with fungal contact and spread.  


Arbuscular mycorrhizae (AM) are the most widespread symbioses on Earth, promoting nutrient supply of most terrestrial plant species. To unravel gene expression in defined stages of Medicago truncatula root colonization by AM fungi, we here combined genome-wide transcriptome profiling based on whole mycorrhizal roots with real-time reverse transcription-PCR experiments that relied on characteristic cell types obtained via laser microdissection. Our genome-wide approach delivered a core set of 512 genes significantly activated by the two mycorrhizal fungi Glomus intraradices and Glomus mossae. Focusing on 62 of these genes being related to membrane transport, signaling, and transcriptional regulation, we distinguished whether they are activated in arbuscule-containing or the neighboring cortical cells harboring fungal hyphae. In addition, cortical cells from nonmycorrhizal roots served as a reference for gene expression under noncolonized conditions. Our analysis identified 25 novel arbuscule-specific genes and 37 genes expressed both in the arbuscule-containing and the adjacent cortical cells colonized by fungal hyphae. Among the AM-induced genes specifying transcriptional regulators were two members encoding CAAT-box binding transcription factors (CBFs), designated MtCbf1 and MtCbf2. Promoter analyses demonstrated that both genes were already activated by the first physical contact between the symbionts. Subsequently, and corresponding to our cell-type expression patterns, they were progressively up-regulated in those cortical areas colonized by fungal hyphae, including the arbuscule-containing cells. The encoded CBFs thus represent excellent candidates for regulators that mediate a sequential reprogramming of root tissues during the establishment of an AM symbiosis. PMID:22034628

Hogekamp, Claudia; Arndt, Damaris; Pereira, Patrícia A; Becker, Jörg D; Hohnjec, Natalija; Küster, Helge



Phosphoantigen-reactive Vgamma9Vdelta2 T lymphocytes suppress in vitro human immunodeficiency virus type 1 replication by cell-released antiviral factors including CC chemokines.  


Vgamma9Vdelta2 T lymphocytes are broadly reactive against various intracellular pathogens and display both lytic and proliferative responses to human immunodeficiency virus (HIV)-infected cells. HIV infection of peripheral blood mononuclear cell cultures led to absolute increases in Vgamma9Vdelta2 T cells accompanied by decreased p24 levels. Strong gammadelta T cell activation with nonpeptidic mycobacterial phosphoantigens (TUBAg1 extract or synthetic isopentenyl pyrophosphate) resulted in potent inhibition of HIV replication through soluble released factors. Subsequent analyses showed that phosphoantigen-activated gammadelta T cells produced substantial amounts of beta-chemokines (macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and regulated-on-activation, normal T-cell-expressed and -secreted beta-chemokine [RANTES]), which represent the natural ligand for the CCR5 HIV coreceptor. Accordingly, anti-beta-chemokine antibodies neutralized the inhibition of monocytotropic HIV strains by gammadelta T cell-released factors. Moreover, a T-tropic HIV strain using the CXCR4 coreceptor for virus entry was potently inhibited. Together, these data reveal that phosphoantigen-activated gammadelta T cells are an important source of CC chemokines and may suppress HIV replication through cell-released antiviral factors. PMID:10438380

Poccia, F; Battistini, L; Cipriani, B; Mancino, G; Martini, F; Gougeon, M L; Colizzi, V



A proximal promoter domain containing a homeodomain-binding core motif interacts with multiple transcription factors, including HoxA5 and Phox2 proteins, and critically regulates cell type-specific transcription of the human norepinephrine transporter gene.  


Expression of the norepinephrine transporter (NET), which mediates the reuptake of norepinephrine into presynaptic nerve terminals, is restricted to noradrenergic (NA) neurons. We have demonstrated previously that the 9.0 kb upstream sequences and the first intron residing in the 5' untranslated area are critical for high-level and NA cell-specific transcription. Here, using transient transfection assays, we show that 4.0 kb of the 5' upstream sequences contains sufficient genetic information to drive reporter gene expression in an NA cell type-specific manner. Three functional domains appear to be potentially important for the regulation of human NET (hNET) gene transcription: an upstream enhancer region at -4.0 to -3.1 kb, a proximal domain at -133 to -75 bp, and a middle silencer region between these two domains. DNase I footprinting analysis of the proximal promoter region shows that a subdomain at -128 to -80 bp is protected in a cell-specific manner. We provide evidence that multiple protein factors interact with the proximal promoter domain to critically regulate the transcriptional activity of the hNET gene. In the middle of this proximal subdomain resides a homeodomain (HD)-binding core motif, which interacts with HD factors, including Phox2a and HoxA5, in an NA-specific manner. Cotransfection analyses suggest that HoxA5 and Phox2a may transactivate the hNET gene promoter. Together with previous studies indicating direct activation of dopamine beta-hydroxylase transcription by Phox2a/2b, the present results support a model whereby Phox2 proteins may coordinately regulate the phenotypic specification of NA neurons by activating both NA biosynthetic and reuptake genes. PMID:11923423

Kim, Chun-Hyung; Hwang, Dong-Youn; Park, Jae-Joon; Kim, Kwang-Soo



Type 2 diabetes - risk factors  


Risk factors for Type 2 diabetes; Diabetes risk factors ... You have a higher risk for diabetes if you have any of the following: Age greater than 45 years Diabetes during a previous pregnancy Excess body weight (especially around ...


Risk factors for breast cancer, including occupational exposures.  


The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs ( For breast cancer the following substances have been classified as "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification "probably carcinogenic to humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women. PMID:22953181

Weiderpass, Elisabete; Meo, Margrethe; Vainio, Harri



Vascular Endothelial Growth Factor Receptor3 (VEGFR-3): A Marker of Vascular Tumors with Presumed Lymphatic Differentiation, Including Kaposi's Sarcoma, Kaposiform and Dabska-Type Hemangioendotheliomas, and a Subset of Angiosarcomas  

Microsoft Academic Search

Recently, a novel monoclonal antibody to vascular endothelial growth factor receptor 3 (VEGFR-3), a tyrosine kinase receptor expressed almost exclusively by lymphatic endothelium in the adult, has been shown to react with a small number of cases of Kaposi's sarcoma (KS) and cutaneous lymphangiomas. We sought to extend these studies to a large number of well-characterized vascular neoplasms to evaluate

Andrew L. Folpe; Tanja Veikkola; Reija Valtola; Sharon W. Weiss



[Which factors cause type-1 diabetes?].  


Type 1 diabetes is due to selective and irreversible destruction of pancreatic beta-cells via an autoimmune process. The pathogenetic course is dependent both upon genetic predisposition for the disease and upon one or more environmental factors--eg, viral infection, dietary factors, and exposure to toxins or mental stress. PMID:1408724

Akerblom, H K



Waste ink liquid absorber and inkjet-type recording apparatus including the same  

US Patent & Trademark Office Database

A waste ink liquid absorber for a waste ink tank of an inkjet-type recording apparatus, which includes: an impregnation liquid containing at least one of the following: a water-hardly-soluble resin; a water-soluble resin; or both of a moisturizing agent and a base. The impregnation liquid is included at least a part including a surface coming into contact with a waste ink Also, a waste ink tank having the waste ink liquid absorber, and an inkjet-type recording apparatus having the waste ink liquid absorber.



Factors Associated With Exacerbation of Heart Failure Include Treatment Adherence and Health Literacy Skills  

Microsoft Academic Search

We determined the factors associated with exacerbation of heart failure, using a cohort (n = 192) nested within a randomized trial at a university-affiliated ambulatory practice. Factors associated with emergency or hospital care included left ventricular ejection fraction, hematocrit and serum sodium levels, refill adherence, and the ability to read a prescription label. Refill adherence of <40% was associated with

W Tu; J Wu; D Morrow; F Smith; DC Brater



A Study of Factors Promoting Success in Computer Science Including Gender Differences  

Microsoft Academic Search

This study was conducted to determine factors that promote success in an introductory college computer science course and to determine what, if any, differences appear between genders on those factors. The model included math background, attribution for success\\/failure, self-efficacy, encouragement, comfort level in the course, work style preference, previous programming experience, previous non-programming computer experience, and gender as possible predictive

Brenda Cantwell Wilson



A Study of Factors Promoting Success in Computer Science Including Gender Differences  

Microsoft Academic Search

This study was conducted to determine factors that promote success in an introductory college computer science course and to determine what, if any, differences appear between genders on those factors. The model included math background, attribution for success\\/failure, self-efficacy, encouragement, comfort level in the course, work style preference, previous programming exp- erience, previous non-programming computer experience, and gender as possible

Brenda Cantwell Wilson



Amplification of progenitors in the mammalian telencephalon includes a new radial glial cell type.  


The mechanisms governing the expansion of neuron number in specific brain regions are still poorly understood. Enlarged neuron numbers in different species are often anticipated by increased numbers of progenitors dividing in the subventricular zone. Here we present live imaging analysis of radial glial cells and their progeny in the ventral telencephalon, the region with the largest subventricular zone in the murine brain during neurogenesis. We observe lineage amplification by a new type of progenitor, including bipolar radial glial cells dividing at subapical positions and generating further proliferating progeny. The frequency of this new type of progenitor is increased not only in larger clones of the mouse lateral ganglionic eminence but also in cerebral cortices of gyrated species, and upon inducing gyrification in the murine cerebral cortex. This implies key roles of this new type of radial glia in ontogeny and phylogeny. PMID:23839311

Pilz, Gregor-Alexander; Shitamukai, Atsunori; Reillo, Isabel; Pacary, Emilie; Schwausch, Julia; Stahl, Ronny; Ninkovic, Jovica; Snippert, Hugo J; Clevers, Hans; Godinho, Leanne; Guillemot, Francois; Borrell, Victor; Matsuzaki, Fumio; Götz, Magdalena



Prevalence of occupational asthma in spray painters exposed to several types of isocyanates, including polymethylene polyphenylisocyanate.  


The prevalence of occupational asthma was assessed in four paint shops of a large assembly plant where 51 employees were exposed to several types of isocyanates, including polymethylene polyphenylisocyanate (PPI). Three employees were first referred by their physician for asthma symptoms. A questionnaire was administered to the other 48 employees. Seven of these were suspected of having work-related asthma. Airway hyperexcitability to inhaled histamine was demonstrated in these ten subjects (three referred and seven screened). The diagnosis of occupational asthma was confirmed in six subjects (three referred and three screened) through specific inhalation challenges in the laboratory to a paint system component containing PPI. Thus, the prevalence of occupational asthma was 11.8% in these paint shops using several types of isocyanates, including PPI. PMID:3585565

Séguin, P; Allard, A; Cartier, A; Malo, J L



Active proliferation of different cell types, including lymphocytes, in human atherosclerotic plaques.  

PubMed Central

Cell proliferation, an important mechanism of atherosclerotic plaque growth, occurs among smooth muscle, inflammatory cell, and other cell types. We have identified different topographical patterns of cell proliferation in human carotid plaques, based on cell type. Cell proliferation was determined with an antibody to the proliferating cell nuclear antigen (PCNA), combined with cell type-specific antibodies. Despite low levels of overall proliferative activity, the intima displayed more proliferative activity than the underlying media (1.61 +/- 0.35% in intima versus 0.05 +/- 0.03% in media; P < 0.01). The preponderant proliferative cell type in the intima was the monocyte/macrophage (46.0% of PCNA-positive cells), with a minority being smooth muscle alpha-actin-positive (9.7%), microvascular endothelial (14.3%), and T cells (13.1%). Smooth muscle cells were the dominant proliferating cell type in the media (44.4% of PCNA-positive cells versus 20% endothelial cells, 13.0% monocyte/macrophages, and 14.3% T cells). Within the plaque, foam-cell-rich regions mostly displayed proliferation among macrophages (66.5%), whereas in vascularized fields PCNA positivity was almost equally shared by endothelial cells (23.8%), monocyte/macrophages (26.3%), smooth muscle alpha-actin-positive cells (14.0%), and to a lesser extent, T cells (8.2%). Logistic and linear regression analyses also demonstrated that location in foam-cell-rich regions was a significant predictor of proliferation only among monocyte/macrophages, whereas location in vascularized regions was a good predictor of PCNA positivity among both inflammatory and noninflammatory cells. These different patterns of cell type proliferation suggest possibly different distributions of putative responsible growth regulatory factors in human atherosclerosis. Images Figure 1 Figure 2

Rekhter, M. D.; Gordon, D.



Efficacy assessment of a new clotting factor concentrate in haemophilia A patients, including prophylactic treatment.  


Currently, efficacy of a new factor concentrate is mostly judged by its ability to achieve haemostasis after a bleeding episode. However, in patients on prophylaxis, the effectiveness in preventing bleeds, and thus joint damage, is most important. An albumin-free recombinant factor VIII (FVIII) concentrate was introduced in the Netherlands in 2004. In this study, the efficacy of a new recombinant plasma/albumin-free FVIII concentrate (rAHF-PFM, Advate) was assessed by comparing bleeding frequency and factor consumption before and after switching to the new product, on both prophylactic and on-demand treatment. Eighty-two previously treated haemophilia A patients with at least 1-year clinical follow-up were included in this study. Data on 410 patient-years were analysed, including 165 patient-years on other clotting factor products, and 245 patient-years on the new concentrate. In total, 19 628 368 IU of other factor concentrates were administered, to treat 839 bleeds, including 578 joint bleeds and cover 104 years of prophylactic treatment. For rAHF-PFM 33 082 250 IU FVIII, were used to treat 1144 bleeds, including 734 joint bleeds and cover 175 years of prophylactic treatment. No inhibitors, seroconversions or other serious adverse events were observed. Annual FVIII consumption per kg and annual number of joint bleeds before and after switching to the new albumin-free recombinant factor concentrate were similar in all patients. In conclusion, rAHF-PFM is equally effective as other clotting factor concentrates for prophylactic treatment in severe haemophilia. PMID:19686467

Den Uijl, I; Mauser-Bunschoten, E P; Roosendaal, G; Schutgens, R; Fischer, K



Analytical expressions for the gate utilization factors of passive multiplicity counters including signal build-up  

SciTech Connect

In the realm of nuclear safeguards, passive neutron multiplicity counting using shift register pulse train analysis to nondestructively quantify Pu in product materials is a familiar and widely applied technique. The approach most commonly taken is to construct a neutron detector consisting of {sup 3}He filled cylindrical proportional counters embedded in a high density polyethylene moderator. Fast neutrons from the item enter the moderator and are quickly slowed down, on timescales of the order of 1-2 {micro}s, creating a thermal population which then persists typically for several 10's {micro}s and is sampled by the {sup 3}He detectors. Because the initial transient is of comparatively short duration it has been traditional to treat it as instantaneous and furthermore to approximate the subsequent capture time distribution as exponential in shape. With these approximations simple expressions for the various Gate Utilization Factors (GUFs) can be obtained. These factors represent the proportion of time correlated events i.e. Doubles and Triples signal present in the pulse train that is detected by the coincidence gate structure chosen (predelay and gate width settings of the multiplicity shift register). More complicated expressions can be derived by generalizing the capture time distribution to multiple time components or harmonics typically present in real systems. When it comes to applying passive neutron multiplicity methods to extremely intense (i.e. high emission rate and highly multiplying) neutron sources there is a drive to use detector types with very fast response characteristics in order to cope with the high rates. In addition to short pulse width, detectors with a short capture time profile are also desirable so that a short coincidence gate width can be set in order to reduce the chance or Accidental coincidence signal. In extreme cases, such as might be realized using boron loaded scintillators, the dieaway time may be so short that the build-up (thermalization transient) within the detector cannot be ignored. Another example where signal build-up might be observed is when a {sup 3}He based system is used to track the evolution of the time correlated signal created by a higher multiplying item within a reflective configuration such as the measurement of a spent fuel assembly. In this work we develop expressions for the GUFs which include signal build-up.

Croft, Stephen [Los Alamos National Laboratory; Evans, Louise G [Los Alamos National Laboratory; Schear, Melissa A [Los Alamos National Laboratory



Behavioral factors to include in guidelines for lifelong oral healthiness: an observational study in Japanese adults  

Microsoft Academic Search

BACKGROUND: The aim of this study was to determine which behavioral factors to include in guidelines for the Japanese public to achieve an acceptable level of oral healthiness. The objective was to determine the relationship between oral health related behaviors and symptoms related to oral disease and tooth loss in a Japanese adult community. METHODS: Oral health status and lifestyle

Ichizo Morita; Haruo Nakagaki; Atsushi Toyama; Matsumi Hayashi; Miho Shimozato; Tsuyoshi Watanabe; Shimpei Tohmatsu; Junko Igo; Aubrey Sheiham



Elementary school principals' perceptions of factors that should be included in principal preparation programs  

Microsoft Academic Search

Recent studies and reports that have increased concerns about the state of the principalship, have found that the systems that prepare principals may be inadequate are not surprising. This study examined elementary school principals' perceptions of the importance of specific factors that should be included in principal preparation programs both in colleges of education and in their school districts to

Patricia M Werner



Properties of gene expression including the non-functional binding of transcription factors to DNA  

NASA Astrophysics Data System (ADS)

Many eukaryotic transcription factors bind to DNA sequences with a remarkable lack of specificity. This suggests that non-functional binding between transcription factors and DNA might not have the detrimental effect on regulation one would naively assume results from competition for binding. In fact, if binding to DNA protects transcription factors from degradation, the number and binding affinity of these 'decoy' binding sites should have no influence on the copy number of transcription factors available for regulation. We calculate the influence of adding decoy binding sites on several important aspects of gene expression including the noise, the time to reach steady state, and bimodal switch rates. Analyzing these effects could shed some light on how a gene functions in the 'dressed' environment of a genomic background.

Burger, Anat; Walczak, Aleksandra; Wolynes, Peter



A Configuration and Control Method of DC Loop Type Distribution System Including Distributed Generators  

NASA Astrophysics Data System (ADS)

In the large-scale factories like ironworks, many power electronic inverter loads exist, and these inverter loads are connected into ac systems by using rectifiers. On the other hand, DGs (Distributed Generators) such as photovoltaic generators and fuel cells, or ESSs (Energy Storage Systems) such as secondary batteries and SMESs (Superconducting Magnetic Energy Strages), which are dc power sources will be introduced to distribution systems more and more. These are connected into ac systems by using inverters. Therefore, it is expected that some countermeasures to achieve a dc distribution system which can reduce power losses due to rectifiers and inverters, should be developed. In this paper, a dc loop type distribution system is proposed as one of the new dc distribution system configurations. The calculation results of power losses for the dc loop type distribution system are compared with those for an ac distribution system. Moreover, this paper shows configurations and simulation results of the inverter, bi-directional rectifier and PFC (Power Factor Corrector) used in this system.

Saisho, Masaki; Ise, Toshifumi; Tsuji, Kiichiro


Ureteric bud cells secrete multiple factors, including bFGF, which rescue renal progenitors from apoptosis.  


Kidney development requires reciprocal interactions between the ureteric bud and the metanephrogenic mesenchyme. Whereas survival of mesenchyme and development of nephrons from mesenchymal cells depends on signals from the invading ureteric bud, growth of the ureteric bud depends on signals from the mesenchyme. This codependency makes it difficult to identify molecules expressed by the ureteric bud that regulate mesenchymal growth. To determine how the ureteric bud signals the mesenchyme, we previously isolated ureteric bud cell lines (UB cells). These cells secrete soluble factors which rescue the mesenchyme from apoptosis. We now report that four heparin binding factors mediate this growth activity. One of these is basic fibroblast growth factor (bFGF), which is synthesized by the ureteric bud when penetrating the mesenchyme. bFGF rescues three types of progenitors found in the mesenchyme: precursors of tubular epithelia, precursors of capillaries, and cells that regulate growth of the ureteric bud. These data suggest that the ureteric bud regulates the number of epithelia and vascular precursors that generate nephrons by secreting bFGF and other soluble factors. PMID:9374839

Barasch, J; Qiao, J; McWilliams, G; Chen, D; Oliver, J A; Herzlinger, D



A One-Equation-Type Subgrid-Scale Model Including No Length Scale  

NASA Astrophysics Data System (ADS)

A subgrid-scale (SGS) model, based on a non-equilibrium model and described by SGS kinetic energy for large-eddy simulations, is presented. The objective of this study is to propose a one-equation-type SGS model including no length scale, unlike the conventional model, and to verify its performance by comparison with other models. For this objective, we apply these models to a plane channel turbulent flow and Rayleigh--Bénard convection. The proposed model can suitably predict the mean velocity and the mean temperature, and it can estimate bulk velocity and Nusselt number values more accurately than the other models on a coarse grid, which indicates its usability as an SGS model.

Koyama, Shoji



Z' factor including siRNA design quality parameter in RNAi screening experiments.  


RNA interference (RNAi) high-content screening (HCS) enables massive parallel gene silencing and is increasingly being used to reveal novel connections between genes and disease-relevant phenotypes. The application of genome-scale RNAi relies on the development of high quality HCS assays. The Z' factor statistic provides a way to evaluate whether or not screening run conditions (reagents, protocols, instrumentation, kinetics, and other conditions not directly related to the test compounds) are optimized. Z' factor, introduced by Zhang et al., ( 1) is a dimensionless value that represents both the variability and the dynamic range between two sets of sample control data. This paper describe a new extension of the Z' factor, which integrates bioinformatics RNAi non-target compounds for screening quality assessment. Currently presented Z' factor is based on positive and negative control, which may not be sufficient for RNAi experiments including oligonucleotides (oligo) with lack of knock-down. This paper proposes an algorithm which extends existing algorithm by using additional controls generetaed from on-target analysis. PMID:22614837

Mazur, S?awomir; Kozak, Karol



Generalized Boltzmann factors induced by Weibull-type distributions  

NASA Astrophysics Data System (ADS)

The inverse Mellin transform technique is utilized to obtain closed form representations of the generalized Boltzmann factors associated with several Weibull-type models such as the generalized gamma, Maxwell, Rayleigh and half-normal distributions. The results complement those already available in the Physics literature in connection with the distribution of certain variables affecting the behavior of nonequilibrium systems subject to complex dynamics, which include for instance computable expressions for the generalized Boltzmann factors induced by the gamma, F, uniform and lognormal statistical models.

Mathai, A. M.; Provost, Serge B.



10 CFR 719.6 - Are there any types of legal matters not included in the coverage of this part?  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Are there any types of legal matters not included in the coverage of this part...719.6 Are there any types of legal matters not included in the coverage of this part? Matters not covered by this part include:...



Rotating bits including a plurality of types of preferential cutting elements  

SciTech Connect

A rotating bit, particularly a rotary bit, is provided with a plurality of teeth incorporating diamond cutting elements of a first and second type. Each type of tooth is particularly adapted to cut a particular type of rock formation. For example, the plurality of the first type of teeth are particularly designed to cut soft to medium-hard rock formations, and the plurality of the second type of teeth are particularly adapted to cut hard or abrasive rock formations. In one embodiment, the first type of teeth are set on the bit face to have a greater exposure from the bit face than the second type of teeth. In that case, the first type of teeth will engage the rock formation first. A second embodiment has the relative disposition of the first and second types of teeth as measured by their disposition from the axis of rotation on the bit reversed. In the case where the teeth, which are adapted for hard rock cutting, extend furthermost from the bit, the rock formation first comes into contact with these teeth and if it should be a hard rock formation, primary cutting action will be accomplished with the hard rock cutting teeth, while the soft rock cutting teeth are held out of contact from the formation to minimize wear of these softer rock cutting teeth. However, when a soft rock formation is encountered, the hard rock teeth will fully embed into the softer rock formation, thereby allowing full engagement of the softer rock formation cutting teeth.

Bidegaray, D. A.



A three phase core-type transformer iron core model with included magnetic cross saturation  

Microsoft Academic Search

Three phase transformers used in the electric power applications are composed either of three single phase transformers or they are three limb core type. The majority of three phase core-type transformer dynamic models neglect magnetic nonlinearity and saturation. This paper presents two magnetically nonlinear iron core models of three phase three-limb transformer. Iron core model I is determined by described

M. Dolinar; D. Dolinar; G. Stumberger; B. Polajzer; J. Ritonja



Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis.  


We report a population based case-control study of exposure to pesticides as risk factor for non-Hodgkin lymphoma (NHL). Male and female subjects aged 18-74 years living in Sweden were included during December 1, 1999, to April 30, 2002. Controls were selected from the national population registry. Exposure to different agents was assessed by questionnaire. In total 910 (91 %) cases and 1016 (92%) controls participated. Exposure to herbicides gave odds ratio (OR) 1.72, 95% confidence interval (CI) 1.18-2.51. Regarding phenoxyacetic acids highest risk was calculated for MCPA; OR 2.81, 95% CI 1.27-6.22, all these cases had a latency period >10 years. Exposure to glyphosate gave OR 2.02, 95% CI 1.10-3.71 and with >10 years latency period OR 2.26, 95% CI 1.16-4.40. Insecticides overall gave OR 1.28, 95% CI 0.96-1.72 and impregnating agents OR 1.57, 95% CI 1.07-2.30. Results are also presented for different entities of NHL. In conclusion our study confirmed an association between exposure to phenoxyacetic acids and NHL and the association with glyphosate was considerably strengthened. PMID:18623080

Eriksson, Mikael; Hardell, Lennart; Carlberg, Michael; Akerman, Mĺns



Factors underlying parental decisions about combination childhood vaccinations including MMR: a systematic review.  


Suboptimal childhood vaccination uptake results in disease outbreaks, and in developed countries is largely attributable to parental choice. To inform evidence-based interventions, we conducted a systematic review of factors underlying parental vaccination decisions. Thirty-one studies were reviewed. Outcomes and methods are disparate, which limits synthesis; however parents are consistently shown to act in line with their attitudes to combination childhood vaccinations. Vaccine-declining parents believe that vaccines are unsafe and ineffective and that the diseases they are given to prevent are mild and uncommon; they mistrust their health professionals, Government and officially-endorsed vaccine research but trust media and non-official information sources and resent perceived pressure to risk their own child's safety for public health benefit. Interventions should focus on detailed decision mechanisms including disease-related anticipated regret and perception of anecdotal information as statistically representative. Self-reported vaccine uptake, retrospective attitude assessment and unrepresentative samples limit the reliability of reviewed data - methodological improvements are required in this area. PMID:20438879

Brown, Katrina F; Kroll, J Simon; Hudson, Michael J; Ramsay, Mary; Green, John; Long, Susannah J; Vincent, Charles A; Fraser, Graham; Sevdalis, Nick



Sipandinolide: a butenolide including a novel type of carbon skeleton from Siparuna andina.  


From a lipophilic extract of leaves of Siparuna andina (Monimiaceae), which exhibited antiplasmodial activity in vitro, two new compounds have been isolated: sipandinolide (1), a compound with a novel type of carbon skeleton and (-)-cis-3-acetoxy-4',5,7-trihydroxyflavanone (2). Their structures were established by spectroscopic methods; 2 showed moderate antiplasmodial activity whereas 1 was inactive. PMID:10865465

Jenett-Siems, K; Siems, K; Jakupovic, J; Solis, P N; Gupta, M P; Mockenhaupt, F P; Bienzle, U; Eich, E



TNF, TNF receptor type 1, and allograft inflammatory factor-1 gene polymorphisms in Japanese patients with type 1 diabetes  

Microsoft Academic Search

The human leukocyte antigen (HLA) class III region, located on chromosome 6p21, has been regarded as one of the susceptible loci for type 1 diabetes. Because it contains many genes related to inflammatory and immune responses, including tumor necrosis factor (TNF), lymphotoxin-? (LT-?), and allograft inflammatory factor 1 (AIF-1) genes, it is unclear which gene within the class III region

Masataka Nishimura; Hiroshi Obayashi; Ikuko Mizuta; Hirokazu Hara; Tetsuo Adachi; Mitsuhiro Ohta; Hisataka Tegoshi; Michiaki Fukui; Goji Hasegawa; Hirofumi Shigeta; Yoshihiro Kitagawa; Koji Nakano; Ryuji Kaji; Naoto Nakamura



Infrared cloud imaging for diurnal remote sensing of cloud statistics including cloud type  

NASA Astrophysics Data System (ADS)

Clouds are a critical component in determining weather and climate. Spatial and temporal statistics of cloudiness are needed in applications ranging from climate research to precision agriculture. Ground-based cloud remote sensing is particularly useful in applications requiring high spatial and temporal resolution. Thermal infrared imaging allows continuous detection of clouds from their thermal emission, with no interruption during sunrise, sunset, or night. In addition to detecting clouds continually during day and night,the third-generation Infrared Cloud Imager (ICI-3) is capable of classifying thin clouds according to their optical depth. This added capability is provided by a rigorous radiometric calibration and compensation of atmospheric emission from the infrared sky images. Data are shown that illustrate the importance of cloud- type classification in determining the radiative effect of variable cloudiness.

Shaw, J. A.; Nugent, P. W.; Simpson, K.; Johnson, J.; Staal, B.



A Touch-Type Corrosion Sensor Including a Coil for High-Sensitive Detection of Initial Rust State  

Microsoft Academic Search

Some nondestructive diagnostic methods including the use of various types of corrosion sensors have recently been investigated. In this context, initial corrosion detection is a particular focus in our study. In order to detect the rust layer formed by some semiconductor materials, we have investigated several conventional touch-type corrosion sensors using the difference between the electrical characteristics of iron and

Naruto Yonemoto; Katsunori Shida



The development of Myxobolus pavlovskii (Myxozoa: Myxobolidae) includes an echinactinomyxon-type actinospore.  


Echinactinomyxon-type actinospores were found in a mixed-species oligochaete culture originating from the Temperate Water Fish Hatchery near Budapest, Hungary. On the basis of DNA sequence analysis, the actinospores were identified as Myxobolus pavlovskii (Akhmerov, 1954), the 18S rDNA sequence from myxospores of which is available in GenBank. Silver carp Hypophthalmichthys molitrix (Valenciennes) fry specimens were successfully infected by cohabitation with the echinactinomyxon-releasing oligochaetes, which confirmed the molecular data congruence. The echinactinomyxons and the myxospores that developed in the gills of exposed fish fry were analysed morphologically and on DNA basis. The infected gill tissue was examined histologically. As typical characters of M. pavlovskii, numerous small plasmodia were observed in the epithelia of gill lamellae. Plasmodia contained thousands of myxospores with polar capsules unequal in size and witl; large intercapsular processes. The 18S rDNA sequence from actinospores and those from myxospores originating from the experimentally infected fish were identical. The oligochaete species releasing actinospores was morphologically determined as Limnodrilus sp. This is the first record of an echinactinomyxon as an alternate stage within the genus Myxobolus. PMID:21776895

Marton, Szilvia; Eszterbauer, Edit



Q-Type Factor Analysis of Healthy Aged Men.  

ERIC Educational Resources Information Center

|Q-type factor analysis was used to re-analyze baseline data collected in 1957, on 47 men aged 65-91. Q-type analysis is the use of factor methods to study persons rather than tests. Although 550 variables were originally studied involving psychiatry, medicine, cerebral metabolism and chemistry, personality, audiometry, dichotic and diotic memory,…

Kleban, Morton H.


Q-Type Factor Analysis of Healthy Aged Men.  

ERIC Educational Resources Information Center

Q-type factor analysis was used to re-analyze baseline data collected in 1957, on 47 men aged 65-91. Q-type analysis is the use of factor methods to study persons rather than tests. Although 550 variables were originally studied involving psychiatry, medicine, cerebral metabolism and chemistry, personality, audiometry, dichotic and diotic memory,…

Kleban, Morton H.


Blood type and the five factors of personality in Asia  

Microsoft Academic Search

Research investigating the association of blood type with personality has yielded mixed results. Two recent studies (Cramer & Imaike, 2002; Rogers & Glendon, 2003) used inventories based on the widely accepted five-factor model and found no significant relationship between blood type and personality. Our study is the third published article to examine this relationship using the five-factor model. We analyzed

Kunher Wu; Kristian D. Lindsted; Jerry W. Lee



Polyprenylated benzoylphloroglucinol-type derivatives including novel cage compounds from Hypericum erectum.  


Hyperici erecti herba (Hypericum erectum THUNB.) showed a suppressive effect on generation of isovaleric acid by Corynebacterium xerosis. An ethyl acetate (AcOEt) soluble fraction of methanol extract of H. erectum showed the activity. The AcOEt fraction was separated by various successive choromatographical methods to give seven new compounds 1-7 along with some known compounds. The structures of the new compounds were elucidated to be polyprenylated benzoylphloroglucinol derivatives by means of HR-MS and NMR spectra including 2D-NMR. Some of these compounds had novel cage structures having benzoyltricyclo[3,3,1,1(3,7)]decane and benzoyltricyclo[4,3,1,1(3,8)]undecane skeletons arising from a polyprenylated phloroglucinol precursor by a transannular cyclization reaction. The isolated compounds were tested for suppressive activity, but they showed only weak activity. PMID:20190438

Ishida, Yohei; Shirota, Osamu; Sekita, Setsuko; Someya, Keita; Tokita, Fumihiko; Nakane, Takahisa; Kuroyanagi, Masanori



Factors underlying parental decisions about combination childhood vaccinations including MMR: A systematic review  

Microsoft Academic Search

Suboptimal childhood vaccination uptake results in disease outbreaks, and in developed countries is largely attributable to parental choice. To inform evidence-based interventions, we conducted a systematic review of factors underlying parental vaccination decisions. Thirty-one studies were reviewed. Outcomes and methods are disparate, which limits synthesis; however parents are consistently shown to act in line with their attitudes to combination childhood

Katrina F. Brown; J. Simon Kroll; Michael J. Hudson; Mary Ramsay; John Green; Susannah J. Long; Charles A. Vincent; Graham Fraser; Nick Sevdalis



Including transcription factor information in the superparamagnetic clustering of microarray data  

NASA Astrophysics Data System (ADS)

In this work, we modify the superparamagnetic clustering algorithm (SPC) by adding an extra weight to the interaction formula that considers which genes are regulated by the same transcription factor. With this modified algorithm which we call SPCTF, we analyze the Spellman et al. microarray data for cell cycle genes in yeast, and find clusters with a higher number of elements compared with those obtained with the SPC algorithm. Some of the incorporated genes by using SPCFT were not detected at first by Spellman et al. but were later identified by other studies, whereas several genes still remain unclassified. The clusters composed by unidentified genes were analyzed with MUSA, the motif finding using an unsupervised approach algorithm, and this allow us to select the clusters whose elements contain cell cycle transcription factor binding sites as clusters worthy of further experimental studies because they would probably lead to new cell cycle genes. Finally, our idea of introducing the available information about transcription factors to optimize the gene classification could be implemented for other distance-based clustering algorithms.

Monsiváis-Alonso, M. P.; Navarro-Muńoz, J. C.; Riego-Ruiz, L.; López-Sandoval, R.; Rosu, H. C.



Mantel-Haenszel analysis of Oxford data. I. Independent effects of several birth factors including fetal irradiation.  


Data from the Oxford Survey of Childhood Cancers were subjected to the Mantel-Haenszel procedures to recognize independent effects of associated factors in retrospective data. Our results showed that several birth factors, including fetal irradiation, social class, maternal age, and sibship position, exerted separate effects on childhood cancers in general, and reticuloendothelial system neoplasms in particular. PMID:994200

Kneale, G W; Stewart, A M



$B\\\\to\\\\rho$ form factors including higher twist contributions and reliability of pQCD approach  

Microsoft Academic Search

We discuss $\\\\btorho$ form factors within the framework of perturbative QCD, including the higher twist contributions and study the validity of such an approach in calculating quantities such as form factors, which in principle and quite generally are thought to be completely non-perturbative objects and are expected to receive large contributions from the non-perturbative regime in the calculations. It is

Namit Mahajan



Apolipoprotein E polymorphisms and type 2 diabetes: a meta-analysis of 30 studies including 5423 cases and 8197 controls.  


Type 2 diabetes mellitus (T2DM) is a highly complicated metabolic disorder for which there is worldwide effort for the identification of susceptibility genes. Polymorphisms of the Apolipoprotein E (ApoE) gene are associated with plasma lipid and lipoprotein levels and influence cardiovascular risk. Since insulin resistance is known to be strongly associated with metabolic dyslipidemia, ApoE polymorphisms have been implicated in predisposition to diabetes but the results of the individual studies were inconclusive. We present here a meta-analysis of population-based case-control genetic-association studies relating ApoE polymorphisms and T2DM. We included in the analysis 30 studies, which reported data of ApoE genotypes in 5423 T2DM patients and 8197 healthy unrelated controls. Multivariate and univariate methods suggest a significant role played by the E2 allele, since carriers of the E2 allele were at elevated risk for T2DM (Odds Ratio=1.18, 95% CI: 1.02, 1.35). There was no evidence for publication bias or other small-study related bias or significant heterogeneity in the analyses. Cumulative meta-analysis revealed no trend of the effect estimates over time and influential analysis excluded the possibility of a single influential study. E2 allele of ApoE seems to be a moderate risk factor for T2DM. Meta-regression analysis provided some weak evidence that the risk conferred by E2 allele is mediated through altering serum lipid levels (Total Cholesterol, LDL and HDL). Further studies are needed in order to elucidate the metabolic mechanism of this association as well as to study its effects on larger populations. PMID:20381392

Anthopoulos, P G; Hamodrakas, S J; Bagos, P G



Modulation of Innate Host Factors by Mycobacterium avium Complex in Human Macrophages Includes Interleukin 17  

PubMed Central

Background.?Although opportunistic infections due to Mycobacterium avium complex (MAC) have been less common since the introduction of highly active antiretroviral therapy, globally, human immunodeficiency virus-1 (HIV-1)–positive patients remain predisposed to these infections. Absence of a properly functioning acquired immune response allows MAC persistence within macrophages localized in lymph nodes coinfected with HIV and MAC. Although a deficiency in interferon ? appears to play a part in the ability of MAC to deflect the macrophage-associated antimicrobial attack, questions about this process remain. Our study examines the ability of MAC to regulate interleukin 17 (IL-17), a proinflammatory cytokine involved in host cell recruitment. Methods.?Coinfected lymph nodes were examined for IL-17 by immunohistochemical analysis. In vitro, macrophages exposed to mycobacteria were evaluated for transcription activities, proteins, and signaling pathways responsible for IL-17 expression. Infected macrophages were also analyzed for expression of interleukin 21 (IL-21) and negative regulators of immune responses. Results.?Infection of macrophages triggered synthesis of IL-17, correlating with IL-17 expression by macrophages in coinfected lymph nodes. Infected macrophages exposed to exogenous IL-17 expressed CXCL10, which favors recruitment of new macrophages as targets for infection. Blockade of nuclear factor ?-light-chain-enhancer of activated B cells and mitogen-activated protein kinase pathways suppressed mycobacteria-induced IL-17 expression. MAC triggered expression of IL-21, IRF4, and STAT3 genes related to IL-17 regulation, as well as expression of the negative immunoregulators CD274(PD-L1) and suppressors of cytokine signaling. Conclusions.?MAC-infected macrophages can provide an alternative source for IL-17 that favors accumulation of new targets for perpetuating bacterial and viral infection while suppressing host antimicrobial immune responses.

Vazquez, Nancy; Rekka, Sofia; Gliozzi, Maria; Feng, Carl G.; Amarnath, Shoba; Orenstein, Jan M.; Wahl, Sharon M.



Psychosocial Factors Associated with Types of Child Maltreatment  

ERIC Educational Resources Information Center

|This explanatory, descriptive study examines whether a relationship exists between certain psychosocial factors or clusters of factors and parents' or caregivers' behaviors regarding the type of maltreatment inflicted on a child. This study examines physical abuse, neglect, and both physical abuse and neglect cases. Results show that physical…

DiLauro, Michelle D.



Transforming Growth Factor type ? and Smad family signaling in stem cell function  

Microsoft Academic Search

Ligands of the Transforming Growth Factor type ? (TGF?) family exert multiple and sometimes opposite effects on most cell types in vivo depending on cellular context, which mainly includes the stage of the target cell, the local environment of this cell or niche, and the identity and the dosage of the ligand. Significant progress has been made in the molecular

Eve Seuntjens; Lieve Umans; An Zwijsen; Maurilio Sampaolesi; Catherine M. Verfaillie; Danny Huylebroeck



Impact of early psychosocial factors (childhood socioeconomic factors and adversities) on future risk of type 2 diabetes, metabolic disturbances and obesity: a systematic review  

Microsoft Academic Search

BACKGROUND: Psychological factors and socioeconomic status (SES) have a notable impact on health disparities, including type 2 diabetes risk. However, the link between childhood psychosocial factors, such as childhood adversities or parental SES, and metabolic disturbances is less well established. In addition, the lifetime perspective including adult socioeconomic factors remains of further interest. We carried out a systematic review with

Teresa Tamayo; Christian Herder; Wolfgang Rathmann



Human Immunodeficiency Virus Type 1Induced Macrophage Gene Expression Includes the p21 Gene, a Target for Viral Regulation  

Microsoft Academic Search

In contrast to CD4 T cells, human immunodeficiency virus type 1 (HIV-1)-infected macrophages typically resist cell death, support viral replication, and consequently, may facilitate HIV-1 transmission. To elucidate how the virus commandeers the macrophage's intracellular machinery for its benefit, we analyzed HIV-1-in- fected human macrophages for virus-induced gene transcription by using multiple parameters, including cDNA expression arrays. HIV-1 infection induced

Nancy Vazquez; Teresa Greenwell-Wild; Nancy J. Marinos; William D. Swaim; Salvador Nares; David E. Ott; Ulrich Schubert; Peter Henklein; Jan M. Orenstein; M. B. Sporn; S. M. Wahl



A Touch-Type Corrosion Sensor Including a Coil for High-Sensitive Detection of Initial Rust State  

NASA Astrophysics Data System (ADS)

Some nondestructive diagnostic methods including the use of various types of corrosion sensors have recently been investigated. In this context, initial corrosion detection is a particular focus in our study. In order to detect the rust layer formed by some semiconductor materials, we have investigated several conventional touch-type corrosion sensors using the difference between the electrical characteristics of iron and rust. However, the sensitivity of these sensors was not sufficient to detect the impedance change of the rust layer due to the breakdown across the layer caused by the large transient supply current at the beginning of the measurement. This was because the impedance change at the breakdown happened to be much smaller than that without breakdown for thick rust layers. Here, we propose a new structure for a touch-type corrosion sensor, which includes a coil connected to a measurement electrode in series, to improve the characteristics of the sensor in the case of a thin rust layer. The transient supply current at the beginning of the measurement of the thickness of a rust layer is reduced by the effect of the connected coil. As a result, consistently accurate measurement by the sensor in the case of a thin rust layer is achieved.

Yonemoto, Naruto; Shida, Katsunori



A Predator-Prey Model with a Holling Type I Functional Response Including a Predator Mutual Interference  

NASA Astrophysics Data System (ADS)

The most widely used functional response in describing predator-prey relationships is the Holling type II functional response, where per capita predation is a smooth, increasing, and saturating function of prey density. Beddington and DeAngelis modified the Holling type II response to include interference of predators that increases with predator density. Here we introduce a predator-interference term into a Holling type I functional response. We explain the ecological rationale for the response and note that the phase plane configuration of the predator and prey isoclines differs greatly from that of the Beddington-DeAngelis response; for example, in having three possible interior equilibria rather than one. In fact, this new functional response seems to be quite unique. We used analytical and numerical methods to show that the resulting system shows a much richer dynamical behavior than the Beddington-DeAngelis response, or other typically used functional responses. For example, cyclic-fold, saddle-fold, homoclinic saddle connection, and multiple crossing bifurcations can all occur. We then use a smooth approximation to the Holling type I functional response with predator mutual interference to show that these dynamical properties do not result from the lack of smoothness, but rather from subtle differences in the functional responses.

Seo, Gunog; Deangelis, Donald L.



Direct reprogramming into desired cell types by defined factors.  


In the field of developmental biology, the concept that cells, once terminally differentiated, are fixed in their cell fate was long believed to be true. However, Dr. Gurdon and colleagues challenged this fundamental doctrine and demonstrated that cellular reprogramming and cell fate conversion are possible by somatic nuclear transfer and cell fusion. The Weintraub laboratory discovered in the 1980s that a single transcription factor, MyoD, can convert fibroblasts into skeletal muscle cells, and subsequent studies also demonstrated that several transcription factors are lineage converting factors within the blood cell lineage. In 2006, Takahashi and Yamanaka discovered that transduction of the four stem cell-specific transcription factors Oct4, Sox2, Klf4, and c-Myc can reprogram mouse fibroblast cells into a pluripotent state. In 2007, they demonstrated that the same four factors similarly reprogram human somatic cells into pluripotent stem cells. These discoveries by Dr. Yamanaka and colleagues fundamentally changed research in the fields of disease modeling and regenerative medicine and also inspired the next stage of cellular reprogramming, i.e., the generation of desired cell types without reverting to stem cells by overexpression of lineage-specific transcription factors. Recent studies demonstrated that a diverse range of cell types, such as pancreatic ? cells, neurons, neural progenitors, cardiomyocytes, and hepatocytes, can be directly induced from somatic cells by combinations of specific factors. In this article, I review the pioneering works of cellular reprogramming and discuss the recent progress and future perspectives of direct reprogramming technology. PMID:23801083

Ieda, Masaki



Factors Related to Amount and Type of Leisure Time Reading.  

ERIC Educational Resources Information Center

|Diaries showing how 920 Irish fifth graders spent their leisure time on three designated days within one week augmented data about the children's personal, school, and home characteristics to aid in determining the primary factors related to the amount and type of leisure time reading. The children reported spending a median time of 60 minutes…

Greaney, Vincent; Quinn, John


FUNDAMENTAL AREAS OF PHENOMENOLOGY (INCLUDING APPLICATIONS): High Sensitivity Transmission-Type SPR Sensor by Using Metallic Dielectric Mixed Gratings  

NASA Astrophysics Data System (ADS)

We theoretically investigate transmission-type SPR sensors with novel metallic-dielectric mixed gratings by rigorous coupled-wave analysis (RCWA), compared to the conventional dielectric gratings based structure. It is found that the transmittance efficiency and the full width at half-maximum (FWHM) of the transmission curve can be modulated by increasing or decreasing the metallic part. Therefore, appropriate proportion of metal part will induce enhancement factor of sensor merit. Furthermore, this novel structure will also bring enhancement of resonant angle shift, which can be explained by plasmonic interpretation based on a surface limited increase of interaction area and excitation of localized surface plasmons (LSPs). The proposed configuration has a wide range of potential applications not only as sensor but also other optical devices.

Wu, Bin; Wang, Qing-Kang



The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer  

SciTech Connect

Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. Conclusions: Comparable prediction models were obtained with LKB, RS, and logistic NTCP models. Including clinical factors improved the predictive power of all models significantly.

Defraene, Gilles, E-mail: [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Van den Bergh, Laura [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Al-Mamgani, Abrahim [Department of Radiation Oncology, Erasmus Medical Center - Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Haustermans, Karin [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Heemsbergen, Wilma [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Van den Heuvel, Frank [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Lebesque, Joos V. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)



Transgenic mice neuronally expressing baculoviral p35 are resistant to diverse types of induced apoptosis, including seizure-associated neurodegeneration  

PubMed Central

Apoptosis is a cell-suicide process that appears to play a central role not only during normal neuronal development but also in several neuropathological disease states. An important component of this process is a proteolytic cascade involving a family of cysteine proteases called caspases. Caspase inhibitors have been demonstrated to be effective in inhibiting neuronal cell death in various apoptotic paradigms. We have created transgenic mice that neuronally express the baculoviral caspase inhibitor p35. Neuronal expression of the p35 protein was found to confer functional caspase inhibitory activity and prevent apoptosis in isolated cerebellar granular cultures induced to undergo apoptosis either via staurosporine treatment or through withdrawal of extracellular potassium. Neuronal expression of p35 was also found to attenuate neurodegeneration associated with the excitotoxic glutamate analogue kainic acid (KA) in vitro and in vivo. Organotypic hippocampal cultures isolated from p35 transgenics demonstrated lowered caspase activity and decreased apoptosis compared with wild type when exposed to KA. In vivo injection of KA also produced decreased caspase activity and cell death in p35 transgenics vs. wild type. These results suggest that the presence of p35 in neurons in vivo is protective against various types of apoptosis, including seizure-related neurodegeneration, and that caspases may be attractive potential targets for preventing neuronal injury associated with diseases such as epilepsy. These mice also provide a valuable tool for exploring the role of caspases in other neuropathological conditions in which apoptosis has been implicated.

Viswanath, Veena; Wu, Zhijin; Fonck, Carlos; Wei, Qize; Boonplueang, Rapee; Andersen, Julie K.



The Type Series of 'Sinemys' Wuerhoensis, a Problematic Turtlefrom the Lower Cretaceous of China, Includes at Least Three Taxa  

SciTech Connect

We re-examine the type series of 'Sinemys' wuerhoensis Yeh(at least 20 specimens, including several shells and skulls on threeslabs of matrix and one isolated skull) from the Early Cretaceous TuguluGroup of China. Our study shows that the type series of 'S.'wuerhoensisis actually a chimera made up of at least three distinct taxa. Theholotype of this taxon should be assigned to the basal eucryptodire genusXinjiangchelys Yeh. As there are no characters that distinguish'S.'wuerhoensis from Xinjiangchelys species, we consider it to be a nomendubium. This new assignment of 'S.'wuerhoensis expands the temporal rangeof Xinjiangchelys from the Late Jurassic into the Early Cretaceous inAsia. The majority of the paratypes of 'S.'wuerhoensis (several shells indorsal and ventral aspect and skulls) are referred to the basaleucryptodire genus Ordosemys Brinkman and Peng. We establish a new namefor these specimens, Ordosemys brinkmania sp. nov. One additionalspecimen in the type series of 'S.'wuerhoensis, a skull, is referred tocf. Pantrionychia Joyce, Parham and Gauthier indet.

Danilov, Igor G.; Parham, James F.



Visible and near infrared spectroscopic investigation of E-type asteroids, including 2867 Steins, a target of the Rosetta mission  

NASA Astrophysics Data System (ADS)

We present the results of a visible spectroscopic survey of igneous asteroids belonging to the small and intriguing E-class, including 2867 Steins, a target of the Rosetta mission. The survey was carried out at the 3.5 m Telescopio Nazionale Galileo (TNG), and at the 3.5 m New Technology Telescope (NTT) of the European Southern Observatory. We obtained new visible spectra for eighteen E-type asteroids, and near infrared spectra for eight of them. We confirm the presence of three different mineralogies in the small E-type populations. We classify each object in the E[I], E[II] or E[III] subgroups [Gaffey, M.J., Kelley, M.S., 2004. Lunar Planet. Sci. XXXV. Abstract 1812] on the basis of the spectral behavior and of the eventual presence of absorption features attributed to sulfides (such the 0.49 ?m band, on E[II]), or to iron bearing silicates (0.9 ?m band, on E[III]). We suggest that some asteroids (i.e. 64 Angelina, 317 Roxane, and 434 Hungaria), which show different spectral behavior comparing our data with those available in literature, have an inhomogeneous surface composition. 2867 Steins, a target of the Rosetta mission, shows a spectral behavior typical of the E[II] subgroup, as already suggested by Barucci et al. [Barucci, M.A., Fulchignoni, M., Fornasier, S., Dotto, E., Vernazza, P., Birlan, M., Binzel, R.P., Carvano, J., Merlin, F., Barbieri, C., Belskaya, I., 2005. Astron. Astrophys. 430, 313 317] and Fornasier et al. [Fornasier, S., Marzari, F., Dotto, E., Barucci, M.A., Migliorini, A., 2007. Astron. Astrophys. 474, 29 32]. Litva and 1990 TN1, initially classified as E-types, show a visible and near infrared behavior consistent with the olivine rich A-class asteroids, while 5806 Archieroy, also supposed to belong to the E-class, has a spectral behavior consistent with the S(V) classification following the Gaffey et al. [Gaffey, M.J., Burbine, T.H., Piatek, J.L., Reed, K.L., Chaky, D.A., Bell, J.F., Brown, R.H., 1993. Icarus 106, 573 602] classification scheme. To fully investigate the E-type population, we enlarged our sample including 6 E-type asteroids spectra available in literature, resulting in a total sample of 21 objects. The analysis of the spectral slope for the 3 different E-type subgroups versus the orbital elements show that E[III] members have the lowest mean spectral slope value inside the whole sample, and that they are located between 2.2 2.7 AU in low inclination orbits. E[II] members has the highest spectral slope inside the sample, half of them are located in the Hungaria region, 2 are NEA and 2 (64 Angelina and 2867 Steins), are in the main belt. A similar distribution is found for the 5 featureless E[I] members, located mainly in the Hungaria region (3 members), one in the middle main belt while one is a NEA (2004 VD17). Finally, for the five E-type asteroids observed both in the visible and near infrared range, plus 2867 Steins, we attempt to model their surface composition using linear geographical mixtures of no more than 3 components, selected from aubrite meteorites and correlated minerals. In particular we suggest that the aubrite Peńa Blanca might have the E[III] Asteroid 317 Roxane as parent body, and that the aubrite ALH78113 might be related to the E[II] subgroup asteroids.

Fornasier, S.; Migliorini, A.; Dotto, E.; Barucci, M. A.



Environmental factors in the etiology of type 1 diabetes.  


Type 1 diabetes is considered to be an autoimmune disease in which T lymphocytes infiltrate the islets of pancreas and destroy the insulin producing beta cell population. Besides antigen specificity, the quality of immune reactivity against islet cell antigen(s) is an important determinant of the beta cell destruction. Much evidence indicates that the function of the gut immune system is central in the pathogenesis, as the regulation of the gut immune system may be aberrant in type 1 diabetes. The role of virus infections in the pathogenesis of type 1 diabetes has been supported by substantial new evidence suggesting that one virus group, enteroviruses, may trigger the beta-cell damaging process in a considerable proportion of patients. The latest evidence comes from studies indicating the presence of viral genome in diabetic patients and from prospective studies confirming epidemiological risk effect. If this association holds still true in ongoing large-scale studies, intervention trials should be considered to confirm causality. Of the dietary putative etiological factors, cow's milk proteins have received the main attention. Many studies indicate an association between early exposure to dietary cow's milk proteins and an increased risk of type 1 diabetes. The question will be answered by a large scale, prospective, randomized, international intervention trial. Another dietary factor in need of more studies is the deficiency of vitamin D. Among toxins, N-nitroso compounds are the main candidates. An interaction of genetic and environmental factors is important in evaluating the possible role of a certain environmental factor in the etiology of type 1 diabetes. PMID:12116173

Akerblom, Hans K; Vaarala, Outi; Hyöty, Heikki; Ilonen, Jorma; Knip, Mikael



Microalbuminuria and risk factors in type 1 and type 2 diabetic patients.  


A prospective study of normoalbuminuric diabetic patients was performed between 1997 and 2002 on 4097 type 1 and 6513 type 2 diabetic patients from the Swedish National Diabetes Register (NDR); mean study period, 4.6 years. The strongest independent baseline risk factors for the development of microalbuminuria (20-200 microg/min) were elevated HbA(1c) and diabetes duration in both types 1 and 2 diabetic patients. Other risk factors were high BMI, elevated systolic and diastolic BP in type 2 patients, and antihypertensive therapy in type 1 patients. A subsequent larger cross-sectional study in 2002 showed that established microalbuminuria was independently associated with HbA(1c), diabetes duration, systolic BP, BMI, smoking and triglycerides in types 1 and 2 diabetic patients, and also with HDL-cholesterol in type 2 patients. Relatively few types 1 and 2 patients with microalbuminuria achieved treatment targets of HbA(1c) < 6.5% (21-48%), BP < 130/85 mmHg (33-13%), cholesterol < 5 mmol/l (48-46%), triglycerides < 1.7 mmol/l (83-48%) and BMI < 25 kg/m(2) (50-18%), respectively. In conclusion, high HbA(1c), BP and BMI were independent risk factors for the development of microalbuminuria in types 1 and 2 diabetic patients. These risk factors as well as triglycerides, HDL-cholesterol and smoking were independently associated with established microalbuminuria. Treatment targets were achieved by a relatively few patients with microalbuminuria. PMID:15713359

Cederholm, J; Eliasson, B; Nilsson, P M; Weiss, L; Gudbjörnsdottir, S



Risk factors in patients with type 2 diabetes mellitus.  


This study was carried out to evaluate the risk factors of type 2 diabetic patients through sociodemographic data, habits of health, anthropometric and biochemist profiles, assisted at a basic public health care unit in Maringá, Paraná. Sixty-six patients, 56 women aged over than 50 years-old were interviewed. High prevalence factors for cardiovascular risk were observed, such as: overweight and obesity, hypertension, dyslipidemia, sedentariness and inadequate diet. Data suggested the need for multidisciplinary intervention programs in health care units associated to educative programs, adjusted diet intake and regular physical activity for these diabetic patients. PMID:18506342

Carolino, Idalina Diair Regla; Molena-Fernandes, Carlos Alexandre; Tasca, Raquel Soares; Marcon, Sonia Silva; Cuman, Roberto Kenji Nakamura


Risk Factors for Severity and Type of the Hip Fracture  

PubMed Central

More severe hip fractures such as displaced femoral neck (FN) fractures and unstable intertrochanteric (IT) fractures lead to poorer outcomes, but risk factors for severe fractures have not been studied. To identify risk factors for severe types of hip fracture, we performed a prospective cohort study and obtained preoperative hip radiographs from women who sustained an incident hip fracture (excluding traumatic fractures). A single radiologist scored the severity of FN fractures by the Garden System: grades I and II, undisplaced; grades III and IV, displaced. The severity of IT hip fractures was rated by the Kyle System: grades I and II, stable; grades III and IV, unstable. A total of 249 women had FN fractures: 75 (30%) were undisplaced. A total of 213 women had IT fractures: 59 (28%) were stable. Both types of hip fracture increased with age, but older age was even more strongly associated with more severe hip fractures. Low BMD was more strongly related to undisplaced FN fractures (p interaction BMD × FN type, p = 0.0008) and stable IT fractures (p interaction BMD × IT type, p = 0.04). Similar findings were observed for estimated volumetric BMD and hip geometric parameters. Corticosteroid use was only associated with displaced FN fractures, and Parkinson's disease was only associated with stable IT fractures. Little difference was reported in the self-reported circumstances surrounding each type of fracture. In conclusion, the lower the BMD, the greater the likelihood of experiencing a hip fracture that is less displaced and more stable.

Cauley, Jane A.; Lui, Li-Yung; Genant, Harry K.; Salamone, Loran; Browner, Warren; Fink, Howard A.; Cohen, Peter; Hillier, Teresa; Bauer, Doug C.; Cummings, Steven R.



Fibroblast growth factor-2 binding to the thrombospondin-1 type III repeats, a novel antiangiogenic domain.  


Thrombospondin-1, an antiangiogenic matricellular protein, binds with high affinity to the angiogenic fibroblast growth factor-2, affecting its bioavailability and activity. The present work aimed at further locating the fibroblast growth factor-2 binding site of thrombospondin-1 and investigating its activity, using recombinant thrombospondin-1 proteins. Only recombinant constructs containing the thrombospondin-1 type III repeats bound fibroblast growth factor-2, whereas other domains, including the known anti-angiogenic type I repeats, were inactive. Binding was specific and inhibited by the anti thrombospondin-1 monoclonal antibody B5.2. Surface plasmon resonance analysis on BIAcore revealed a binding affinity (K(d)) of 310nM for the type III repeats and 11nM for intact thrombospondin-1. Since the type III repeats bind calcium, the effect of calcium on thrombospondin-1 binding to fibroblast growth factor-2 was investigated. Binding was modulated by calcium, as thrombospondin-1 or the type III repeats bound to fibroblast growth factor-2 only in calcium concentrations <0.3mM. The type III repeats inhibited binding of fibroblast growth factor-2 to endothelial cells, fibroblast growth factor-2-induced endothelial cell proliferation in vitro and angiogenesis in the chorioallantoic membrane assay in vivo, thus indicating the antiangiogenic activity of the domain. In conclusion, this study demonstrates that the fibroblast growth factor-2 binding site of thrombospondin-1 is located in the type III repeats. The finding that this domain is active in inhibiting angiogenesis indicates that the type III repeats represent a novel antiangiogenic domain of thrombospondin-1. PMID:17996481

Margosio, Barbara; Rusnati, Marco; Bonezzi, Katiuscia; Cordes, Blue-Leaf A; Annis, Douglas S; Urbinati, Chiara; Giavazzi, Raffaella; Presta, Marco; Ribatti, Domenico; Mosher, Deane F; Taraboletti, Giulia




PubMed Central

Thrombospondin-1, an antiangiogenic matricellular protein, binds with high affinity to the angiogenic fibroblast growth factor-2, affecting its bioavailability and activity. The present work aimed at further locating the fibroblast growth factor-2 binding site of thrombospondin-1 and investigating its activity, using recombinant thrombospondin-1 proteins. Only recombinant constructs containing the thrombospondin-1 type III repeats bound fibroblast growth factor-2, whereas other domains, including the known anti-angiogenic type I repeats, were inactive. Binding was specific and inhibited by the anti thrombospondin-1 monoclonal antibody B5.2. Surface plasmon resonance analysis on BIAcore revealed a binding affinity (Kd) of 310 nM for the type III repeats and 11 nM for intact thrombospondin-1. Since the type III repeats bind calcium, the effect of calcium on thrombospondin-1 binding to fibroblast growth factor-2 was investigated. Binding was modulated by calcium, as thrombospondin-1 or the type III repeats bound to fibroblast growth factor-2 only in calcium concentrations <0.3 mM. The type III repeats inhibited binding of fibroblast growth factor-2 to endothelial cells, fibroblast growth factor-2-induced endothelial cell proliferation in vitro and angiogenesis in the chorioallantoic membrane assay in vivo, thus indicating the antiangiogenic activity of the domain. In conclusion, this study demonstrates that the fibroblast growth factor-2 binding site of thrombospondin-1 is located in the type III repeats. The finding that this domain is active in inhibiting angiogenesis indicates that the type III repeats represent a novel antiangiogenic domain of thrombospondin-1.

Margosio, Barbara; Rusnati, Marco; Bonezzi, Katiuscia; Cordes, Blue-leaf A.; Annis, Douglas S.; Urbinati, Chiara; Giavazzi, Raffaella; Presta, Marco; Ribatti, Domenico; Mosher, Deane F.; Taraboletti, Giulia



Parallel Type Voltage Sag Compensator with Reduced Capacitor by Boost Type Power Factor Correction Rectifier  

NASA Astrophysics Data System (ADS)

A new circuit of parallel type voltage sag compensator is proposed in this paper. The proposed voltage sag compensator can reduce the necessary capacity of the energy storage capacitor for compensation by boost type power factor correction rectifier charging the capacitor during a voltage sag. As a result the proposed system can reduce the size and maintenances of the apparatus. This paper shows principle and control system of the proposed circuit. Compensation characteristics were demonstrated by simulation and experiment.

Kojima, Tetsuya; Takauchi, Toshihiko; Ise, Toshifumi; Iyoda, Isao; Kono, Yoshiyuki; Temma, Koji; Sasao, Hiroyuki; Yamasaki, Kiyomi; Inoue, Nobuyoshi; Takeuchi, Yasunori


Prevalence of known prognostic factors in female breast carcinoma including oestrogen receptor, progesterone receptor and Her-2/neu status--a study in a tertiary care centre.  


Breast cancer is second most common cancer in Indian women. It is often curable by various treatment modalities when detected in early stage. Prognosis and selection of therapy in breast cancer depends upon various factors including clinical parameters, histopathological subtype and molecular characteristics of primary tumour. The aim of this study was to determine the prevalence of different prognostics factors including immunohistochemical marker ie, oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (Her-2/neu) status in female breast carcinoma in a tertiary care centre. In this study 80 females patients who were found to have carcinoma of breast by fine needle aspiration cytology (FNAC) and consequently confirmed by histopathology were followed up for one year. Immunohistochemical staining for molecular markers like oestrogen receptor (ER), progesterone receptor (PR) and Her-2/neu were done in selected 48 cases. Various clinical parameters, cytopathological and hispathological findings as well as immunohistochemical studies were correlated to know the prevalence of these important prognostic factors. It was found that majority of patients were under 50 years of age group with high parity status. Significant patients had breast lump > 4 cm in size. Infiltrating duct carcinoma not otherwise specified (NOS) was the most common histological type showing predominantly microscopic grade II as per Nottingham's Modification of Bloom Richardson grading system. Immunohistochemistry showed 75% ER positivity, 66.66% PR positivity and 25% Her-2/neu positivity. PMID:23936949

Chakrabarti, Suchismita; Karmakar, Rupam; Barui, Gopinath; Maity, Pradip Kumar; Bandyopadhyay, Anindya; Roy, Anup



A Telemedicine System That Includes a Personal Assistant Improves Glycemic Control in Pump-Treated Patients with Type 1 Diabetes  

PubMed Central

Background The DIABTel system, a Web-based telemedicine application, integrates a whole communication system (glucometer, insulin pump, wireless hand-held assistant) for medical remote advice. We sought to evaluate, in terms of glycemic control, the DIABTel system in a randomized crossover clinical study. Methods Ten patients with type 1 diabetes [5 women, age 40.6 (21–62) years, diabetes duration 14.7 (3–52) years] were included. During the 4-week active phase, data sent by patients were analyzed by the physician and modifications of the basal rate and bolus were advised in the following 24 hours. During the control phase, patients sent glucose data without any feedback from the medical center. Results The mean numbers of daily glucose values and bolus sent by patients during the active period were 4.46 ± 0.91 and 4.58 ± 0.89, respectively. The personal digital assistant functionalities used more frequently by patients were (times per week) data visualization (8.1 ± 6.8), data download from the insulin pump (6.8 ± 3.3), and synchronization with the telemedicine server (8.5 ± 4.9). After the experimental phase, serum fructosamine decreased significantly (393 ± 32 vs 366 ± 25 µmol/liter; p < 0.05) and hemoglobin A1c (HbA1c) tended to decrease (8.0 ± 0.6 vs 7.78 ± 0.6; p = 0.073), whereas no changes were observed during the control phase. The number of treatment modifications proposed and performed by the patients correlated with the change observed in HbA1c during the active phase (r = ?0.729, p = 0.017). Conclusions The DIABTel system, a telemedicine system that includes a wireless personal assistant for remote treatment advising, allows better glycemic control in pump-treated patients with type 1 diabetes. To our knowledge, this is the first study that demonstrates improved glycemic control with the use of a telemedicine system that incorporates insulin delivery data.

Rigla, Mercedes; Hernando, M. Elena; Gomez, Enrique J.; Brugues, Eulalia; Garcia-Saez, Gema; Torralba, Veronica; Prados, Agustina; Erdozain, Luisa; Vilaverde, Joana; de Leiva, Alberto



Effect of fuels and domestic heating appliance types on emission factors of selected organic pollutants.  


This study reports on the first complex data set of emission factors (EFs) of selected pollutants from combustion of five fuel types (lignite, bituminous coal, spruce, beech, and maize) in six different domestic heating appliances of various combustion designs. The effect of fuel as well as the effect of boiler type was studied. In total, 46 combustion runs were performed, during which numerous EFs were measured, including the EFs of particulate matter (PM), carbon monoxide, polyaromatic hydrocarbons (PAH), hexachlorobenzene (HxCBz), polychlorinated dibenzo-p-dioxins and furans (PCDD/F), etc. The highest EFs of nonchlorinated pollutants were measured for old-type boilers with over-fire and under-fire designs and with manual stoking and natural draft. Emissions of the above-mentioned pollutants from modern-type boilers (automatic, downdraft) were 10 times lower or more. The decisive factor for emission rate of nonchlorinated pollutants was the type of appliance; the type of fuel plays only a minor role. Emissions of chlorinated pollutants were proportional mainly to the chlorine content in fuel, but the type of appliance also influenced the rate of emissions significantly. Surprisingly, higher EFs of PCDD/F from combustion of chlorinated bituminous coal were observed for modern-type boilers (downdraft, automatic) than for old-type ones. On the other hand, when bituminous coal was burned, higher emissions of HxCBz were found for old-type boilers than for modern-type ones. PMID:21932830

Šyc, Michal; Horák, Ji?í; Hopan, František; Krpec, Kamil; Tomšej, Tomáš; Ocelka, Tomáš; Pekárek, Vladimír



Risk Factors for Type 2 Diabetes Among Women with Gestational Diabetes: A Systematic Review  

Microsoft Academic Search

We conducted a systematic review of studies examining risk factors for the development of type 2 diabetes among women with previous gestational diabetes. Our search strategy yielded 14 articles that evaluated 9 categories of risk factors of type 2 diabetes in women with gestational diabetes: anthropometry, pregnancy-related factors, postpartum factors, parity, family history of type 2 diabetes, maternal lifestyle factors,

Kesha Baptiste-Roberts; Bethany B. Barone; Tiffany L. Gary; Sherita H. Golden; Lisa M. Wilson; Eric B. Bass; Wanda K. Nicholson



Stromal Cell-Derived Factor1 Chemokine Gene Variant in Patients with Type 1 Diabetes and Autoimmune Thyroid Disease  

Microsoft Academic Search

Type 1 diabetes is a heterogenous autoimmune disease and is fre- quently associated with other organ-specific autoimmune diseases, including autoimmune thyroid disease (AITD). Type 1 diabetic patients with AITD are known to have clinical and immunological features distinct from patients with- out AITD. This study investigated whether stromal cell-derived factor (SDF)- 1 gene polymorphism is associated with susceptibility to type




Vascular-protective effects of high-density lipoprotein include the downregulation of the angiotensin II type 1 receptor.  


There is growing evidence that a cross-talk exists between the renin-angiotensin (Ang) system and lipoproteins. We investigated the role of high-density lipoprotein (HDL) on Ang II type 1 receptor (AT1R) regulation and subsequent Ang II-mediated signaling under diabetic conditions. To investigate the effect of HDL on AT1R expression in vivo, apolipoprotein A-I gene transfer was performed 5 days after streptozotocin injection. Six weeks after apolipoprotein A-I gene transfer, the 1.9-fold (P=0.001) increase of HDL cholesterol was associated with a 4.7-fold (P<0.05) reduction in diabetes mellitus-induced aortic AT1R expression. Concomitantly, NAD(P)H oxidase activity, Nox 4, and p22(phox) mRNA expression were reduced 2.6-fold, 2.0-fold, and 1.5-fold (P<0.05), respectively, whereas endothelial NO synthase dimerization was increased 3.3-fold (P<0.005). Apolipoprotein A-I transfer improved NO bioavailability as indicated by ameliorated acetylcholine-dependent vasodilation in the streptozotocin-Ad.hapoA-I group compared with streptozotocin-induced diabetes mellitus. In vitro, HDL reduced the hyperglycemia-induced upregulation of the AT1R in human aortic endothelial cells. This was associated with a 1.3-fold and 2.2-fold decreases in reactive oxygen species and NAD(P)H oxidase activity, respectively (P<0.05). Finally, HDL reduced the responsiveness to Ang II, as indicated by decreased oxidative stress in the hyperglycemia+HDL+Ang II group compared with the hyperglycemia+Ang II group. In conclusion, vascular-protective effects of HDL include the downregulation of the AT1R. PMID:19273745

Van Linthout, Sophie; Spillmann, Frank; Lorenz, Mario; Meloni, Marco; Jacobs, Frank; Egorova, Marina; Stangl, Verena; De Geest, Bart; Schultheiss, Heinz-Peter; Tschöpe, Carsten



Synergistic and multidimensional regulation of plasminogen activator inhibitor type 1 expression by transforming growth factor type ? and epidermal growth factor  

SciTech Connect

The major physiological inhibitor of plasminogen activator, type I plasminogen activator inhibitor (PAI-1), controls blood clotting and tissue remodeling events that involve cell migration. Transforming growth factor type ? (TGF?) and epidermal growth factor (EGF) interact synergistically to increase PAI-1 mRNA and protein levels in human HepG2 and mink Mv1Lu cells. Other growth factors that activate tyrosine kinase receptors can substitute for EGF. EGF and TGF? regulate PAI-1 by synergistically activating transcription, which is further amplified by a decrease in the rate of mRNA degradation, the latter being regulated only by EGF. The combined effect of transcriptional activation and mRNA stabilization results in a rapid 2-order of magnitude increase in the level of PAI-1. TGF? also increases the sensitivity of the cells to EGF, thereby recruiting the cooperation of EGF at lower than normally effective concentrations. The contribution of EGF to the regulation of PAI-1 involves the MAPK pathway, and the synergistic interface with the TGF? pathway is downstream of MEK1/2 and involves phosphorylation of neither ERK1/2 nor Smad2/3. Synergism requires the presence of both Smad and AP-1 recognition sites in the promoter. This work demonstrates the existence of a multidimensional cellular mechanism by which EGF and TGF? are able to promote large and rapid changes in PAI-1 expression.

Song, Xiaoling; Thalacker, F.W.; Nilsen-Hamilton, Marit



Synergistic and multidimensional regulation of plasminogen activator inhibitor type 1 expression by transforming growth factor type ? and epidermal growth factor.  


The major physiological inhibitor of plasminogen activator, type I plasminogen activator inhibitor (PAI-1), controls blood clotting and tissue remodeling events that involve cell migration. Transforming growth factor type ? (TGF?) and epidermal growth factor (EGF) interact synergistically to increase PAI-1 mRNA and protein levels in human HepG2 and mink Mv1Lu cells. Other growth factors that activate tyrosine kinase receptors can substitute for EGF. EGF and TGF? regulate PAI-1 by synergistically activating transcription, which is further amplified by a decrease in the rate of mRNA degradation, the latter being regulated only by EGF. The combined effect of transcriptional activation and mRNA stabilization results in a rapid 2-order of magnitude increase in the level of PAI-1. TGF? also increases the sensitivity of the cells to EGF, thereby recruiting the cooperation of EGF at lower than normally effective concentrations. The contribution of EGF to the regulation of PAI-1 involves the MAPK pathway, and the synergistic interface with the TGF? pathway is downstream of MEK1/2 and involves phosphorylation of neither ERK1/2 nor Smad2/3. Synergism requires the presence of both Smad and AP-1 recognition sites in the promoter. This work demonstrates the existence of a multidimensional cellular mechanism by which EGF and TGF? are able to promote large and rapid changes in PAI-1 expression. PMID:22334677

Song, Xiaoling; Thalacker, Frederic W; Nilsen-Hamilton, Marit



Sequence and chromatin determinants of cell-type-specific transcription factor binding  

PubMed Central

Gene regulatory programs in distinct cell types are maintained in large part through the cell-type–specific binding of transcription factors (TFs). The determinants of TF binding include direct DNA sequence preferences, DNA sequence preferences of cofactors, and the local cell-dependent chromatin context. To explore the contribution of DNA sequence signal, histone modifications, and DNase accessibility to cell-type–specific binding, we analyzed 286 ChIP-seq experiments performed by the ENCODE Consortium. This analysis included experiments for 67 transcriptional regulators, 15 of which were profiled in both the GM12878 (lymphoblastoid) and K562 (erythroleukemic) human hematopoietic cell lines. To model TF-bound regions, we trained support vector machines (SVMs) that use flexible k-mer patterns to capture DNA sequence signals more accurately than traditional motif approaches. In addition, we trained SVM spatial chromatin signatures to model local histone modifications and DNase accessibility, obtaining significantly more accurate TF occupancy predictions than simpler approaches. Consistent with previous studies, we find that DNase accessibility can explain cell-line–specific binding for many factors. However, we also find that of the 10 factors with prominent cell-type–specific binding patterns, four display distinct cell-type–specific DNA sequence preferences according to our models. Moreover, for two factors we identify cell-specific binding sites that are accessible in both cell types but bound only in one. For these sites, cell-type–specific sequence models, rather than DNase accessibility, are better able to explain differential binding. Our results suggest that using a single motif for each TF and filtering for chromatin accessible loci is not always sufficient to accurately account for cell-type–specific binding profiles.

Arvey, Aaron; Agius, Phaedra; Noble, William Stafford; Leslie, Christina



Mutated IDH1 is a favorable prognostic factor for type 2 gliomatosis cerebri.  


The prognostic significance of IDH1 mutations has been demonstrated in gliomas. It is unclear whether IDH1 mutation is also a prognostic factor in gliomatosis cerebri (GC). Primary GCs can be grouped into type 1 GCs, which have the classical diffuse growth pattern without mass formation, and type 2 GCs, which form neoplastic masses in addition to classic diffuse lesions. In this study, the prognostic relevance of IDH1/2 mutations in 74 GCs (43 type 1 and 31 type 2) was evaluated. We detected 33 (44.6%) IDH1 mutations, including R132H and R132S, by bidirectional Sanger sequencing. No mutations were detected in IDH2. The percentage of 2-year overall survival for wild-type IDH1 patients was 46 vs. 72% for patients with IDH1-mutated tumors. Mutations of IDH1 were strongly correlated with both increased overall survival (OS) and progression-free survival (PFS) in patients with type 2 GCs, and IDH1 mutations were also an independent prognostic factor predicting increased OS and PFS in type 2 GC patients in multivariate analysis. However, IDH1 mutations did not correlate with survival outcomes in patients with type 1 GCs. Finally, the subgroup of GC, which has IDH1 wild-type and additional solid component showed the worst prognosis. PMID:21929658

Kwon, Mi Jung; Kim, Sung Tae; Kwon, Mi Jeong; Kong, Doo-Sik; Lee, Dageun; Park, Sanghui; Kang, So Young; Song, Ji-Young; Nam, Do-Hyun; Kato, Yukinari; Choi, Yoon-La; Suh, Yeon-Lim



Expression of key genes of fatty acid oxidation, including adiponectin receptors, in skeletal muscle of Type 2 diabetic patients  

Microsoft Academic Search

Aims\\/hypothesis  Defective oxidation of long-chain fatty acids is a feature of insulin resistance and Type 2 diabetes. Our aim was to compare the expression levels of the genes encoding the major proteins and enzymes of this pathway in skeletal muscle of healthy subjects and Type 2 diabetic patients.Methods  The basal and insulin-regulated mRNA concentration of 16 genes was quantified using real-time PCR

C. Debard; M. Laville; V. Berbe; E. Loizon; C. Guillet; B. Morio-Liondore; Y. Boirie; H. Vidal



42 CFR 137.202 - What types of information will Self-Governance Tribes be expected to include in the reports?  

Code of Federal Regulations, 2011 CFR

...What types of information will Self-Governance Tribes be expected to include in the...HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Operational Provisions Health Status...What types of information will Self-Governance Tribes be expected to include in...



13 CFR 123.401 - What types of mitigation measures can your business include in an application for a pre-disaster...  

Code of Federal Regulations, 2012 CFR

...2012-01-01 false What types of mitigation measures can your business include in an application...123.401 What types of mitigation measures can your business include in an application...application, each of your business' mitigation measures must satisfy the following...



Association of methotrexate and tumour necrosis factor antagonists with risk of infectious outcomes including opportunistic infections in the CORRONA registry  

PubMed Central

Objective To examine the association of methotrexate (MTX) and tumour necrosis factor (TNF) antagonists with the risk of infectious outcomes including opportunistic infections in patients with rheumatoid arthritis (RA). Methods Patients with RA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry prescribed MTX, TNF antagonists or other disease-modifying antirheumatic drugs (DMARDs) were included. The primary outcomes were incident overall and opportunistic infections. Incident rate ratios were calculated using generalised estimating equation Poisson regression models adjusted for demographics, comorbidities and RA disease activity measures. Results A total of 7971 patients with RA were followed. The adjusted rate of infections per 100 person-years was increased among users of MTX (30.9, 95% CI 29.2 to 32.7), TNF antagonists (40.1, 95% CI 37.0 to 43.4) and a combination of MTX and TNF antagonists (37.1, 95% CI 34.9 to 39.3) compared with users of other non-biological DMARDs (24.5, 95% CI 21.8 to 27.5). The adjusted incidence rate ratio (IRR) was increased in patients treated with MTX (IRR 1.30, 95% CI 1.12 to 1.50) and TNF antagonists (IRR 1.52, 95% CI 1.30 to 1.78) compared with those treated with other DMARDs. TNF antagonist use was associated with an increased risk of opportunistic infections (IRR 1.67, 95% CI 0.95 to 2.94). Prednisone use was associated with an increased risk of opportunistic infections (IRR 1.63, 95% CI 1.20 to 2.21) and an increased risk of overall infection at doses >10 mg daily (IRR 1.30, 95% CI 1.11 to 1.53). Conclusions MTX, TNF antagonists and prednisone at doses >10 mg daily were associated with increased risks of overall infections. Low-dose prednisone and TNF antagonists (but not MTX) increased the risk of opportunistic infections.

Greenberg, J D; Reed, G; Kremer, J M; Tindall, E; Kavanaugh, A; Zheng, C; Bishai, W; Hochberg, M C



Risk Factors and Primary Prevention Trials for Type 1 Diabetes  

PubMed Central

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease resulting in the designated immune destruction of insulin producing ?-cells, usually diagnosed in youth, and associated with important psychological, familial, and social disorders. Once diagnosed, patients need lifelong insulin treatment and will experience multiple disease-associated complications. There is no cure for T1DM currently. The last decade has witnessed great progress in elucidating the causes and treatment of the disease based on numerous researches both in rodent models of spontaneous diabetes and in humans. This article summarises our current understanding of the pathogenesis of T1DM, the roles of the immune system, genes, environment and other factors in the continuing and rapid increase in T1DM incidence at younger ages in humans. In addition, we discuss the strategies for primary and secondary prevention trials of T1DM. The purpose of this review is to provide an overview of this disorder's pathogenesis, risk factors that cause the disease, as well as to bring forward an ideal approach to prevent and cure the disorder.

Wu, Yan-Ling; Ding, Yan-Ping; Gao, Jian; Tanaka, Yoshimasa; Zhang, Wen



43 CFR 404.9 - What types of infrastructure and facilities may be included in an eligible rural water supply...  

Code of Federal Regulations, 2010 CFR

... (b) Storage tanks and small impoundments; (c) Water treatment facilities for potable water supplies, including desalination facilities; (d) Buildings necessary to house equipment and serve as a center for operations; (e) Power...



43 CFR 404.9 - What types of infrastructure and facilities may be included in an eligible rural water supply...  

Code of Federal Regulations, 2010 CFR

... (b) Storage tanks and small impoundments; (c) Water treatment facilities for potable water supplies, including desalination facilities; (d) Buildings necessary to house equipment and serve as a center for operations; (e) Power...



25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?  

Code of Federal Regulations, 2011 CFR

...under a recreation, tourism, and trails program...Transportation planning for tourism and recreation travel...including pedestrians and bicycles; (5) Provision...C. 319); (13) Bicycle Transportation and pedestrian...eligible for recreation, tourism, and trails...



25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?  

Code of Federal Regulations, 2010 CFR

...under a recreation, tourism, and trails program...Transportation planning for tourism and recreation travel...including pedestrians and bicycles; (5) Provision...C. 319); (13) Bicycle Transportation and pedestrian...eligible for recreation, tourism, and trails...



25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?  

Code of Federal Regulations, 2010 CFR

...under a recreation, tourism, and trails program...Transportation planning for tourism and recreation travel...including pedestrians and bicycles; (5) Provision...C. 319); (13) Bicycle Transportation and pedestrian...eligible for recreation, tourism, and trails...



Theissenia reconsidered, including molecular phylogeny of the type species T. pyrenocrata and a new genus Durotheca (Xylariaceae, Ascomycota).  


The genus Durotheca is introduced with D. depressa sp. nov., as type. Hypoxylon comedens is transferred to Durotheca, based on its morphology with further evidence from molecular phylogenetic studies; a combined ?-tubulin and ?-actin gene dataset. Theissenia cinerea is synonymized with D. comedens, and the type of Theissenia, T. pyrenocrata, is shown to occupy a basal, rather distant position in a monotypic clade in relation to sequenced taxa of Durotheca. This clade has an unresolved position in relation to the two informal subfamilies "Xylarioideae" and "Hypoxyloideae" within the Xylariaceae. New distributional data for D. comedens and T. pyrenocrata are presented, with the former found to be widespread in South-East Asia and the latter is reported as new from western Amazonia (Ecuador). One further species described in Theissenia, T. rogersii, is transferred to Durotheca, whilst T. eurima is accepted in Theissenia. PMID:23898413

Lćssře, Thomas; Srikitikulchai, Prasert; D Luangsa-Ard, J Jennifer; Stadler, Marc



High Quality Power Supply Method for Islanding Microgrid by use of Several Types of DG Systems including Rotating Machines  

NASA Astrophysics Data System (ADS)

When a microgrid is operated in the islanding mode, the operator must satisfy the power quality demand by compensating the active and reactive power using several types of distributed power generation (DG) systems. In this paper, a method to stabilize the system frequency fluctuations and voltage fluctuations of the islanding microgrid is suggested. Extending the suggested “combined cascade control method” which can realize the power compensation without interferences between several types of DGs, “hybrid control” strucuture is proposed and negative effects of control and measurement signal delays on a control are reduced. Moreover, a control of the state of charge (SoC) of energy storage devices is added. For the stabilization of the system voltage, the energy storage is driven by “STATCOM model control”. Experiments have been carried out to confirm the effects of these methods by use of the model microgrid system, and satisfying results were received.

Kikuchi, Takuro; Baba, Jumpei; Kawachi, Shunsuke; Shimoda, Eisuke; Numata, Shigeo; Yamane, Toshihiro; Masada, Eisuke; Nitta, Tanzo


Longitudinal Study of Finnish Campylobacter jejuni and C. coli Isolates from Humans, Using Multilocus Sequence Typing, Including Comparison with Epidemiological Data and Isolates from Poultry and Cattle?  

PubMed Central

We describe a study on the application of multilocus sequence typing for the analysis of Campylobacter jejuni and C. coli isolates from human domestically acquired infections in the Helsinki-Uusimaa area of Finland in 1996, 2002, and 2003. In addition, isolates from poultry meat and fecal samples of cattle from the seasonal peak (July to September) in 2003 were included in the study. In total, 361 Finnish C. jejuni and C. coli strains were typed. Sequence type 45 (ST-45) (45%), ST-21 (21%), and ST-677 (11%) clonal complexes were the most prevalent. The ST-45 and ST-677 complexes were overrepresented in comparison with previous studies. The longitudinal study revealed an association between C. coli (ST-828 complex) infection and elderly patients (?60 years). Analysis of exposure factors, determined by a previous case-control study conducted during the seasonal peak in 2002, revealed that the ST-48 complex was significantly (P < 0.05) associated with the tasting or eating of raw minced meat. New and unassigned STs were associated with swimming in natural bodies of water, whereas the ST-677 complex was related to drinking nonchlorinated water from a small water plant or water from natural sources. The ST-45 complex was associated with contact with pet cats and dogs. In 2003, ST-45 occurrence was significantly associated with poultry whereas ST-50 was associated with isolates from humans. In contrast, ST-53, ST-58, ST-61, and ST-883 were significantly associated with isolates from cattle. Further studies are needed to reveal the significance of the observed associations.

Karenlampi, Rauni; Rautelin, Hilpi; Schonberg-Norio, Daniela; Paulin, Lars; Hanninen, Marja-Liisa



Porphyria Cutanea Tarda: Multiplicity of Risk Factors Including HFE Mutations, Hepatitis C, and Inherited Uroporphyrinogen Decarboxylase Deficiency  

Microsoft Academic Search

The coexistence of factors considered to contribute to development of porphyria cutanea tarda was studied in 39 consecutive patients. Highly prevalent factors were alcohol intake in 79%, smoking in 86%, hepatitis C virus infection in 74%, estrogen use in 73% of 11 females, and at least one mutation in the HFE (hereditary hemochromatosis) gene in 65%. The C282Y mutation was

Norman G. Egger; Douglas E. Goeger; Deborah A. Payne; Emil P. Miskovsky; Steven A. Weinman; Karl E. Anderson



Towards a Four-Dimensional Model of Burnout: A Multigroup Factor-Analytic Study Including Depersonalization and Cynicism  

Microsoft Academic Search

This article investigated whether cynicism and depersonalization are two different dimensions of burnout or whether they may be collapsed into one construct of mental distance. Using confirmatory factor analyses in two samples of teachers (n = 483) and blue-collar workers (n = 474), a superior fit was found for the four-factor model that contained cynicism, depersonalization, exhaustion, and professional efficacy

Marisa Salanova; Susana Llorens; Mónica García-Renedo; Raül Burriel; Edgar BresÓ; Wilmar B. Schaufeli



Non-Mitogenic Survival-Enhancing Autocrine Factors Including Cyclophilin A Contribute to Density-Dependent mESC Growth  

PubMed Central

An improved understanding of the role of extracellular factors in controlling the embryonic stem cell (ESC) phenotype will aid the development of cell-based therapies. While the role of extracellular factors in controlling the pluripotency and differentiation of embryonic stem cells (ESCs) has been the subject of much investigation, the identity and role of extrinsic factors in modulating ESC growth under conditions supporting self-renewal remain largely unknown. We demonstrate that mouse ESC growth is density-dependent and that one of the mechanisms underlying this phenomenon is the action of survival-enhancing autocrine factors. Proteomic analysis of proteins secreted by mouse ESCs demonstrates significant levels of Cyclophilin A which increases the growth rate of mouse ESCs in a dose-dependent manner. Additionally, inhibition of the Cyclophilin A receptor – CD147 decreases the growth rate of mESCs. These findings identify Cyclophilin A as a novel survival-enhancing autocrine factor in mouse ESC cultures.

Mittal, Nikhil; Voldman, Joel



HIV type 1 viral infectivity factor and the RUNX transcription factors interact with core binding factor ? on genetically distinct surfaces.  


Human immunodeficiency virus type 1 (HIV-1) requires the cellular transcription factor core binding factor subunit ? (CBF?) to stabilize its viral infectivity factor (Vif) protein and neutralize the APOBEC3 restriction factors. CBF? normally heterodimerizes with the RUNX family of transcription factors, enhancing their stability and DNA-binding affinity. To test the hypothesis that Vif may act as a RUNX mimic to bind CBF?, we generated a series of CBF? mutants at the RUNX/CBF? interface and tested their ability to stabilize Vif and impact transcription at a RUNX-dependent promoter. While several CBF? amino acid substitutions disrupted promoter activity, none of these impacted the ability of CBF? to stabilize Vif or enhance degradation of APOBEC3G. A mutagenesis screen of CBF? surface residues identified a single amino acid change, F68D, that disrupted Vif binding and its ability to degrade APOBEC3G. This mutant still bound RUNX and stimulated RUNX-dependent transcription. These separation-of-function mutants demonstrate that HIV-1 Vif and the RUNX transcription factors interact with cellular CBF? on genetically distinct surfaces. PMID:22725134

Hultquist, Judd F; McDougle, Rebecca M; Anderson, Brett D; Harris, Reuben S



Retinal image quality with the different types of intraocular lenses including new idea of the hybrid IOLs  

NASA Astrophysics Data System (ADS)

Cataract is one of the most frequent reasons of blindness all around the world. Its treatment relies on removing the pathologically altered crystalline lens and replacing it with an artificial intraocular lens (IOL). There exists plenty of types of such implants, which differ in the optical materials and designs (shapes). However one of the important features, which is rather overlooked in the development of the intraocular implants is the chromatic aberration and its influence on the retinal image quality. In this study authors try to estimate the influence of the design and optical material of the implant on the retinal image quality in the polychromatic light, taking into consideration several exemplary types of IOLs which are commercially available. Authors also propose the partially achromatized hybrid IOLs, the longitudinal chromatic aberration (LCA)of which reduces the total LCA of the phakic eye to the level of a healthy eye's LCA. Several image characteristics, as the polychromatic Point Spread Function (PSF) and the Modulation Transfer Function (MTF) and the polychromatic encircled energy are estimated. The results of the simulations show the significance of the partial chromatic aberration correction.

Siedlecki, D.; Zaj?c, M.; Nowak, J.



Fibroblast growth factor receptor 3 is highly expressed in rarely dividing human type A spermatogonia.  


Human spermatogonia (Spg) and their fetal precursors express fibroblast growth factor receptor 3 (FGFR3). To further elucidate the role of FGFR3 in the control of Spg self-renewal, proliferation, and/or differentiation, and to narrow down the FGFR3-positive cell type(s) in the normal adult human testis, tissue sections and whole mount preparations of seminiferous tubules were analyzed combining immunofluorescence and confocal fluorescence microscopy. FGFR3 protein was chiefly observed in cellular membranes and cytoplasmic vesicles of a subpopulation of type A Spg, which comprised the chromatin rarefaction zone-containing type A(dark). Cytoplasmic expression of FGFR3 and nuclear expression of proliferation-associated antigen KI-67 were mutually exclusive. Similarly, FGFR3-positive Spg were negative for Doublesex and Mab-3 related transcription factor 1 (DMRT1). By contrast, undifferentiated embryonic cell transcription factor 1 (UTF1) and survival time-associated PHD finger in ovarian cancer 1 protein (SPOC1) were co-expressed in the nuclei of FGFR3-positive Spg. Whole mounted seminiferous tubules illustrated the clonogenic arrangement of the FGFR3/UTF1 double-positive Spg, which mainly occurred as pairs or quadruplets and, different from the KIT-positive Spg, showed no overlap with KI-67 labeled clusters. Taken together, in the adult human testis, FGFR3 expression is a feature of small clones of rarely dividing type A Spg which resemble "undifferentiated" Spg, including the spermatogonial stem cells. PMID:22777346

von Kopylow, Kathrein; Staege, Hannah; Schulze, Wolfgang; Will, Hans; Kirchhoff, Christiane



[Epidemiology of type II diabetes, diagnosis, prevalence, risk factors, complications].  


The prevalence of type 2 diabetes varies from 1.1% in sub-Saharian Africa to 3.3% in developing countries and to 5.6% in the industrialised countries, which brings the number of diabetics in the world to 135 millions. The projections of the WHO suggest a 35% increase in the prevalence of diabetes. This increase is explained by a progressively more sedentary life style, the overabundant and attractive food sources, the increase in life expectancy leading to diabetogenic ageing and, more specifically for Europe, the baby-boom effect after the Second World War, and finally, the changes in diagnostic criteria (fasting glucose > or = 1.26 g/L (7 mM) on two occasions, serum glucose > or = 2 g/L 2 hours after a loading dose of 75 g of glucose, in terms of prevalence of diagnosis and the prediction of specific diabetic complications). Age, birth weight (over or underweight) and heredity are established non-modifiable risk factors, whereas it is possible to change high risk behaviour, overweight, the syndrome of insulin resistance and hyperglycaemia. The major role of hyperglycaemia in the specific microangiographic complications of diabetes which are aggravated by hypertension, has been established. Hyperglycaemia does not seem to be a major risk factor in macroangiographic complications, especially coronary artery disease, in contrast to smoking, hypertension and certain lipid or fibrinolytic abnormalities. Epidemiological analysis of diabetes shows its invalidating feature, especially in terms of fatal vascular risk, which may be attenuated by correction of all associated metabolic abnormalities. The progression of the incidence of diabetes should alert the physician to be more attentive in the diagnosis and management of diabetes, especially with regards to early dietary intervention. PMID:11296457

Eschwčge, E



Five year follow-up of two sisters with type II sialidosis: systemic and ophthalmic findings including OCT analysis.  


The authors report a 5-year follow-up examination of two sisters diagnosed as having a juvenile form of type II sialidosis. Diagnosis occurred during a routine ophthalmic examination when the girls were 5 and 3 years old after bilateral macular cherry-red spots were revealed. Main clinical findings were hypotonia, hepatosplenomegaly, hearing loss, dysostosis, and respiratory distress. Ophthalmic symptoms were low visual acuity and nystagmus. Spectral-domain optical coherence tomography examination showed increased reflectivity of the retinal ganglion cells. Sialidosis may present as a mild form with slow progression. The cherry-red spots may be the first clue for proper diagnosis of storage disease. Spectral-domain optical coherence tomography examination unveiled the accumulation of sialic acid in the retinal ganglion cells and could potentially be used to monitor the progression of storage diseases. PMID:23819954

Rosenberg, Rémi; Halimi, Emmanuel; Mention-Mulliez, Karine; Cuisset, Jean-Marie; Holder, Muriel; Defoort-Dhellemmes, Sabine



An imaging study of body composition including lipodeposition pattern in a patient of familial partial lipodystrophy (Dunnigan type).  


Familial Partial Lipodystrophy, Dunnigan type (FPLD), is characterised by loss of subcutaneous fat from the limbs and an excessive accumulation of fat on the neck, shoulder girdle and face. Affected individuals have insulin resistance, dyslipidaemia and early cardiovascular events. Body composition (BC) with details of adipose tissue distribution were studied by Dual-Energy X-ray Absorptiometry (DEXA) and Magnetic Resonance Imaging (MRI) ina heterozygote for the FPLD mutation LMNA R482W, and in an age, sex and body mass index (BMI) matched normal control. DEXA revealed a marked decrease in total as well as regional fat percentage in the patient compared to a normal control. Marked reductions in subcutaneous fat in the extremities with substantial lipodeposition in the nape of the neck were confirmed with. MRI. The importance of increased perinephric, retroperitoneal and intermuscular fat in the thighs found in this patient, needs to be explored vis-ŕ-vis the pathogenesis of insulin resistance found in FPLD. PMID:16459536

Pandey, S N; Pungavkar, S A; Vaidya, R A; Patkar, D; Hegele, R A; Sheth, Frenny J; Sheth, J; Shah, S S; Vaidya, A B



Factors affecting insulin adherence to type I glass bottles  

SciTech Connect

Some physicochemical factors that could account for insulin adherence to type I glass bottles from admixtures of insulin with 5% dextrose (D5W) and 0.9% sodium chloride (NS) injections were studied. Samples of three volumes of NS or D5W containing insulin /sup 125/I were mixed in three sizes of bottles to test the effect of surface area and volume. Appropriate volumes of insulin were combined with insulin /sup 125/I and D5W or NS to yield solutions containing nine concentrations of insulin to test the effect of insulin concentration. Appropriate volumes of KCl injection to yield six concentrations were combined with insulin /sup 125/I and NS or D5W to test the effect of KCl concentration. All samples were assayed by gamma scintillation. In general, there was a direct relationship between the percentage of insulin adhering and the container surface area. In D5W admixtures, as the fill volume at constant insulin /sup 125/I concentration was doubled and quadrupled, the adherence of insulin decreased in all three bottle sizes (200, 250, and 500 ml). In NS admixtures, however, this effect was seen only with the 250-ml bottle. Increasing insulin concentrations over the range of 50-300 units/liter in D5W and 0-50 units/liter in NS resulted in decreased adherence. The addition of 1-60 meq/liter of KCl resulted in a significant decrease of insulin adhering from D5W and an insignificant decrease from NS admixtures. The percentage of insulin adhering to type I glass surfaces may be reduced to 25% or less by preparing i.v. admixtures in full bottles of D5W or NS at insulin concentrations of 25 to 300 units/liter. The addition of KCl, when therapeutically appropriate, will further decrease the extent of insulin adherence.

Mitrano, F.P.; Newton, D.W.



42 CFR 137.202 - What types of information will Self-Governance Tribes be expected to include in the reports?  

Code of Federal Regulations, 2010 CFR

...INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Operational Provisions Health Status Reports § 137.202 What types of information will Self-Governance Tribes be expected to include in the...



Oxytocin and Psychological Factors Affecting Type 2 Diabetes Mellitus  

PubMed Central

Background. The aim of this study was to investigate the association of oxytocin with trait and state psychological factors in type 2 diabetic patients. Methods. OXT and psychological variables were analyzed from 86 controlled diabetic patients (glycosylated haemoglobin A1c (HbA1c) < 7%) from 45 uncontrolled diabetic patients (HbA1c ? 7). Psychological characteristics were assessed with the Eysenck Personality Questionnaire (EPQ), while state psychological characteristics were measured with the Symptom Checklist 90-R (SCL 90-R). Blood samples were taken for measuring oxytocin in both subgroups during the initial phase of the study. One year later, the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments. Results. During the first evaluation of the uncontrolled diabetic patients, a statistically significant positive relationship between the levels of OXT and psychoticism in EPQ rating scale (P < 0.013) was observed. For controlled diabetic patients, a statistically significant negative relationship between oxytocin and somatization (P < 0.030), as well as obsessive-compulsive scores (P < 0.047) in SCL-90 rating scale, was observed. During the second assessment, the values of OXT decreased when the patients managed to control their metabolic profile. Conclusions. The OXT is in association with psychoticism, somatization, and obsessionality may be implicated in T2DM.

Kontoangelos, K.; Raptis, A. E.; Papageorgiou, C. C.; Tsiotra, P. C.; Papadimitriou, G. N.; Rabavilas, A. D.; Dimitriadis, G.; Raptis, S. A.



Enlarging the scope of cell penetrating prenylated peptides to include farnesylated "CAAX" box sequences and diverse cell types  

PubMed Central

Protein prenylation is a post-translational modification that is present in a large number of proteins; it has been proposed to be responsible for membrane association and protein-protein interactions which contribute to its role in signal transduction pathways. Research has been aimed at inhibiting prenylation with farnesyltransferase inhibitors (FTIs) based on the finding that the farnesylated protein Ras is implicated in 30% of human cancers. Despite numerous studies on the enzymology of prenylation in vitro, many questions remain about the process of prenylation as it occurs in living cells. Here we describe the preparation of a series of farnesylated peptides that contain sequences recognized by protein farnesyltransferase. Using a combination of flow cytometry and confocal microscopy, we show that these peptides enter a variety of different cell types. A related peptide where the farnesyl group has been replaced by a disulfide-linked decyl group is also shown to be able to efficiently enter cells. These results highlight the applicability of these peptides as a platform for further study of protein prenylation and subsequent processing in live cells.

Ochocki, Joshua D.; Igbavboa, Urule; Wood, W. Gibson; Wattenberg, Elizabeth V.; Distefano, Mark D.



An Examination of the Factor Structure of Four of the Cognitive Abilities Included in the Educational Testing Service Kit of Factor-Referenced Cognitive Tests.  

ERIC Educational Resources Information Center

The Educational Testing Service Kit of Factor-Referenced Cognitive Tests contains 72 tests that are supposed to be markers of 23 latent cognitive constructs. Examination of the factor structure of four of these tests with 165 undergraduates suggests caution in using the measures as markers of distinct factors. (SLD)

Babcock, Renee L.; Laguna, Kerrie



Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I  

SciTech Connect

von Willebrand disease (vWD) is the most common inherited bleeding disorder in humans. The disease is caused by qualitative and quantitative abnormalities of the von Willebrand factor (vWF). Genomic DNA from 25 patients with vWD type III, the most severe form of the disease, was studied using PCR followed by restriction-enzyme analysis and direct sequencing of the products. Nonsense mutations (CGA[yields]TGA) were detected in exons 28, 32, and 45 by screening of all 11 CGA arginine codons of the vWF gene. Two patients were found to be homozygous and five heterozygous for the mutation. Both parents and some of the relatives of the homozygous patients carry the mutation. These are the first reported examples of homozygous point mutations associated with the severe form of vWD. In the three heterozygous probands, one of the parents carried the mutation and had vWD type I. Family studies including parents and family members with or without vWD type I indicted that these three heterozygous patients are likely to be compound heterozygous. Twenty-one individuals from these seven families with vWD type I found to be heterozygous for the mutation. 21 refs., 5 figs., 4 tabs.

Zhang, Z.P.; Lindstedt, M.; Falk, G.; Blombaeck, M.; Egberg, N.; Anvret, M. (Karolinska Hospital, Stockholm (Sweden))



Novel mutations including deletions of the entire OFD1 gene in 30 families with type 1 orofaciodigital syndrome: a study of the extensive clinical variability.  


OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X-linked condition with lethality in males. Mutations in OFD1 also cause X-linked Joubert syndrome (JBTS10) and Simpson-Golabi-Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnostic criteria. A first, detailed evaluation of brain MRIs from seven patients with cognitive defects illustrated extensive variability with the complete brain phenotype consisting of complete agenesis of the corpus callosum, large single or multiple interhemispheric cysts, striking cortical infolding of gyri, ventriculomegaly, mild molar tooth malformation and moderate to severe cerebellar vermis hypoplasia. Although the OFD1 gene apparently escapes X-inactivation, skewed inactivation was observed in seven of 14 patients. The direction of skewing did not correlate with disease severity, reinforcing the hypothesis that additional factors contribute to the extensive intrafamilial variability. PMID:23033313

Bisschoff, Izak J; Zeschnigk, Christine; Horn, Denise; Wellek, Brigitte; Rieß, Angelika; Wessels, Maja; Willems, Patrick; Jensen, Peter; Busche, Andreas; Bekkebraten, Jens; Chopra, Maya; Hove, Hanne Dahlgaard; Evers, Christina; Heimdal, Ketil; Kaiser, Ann-Sophie; Kunstmann, Erdmut; Robinson, Kristina Lagerstedt; Linné, Maja; Martin, Patricia; McGrath, James; Pradel, Winnie; Prescott, Katrina E; Roesler, Bernd; Rudolf, Gorazd; Siebers-Renelt, Ulrike; Tyshchenko, Nataliya; Wieczorek, Dagmar; Wolff, Gerhard; Dobyns, William B; Morris-Rosendahl, Deborah J



Utilization of alkaline phosphatase fusions to identify secreted proteins, including potential efflux proteins and virulence factors from Helicobacter pylori  

Microsoft Academic Search

The targeted genomic strategy of random fusions to a partial gene encoding a signal sequence-deficient fragment of bacterial alkaline phosphatase was utilized to screen for secreted proteins in Helicobacter pylori. The rationale for targeting extracytoplasmic proteins was based on the hypothesis that most virulence factors and vaccine candidates are secreted or exported proteins. In addition, extracytosolic proteins represent good potential

James E Bina; Francis Nano; Robert E. W Hancock



Fraud Prediction and the Human Factor: An Approach to Include Human Behavior in an Automated Fraud Audit  

Microsoft Academic Search

Every year, fraud as a subset of insider threats causes billions US dollar of damage worldwide. We suggest a generic architectural model to unify the classic fraud audit approach with human behavior taking into account the fraud triangle in order to achieve better fraud detection and prevention. The human factor is extensively integrated into the audit as a qualitative component,

Stefan Hoyer; Halyna Zakhariya; Thorben Sandner; Michael H. Breitner



Practical Ranges of Loudness Levels of Various Types of Environmental Noise, Including Traffic Noise, Aircraft Noise, and Industrial Noise  

PubMed Central

In environmental noise control one commonly employs the A-weighted sound level as an approximate measure of the effect of noise on people. A measure that is more closely related to direct human perception of noise is the loudness level. At constant A-weighted sound level, the loudness level of a noise signal varies considerably with the shape of the frequency spectrum of the noise signal. In particular the bandwidth of the spectrum has a large effect on the loudness level, due to the effect of critical bands in the human hearing system. The low-frequency content of the spectrum also has an effect on the loudness level. In this note the relation between loudness level and A-weighted sound level is analyzed for various environmental noise spectra, including spectra of traffic noise, aircraft noise, and industrial noise. From loudness levels calculated for these environmental noise spectra, diagrams are constructed that show the relation between loudness level, A-weighted sound level, and shape of the spectrum. The diagrams show that the upper limits of the loudness level for broadband environmental noise spectra are about 20 to 40 phon higher than the lower limits for narrowband spectra, which correspond to the loudness levels of pure tones. The diagrams are useful for assessing limitations and potential improvements of environmental noise control methods and policy based on A-weighted sound levels.

Salomons, Erik M.; Janssen, Sabine A.



Prevalence and Risk Factors of Prolonged QTc Interval among Chinese Patients with Type 2 Diabetes  

PubMed Central

Objectives. The aim of this study was to evaluate the prevalence and the risk factors of prolonged QTc interval among Chinese patients with type 2 diabetes. Methods. The retrospective study included 3156 outpatients from the Diabetes Centre, the 306th Hospital of PLA, during the period from September 2003 to June 2010. QT interval was measured manually in the 12-lead conventional electrocardiogram. The QT interval corrected for heart rate (QTc) was calculated using Bazett's formula. Additional demographic and laboratory data were also collected. Potential risk factors of prolonged QTc interval were assessed using multivariable regression. Results. The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes was 30.1%. Height (OR 0.156, 95% CI 0.032~0.748), waist circumference (OR 1.025, 95% CI 1.010~1.040), diastolic blood pressure (OR 1.016, 95% CI 1.007~1.026), postprandial glucose (OR 1.040, 95% CI 1.022~1.059), fasting insulin (OR 1.014, 95% CI 1.003~1.025), and presence of microalbuminuria (OR 1.266, 95% CI 1.033~1.551) were significant risk factors. Conclusions. The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes is high. Risk factors for prolongation of QTc interval were low height, high waist circumference, increasing diastolic blood pressure levels, high postprandial glucose levels, high fasting insulin levels, and presence of microalbuminuria.

Li, Xiang; Ren, Hui; Xu, Zhang-rong; Liu, Yan-jun; Yang, Xiao-pin; Liu, Jian-qin



40 CFR 273.81 - Factors for petitions to include other wastes under 40 CFR part 273.  

Code of Federal Regulations, 2013 CFR

... STANDARDS FOR UNIVERSAL WASTE MANAGEMENT Petitions To Include the petitioner (e.g., waste management requirements appropriate to...diverted from non-hazardous waste management systems (e.g., the...



40 CFR 273.81 - Factors for petitions to include other wastes under 40 CFR part 273.  

Code of Federal Regulations, 2010 CFR

...part 273; (b) The waste or category of waste is not exclusive to...including, for example, households, retail and commercial...facilities); (c) The waste or category of waste...wastes, and specific management standards proposed...



40 CFR 273.81 - Factors for petitions to include other wastes under 40 CFR part 273.  

Code of Federal Regulations, 2010 CFR

...part 273; (b) The waste or category of waste is not exclusive to...including, for example, households, retail and commercial...facilities); (c) The waste or category of waste...wastes, and specific management standards proposed...



Overview of the Taxonomy of Environmental Types and the Factor Structure of the Salter Environmental Type Assessment.  

ERIC Educational Resources Information Center

|The Salter Environmental Type Assessment (SETA) was created to be a commensurate measure for the Myers-Briggs Type Indicator and to improve the efficacy of the person-environmental interaction paradigm to student affairs. A confirmatory factor analysis of SETA profiles supported the four dimensions in environmental type theory. The utility of…

Salter, Daniel W.; Vandiver, Beverly J.



Perceptions of principals and teachers on agreement and value of factors included on an upward appraisal of the principal  

Microsoft Academic Search

The purpose of this study was to determine teachers' and principals' perceptions of items that should be included on an upward appraisal instrument and the importance of these items in evaluating the effectiveness of the principal's performance from teachers' perspectives. A nonexperimental, descriptive research design was incorporated as the basis for this study. An original survey was developed by the

Nancy J Campbell



Genetic Interactions between Brn3 Transcription Factors in Retinal Ganglion Cell Type Specification  

PubMed Central

Background Visual information is conveyed from the retina to the brain via 15–20 Retinal Ganglion Cell (RGC) types. The developmental mechanisms by which RGC types acquire their distinct molecular, morphological, physiological and circuit properties are essentially unknown, but may involve combinatorial transcriptional regulation. Brn3 transcription factors are expressed in RGCs from early developmental stages, and are restricted in adults to distinct, partially overlapping populations of RGC types. Previously, we described cell autonomous effects of Brn3b (Pou4f2) and Brn3a (Pou4f1) on RGC axon and dendrites development. Methods and Findings We now have investigated genetic interactions between Brn3 transcription factors with respect to RGC development, by crossing conventional knock-out alleles of each Brn3 gene with conditional knock-in reporter alleles of a second Brn3 gene, and analyzing the effects of single or double Brn3 knockouts on RGC survival and morphology. We find that Brn3b loss results in axon defects and dendritic arbor area and lamination defects in Brn3a positive RGCs, and selectively affects survival and morphology of specific Brn3c (Pou4f3) positive RGC types. Brn3a and Brn3b interact synergistically to control RGC numbers. Melanopsin positive ipRGCs are resistant to combined Brn3 loss but are under the transcriptional control of Isl1, expanding the combinatorial code of RGC specification. Conclusions Taken together these results complete our knowledge on the mechanisms of transcriptional control of RGC type specification. They demonstrate that Brn3b is required for the correct development of more RGC cell types than suggested by its expression pattern in the adult, but that several cell types, including some Brn3a, Brn3c or Melanopsin positive RGCs are Brn3b independent.

Kretschmer, Friedrich; Mu, Xiuqian; Badea, Tudor C.



Polycystic Ovary Syndrome Is a Risk Factor for Type 2 Diabetes  

PubMed Central

Polycystic ovary syndrome (PCOS) recently has been identified as a risk factor associated with type 2 diabetes. However, the evidence derives from cross-sectional observational studies, retrospective studies, or short-term prospective studies. This long-term prospective study of a large cohort of women with PCOS, followed from youth to middle age, aimed at estimating, for the first time, the incidence and potential predictors of type 2 diabetes in this population. A total of 255 women with PCOS were followed for at least 10 years (mean follow-up 16.9 years). Six women were patients with diabetes at baseline, and another 42 women developed type 2 diabetes during the follow-up. The incidence rate of type 2 diabetes in the study population was 1.05 per 100 person-years. The age-standardized prevalence of diabetes at the end of follow-up was 39.3%, which is significantly higher with respect to that of the general Italian female population of a similar age (5.8%). The likelihood of developing type 2 diabetes significantly increased as BMI, fasting glucose, and glucose area under the curve at baseline increased and significantly decreased as sex hormone–binding globulin (SHBG) levels at follow-up increased. This study demonstrates that the risk of type 2 diabetes is markedly elevated in middle-aged women with PCOS and suggests including BMI, glucose, and SHBG-circulating levels in the risk stratification.

Gambineri, Alessandra; Patton, Laura; Altieri, Paola; Pagotto, Uberto; Pizzi, Carmine; Manzoli, Lamberto; Pasquali, Renato



Elevated serum tumor necrosis factor-alpha concentrations and bioactivity in Type 2 diabetics and patients with android type obesity.  


The role of tumor necrosis factor-alpha in insulin resistance has been studied in 59 patients with Type 2 diabetes, 28 with android type obesity and 35 healthy lean controls. Immunoreactive concentrations and bioactivity of serum tumor necrosis factor-alpha have repeatedly been determined in 8 weeks intervals for 12 months, five times per patients, by using ELISA and L929 cell cytotoxicity bioassay. Significantly higher immunoreactive tumor necrosis factor-alpha concentrations and bioactivity have been found in both, the Type 2 diabetic and obese groups as compared to the healthy persons. Tumor necrosis factor-alpha concentrations and bioactivity have showed a significant positive linear correlation with the elevated basal serum C-peptide levels and body mass indexes in both groups of patients. According to these data the cytokine might play a role in insulin resistance in obesity as well in Type 2 diabetes. PMID:9925347

Winkler, G; Salamon, F; Harmos, G; Salamon, D; Speer, G; Szekeres, O; Hajós, P; Kovács, M; Simon, K; Cseh, K



A New Approach to the Determination of the Steady-State Inflated Shape and Included Volume of Several Parachute Types in 24-Gore and 30-Gore Configurations.  

National Technical Information Service (NTIS)

AD-702041 documented a new method of determining the steady-state inflated shape and included volume of several types of parachutes in 12-gore and 16-gore configurations. This report uses the methods and technique of AD-702 041 to extend the data to 24-go...

W. P. Ludtke



Lifestyle modification improves risk factors in type 2 diabetes relatives  

Microsoft Academic Search

Aims:To investigate the short-term (16 weeks) effect of lifestyle intervention on insulin sensitivity, anthropometric and metabolic variables in non-diabetic first-degree relatives of type 2 diabetic patients (FDR).

Hilde K. Brekke; Ragnhild A. Lenner; Marja-Riitta Taskinen; Jan-Eric Mĺnsson; Tohru Funahashi; Yuji Matsuzawa; Per-Anders Jansson



Risk Factors for Type 2 Diabetes: Lessons Learned from Japanese Americans in Seattle  

PubMed Central

Migrant Japanese populations in both the United States and Brazil have for a long time shown a higher prevalence of type 2 diabetes than in native Japanese, suggesting an interaction of lifestyle and genetic predisposition in the etiology of type 2 diabetes. The overall objective of the Seattle Japanese American Community Diabetes Study was to learn more about the etiology and pathogenesis of type 2 diabetes in Japanese Americans. This metabolically based epidemiologic study included extensive assessments of insulin sensitivity, insulin response, and adiposity with the latter including measurements of body fat distribution by both anthropometry and computed tomography. Because of this, the importance of visceral adiposity as a risk factor for abnormal glucose tolerance, hypertension, coronary heart disease, and the metabolic syndrome was demonstrated. In conjunction with an examination of diet and physical activity patterns, the result was a clearer understanding of the etiology and pathogenesis of type 2 diabetes in Japanese Americans. Wepropose that a lifestyle that fosters increased weight gain, especially in the visceral adipose depot, promotes the development of insulin resistance which in turn exposes an underlying reduced beta-cell reserve in susceptible individuals, resulting in glucose intolerance and eventually in many the development of diabetes. We have shown that it may be possible to delay or prevent the development of diabetes through dietary and exercise interventions in individuals identified as having impaired glucose tolerance. The lessons learned from studying migrant Japanese in Seattle may in many ways be applicable to other populations of Asian origin.

Fujimoto, Wilfred Y.; Boyko, Edward J.; Hayashi, Tomoshige; Kahn, Steven E.; Leonetti, Donna L.; McNeely, Marguerite J.; Shuman, William P.



Effects of botulinum toxin type D on secretion of tumor necrosis factor from human monocytes  

SciTech Connect

Botulinum toxins are potent neurotoxins which block the release of neurotransmitters. The effects of these toxins on hematopoietic cells, however, are unknown. Monocytes secrete a variety of polypeptide growth factors, including tumor necrosis factor (TNF). In the study reported here, the effects of botulinum toxin type D on the secretion of TNF from human monocytes were examined. The results demonstrate that biotulinum toxin type D inhibits the release of TNF from monocytes activated by lipopolysaccharide (LPS) but not by 12-O-tetradecanoylphorbol-13-acetate. Botulinum toxin type D had no detectable effect on intracellular TNF levels in LPS-treated monocytes, indicating that the effects of this toxin involve the secretory process. This inhibitory effect of botulinum toxin type D on TNF secretion from LPS-treated monocytes was partially reversed by treatment with 12-O-tetradecanoylphorbol-13-acetate or introduction of guanosine 5'-(/gamma/-thio)t-riphosphate into these cells. The results demonstrate that TNF secretion is regulated by at least two distinct guanine nucleotide-binding proteins, one responsible for the activation of phospholiphase C and another which acts as a substrate for botulinum toxin type D. ADP-ribosylation of monocyte membranes by botulinum toxin type D demonstrated the presence of three substrates with M/sub r/s of 45,000, 21,000, and 17,000. While the role of these substrates in exocytosis is unknown, the results suggest that the M/sub r/ 21,000 substrate is involved in a process other than TNF secretion.

Imamura, K.; Spriggs, D.; Ohno, T.; Kufe, D.



[Contributory factors for glaucomatous disc cupping. 4. Generalized expansion type and localized type].  


It is widely recognized that there are two types progressive disc cupping in glaucoma. One of them is the localized type (L type) in which the cupping extends to a certain direction and the other is the generalized expansion type (G type) in which the cupping expands generally. We evaluated the optic disc in 86 eyes with primary open angle glaucoma (G type 44 eyes L type 42 eyes) to evaluate correlations of age and visual field defects between the 2 groups. Our study revealed that G type patients were significantly younger than those with L type when matched according to visual field defects. We also found that G type was revealed as the nasal step alone but not in L type. These results suggest that in G type, the optic nerve head is diffusely damaged by elevated intraocular pressure and the total nerve fibers are destroyed uniformly. On the other hand, in L type, the vulnerable portion of the optic nerve head is selectively damaged and nerve fibers constituting the optic rim area are destroyed. As a result, L type is likely to form cupping notch and reveal Bjerrum scotoma. These facts correspond to the anatomical structures of nerve fiber layers. PMID:2773699

Tetsumoto, K; Nakahashi, K; Iga, T; Mizokami, K



HIV Type 1 Fails to Trigger Innate Immune Factor Synthesis in Differentiated Oral Epithelium  

PubMed Central

Abstract The oral mucosa is relatively resistant to human immunodeficiency virus type 1 (HIV-1) transmission. The mechanisms contributing to this resistance remain incompletely understood, but may include HIV-induced synthesis of innate immune factors. We used fully differentiated oral epithelium as a surrogate for the oral mucosa in vivo, exposed it to X4- and R5-tropic HIV-1 in culture, and quantified mRNA expression of six innate immune factors. Neither virus increased expression of human beta defensin 2 (hBD-2) mRNA over supernatants from uninfected lymphoblast controls. HIV-1 also failed to induce mRNA of four additional innate immunity-related genes. Similar results were obtained with oral monolayer epithelial cells. Interestingly, the X4-tropic virus inhibited mRNA expression of hBD-2, and of three of the other factors, at higher dosages in the differentiated oral epithelium but not the monolayers. The failure of HIV-1 to induce innate immune factors in the differentiated epithelium was not due to a lack of tissue penetration, as we detected fluorescence-tagged virions up to 30??m deep from the apical surface. HIV-1 does not trigger de novo innate immune factor synthesis in oral epithelium, pointing to the role of a constitutive innate immunity for protection against HIV-1 in the oral cavity.

Hladik, Florian; Klausner, Mitchell; Harb, Socorro; Dale, Beverly A.; Coombs, Robert W.



Key factors for the encapsulation of Keggin-type heteropoly acids in the supercages of Y-type zeolite  

Microsoft Academic Search

The influences of the properties of the zeolite support on the amount of encapsulation of Keggin-type heteropoly acid (HPA) molecules in the supercages of Y-type zeolite were investigated to clarify the key factors for the production of a solid acid catalyst which maintains activity in aqueous solutions. The investigated properties were the SiO2\\/Al2O3 ratio and the type and amount of

S. R Mukai; L Lin; T Masuda; K Hashimoto




Microsoft Academic Search

There is now considerable evidence that spontaneous leukemias in mice are caused by C-type RNA viruses. These viruses appear to be capable of existing in the animal in an unexpressed form for many generations. In inbred mouse strains such as C58 and AKR, in which virus can be detected early in life, leukemia develops at high frequency in young animals



Curriculum Type as a Differentiating Factor in Medical Licensing Examinations.  

ERIC Educational Resources Information Center

|This study assessed the effects of the type of medical curriculum on differential item functioning (DIF) and group differences at the test level in Level 1 of the Comprehensive Osteopathic Medical Licensing Examinations (COMLEX). The study also explored the relationship of the DIF and group differences at the test level. There are generally two…

Shen, Linjun



Microsoft Academic Search

SUMMARY The influences of line, sex, bundle size and additive genetic variation on porcine muscle fiber type, diameter and number were investi- gated on 136 barrows and 131 gilts. Relation- ships among several porcine histological, carcass and growth measurements were also studied. Differences among the lines of swine were less prevalent for measures of fiber diameter than for staining properties

L. R. Miller; V. A. Garwood; M. D. Judge


A3 Domain Region 1803-1818 Contributes to the Stability of Activated Factor VIII and Includes a Binding Site for Activated Factor IX.  


A recent chemical footprinting study in our laboratory suggested that region 1803-1818 might contribute to A2 domain retention in activated factor VIII (FVIIIa). This site has also been implicated to interact with activated factor IX (FIXa). Asn-1810 further comprises an N-linked glycan, which seems incompatible with a role of the amino acids 1803-1818 for FIXa or A2 domain binding. In the present study, FVIIIa stability and FIXa binding were evaluated in a FVIII-N1810C variant, and two FVIII variants in which residues 1803-1810 and 1811-1818 are replaced by the corresponding residues of factor V (FV). Enzyme kinetic studies showed that only FVIII/FV 1811-1818 has a decreased apparent binding affinity for FIXa. Flow cytometry analysis indicated that fluorescent FIXa exhibits impaired complex formation with only FVIII/FV 1811-1818 on lipospheres. Site-directed mutagenesis revealed that Phe-1816 contributes to the interaction with FIXa. To evaluate FVIIIa stability, the FVIII/FV chimeras were activated by thrombin, and the decline in cofactor function was followed over time. FVIII/FV 1803-1810 and FVIII/FV 1811-1818 but not FVIII-N1810C showed a decreased FVIIIa half-life. However, when the FVIII variants were activated in presence of FIXa, only FVIII/FV 1811-1818 demonstrated an enhanced decline in cofactor function. Surface plasmon resonance analysis revealed that the FVIII variants K1813A/K1818A, E1811A, and F1816A exhibit enhanced dissociation after activation. The results together demonstrate that the glycan at 1810 is not involved in FVIII cofactor function, and that Phe-1816 of region 1811-1818 contributes to FIXa binding. Both regions 1803-1810 and 1811-1818 contribute to FVIIIa stability. PMID:23884417

Bloem, Esther; Meems, Henriet; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B



Factors That Influence Parental Attitudes toward Enrollment in Type 1 Diabetes Trials  

PubMed Central

Aims To assess parental attitudes towards type 1 diabetes clinical trials (T1DCTs) and factors that impact willingness to enroll their children with and without diabetes. Methods A cross-sectional survey of parents of children with type 1 diabetes was administered at an academic clinic and a diabetes educational event. Results Survey response rate was 36%. Of 166 participating parents, 76% were aware of T1DCTs. More parents reported willingness to enroll children with diabetes (47%) than unaffected children (36%). Only 18% recalled being asked to enroll their children, and of these, 60% agreed to enroll at least some of those times. Less than 30% were comfortable with placebos. Factors predicting willingness to enroll children with diabetes included healthcare provider trust, comfort with consent by proxy, low fear of child being a “guinea pig,” and comfort with placebo. Factors predicting willingness to enroll unaffected children were provider trust, comfort with consent by proxy, comfort with placebo, and perceived ease of understanding T1DCT information. Conclusions Parents report moderate willingness to enroll children in T1DCTs. Willingness is diminished by common trial methodologies. Although most parents recalled receiving trial-related information, significantly fewer recalled being asked to participate. Efforts to optimize effective communication around identified areas of parental concern may increase T1DCT participation.

Buscariollo, Daniela L.; Davidson, Mario A.; Black, Margo; Russell, William E.; Rothman, Russell L.; Moore, Daniel J.



Risk factors of herpes simplex type 1 (HSV1) infection and lifestyle factors associated with HSV1 manifestations  

Microsoft Academic Search

This study investigated risk factors for herpes simplex virus type 1 (HSV-1) infection in a population of university students in Germany and Spain. In addition, factors associated with the occurrence of oral lesions were studied. Serum samples were collected from 596 Spanish students from the Navarra Public University in Pamplona and 174 German students from the University of Bielefeld aged

Christiane Stock; Francisco Guillén-Grima; Juan Hermoso de Mendoza; Blanca Marin-Fernandez; Ines Aguinaga-Ontoso; Alexander Krämer



Sociodemographic and clinical factors associated with antidepressant type in a national sample of the home health care elderly  

Microsoft Academic Search

ObjectiveThe study examined in home health care (HHC) the demographic, functional and clinical factors by antidepressant (AD) type including selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) and “Other” ADs such as bupropion and mirtazapine.

Judith Weissman; Barnett S. Meyers; Samiran Ghosh; Martha L. Bruce



Type II? factors satisfying the spatial isomorphism conjecture.  


This paper addresses a conjecture in the work by Kadison and Kastler [Kadison RV, Kastler D (1972) Am J Math 94:38-54] that a von Neumann algebra M on a Hilbert space H should be unitarily equivalent to each sufficiently close von Neumann algebra N, and, moreover, the implementing unitary can be chosen to be close to the identity operator. This conjecture is known to be true for amenable von Neumann algebras, and in this paper, we describe classes of nonamenable factors for which the conjecture is valid. These classes are based on tensor products of the hyperfinite II(1) factor with crossed products of abelian algebras by suitably chosen discrete groups. PMID:23184993

Cameron, Jan; Christensen, Erik; Sinclair, Allan M; Smith, Roger R; White, Stuart A; Wiggins, Alan D



Alcohol as a Risk Factor for Type 2 Diabetes  

PubMed Central

OBJECTIVE To clarify the dose-response relationship between alcohol consumption and type 2 diabetes. RESEARCH DESIGN AND METHODS A systematic computer-assisted and hand search was conducted to identify relevant articles with longitudinal design and quantitative measurement of alcohol consumption. Adjustment was made for the sick-quitter effect. We used fractional polynomials in a meta-regression to determine the dose-response relationships by sex and end point using lifetime abstainers as the reference group. RESULTS The search revealed 20 cohort studies that met our inclusion criteria. A U-shaped relationship was found for both sexes. Compared with lifetime abstainers, the relative risk (RR) for type 2 diabetes among men was most protective when consuming 22 g/day alcohol (RR 0.87 [95% CI 0.76–1.00]) and became deleterious at just over 60 g/day alcohol (1.01 [0.71–1.44]). Among women, consumption of 24 g/day alcohol was most protective (0.60 [0.52–0.69]) and became deleterious at about 50 g/day alcohol (1.02 [0.83–1.26]). CONCLUSIONS Our analysis confirms previous research findings that moderate alcohol consumption is protective for type 2 diabetes in men and women.

Baliunas, Dolly O.; Taylor, Benjamin J.; Irving, Hyacinth; Roerecke, Michael; Patra, Jayadeep; Mohapatra, Satya; Rehm, Jurgen



High-Throughput Human Immunodeficiency Virus Type 1 (HIV1) Full Replication Assay That Includes HIV1 Vif as an Antiviral Target  

Microsoft Academic Search

Antiviral screens have proved useful for the identification of novel human immunodeficiency virus type 1 (HIV-1) inhibitors. In this study, we describe an HIV-1 full replication (HIV-1 Rep) assay that incorporates all of the targets required for replication in T-cell lines, including the HIV-1 Vif gene. The HIV-1 Rep assay was designed to exhibit optimal sensitivity to late-stage as well

Joan Cao; Jason Isaacson; Amy K. Patick; Wade S. Blair



Transforming Growth Factor ? Receptor Type 1 Is Essential for Female Reproductive Tract Integrity and Function  

Microsoft Academic Search

The transforming growth factor ? (TGF?) superfamily proteins are principle regulators of numerous biological functions. Although recent studies have gained tremendous insights into this growth factor family in female reproduction, the functions of the receptors in vivo remain poorly defined. TGF? type 1 receptor (TGFBR1), also known as activin receptor-like kinase 5, is the major type 1 receptor for TGF?

Qinglei Li; Julio E. Agno; Mark A. Edson; Ankur K. Nagaraja; Takashi Nagashima; Martin M. Matzuk



Type D Personality as a Prognostic Factor in Heart Disease: Assessment and Mediating Mechanisms  

Microsoft Academic Search

Type D personality, a synergy between negative affectivity and social inhibition, has established itself as a serious risk factor for morbidity and mortality in patients suffering from cardiovascular disease. In this review, we summarize studies on the validity of the assessment methods of Type D, emphasizing its role as an independent vulnerability factor in the progression of cardiovascular disease. We

Nina Kupper; Johan Denollet



Microalbuminuria in type 1 diabetes: Rates, risk factors and glycemic threshold  

Microsoft Academic Search

Microalbuminuria in type 1 diabetes: Rates, risk factors and glycemic threshold.BackgroundThe occurrence of microalbuminuria in type 1 diabetes is strongly predictive of renal and cardiovascular disease and is still likely to occur despite improvements in glycemic control. A better understanding of microalbuminuria is required to inform new interventions. We determined the incidence and risk factors for microalbuminuria [albumin excretion rate

Nish Chaturvedi; Simona Bandinelli; Ruggero Mangili; Guiseppe Penno; Raoul E Rottiers; John H Fuller



Prevalence, risk factors and complications associated with type 2 diabetes in migrant South Asians.  


It is estimated that type 2 diabetes (T2D) currently affects about 246 million people worldwide, with South Asians, especially Indians, having both the largest number of cases and the fastest growing prevalence. South Asian ethnicity has been identified as a major risk factor for the development of T2D with central adiposity, insulin resistance and an unfavourable lipid profile being identified as predominant signals of alarm. Leading databases, including Web of Science, Medline, PubMed and Science Direct, were consulted and manual searches were conducted for cited references in leading diabetes-related journals. In all, 152 articles were included for the final assessment reported in this review. Genetic predisposition, central adiposity and unfavourable lifestyle, including physical inactivity and an unhealthy diet, were associated with the prevalence of T2D in migrant South Asians. 'Westernization', acculturation, socio-economic factors and lack of knowledge about the disease have also been identified as contributors to the development of T2D in this population. Higher prevalence of T2D in migrant South Asians may not be entirely attributed to genetic predisposition; hence, ethnicity and associated modifiable risk factors need further investigation. Preventive measures and appropriate interventions are currently limited by the lack of ethnic-specific cut-off points for anthropometric and biological markers, as well as by the absence of reliable methods for dietary and physical activity assessment. This article describes the prevalence rate, risk factors and complications associated with T2D in migrant South Asians living in different countries. PMID:21591242

Garduńo-Diaz, Sara D; Khokhar, Santosh



Identification of another member of the transforming growth factor type beta gene family.  

PubMed Central

We report here the complete amino acid sequence of another member of the type beta transforming growth factor gene family, deduced from the nucleotide sequence of three overlapping cDNA clones. The C-terminal 112 amino acids share approximately 80% sequence identity with type beta 1 and beta 2 transforming growth factors, with many of the remaining differences being conservative substitutions. By analogy to type beta 1 and type beta 2 transforming growth factors, we predict the protein to be synthesized as a 412 amino acid precursor that undergoes proteolytic cleavage to produce the mature polypeptide. Images

ten Dijke, P; Hansen, P; Iwata, K K; Pieler, C; Foulkes, J G



Power Factor Anisotropy of p-Type and n-Type Conductive Thermoelectric Bi-Sb-Te Thin Films  

NASA Astrophysics Data System (ADS)

The best films for thermoelectric applications near room temperature are based on the compounds Bi2Te3, Sb2Te3, and Bi2Se3, which as single crystals have distinct anisotropy in their electrical conductivity ? regarding the trigonal c-axis, whereas the Seebeck coefficient S is nearly isotropic. For p- and n-type alloys, P ?c > P ||c, and the power factors P ?c of single crystals are always higher compared with polycrystalline films, where the power factor is defined as P = S 2 ?, ?c and ||c are the direction perpendicular and parallel to the c-axis, respectively. For the first time in sputter-deposited p-type (Bi0.15Sb0.85)2Te3 and n-type Bi2(Te0.9Se0.1)3 thin films, the anisotropy of the electrical conductivity has been measured directly as it depends on the angle ? between the electrical current and the preferential orientation of the polycrystals (texture) using a standard four-probe method. The graphs of ?( ?) show the expected behavior, which can be described by a weighted mixture of ? ?c and ? ||c contributions. Because ( ? ?c/ ? ||c) p < ( ? ?c/ ? ||c) n , the n-type films have stronger anisotropy than the p-type films. For this reason, the angular weighted contributions of P ||c lead to a larger drop in the power factor of polycrystalline n-type films compared with p-type films.

Rothe, K.; Stordeur, M.; Leipner, H. S.



Alcohol types and sociodemographic characteristics as risk factors for Barrett's esophagus  

PubMed Central

Background & Aims Little is known about the effects of alcohol use and sociodemographics on the risk of Barrett’s esophagus, a precursor to esophageal adenocarcinoma. We evaluated the association between alcohol use, alcohol type, sociodemographic profiles, other lifestyle factors and the risk of Barrett’s esophagus. Methods Using a case-control study within the Kaiser Permanente Northern California membership, patients with a new diagnosis of Barrett’s esophagus (n=320) diagnosed between 2002–2005 were matched to persons with gastroesophageal reflux disease (GERD) (n=316) and to population controls (n=317). We collected information using validated questionnaires during direct in-person interviews. Analyses used multivariate unconditional logistic regression. Results Total alcohol use was not significantly associated with the risk of Barrett’s esophagus, although stratification by beverage type showed an inverse association for wine drinkers compared to nondrinkers (7+ drinks wine/week vs. none: OR=0.44, 95%CI (0.20–0.99); multivariate analysis). Among population controls, those who preferred wine were more likely to have college degrees and regularly take vitamin supplements than those who preferred beer or liquor, although adjustment for these factors or GERD symptoms did not eliminate the inverse association between wine consumption and Barrett’s esophagus. Education status was significantly inversely associated with the risk of Barrett’s esophagus. Conclusions There are associations between alcohol types, socioeconomic status and the risk of Barrett’s esophagus. Although choice of alcoholic beverages was associated with several factors, multiple adjustments (including for GERD) did not eliminate the association between alcohol and Barrett’s esophagus. Further research to evaluate the associations among socioeconomic status, GERD, and Barrett’s esophagus is warranted.

Kubo, Ai; Levin, T.R.; Block, Gladys; Rumore, Gregory; Quesenberry, Charles P.; Buffler, Patricia; Corley, Douglas A.



Systematic identification of type I and type II interferon-induced antiviral factors.  


Type I and type II interferons (IFNs) are cytokines that establish the cellular antiviral state through the induction of IFN-stimulated genes (ISGs). We sought to understand the basis of the antiviral activity induced by type I and II IFNs in relation to the functions of their ISGs. Based on gene expression studies, we systematically identified antiviral ISGs by performing blinded, functional screens on 288 type I and type II ISGs. We assessed and validated the antiviral activity of these ISGs against an RNA virus, vesicular stomatitis virus (VSV), and a DNA virus, murine gammaherpes virus (MHV-68). Overall, we identified 34 ISGs that elicited an antiviral effect on the replication of either one or both viruses. Fourteen ISGs have uncharacterized antiviral functions. We further defined ISGs that affect critical life-cycle processes in expression of VSV protein and MHV-68 immediate-early genes. Two previously undescribed antiviral ISGs, TAP1 and BMP2, were further validated. TAP1-deficient fibroblasts were more susceptible to VSV infection but less so to MHV-68 infection. On the other hand, exogenous BMP2 inhibits MHV-68 lytic growth but did not affect VSV growth. These results delineate common and distinct sets of type I and type II IFN-induced genes as well as identify unique ISGs that have either broad or specific antiviral effects on these viruses. PMID:22371602

Liu, Su-Yang; Sanchez, David Jesse; Aliyari, Roghiyh; Lu, Sun; Cheng, Genhong



Systematic identification of type I and type II interferon-induced antiviral factors  

PubMed Central

Type I and type II interferons (IFNs) are cytokines that establish the cellular antiviral state through the induction of IFN-stimulated genes (ISGs). We sought to understand the basis of the antiviral activity induced by type I and II IFNs in relation to the functions of their ISGs. Based on gene expression studies, we systematically identified antiviral ISGs by performing blinded, functional screens on 288 type I and type II ISGs. We assessed and validated the antiviral activity of these ISGs against an RNA virus, vesicular stomatitis virus (VSV), and a DNA virus, murine gammaherpes virus (MHV-68). Overall, we identified 34 ISGs that elicited an antiviral effect on the replication of either one or both viruses. Fourteen ISGs have uncharacterized antiviral functions. We further defined ISGs that affect critical life-cycle processes in expression of VSV protein and MHV-68 immediate-early genes. Two previously undescribed antiviral ISGs, TAP1 and BMP2, were further validated. TAP1-deficient fibroblasts were more susceptible to VSV infection but less so to MHV-68 infection. On the other hand, exogenous BMP2 inhibits MHV-68 lytic growth but did not affect VSV growth. These results delineate common and distinct sets of type I and type II IFN-induced genes as well as identify unique ISGs that have either broad or specific antiviral effects on these viruses.

Liu, Su-Yang; Sanchez, David Jesse; Aliyari, Roghiyh; Lu, Sun; Cheng, Genhong



A PID type fuzzy controller with self-tuning scaling factors  

Microsoft Academic Search

By relating to the conventional PID control theory, we propose a new fuzzy controller structure, namely PID type fuzzy controller. In order to improve further the performance of the transient state and the steady state of the PID type controller, we develop a method to tune the scaling factors of the PID type fuzzy controller on line. Simulation of the

Zhi-Wei Woo; Hung-Yuan Chung; Jin-Jye Lin



A case-control study on risk factors for Type 1 diabetes in Taipei City  

Microsoft Academic Search

To search for non-genetic risk factors for Type 1 diabetes among Chinese, a total of 117 Type 1 diabetes patients identified from the Taipei Type 1 Diabetes Registry and 193 frequency-matched controls with normal glucose tolerance were recruited. The controls were selected from classmates or colleagues of cases with similar distributions of age, sex, and parental and individual educational levels.

T.-Y Tai; C.-Y Wang; L. L.-K Lin; L.-T Lee; S.-T Tsai; C.-J Chen



Loss of Drosophila A-type lamin C initially causes tendon abnormality including disintegration of cytoskeleton and nuclear lamina in muscular defects.  


Lamins are the major components of nuclear envelope architecture, being required for both the structural and informational roles of the nuclei. Mutations of lamins cause a spectrum of diseases in humans, including muscular dystrophy. We report here that the loss of the A-type lamin gene, lamin C in Drosophila resulted in pupal metamorphic lethality caused by tendon defects, matching the characteristics of human A-type lamin revealed by Emery-Dreifuss muscular dystrophy (EDMD). In tendon cells lacking lamin C activity, overall cell morphology was affected and organization of the spectraplakin family cytoskeletal protein Shortstop which is prominently expressed in tendon cells gradually disintegrated, notably around the nucleus and in a manner correlating well with the degradation of musculature. Furthermore, lamin C null mutants were efficiently rescued by restoring lamin C expression to shortstop-expressing cells, which include tendon cells but exclude skeletal muscle cells. Thus the critical function of A-type lamin C proteins in Drosophila musculature is to maintain proper function and morphology of tendon cells. PMID:22982669

Uchino, Ryo; Nonaka, Yu-Ki; Horigome, Tuneyoshi; Sugiyama, Shin; Furukawa, Kazuhiro



Risk factors for the development of retroprosthetic membranes with Boston Keratoprosthesis type 1: multicenter study results  

PubMed Central

Objective The purpose of this study was to identify possible risk factors for retroprosthetic membrane (RPM) development in a large multicenter cohort of patients receiving a Boston type 1 keratoprosthesis. Design Cohort study. Participants The final analysis included 265 eyes of 265 patients who underwent implantation of a Boston Keratoprosthesis Type I device between January 2003 and July 2008 by one of 19 surgeons at 18 medical centers. Methods Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and subsequently analyzed at a central data collection site. Main Outcome Measures The primary outcome was the presence or absence of a retroprosthetic membrane (RPM) during the follow-up period. Results 265 Boston Type 1 keratoprosthesis surgical procedures (265 patients) from 19 surgeons at 18 surgical centers were included in the analysis. The average age of patients was 63.3±19.1 years, 48.5% of the patients were female, and 52.5% of procedures were performed on the right eye. The mean follow-up time was 17.8±14.9 months. The majority (85.4%; n=222) had undergone an average of 2.2±1.2 (range 1–8) penetrating keratoplasties prior to keratoprosthesis implantation, and 38 eyes (14.6%) received a primary keratoprosthesis. The overall RPM formation rate was 31.7% (n=84). The most significant risk factor for RPM development was infectious keratitis (as a surgical indication for keratoprosthesis surgery itself), resulting in a rate of RPM formation of 70.6%. As an independent risk factor, the hazard ratio (HR) of RPM development in these eyes was 3.20 (95% confidence interval: 1.66, 6.17). Aniridia was also an independent risk factor for RPM development (HR=3.13; 95% confidence interval: 1.10, 8.89). Conclusions RPM formation is a common complication of keratoprosthesis surgery, occurring in approximately one third of cases. Eyes at the highest risk of RPM development are those receiving corneal replacement for infectious keratitis and aniridia.

Rudnisky, Christopher J.; Belin, Michael W.; Al-Arfaj, Khalid; Ament, Jared D.; Zerbe, Brian J.; Ciolino, Joseph B.



Reconstructive or cosmetic plastic surgery? Factors influencing the type of practice established by Canadian plastic surgeons  

PubMed Central

BACKGROUND: Some argue that the specialty of plastic surgery is facing a changing identity. Challenged by factors such as increasing competition in the cosmetic marketplace and decreasing reimbursement for reconstructive procedures, many American plastic surgeons have increasingly adopted cosmetic-focused practices. The present study investigated the currently unknown practice profiles of Canadian plastic surgeons to determine the reconstructive-cosmetic mix, as well as factors that influence practice type to determine whether a similar pattern exists in Canada. METHODS: An anonymous online survey regarding practice profiles was distributed to all 352 Canadian plastic surgeons with e-mail accounts registered with the Canadian Society of Plastic Surgeons and/or the Canadian Society for Aesthetic Plastic Surgery. RESULTS: The survey response rate was 34% (120 responses), of which 75% of respondents currently had a reconstructive practice and 25% had a cosmetic practice. Reconstructive surgeons had more educational debt following their training, spent more time on emergency call, academics and teaching and, when deciding which type of practice to establish, were more influenced by academic opportunities and less influenced by financial and nonfinancial metrics. Similarities between the groups included hours worked per week and academic achievements. CONCLUSIONS: The field of reconstructive plastic surgery appears to be thriving in Canada. While a transition from reconstructive to cosmetic practice is common, compared with their American colleagues, a greater proportion of Canadian plastic surgeons maintain reconstructive practices. Differences between reconstructive and cosmetic plastic surgeons are discussed.

McInnes, Colin W; Courtemanche, Douglas J; Verchere, Cynthia G; Bush, Kevin L; Arneja, Jugpal S



What Preoperative Factors, Including a Bone Bruise, are Associated with Knee Pain/Symptoms at Index ACLR? A MOON Cohort Study  

PubMed Central

BACKGROUND Increased knee pain at the time of ACL reconstruction may potentially predict more difficult rehabilitation, prolonged recovery, and/or be predictive of increased knee pain at two years. HYPOTHESIS We hypothesize that a bone bruise and/or other preoperative factors are associated with more knee pain/symptoms at the time of index ACL reconstruction, and the presence of a bone bruise would be associated with specific demographic and injury-related factors. STUDY DESIGN Prospective cohort. METHODS In 2007, the Multicenter Orthopaedic Outcomes Network (MOON) database began to prospectively collect surgeon-reported MRI bone bruise status. A multivariable analysis was performed to: 1) determine if a bone bruise, among other preoperative factors, is associated with more knee symptoms/pain, and 2) examine the association of factors related to bone bruise. To evaluate the association of a bone bruise with knee pain/symptoms, linear multiple regression models were fit using the continuous scores of the KOOS symptoms and pain subscales and the SF-36 bodily pain subscale as dependent variables. To examine the association between a bone bruise and risk factors, a logistic regression model was used in which the dependent variable was the presence or absence of a bone bruise. RESULTS Baseline data for 525 subjects was used for analysis, and a bone bruise was present in 419 (80%). The cohort is 58% male, median age 23 yrs. Median Marx activity level was 13. Factors associated with more pain were higher body mass index (p< 0.0001), female sex (p= 0.001), lateral collateral ligament injury (p=0.012), and older age (p= 0.038). Factors associated with more symptoms were a concomitant lateral collateral ligament injury (p=0.014), higher body mass index (p< 0.0001), and female sex (p< 0.0001). Bone bruise is not associated with symptoms/pain at the time of index ACL reconstruction. None of the factors included in the SF-36 bodily pain model were found to be significant. After controlling for other baseline factors, the following factors were associated with a bone bruise: younger age (p=0.034) and not jumping at the time of injury (p=0.006). CONCLUSION Following ACL injury, risk factors associated with a bone bruise are younger age and not jumping at the time of injury. Bone bruise is not associated with symptoms/pain at the time of index ACL reconstruction.

Dunn, Warren R.; Spindler, Kurt P.; Amendola, Annunziato; Andrish, Jack T.; Brophy, Robert H.; Flanigan, David C.; Jones, Morgan H.; Kaeding, Christopher C.; Marx, Robert G.; Matava, Matthew J.; McCarty, Eric C.; Parker, Richard D.; Wolcott, Michelle L.; Vidal, Armando F.; Wolf, Brian R.; Huston, Laura J.; Harrell, Frank E.; An, Angel Qi; Wright, Rick W.



Hypoxia-Inducible Factor Regulates Expression of Surfactant Protein in Alveolar Type II Cells In Vitro  

PubMed Central

Alveolar type II (ATII) cells cultured at an air–liquid (A/L) interface maintain differentiation, but they lose these properties when they are submerged. Others showed that an oxygen tension gradient develops in the culture medium as ATII cells consume oxygen. Therefore, we wondered whether hypoxia inducible factor (HIF) signaling could explain differences in the phenotypes of ATII cells cultured under A/L interface or submerged conditions. ATII cells were isolated from male Sprague-Dawley rats and cultured on inserts coated with a mixture of rat-tail collagen and Matrigel, in medium including 5% rat serum and 10 ng/ml keratinocyte growth factor, with their apical surfaces either exposed to air or submerged. The A/L interface condition maintained the expression of surfactant proteins, whereas that expression was down-regulated under the submerged condition, and the effect was rapid and reversible. Under submerged conditions, there was an increase in HIF1? and HIF2? in nuclear extracts, mRNA levels of HIF inducible genes, vascular endothelial growth factor, glucose transporter–1 (GLUT1), and the protein level of pyruvate dehydrogenase kinase isozyme–1. The expression of surfactant proteins was suppressed and GLUT1 mRNA levels were induced when cells were cultured with 1 mM dimethyloxalyl glycine. The expression of surfactant proteins was restored under submerged conditions with supplemented 60% oxygen. HIF signaling and oxygen tension at the surface of cells appears to be important in regulating the phenotype of rat ATII cells.

Ahmad, Aftab; Kewley, Emily; Mason, Robert J.



Prevalence and risk factors for herpes simplex virus type 2 infections in East Croatia.  


The aim of the study was to establish the seroprevalence of herpes simplex virus type 2 (HSV-2) among sexually active adults from East Croatia and to evaluate its correlates with demographic and behavioural risk factors. This cross-sectional study was conducted from the 1st June until the 30th September 2005 at the Department of Transfusion Medicine, Osijek University Hospital Center. The study included 423 blood donors composed of 366 (86.5%) men and 57 (13.5%) women. Demographic data and data on the risky sexual behaviour during the lifetime were collected with usage of an anonymous questionnaire consisting of 15 questions. Western blot testing revealed that 3.3% (14/423) subjects were positive for the presence of IgG antibodies to herpes simplex virus 2, i.e. 10 (2.7%) men and 4 (7.0%) women. A higher HSV-2 seroprevalence was associated with female sex, older age, marital status (with single subjects been under the greater risk), irregular condom use on sexual intercourses with new partners and with higher number (five or more) of sexual partners during lifetime. Among determined risk factors in the study population, only the connection between the HSV-2 positivity and the older age was statistically significant. The study has showed that the demographic rather than the behavioural risk factors are associated with higher prevalence of HSV-2 antibodies in the observed population. PMID:21661348

Miskulin, Maja; Miskulin, Ivan; Milas, Josip; Antolovi?-Pozgain, Arlen; Rudan, Stjepan; Vuksi?, Melita



Source apportionment of PM10 in a North-Western Europe regional urban background site (Lens, France) using Positive Matrix Factorization and including primary biogenic emissions  

NASA Astrophysics Data System (ADS)

In this work, the source of ambient particulate matter (PM10) collected over a one year period at an urban background site in Lens (France) were determined and investigated using a~Positive Matrix Factorization receptor model (US EPA PMF v3.0). In addition, a Potential Source Contribution Function (PSCF) was performed by means of the Hysplit v4.9 model to assess prevailing geographical origins of the identified sources. A selective iteration process was followed for the qualification of the more robust and meaningful PMF solution. Components measured and used in the PMF include inorganic and organic species: soluble ionic species, trace elements, elemental carbon (EC), sugars alcohols, sugar anhydride, and organic carbon (OC). The mean PM10 concentration measured from March 2011 to March 2012 was about 21 ?g m-3 with typically OM, nitrate and sulfate contributing to most of the mass and accounting respectively for 5.8, 4.5 and 2.3 ?g m-3 on a yearly basis. Accordingly, PMF outputs showed that the main emission sources were (in a decreasing order of contribution): secondary inorganic aerosols (28% of the total PM10 mass), aged marine emissions (19%), with probably predominant contribution of shipping activities, biomass burning (13%), mineral dust (13%), primary biogenic emissions (9%), fresh sea salts (8%), primary traffic emissions (6%) and heavy oil combustion (4%). Significant temporal variations were observed for most of the identified sources. In particular, biomass burning emissions were negligible in summer but responsible for about 25% of total PM10 and 50% of total OC at wintertime. Conversely, primary biogenic emissions were found to be negligible in winter but to represent about 20% of total PM10 and 40% of total OC in summer. The latter result calls for more investigations of primary biogenic aerosols using source apportionment studies, which quite usually disregards this type of sources. This study furthermore underlines the major influence of secondary processes during daily threshold exceedances. Finally, apparent discrepancies that could be generally observed between filter-based studies (such as the present one) and Aerosol Mass Spectrometer-based PMF analyses (organic fractions) are also discussed here.

Waked, A.; Favez, O.; Alleman, L. Y.; Piot, C.; Petit, J.-E.; Delaunay, T.; Verlinden, E.; Golly, B.; Besombes, J.-L.; Jaffrezo, J.-L.; Leoz-Garziandia, E.



Mutation Analysis of NR5A1 Encoding Steroidogenic Factor 1 in 77 Patients with 46, XY Disorders of Sex Development (DSD) Including Hypospadias  

Microsoft Academic Search

BackgroundMutations of the NR5A1 gene encoding steroidogenic factor-1 have been reported in association with a wide spectrum of 46,XY DSD (Disorder of Sex Development) phenotypes including severe forms of hypospadias.Methodology\\/Principal FindingsWe evaluated the frequency of NR5A1 gene mutations in a large series of patients presenting with 46,XY DSD and hypospadias. Based on their clinical presentation 77 patients were classified either

Slimane Allali; Jean-Baptiste Muller; Raja Brauner; Diana Lourenço; Radia Boudjenah; Vasiliki Karageorgou; Christine Trivin; Henri Lottmann; Stephen Lortat-Jacob; Claire Nihoul-Fékété; Olivier de Dreuzy; Ken McElreavey; Anu Bashamboo; Joerg Gromoll



Expression of the E2F1 Transcription Factor Overcomes Type beta Transforming Growth Factor-Mediated Growth Suppression  

Microsoft Academic Search

Inhibition of cell growth by type beta transforming growth factor (TGF-beta) occurs in mid-G_1 and is associated with decreased G_1 cyclin-dependent kinase activity and maintenance of the retinoblastoma tumor suppressor protein Rb in an underphosphorylated, growth-suppressive state. A variety of recent experiments suggest that a functional target of Rb is the E2F transcription factor. In addition, the growth-suppressive effects of

James K. Schwarz; Craig H. Bassing; Imre Kovesdi; Michael B. Datto; Michael Blazing; Samuel George; Xiao-Fan Wang; Joseph R. Nevis



Type beta Transforming Growth Factor is the Primary Differentiation-Inducing Serum Factor for Normal Human Bronchial Epithelial Cells  

Microsoft Academic Search

Type beta transforming growth factor (TGF-beta ) was shown to be the serum factor responsible for inducing normal human bronchial epithelial (NHBE) cells to undergo squamous differentiation. NHBE cells were shown to have high-affinity receptors for TGF-beta . TGF-beta induced the following markers of terminal squamous differentiation in NHBE cells: (i) increase in Ca ionophore-induced formation of crosslinked envelopes; (ii)

Tohru Masui; Lalage M. Wakefield; John F. Lechner; Moira A. La Veck; Michael B. Sporn; Curtis C. Harris



Insulin dose and cardiovascular risk factors in type 1 diabetic children and adolescents.  


Associations between a high daily insulin dose and cardiovascular risk factors, including those of the insulin-resistance syndrome, were studied in 479 Type 1 diabetic children 6 to 18 years of age. Insulin dose increased over the first two years after diagnosis of diabetes (p = 0.0001) and was significantly higher in girls (p = 0.01). For those children with diabetes duration of more than 2 years, the insulin requirement increased up to 13-14 years of age (p < 0.05) and was higher in pubertal than pre-pubertal children (p < 0.05). For girls, the requirement was higher in puberty than in post-puberty (p < 0.05) and increased with diabetes duration (p < 0.05). Triglyceride concentrations were associated positively and significantly with the insulin dose of both boys and girls, after adjustment for age, pubertal stage, diabetes duration, and metabolic control (fructosamine levels). No other consistent associations were found between insulin dose and other cardiovascular risk factors: body mass index, central adiposity, arterial blood pressures, serum total cholesterol, apoA1, apoB, Lp(a), uric acid, or urinary albumin excretion. Parental obesity, hypertension and diabetes were not related to the insulin dose of children. The results did not differ when the population was limited to the 375 children with diabetes duration of more than 2 years. It is concluded that in these Type 1 diabetic children the insulin dose for a given level of metabolic control (our surrogate measure of insulin resistance) was related to a single cardiovascular risk factor: triglyceride concentrations. PMID:9592639

Balkau, B; Tichet, J; Caces, E; Vol, S; Eschwege, E; Cahane, M



Signature-Tagged Mutagenesis of Edwardsiella ictaluri Identifies Virulence-Related Genes, Including a Salmonella Pathogenicity Island 2 Class of Type III Secretion Systems?  

PubMed Central

Edwardsiella ictaluri is the leading cause of mortality in channel catfish culture, but little is known about its pathogenesis. The use of signature-tagged mutagenesis in a waterborne infection model resulted in the identification of 50 mutants that were unable to infect/survive in catfish. Nineteen had minitransposon insertions in miscellaneous genes in the chromosome, 10 were in genes that matched to hypothetical proteins, and 13 were in genes that had no significant matches in the NCBI databases. Eight insertions were in genes encoding proteins associated with virulence in other pathogens, including three in genes involved in lipopolysaccharide biosynthesis, three in genes involved in type III secretion systems (TTSS), and two in genes involved in urease activity. With the use of a sequence from a lambda clone carrying several TTSS genes, Blastn analysis of the partially completed E. ictaluri genome identified a 26,135-bp pathogenicity island containing 33 genes of a TTSS with similarity to the Salmonella pathogenicity island 2 class of TTSS. The characterization of a TTSS apparatus mutant indicated that it retained its ability to invade catfish cell lines and macrophages but was defective in intracellular replication. The mutant also invaded catfish tissues in numbers equal to those of invading wild-type E. ictaluri bacteria but replicated poorly and was slowly cleared from the tissues, while the wild type increased in number.

Thune, Ronald L.; Fernandez, Denise H.; Benoit, Jennifer L.; Kelly-Smith, Maria; Rogge, Matthew L.; Booth, Natha J.; Landry, Christie A.; Bologna, Rachel A.



The Opportunistic Pathogen Propionibacterium acnes: Insights into Typing, Human Disease, Clonal Diversification and CAMP Factor Evolution  

PubMed Central

We previously described a Multilocus Sequence Typing (MLST) scheme based on eight genes that facilitates population genetic and evolutionary analysis of P. acnes. While MLST is a portable method for unambiguous typing of bacteria, it is expensive and labour intensive. Against this background, we now describe a refined version of this scheme based on two housekeeping (aroE; guaA) and two putative virulence (tly; camp2) genes (MLST4) that correctly predicted the phylogroup (IA1, IA2, IB, IC, II, III), clonal complex (CC) and sequence type (ST) (novel or described) status for 91% isolates (n?=?372) via cross-referencing of the four gene allelic profiles to the full eight gene versions available in the MLST database ( Even in the small number of cases where specific STs were not completely resolved, the MLST4 method still correctly determined phylogroup and CC membership. Examination of nucleotide changes within all the MLST loci provides evidence that point mutations generate new alleles approximately 1.5 times as frequently as recombination; although the latter still plays an important role in the bacterium's evolution. The secreted/cell-associated ‘virulence’ factors tly and camp2 show no clear evidence of episodic or pervasive positive selection and have diversified at a rate similar to housekeeping loci. The co-evolution of these genes with the core genome might also indicate a role in commensal/normal existence constraining their diversity and preventing their loss from the P. acnes population. The possibility that members of the expanded CAMP factor protein family, including camp2, may have been lost from other propionibacteria, but not P. acnes, would further argue for a possible role in niche/host adaption leading to their retention within the genome. These evolutionary insights may prove important for discussions surrounding camp2 as an immunotherapy target for acne, and the effect such treatments may have on commensal lineages.

McDowell, Andrew; Nagy, Istvan; Magyari, Marta; Barnard, Emma; Patrick, Sheila



Espin Actin-Cytoskeletal Proteins Are in Rat Type-I Spiral Ganglion Neurons and Include Splice-Isoforms with a Functional Nuclear Localization Signal  

PubMed Central

The espins are Ca2+-resistant actin-bundling proteins that are enriched in hair cell stereocilia and sensory cell microvilli. Here, we report a novel localization of espins to a large proportion of rat type-I spiral ganglion neurons (SGNs) and their projections to the cochlear nucleus (CN). Moreover, we show that a fraction of these espins is in the nucleus of SGNs owing to the presence of splice-isoforms that contain a functional nuclear localization signal (NLS). Espin antibody labeled ~83% of type-I SGNs, and the labeling intensity increased dramatically during early postnatal development. Type-II SGNs and vestibular ganglion neurons were unlabeled. In the CN, espin-positive auditory nerve fibers showed a projection pattern typical of type-I SGNs, with intense labeling in the nerve root region and posteroventral CN (PVCN). The anteroventral CN (AVCN) showed moderate labeling, while the dorsal CN showed weak labeling that was restricted to the deep layer. Espin-positive synaptic terminals were enriched around nerve root neurons and octopus cells in the PVCN and were also found on globular bushy cells and multipolar neurons in the PVCN and AVCN. SGNs expressed multiple espin transcripts and proteins, including splice-isoforms that contain a nonapeptide, which is rich in positively charged amino acids and creates a bipartite NLS. The nonapeptide was necessary to target espin isoforms to the nucleus and was sufficient to target an unrelated protein to the nucleus when joined with the upstream di-arginine-containing octapeptide. The presence of cytoplasmic and nuclear espins in SGNs suggest additional roles for espins in auditory neuroscience.




Initiation of Liver Growth by Tumor Necrosis Factor: Deficient Liver Regeneration in Mice Lacking Type I Tumor Necrosis Factor Receptor  

Microsoft Academic Search

The mechanisms that initiate liver regeneration after resection of liver tissue are not known. To determine whether cytokines are involved in the initiation of liver growth, we studied the regeneration of the liver after partial hepatectomy (PH) in mice lacking type I tumor necrosis factor receptor (TNFR-I). DNA synthesis after PH was severely impaired in these animals, and the expected

Yasuhiro Yamada; Irina Kirillova; Jacques J. Peschon; Nelson Fausto



Nuclear factor erythroid 2-related factor 2 deletion impairs glucose tolerance and exacerbates hyperglycemia in type 1 diabetic mice.  


The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) induces a battery of cytoprotective genes after oxidative stress. Nrf2 aids in liver regeneration by altering insulin signaling; however, whether Nrf2 participates in hepatic glucose homeostasis is unknown. Compared with wild-type mice, mice lacking Nrf2 (Nrf2-null) have lower basal serum insulin and prolonged hyperglycemia in response to an intraperitoneal glucose challenge. In the present study, blood glucose, serum insulin, urine flow rate, and hepatic expression of glucose-related genes were quantified in male diabetic wild-type and Nrf2-null mice. Type 1 diabetes was induced with a single intraperitoneal dose (200 mg/kg) of streptozotocin (STZ). Histopathology and serum insulin levels confirmed depleted pancreatic beta-cells in STZ-treated mice of both genotypes. Five days after STZ, Nrf2-null mice had higher blood glucose levels than wild-type mice. Nine days after STZ, polyuria occurred in both genotypes with more urine output from Nrf2-null mice (11-fold) than wild-type mice (7-fold). Moreover, STZ-treated Nrf2-null mice had higher levels of serum beta-hydroxybutyrate, triglycerides, and fatty acids 10 days after STZ compared with wild-type mice. STZ reduced hepatic glycogen in both genotypes, with less observed in Nrf2-null mice. Increased urine output and blood glucose in STZ-treated Nrf2-null mice corresponded with enhanced gluconeogenesis (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase)- and reduced glycolysis (pyruvate kinase)-related mRNA expression in their livers. Furthermore, the Nrf2 activator oltipraz lowered blood glucose in wild-type but not Nrf2-null mice administered STZ. Collectively, these data indicate that the absence of Nrf2 worsens hyperglycemia in type I diabetic mice and Nrf2 may represent a therapeutic target for reducing circulating glucose levels. PMID:20086057

Aleksunes, Lauren M; Reisman, Scott A; Yeager, Ronnie L; Goedken, Michael J; Klaassen, Curtis D



Antidepressant Medication as a Risk Factor for Type 2 Diabetes and Impaired Glucose Regulation: Systematic review.  


OBJECTIVE Antidepressant use has risen sharply over recent years. Recent concerns that antidepressants may adversely affect glucose metabolism require investigation. Our aim was to assess the risk of type 2 diabetes associated with antidepressants through a systematic review. RESEARCH DESIGN AND METHODS Data sources were MEDLINE, Embase, PsycINFO, The Cochrane Library, Web of Science, meeting abstracts of the European Association for the Study of Diabetes, American Diabetes Association, and Diabetes UK, Current Controlled Trials,, U.K. Clinical Research Network, scrutiny of bibliographies of retrieved articles, and contact with relevant experts. Relevant studies of antidepressant effects were included. Key outcomes were diabetes incidence and change in blood glucose (fasting and random). RESULTS Three systemic reviews and 22 studies met the inclusion criteria. Research designs included 1 case series and 21 observational studies comprising 4 cross-sectional, 5 case-control, and 12 cohort studies. There was evidence that antidepressant use is associated with type 2 diabetes. Causality is not established, but rather, the picture is confused, with some antidepressants linked to worsening glucose control, particularly with higher doses and longer duration, others linked with improved control, and yet more with mixed results. The more recent, larger studies, however, suggest a modest effect. Study quality was variable. CONCLUSIONS Although evidence exists that antidepressant use may be an independent risk factor for type 2 diabetes, long-term prospective studies of the effects of individual antidepressants rather than class effects are required. Heightened alertness to potential risks is necessary until these are complete. PMID:24065841

Barnard, Katharine; Peveler, Robert C; Holt, Richard I G




Microsoft Academic Search

To understand the potential risk factors and protective factors for invasive Haemophilus influenzae type b (Hib) disease, we conducted a case-control study among Navajo children less than two years of age resident on the Navajo Nation. We analyzed household interview data for 60 cases that occurred between August 1988 and February 1991, and for 116 controls matched by age, gender,




A self-consistent global model of solenoidal-type inductively coupled plasma discharges including the effects of radio-frequency bias power  

SciTech Connect

We developed a self-consistent global simulator of solenoidal-type inductively coupled plasma discharges and observed the effect of the radio-frequency (rf) bias power on the plasma density and the electron temperature. We numerically solved a set of spatially averaged fluid equations for charged particles, neutrals, and radicals. Absorbed power by electrons is determined by using an analytic electron heating model including the anomalous skin effect. To analyze the effects of rf bias power on the plasma properties, our model also combines the electron heating and global transport modules with an rf sheath module in a self-consistent manner. The simulation results are compared with numerical results by using the commercial software package cfd-ace + (ESI group) and experimental measurements by using a wave cutoff probe and a single Langmuir probe.

Kwon, D. C.; Chang, W. S.; Song, M. Y.; Yoon, J.-S. [Convergence Plasma Research Center, National Fusion Research Institute, Daejeon 305-333 (Korea, Republic of); Park, M. [Department of Physics, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); You, D. H. [Kyoungwon Tech, Inc., Seongnam 462-806 (Korea, Republic of); You, S. J. [Center for Vacuum Technology, Korea Research Institute of Standard and Science, Daejeon 305-340 (Korea, Republic of); Im, Y. H. [Division of Chemical Engineering, Chonbuk National University, Jeonju 561-756 (Korea, Republic of)



Birth injury as a causative factor of syringomyelia with Chiari type I deformity.  

PubMed Central

The epidemiology of syringomyelia with Chiari type I deformity was investigated with particular reference to perinatal problems. All subjects in our study were born by vaginal delivery and had a high incidence of perinatal accidents (abnormal presentations, birth injuries, and neonatal asphyxia). This study suggests that these may be strong causative factors for syringomyelia associated with Chiari type I deformity.

Hida, K; Iwasaki, Y; Imamura, H; Abe, H



Proximal Type I Endoleak After Endovascular Abdominal Aortic Aneurysm Repair: Predictive Factors  

Microsoft Academic Search

Proximal type I endoleaks after endovascular abdominal aortic aneurysm repair (EVAR) are associated with a high risk of rupture. Risk factors for developing this complication are not fully elucidated. We aimed to define preoperative predictors for proximal type I endoleak and describe its clinical outcome. From a consecutive series of 257 patients who underwent EVAR, we selected 202 who had

Sergio M. Sampaio; Jean M. Panneton; Geza I. Mozes; James C. Andrews; Thomas C. Bower; Manju Karla; Audra A. Noel; Kenneth J. Cherry; Timothy Sullivan; Peter Gloviczki



Prevalence of Asymptomatic Bacteriuria and Associated Host Factors in Women with Diabetes type 2  

Microsoft Academic Search

Background: Asymptomatic bacteriuria (ASB) is common among women with diabetes. The aim of this study was determine the prevalence of and risk factors for ASB in women with diabetes type 2 in Shahre-kord city of Iran. Methods: In a six months period (April- September 2005), a total of 100 women with diabetes (type 2) and 100 healthy women without diabetes

Moezzi M


Suicide, Schizophrenia, and Schizoid-Type Psychosis: Role of Life Events and Childhood Factors  

ERIC Educational Resources Information Center

|The first objective was to identify the provoking events of suicide in patients with schizophrenia or schizoid-type disorder, and to assess the humiliation component of these events. The second objective was to verify if quality of care during childhood is a vulnerability factor for suicide in patients with schizophrenia or schizoid-type

Tousignant, Michel; Pouliot, Louise; Routhier, Danielle; Vrakas, Georgia; McGirr, Alexander; Turecki, Gustavo



Risk factor analysis for proximal and distal reoperations after surgery for acute type A aortic dissection  

Microsoft Academic Search

Objective: This study was undertaken to determine significant risk factors for proximal or distal reoperations after surgical correction of acute type A aortic dissection. Methods: Between 1980 and 2000, a total of 160 consecutive patients (mean age 57.5 ± 13.3 years, 126 men) underwent surgery for acute type A aortic dissection. Proximal repair was performed by means of ascending aorta

Matthias Kirsch; Céline Soustelle; Rémi Houël; Marie Line Hillion; Daniel Loisance



[Biomarkers and risk factors of cardiovascular system disease in diabetics type 2].  


The content of glycated hemoglobin, a biomarker of diabetes in patients with type 2 diabetes correlates with risk factors for cardiovascular disease: hypertension, BMI and ratio of total cholesterol to HDL cholesterol. Therefore, increase in glycosylated hemoglobin should be considered a predictor of cardiovascular disease in patients with type 2 diabetes. PMID:23951913


Prevalence and associated factors of lens opacities among Chinese type 2 diabetics in Kinmen, Taiwan  

Microsoft Academic Search

The aim of this study is to assess the prevalence and associated risk factors of lens opacities among type 2 diabetics in\\u000a Kinmen, Taiwan. A community-based mass screening ascertained 971 type 2 diabetics from 1991 to 1993. From that population,\\u000a a total of 578 (59.5%) patients with type 2 diabetes underwent eye screening in 1999 with a 45° thin slit-lamp

Shih-Jen Chen; Jorn-Hon Liu; Hui-Chuan Shih; Pesus Chou; Ching-Yao Tsai; Tao-Hsin Tung



Preoperative risk factors for hospital mortality in acute type A aortic dissection  

Microsoft Academic Search

Background. Acute type A dissection is associated with postoperative complications and a high mortality rate. This study was performed to determine the perioperative risk factors leading to hospital mortality in patients with acute type A aortic dissection.Methods. One hundred twenty-two patients with acute type A aortic dissection treated surgically within 48 hours after onset were enrolled in this study. Thirty-two

Koji Kawahito; Hideo Adachi; Atsushi Yamaguchi; Takashi Ino



Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications  

PubMed Central

Faced with a global epidemic of type 2 diabetes (T2D), it is critical that researchers improve our understanding of the pathogenesis of T2D and related vascular complications. These findings may ultimately lead to novel treatment options for disease prevention or delaying progression. Two major paradigms jointly underlie the development of T2D and related coronary artery disease, diabetic nephropathy, and diabetic retinopathy. These paradigms include the genetic risk variants and behavioral/environmental factors. This article systematically reviews the literature supporting genetic determinants in the pathogenesis of T2D and diabetic vasculopathy, and the functional implications of these gene variants on the regulation of beta-cell function and glucose homeostasis. We update the discovery of diabetes and diabetic vasculopathy risk variants, and describe the genetic technologies that have uncovered them. Also, genomic linkage between obesity and T2D is discussed. There is a complementary role for behavioral and environmental factors modulating the genetic susceptibility and diabetes risk. Epidemiological and clinical data demonstrating the effects of behavioral and novel environmental exposures on disease expression are reviewed. Finally, a succinct overview of recent landmark clinical trials addressing glycemic control and its impact on rates of vascular complications is presented. It is expected that novel strategies to exploit the gene- and exposure-related underpinnings of T2D will soon result.

Murea, Mariana; Ma, Lijun; Freedman, Barry I.



Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of multiple types of cancer.  


The fibroblast growth factor (FGF) pathway promotes tumor growth and angiogenesis in many solid tumors. Although there has long been interest in FGF pathway inhibitors, development has been complicated: An effective FGF inhibitor must block the activity of multiple mitogenic FGF ligands but must spare the metabolic hormone FGFs (FGF-19, FGF-21, and FGF-23) to avoid unacceptable toxicity. To achieve these design requirements, we engineered a soluble FGF receptor 1 Fc fusion protein, FP-1039. FP-1039 binds tightly to all of the mitogenic FGF ligands, inhibits FGF-stimulated cell proliferation in vitro, blocks FGF- and vascular endothelial growth factor (VEGF)-induced angiogenesis in vivo, and inhibits in vivo growth of a broad range of tumor types. FP-1039 antitumor response is positively correlated with RNA levels of FGF2, FGF18, FGFR1c, FGFR3c, and ETV4; models with genetic aberrations in the FGF pathway, including FGFR1-amplified lung cancer and FGFR2-mutated endometrial cancer, are particularly sensitive to FP-1039-mediated tumor inhibition. FP-1039 does not appreciably bind the hormonal FGFs, because these ligands require a cell surface co-receptor, klotho or ?-klotho, for high-affinity binding and signaling. Serum calcium and phosphate levels, which are regulated by FGF-23, are not altered by administration of FP-1039. By selectively blocking nonhormonal FGFs, FP-1039 treatment confers antitumor efficacy without the toxicities associated with other FGF pathway inhibitors. PMID:23536011

Harding, Thomas C; Long, Li; Palencia, Servando; Zhang, Hongbing; Sadra, Ali; Hestir, Kevin; Patil, Namrata; Levin, Anita; Hsu, Amy W; Charych, Deborah; Brennan, Thomas; Zanghi, James; Halenbeck, Robert; Marshall, Shannon A; Qin, Minmin; Doberstein, Stephen K; Hollenbaugh, Diane; Kavanaugh, W Michael; Williams, Lewis T; Baker, Kevin P



Physician and patient management of type 2 diabetes and factors related to glycemic control in Spain  

PubMed Central

The objective of this study was to assess current treatment patterns, blood glucose test strip usage, and treatment compliance in patients with type 2 diabetes mellitus (T2DM) in primary care centers in Spain, and to assess factors related to glycemic control. We conducted a retrospective chart review of patients with T2DM and measured treatment compliance using the Morisky-Green questionnaire. 294 patients were included in the study from a population of patients attending 30 primary care centers throughout Spain. Results showed that the majority of patients were treated with oral monotherapy (36%) and oral combination therapy (35%). Less than half of the patients had good glycemic control (HbA1c ? 6.5%). Half of the patients treated pharmacologically reported good compliance with treatment. Logistic regression analyses performed to identify factors associated with glycemic control showed that high body mass index (BMI) and poor compliance were the strongest predictors of poor HbA1c control (OR: 2.198 and 1.789, respectively, p < 0.05). In conclusion, in the course of managing diabetes, physicians and patients should attempt to improve compliance and lower BMI, which could lead to better glycemic control.

Yurgin, Nicole Rae; Boye, Kristina Secnik; Dilla, Tatiana; Surinach, Nuria Lara; Llach, Xavier Badia



Risk factors of type 2 diabetes in population of Jammu and Kashmir, India  

PubMed Central

We sought to identify risk factors for type 2 diabetes (T2D) in Jammu and Kashmir populations, India. A total of 424 diabetic and 226 non-diabetic subjects from Jammu, and 161 diabetic and 100 non-diabetic subjects from Kashmir were screened for various parameters including fasting blood glucose level, 2 hour glucose level, urea, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL-C), uric acid, systolic and diastolic blood pressure level. We found that subjects aged 40-49 years had the highest rate of diabetes, with family income playing not much of a role. Kashmiri migrants or populations with rapid cultural, environmental, social or lifestyle change along with reduced physical activity, obesity and unhealthy lifestyle (smoking and alcohol consumption) were found to have higher rates of diabetes. High blood glucose, triglycerides and low HDL-C levels were found to be contributing to disease outcome. High blood pressure also contributed to a higher risk of developing T2D. Our study supports earlier reports confirming the contribution of comfortable life style, Western dietary habits and rapid life style change along with many other factors to the prevalence of diabetes. This may contribute to the epidemic proportion of diabetes in Jammu and Kashmir. Early diagnosis and routine screening for undiagnosed diabetes in obese subjects and subjects with parental diabetes history is expected to decrease the burden of chronic diabetic complications worldwide.

Mahajan, Ankit; Sharma, Swarkar; Dhar, Manoj K.; Bamezai, Rameshwar N.K.



In vivo demonstration of cell types in bone that harbor epidermal growth factor receptors  

SciTech Connect

The binding and internalization of (/sup 125/I)iodoepidermal growth factor (EGF) by bone cells of the rat was demonstrated in situ by quantitative radioautography. Specific binding sites were observed on a cell profile enriched in endocytic components, including lysosome-like structures, a rough endoplasmic reticulum-rich cell profile, and a cell profile that histologically resembles an undifferentiated precursor cell. By the criteria of gel filtration and precipitability by trichloroacetic acid, most of the bound (/sup 125/I)iodo-EGF was considered intact. By morphological criteria none of the cell profiles that bound (/sup 125/I)iodo-EGF corresponded to fully formed osteoclasts or osteoblasts. The endocytic cell was found in the epiphyseal plate between the invading capillary and the transverse and longitudinal cartilage septa as well as near osteoclasts in the zone of mixed spicules. The rough endoplasmic reticulum-rich cell was present in vacated chondrocyte lacunae of the epiphyseal plate close to the metaphysis, and the poorly differentiated cell was observed between the mixed spicules of the metaphysis. Similar cell types were also found in the alveolar bone surrounding the incisors. These cells may be the origin of established bone cell lines that harbor high concentrations of EGF receptors and may also be responsible for the humoral hypercalcemia in response to the reported actions of injected EGF or transforming growth factor-alpha as well as that of malignancy.

Martineau-Doize, B.; Lai, W.H.; Warshawsky, H.; Bergeron, J.J.



Risk factors of type 2 diabetes in population of Jammu and Kashmir, India.  


We sought to identify risk factors for type 2 diabetes (T2D) in Jammu and Kashmir populations, India. A total of 424 diabetic and 226 non-diabetic subjects from Jammu, and 161 diabetic and 100 non-diabetic subjects from Kashmir were screened for various parameters including fasting blood glucose level, 2 hour glucose level, urea, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL-C), uric acid, systolic and diastolic blood pressure level. We found that subjects aged 40-49 years had the highest rate of diabetes, with family income playing not much of a role. Kashmiri migrants or populations with rapid cultural, environmental, social or lifestyle change along with reduced physical activity, obesity and unhealthy lifestyle (smoking and alcohol consumption) were found to have higher rates of diabetes. High blood glucose, triglycerides and low HDL-C levels were found to be contributing to disease outcome. High blood pressure also contributed to a higher risk of developing T2D. Our study supports earlier reports confirming the contribution of comfortable life style, Western dietary habits and rapid life style change along with many other factors to the prevalence of diabetes. This may contribute to the epidemic proportion of diabetes in Jammu and Kashmir. Early diagnosis and routine screening for undiagnosed diabetes in obese subjects and subjects with parental diabetes history is expected to decrease the burden of chronic diabetic complications worldwide. PMID:24086170

Mahajan, Ankit; Sharma, Swarkar; Dhar, Manoj K; Bamezai, Rameshwar N K



Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid–type III polyketide synthase  

Microsoft Academic Search

Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two ?3,000-residue D. discoideum proteins, termed 'steely', as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to

Michael B Austin; Tamao Saito; Marianne E Bowman; Stephen Haydock; Atsushi Kato; Bradley S Moore; Robert R Kay; Joseph P Noel



Factors associated with successful completion of the chronic disease self-management program by adults with type 2 diabetes.  


This study examines factors associated with completion (attendance ?4 of 6 sessions) of the Chronic Disease Self-Management Program (CDSMP) by adults with type 2 diabetes. Patients with glycated hemoglobin ? 7.5 within 6 months were enrolled and completed self-report measures on demographics, health status, and self-care (n = 146). Significant differences in completion status were found for several self-care factors including healthful eating plan, spacing carbohydrates, frequent exercise, and general health. Completion was not influenced by race/ethnicity or socioeconomics. Results suggest better attention to exercise and nutrition at the start of CDSMP may be associated with completion, regardless of demographic subgroup. PMID:23455685

Helduser, Janet W; Bolin, Jane N; Vuong, Ann M; Moudouni, Darcy M; Begaye, Dawn S; Huber, John C; Ory, Marcia G; Forjuoh, Samuel N



Arabidopsis growth-regulating factor7 functions as a transcriptional repressor of abscisic acid- and osmotic stress-responsive genes, including DREB2A.  


Arabidopsis thaliana DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN2A (DREB2A) functions as a transcriptional activator that increases tolerance to osmotic and heat stresses; however, its expression also leads to growth retardation and reduced reproduction. To avoid these adverse effects, the expression of DREB2A is predicted to be tightly regulated. We identified a short promoter region of DREB2A that represses its expression under nonstress conditions. Yeast one-hybrid screening for interacting factors identified GROWTH-REGULATING FACTOR7 (GRF7). GRF7 bound to the DREB2A promoter and repressed its expression. In both artificial miRNA-silenced lines and a T-DNA insertion line of GRF7, DREB2A transcription was increased compared with the wild type under nonstress conditions. A previously undiscovered cis-element, GRF7-targeting cis-element (TGTCAGG), was identified as a target sequence of GRF7 in the short promoter region of DREB2A via electrophoretic mobility shift assays. Microarray analysis of GRF7 knockout plants showed that a large number of the upregulated genes in the mutant plants were also responsive to osmotic stress and/or abscisic acid. These results suggest that GRF7 functions as a repressor of a broad range of osmotic stress-responsive genes to prevent growth inhibition under normal conditions. PMID:22942381

Kim, June-Sik; Mizoi, Junya; Kidokoro, Satoshi; Maruyama, Kyonoshin; Nakajima, Jun; Nakashima, Kazuo; Mitsuda, Nobutaka; Takiguchi, Yuko; Ohme-Takagi, Masaru; Kondou, Youichi; Yoshizumi, Takeshi; Matsui, Minami; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko



Factors affecting the motivation of healthcare professionals providing care to Emiratis with type 2 diabetes  

PubMed Central

Objective We aimed to identify facilitators of and barriers to healthcare professionals' motivation in a diabetes centre in the United Arab Emirates (UAE). Design A qualitative research approach was employed using semistructured interviews to assess perception of and attitudes regarding healthcare professionals' motivation in providing good quality diabetes care. Setting A diabetes centre located in Abu-Dhabi, UAE. Participants Healthcare professionals including specialist physicians, dieticians, podiatrists, health educators and nurses were recruited through purposive sampling. Main outcome measures After data collection, the audiotaped interviews were transcribed verbatim and subjected to content analysis. Results Nine semistructured interviews were conducted with healthcare professionals of various professional backgrounds. Important facilitators and barriers related to patient, professional, organization and cultural factors were identified. Barriers that related to heavy workload, disjointed care, lack of patient compliance and awareness, and cultural beliefs and attitudes about diabetes were common. Key facilitators included the patient's role in achieving therapeutic outcomes as well as compliance, cooperation and communication. Conclusion This qualitative study provides some unique insights about factors affecting healthcare professionals' motivation in providing good quality care. To improve the motivation of healthcare professionals in the management of diabetes and therefore the quality of diabetes care, several steps are needed. Importantly, the role of primary care should be reinforced and strengthened regarding the management of type 2 diabetes mellitus, privacy of the consultation time should be highly protected and regulated, and awareness of the Emirate culture and its impact on health should be disseminated to the healthcare professionals providing care to Emirates with diabetes. Also, greater emphasis should be placed on educating Emiratis with diabetes on, and involving them in, the management of their condition.

Alhyas, Layla; Nielsen, Jessica D Jones; Dawoud, Dalia; Majeed, Azeem



Incineration of different types of medical wastes: emission factors for gaseous emissions  

NASA Astrophysics Data System (ADS)

Previous research works showed that to protect public health, the hospital incinerators should be provided with air pollution control devices. As most hospital incinerators do not possess such equipment, efficient methodologies should be developed to evaluate the safety of incineration procedure. Emission factors (EF) can be used for an easy estimation of legal parameters. Nevertheless, the actual knowledge is yet very scarce, mainly because EF previously published do not include enough information about the incinerated waste composition, besides considering many different waste classifications. This paper reports the first EF estimated for CO, SO 2, NO x and HCl, associated to the incineration of medical waste, segregated in different types according to the classification of the Portuguese legislation. The results showed that those EF are strongly influenced by incinerated waste composition, directly affected by incinerated waste type, waste classification, segregation practice and management methodology. The correspondence between different waste classifications was analysed comparing the estimated EF with the sole results previously published for specific waste types, being observed that the correspondence is not always possible. The legal limit for pollutant concentrations could be obeyed for NO x, but concentrations were higher than the limit for CO (11-24 times), SO 2 (2-5 times), and HCl (9-200 times), confirming that air pollution control devices must be used to protect human health. The small heating value of medical wastes with compulsory incineration implied the requirement of a bigger amount of auxiliary fuel for their incineration, which affects the emitted amounts of CO, NO x and SO 2 (28, 20 and practically 100% of the respective values were related with fuel combustion). Nevertheless, the incineration of those wastes lead to the smallest amount of emitted pollutants, the emitted amount of SO 2 and NO x reducing to 93% and the emitted amount of CO and HCl to more than 99%.

Alvim-Ferraz, M. C. M.; Afonso, S. A. V.


High levels of circulating soluble receptors for tumor necrosis factor in hairy cell leukemia and type B chronic lymphocytic leukemia.  

PubMed Central

The presence of soluble tumor necrosis factor (TNF) binding proteins (BP) was investigated in the sera of healthy volunteer blood donors and cancer patients. Two distinct types of TNFBP, types A and B, which are immunologically related to the cellular 75-kD TNF receptor (TNFR) and the cellular 55-kD TNFR, respectively, were assessed by immunoassays using nonblocking anti-receptor antibodies and 125I-recombinant human TNF alpha. As compared to the titers observed in 25 healthy controls, TNFBP types A and B titers were found to be elevated in almost all sera obtained from patients with underlying malignant disease. The highest amounts of TNFBP were seen in the sera of patients with B cell malignancies including hairy cell leukemia (HCL) and type B chronic lymphocytic leukemia. Treatment of HCL patients with recombinant human interferon-alpha was associated with decrease of circulating TNFBP.

Digel, W; Porzsolt, F; Schmid, M; Herrmann, F; Lesslauer, W; Brockhaus, M



Hepatocyte nuclear factor 6, a transcription factor that contains a novel type of homeodomain and a single cut domain.  

PubMed Central

Tissue-specific transcription is regulated in part by cell type-restricted proteins that bind to defined sequences in target genes. The DNA-binding domain of these proteins is often evolutionarily conserved. On this basis, liver-enriched transcription factors were classified into five families. We describe here the mammalian prototype of a sixth family, which we therefore call hepatocyte nuclear factor 6 (HNF-6). It activates the promoter of a gene involved in the control of glucose metabolism. HNF-6 contains two different DNA-binding domains. One of these corresponds to a novel type of homeodomain. The other is homologous to the Drosophila cut domain. A similar bipartite sequence is coded by the genome of Caenorhabditis elegans. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5

Lemaigre, F P; Durviaux, S M; Truong, O; Lannoy, V J; Hsuan, J J; Rousseau, G G



Health care providers' perspective on using family history in the prevention of type 2 diabetes: a qualitative study including different disciplines  

PubMed Central

Background Family history (FH) is considered an important factor to detect individuals at increased risk developing type 2 diabetes (T2D). Moreover, FH information could be used to personalise risk messages, which are assumed to increase risk-reducing behaviours. In this study, we aimed to explore Dutch health care professionals’ attitudes regarding current or future uptake of a more extensive use of FH information and the family system in diabetes prevention. Methods Semi-structured interviews were conducted with nineteen health care professionals from six general practices and four outpatient diabetes clinics. The use of FH information in opportunistic screening for T2D was explored, as well as the usability of a direct versus patient-mediated targeting strategy to reach persons with a FH of T2D. Three researchers analysed the interview transcripts separately. Results Dutch health care professionals considered FH an important risk factor in opportunistic screening for T2D. However, none of them used FH to promote risk-reducing behaviours. Directly targeting and educating patients known to have a FH of T2D was desirable for most primary care professionals, but not considered feasible. Findings indicated that FH information was not systematically gathered in primary care settings and electronic medical records were not equipped to retrieve persons with T2D running in their family. The idea of asking patients to pass on risk and preventive information was new to all interviewees, but was considered an acceptable strategy to reach persons with a FH of diabetes. Nevertheless, there were concerns about the accuracy of the messages delivered by the patients to their relatives. Practical barriers with regard to time, expertise, and financial reimbursement were also mentioned. Conclusions There is great interest among healthcare professionals in primary as well as secondary care about the use of FH to prevent T2D, but there are significant barriers against such use. The removal of these barriers would depend on evidence showing the cost-effectiveness of FH-based strategies designed to prevent T2D.



Intravenous DDAVP and factor VIII-von Willebrand factor concentrate for the treatment and prophylaxis of bleedings in patients With von Willebrand disease type 1, 2 and 3.  


The current standard set of von Willebrand factor (VWF) parameters used to differentiate type 1 from type 2 VWD include bleeding times (BTs), factor VIII coagulant activity (FVIII:C), VWF antigen (VWF:Ag), VWF ristocetine cofactor activity (VWF:RCo), VWF collagen binding activity (VWF:CB), ristocetine induced platelet aggregation (RIPA), and analysis of VWF multimers in low and high resolution agarose gels and the response to DDAVP. The BTs and RIPA are normal in asymptomatic carriers of a mutant VWF allele, in dominant type 1, and in recessive type 2N VWD, and this category has a normal response of VWF parameters to DDAVP. The response of FVIII:C is compromised in type 2N VWD. The BTs and RIPA are usually normal in type Vicenza and mild type 2A VWD, and these two VWD variants show a transiently good response of BT and VWF parameters followed by short in vivo half life times of VWF parameters. The BTS are strongly prolonged and RIPA typically absent in recessive severe type 1 and 3 VWD, in dominant type 2A and in recessive type 2C (very likely also 2D) VWD and consequently associated with low or absent platelet VWF, and no or poor response of VWF parameters to DDAVP. The BTs are prolonged and RIPA increased in dominant type 2B VWD, that is featured by normal platelet VWF and a poor response of BT and functional VWF to DDAVP. The BTs are prolonged and RIPA decreased in dominant type 2A and 2U, that all have low VWF platelet, very low VWF:RCo values as compared to VWF:Ag, and a poor response of functional VWF to DDAVP. VWD type 2M is featured by the presence of all VWF multimers in a low resolution agarose gel, normal or slightly prolonged BT, decreased RIPA, a poor response of VWF:RCo and a good response of FVIII and VWF:CB to DDAVP and therefore clearly in between dominant type 1 and 2U. The existing recommendations for prophylaxis and treatment of bleedings in type 2 VWD patients with FVIII/VWF concentrates are mainly derived from pharmocokinetic studies in type 3 VWD patients. FVIII/VWF concentrates should be characterised by labelling with FVIII:C, VWF:RCo, VWF:CB and VWF multimeric pattern to determine their safety and efficacy in prospective management studies. As the bleeding tendency is moderate in type 2 and severe in type 3 VWD and the FVIII:C levels are near normal in type 2 and very low in type 3 VWD patients. Proper recommendations of FVIII/VWF concentrates using VWF:RCo unit dosing for the prophylaxis and treatment of bleeding episodes are proposed and has to be stratified for the severity of bleeding, the type of surgery either minor or major and for type 2 and type 3 VWD as well. PMID:17164493

Michiels, Jan Jacques; van Vliet, Huub H D M; Berneman, Zwi; Gadisseur, Alain; van der Planken, Marc; Schroyens, Wilfried; van der Velden, Ann; Budde, Ulrich



Laminar flow in chevron-type plate heat exchangers: CFD analysis of tortuosity, shape factor and friction factor  

Microsoft Academic Search

Laminar or low Reynolds number flows are usually obtained when liquid foods with high viscosity are processed in plate heat exchangers (PHEs). The tortuosity coefficient is a key parameter used by PHEs manufacturers to estimate Fanning friction factors and convective heat transfer coefficients. Using the finite-element computational fluid dynamics program POLYFLOW®, fully developed laminar flows in double-sine chevron-type PHEs passages

Carla S. Fernandes; Ricardo P. Dias; Joăo M. Nóbrega; Joăo M. Maia



Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions  

PubMed Central

Regulatory elements recruit transcription factors that modulate gene expression distinctly across cell types, but the relationships among these remains elusive. To address this, we analyzed matched DNase-seq and gene expression data for 112 human samples representing 72 cell types. We first defined more than 1800 clusters of DNase I hypersensitive sites (DHSs) with similar tissue specificity of DNase-seq signal patterns. We then used these to uncover distinct associations between DHSs and promoters, CpG islands, conserved elements, and transcription factor motif enrichment. Motif analysis within clusters identified known and novel motifs in cell-type-specific and ubiquitous regulatory elements and supports a role for AP-1 regulating open chromatin. We developed a classifier that accurately predicts cell-type lineage based on only 43 DHSs and evaluated the tissue of origin for cancer cell types. A similar classifier identified three sex-specific loci on the X chromosome, including the XIST lincRNA locus. By correlating DNase I signal and gene expression, we predicted regulated genes for more than 500K DHSs. Finally, we introduce a web resource to enable researchers to use these results to explore these regulatory patterns and better understand how expression is modulated within and across human cell types.

Sheffield, Nathan C.; Thurman, Robert E.; Song, Lingyun; Safi, Alexias; Stamatoyannopoulos, John A.; Lenhard, Boris; Crawford, Gregory E.; Furey, Terrence S.



TMEFF2 Is a PDGF-AA Binding Protein with Methylation-Associated Gene Silencing in Multiple Cancer Types Including Glioma  

PubMed Central

Background TMEFF2 is a protein containing a single EGF-like domain and two follistatin-like modules. The biological function of TMEFF2 remains unclear with conflicting reports suggesting both a positive and a negative association between TMEFF2 expression and human cancers. Methodology/Principal Findings Here we report that the extracellular domain of TMEFF2 interacts with PDGF-AA. This interaction requires the amino terminal region of the extracellular domain containing the follistatin modules and cannot be mediated by the EGF-like domain alone. Furthermore, the extracellular domain of TMEFF2 interferes with PDGF-AA–stimulated fibroblast proliferation in a dose–dependent manner. TMEFF2 expression is downregulated in human brain cancers and is negatively correlated with PDGF-AA expression. Suppressed expression of TMEFF2 is associated with its hypermethylation in several human tumor types, including glioblastoma and cancers of ovarian, rectal, colon and lung origins. Analysis of glioma subtypes indicates that TMEFF2 hypermethylation and decreased expression are associated with a subset of non-Proneural gliomas that do not display CpG island methylator phentoype. Conclusions/Significance These data provide the first evidence that TMEFF2 can function to regulate PDGF signaling and that it is hypermethylated and downregulated in glioma and several other cancers, thereby suggesting an important role for this protein in the etiology of human cancers.

Lin, Kui; Taylor, James R.; Wu, Thomas D.; Gutierrez, Johnny; Elliott, J. Michael; Vernes, Jean-Michel; Koeppen, Hartmut; Phillips, Heidi S.; de Sauvage, Frederic J.; Meng, Y. Gloria



Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and ??, ??, and ??/?? T-cell origin: a comprehensive clinicopathologic and phenotypic study.  


Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of ?? or ?? type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 ?? enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) ?,? and, in cases tested, ? negative (presumptive NK origin); 5% were TCR ??, 3% were TCR ??, 1% were TCR ??/??, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only ?? T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with ?? EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ?2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal ?? EATL. PMID:22314189

Pongpruttipan, Tawatchai; Sukpanichnant, Sanya; Assanasen, Thamathorn; Wannakrairot, Pongsak; Boonsakan, Paisarn; Kanoksil, Wasana; Kayasut, Kanita; Mitarnun, Winyou; Khuhapinant, Archrob; Bunworasate, Udomsak; Puavilai, Teeraya; Bedavanija, Anan; Garcia-Herrera, Adriana; Campo, Elias; Cook, James R; Choi, John; Swerdlow, Steven H



Some Factors Associated with Children's Solving Performance on Four Types of Mathematical Open Sentences.  

ERIC Educational Resources Information Center

This study investigated three factors associated with third grade children's ability to solve open sentences of the types N + a = b, a + N = b, a - N = b, and N - a = b, where a and b are given whole numbers and N is to be found. Two factors were: (1) the size of the numbers a and b; and (2) the context of the sentence, whether presented alone or…

Grouws, Douglas A.


Improvement of the modulation factor for a Compton scattering type polarimeter using subdivided scintillators  

Microsoft Academic Search

We are developing a Compton scattering type polarimeter, using plastic scintillators as scatterers and NaI(Tl) scintillators as detectors of scattered X rays. To improve the modulation factor keeping the good detection efficiency, we investigated the effect of subdivided plastic and NaI(Tl) scintillators for the modulation factor and the detection efficiency with basic tests and computer simulations. By measuring both x

S. Gunji; E. Kudo; H. Sakurai



Insulin Promoter Factor 1 variation is associated with type 2 diabetes in African Americans  

Microsoft Academic Search

BACKGROUND: Defective insulin secretion is a key defect in the pathogenesis of type 2 diabetes (T2DM). The ?-cell specific transcription factor, insulin promoter factor 1 gene (IPF1), is essential to pancreatic development and the maintenance of ?-cell mass. We hypothesized that regulatory or coding variants in IPF1 contribute to defective insulin secretion and thus T2DM. METHODS: We screened 71 Caucasian

Mohammad A Karim; Xiaoqin Wang; Terri C Hale; Steven C Elbein



Purification and biological properties of type beta transforming growth factor from mouse transformed cells.  


Transforming growth factor type beta (TGF beta) has been purified from serum-free culture fluids of transformed mouse L-929 cells which are capable of continual growth in serum-free medium in the absence of any exogenously added polypeptide growth factors. TGF beta has been purified to homogeneity as judged by NH2-terminal amino acid sequence analysis. Analysis of the purified polypeptide by gel electrophoresis indicates that TGF beta is composed of two polypeptide chains of Mr 12,500 cross-linked by disulfide bonds. TGF beta was characterized by its ability to induce anchorage-dependent normal rat kidney (NRK) cells to grow in soft agar in the presence of epidermal growth factor (EGF). TGF beta was also able to enhance both EGF-induced DNA synthesis and cell proliferation on growth-arrested NRK cells in monolayer cultures under serum-free conditions. We also show that in mouse melanoma B-16 cells under serum-free conditions TGF beta stimulates both DNA synthesis in monolayer cultures and anchorage-independent growth in soft agar. Paradoxically, the anchorage-independent growth in the presence of serum of many human cell lines, including melanomas, and mammary, prostatic, vulvar, and lung carcinomas is inhibited by TGF beta at saturating concentrations similar to those that stimulate colony formation of the rodent cell lines L-929 and B-16 under serum-free conditions. The peculiar action of TGF beta is further revealed by the observations that while EGF and TGF beta synergize to induce inhibition of anchorage-independent growth of A-431 human vulvar carcinoma cells, their effects on the anchorage-independent growth of one human lung carcinoma cell line (A-549) and two human prostatic carcinoma cell lines (PC-3 and DU-145) are antagonistic. Moreover, we show that in the rodent and human cell lines TGF beta interacts with specific cellular receptors which may mediate the actions of TGF beta. We conclude that the expression of both TGF beta and TGF beta receptors by L-929 cells and the stimulation of growth of L-929 cells in serum-free medium by TGF beta suggests that TGF beta may be important for maintaining the transformed state of this tumor cell line, and the way in which a cell responds to TGF beta is dependent on the presence or absence of growth factors contained in the serum. PMID:3489522

Fernandez-Pol, J A; Klos, D J; Grant, G A



Evaluating the impacts of membrane type, coating, fouling, chemical properties and water chemistry on reverse osmosis rejection of seven nitrosoalklyamines, including NDMA.  


Reverse osmosis (RO) treatment has been found to be effective for a wide range of organics but generally small, polar, uncharged molecules such as N-nitrosodimethylamine (NDMA) can be poorly rejected. The rejection of seven N-nitrosoalkylamines with molecular masses in the range of 78-158Da, including NDMA, N-nitrosodiethylamine (NDEA), N-nitrosomethylethylamine (NMEA), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosopyrrolidine (NPyr), N-nitrosopiperidine (NPip) by three commercial brackish-water reverse osmosis membranes was studied in flat-sheet cells under cross-flow conditions. The membranes used were ESPA3 (Hydranautics), LFC3 (Hydranautics) and BW-30 (Dow/Filmtec), commonly used in water reuse applications. The effects of varying ionic strength and pH, dip-coating membranes with PEBAX 1657, a hydrophilic polymer, and artificial fouling with alginate on nitrosamine rejection were quantified. Rejection in deionized (DI) water increased with molecular mass from 56 to 70% for NDMA, to 80-91% for NMEA, 89-97% for NPyr, 92-98% for NDEA, and to beyond the detection limits for NPip, NDPA and NDBA. For the nitrosamines with quantifiable transmission, linear correlations (r(2)>0.97) were found between the number of methyl groups and the log(transmission), with factor 0.35 to 0.55 decreases in transmission per added methyl group. A PEBAX coating lowered the ESPA3 rejection of NDMA by 11% but increased the LFC3 and BW30 rejection by 6% and 15%, respectively. Artificially fouling ESPA3 membrane coupons with 170g/m(2) alginate decreased the rejection of NDMA by 18%. A feed concentration of 100mM NaCl decreased rejection of NDMA by 15% and acidifying the DI water feed to pH=3 decreased the rejection by 5%, whereas increasing the pH to 10 did not have a significant (p<0.05) effect. PMID:17582457

Steinle-Darling, Eva; Zedda, Marco; Plumlee, Megan H; Ridgway, Harry F; Reinhard, Martin



Specific binding of insulin-like growth factors 1 and 2 to the type 1 and type 2 receptors respectively.  

PubMed Central

1. Competitive binding and receptor cross-linking experiments have been used to examine the receptor-ligand interactions between three bovine insulin-like growth factors (IGF) and monolayer cultures of myoblasts and fibroblasts. 2. Labelled IGF-2 bound predominantly to the type 2 receptor with negligible label cross-linked to the type 1 receptor, notwithstanding the ability of IGF-2 to compete effectively for the binding of IGF-1 to the type 1 receptor. Approx. 100-fold higher concentrations of IGF-1 or the N-terminal truncated (des-Gly-Pro-Glu) IGF-1 (-3N:IGF-1) were required to produce competition equivalent to IGF-2. 3. All IGF peptides, but especially IGF-1, enhanced the binding of labelled IGF-2 to the type 2 receptor of lung fibroblasts. This unusual effect was probably a consequence of the displacement of labelled IGF-2 otherwise bound to a medium protein, a conclusion supported by the demonstration of a 38 kDa membrane protein cross-linked to labelled IGF-2. 4. Both IGF-1 and -3N:IGF-1 bound only to the type 1 IGF receptor in L6 myoblasts, rat vascular smooth-muscle cells and human lung fibroblasts. The peptides competed for labelled IGF-1 binding with potencies in the order -3N:IGF-1 greater than IGF-1 greater than IGF-2 much greater than insulin. Since the IGF peptides were equipotent in skin fibroblasts, it was proposed that the apparently higher affinity of -3N:IGF-1 for receptors in the other cell types was instead a consequence of a low affinity of this peptide for the competing 38 kDa binding protein. Images Fig. 2. Fig. 4.

Ballard, F J; Ross, M; Upton, F M; Francis, G L



Plasma levels of tumour necrosis factor-? in patients with chronic periodontitis and type 2 diabetes  

Microsoft Academic Search

Objectives: Studies suggest that elevated circulating tumour necrosis factor-a (TNF-a) may contribute to insulin resistance in patients with type 2 diabetes. The source of plasma TNF has been thought to be adipocytes associated with obesity, but inflammation and infection result in TNF-a production as well. Methods: We studied 46 patients with type 2 diabetes and chronic periodontitis to determine the

S. Engebretson; R. Chertog; A. Nichols; J. Hey-Hadavi; R. Celenti; J. Grbic



Lifestyle risk factors for atherosclerosis in adults with type 1 diabetes  

Microsoft Academic Search

The objective of this study was to compare the amount of self-reported physical activity, alcohol and tobacco use in a large sample of adults with type 1 diabetes and non-diabetic subjects. A second aim is to test the hypothesis that these lifestyle risk factors are associated cross-sectionally with coronary artery calcification. In 2000-2002, the Coronary Artery Calcification in Type 1

Franziska K Bishop; David M Maahs; Janet K Snell-Bergeon; Lorraine G Ogden; Greg L Kinney; Marian Rewers



Lifestyle risk factors for atherosclerosis in adults with type 1 diabetes  

Microsoft Academic Search

The objective of this study was to compare the amount of self-reported physical activity, alcohol and tobacco use in a large sample of adults with type 1 diabetes and non-diabetic subjects. A second aim is to test the hypothesis that these lifestyle risk factors are associated cross-sectionally with coronary artery calcification. In 2000—2002, the Coronary Artery Calcification in Type 1

Franziska K Bishop; David M Maahs; Janet K Snell-Bergeon; Lorraine G Ogden; Greg L Kinney; Marian Rewers



Type 2 diabetes mellitus in adolescence: Lipid and cardiovascular risk factors  

Microsoft Academic Search

This review discusses the important consequences of dyslipidemia and arteriosclerosis in type 2 diabetes as documented in\\u000a studies in adults. It then examines the relatively recent upsurge in type 2 diabetes in children and adolescents, its characteristics,\\u000a and its importance in directing our attention to cardiovascular risk factors in this age group. The discussion concludes with\\u000a an examination of the

Kenneth Lee Jones; Asheesh Kumar Dewan



Virulence Factors of Escherichia coli Isolates That Produce CTX-M-Type Extended-Spectrum  -Lactamases  

Microsoft Academic Search

This study determined the phylogenetic groups and virulence factors of 37 Escherichia coli isolates producing types of CTX-M compared with those of 19 isolates producing different types of extended-spectrum -lacta- mases (ESBLs) in a well-defined North American population. Most CTX-M-14 producers (97%) were from phylogenic group D; 67% of the CTX-M-15 producers were from group B2. A single CTX-M-14-producing strain

Johann D. D. Pitout; Kevin B. Laupland; Deirdre L. Church; Megan L. Menard; James R. Johnson



Insulin resistance: From predisposing factor to therapeutic target in type 2 diabetes  

Microsoft Academic Search

Background: Insulin resistance contributes to the pathogenesis of type 2 diabetes and is closely linked with cardiovascular risk factors and premature cardiovascular dioease.Objective: The purpose of this paper was to review the importance of insulin resistance as a core defect in type 2 diabetes, a potential contributor to accelerated atherosclerosis, and a potential target for insulin-sensitizing agents.Methods: Articles considered for

Robert R. Henry



Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation  

Microsoft Academic Search

Patients with type 2 diabetes are at considerable risk of excessive morbidity and mortality from cardiovascular disease (CVD). We investigated the clinical effectiveness of Pycnogenol, a flavonoid-rich dietary supplement, in reducing antihypertensive medication use and CVD risk factors in subjects with type 2 diabetes. Forty-eight individuals were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. Patients were diagnosed

Sherma Zibadi; Peter J. Rohdewald; Danna Park; Ronald Ross Watson



Induction of tumor necrosis factor alpha by the group- and type-specific polysaccharides from type III group B streptococci.  

PubMed Central

Previous studies suggested that circulating tumor necrosis factor alpha (TNF-alpha) may have a pathophysiologic role in experimental neonatal sepsis induced by group B streptococci (GBS). This study was undertaken to investigate the ability of the type III and group-specific polysaccharides of GBS to induce TNF-alpha production and TNF-alpha-dependent lethality in neonatal rats. The cytokine was detected in plasma samples by the L929 cytotoxicity assay. Intracardiac injections of either polysaccharide induced dose-dependent, transient elevations in plasma TNF-alpha levels that returned to baseline values after 5 h. The group-specific antigen induced significantly higher mean peak TNF-alpha levels than the type III antigen (125 +/- 47 versus 44 +/- 15 U/ml with 70 mg/kg of body weight). Glycogen (70 mg/kg), used as a negative control, did not induce TNF-alpha. The lipopolysaccharide-neutralizing agent polymyxin B did not decrease TNF-alpha levels induced by either polysaccharide, ruling out contamination with endotoxin as a possible cause of TNF-alpha induction. Fifty percent lethal doses of the type III and group-specific antigens given as intracardiac injections were 105 and 16 mg/kg, respectively. Salmonella endotoxin, used as a positive control, had a 50% lethal dose of 0.1 mg/kg. The lethal activities of GBS polysaccharides, as well as endotoxin, were completely prevented by pretreatment of neonatal rats with the respective specific antibodies or anti-murine TNF-alpha serum. To assess the relative importance of the type-specific substance in TNF-alpha induction by whole bacteria, two unrelated GBS transposon mutants devoid of only the type-specific capsular polysaccharide (COH1-13 and COH31-15) were employed. Each of the heat-killed unencapsulated mutants was able to produce plasma TNF-alpha level elevations or TNF-alpha-dependent lethality but was significantly less efficient in these activities than the corresponding encapsulated wild-type strain. These data suggest that the presence of type-specific material on GBS is not necessary for the stimulation of TNF-alpha production. Type III capsular polysaccharide, however, can significantly increase the ability of GBS to induce TNF-alpha. Further studies will be needed to assess the importance of TNF-alpha induction by the group- and type-specific antigens in the pathophysiology of GBS disease.

Mancuso, G; Tomasello, F; von Hunolstein, C; Orefici, G; Teti, G



Temperature-dependent Debye-Waller factors for semiconductors with the wurtzite-type structure.  


We computed Debye-Waller factors in the temperature range from 0.1 to 1000 K for AlN, GaN, InN, ZnO and CdO with the wurtzite-type structure. The Debye-Waller factors were derived from phonon densities of states obtained from Hellmann-Feynman forces computed within the density-functional-theory formalism. The temperature dependences of the Debye-Waller factors were fitted and fit parameters are given. PMID:19349666

Schowalter, M; Rosenauer, A; Titantah, J T; Lamoen, D



The three dimensional structure of the type I insulin-like growth factor receptor  

PubMed Central

Ever since the discovery of insulin and its role in the regulation of glucose metabolism, there has been great interest in the molecule itself, the insulin-like growth factors (IGFs), and their receptors (IR and IGF-R). These receptors form a subfamily of tyrosine kinase receptors which are large, transmembrane proteins consisting of several structural domains. Their ectodomains have a similar arrangement of two homologous domains (L1 and L2) separated by a Cys rich region. The C-terminal half of their ectodomains consists of three fibronectin type 3 repeats, and an insert domain that contains the ?–? cleavage site. This review summarises the key developments in the understanding of the structure of this family of receptors and their relation to other multidomain proteins. Data presented will include multiple sequence analyses, single molecule electron microscope images of the IGF-1R, insulin receptor (IR), and IR–Fab complexes, and the three dimensional structure of the first three domains of the IGF-1R determined to 2.6 ? resolution by x ray crystallography. The L domains each adopt a compact shape consisting of a single stranded, right handed ?-helix. The Cys rich region is composed of eight disulphide bonded modules, seven of which form a rod shaped domain with modules associated in an unusual manner.

Ward, C W; Garrett, T P J; McKern, N M; Lou, M; Cosgrove, L J; Sparrow, L G; Frenkel, M J; Hoyne, P A; Elleman, T C; Adams, T E; Lovrecz, G O; Lawrence, L J; Tulloch, P A



Vascular endothelial growth factor-induced elimination of the type 1 interferon receptor is required for efficient angiogenesis  

PubMed Central

Angiogenesis is stimulated by vascular endothelial growth factor (VEGF) and antagonized by type 1 interferons, including IFN-?/?. On engaging their respective receptors (VEGFR2 and IFNAR), both stimuli activate protein kinase D2 (PKD2) and type 1 IFNs require PKD2 activation and recruitment to IFNAR1 to promote the phosphorylation-dependent ubiquitination, down-regulation, and degradation of the cognate receptor chain, IFNAR1. Data reveal that PKD2 activity is dispensable for VEGF-stimulated down-regulation of VEGFR2. Remarkably, VEGF treatment promotes the recruitment of PKD2 to IFNAR1 as well as ensuing phosphorylation, ubiquitination, and degradation of IFNAR1. In cells exposed to VEGF, phosphorylation-dependent degradation of IFNAR1 leads to an inhibition of type 1 IFN signaling and is required for efficient VEGF-stimulated angiogenesis. Importance of this mechanism for proangiogenic or antiangiogenic responses in cells exposed to counteracting stimuli and the potential medical significance of this regulation are discussed.

Zheng, Hui; Qian, Juan; Carbone, Christopher J.; Leu, N. Adrian; Baker, Darren P.



OASL1 inhibits translation of the type I interferon-regulating transcription factor IRF7.  


The production of type I interferon is essential for viral clearance but is kept under tight control to avoid unnecessary tissue damage from hyperinflammatory responses. Here we found that OASL1 inhibited translation of IRF7, the master transcription factor for type I interferon, and thus negatively regulated the robust production of type I interferon during viral infection. OASL1 inhibited the translation of IRF7 mRNA by binding to the 5' untranslated region (UTR) of IRF7 and possibly by inhibiting scanning of the 43S preinitiation complex along the message. Oasl1-/- mice were resistant to viral infection because of the greater abundance of type I interferon, which suggests that OASL1 could be a potential therapeutic target for boosting the production of type I interferon during viral infection. PMID:23416614

Lee, Myeong Sup; Kim, Byungil; Oh, Goo Taeg; Kim, Young-Joon



MTHFR C677T genotype as a risk factor for epilepsy including post-traumatic epilepsy in a representative military cohort.  


The well-studied C677T variant in the methylenetetrahydrofolate reductase (MTHFR) enzyme is a biologically plausible genetic risk factor for seizures or epilepsy. First, plasma/serum levels of homocysteine, a pro-convulsant, are moderately elevated in individuals with the homozygote TT genotype. Furthermore, the TT genotype has been previously linked with migraine with aura-a comorbid condition-and with alcohol withdrawal seizures. Finally, several small studies have suggested that the TT genotype may be overrepresented in epilepsy patients. In this study, we consider whether the MTHFR C677T or A1298C variants are associated with risk of epilepsy including post-traumatic epilepsy (PTE) in a representative military cohort. Study subjects were selected from the cohort of military personnel on active duty during the years 2003 through 2007 who had archived serum samples at the DoD Serum Repository, essentially all active duty personnel during this time frame. We randomly selected 800 epilepsy patients and 800 matched controls based on ICD-9-CM diagnostic codes. We were able to isolate sufficient genetic material from the archived sera to genotype approximately 85% of our study subjects. The odds of epilepsy were increased in subjects with the TT versus CC genotype (crude OR=1.52 [1.04-2.22], p=0.031; adjusted OR=1.57 [1.07-2.32], p=0.023). In our sensitivity analysis, risk was most evident for patients with repeated rather than single medical encounters for epilepsy (crude OR=1.85 [1.14-2.97], p=0.011, adjusted OR=1.95 [1.19-3.19], p=0.008), and particularly for PTE (crude OR=3.14 [1.41-6.99], p=0.005; adjusted OR=2.55 [1.12-5.80], p=0.026). Our early results suggest a role for the common MTHFR C677T variant as a predisposing factors for epilepsy including PTE. Further exploration of baseline homocysteine and folate levels as predictors of seizure risk following traumatic brain injury is warranted. PMID:21787169

Scher, Ann I; Wu, Holly; Tsao, Jack W; Blom, Henk J; Feit, Preethy; Nevin, Remington L; Schwab, Karen A



Effect of stem cell factor on myelopoiesis potential in human Dexter-type culture systems.  


Hematopoiesis is influenced by the presence of the hematopoietic microenvironment, and Dexter-type liquid culture systems represent an in vitro representation of some aspects of the microenvironment that are optimal for the propagation of myeloid progenitors. Marrow stromal layers, which constitute part of these culture systems, produce growth factors, including stem cell factor (SCF), a ligand for the c-kit proto-oncogene that has been found to increase detection of myeloid, erythroid, and megakaryocytic progenitors in short-term marrow colony assays. In this work, the role of SCF in Dexter-type culture systems was examined to better define its contribution to steady-state myelopoiesis. When cultured in the continued presence of 100 ng/mL SCF, both primary and recharged cultures demonstrated significantly greater CFU-GM output, with quantitative differences noted throughout culture duration (up to 6 weeks). This increase in CFU-GM could be inhibited specifically with the addition of 1:1500 SR-1, a neutralizing anti-c-kit monoclonal antibody (MAb) that neutralizes the biological effects of SCF, and the increase was noted both with recharged light-density marrow cells and purified CD34+ progenitor cells. On the other hand, when primary or recharged marrow cultures were established in the absence of exogenous SCF, but in the continuous presence of SR-1, no inhibition of CFU-GM output was observed. When light-density marrow cells were purged of pre-existing CFU-GM by 4-hydroperoxycyclophosphamide (4-HC) and were seeded over irradiated stromal layers, exogenous SCF resulted in detection of CFU-GM from 4-HC-treated cells as early as 1 week of culture, as compared to the lack of significant emergence of CFU-GMs at 4 weeks in the control cultures. This SCF effect was also inhibited by SR-1. Purified CD34+ progenitor cells did not adhere to SCF immobilized to tissue culture plates, and the adhesion of such progenitors to murine Steel lines transfected with membrane-bound SCF was not greater than to the parent nontransfected Steel line, suggesting that the effect of SCF was not on CD34+ cell adhesion. These studies confirm the action of SCF at a pre-CFU level, and they demonstrate the ability of SCF to stimulate increased production of myeloid progenitors in long-term liquid culture systems. PMID:7533098

Liesveld, J L; Broudy, V C; Harbol, A W; Abboud, C N



Salient factors in child molestation: Moral development, social competence, and type of offender  

Microsoft Academic Search

The current study was designed to build on and extend the existing knowledge base of factors that cause, maintain, and influence child molestation. Theorized links among the type of offender and the offender's levels of moral development and social competence in the perpetration of child molestation were investigated. The conceptual framework for the study is based on the cognitive developmental

Colleen Catherine McCoury



Mexican American Parents' Perceptions of Childhood Risk Factors for Type 2 Diabetes  

ERIC Educational Resources Information Center

A study was conducted to identify the norms, values, and perceptions of urban immigrant Mexican American (MA) parents of school children relative to physical activity, healthy eating, and child risk factors for type 2 diabetes. Investigators facilitated five focus groups in an urban elementary school setting and analyzed data using qualitative…

Head, Barbara J.; Barr, Kathleen L.; Baker, Sharon K.



The Type 1 growth factor receptors and their ligands considered as a complex system  

Microsoft Academic Search

The Type 1 family of growth factors and their receptors play an important role in normal development, wound healing and in diseases such as cancer. The products of the four receptor genes and the ten genes specifying ligands interact in a complex pattern. Such systems may develop emergent properties which cannot be predicted from a reductionist analysis of the interactions

W J Gullick



Factors associated with psychological and behavioral functioning in people with type 2 diabetes living in France  

Microsoft Academic Search

BACKGROUND: To identify demographic and clinical factors associated with psychological and behavioral functioning (PBF) in people with type 2 diabetes living in France. METHODS: In March 2002, approximately 10,000 adults, who had been reimbursed for at least one hypoglycemic treatment or insulin dose during the last quarter of 2001, received a questionnaire about their health status and PBF (3,646 responders).

Stephanie Boini; Marie-Line Erpelding; Anne Fagot-Campagna; Mounir Mesbah; Judith Chwalow; Alfred Penfornis; Vincent Coliche; Etienne Mollet; Keith Meadows; Serge Briançon



Admixture in Mexico City: implications for admixture mapping of Type 2 diabetes genetic risk factors  

Microsoft Academic Search

Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases showing prevalence differ- ences between major continental groups. Type 2 dia- betes (T2D) is at least twice as prevalent in Native American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis of this

Veronica L. Martinez-Marignac; Adan Valladares; Emily Cameron; Andrea Chan; Arjuna Perera; Rachel Globus-Goldberg; Niels Wacher; Jesus Kumate; Paul McKeigue; David O'Donnell; Mark D. Shriver; Miguel Cruz; Esteban J. Parra



Noninvasive Screening for Risk Factors of Type 2 Diabetes in Young, Rural, Caucasian Children  

ERIC Educational Resources Information Center

|School nurses play an important role in identifying students who are at risk for Type 2 diabetes mellitus (T2DM). Few studies have screened Caucasian students, and none have targeted rural, low-income, elementary children. The five noninvasive risk factors used for this study were family history, high body mass index (BMI) for age/sex,…

Peterson, Sharon; Sheffer, Sarah; Long Roth, Sara; Bennett, Paul A.; Lloyd, Les



Mexican American Parents' Perceptions of Childhood Risk Factors for Type 2 Diabetes  

ERIC Educational Resources Information Center

|A study was conducted to identify the norms, values, and perceptions of urban immigrant Mexican American (MA) parents of school children relative to physical activity, healthy eating, and child risk factors for type 2 diabetes. Investigators facilitated five focus groups in an urban elementary school setting and analyzed data using qualitative…

Head, Barbara J.; Barr, Kathleen L.; Baker, Sharon K.



Early and late risk factors in surgical treatment of acute type A aortic dissection  

Microsoft Academic Search

Background. Morbidity and mortality of emergency repair of type A dissecting aneurysms of the aorta are high. This is an attempt to investigate the risk determinants of early and late results.Methods. A series of preoperative and operative variables were retrospectively collected from the clinical records of 291 patients operated on between January 1, 1979, and December 31, 1995. Risk factors

Stefano Pansini; Pier Vincenzo Gagliardotto; Esmeralda Pompei; Francesco Parisi; Gianluca Bardi; Enzo Castenetto; Fulvio Orzan; Michele di Summa



VirB8: a conserved type IV secretion system assembly factor and drug target.  


Type IV secretion systems are used by many gram-negative bacteria for the translocation of macromolecules (proteins, DNA, or DNA-protein complexes) across the cell envelope. Among them are many pathogens for which type IV secretion systems are essential virulence factors. Type IV secretion systems comprise 8-12 conserved proteins, which assemble into a complex spanning the inner and the outer membrane, and many assemble extracellular appendages, such as pili, which initiate contact with host and recipient cells followed by substrate translocation. VirB8 is an essential assembly factor for all type IV secretion systems. Biochemical, cell biological, genetic, and yeast two-hybrid analyses showed that VirB8 undergoes multiple interactions with other type IV secretion system components and that it directs polar assembly of the membrane-spanning complex in the model organism Agrobacterium tumefaciens. The availability of the VirB8 X-ray structure has enabled a detailed structure-function analysis, which identified sites for the binding of VirB4 and VirB10 and for self-interaction. Due to its multiple interactions, VirB8 is an excellent model for the analysis of assembly factors of multiprotein complexes. In addition, VirB8 is a possible target for drugs that target its protein-protein interactions, which would disarm bacteria by depriving them of their essential virulence functions. PMID:17215876

Baron, Christian



Mediating factors of coping process in parents of children with type 1 diabetes  

PubMed Central

Background Type 1 diabetes is a lifelong condition for children and their parents, the management for which imposes a vast responsibility. This study explores the mediating factors that affect Iranian parents’ coping processes with their children’s type 1 diabetes. Methods Research was conducted using the grounded theory method. Participants were selected purposefully, and we continued with theoretical sampling. Constant comparative analysis was used to analyze the data. Results The mediating factors of the parental coping process with their child’s diabetes consist of the child’s cooperation, crises and experiences, economic challenges, and parental participation in care. Conclusion Findings highlight the necessity of well-informed nurses with insightful understanding of the mediating factors in parental coping with juvenile diabetes in order to meet the particular needs of this group.



Comparison of Cardiovascular Risk Factors Between Slavic Immigrant Women with Type 2 Diabetes and Non-Immigrant, Non-Hispanic White Women with Type 2 Diabetes  

Microsoft Academic Search

Purpose: This study compares cardiovascular risk factors among immigrant women with type 2 diabetes. The study sample consists of women immigrants from the former Soviet Union (Slavic immigrants) and non-immigrant, non-Hispanic, white women with type 2 diabetes. Method: Lifestyle behaviors and healthcare access were assessed using questions from the 2002 Behavioral Risk Factor Surveillance System interview. Pharmacological regimes were analyzed

Allan Sanders; Cynthia Corbett; Stephen M. Setter; PharmD CDE CGP FASCP; Jason L. Iltz PharmD; Carol Allen; Lorna Schumann; Natalia Barko



Nonsex Genes in the Mating Type Locus of Candida albicans Play Roles in a/? Biofilm Formation, Including Impermeability and Fluconazole Resistance  

PubMed Central

The mating type locus (MTL) of Candida albicans contains the mating type genes and has, therefore, been assumed to play an exclusive role in the mating process. In mating-incompetent a/? cells, two of the mating type genes, MTLa1 and MTL?2, encode components of the a1-?2 corepressor that suppresses mating and switching. But the MTL locus of C. albicans also contains three apparently unrelated “nonsex” genes (NSGs), PIK, PAP and OBP, the first two essential for growth. Since it had been previously demonstrated that deleting either the a/? copy of the entire MTL locus, or either MTLa1 or MTL?2, affected virulence, we hypothesized that the NSGs in the MTL locus may also play a role in pathogenesis. Here by mutational analysis, it is demonstrated that both the mating type and nonsex genes in the MTL locus play roles in a/? biofilm formation, and that OBP is essential for impermeability and fluconazole resistance.

Pujol, Claude; Sahni, Nidhi; Yi, Song; Soll, David R.



Prediction of infinite dilution activity coefficients for systems including water based on the group contribution model with mixture-type groups  

Microsoft Academic Search

Group contribution models such as ASOG or UNIFAC were known to be inaccurate in the prediction of infinite dilution activity coefficients (??) for most of the systems containing water. To overcome the weakness inherent with the UNIFAC models, Zhang et al. (Fluid Phase Equil. 149 (1998) 27) have recently proposed a group-contribution-based model with mixture-type groups, where the mixture-type group

Suojiang Zhang; Toshihiko Hiaki; Kazuo Kojima



[Study on the frequency of caries and associated factors in type 1 diabetes mellitus].  


Subjects with diabetes mellitus (DM) are more prone to certain disturbances of oral cavity but there are controversies concerning caries. This cross-sectional study investigated the frequency of caries and associated factors, in a sample of population with or without type 1 DM, including non-diabetic (53 women, 31 men) and 30 diabetic subjects (19 women, 11 men) aged 17-28 years. Diagnosis of dental caries was based on the DMF-T index (D= decay; M= miss; F= fill; T= teeth); in addition, a plaque control record (PCR) was obtained. A preponderance of female sex was found within the groups studied but such proportions did not differ when comparing diabetic and non-diabetic groups. Mean ages were 21.0 +/- 2.2 and 19.5+/-1.8 years, respectively for subjects without and with DM (p< 0.05). Education level was higher in the non-diabetic group as well as the DMF-T index (10.5 +/-5.8 vs. 6.7+/-5.7, p< 0.01). Linear regression analysis (n= 114) showed significant associations of DMF-T with age, sucrose intake, daily frequency of tooth brushing, of dental floss use, PCR and of visits to the dentist. By ANOVA model with age as a covariate the non-diabetic condition (p= 0.047), sucrose index and PCR (r(2)= 0.820) were independently associated with the DMF-T. In the diabetic-specific model, with only the diabetic subjects included and sucrose index as a covariate, DM duration, fundus abnormality and PCR were significantly associated with the presence of caries (r(2)= 0.816). The sample of type 1 diabetic subjects suggest that they are less prone to caries than non-diabetics, despite having a higher frequency of meals, less tooth brushing and dental floss use. We speculate that DM duration may contribute to the occurrence of caries and restricted sucrose consumption to lower frequency of caries in diabetic subjects. PMID:16936993

do Amaral, Fábio M Franco; Ramos, Patrícia G de A; Ferreira, Sandra Roberta G



Cross-Sectional Associations of Blood Elements, Clotting Factors, Nephropathy, and Retinal Outcomes in Long Duration Type 1 Diabetes  

PubMed Central

Purpose To determine the association of blood elements, selected clotting factors, and nephropathy with proliferative diabetic retinopathy (PDR) and macular edema (ME) in those with long duration type 1 diabetes. Methods Participants (n=442) were seen in 2005–2007 at the 25-year follow-up of a population-based study of diabetic retinopathy, and were eligible for this analysis. Fundus photographs were graded using a standard retinopathy severity scheme. Laboratory measures included hematocrit, white blood cell and platelet counts, serum fibrinogen, interleukin-6, and von Willebrand factor. Results In models including duration of diabetes, hypertension, and diabetic nephropathy, only hematocrit was marginally associated (odds ratio; 95% confidence interval; P value for trend per quintile) with decreased odds of PDR (0.87; 0.74–1.01; P=0.06). Stratifying by nephropathy status, in those with and without nephropathy, there were no significant associations of any laboratory measures with PDR or ME. None of the variables we examined were associated with ME in individuals with or without nephropathy. Conclusion In persons with long duration type 1 diabetes, none of the blood elements or clotting factors was associated with increased odds of PDR or ME. Investigation of common pathways that lead to diabetic nephropathy and diabetic retinal outcomes should be a research priority in efforts to prevent vision-threatening complications of diabetes and nephropathy.

Klein, Barbara E. K.; Klein, Ronald; Howard, Kerri P.; Lee, Kristine E.



Novel biochemical risk factors for type 2 diabetes: pathogenic insights or prediction possibilities?  

Microsoft Academic Search

This review critically appraises studies examining the association of novel factors with diabetes. We show that many of the\\u000a most studied novel and apparently ‘independent’ risk factors are correlated with each other by virtue of their common origins\\u000a or pathways, and that residual confounding is likely. Available studies also have other limitations, including differences\\u000a in methodology or inadequate statistical analyses.

N. Sattar; S. G. Wannamethee; N. G. Forouhi



Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease.  


Endocannabinoids act as neuromodulatory and neuroprotective cues by engaging type 1 cannabinoid receptors. These receptors are highly abundant in the basal ganglia and play a pivotal role in the control of motor behaviour. An early downregulation of type 1 cannabinoid receptors has been documented in the basal ganglia of patients with Huntington's disease and animal models. However, the pathophysiological impact of this loss of receptors in Huntington's disease is as yet unknown. Here, we generated a double-mutant mouse model that expresses human mutant huntingtin exon 1 in a type 1 cannabinoid receptor-null background, and found that receptor deletion aggravates the symptoms, neuropathology and molecular pathology of the disease. Moreover, pharmacological administration of the cannabinoid ?(9)-tetrahydrocannabinol to mice expressing human mutant huntingtin exon 1 exerted a therapeutic effect and ameliorated those parameters. Experiments conducted in striatal cells show that the mutant huntingtin-dependent downregulation of the receptors involves the control of the type 1 cannabinoid receptor gene promoter by repressor element 1 silencing transcription factor and sensitizes cells to excitotoxic damage. We also provide in vitro and in vivo evidence that supports type 1 cannabinoid receptor control of striatal brain-derived neurotrophic factor expression and the decrease in brain-derived neurotrophic factor levels concomitant with type 1 cannabinoid receptor loss, which may contribute significantly to striatal damage in Huntington's disease. Altogether, these results support the notion that downregulation of type 1 cannabinoid receptors is a key pathogenic event in Huntington's disease, and suggest that activation of these receptors in patients with Huntington's disease may attenuate disease progression. PMID:20929960

Blázquez, Cristina; Chiarlone, Anna; Sagredo, Onintza; Aguado, Tania; Pazos, M Ruth; Resel, Eva; Palazuelos, Javier; Julien, Boris; Salazar, María; Börner, Christine; Benito, Cristina; Carrasco, Carolina; Diez-Zaera, María; Paoletti, Paola; Díaz-Hernández, Miguel; Ruiz, Carolina; Sendtner, Michael; Lucas, José J; de Yébenes, Justo G; Marsicano, Giovanni; Monory, Krisztina; Lutz, Beat; Romero, Julián; Alberch, Jordi; Ginés, Silvia; Kraus, Jürgen; Fernández-Ruiz, Javier; Galve-Roperh, Ismael; Guzmán, Manuel



Does high sugar consumption exacerbate cardiometabolic risk factors and increase the risk of type 2 diabetes and cardiovascular disease?  

PubMed Central

Consumption of sugar has been relatively high in the Nordic countries; the impact of sugar intake on metabolic risk factors and related diseases has been debated. The objectives were to assess the effect of sugar intake (sugar-sweetened beverages, sucrose and fructose) on association with type 2 diabetes, cardiovascular disease and related metabolic risk factors (impaired glucose tolerance, insulin sensitivity, dyslipidemia, blood pressure, uric acid, inflammation markers), and on all-cause mortality, through a systematic review of prospective cohort studies and randomised controlled intervention studies published between January 2000 and search dates. The methods adopted were as follows: the first search was run in PubMed in October 2010. A second search with uric acid as risk marker was run in April 2011. The total search strategy was rerun in April 2011 in SveMed+. An update was run in PubMed in January 2012. Two authors independently selected studies for inclusion from the 2,743 abstracts according to predefined eligibility criteria. The outcome was that out of the 17 studies extracted, 15 were prospective cohort studies and two were randomised controlled crossover trials. All of the studies included only adults. With respect to incident type 2 diabetes (nine studies), four of six prospective cohort studies found a significant positive association for sugar-sweetened beverage intake. In general, larger cohort studies with longer follow-up more often reported positive associations, and BMI seemed to mediate part of the increased risk. For other metabolic or cardiovascular risk factors or outcomes, too few studies have been published to draw conclusions. In conclusion, data from prospective cohort studies published in the years 2000–2011 suggest that sugar-sweetened beverages probably increase the risk of type 2 diabetes. For related metabolic risk factors, cardiovascular disease or all-cause mortality and other types of sugars, too few studies were available to draw conclusions.

Sonestedt, Emily; ?verby, Nina Cecilie; Laaksonen, David E.; Birgisdottir, Bryndis Eva



Microbiological characteristics of clinical isolates of Cryptococcus neoformans in Taiwan: serotypes, mating types, molecular types, virulence factors, and antifungal susceptibility.  


This study investigated the microbiological characteristics of 100 clinical isolates of Cryptococcus neoformans species complex, including serotypes, mating types, molecular types, antifungal susceptibility and virulence. The isolates were collected at National Taiwan University Hospital from 1999 to 2004. Eight isolates of C. neoformans from pigeon droppings were also evaluated. Among these isolates, 99 were C. neoformans var. grubii serotype A and one was C. neoformans var. gattii serotype B. All of these isolates were alpha mating types. PCR fingerprinting, generated by primers M13 and (GACA)(4), and URA5 gene restriction fragment length polymorphism analysis revealed that C. neoformans var. grubii isolates belonged to the VNI (98 isolates) and the VNII (one isolate) types, and the single C. neoformans var. gattii was VGI type. The similar profiles of clinical and environmental isolates suggest that patients might acquire these yeasts from the environment. The MIC(90) for fluconazole, itraconazole, 5-flucytosine, voriconazole and amphotericin B against all C. neoformans isolates were 8, 0.5, 4, 0.125 and 0.5 mg/L, respectively. All clinical isolates produced urease, phospholipase, capsule and melanin, but these activities varied with individual isolates. Analysis of six clinical and two environmental isolates with various levels of phospholipase activity indicated a correlation between phospholipase activity and the ability to adhere to the lung epithelial cell line, A549. The extent of cell damage, as indicated by lactate dehydrogenase release, also paralleled the phospholipase activity of these isolates. In addition, production of melanin contributed significant protection against amphotericin B killing of the isolates tested. PMID:19694765

Liaw, S-J; Wu, H-C; Hsueh, P-R



Keratinocyte growth factor-induced hyperplasia of rat alveolar type II cells in vivo is resolved by differentiation into type I cells and by apoptosis  

Microsoft Academic Search

Keratinocyte growth factor-induced hyperplasia of rat alveolar type II cells in vivo is re- solved by differentiation into type I cells and by apoptosis. H. Fehrenbach, M. Kasper, T. Tschernig, T. Pan, D. Schuh, J.M. Shannon, M. Muller, R.J. Mason.#ERS Journals Ltd 1999. ABSTRACT: Keratinocyte growth factor (KGF) is a potent mitogen of alveolar epi- thelial type II cells (AEII).

H. Fehrenbach; M. Kasper; T. Tschernig; T. Pan; D. Schuh; J. M. Shannon; M. Müller; R. J. Mason



Serum response factor indirectly regulates type I interferon-signaling in macrophages.  


Serum response factor (SRF) is required for diverse aspects of development and homeostasis, but potential roles in the regulation of inflammation and immunity have not been systematically investigated. Here, we demonstrate that SRF is unexpectedly required for optimal responses of elicited peritoneal macrophages to type I interferons. Knockdown of SRF expression in these cells impairs induction of numerous interferon (IFN)-stimulated genes (ISGs) in response to zymosan, LPS, and poly I:C. This effect is primarily due to a defect in the ability of induced type I interferons to mediate secondary activation of ISGs. SRF does not appear to be required for expression of established components of the type I interferon signaling pathway, with IFN-?-dependent phosphorylation of STAT1 and STAT2 normally occurring in SRF-depleted macrophages. Collectively, these findings suggest that SRF can indirectly modulate type I interferon-signaling, without interfering with the classic JAK/STAT/ISGF3 pathway. PMID:23705899

Xie, Lan; Sullivan, Amy L; Collier, Jana G; Glass, Christopher K



43 CFR 404.10 - Are there certain types of infrastructure and facilities that may not be included in a rural...  

Code of Federal Regulations, 2012 CFR

...facilities that may not be included in a rural water supply project? 404.10 Section 404...DEPARTMENT OF THE INTERIOR RECLAMATION RURAL WATER SUPPLY PROGRAM Overview § 404.10...facilities that may not be included in a rural water supply project? Yes. A rural...



Fragility and spiralization anomalies of the chromosomes in three cases, including fraternal twins, with Fanconi’s anemia, type Estren-Dameshek  

Microsoft Academic Search

Fraternal twins, offspring of consanguineous parents, developed pancytopenia, the boy at 7, the girl at 12 years of age. A third patient became anemic at 3 years. All three are free of associated malformations. In blood cultures the incidence of chromatid breaks, exchanges, and chromosome-type aberrations was elevated to 24 %, 18 %, and 28 %, respectively. In addition, in

W. Schmid; G. Fanconi



Hope More, Worry Less: Hope as a Potential Resilience Factor in Mothers of Very Young Children With Type 1 Diabetes  

Microsoft Academic Search

Little research has explored potential resilience factors in parenting a child with a chronic illness—or factors that help protect against the experience of psychological distress. This study explored the relation between hope (a resilience factor) and anxiety (a distress factor) in mothers of very young children with type 1 diabetes. Seventy-five mothers of children aged 2 through 5 years diagnosed

Lauren Mednick; Fran Cogen; Celia Henderson; Cynthia A. Rohrbeck; Doee Kitessa; Randi Streisand



The use of a simulator to include human factors issues in the interface design of a nuclear power plant control room  

Microsoft Academic Search

Technology plays an important role in advanced control rooms that relies on complex technical equipment and interfaces. Human error has many causes such as performance shaping factors, organizational factors and interface design. In the safe operation of nuclear power plant, the performance of the control room crew plays an important role. In this respect, a well-designed control room and human–system

Isaac José Antonio Luquetti dos Santos; Douglas Vidal Teixeira; Fernando Toledo Ferraz; Paulo Victor Rodrigues Carvalho



Diabetes mellitus type 2 in urban Ghana: characteristics and associated factors  

PubMed Central

Background Sub-Saharan Africa faces a rapid spread of diabetes mellitus type 2 (DM2) but its potentially specific characteristics are inadequately defined. In this hospital-based study in Kumasi, Ghana, we aimed at characterizing clinical, anthropometric, socio-economic, nutritional and behavioural parameters of DM2 patients and at identifying associated factors. Methods Between August 2007 and June 2008, 1466 individuals were recruited from diabetes and hypertension clinics, outpatients, community, and hospital staff. Fasting plasma glucose (FPG), serum lipids and urinary albumin were measured. Physical examination, anthropometry, and interviews on medical history, socio-economic status (SES), physical activity and nutritional behaviour were performed. Results The majority of the 675 DM2 patients (mean FPG, 8.31 mmol/L) was female (75%) and aged 40-60 years (mean, 55 years). DM2 was known in 97% of patients, almost all were on medication. Many had hypertension (63%) and microalbuminuria (43%); diabetic complications occurred in 20%. Overweight (body mass index > 25 kg/m2), increased body fat (> 20% (male), > 33% (female)), and central adiposity (waist-to-hip ratio > 0.90 (male), > 0.85 (female)) were frequent occurring in 53%, 56%, and 75%, respectively. Triglycerides were increased (? 1.695 mmol/L) in 31% and cholesterol (? 5.17 mmol/L) in 65%. Illiteracy (46%) was high and SES indicators generally low. Factors independently associated with DM2 included a diabetes family history (adjusted odds ratio (aOR), 3.8; 95% confidence interval (95%CI), 2.6-5.5), abdominal adiposity (aOR, 2.6; 95%CI, 1.8-3.9), increased triglycerides (aOR, 1.8; 95%CI, 1.1-3.0), and also several indicators of low SES. Conclusions In this study from urban Ghana, DM2 affects predominantly obese patients of rather low socio-economic status and frequently is accompanied by hypertension and hyperlipidaemia. Prevention and management need to account for a specific risk profile in this population.



A bHLH-type transcription factor, ABA-INDUCIBLE BHLH-TYPE TRANSCRIPTION FACTOR/JA-ASSOCIATED MYC2-LIKE1, acts as a repressor to negatively regulate jasmonate signaling in arabidopsis.  


Jasmonates (JAs) are plant hormones that regulate the balance between plant growth and responses to biotic and abiotic stresses. Although recent studies have uncovered the mechanisms for JA-induced responses in Arabidopsis thaliana, the mechanisms by which plants attenuate the JA-induced responses remain elusive. Here, we report that a basic helix-loop-helix-type transcription factor, ABA-INDUCIBLE BHLH-TYPE TRANSCRIPTION FACTOR/JA-ASSOCIATED MYC2-LIKE1 (JAM1), acts as a transcriptional repressor and negatively regulates JA signaling. Gain-of-function transgenic plants expressing the chimeric repressor for JAM1 exhibited substantial reduction of JA responses, including JA-induced inhibition of root growth, accumulation of anthocyanin, and male fertility. These plants were also compromised in resistance to attack by the insect herbivore Spodoptera exigua. Conversely, jam1 loss-of-function mutants showed enhanced JA responsiveness, including increased resistance to insect attack. JAM1 and MYC2 competitively bind to the target sequence of MYC2, which likely provides the mechanism for negative regulation of JA signaling and suppression of MYC2 functions by JAM1. These results indicate that JAM1 negatively regulates JA signaling, thereby playing a pivotal role in fine-tuning of JA-mediated stress responses and plant growth. PMID:23673982

Nakata, Masaru; Mitsuda, Nobutaka; Herde, Marco; Koo, Abraham J K; Moreno, Javier E; Suzuki, Kaoru; Howe, Gregg A; Ohme-Takagi, Masaru



Dynamic Evolution of the Human Immunodeficiency Virus Type 1 Pathogenic Factor, Nef  

Microsoft Academic Search

The human immunodeficiency virus type 1 (HIV-1) early gene product Nef is a multifunctional protein that alters numerous pathways of T-cell function, including endocytosis, signal transduction, vesicular trafficking, and immune modulation, and is a major determinant of pathogenesis. Individual Nef functions include PAK-2 activation, CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, and enhancement of viral particle infectivity. How

Eduardo O'Neill; Lillian S. Kuo; John F. Krisko; Diana R. Tomchick; J. Victor Garcia; John L. Foster



Immunogenic Display of Diverse Peptides, Including a Broadly Cross-Type Neutralizing Human Papillomavirus L2 epitope, on Virus-like Particles of the RNA Bacteriophage PP7  

PubMed Central

The immunogenicity of an antigen can be dramatically increased by displaying it in a dense, multivalent context, such as on the surface of a virus or virus-like particle (VLP). Here we describe a highly versatile VLP platform for peptide display based on VLPs of the RNA bacteriophage PP7. We show that this platform can be used for the engineered display of specific peptide sequences as well as for the construction of random peptide libraries. Peptides representing the FLAG epitope, the V3 loop of HIV gp120, and a broadly cross-type neutralizing epitope from L2, the minor capsid protein of Human Papillomavirus type 16 (HPV16), were inserted into an exposed surface loop of a form of PP7 coat protein in which the two identical polypeptides of coat were fused together to form a single-chain dimer. The recombinant proteins assembled into VLPs, displayed these peptides on their surfaces, and induced high titer antibody responses. The single-chain dimer was also highly tolerant of random 6-, 8-, and 10-amino acid insertions. PP7 VLPs displaying the HPV16 L2 epitope generated robust anti-HPV16 L2 serum antibodies after intramuscular injection that protected mice from genital infection with HPV16 pseudovirus as well as a heterologous HPV pseudovirus type, HPV45. Thus, PP7 VLPs are well-suited for the display of a wide diversity of peptides in a highly immunogenic format.

Caldeira, Jerri do Carmo; Medford, Alexander; Kines, Rhonda C.; Lino, Christopher A.; Schiller, John T.; Chackerian, Bryce; Peabody, David S.



Risk factors for type 2 diabetes mellitus and cardiovascular diseases in Hispanic adolescents  

Microsoft Academic Search

This cross-sectional study evaluated risk factors (RF) for type 2 diabetes (T2DM) and cardiovascular diseases (CVD) in 100 Hispanic adolescents(50 overweight, 50 non-overweight) aged 12-16 years, and their associations with body mass index (BMI), diet, physical activity (PA), gender, and birth weight (BW). The RF studied were fasting plasma glucose (FPG), insulin sensitivity (IS), total cholesterol (TC), triacylglycerols (TG), low-density

Gianna Perez Gomez



Diabetes risk factors and chromium intake in moderately obese subjects with type 2 diabetes mellitus  

Microsoft Academic Search

Purpose – Many foods naturally contain dietary Cr, but lost during processing and cooking. Type 2 diabetes mellitus (T2DM) has been associated with poor glycemic control and low Cr status. The objectives of the current study were to evaluate the dietary Cr intake and its relationship with diabetes risk factors in moderately obese subjects with T2DM. Design\\/methodology\\/approach – Thirty-six subjects

Vijaya Juturu; Anne Daly; Jeff Geohas; Manley Finch; James R. Komorowski



Osteoblasts Synthesize and Respond to Transforming Growth Factor-Type (3 In Vitro  

Microsoft Academic Search

Transforming growth factor-type 13 (TGF-13) has been identified as a constituent of bone matrix (Seyedin, S. M., A. Y. Thompson, H. Bentz, D. M. Rosen, J. M. McPherson, A. Conti, N. R. Siegel, G. R. Gallupi, and K. A. Piez, 1986, J. Biol. Chem. 261:5693-5695). We used both developing bone and bone-forming cells in vitro to demonstrate the cellular origin

Pamela Gehron Robey; Marian E Young; Kathleen C. Flanders; Nanette S. Roche; Paturu Kondaiah; John D. Termine; Michael B. Sporn; Anita B. Roberts



Effects of policosanol in patients with type II hypercholesterolemia and additional coronary risk factors  

Microsoft Academic Search

Introduction: This study was undertaken to evaluate the efficacy, safety, and tolerability of policosanol, a new cholesterol-lowering drug, in patients with type II hypercholesterolemia and additional coronary risk factors.Patients and methods: After 5 weeks of a standard step-1 lipid-lowering diet, 437 patients were randomized to receive, under double-blind conditions, 5 mg policosanol or placebo once a day with the evening

Rosa Más; Gladys Castańo; José Illnait; Lilia Fernández; Julio Fernández; Celia Alemán; Virginia Pontigas; Magnolia Lescay



Admixture in Mexico City: implications for admixture mapping of Type 2 diabetes genetic risk factors  

Microsoft Academic Search

Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases\\u000a showing prevalence differences between major continental groups. Type 2 diabetes (T2D) is at least twice as prevalent in Native\\u000a American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis\\u000a of this complex disease.

Veronica L. Martinez-Marignac; Adan Valladares; Emily Cameron; Andrea Chan; Arjuna Perera; Rachel Globus-Goldberg; Niels Wacher; Jesús Kumate; Paul McKeigue; David O’Donnell; Mark D. Shriver; Miguel Cruz; Esteban J. Parra



Ring-type V-groove surface plasmon microresonator: The modal structure and Q-factor  

NASA Astrophysics Data System (ADS)

We consider the formation of the surface plasmon polariton (SPP) mode in the ring-type V-groove structure. Closed-form expressions for the mode field distributions, resonant frequency, and total quality factor are obtained for the structure in a broad wavelength range. The model serves as a practical guide to design a SPP microcavity with sub-wavelength confinement in the transverse cross sectional directions.

Vardanyan, Artashes; Haroyan, Hovhannes; Babajanyan, Arsen; Nerkararyan, Khachatur; Lee, Kiejin; Friedman, Barry



Anxious personality is a risk factor for developing complex regional pain syndrome type I  

Microsoft Academic Search

The aim of this study was to investigate the role of psychological factors in the development of complex regional pain syndrome\\u000a (CRPS) type I following the fracture of the distal radius. Fifty patients (average age 57.70 ± 13.43 years) with a distal\\u000a radius fracture were enrolled in the present study. All of the patients were treated by closed reduction and cast immobilization.\\u000a The

Banu Dilek; Beyazit Yemez; Ramazan Kizil; Esin Kartal; Selmin Gulbahar; Ozden Sari; Elif Akalin


Tumor Necrosis Factor-a Upregulates Angiotensin II Type 1 Receptors on Cardiac Fibroblasts  

Microsoft Academic Search

Angiotensin II (Ang II) plays an important role in post-myocardial infarction (MI) remodeling. Most Ang II effects related to remodeling involve activation of the type 1 receptor (AT 1). Although the AT1 receptor is upregulated on cardiac fibroblasts post-MI, little is known about the mechanisms involved in the process. Consequently, we tested whether growth factors known to be present in

Devorah Gurantz; Randy T. Cowling; Francisco J. Villarreal; Barry H. Greenberg


Analysis of T cell hybridomas. II. Comparisons among three distinct types of monoclonal suppressor factors  

PubMed Central

Five hybridoma T cell lines were prepared by fusion of Ts3 cells with the BW 5147 thymoma. The culture supernatants from these T cell hybrids contained a factor, TsF3, which specifically suppressed 4-hydroxy-3- nitrophenyl acetyl hapten (NP(-hapten cutaneous sensitivity responses. The properties of this new series of hybridoma factors was compared with those of two previously characterized types of NP-specific suppressor factors (TsF1 and TsF2). TsF3 activity was only observed if the factor was administered during the effector phases of the immune response. TsF3 bears I-J and C57BL anti-NP antibody idiotypic determinants and has binding specificity for the NP hapten. Furthermore, TsF3 does not suppress H-2 (I-J)-incompatible mice. In addition to this H-2 restriction, the monoclonal TsF3 factors also demonstrated an Igh genetic restriction. Finally, the TsF3 factors could be distinguished by their ability to suppress cyclophosphamide- treated recipients.



Avoiding toxins including spermatotoxic medications.  


Global rates of infertility are significant, especially in many developing countries. In developed countries, infertility affects up to 15% of the reproductive-age population, with male factors involved in 50% of cases. During medical evaluation, a review of current and past medications and social habits is essential, as they may adversely affect fertility. In addition, knowledge of exposure is important for counseling regarding future fertility, as many such toxic exposures have reversible effects. We reviewed the English literature over the past 35 years for all types of studies that have examined drug, medication, and other exposures that have been linked to altered semen quality and male fertility. Both human and animal studies were included in this analysis. The goal of this review is to delineate the medication and habitual risk factors that have been associated with male infertility. PMID:23775384

Stearns, Gillian; Turek, Paul J



Factors associated with psychological and behavioral functioning in people with type 2 diabetes living in France  

PubMed Central

Background To identify demographic and clinical factors associated with psychological and behavioral functioning (PBF) in people with type 2 diabetes living in France. Methods In March 2002, approximately 10,000 adults, who had been reimbursed for at least one hypoglycemic treatment or insulin dose during the last quarter of 2001, received a questionnaire about their health status and PBF (3,646 responders). For this analysis, the 3,090 persons with type 2 diabetes, aged 18-85 years old were selected. PBF was measured with the adapted version of the Diabetes Health Profile for people with type 2 diabetes. This permitted the calculation of three functional scores - psychological distress (PD), barriers to activity (BA), and disinhibited eating (DE) - from 0 (worst) to 100 (best). Results Major negative associations were observed with PBF for microvascular complications (a difference of 6.7 in the BA score between persons with and without microvascular complications) and severe hypoglycemia (difference of 7.9 in the BA score), insulin treatment (-8.5 & -9.5 in the PD & BA scores respectively, as compared to treatment with oral hypoglycemic agents), non-adherence to treatment (-12.3 in the DE score for persons forgetting their weekly treatment), increasing weight (-8.5 & -9.7 in the PD & DE scores respectively, as compared to stable weight), at least one psychiatrist visit in 2001 (-8.9 in the DE score), and universal medical insurance coverage (-7.9 in the PD score) (due to low income). Conclusion Prevention and management of microvascular complications or adherence to treatment (modifiable factors) could be essential to preserving or improving PBF among people with type 2 diabetes. A specific approach to type 2 diabetes management may be required in groups with a low socioeconomic profile (particularly people with universal medical insurance coverage), or other non modifiable factors.



Optimal Design of Rotary-Type Voice Coil Motor Using Multisegmented Magnet Array for Small Form Factor Optical Disk Drive  

NASA Astrophysics Data System (ADS)

For a small form factor optical disk drive (SFFODD), a high-performance actuator satisfying the requirements for small size, high speed, and low-power consumption simultaneously is required. In this paper, we propose a rotary-type voice coil motor (VCM) using a multisegmented magnet array (MSMA) for the SFFODD. The VCM is designed to move the entire system including miniaturized optical components, which are necessary in reading and writing data. To increase the actuating force of the VCM, the MSMA, a novel magnetic circuit, is adopted because it can provide a higher flux density than a conventional magnet array in the rotary-type VCM. To obtain the best performance from the VCM in the limit of actuator size, design optimization is performed. The manufactured actuator with optimally designed parameters is described and the potential performance of track seeking is evaluated and presented.

Jeong, Jaehwa; Gweon, Dae-Gab



Diaper Type as a Risk Factor in Urinary Tract Infection of Children  

PubMed Central

Objective Urinary tract is one of the most common sources of infection in children under the age of two years. Many known and unknown risk factors predispose to this important disease in children. This study was conducted to determine whether using a specific type of diaper plays a role in urinary tract infection (UTI) in girls under the age of 2 years. Methods This case control study was performed in hospitalized children; girls with their first urinary tract infection were selected as cases, and those admitted for other reasons comprised the control group. Two groups were matched for age (±1 month), and other known risk factors for UTI. Type of diapers (superabsorbent, standard disposable and washable cotton), used for these children during six months, from October 2007 to March 2008, were compared in both groups. Findings 59 matched pair infant girls less than 2 years were selected. It was revealed that in cases with UTI superabsorbent diapers were used more frequently than in controls (Odds ratio=3.29, P-value=0.005) There were no significant differences in other factors like number of diapers used per day, the time between defecation and diaper change, mothers’ educational level, level of family income and mother's occupation. Conclusion The use of superabsorbent diapers could be a risk factor for urinary tract infection in infant girls.

Fahimzad, Alireza; Taherian, Masoomeh; Dalirani, Reza; Shamshiri, Ahmadreza



Cardiovascular Risk Factors in Turkish Immigrants with Type 2 Diabetes Living in The Netherlands  

Microsoft Academic Search

The cross sectional study investigated the association of tobacco smoke, vitamin D status, anthropometric parameters, and kidney function in Turkish immigrants with type 2 diabetes (T2D) living in the Netherlands. Study sample included a total of 110 participants aged 30 years and older (males= 46; females= 64). Serum cotinine, a biomarker for smoke exposure, was measured with a solid-phase competitive

Shiryn D Sukhram



Cardiovascular risk factors in Turkish immigrants with type 2 diabetes living in the Netherlands  

Microsoft Academic Search

The cross sectional study investigated the association of tobacco smoke, vitamin D status, anthropometric parameters, and kidney function in Turkish immigrants with type 2 diabetes (T2D) living in the Netherlands. Study sample included a total of 110 participants aged 30 years and older (males= 46; females= 64). Serum cotinine, a biomarker for smoke exposure, was measured with a solid-phase competitive

Shiryn D Sukhram



Genetics, Obesity, and Environmental Risk Factors Associated with Type 2 Diabetes  

Microsoft Academic Search

Aim To determine the association between consanguineous marriages, obesity, and environmental risk fac- tors associated with type 2 diabetes, in the adult Qatari population. Methods The case-control study was carried out among diabetic patients and healthy subjects at the Primary Healthcare Clinics (PHCs) and the survey was conducted from February to November 2003.The study included 338 cases (with diabetes) and

Abdulbari Bener; Mahmoud Zirie; Ammar Al-Rikabi



Transforming growth factor type. beta. can act as a potent competence factor for AKR-2B cells  

SciTech Connect

Transforming growth factor type {beta} (TGF{beta}) is a pleiotropic regulator of cell growth with specific high-affinity cell-surface receptors on a large number of cells; its mechanism of action, however, is poorly defined. In this report, the authors utilized the mouse fibroblast line AKR-2B to explore the question of the temporal requirements during the cell cycle in regard to both the growth inhibitory and the growth stimulatory action of TGF{beta}. The results indicate that AKR-2B cells are most sensitive to the inhibitory action of TGF{beta} during early to mid-G{sub 1}. In addition, TGF{beta} need be present only briefly in order to exert its inhibitory effect on EGF-induced DNA synthesis. Likewise, the stimulatory effect of TGF{beta} in the absence of EGF requires only an equally brief exposure to TGF{beta}. Use of homogeneous {sup 125}I-labeled TGF{beta} in a cell-binding assay demonstrates that TGF{beta} bound to cell-surface receptors can readily exchange into the culture medium, helping to rule out the possibility that persistent receptor-bound TGF{beta} is the source of a continuous stimulus. The data indicate that TGF{beta} exposure induces a stable state in the cell similar to but distinct from the state of competence induced by platelet-derived growth factor (PDGF).

Goustin, A.S.; Nuttall, G.A.; Leof, E.B.; Ranganathan, G.; Moses, H.L. (Mayo Clinic and Foundation, Rochester, MN (USA))



Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression.  

PubMed Central

Inhibition of cell growth by type beta transforming growth factor (TGF-beta) occurs in mid-G1 and is associated with decreased G1 cyclin-dependent kinase activity and maintenance of the retinoblastoma tumor suppressor protein Rb in an underphosphorylated, growth-suppressive state. A variety of recent experiments suggest that a functional target of Rb is the E2F transcription factor. In addition, the growth-suppressive effects of TGF-beta can be overcome by expression of viral oncogene products that dissociate E2F from Rb and Rb-related polypeptides. These results suggest the possibility that control of E2F may be a downstream event of TGF-beta action. Consistent with that possibility is the observation that E2F1 RNA levels are drastically reduced in TGF-beta-treated cells. We have also used a recombinant adenovirus containing the human E2F1 gene to overexpress the E2F1 product in mink lung epithelial cells that were growth arrested with TGF-beta. We find that overexpression of E2F1 can overcome the TGF-beta-mediated effect as measured by the activation of cellular DNA synthesis. These results suggest that a likely downstream target for the cyclin-dependent kinases, which are controlled by TGF-beta, is the activation of E2F. Images Fig. 1 Fig. 2

Schwarz, J K; Bassing, C H; Kovesdi, I; Datto, M B; Blazing, M; George, S; Wang, X F; Nevins, J R



New types of clotting factors and defense molecules found in horseshoe crab hemolymph: their structures and functions.  


Invertebrate animals, which lack adaptive immune systems, have developed defense systems, so-called innate immunity, that respond to common antigens on the surface of potential pathogens. One such defense system is involved in the cellular responses of horseshoe crab hemocytes to invaders. Hemocytes contain two types, large (L) and small (S), of secretory granules, and the contents of these granules are released in response to invading microbes via exocytosis. Recent biochemical and immunological studies on the granular components of L- and S-granules demonstrated that the two types of granules selectively store granule-specific proteins participating in the host defense systems. L-Granules contain all the clotting factors essential for hemolymph coagulation, protease inhibitors including serpins and cystatin, and anti-lipopolysaccharide (LPS) factor and several tachylectins with LPS binding and bacterial agglutinating activities. On the other hand, S-granules contain various new cysteine-rich basic proteins with antimicrobial or bacterial agglutinating activities, such as tachyplesins, big defensin, tachycitin, and tachystatins. The co-localization of these proteins in the granules and their release into the hemolymph suggest that they serve synergistically to construct an effective host defense system against invaders. Here, the structures and functions of these new types of defense molecules found in the Japanese horseshoe crab (Tachypleus tridentatus) are reviewed. PMID:9504402

Iwanaga, S; Kawabata, S; Muta, T



Human CD25 ? CD4 ? T Suppressor Cell Clones Produce Transforming Growth Factor ? , but not Interleukin 10, and Are Distinct from Type 1 T Regulatory Cells  

Microsoft Academic Search

T regulatory (Tr) cells are essential for the induction of peripheral tolerance. Several types of Tr cells exist, including CD4 ? T cells which express CD25 constitutively and suppress immune responses via direct cell-to-cell interactions, and type 1 T regulatory (Tr1) cells, which function via secretion of interleukin (IL)-10 and transforming growth factor (TGF)- ? . The relationship between CD25

Megan K. Levings; Romina Sangregorio; Claudia Sartirana; Anna Lisa Moschin; Manuela Battaglia; Paul C. Orban


Impact of Plasmids, Including Those EncodingVirB4/D4 Type IV Secretion Systems, on Salmonella enterica serovar Heidelberg Virulence in Macrophages and Epithelial Cells.  


Salmonella enterica serovar Heidelberg (S. Heidelberg) can cause foodborne illness in humans following the consumption of contaminated meat and poultry products. Recent studies from our laboratory have demonstrated that certain S. Heidelberg isolated from food-animal sources harbor multiple transmissible plasmids with genes that encode antimicrobial resistance, virulence and a VirB4/D4 type-IV secretion system. This study examines the potential role of these transmissible plasmids in bacterial uptake and survival in intestinal epithelial cells and macrophages, and the molecular basis of host immune system modulation that may be associated with disease progression. A series of transconjugant and transformant strains were developed with different combinations of the plasmids to determine the roles of the individual and combinations of plasmids on virulence. Overall the Salmonella strains containing the VirB/D4 T4SS plasmids entered and survived in epithelial cells and macrophages to a greater degree than those without the plasmid, even though they carried other plasmid types. During entry in macrophages, the VirB/D4 T4SS encoding genes are up-regulated in a time-dependent fashion. When the potential mechanisms for increased virulence were examined using an antibacterial Response PCR Array, the strain containing the T4SS down regulated several host innate immune response genes which likely contributed to the increased uptake and survival within macrophages and epithelial cells. PMID:24098597

Gokulan, Kuppan; Khare, Sangeeta; Rooney, Anthony W; Han, Jing; Lynne, Aaron M; Foley, Steven L



Impact of Plasmids, Including Those EncodingVirB4/D4 Type IV Secretion Systems, on Salmonella enterica serovar Heidelberg Virulence in Macrophages and Epithelial Cells  

PubMed Central

Salmonella enterica serovar Heidelberg (S. Heidelberg) can cause foodborne illness in humans following the consumption of contaminated meat and poultry products. Recent studies from our laboratory have demonstrated that certain S. Heidelberg isolated from food-animal sources harbor multiple transmissible plasmids with genes that encode antimicrobial resistance, virulence and a VirB4/D4 type-IV secretion system. This study examines the potential role of these transmissible plasmids in bacterial uptake and survival in intestinal epithelial cells and macrophages, and the molecular basis of host immune system modulation that may be associated with disease progression. A series of transconjugant and transformant strains were developed with different combinations of the plasmids to determine the roles of the individual and combinations of plasmids on virulence. Overall the Salmonella strains containing the VirB/D4 T4SS plasmids entered and survived in epithelial cells and macrophages to a greater degree than those without the plasmid, even though they carried other plasmid types. During entry in macrophages, the VirB/D4 T4SS encoding genes are up-regulated in a time-dependent fashion. When the potential mechanisms for increased virulence were examined using an antibacterial Response PCR Array, the strain containing the T4SS down regulated several host innate immune response genes which likely contributed to the increased uptake and survival within macrophages and epithelial cells.

Gokulan, Kuppan; Khare, Sangeeta; Rooney, Anthony W.; Han, Jing; Lynne, Aaron M.; Foley, Steven L.



Confirmation of HLA class II independent type 1 diabetes associations in the major histocompatibility complex including HLA-B and HLA-A  

PubMed Central

Aim Until recently, human leucocyte antigen (HLA) class II-independent associations with type 1 diabetes (T1D) in the Major Histocompatibility Complex (MHC) region were not adequately characterized owing to insufficient map coverage, inadequate statistical approaches and strong linkage disequilibrium spanning the entire MHC. Here we test for HLA class II-independent associations in the MHC using fine mapping data generated by the Type 1 Diabetes Genetics Consortium (T1DGC). Methods We have applied recursive partitioning to the modelling of the class II loci and used stepwise conditional logistic regression to test ~1534 loci between 29 and 34 Mb on chromosome 6p21, typed in 2240 affected sibpair (ASP) families. Results Preliminary analyses confirm that HLA-B (at 31.4 Mb), HLA-A (at 30.0 Mb) are associated with T1D independently of the class II genes HLA-DRB1 and HLA-DQB1 (P = 6.0 × 10?17 and 8.8 × 10?13, respectively). In addition, a second class II region of association containing the single-nucleotide polymorphism (SNP), rs439121, and the class II locus HLA-DPB1, was identified as a T1D susceptibility effect which is independent of HLA-DRB1, HLA-DQB1 and HLA-B (P = 9.2 × 10?8). A younger age-at-diagnosis of T1D was found for HLA-B*39 (P = 7.6 × 10?6), and HLA-B*38 was protective for T1D. Conclusions These analyses in the T1DGC families replicate our results obtained previously in ~2000 cases and controls and 850 families. Taking both studies together, there is evidence for four T1D-associated regions at 30.0 Mb (HLA-A), 31.4 Mb (HLA-B), 32.5 Mb (rs9268831/HLA-DRA) and 33.2 Mb (rs439121/HLA-DPB1) that are independent of HLA-DRB1/HLA-DQB1. Neither study found evidence of independent associations at HLA-C, HLA-DQA1 loci nor in the UBD/MAS1L or ITPR3 gene regions. These studies show that to find true class II-independent effects, large, well-powered sample collections are required and be genotyped with a dense map of markers. In addition, a robust statistical methodology that fully models the class II effects is necessary. Recursive partitioning is a useful tool for modelling these multiallelic systems.

Howson, J. M. M.; Walker, N. M.; Clayton, D.; Todd, J. A.



Extended-spectrum ?-lactamase-producing Escherichia coli in Spain belong to a large variety of multilocus sequence typing types, including ST10 complex\\/A, ST23 complex\\/A and ST131\\/B2  

Microsoft Academic Search

In this study, we investigated the population structure of extended-spectrum ?-lactamase (ESBL)-producing Escherichia coli in Spain and determined possible associations between specific multilocus sequence typing (MLST) types and ESBL types. Ninety-two ESBL-producing E. coli isolates from 11 Spanish hospitals were studied. The predominant ESBLs in this collection were CTX-M-14 (45.7%), SHV-12 (21.7%) and CTX-M-9 (20.6%). Phylogenetic groups and MLST types

Jesús Oteo; Karol Diestra; Carlos Juan; Verónica Bautista; Ângela Novais; María Pérez-Vázquez; Bartolome Moyá; Elisenda Miró; Teresa M. Coque; Antonio Oliver; Rafael Cantón; Ferran Navarro; José Campos



Growth differentiation factor-9 signaling is mediated by the type I receptor, activin receptor-like kinase 5.  


Growth differentiation factor-9 (GDF-9) is an oocyte-derived growth factor and a member of the TGF-beta superfamily that includes TGF-beta, activin, and bone morphogenetic proteins (BMPs). GDF-9 is indispensable for the development of ovarian follicles from the primary stage, and treatment with GDF-9 enhances the progression of early follicles into small preantral follicles. Similar to other TGF-beta family ligands, GDF-9 likely initiates signaling mediated by type I and type II receptors with serine/threonine kinase activity, followed by the phosphorylation of intracellular transcription factors named Smads. We have shown previously that GDF-9 interacts with the BMP type II receptor (BMPRII) in granulosa cells, but the type I receptor involved is unknown. Using P19 cells, we now report that GDF-9 treatment stimulated the CAGA-luciferase reporter known to be responsive to TGF-beta mediated by the type I receptor, activin receptor-like kinase (ALK)5. In contrast, GDF-9 did not stimulate BMP-responsive reporters. In addition, treatment with GDF-9 induced the phosphorylation of Smad2 and Smad3 in P19 cells, and the stimulatory effect of GDF-9 on the CAGA-luciferase reporter was blocked by the inhibitory Smad7, but not Smad6. We further reconstructed the GDF-9 signaling pathway using Cos7 cells that are not responsive to GDF-9. After overexpression of ALK5, with or without exogenous Smad3, the Cos7 cells gained GDF-9 responsiveness based on the CAGA-luciferase reporter assay. The roles of ALK5 and downstream pathway genes in mediating GDF-9 actions were further tested in ovarian cells. In cultured rat granulosa cells from early antral follicles, treatment with GDF-9 stimulated the CAGA-luciferase reporter activity and induced the phosphorylation of Smad3. Furthermore, transfection with small interfering RNA for ALK5 or overexpression of the inhibitory Smad7 resulted in dose-dependent suppression of GDF-9 actions. In conclusion, although GDF-9 binds to the BMP-activated type II receptor, its downstream actions are mediated by the type I receptor, ALK5, and the Smad2 and Smad3 proteins. Because ALK5 is a known receptor for TGF-beta, diverse members of the TGF-beta family of ligands appear to interact with a limited number of receptors in a combinatorial manner to activate two downstream Smad pathways. PMID:14684852

Mazerbourg, Sabine; Klein, Cynthia; Roh, Jaesook; Kaivo-Oja, Noora; Mottershead, David G; Korchynskyi, Olexander; Ritvos, Olli; Hsueh, Aaron J W



Four Variants of the Citrobacter freundii AmpC-Type Cephalosporinases, Including Novel Enzymes CMY-14 and CMY-15, in a Proteus mirabilis Clone Widespread in Poland  

PubMed Central

Twenty-nine Proteus mirabilis isolates from 17 Polish hospitals were analyzed. The isolates were resistant to a variety of antimicrobials, and their patterns of resistance to ?-lactams resembled those of the constitutive class C cephalosporinase (AmpC) producers. Indeed, ?-lactamases with a pI of ?9.0 were found in all of the isolates, and they were subsequently identified as four AmpC-type cephalosporinases, CMY-4, -12, -14, and -15, of which the two last ones were novel enzyme variants. The enzymes were of Citrobacter freundii origin and were closely related to each other, with CMY-4 likely being the evolutionary precursor of the remaining ones. The blaCMY genes were located exclusively in chromosomal DNA, within EcoRI restriction fragments of the same size of ?10 kb. In the CMY-12- and -15-producing isolates, an additional fragment of ?4.5 kb hybridized with the blaCMY probe as well, which could have arisen from a duplication event during the evolution of the genes. In all of the isolates, the ISEcp1 mobile element, which most probably is involved in mobilization of the C. freundii ampC gene, was placed at the same distance from the 5? ends of the blaCMY genes, and sequences located between them were identical in isolates carrying each of the four genes. These data suggested that a single chromosome-to-chromosome transfer of the ampC gene from C. freundii to P. mirabilis could have initiated the spread and evolution of the AmpC-producing P. mirabilis in Poland. The hypothesis seems to be confirmed by pulsed-field gel electrophoresis typing, which revealed several cases of close relatedness between the P. mirabilis isolates from distant centers and showed an overall similarity between the majority of the multiresistant isolates.

Literacka, Elzbieta; Empel, Joanna; Baraniak, Anna; Sadowy, Ewa; Hryniewicz, Waleria; Gniadkowski, Marek



The predisposition to type 1 diabetes linked to the human leukocyte antigen complex includes at least one non-class II gene.  

PubMed Central

The human leukocyte antigen (HLA) complex, encompassing 3.5 Mb of DNA from the centromeric HLA-DPB2 locus to the telomeric HLA-F locus on chromosome 6p21, encodes a major part of the genetic predisposition to develop type 1 diabetes, designated "IDDM1." A primary role for allelic variation of the class II HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci has been established. However, studies of animals and humans have indicated that other, unmapped, major histocompatibility complex (MHC)-linked genes are participating in IDDM1. The strong linkage disequilibrium between genes in this complex makes mapping a difficult task. In the present paper, we report on the approach we have devised to circumvent the confounding effects of disequilibrium between class II alleles and alleles at other MHC loci. We have scanned 12 Mb of the MHC and flanking chromosome regions with microsatellite polymorphisms and analyzed the transmission of these marker alleles to diabetic probands from parents who were homozygous for the alleles of the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. Our analysis, using three independent family sets, suggests the presence of an additional type I diabetes gene (or genes). This approach is useful for the analysis of other loci linked to common diseases, to verify if a candidate polymorphism can explain all of the association of a region or if the association is due to two or more loci in linkage disequilibrium with each other.

Lie, B A; Todd, J A; Pociot, F; Nerup, J; Akselsen, H E; Joner, G; Dahl-J?rgensen, K; R?nningen, K S; Thorsby, E; Undlien, D E



Basal and stimulated plasma atrial natriuretic factor in type 2 diabetes.  


Subjects with Type 2 diabetes have been reported to have elevated total exchangeable sodium when compared with normal subjects. Sodium retention may contribute to the development of hypertension in these subjects. Atrial natriuretic factor may play a role in sodium and blood pressure homeostasis in Type 2 diabetes. We have studied plasma atrial natriuretic factor in 17 subjects with Type 2 diabetes (9M:8F; aged 49 +/- 2 years) (mean +/- SE) and in 17 age- (49 +/- 2 years) and sex-matched controls. Mean fasting blood sugar was 8.3 +/- 0.6 mmol l-1 in the diabetic subjects. After fasting from 2200h, subjects remained upright from 0745h until 0945h when blood was taken for plasma atrial natriuretic factor, plasma renin activity and serum aldosterone. Two litres of 0.15 mmol l-1 NaCl was infused intravenously between 1000h and 1400h while the subjects remained supine. Blood was taken hourly. At 0945h plasma atrial natriuretic factor was 3.8 +/- 0.4 pmol l-1 in diabetic subjects and 6.1 +/- 1.6 pmol l-1 in controls (NS), at 1000h after 15 mins supine 3.5 +/- 0.3 and 7.9 +/- 2.3 pmol l-1 respectively (p < 0.05) and increased to 9.4 +/- 1.5 and 9.4 +/- 1.2 pmol l-1 in diabetic subjects and controls at 1400h (NS; both p < 0.01 vs basal values). Serum aldosterone, plasma renin activity, blood pressure and urinary sodium output for 12h before, 4h during and 8h after the NaCl infusion were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1841825

McKnight, J A; Sheridan, B; Roberts, G; Atkinson, A B



Factor-analytic models for genotype x environment type problems and structured covariance matrices  

PubMed Central

Background Analysis of data on genotypes with different expression in different environments is a classic problem in quantitative genetics. A review of models for data with genotype × environment interactions and related problems is given, linking early, analysis of variance based formulations to their modern, mixed model counterparts. Results It is shown that models developed for the analysis of multi-environment trials in plant breeding are directly applicable in animal breeding. In particular, the 'additive main effect, multiplicative interaction' models accommodate heterogeneity of variance and are characterised by a factor-analytic covariance structure. While this can be implemented in mixed models by imposing such structure on the genetic covariance matrix in a standard, multi-trait model, an equivalent model is obtained by fitting the common and specific factors genetic separately. Properties of the mixed model equations for alternative implementations of factor-analytic models are discussed, and extensions to structured modelling of covariance matrices for multi-trait, multi-environment scenarios are described. Conclusion Factor analytic models provide a natural framework for modelling genotype × environment interaction type problems. Mixed model analyses fitting such models are likely to see increasing use due to the parsimonious description of covariance structures available, the scope for direct interpretation of factors as well as computational advantages.

Meyer, Karin



C-type natriuretic peptide inhibits growth factor-dependent DNA synthesis in smooth muscle cells.  


We have examined the ability of C-type natriuretic peptide (CNP) to interact with guanylate cyclase-coupled natriuretic peptide receptors by measuring its ability to stimulate intracellular guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in cultured bovine aortic endothelial (BAE) and bovine aortic smooth muscle (BASM) cells. Our experiments indicate that CNP is unable to stimulate the production of cGMP in BAE cells, whereas both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) markedly elevate cGMP levels in these cells (ANP = BNP > CNP). In contrast, CNP is the most effective of the three peptides with respect to the stimulation of cGMP levels in BASM cells, fetal human vascular smooth muscle cells, and rat A10 cells (CNP > ANP > BNP), with the maximal level of stimulation being approximately 5- to 10-fold over that observed for ANP. We have also shown that CNP is able to inhibit serum- and growth factor-induced DNA synthesis in BASM cells. Low concentrations of CNP (20 x 10(-9) M) inhibit up to 80% of the [3H]-thymidine incorporation induced by basic fibroblast growth factor, platelet derived growth factor, epidermal growth factor (EGF), and heparin binding EGF-like growth factor. These data indicate that, although CNP has been detected only in the central nervous system and not in the circulation, it may possess multiple effects on vascular tissue. PMID:1359791

Porter, J G; Catalano, R; McEnroe, G; Lewicki, J A; Protter, A A



The Presence of Family History and the Development of Type 2 Diabetes Mellitus Risk Factors in Rural Children  

ERIC Educational Resources Information Center

|Type 2 diabetes mellitus is reaching epidemic proportions among children and adolescents. School health fairs offer an opportunity to identify children with risk factors for the development of type 2 diabetes mellitus. This study identified selected risk factors (i.e., high-risk racial/ethnic group, obesity, elevated blood pressure, elevated…

Adams, Marsha Howell; Barnett Lammon, Carol Ann



Developmental Trends in Type A Behavior as Predictors for the Development of Somatic Coronary Heart Disease Risk Factors  

Microsoft Academic Search

Developmental trends in type A behavior and somatic risk factors of coronary heart disease were studied in 842 healthy adolescents and young adults. Type A behavior was measured using the AFMS and the somatic risk factors adopted were serum total cholesterol, LDL and HDL cholesterol, systolic blood pressure, diastolic blood pressure, pulse frequency and body mass index. The results showed

Liisa Keltikangas-Järvinen; Katri Räikkönen



Type A Behavior Pattern: Is It a Risk Factor for Open-Angle Chronic Glaucoma?  


AIM:: To evaluate the presence of type A behavior in patients affected by open-angle glaucoma (OAG) and the possible role of psychophysiological stress as a risk factor for OAG. MATERIALS AND METHODS:: Fifty patients, 30 women and 20 men, affected by OAG, underwent ophthalmological examination consisting of complete biomicroscopy, tonometry and daily tonometric curve, examination of the visual field by means of computerized perimeter "Octopus 1-2-3," and its assessment with the Glaucoma Staging System 2, morphologic monitoring of the retinal nerve fiber layer with GDx VCC and psychological assessment (Hamilton Anxiety Rating Scale) to evaluate the presence of anxiety and its level; type A/B personality questionnaire (Jenkin Modified Activity Survey; Ercta-B test for the further evaluation of type A personality; STAY test; Brief-cope test; Life event. RESULTS:: Sixty-four percent of the subjects, 17 women and 13 men, showed type A behavior, and in these patients both trait and state anxiety were much more evident (P=0.001). In the type A subjects, there was a much more significant visual field involvement (P=0.001); this involvement showed a negative correlation (P=0.024) with the Brief-cope scale. CONCLUSIONS:: The personality study is an extremely important part of the diagnostic work-up and treatment of OAG. PMID:23059484

Bubella, Raffaella Morreale; Bubella, Daniele Morreale; Cillino, Salvatore



Characterisation of "caramel-type" thermal decomposition products of selected monosaccharides including fructose, mannose, galactose, arabinose and ribose by advanced electrospray ionization mass spectrometry methods.  


The chemical analysis of caramel, formed upon heating of carbohydrates, remains a significant challenge due to the complexity of the resulting product mixture. Identification of the products formed upon heating of monosaccharides including fructose, mannose, galactose, arabinose and ribose is essential to understand the composition and properties of carbohydrate-rich processed foods. In this work, we report on the use of combined mass spectrometry techniques, including high performance liquid chromatography and electrospray ionization multi-stage tandem mass spectrometry (ESI-MS(n)). The composition of the obtained caramel was examined by high resolution mass spectrometry along with van Krevelen and Kendrick analysis. We found that caramel is composed of oligomers with up to six carbohydrate units formed through unselective glycosidic bond formation, their dehydrated products by losing up to eight water molecules, hydrated products and disproportionation products. An accurate mass measurement and subsequent fragment ion studies of all caramel samples (around 40 compounds) can thus be identified. Glycosidic bond and ring cleavages of sugar moieties were the major observable fragmentation pathways during this experiment. The innovative analytical strategies for the complex mixture analysis used provide a comprehensive account of the chemical composition of caramel, one of the most popular dietary materials over the world. PMID:23529212

Golon, Agnieszka; Kuhnert, Nikolai



Detection of a microbial consortium, including type 2 methanotrophs, by use of phospholipid fatty acids in an aerobic halogenated hydrocarbon-degrading soil column enriched with natural gas  

SciTech Connect

The phospholipid ester-linked normal and lipopolysaccharide-layer hydroxy fatty acids from microbes in a natural gas (85% methane)-stimulated soil column capable of degrading halogenated hydrocarbons were analyzed in detail by capillary column GC-MS. Microbial biomass, calculated from phospholipid fatty acid (PLFA) concentrations to be 5.6 x 10/sup 9/ bacteria/g (dry weight), was greater in the hydrocarbon-degrading column than in either an azide-inhibited soil column or an untreated surface soil. Microbial community structure information, using GC-MS analysis of derivatized monounsaturated PLFA, indicated that the major component (16 to 18%) of the PLFA in the hydrocarbon-degrading column was the PLFA 28:1 delta 10c. The novel PLFA has been reported as a major component in type II methanotrophs. Based on these differences, the potential exists to use these methods to monitor shifts in microbial biomass and community structure in aquifers where indigenous bacteria are stimulated to biotransform pollutant compounds.

Nichols, P.D.; Henson, J.M.; Antworth, C.P.; Parsons, J.; Wilson, J.T.



Production of growth factors by type 5 adenovirus transformed rat embryo cells.  


Transformation of Sprague-Dawley rat embryo (RE) cells and a cloned Fischer rat embryo cell line (CREF) with wild-type (Ad5) or a temperature-sensitive DNA-minus mutant (H5ts125) of type 5 adenovirus results in a reduction in binding of epidermal growth factor (EGF) to cell surface receptors. A reduction in EGF binding is also seen in a Syrian hamster embryo cell line transformed by a hexon mutant of Ad5. In contrast, a human embryonic kidney cell line (293) transformed by sheared Ad5 DNA or transfected clones of KB cells expressing the E1 transforming region of Ad5 do not show a decrease in receptor binding. When cocultivated, the adenovirus transformed rat cells were able to induce the growth in agar of normal CREF cells. Medium from Ad5 transformed RE cells stimulated the growth in agar of CREF cells and also inhibited [125I]-EGF binding in CREF cells. When fractionated by gel filtration, two peaks of [125I]-EGF inhibiting activities were obtained with apparent molecular weights of 35,000 and 16,000. These results provide the first evidence that cells transformed by an adenovirus can produce a growth factor(s) that inhibits EGF-receptor binding and induces anchorage-independent growth of normal cells. PMID:6300150

Fisher, P B; Boersig, M R; Graham, G M; Weinstein, I B



Activating Transcription Factor 6 (ATF6) Sequence Polymorphisms in Type 2 Diabetes and Pre-Diabetic Traits  

PubMed Central

Activating transcription factor 6 (ATF6) is located within the region of linkage to type 2 diabetes on chromosome 1q21-q23 and is a key activator of the endoplasmic reticulum stress response. We evaluated 78 single nucleotide polymorphisms (SNPs) spanning >213 kb in 95 people, from which we selected 64 SNPs for evaluation in 191 Caucasian case subjects from Utah and between 165 and 188 control subjects. Six SNPs showed nominal associations with type 2 diabetes (P = 0.001-0.04), including the nonsynonymous SNP rs1058405 (M67V) in exon 3 and rs11579627 in the 3? flanking region. Only rs1159627 remained significant on permutation testing. The associations were not replicated in 353 African-American case subjects and 182 control subjects, nor were ATF6 SNPs associated with altered insulin secretion or insulin sensitivity in nondiabetic Caucasian individuals. No association with type 2 diabetes was found in a subset of 44 SNPs in Caucasian (n = 2,099), Pima Indian (n = 293), and Chinese (n = 287) samples. Allelic expression imbalance was found in transformed lymphocyte cDNA for 3? untranslated region variants, thus suggesting cis-acting regulatory variants. ATF6 does not appear to play a major role in type 2 diabetes, but further work is required to identify the cause of the allelic expression imbalance.

Chu, Winston S.; Das, Swapan Kumar; Wang, Hua; Chan, Juliana C.; Deloukas, Panos; Froguel, Philippe; Baier, Leslie J.; Jia, Weiping; McCarthy, Mark I.; Ng, Maggie C.Y.; Damcott, Coleen; Shuldiner, Alan R.; Zeggini, Eleftheria; Elbein, Steven C.



Short communication: activating transcription factor 4 (ATF4) promotes HIV type 1 activation.  


Activating transcription factor 4 (ATF4) is a central factor in the cellular response to multiple stresses, including altered metabolic conditions, anoxia and hypoxia, and redox stress. ATF4 is triggered by endoplasmic reticulum stress and consequent unfolded protein response. This report identifies for the first time ATF4 as a transcription factor upregulated by HIV-1 infection. Upregulation of ATF4 enhances HIV replication, by synergistic interactions with HIV Tat. Moreover, in specific cell lines ATF4 has a direct transactivating potential on the LTR, even in the absence of Tat. We also provide evidence that expression of ATF4 induces HIV reactivation in chronically infected cell lines. These results show for the first time that ATF4 induction might have an important role in HIV replication, and suggest that ATF4 might represent a convergent signaling molecule for different stressors important in regulating the HIV-1 cycle. PMID:22050711

Caselli, Elisabetta; Benedetti, Sabrina; Gentili, Valentina; Grigolato, Jessica; Di Luca, Dario



Petrographic and Geochemical Characterization of Ore-Bearing Intrusions of the Noril'sk type, Siberia; With Discussion of Their Origin, Including Additional Datasets and Core Logs  

USGS Publications Warehouse

The Noril'sk I, Talnakh, and Kharaelakh intrusions of the Noril'sk district host one of the outstanding metal concentrations in the world; contained Cu-Ni resources are comparable to the deposits at Sudbury, Ontario and the platinum group element (PGE) resource is second only to that of the Bushveld Complex. Our opportunity to cooperatively sample and study this district in Siberian Russia arose in 1990 through a memorandum of understanding between the U.S. Geological Survey and the former Ministry of Geology of the U.S.S.R. The world-class significance of these deposits and the possibility that understanding their geologic context, including construction of a credible 'ore-deposit model,' will lead to discovery of similar deposits elsewhere, inspired extensive studies of the ores, the mafic-intrusions which host them, and associated flood basalts.

Compiled by Czamanske, Gerald K.



Nitrate reduction by Desulfovibrio desulfuricans: a periplasmic nitrate reductase system that lacks NapB, but includes a unique tetraheme c-type cytochrome, NapM.  


Many sulphate reducing bacteria can also reduce nitrite, but relatively few isolates are known to reduce nitrate. Although nitrate reductase genes are absent from Desulfovibrio vulgaris strain Hildenborough, for which the complete genome sequence has been reported, a single subunit periplasmic nitrate reductase, NapA, was purified from Desulfovibrio desulfuricans strain 27774, and the structural gene was cloned and sequenced. Chromosome walking methods have now been used to determine the complete sequence of the nap gene cluster from this organism. The data confirm the absence of a napB homologue, but reveal a novel six-gene organisation, napC-napM-napA-napD-napG-napH. The NapC polypeptide is more similar to the NrfH subgroup of tetraheme cytochromes than to NapC from other bacteria. NapM is predicted to be a tetra-heme c-type cytochrome with similarity to the small tetraheme cytochromes from Shewanella oneidensis. The operon is located close to a gene encoding a lysyl-tRNA synthetase that is also found in D. vulgaris. We suggest that electrons might be transferred to NapA either from menaquinol via NapC, or from other electron donors such as formate or hydrogen via the small tetraheme cytochrome, NapM. We also suggest that, despite the absence of a twin-arginine targeting sequence, NapG might be located in the periplasm where it would provide an alternative direct electron donor to NapA. PMID:15972253

Marietou, Angeliki; Richardson, David; Cole, Jeff; Mohan, Sudesh



Sociodemographic and Clinical Factors Associated with Antidepressant Type in a National Sample of the Home HealthCare Elderly  

PubMed Central

Objective The study examined in HHC, demographic, functional and clinical factors by antidepressant type including SSRIs, SNRIs, TCAs and “Other” antidepressants such as buproprion and mirtazapine. Method Cross-sectional sample (n= 909) analyzed the 2007 National Home Health and Hospice Care Survey, patients 65 years plus (mean 78.79 years, CI = 77.88-79.69 years) taking one antidepressant. Results SSRIs were most commonly used (63.89%) then “Other” antidepressants (14.29%) , TCAs (11.31%) and SNRIs. In a multinomial regression referencing SSRIs, blacks had increased odds of tricyclic use compared to whites (OR = 5.96, CI = 1.85-19.19). . Hispanics had decreased odds of “Other” AD (OR= 0.13, CI= 0.02-0.73) and SNRI use (OR= 0.06, CI= 0.008-0.45) compared to non-Hispanics. HHC elderly taking psychotropic medications besides ADs were less likely to use SNRIs (OR= 0.31, CI= 0.11-0.88) and tricyclics (OR =0.27, CI= 0.08-0.87). Advancing age was marginally associated with tricyclic use (OR= 1.04, CI= 0.99-1.09). Conclusion Race/ethnicity and age differences by antidepressant typeincluding blacks’ increased TCA use, Hispanics decreased SNRI and “Other antidepressant” use, and older elderly increased tricyclic use -- suggests systematic differences in prescribing practice variations including differences by geography, patient preferences, or access to care in the HHC elderly.

Weissman, Judith; Meyers, Barnett S.; Ghosh, Samiran; Bruce, Martha L.




NSDL National Science Digital Library

This interactive Java applet helps students explore the relationship between area and multiplication. First, users are asked to input all factor pairs of a given number. Then, selecting each of those factor pairs, the user draws the respective rectangular array by clicking and dragging across a grid. Options include the use of the commutative property (e.g., user must enter both 2x4 and 4x2 for factors of 8 and represent them with different arrays), entering a number of the user's own choice, and an optional scoring feature allowing the user to keep track of the number correct.



Cold Heat Storage Characteristics of O/W-type Latent Heat Emulsion Including Continuum Phase of Water Treated with a Freezing Point Depression  

NASA Astrophysics Data System (ADS)

This paper deals with flow and cold heat storage characteristics of the oil (tetradecane, C14H30, freezing point 278.9 K, Latent heat 229 kJ/kg)/water emulsion as a latent heat storage material having a low melting point. The test emulsion includes a water-urea solution as a continuum phase. The freezing point depression of the continuum phase permits enhancement of the heat transfer rate of the emulison, due to the large temperature difference between the latent heat storage material and water-urea solution. The velocity of emulsion flow and the inlet temperature of coolant in a coiled double tube heat exchanger are chosen as the experimental parameters. The pressure drop, the heat transfer coefficient of the emulsion in the coiled tube are measured in the temperture region over solid and liquid phase of the latent heat storage material. The finishing time of the cold heat storage is defined experimentally in the range of sensible and latent heat storage. It is clarified that the flow behavior of the emulsion as a non-Newtonian fluid has an important role in cold heat storage. The useful nondimentional correlation equations for the additional pressure loss coefficient, the heat transfer coefficient and the finishing time of the cold heat storage are derived in terms of Dean number and heat capacity ratio.

Inaba, Hideo; Morita, Shin-Ichi


Cellular expression of the immediate early transcription factors Nurr1 and NGFI-B suggests a gene regulatory role in several brain regions including the nigrostriatal dopamine system  

Microsoft Academic Search

Nurr1 and NGFI-B are closely related orphan members of the steroid-thyroid hormone receptor family involved in immediate early responses to stimuli such as growth factors. In-situ hybridization in the developing and adult mouse and rat demonstrated Nurr1 mRNA in several regions during early central nervous system (CNS) development. Expression persisted through the pre- and postnatal periods and was also found

Rolf H Zetterström; Reg Williams; Thomas Perlmann; Lars Olson



Cellular Targets for Activation by the E2F1 Transcription Factor Include DNA Synthesis and G 1 \\/S-Regulatory Genes  

Microsoft Academic Search

Although a number of transfection experiments have suggested potential targets for the action of the E2F1 transcription factor, as is the case for many transcriptional regulatory proteins, the actual targets in their normal chromosomal environment have not been demonstrated. We have made use of a recombinant adeno- virus containing the E2F1 cDNA to infect quiescent cells and then measure the




Transforming Growth Factor ? Receptor Type 1 Is Essential for Female Reproductive Tract Integrity and Function  

PubMed Central

The transforming growth factor ? (TGF?) superfamily proteins are principle regulators of numerous biological functions. Although recent studies have gained tremendous insights into this growth factor family in female reproduction, the functions of the receptors in vivo remain poorly defined. TGF? type 1 receptor (TGFBR1), also known as activin receptor-like kinase 5, is the major type 1 receptor for TGF? ligands. Tgfbr1 null mice die embryonically, precluding functional characterization of TGFBR1 postnatally. To study TGFBR1–mediated signaling in female reproduction, we generated a mouse model with conditional knockout (cKO) of Tgfbr1 in the female reproductive tract using anti-Müllerian hormone receptor type 2 promoter-driven Cre recombinase. We found that Tgfbr1 cKO females are sterile. However, unlike its role in growth differentiation factor 9 (GDF9) signaling in vitro, TGFBR1 seems to be dispensable for GDF9 signaling in vivo. Strikingly, we discovered that the Tgfbr1 cKO females develop oviductal diverticula, which impair embryo development and transit of embryos to the uterus. Molecular analysis further demonstrated the dysregulation of several cell differentiation and migration genes (e.g., Krt12, Ace2, and MyoR) that are potentially associated with female reproductive tract development. Moreover, defective smooth muscle development was also revealed in the uteri of the Tgfbr1 cKO mice. Thus, TGFBR1 is required for female reproductive tract integrity and function, and disruption of TGFBR1–mediated signaling leads to catastrophic structural and functional consequences in the oviduct and uterus.

Li, Qinglei; Agno, Julio E.; Edson, Mark A.; Nagaraja, Ankur K.; Nagashima, Takashi; Matzuk, Martin M.



Differences between juvenile offenders with and without intellectual disability in offense type and risk factors.  


The present study aimed to examine differences between American juvenile offenders with and without intellectual disability (ID) in offense type and risk factors. The sample consisted of adolescents with ID (n=102) and without ID (n=526) who appeared before the courts for a criminal act and for whom the Washington State Juvenile Court Assessment (WSJCA) was completed. Results showed that adolescents with ID had committed more offenses against persons compared to adolescents without ID. Few differences in risk factors were found between juvenile offenders with and without ID in the domains of school, family and use of free time. Juvenile offenders without ID more often had problems in the relationship and alcohol/drugs domain, whereas juveniles with ID more often experienced problems in the domains of attitude, aggression and skills. PMID:22750352

Asscher, Jessica J; van der Put, Claudia E; Stams, Geert Jan J M



Attenuation of fibroblast growth factor signaling by poly-N-acetyllactosamine type glycans.  


Fibroblast growth factors (FGFs) and their receptors are expressed in a variety of mammalian tissues, playing a role in development and cell proliferation. While analyzing human sperm motility, we found that sperm treated with endo-?-galactosidase (EBG), which specifically hydrolyzes poly-N-acetyllactosamine type glycans (polyLacs), enhanced motility. Mass spectrometry analysis revealed that sperm-associated polyLacs are heavily fucosylated, consistent with Lewis Y antigen. Immunohistochemistry of epididymis using an anti-Lewis Y antibody before and after EBG treatment suggested that polyLacs carrying the Lewis Y epitope are synthesized in epididymal epithelia and secreted to seminal fluid. EBG-treated sperm elevated cAMP levels and calcium influx, indicating activation of fibroblast growth factor signaling. Seminal fluid polyLacs bound to FGFs in vitro, and impaired FGF-mediated signaling in HEK293T cells. PMID:23968720

Sugihara, Kazuhiro; Shibata, Toshiaki K; Takata, Kayoko; Kimura, Takako; Kanayama, Naohiro; Williams, Roy; Hatakeyama, Shingo; Akama, Tomoya O; Kuo, Chu-Wei; Khoo, Kay-Hooi; Fukuda, Michiko N



The type 1 insulin-like growth factor receptor and resistance to DACH1.  


The mammalian homolog of the Drosophila dachshund gene (DACH1) has been reported as a tumor suppressor in human breast and prostate cancers. It downregulates the epidermal growth factor receptor (EGFR) and cyclin D1. The signaling pathway of the type 1 insulin-like growth factor receptor (IGF-IR) is known to be responsible for the development of resistance to treatment of human cancer with antibodies to the EGFR. We have asked whether DACH1 still exerts its tumor suppressor activity in cells dependent on the IGF-IR for growth. We find that in cells growing in IGF-1 (and unresponsive to EGF), DACH1 is devoid of tumor suppressor activity. PMID:21558809

DeAngelis, Tiziana; Wu, Kongming; Pestell, Richard; Baserga, Renato



The v-sis protein retains biological activity as a type II membrane protein when anchored by various signal-anchor domains, including the hydrophobic domain of the bovine papilloma virus E5 oncoprotein  

PubMed Central

Membrane-anchored forms of the v-sis oncoprotein have been previously described which are oriented as type I transmembrane proteins and which efficiently induce autocrine transformation. Several examples of naturally occurring membrane-anchored growth factors have been identified, but all exhibit a type I orientation. In this work, we wished to construct and characterize membrane-anchored growth factors with a type II orientation. These experiments were designed to determine whether type II membrane-anchored growth factors would in fact exhibit biological activity. Additionally, we wished to determine whether the hydrophobic domain of the E5 oncoprotein of bovine papilloma virus (BPV) can function as a signal-anchor domain to direct type II membrane insertion. Type II derivatives of the v-sis oncoprotein were constructed, with the NH2 terminus intracellular and the COOH terminus extracellular, by substituting the NH2 terminal signal sequence with the signal-anchor domain of a known type II membrane protein. The signal-anchor domains of neuraminidase (NA), asialoglycoprotein receptor (ASGPR) and transferrin receptor (TR) all yielded biologically active type II derivatives of the v-sis oncoprotein. Although transforming all of the type II signal/anchor-sis proteins exhibited a very short half-life. The short half-life exhibited by the signal/anchor-sis constructs suggests that, in some cases, cellular transformation may result from the synthesis of growth factors so labile that they activate undetectable autocrine loops. The E5 oncoprotein encoded by BPV exhibits amino acid sequence similarity with PDGF, activates the PDGF beta-receptor, and thus resembles a miniature membrane-anchored growth factor with a putative type II orientation. The hydrophobic domain of the E5 oncoprotein, when substituted in place of the signal sequence of v-sis, was indistinguishable compared with the signal-anchor domains of NA, TR, and ASGPR, demonstrating its ability to function as a signal-anchor domain. NIH 3T3 cells transformed by the signal/anchor-sis constructs exhibited morphological reversion upon treatment with suramin, indicating a requirement for ligand/receptor interactions in a suramin- sensitive compartment, most likely the cell surface. In contrast, NIH 3T3 cells transformed by the E5 oncoprotein did not exhibit morphological reversion in response to suramin.



Regulation of Intestinal Epithelial Cell Growth by Transforming Growth Factor Type beta  

Microsoft Academic Search

A nontransformed rat jejunal crypt cell line (IEC-6) expresses transforming growth factor type beta 1 (TGF-beta 1) mRNA, secrets latent 125I-labeled TGF-beta 1 competing activity into culture medium, and binds 125I-labeled TGF-beta 1 to specific, high-affinity (Kd = 3.7 pM) cell surface receptors. IEC-6 cell growth is markedly inhibited by TGF-beta 1 and TGF-beta 2 with half-maximal inhibition occurring between

John A. Barnard; R. Daniel Beauchamp; Robert J. Coffey; Harold L. Moses



Coxsackievirus infection as an environmental factor in the etiology of type 1 diabetes.  


Susceptibility to type 1 diabetes (T1D) is dictated by a complex interplay between genetic determinants and environmental influences. Accumulating evidence strongly supports viral infection as an important factor in the etiology of T1D. To this effect, several viruses have been associated with the capacity to induce or exacerbate T1D in both humans and mice. The most convincing evidence linking viral infection and autoimmunity comes from studies on enteroviruses, particularly coxsackievirus. In this review we will discuss the evidence associating coxsackievirus infection to T1D and present the current state of knowledge on the potential mechanism of coxsackievirus-mediated T1D. PMID:19393207

Richer, Martin J; Horwitz, Marc S



Epidermal growth factor receptor status of histological sub-types of breast cancer.  

PubMed Central

The histological breakdown of a consecutive series of 264 surgically resected malignant lesions of the breast was studied. Oestrogen and epidermal growth factor receptor status was quantified and presented along with size and lymph node status of the non-ductal lesions. Those non-ductal tumours containing EGF receptors have all recurred within two years of resection. Twenty-one percent of the lobular carcinomas contained EGF receptors compared to 34% of ductal carcinomas. EGF receptor status appeared to be associated with an increased risk of early recurrence and death whatever the histological sub-type of the breast cancer.

Sainsbury, J. R.; Nicholson, S.; Angus, B.; Farndon, J. R.; Malcolm, A. J.; Harris, A. L.



Linewidth enhancement factor of a type-I quantum-cascade laser  

NASA Astrophysics Data System (ADS)

Experimental results using the amplified spontaneous emission spectroscopy of a type-I quantum-cascade laser are presented. Using the Hakki-Paoli method, the optical gain spectra of the laser are extracted for the wavelength of 8.2 ?m at various subthreshold current levels. The change in refractive index with increased bias current is obtained from the peak wavelength shifts of the Fabry-Pérot spectrum. A low value of -0.5 for the linewidth enhancement factor is found. A group index of around 3.47 has also been determined from Fabry-Pérot modal spacings.

Lerttamrab, M.; Chuang, S. L.; Gmachl, C.; Sivco, D. L.; Capasso, F.; Cho, A. Y.



Linewidth enhancement factor of a type-II interband-cascade laser  

NASA Astrophysics Data System (ADS)

Experimental results using the amplified spontaneous emission spectroscopy of a type-II interband-cascade laser are presented. Using the Hakki-Paoli method, the optical gain spectra of the laser are extracted for the wavelength of 3.13 ?m at various subthreshold current levels. A group index of around 3.33 is determined from Fabry-Pérot modal spacing. The change in refractive index with increased bias current is obtained from the peak wavelength shifts of the Fabry-Pérot spectrum. A low value of 0.71 for the linewidth enhancement factor at the lasing wavelength near threshold is found.

Lerttamrab, M.; Chuang, S. L.; Yang, R. Q.; Hill, C. J.



[Functional analysis of transforming growth factor-beta type I receptor].  


Proteins in the transforming growth factor-beta (TGF-beta) superfamily exert their effects by forming heteromeric complexes of their type I and type II serine/threonine kinase receptors. Binding of TGF-beta to its constitutively active type II receptor (T beta R-II) recruits the type I receptor (T beta R-I) into the complex; T beta R-I is thereafter phosphorylated in GS domain located just N-terminal to the kinase domain and activated, which is necessary for TGF-beta signaling. Here we investigated the role of cytoplasmic juxtamembrane region located between the transmembrane domain and the GS domain of T beta R-I by mutational analyses using mutant lung epithelial cells which lack endogenous T beta R-I. Upon transfection, wild-type T beta R-I restored the TGF-beta signals for growth inhibition and production of plasminogen activator inhibitor 1 (PAI)-1 and fibronectin. A deletion-mutant, T beta R-I/JD 1 (delta 150-181), which lacks the juxtamembrane region preceding the GS domain bound TGF-beta in concert with T beta R-II and transduced a signal leading to production of PAI-1 but not growth inhibition. Recombinant receptors with mutations that change serine172 to alanine (S172A) or threonine176 to valine (T176V) were similar to wild-type T beta R-I in their abilities to bind TGF-beta, formed complexes with T beta R-II, and transduced a signal for PAI-1 and fibronectin. Similar to T beta R-I/JD1 (delta 150-181), however, these missense mutant receptors were impaired to mediate a growth inhibitory signal. These observations indicate that serine172 and threonine176 of T beta R-I are dispensable for extracellular matrix protein production but essential to the growth inhibition by TGF-beta. PMID:8725356

Saitoh, M



Factors affecting pharyngeal Haemophilus influenzae type b colonization rates in children.  


Over 1,300 children were studied in an analysis of factors that might affect pharyngeal colonization with Haemophilus influenzae type b. Our semiquantitative methods for the culture of H. influenzae type b, consisting of inoculation of 0.001 ml of throat swab fluid on antiserum agar plates and division of the results into three grades of intensity, showed agreement as to intensity of colonization in over 80% of repeat throat cultures. Our data also suggest that throat swabs are more efficient than nasopharyngeal swabs for detecting colonization, particularly for older children. All 17 H. influenzae type b carriers found with either method were detected with throat swabs, but six had negative nasopharyngeal cultures; four of these six were lightly colonized older children. Furthermore, colony counts were apt to be higher on plates inoculated with throat swab fluids. The frequency of pharyngeal H. influenzae type b colonization in children visiting health department clinics and pediatricians' offices was low during the first 6 months of life (0.7%) but averaged 3 to 5% throughout the rest of childhood. Approximately two-thirds of the carriers were colonized at an intensity too low to be detected by standard laboratory techniques. No influence on colonization rates was found for sex, race, season, economic status, or common childhood infectious diseases such as coryza or otitis media. PMID:1086855

Michaels, R H; Poziviak, C S; Stonebraker, F E; Norden, C W



Maternal Enterovirus Infection as a Risk Factor for Type 1 Diabetes in the Exposed Offspring  

PubMed Central

OBJECTIVE Maternal enterovirus infections during pregnancy have been linked to an increased risk of type 1 diabetes in the offspring. The aim of this study was to evaluate this association in a unique series of pregnant mothers whose child progressed to clinical type 1 diabetes. RESEARCH DESIGN AND METHODS Maternal and in utero enterovirus infections were studied in 171 offspring who presented with type 1 diabetes before the age of 11 years and in 316 control subjects matched for date and place of birth, sex, and HLA-DQ risk alleles for diabetes. Acute enterovirus infections were diagnosed by increases in enterovirus IgG and IgM in samples taken from the mother at the end of the first trimester of pregnancy and cord blood samples taken at delivery. RESULTS Signs of maternal enterovirus infection were observed in altogether 19.3% of the mothers of affected children and in 12.0% of the mothers of control children (P = 0.038). This difference was seen in different HLA risk groups and in both sexes of the offspring, and it was unrelated to the age of the child at the diagnosis of diabetes or the age of the mother at delivery. CONCLUSIONS These results suggest that an enterovirus infection during pregnancy is not a major risk factor for type 1 diabetes in childhood but may play a role in some susceptible subjects.

Viskari, Hanna; Knip, Mikael; Tauriainen, Sisko; Huhtala, Heini; Veijola, Riitta; Ilonen, Jorma; Simell, Olli; Surcel, Helja-Marja; Hyoty, Heikki



Nordihydroguaiaretic acid inhibits transforming growth factor ? type 1 receptor activity and downstream signaling  

PubMed Central

It has been well documented that nordihydroguaiaretic acid (NDGA), a phenolic lignan isolated from the creosote bush, Larrea tridentate, has anti-cancer activity in vitro and in vivo. Several mechanisms have been identified that could contribute to these actions, as NDGA directly inhibits metabolic enzymes and receptor tyrosine kinases that are established anti-cancer targets. In the present study, we show that NDGA inhibits the transforming growth factor ? (TGF-?) type I receptor, a serine threonine kinase receptor. In cultured cells, NDGA treatment repressed Smad2 phosphorylation induced by TGF-? treatment and by a constitutively active mutant of TGF-? type I receptor (T202D). NDGA also inhibited downstream transcriptional activation mediated by both TGF-? treatment and the constitutively active mutant receptor. In vitro, NDGA inhibited TGF-? type I receptor mediated Smad2 phosphorylation in crude cell lysates and in a purified preparation. Importantly, screening select analogs demonstrated that modification of NDGA’s structure resulted in altered potency against the receptor. These results indicated that the structure of NDGA can be modified to achieve increased potency. Together our data provide a novel mechanism for NDGA activity which could help explain its anti-cancer activity, and suggest that NDGA could serve as a structural motif for developing serine/threonine kinase inhibitors with selectivity for TGF-? type I receptor.

Li, Fusheng; Anderson, Marc O.; Youngren, Jack F.



Risk factors for aseptic loosening of M?ller-type straight stems  

PubMed Central

Background and purpose Even small differences in design variables for the femoral stem may influence the outcome of a hip arthroplasty. We performed a risk factor analysis for aseptic loosening of 4 different versions of cemented Müller-type straight stems with special emphasis on design modifications (2 shapes, MSS or SL, and 2 materials, CoNiCrMo (Co) or Ti-6Al-7Nb (Ti)). Methods We investigated 828 total hip replacements, which were followed prospectively in our in-house register. All stems were operated in the same setup, using Sulfix-6 bone cement and a second-generation cementing technique. Demographic and design-specific risk factors were analyzed using an adjusted Cox regression model. Results The 4 versions showed marked differences in 15-year stem survival with aseptic loosening as the endpoint: 94% (95% CI: 89–99) for MSS Co, 83% (CI: 75–91) for SL Co, 81% (CI: 76–87) for MSS Ti and 63% (CI: 56–71) for SL Ti. Cox regression analysis showed a relative risk (RR) for aseptic loosening of 3 (CI: 2–5) for stems made of Ti and of 2 (CI: 1–2) for the SL design. The RR for aseptic stem loosening increased to 8 (CI: 4–15) when comparing the most and the least successful designs (MSS Co and SL Ti). Interpretation Cemented Müller-type straight stems should be MSS-shaped and made of a material with high flexural strength (e.g. cobalt-chrome). The surface finish should be polished (Ra < 0.4 µm). These technical aspects combined with modern cementing techniques would improve the survival of Müller-type straight stems. This may be true for all types of cemented stems.

Gersbach, Silke; Butscher, Andre; Ilchmann, Thomas



Socio-economic factors and diabetes consequences among patients with type 2 diabetes  

PubMed Central

Background: Considering the effect of socio-economic factors on the emergence of chronic diseases and the importance of this aspect of diseases for policy makers and authorities of health care organizations, this study tried to investigate the role of these factors in type 2 diabetes and its consequences, which can be used in health policy making for preventing from this disease. Materials and Methods: This descriptive-analytical study was conducted on 384 diabetic patients who were admitted to a diabetes center in the city of Isfahan. The participants were selected using simple random sampling. A questionnaire with 42 questions was used for gathering the data which were analyzed using chi-square and Fisher's statistical tests. Results: The studied population consisted of 52.1% male and 47.9% female participants. There was a statistically significant relationship between diabetes complications, age group, educational level, job status, relationship with family members, number of family visits and the reassurance provided by the family, type of leisure time activities, health status, years with diabetes, smoking, type of treatment, fried food consumption and income (P < 0.001), sense of security and communication in living environment (P < 0.002) and daily intake of vegetables (P < 0.02). Conclusion: It seems that the application of supportive resources and secondary strategies is an essential issue in the patients with chronic diseases, particularly diabetes. Empowering strategies can induce basic changes in order to increase positive expectations, hope, self-esteem and self- confidence in patients; this is the exact strategy which must be used to efficiently control diabetes and its different types of complications among patients.

Tol, Azar; Sharifirad, Gholamreza; Shojaezadeh, Davoud; Tavasoli, Elahe; Azadbakht, Leila



Characterization of a Bacillus subtilis sporulation operon that includes genes for an RNA polymerase sigma factor and for a putative DD-carboxypeptidase.  

PubMed Central

At early stages of sporulation, the spoIIA locus is transcribed as a tricistronic (1.7-kb) operon, coding for sigma F and for two proteins that modulate the activity of sigma F. The locus is transcribed as a longer (2.9-kb) transcript at the late stages of sporulation. We show here that the longer transcript contains an additional open reading frame whose product has extensive sequence homology with DD-carboxypeptidases; the corresponding gene is designated dacF. Cotranscription of a morphogene, such as dacF, with the gene for a sigma factor suggests a way to couple transcription regulation with morphogenesis. The predicted N-terminal sequence of the DacF protein and the inhibition of sporulation by a translational dacF-lacZ fusion both suggest that the protein has a signal peptide for transport into or across a membrane. Expression of a dacF-lacZ transcriptional fusion was in the forespore. The 5' end of the 2.9-kb transcript was determined by primer extension analysis. The region 5' to the end showed no homology to promoters recognized by known sigma factors but was homologous to the corresponding region of the forespore-specific 0.3-kb gene of Bacillus subtilis. Images

Wu, J J; Schuch, R; Piggot, P J



Heterogeneity of Receptor Function in Colon Carcinoma Cells Determined by Cross-talk between Type I Insulin-like Growth Factor Receptor and Epidermal Growth Factor Receptor  

Microsoft Academic Search

This study identifies a novel cross-talk paradigm between the type I insulin-like growth factor receptor (IGF1R) and epidermal growth factor receptor (EGFR) in colon cancer cells. IGF1R activation by ligand exposure in growth factor- deprived cells induces Akt activation in the FET, CBS, and GEO colon cancer cell lines. Investigation of IGF1R-mediated signaling pathways using small interfering RNA approaches indicated

Yi Peter Hu; Sandip B. Patil; Michelle Panasiewicz; Wenhui Li; Jennie Hauser; Lisa E. Humphrey; Michael G. Brattain



Effects of growth factors on the differentiation of murine ESC into type II pneumocytes.  


We have previously shown that embryonic stem cells (ESC) can be directed to differentiate into alveolar type II cells by provision of a serum-free medium designed for in vitro maintenance of mature alveolar epithelial cells (small airway growth medium: SAGM), although the target cell yield was low. SAGM comprises a basal serum-free medium (SABM) plus a series of defined supplements. In order to try increase the proportion of pneumocytes in differentiated cultures, we aimed in this study to determine the effects on murine ESC of each of the individual growth factors in SAGM. In accordance with our previous reports, expression of surfactant protein C (SPC) and its mRNA was used to monitor differentiation of type II pneumocytes. Surprisingly, we found that addition of each factor separately to SABM decreased the expression of SPC mRNA when compared with the effect of SABM alone. Thus, it seems that the observed enhancement by SAGM of pneumocyte differentiation from murine ESC can, in fact, be attributed to the provision of a serum-free environment. PMID:17907951

Samadikuchaksaraei, Ali; Bishop, Anne E



Transcription factors binding to the mouse HTF9 housekeeping promoter differ between cell types.  

PubMed Central

The mouse CpG island HTF9 harbours a bidirectional promoter shared by two housekeeping genes that are arranged head-to-head. We have previously identified several protein binding-elements across the CpG island, yet a short region around the initiation region was found to be capable of bidirectional transcription in transient expression assays, suggesting that the multiple elements of the HTF9 promoter are functionally redundant. We have now compared the binding activities in nuclear extracts from different cell types. Two protein-binding elements of HTF9 interact with widely distributed factors. A potentially strong Sp1 binding site was also identified, however Sp1 appeared to bind efficiently to its target sequence with extracts prepared from proliferating cultured cells, but not from adult organs. On the other hand, the CCAAT box upstream of one gene (HTF9-A) interacted with a liver-enriched factor, whereas no binding was detected with cultured fibroblasts extracts. Consistently, deletion of the CCAAT box affected transient expression from the HTF9-A promoter in hepatocyte, but not in fibroblast, cultures. Our results suggest that ubiquitous expression of housekeeping promoters results from the activation of alternative elements in different cell types. Images

Somma, M P; Gambino, I; Lavia, P



[Analysis on the characteristics and interference factors of different types of measurement instruments for meridian-acupoint resistance].  


The meridian-acupoint has response function and effect function. As a direct reflection between acupoint and diseased area, the response function is the foundation of the effect function, and skin resistance of acupoint is usually used as an objective indice for research of meridian-acupoint response. Among the skin resistance-based researches on specificity of meridian-acupoint reaction, the selection of instrument is a key point. At present the main measurement instruments for meridian-acupoint resistance include dual-electrode device and four-electrode device. After analyzing the characteristics and inter-ference factors of different types of measurement instruments for meridian-acupoint resistance, dual-electrode device is suitable for qualitative analysis, for its control of interference factors needs to improve. The four-electrode device is good at quantitative research, for it is easier to control interference factors. Yet, there is more for research department to do to improve the instrument design by modern scientific technique in order to meet need for research. PMID:22997803

She, Yan-Fen; Zhu, Jiang



Response to Therapy and Outcomes in Oropharyngeal Cancer Are Associated With Biomarkers Including Human Papillomavirus, Epidermal Growth Factor Receptor, Gender, and Smoking  

SciTech Connect

Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specific survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile.

Kumar, Bhavna [Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI (United States); Cordell, Kitrina G. [Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI (United States); Department of Pathology, University of Michigan, Ann Arbor, MI (United States); Lee, Julia S. [Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI (United States); Prince, Mark E.; Tran, Huong H.; Wolf, Gregory T. [Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI (United States); Urba, Susan G. [Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI (United States); Department of Internal Medicine, University of Michigan, Ann Arbor, MI (United States); Worden, Francis P. [Department of Internal Medicine, University of Michigan, Ann Arbor, MI (United States); Chepeha, Douglas B.; Teknos, Theodoros N. [Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI (United States); Eisbruch, Avraham; Tsien, Christina I. [Department of Radiation Oncology, Division of Hematology-Oncology, University of Michigan, Ann Arbor, MI (United States); Taylor, Jeremy [Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI (United States); Department of Biostatistics, University of Michigan, Ann Arbor, MI (United States); D'Silva, Nisha J. [Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI (United States); Department of Pathology, University of Michigan, Ann Arbor, MI (United States); Yang, Kun; Kurnit, David M. [Department of Pediatrics, University of Michigan, Ann Arbor, MI (United States); Bradford, Carol R. [Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI (United States)] (and others)



Factors Associated with Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes Mellitus  

PubMed Central

Objective. To investigate the risk factors of DR in Chinese T2DM patients. Methods. 2009 patients with T2DM were included in this cross-sectional study. All patients underwent eye examination, and the DR stage was defined by an ophthalmologist. Correlation analysis was performed to evaluate the relation between DR and clinical variables. Logistic regression models were used to assess risk for those factors associated with DR. Results. A total of 597 T2DM patients (29.7%) had DR, of which 548 (27.3%) were nonproliferative diabetic retinopathy and 49 (2.4%) were proliferative diabetic retinopathy. Positive correlations were found between DR and duration of diabetes, systolic blood pressure (SBP), diastolic blood pressure, glycated hemoglobin, glycated albumin, 24 hurinary albumin excretion, peripheral atherosclerosis (PA), diabetes nephropathy (DN), diabetic peripheral neuropathy, and anemia. Negative correlations were found between DR and C-peptide and glomerular filtration rate. Logistic regression analysis revealed that duration of diabetes, SBP, DN, anemia, PA, and C-peptide were each independent risk factors of DR. Conclusion. The duration of diabetes, SBP, DN, anemia, and PA are positively associated with DR in Chinese T2DM patients, while C-peptide is negatively associated with DR. Monitoring and evaluation of these related factors will likely contribute to the prevention and treatment of DR.

He, Bin-Bin; Wei, Li; Gu, Yun-Juan; Han, Jun-Feng; Li, Ming; Liu, Yu-Xiang; Bao, Yu-Qian; Jia, Wei-Ping



A kinase subdomain of transforming growth factor-? (TGF-?) type I receptor determines the TGF-? intracellular signaling specificity  

Microsoft Academic Search

Transforming growth factor-? (TGF-?) signals through a heteromeric complex of related type I and type II serine\\/threonine kinase receptors. In Mv1Lu cells the type I receptor T?RI mediates TGF-?-induced gene expression and growth inhibition, while the closely related type I receptors Tsk7L and TSR1 are inactive in these responses. Using chimeras between T?RI and Tsk7L or TSR1, we have defined

Xin-Hua Feng; Rik Derynck



Diffuse-Type Gastric Carcinoma: Progression, Angiogenesis, and Transforming Growth Factor ? Signaling  

PubMed Central

Background Diffuse-type gastric carcinoma is a cancer with poor prognosis that has high levels of transforming growth factor ? (TGF-?) expression and thick stromal fibrosis. However, the association of TGF-? signaling with diffuse-type gastric carcinoma has not been investigated in detail. Methods We used a lentiviral infection system to express a dominant-negative TGF-? type II receptor (dnT?RII) or green fluorescent protein (GFP) as a control in the diffuse-type gastric carcinoma cell lines, OCUM-2MLN and OCUM-12. These infected cells and the corresponding parental control cells were subcutaneously or orthotopically injected into nude mice. Angiogenesis was inhibited by infecting cells with a lentivirus carrying the gene for angiogenic inhibitor thrombospondin-1 or by injecting mice intraperitoneally with the small-molecule angiogenic inhibitor sorafenib or with anti-vascular endothelial growth factor (VEGF) neutralizing antibody (six or eight mice per group). Expression of phospho-Smad2 and thrombospondin-1 was investigated immunologically in human gastric carcinoma tissues from 102 patients. All statistical tests were two-sided. Results Expression of dnT?RII into OCUM-2MLN cells did not affect their proliferation in vitro, but it accelerated the growth of subcutaneously or orthotopically transplanted tumors in vivo (eg, for mean volume of subcutaneous tumors on day 10 relative to that on day 0: dnT?RII tumors = 3.49 and GFP tumors = 2.46, difference = 1.02, 95% confidence interval [CI] = 0.21 to 1.84; P = .003). The tumors expressing dnT?RII had higher levels of angiogenesis than those expressing GFP because of decreased thrombospondin-1 production. Similar results were obtained with OCUM-12 cells. Expression of thrombospondin-1 in the dnT?RII tumor or treatment with sorafenib or anti-VEGF antibody reduced tumor growth, whereas knockdown of thrombospondin-1 expression resulted in more accelerated growth of OCUM-2MLN tumors than of GFP tumors (eg, mean tumor volumes on day 14 relative to those on day 0: thrombospondin-1–knockdown tumors = 4.91 and GFP tumors = 3.79, difference = 1.12, 95% CI = 0.80 to 1.44; P < .001). Positive association between phosphorylated Smad2 and thrombospondin-1 immunostaining was observed in human gastric carcinoma tissues. Conclusions Disruption of TGF-? signaling in diffuse-type gastric carcinoma models appeared to accelerate tumor growth, apparently through increased tumor angiogenesis that was induced by decreased expression of thrombospondin-1.

Komuro, Akiyoshi; Yashiro, Masakazu; Iwata, Caname; Morishita, Yasuyuki; Johansson, Erik; Matsumoto, Yoshiko; Watanabe, Akira; Aburatani, Hiroyuki; Miyoshi, Hiroyuki; Kiyono, Kunihiko; Shirai, Yo-taro; Suzuki, Hiroshi I.; Hirakawa, Kosei; Kano, Mitsunobu R.



Effect of blood collection tube types on the measurement of human epidermal growth factor.  


We observed significant differences in measured human epidermal growth factor (hEGF) levels for the same individual's serum/plasma samples between different tube types (glass, polystyrene, plastic with clot activator, plastic without clot activator, plastic with EDTA, polypropylene tubes). For all individuals, hEGF levels in plasma were found to be below the detection limit. The discrepancy of the hEGF levels in serum and plasma was attributed to the platelet derived EGF by analyzing platelet lyzate with size exclusion chromotography and demonstrating the immunoreactivity of the fractions corresponding to the pre-proEGF and/or proEGF elution time. Besides, samples of females showed much higher EGF levels than those of males in certain test tube types. As a conclusion, all blood samples should be taken and stored in the same type of test tubes in order to make precise measurements for hEGF. And, the measured hEGF level in blood is susceptible to changes with blood clotting. PMID:17236396

Yucel, Aysegul; Karakus, Resul; Cemalettin, Aybay



Type II Transforming Growth Factor-? Receptor Recycling Is Dependent upon the Clathrin Adaptor Protein Dab2  

PubMed Central

Transforming growth factor (TGF)-? family proteins form heteromeric complexes with transmembrane serine/threonine kinases referred to as type I and type II receptors. Ligand binding initiates a signaling cascade that generates a variety of cell type-specific phenotypes. Whereas numerous studies have investigated the regulatory activities controlling TGF-? signaling, there is relatively little information addressing the endocytic and trafficking itinerary of TGF-? receptor subunits. In the current study we have investigated the role of the clathrin-associated sorting protein Disabled-2 (Dab2) in TGF-? receptor endocytosis. Although small interfering RNA-mediated Dab2 knockdown had no affect on the internalization of various clathrin-dependent (i.e., TGF-?, low-density lipoprotein, or transferrin) or -independent (i.e., LacCer) cargo, TGF-? receptor recycling was abrogated. Loss of Dab2 resulted in enlarged early endosomal antigen 1-positive endosomes, reflecting the inability of cargo to traffic from the early endosome to the endosomal recycling compartment and, as documented previously, diminished Smad2 phosphorylation. The results support a model whereby Dab2 acts as a multifunctional adaptor in mesenchymal cells required for TGF-? receptor recycling as well as Smad2 phosphorylation.

Penheiter, Sumedha G.; Deep Singh, Raman; Repellin, Claire E.; Wilkes, Mark C.; Edens, Maryanne; Howe, Philip H.; Pagano, Richard E.



Trefoil factor 2 negatively regulates Type 1 immunity against Toxoplasma gondii  

PubMed Central

Interleukin 12 (IL-12)-mediated Type 1 inflammation confers host-protection against the parasitic protozoan Toxoplasma gondii. However, production of interferon gamma (IFN-?), another Type 1 inflammatory cytokine, also drives lethality from excessive injury to the intestinal epithelium. As mechanisms that restore epithelial barrier function following infection remain poorly understood, this study investigated the role of Trefoil factor 2 (TFF2), a well-established regulator of mucosal tissue repair. Paradoxically, TFF2 antagonized IL-12 release from DC’s and macrophages, which protected TFF2 deficient mice (TFF2?/?) from T. gondii pathogenesis. Dysregulated intestinal homeostasis in naďve TFF2?/? mice correlated with increased IL-12/23p40 levels and enhanced T cell recruitment at baseline. Infected TFF2?/? mice displayed low rates of parasite replication and reduced gut immunopathology, whereas WT mice experienced disseminated infection and lethal ileitis. p38 MAPK activation and IL-12p70 production was more robust from TFF2?/? CD8+ DC compared to WT CD8+ DC and treatment of WT DC with rTFF2 suppressed TLR-induced IL-12/23p40 production. Neutralization of IFN-? and IL-12 in TFF2?/? animals abrogated resistance shown by enhanced parasite replication and infection-induced morbidity. Hence, TFF2 regulated intestinal barrier function and Type 1 cytokine release from myeloid phagocytes, which dictated the outcome of oral T. gondii infection in mice.

McBerry, Cortez; Egan, Charlotte E.; Rani, Reena; Yang, Yanfen; Wu, David; Boespflug, Nicholas; Boon, Louis; Butcher, Barbara; Mirpuri, Julie; Hogan, Simon P.; Denkers, Eric Y.; Aliberti, Julio; Herbert, De'Broski R.



Transforming growth factor-beta 1 stimulates glomerular mesangial cell synthesis of the 72-kd type IV collagenase.  

PubMed Central

Transforming growth factor-beta 1 (TGF-beta 1) is generally considered to exert positive effects on the accumulation of extracellular matrices. These occur as the net result of enhanced matrix protein synthesis, diminished matrix metalloproteinase (MMP) synthesis, and augmented production of specific inhibitors, including the tissue inhibitor of metalloproteinases (TIMP-1). Given that glomerular TGF-beta 1 synthesis is induced by inflammation, the effects of this cytokine on synthesis of the 72-kd type IV collagenase and TIMP-1 by cultured human mesangial cells were evaluated. Concentrations of TGF-beta 1 of 5 ng/ml and above specifically stimulated the synthesis of the 72-kd type IV collagenase. This effect was independent of the stimulatory effect of TGF-beta 1 on TIMP-1 synthesis, which was maximal in a lower concentration range (0.1 to 1 ng/ml). Most significantly, the net effect at the higher concentrations of TGF-beta 1 was an excess of enzyme over the TIMP-1 inhibitor. Northern blot analysis of TGF-beta 1-stimulated human mesangial cells demonstrated a specific increase in the abundance of the 3.1 kb mRNA transcript encoding the 72-kd type IV collagenase, presumably mediated by a direct stimulation of 72-kd type IV collagenase mRNA transcription observed as early as 3 hours after exposure to TGF-beta 1. These studies were extended to an analysis of the expression of TGF-beta 1 and 72-kd type IV collagenase mRNAs in normal and nephritic rats. In normal animals, basal TGF-beta 1 and 72-kd type IV collagenase mRNA expression was observed in a strictly mesangial distribution. After induction of acute immune complex-mediated glomerulonephritis, there was a major increase in TGF-beta 1 and 72-kd type IV collagenase mRNA expression, which was strictly limited to the expanded, hypercellular mesangial compartment. Enhanced synthesis of the mesangial type IV collagenase in response to TGF-beta 1 released during glomerular inflammatory processes could have an important role in the extensive glomerular matrix remodeling that accompanies these disorders. Images Figure 3 Figure 4 Figure 6 Figure 7 Figure 9 Figure 10

Marti, H. P.; Lee, L.; Kashgarian, M.; Lovett, D. H.



[A type behavior as a risk factor in siblings with diabetes mellitus].  


The objective of the study was to investigate the prevalence of the "a" type behavior among close relatives (including siblings) of the subjects with diabetes mellitus. For this purpose there were examined 50 practically healthy siblings aged between 20 and 40, among them 27 (54%) females and 23 (46%) males. The method of the structural interview was applied. In addition to this, they were subjected to the tests of glucose tolerance. The considerable number of the siblings (46%) showed the "a" type behavior of various kinds, and 44% -- the disruption of glucose tolerance, which produces the preliminary conditions for the diabetes manifestations and gives us the grounds for applying further preventive activities. PMID:16308438

Gogiberidze, K O; Kavtaradze, G V; Gogiberidze, O G



Zirconium-titanium placers of the Voronezh Anteclise: Types, epochs and factors of formation, and forecast  

NASA Astrophysics Data System (ADS)

The early and late Frasnian, Barremian-Aptian, Cenomanian, early Santonian, early Campanian, and Oligocene-Miocene epochs of the formation of various types of zirconium-titanium placers are distinguished in the Voronezh Anteclise. The factors of their formation are considered, and a forecast of prospecting has been made. Lower Frasnian sedimentary rocks occur in the southeast, where the placers are related to the ilmenite-bearing volcanosedimentary rocks of the Yastrebovo Sequence. The upper Frasnian productive quartz sand of the Petino Sequence occurs in the central part of the Voronezh Anteclise. The Barremian-Aptian productive quartz sand and kaolinite clay occur in the northern and northeastern parts of the anteclise (Ryazan and Lipetsk oblasts). The placers formed in the Cenomanian are known in the Tambov oblast in the northeast of the Voronezh Anteclise and are related to phosphate-bearing glauconite-quartz sand. The early Campanian phosphorite-glauconite-quartz formation is widespread in the northwest of the Voronezh Anteclise at the junction with the northeastern wall of the Dnieper-Donets Basin (Bryansk oblast). The Oligocene-Miocene epoch was characterized by quartz sands abundant in the northwestern and south-western areas. The formation of zirconium-titanium placers is controlled by structural-tectonic, facies, volcanic, paleogeographic, stratigraphic, and evolutional factors. The indispensable condition for heavy mineral concentration is existence of positive forms of underwater topography. These are mostly structural elements of the third and fourth orders on the slopes of the Voronezh Anteclise at the boundaries of the adjacent negative structures. As concerns the facies factor, the occurrence of coastal and shallow-water marine facies with alternating and medium hydrodynamic activity and predominance of sand fractions 0.25-0.05 mm are criteria of elevated concentration of heavy minerals in sand. One of the conditions providing concentration of heavy minerals is a multiple rewashing of sands close to a relatively stable shoreline. The volcanic factor is determinant for the lower Frasnian marine placers fed by volcanic sources. The Cretaceous and Paleogene zirconium-titanium placers were formed owing to scouring of the older Paleozoic and Mesozoic sedimentary rocks of the Voronezh Anteclise, as well as the Baltic Shield, Moscow Syneclise, and the Volga-Ural Anteclise. The age of placers was estimated with accuracy up to substages (lower Aptian, lower Santonian, lower Campanian). The evolution factor is expressed in variation of localization and composition of placers in time and space. The forecast of potentially ore-bearing areas is based on optimal combinations of favorable factors.

Savko, A. D.; Zvonarev, A. E.; Ivanov, D. A.



Immunohistochemical study of epidermal growth factor receptor (EGFR) in various types of renal injury.  


Epidermal growth factor (EGF), a polypeptide with a potent mitogen activity, and its receptor [EGFR] have been previously identified in the kidney, but their expression in normal and diseased kidneys has not been fully elucidated. In order to evaluate EGFR in various histological types of renal injury, EGFR expression was studied by the immunohistochemical avidin-biotin complex (ABC) method with a monoclonal antibody EGFR1 on paraffin sections from 10 normal kidneys, 56 renal biopsies with various types of glomerulonephritis (GN), and 20 renal grafts with rejection. EGFR expression was observed in (a) 3 of 10 (30%) normal kidneys, (b) 17 of 39 (43.6%) renal biopsies with various types of GN mainly in membranous GN (57%) and in focal segmental glomerulosclerosis (FSG) (62.5%), (c) 6 of 17 (35.3%) biopsies with various types of systemic lupus erythematosus GN, and (d) 12 of 20 (60%) renal grafts with acute (42.9%) and chronic (69.2%) rejection. EGFR was mainly localized to the epithelial cells of the distal and collecting tubules and extraglomelar vessels, while it was observed less frequently in parietal epithelial cells and along glomerular basement membranes. Notably EGFR was detected in the epithelial cells adjacent to adhesions with Bowman's capsule and in the connective tissue of fibrocellular crescents. In conclusion, EGFR expression was observed more frequently in diseased than in normal kidneys. The increased incidence of EGFR expression in FSG, in chronic rejection, in small adhesions with Bowman's capsule and fibrocellular crescents suggest that EGF/EGFR may be correlated with a disturbed extracellular matrix production resulting in formation of early sclerotic lesions. PMID:7970118

Nakopoulou, L; Stefanaki, K; Boletis, J; Papadakis, J; Kostakis, A; Vosnides, G; Zeis, P M



Transcriptional regulators of the Schizosaccharomyces pombe fbp1 gene include two redundant Tup1p-like corepressors and the CCAAT binding factor activation complex.  

PubMed Central

The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK). To identify transcriptional regulators acting downstream from or in parallel to PKA, we screened an adh-driven cDNA plasmid library for genes that increase fbp1 transcription in a strain with elevated PKA activity. Two such clones express amino-terminally truncated forms of the S. pombe tup12 protein that resembles the Saccharomyces cerevisiae Tup1p global corepressor. These clones appear to act as dominant negative alleles. Deletion of both tup12 and the closely related tup11 gene causes a 100-fold increase in fbp1-lacZ expression, indicating that tup11 and tup12 are redundant negative regulators of fbp1 transcription. In strains lacking tup11 and tup12, the atf1-pcr1 transcriptional activator continues to play a central role in fbp1-lacZ expression; however, spc1 MAPK phosphorylation of atf1 is no longer essential for its activation. We discuss possible models for the role of tup11- and tup12-mediated repression with respect to signaling from the MAPK and PKA pathways. A third clone identified in our screen expresses the php5 protein subunit of the CCAAT-binding factor (CBF). Deletion of php5 reduces fbp1 expression under both repressed and derepressed conditions. The CBF appears to act in parallel to atf1-pcr1, although it is unclear whether or not CBF activity is regulated by PKA.

Janoo, R T; Neely, L A; Braun, B R; Whitehall, S K; Hoffman, C S



Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD  

PubMed Central

Background We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone) before autologous stem cell transplantation (ASCT). Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone) or VTD (bortezomib/thalidomide/dexamethasone) induction, and analysed prognostic factors for outcome. Patients and methods Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N?=?25), PAD (N?=?31), VTD (N?=?35)]. and received thalidomide maintenance for 2?years post-ASCT. Results 43 (47.3%) patients had International Staging System (ISS) III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS) and event-free (EFS) survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS. Conclusions These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals.



Load Effects of Nola-Type Induction Motor Power-Factor Controllers on Fuel-Cell Inverters.  

National Technical Information Service (NTIS)

This report covers tests performed on power inverters using Nola-type power factor controllers (PFC) and fractional horsepower single-phase induction motors as loading devices. The inverters were designed for integral operation with fuel cell power plants...



Similar cardiovascular risk factor profile in screen-detected and known type 2 diabetic subjects  

PubMed Central

Objective To compare the cardiovascular disease (CVD) risk factor profile in subjects with screen-detected type 2 diabetes (SDM) and subjects with known type 2 diabetes (KDM). Design Population-based, cross-sectional survey. Setting and subjects In a single, semi-rural general practice 2082 subjects were between 20 and 69 years. Of those, 1970 subjects were invited, and a total of 1374 (69.7%) subjects were examined by blood tests, anthropometric measures, and self-administered questionnaires. Results Before the survey 19 persons were known to have type 2 diabetes. The screening revealed another 31 individuals with type 2 diabetes, diagnosed according to the 1999 World Health Organization criteria. Age, levels of blood pressure, BMI, and dyslipidaemia, and markers of haemostasis and inflammation were comparable in the two groups. Median age in the KDM group was 58 vs. 57 years in the SDM group, p = 0.82, 79% were male vs. 61%, p = 0.23. In both groups 74% had blood pressure ? 130/85 mmHg, p = 1.00. In both groups 90% had BMI ? 25, p = 1.00, and about half in both groups had BMI ? 30, p = 0.56. In the KDM group 63% had dyslipidaemia (low HDL cholesterol or elevated triglycerides) vs. 80% in the SDM group, p = 0.32. Median levels of plasminogen-activator-inhibitor (PAI-1), tissue plasminogen activator (t-PA), as well as fibrinogen and C-reactive protein (CRP) were without statistically significant differences in the two groups, p > 0.1. In contrast, in markers of glycaemic regulation statistically significant differences were found between groups. Median HbA1 was 8.0 vs. 6.5, p < 0.001. Median fasting whole blood glucose level was 8.8 mmol/L vs. 6.3 mmol/L, p < 0.001, and glucose at two hours during OGTT was 16.9 mmol/L vs. 11.2 mmol/L, p < 0.001. Median fasting serum insulin level was 52 pmol/L vs. 80 pmol/L, p = 0.039 and at two hours 127 pmol/L vs. 479 pmol/L, p < 0.001. Conclusions The CVD risk-factor profile of SDM patients was similar to the expected adverse profile of patients with KDM. This indicates an already increased risk of cardiovascular disease in diabetic patients before the diabetes becomes clinically manifest, supporting the need for early diagnosis.

Heldgaard, Poul Erik; Henriksen, Jan Erik; Sidelmann, Johannes J.; Olivarius, Niels de Fine; Siersma, Volkert D.; Gram, J?rgen B.



Risk of skin and soft tissue infections (including shingles) in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register  

PubMed Central

Introduction Anti-tumour necrosis factor (TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). In 2001, BSRBR was established to evaluate the safety of these agents. This paper addresses the safety of anti-TNF therapy in RA with specific reference to serious skin and soft tissue infections (SSSI) and shingles. Methods A cohort of anti-TNF-treated patients was recruited alongside a comparator group with active RA treated with non-biological disease-modifying antirheumatic drugs (nbDMARD). 11 881 anti-TNF and 3673 nbDMARD patients were analysed. Follow-up was by 6-monthly questionnaires to patients and clinicians. Analyses considered SSSI and shingles separately. Incidence rates (IR) were calculated and then compared using survival analyses. Results The crude IR for SSSI were: anti-TNF 1.6/100 patient-years (95% CI 1.4 to 1.8); nbDMARD 0.7/100 patient-years (95% CI 0.5 to 1.0) and shingles: anti-TNF 1.6/100 patient-years (95% CI 1.3 to 2.0); nbDMARD 0.8/100 patient-years (95% CI 0.6 to 1.1). Adjusted HR were SSSI 1.4 (95% CI 0.9 to 2.4), shingles 1.8 (95% CI 1.2 to 2.8). For SSSI, no significant differences were seen between anti-TNF agents. For shingles, the lowest risk was observed for adalimumab (adjusted HR vs nbDMARD) 1.5 (95% CI 1.1 to 2.0) and highest for infliximab (HR 2.2; 95% CI 1.4 to 3.4)). Conclusion A significantly increased risk of shingles was observed in the anti-TNF-treated cohort. The risk of SSSI tended towards being greater with anti-TNF treatment but was not statistically significant. As with any observational dataset cause and effect cannot be established with certainty as residual confounding may remain. This finding would support the evaluation of zoster vaccination in this population.

Galloway, James B; Mercer, Louise K; Moseley, Alison; Dixon, William G; Ustianowski, Andrew P; Helbert, Matthew; Watson, Kath D; Lunt, Mark; Hyrich, Kimme L; Symmons, Deborah PM



Type beta Transforming Growth Factor Reversibly Inhibits the Early Proliferative Response to Partial Hepatectomy in the Rat  

Microsoft Academic Search

Type beta transforming growth factor (TGF-beta ), a factor produced by many cell types, is a potent inhibitor of hepatocyte DNA synthesis in vitro. To determine whether TGF-beta can influence hepatocyte proliferation in vivo, its effects were examined on the regenerative response of liver to partial hepatectomy (PH) in the rat. Porcine platelet-derived TGF-beta 1 (0.5 mu g), administered intravenously

William E. Russell; Robert J. Coffey; Andre J. Ouellette; Harold L. Moses



Adiponectin represents an independent cardiovascular risk factor predicting serum HDL-cholesterol levels in type 2 diabetes  

Microsoft Academic Search

Low levels of high-density lipoprotein (HDL)-cholesterol represent an independent cardiovascular risk factor and, besides reduced physical activity, mechanisms leading to decreased HDL-cholesterol levels are not known. We aimed to test the hypothesis, that adiponectin provides a missing link between type 2 diabetes and low levels of HDL-cholesterol, independent from common metabolic risk factors. 523 patients with type 2 diabetes were

B Zietz; H Herfarth; G Paul; A Ehling; U Müller-Ladner; J Schölmerich; A Schäffler



AtfA bZIP-type transcription factor regulates oxidative and osmotic stress responses in Aspergillus nidulans  

Microsoft Academic Search

The aim of the study was to demonstrate that the bZIP-type transcription factor AtfA regulates different types of stress responses\\u000a in Aspergillus nidulans similarly to Atf1, the orthologous ‘all-purpose’ transcription factor of Schizosaccharomyces pombe. Heterologous expression of atfA in a S. pombe ?atf1 mutant restored the osmotic stress tolerance of fission yeast in surface cultures to the same level as

Anita Balázs; Imre Pócsi; Zsuzsanna Hamari; Éva Leiter; Tamás Emri; Márton Miskei; Judit Oláh; Viktória Tóth; Nikoletta Heged?s; Rolf A. Prade; Mónika Molnár; István Pócsi



Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian (Hungarian) sample  

Microsoft Academic Search

BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1?) is a transcription factor that plays an important role in neo-vascularisation, embryonic pancreas beta-cell mass development, and beta cell protection. Recently a non synonymous single nucleotide polymorphism (g.C45035T SNP, rs11549465) of HIF-1? gene, resulting in the p.P582S amino acid change has been shown to be associated with type 2 diabetes (T2DM) in a Japanese

Geza Nagy; Reka Kovacs-Nagy; Eva Kereszturi; Aniko Somogyi; Anna Szekely; Nora Nemeth; Nora Hosszufalusi; Pal Panczel; Zsolt Ronai; Maria Sasvari-Szekely



Factor XIIIa-positive dendrocyte rarefaction in Ehlers-Danlos syndrome, classic type.  


The Ehlers-Danlos syndrome (EDS) represents a heterogeneous group of connective tissue disorders recognized by distinct clinical, microscopic, and biochemical aspects. In particular, some histologic and ultrastructural clues have been reported in the literature. We present a novel immunohistochemical aid to the diagnosis of the most frequent type of EDS. Factor XIIIa-positive dendrocytes are almost absent in the reticular dermis and markedly reduced in number and size in the adventitial dermis. By contrast, the densities of vimentin-positive cells and CD34-positive cells were unremarkable. The biologic significance of this finding is unknown. However, at least a subset of dermal dendrocytes interacts with fibroblasts. This mechanism could be affected in the classic form of EDS. PMID:11801775

Hermanns-Lę, T; Piérard, G E



Neuronal (Type I) Nitric Oxide Synthase Regulates Nuclear Factor kappa B Activity and Immunologic (Type II) Nitric Oxide Synthase Expression  

Microsoft Academic Search

Nitric oxide subserves diverse physiologic roles in the nervous system. NO is produced from at least three different NO synthase (NOS) isoforms: neuronal NOS (nNOS), endothelial NOS, and immunologic NOS (iNOS). We show that nNOS is the predominant isoform constitutively expressed in glia. NO derived from nNOS in glia inhibits the transcription factor nuclear factor kappa B (NFkappa B) as

Hitoshi Togashi; Masayuki Sasaki; Elliot Frohman; Eichi Taira; Rajiv R. Ratan; Ted M. Dawson; Valina L. Dawson



Identification of cysteine-rich domains of the type 1 tumor necrosis factor receptor involved in ligand binding.  


The extracellular portion of the type 1 (p55) and type 2 (p75) tumor necrosis factor (TNF) receptors contains a repetitive amino acid sequence pattern of four cysteine-rich domains (CRDs). This pattern is found also in several other cell surface proteins, including the p75 nerve growth factor receptor and the CD40, 4-1BB, OX40, Fas, and CD27 antigens. To investigate whether CRDs play a role in TNF binding, we have constructed soluble variants of the extracellular portion of human type 1 TNF receptor (sTNFR1), in which CRD1 (N-terminal) or CRD4 (C-terminal) was deleted by mutagenesis. These variants or a wild type sTNFR1 were linked in their C terminus to the hinge and Fc portion of IgG1 heavy chain to create sTNFR1-IgG chimeras (immunoadhesins). Deletion of either CRD1 or -4 did not cause any major perturbations in the structure of the sTNFR1 variants, as evidenced by their efficient expression and secretion from transfected cells, and by their binding to conformation-dependent monoclonal antibodies that recognize diverse epitopes on sTNFR1. The wild type sTNFR1 immunoadhesin exhibited high affinity binding to TNF alpha (Kd = 65 pM) and TNF beta (Kd = 640 pM). Deletion of CRD4 resulted in about a 10-fold reduction in affinity for TNF alpha (Kd = 660 pM) and for TNF beta (Kd = 5.7 nM). In contrast, deletion of CRD1 resulted in a complete loss of binding to TNF alpha and to TNF beta. These results indicate that CRD4 is important but not necessary for TNF binding, while CRD1 is required. In addition, the results suggest some overlap between the TNFR1 binding sites for TNF alpha and TNF beta, despite low amino acid sequence homology between these cytokines. PMID:1313418

Marsters, S A; Frutkin, A D; Simpson, N J; Fendly, B M; Ashkenazi, A



Expression of Transforming Growth Factor-? Type I and Type II Receptors Is Altered in Rat Lungs Undergoing Bleomycin-Induced Pulmonary Fibrosis  

Microsoft Academic Search

Transforming growth factor-? (TGF-?) is a family of autocrine\\/paracrine\\/endocrine cytokines involved in controlling cell growth and extracellular matrix metabolism. TGF-? exerts its biological effects via binding to type I (T?RI) and type II (T?RII) receptors. To gain insight into the possible role of TGF-? receptors in the pathogenesis of pulmonary fibrosis, we investigated the expression of TGF-? receptors and their

Yun Zhao; Deepti U. Shah



Myocardin-related Transcription Factor-A Complexes Activate Type I Collagen Expression in Lung Fibroblasts*  

PubMed Central

Pulmonary fibrosis is characterized by the excessive deposition of a collagen-rich extracellular matrix. The accumulation of collagen within the lung interstitium leads to impaired respiratory function. Furthermore, smooth muscle actin-positive myofibroblasts within the fibrotic lung contribute to disease progression. Because collagen and smooth muscle cell ?-actin are coordinately expressed in the setting of fibrosis, the hypothesis was tested that specific transcriptional regulators of the myocardin family might also regulate collagen gene expression in myofibroblasts. Myocardin-related transcription factors (MRTFs), through their interaction with the serum-response factor (SRF) on CArG box regulatory elements (CC(A/T)6GG), are important regulators of myofibroblast differentiation. MRTF-A transactivated type I collagen gene reporters as much as 100-fold in lung myofibroblasts. Loss of functional MRTF-A using either a dominant negative MRTF-A isoform, shRNA targeting MRTF-A, or genetic deletion of MRTF-A in lung fibroblasts significantly disrupted type I collagen synthesis relative to controls. Analysis of the COL1A2 proximal promoter revealed a noncanonical CArG box (CCAAACTTGG), flanked by several Sp1 sites important for MRTF-A activation. Chromatin immunoprecipitation experiments confirmed the co-localization of MRTF-A, SRF, and Sp1 bound to the same region of the COL1A2 promoter. Mutagenesis of either the noncanonical CArG box or the Sp1 sites significantly disrupted MRTF-A activation of COL1A2. Together, our findings show that MRTF-A is an important regulator of collagen synthesis in lung fibroblasts and exhibits a dependence on both SRF and Sp1 function to enhance collagen expression.

Luchsinger, Larry L.; Patenaude, Cassandra A.; Smith, Barbara D.; Layne, Matthew D.



Risk Factors for Childhood Overweight in Offspring of Type 1 Diabetic Women With Adequate Glycemic Control During Pregnancy  

PubMed Central

OBJECTIVE Pregnancy in type 1 diabetic women remains a high-risk situation for both mother and child. In this study, we investigated long-term effects on body composition, prevalence of overweight, and insulin resistance in children of type 1 diabetic women who had had adequate glycemic control during pregnancy (mean A1C 6.2%), and we related their outcome to perinatal factors, including macrosomia (birth weight >90th percentile). RESEARCH DESIGN AND METHODS Anthropometric measurements were performed at 6–8 years of age in 213 offspring of type 1 diabetic mothers who participated in a previous nationwide study. Homeostasis model assessment of insulin resistance (HOMA-IR) was determined from a fasting blood sample in 155 of these children. In addition, we studied BMI standard deviation score (SDS) growth trajectories. Results were compared with national reference data. RESULTS The prevalence of overweight in the study population was not different from that in the reference population. However, children who were born macrosomic showed twice as much overweight as nonmacrosomic children. Macrosomia and maternal overweight were independent predictors of childhood overweight. Overweight children showed an increase in BMI SDS starting already after 6 months of age and had a significantly increased HOMA-IR. CONCLUSIONS In type 1 diabetic women with adequate glycemic control during pregnancy, long-term effects on body composition and overweight in their offspring at school age are limited and related mainly to macrosomia at birth. Possible targets for prevention of childhood overweight are fetal macrosomia, maternal overweight, and an increase in BMI SDS during the first years of life.

Rijpert, Maarten; Evers, Inge M.; de Vroede, Monique A.M.J.; de Valk, Harold W.; Heijnen, Cobi J.; Visser, Gerard H.A.



Factors associated with changes in endothelin-1 gene expression in patients with diabetic retinopathy in type 2 diabetes mellitus  

PubMed Central

Purpose To (i) investigate expression of the endothelin-1 (ET-1) gene in peripheral blood mononuclear cells (PBMCs) of patients with type 2 diabetes mellitus (DM) and (ii) determine what correlations, if any, exist between expression of ET-1 in patients with type 2 DM and treatment, clinical features, and biochemical markers in diabetic retinopathy (DR). Methods The study group included 58 patients with type 2 DM, subdivided into three subgroups: those without DR (n=19), those with nonproliferative DR (NPDR; n=28), and those with proliferative DR (PDR; n=11). The control group consisted of 60 individuals. In all groups the mRNA level of ET-1 was estimated using real-time quantitative reverse transcription PCR. Results The mRNA level of ET-1 in patients with NPDR was significantly higher than in those without DR. An increase in ET-1 expression was observed in patients with PDR as opposed to those without DR. Compared to controls, the mRNA level of ET-1 was significantly higher both in patients with NPDR and those with PDR. Duration of DM, insulin therapy, and serum creatinine levels were associated with increased mRNA level of ET-1, whereas medication with sulfonylurea or angiotensin-converting enzyme inhibitors had the opposite effect. Conclusions Expression of ET-1 in PBMCs may be associated with severity of DR in patients with type 2 DM. Long-standing clinical course of DR; medication with insulin, sulfonylurea, or ACE inhibitors; and serum creatinine levels are factors possibly associated with changes in ET-1 expression in PBMCs.

Nowak, Agnieszka; Gola, Joanna; Kowalczyk, Malgorzata; Kapral, Malgorzata; Mazurek, Urszula



Edaphic factors affecting the vertical distribution of radionuclides in the different soil types of Belgrade, Serbia.  


The specific activities of natural radionuclides ((40)K, (226)Ra and (232)Th) and Chernobyl-derived (137)Cs were measured in soil profiles representing typical soil types of Belgrade (Serbia): chernozems, fluvisols, humic gleysols, eutric cambisols, vertisols and gleyic fluvisols. The influence of soil properties and content of stable elements on radionuclide distribution down the soil profiles (at 5 cm intervals up to 50 cm depth) was analysed. Correlation analysis identified associations of (40)K, (226)Ra and (137)Cs with fine-grained soil fractions. Significant positive correlations were found between (137)Cs specific activity and both organic matter content and cation exchange capacity. Saturated hydraulic conductivity and specific electrical conductivity were also positively correlated with the specific activity of (137)Cs. The strong positive correlations between (226)Ra and (232)Th specific activities and Fe and Mn indicate an association with oxides of these elements in soil. The correlations observed between (40)K and Cr, Ni, Pb and Zn and also between (137)Cs and Cd, Cr, Pb and Zn could be attributed to their common affinity for clay minerals. These results provide insight into the main factors that affect radionuclide migration in the soil, which contributes to knowledge about radionuclide behaviour in the environment and factors governing their mobility within terrestrial ecosystems. PMID:22072061

Dragovi?, Snežana; Gaji?, Boško; Dragovi?, Ranko; Jankovi?-Mandi?, Ljiljana; Slavkovi?-Beškoski, Latinka; Mihailovi?, Nevena; Mom?ilovi?, Milan; ?uji?, Mirjana



Increased type II transforming growth factor-beta receptor expression in liver cells during cholesterol challenge.  


A large body of evidences implicates transforming growth factor-beta (TGF-beta) in the pathogenesis of atherosclerosis. In this context, TGF-beta receptor dysfunction has been suggested to be relevant. We tested the effect of hypercholesterolemia, a well-known risk factor for atherosclerosis, on liver type II TGF-beta receptor (TbetaR-II) expression in atherosclerosis-susceptible C57BL/6 mouse strain fed atherogenic diet. In addition, the relationship between cholesterol and TbetaR-II expression was verified by cholesterol challenge on human hepatoma cell (HepG2) cultures. The susceptible C57BL/6 mice fed atherogenic diet exhibited significant mRNA and immunohistochemical TbetaR-II liver expression at 2, 5, 9 and 15 weeks as compared to animals fed a regular diet. The TbetaR-II profile on HepG2 resulted in a time-dependent increased expression when the cells were incubated with soluble free cholesterol, associated with an increased TGF-beta-dependent biological activity as detected by luciferase assay of reporter gene. These data provide evidence for a cholesterol-dependent TbetaR-II induction that may play a potentially relevant role in the development of hypercholesterolemia and atherogenesis. PMID:10996339

Baccante, G; Mincione, G; Di Febbo, C; Coppa, A; Angelucci, D; Lapenna, D; Cuccurullo, F; Colletta, G; Porreca, E



Interaction analysis of grapevine MIKC(c)-type MADS transcription factors and heterologous expression of putative véraison regulators in tomato.  


MIKC(c)-type MADS-domain transcription factors include important regulators of floral development that interact in protein complexes to control the development of floral organs, as described by the ABC model. Members of the SEPALLATA (SEP) and AGAMOUS (AG) MADS clades include proteins involved in stamen and carpel specification and certain members of these families, such as tomato (Solanum lycopersicon) SlRIN and SlTAGL1, have been shown to regulate fruit development and ripening initiation. A number of expression studies have shown that several floral homeotic MADS genes are expressed during grapevine (Vitis vinifera) berry development, including potential homologues of these characterized ripening regulators. To gain insight into the regulation of berry development and ripening in grapevine, we studied the interactions and functions of grapevine floral homeotic MADS genes. Using the yeast 2- and 3-hybrid systems, we determined that the complexes formed during fruit development and ripening may involve several classes of floral homeotic MADS proteins. We found that a heterologously expressed grapevine SEP gene, VviSEP4, is capable of partially complementing the non-ripening phenotype of the tomato rin mutant, indicating that a role for this gene in ripening regulation may be conserved in fleshy fruit ripening. We also found that ectopic expression of a grapevine AG clade gene, VviAG1, in tomato results in the development of fleshy sepals with the chemical characteristics of tomato fruit pericarp. Additionally, we performed 2-hybrid screens on a library prepared from Pinot noir véraison-stage berry and identified proteins that may interact with the MADS factors that are expressed during berry development and that may represent regulatory functions in grape berry development. PMID:23787144

Mellway, Robin D; Lund, Steven T



Inhibition of DNA Synthesis in rat hepatocytes by Platelet-derived Type Ăź Transforming Growth Factor1  

Microsoft Academic Search

Platelet-derived type fi transforming growth factor (TGFjS)is a potent inhibitor of DNA synthesis in primary monolayer cultures of adult rat hepatocytes. TGF\\/9induced a 50% inhibition of epidermal growth factor (I (.1 l-mcdiatcd DNA synthesis at approximately 5 x IO\\

Brian I. Carr; Izumi Hayashi; Earl L. Branum; Harold L. Moses


Risk factors for type 2 diabetes in a sixth-grade multi-racial cohort: The HEALTHY study  

Technology Transfer Automated Retrieval System (TEKTRAN)

HEALTHY is a 3-year middle school intervention program designed to reduce risk factors for type 2 diabetes. The prevalence of diabetes risk factors at baseline in a cohort of 6,358 sixth-grade students is reported. Forty-two schools at seven U.S. sites were randomly assigned to intervention or contr...


Assessment of Job Stress Factors and Organizational Personality Types for Procedure-Based Jobs in Nuclear Power Plants  

Microsoft Academic Search

The purpose of this study is to assess the organizational types and the job stress factors that affect procedure-based job performances in nuclear power plants. We derived 24 organizational factors affecting job stress level in nuclear power plants from the job stress analysis models developed by NIOSH, JDI, and IOR. Considering the safety characteristics in the operating tasks of nuclear

Dae-Ho KIM; Yong-Hee LEE; Jung-Woon LEE



Corticotropin Releasing Factor Receptor Type 1: Molecular Cloning and Investigation of Alternative Splicing in the Hamster Skin  

Microsoft Academic Search

The coding region of the hamster corticotropin releasing factor receptor type 1 was sequenced. Hamster gene appeared to be similar to mouse, rat, and human sequences with 95%, 94%, and 91% homology, respectively. Protein substitutions were generally found in the corticotropin releasing factor-binding domain. Thus, this domain can be more prone to mutations leading to changes in amino acid sequence.

Alexander Pisarchik; Andrzej Slominski



Expression of Human Blood Coagulation Factor XI: Characterization of the Defect in Factor XI Type I11 Deficiency  

Microsoft Academic Search

Human factor XI (FXI) is a blood coagulation factor participat- ing in the early phase of the intrinsic pathway of blood coagulation. It circulates in blood as a glycoprotein com- posed of two identical chains held together by a single disulfide bond between the fourth apple domains. FXI has been expressed in baby hamster kidney (BHK) cells, where it was

Joost C. M. Meijers; Earl W. Davie; Dominic W. Chung



SuperCAT: a supertree database for combined and integrative multilocus sequence typing analysis of the Bacillus cereus group of bacteria (including B. cereus, B. anthracis and B. thuringiensis)  

Microsoft Academic Search

The Bacillus cereus group of bacteria is an important group including mammalian and insect pathogens, such as B. anthracis, the anthrax bac- terium, B. thuringiensis, used as a biological pes- ticide and B. cereus, often involved in food poisoning incidents. To characterize the popula- tion structure and epidemiology of these bacteria, five separate multilocus sequence typing (MLST) schemes have been

Nicolas J. Tourasse; Anne-brit Kolstř



Transgenic mice overexpressing insulin-like growth factor-II in ? cells develop type 2 diabetes  

PubMed Central

During embryonic development, insulin-like growth factor-II (IGF-II) participates in the regulation of islet growth and differentiation. We generated transgenic mice (C57BL6/SJL) expressing IGF-II in ? cells under control of the rat Insulin I promoter in order to study the role of islet hyperplasia and hyperinsulinemia in the development of type 2 diabetes. In contrast to islets from control mice, islets from transgenic mice displayed high levels of IGF-II mRNA and protein. Pancreases from transgenic mice showed an increase in ?-cell mass (about 3-fold) and in insulin mRNA levels. However, the organization of cells within transgenic islets was disrupted, with glucagon-producing cells randomly distributed throughout the core. We also observed enhanced glucose-stimulated insulin secretion and glucose utilization in islets from transgenic mice. These mice displayed hyperinsulinemia, mild hyperglycemia, and altered glucose and insulin tolerance tests, and about 30% of these animals developed overt diabetes when fed a high-fat diet. Furthermore, transgenic mice obtained from the N1 backcross to C57KsJ mice showed high islet hyperplasia and insulin resistance, but they also developed fatty liver and obesity. These results indicate that local overexpression of IGF-II in islets might lead to type 2 diabetes and that islet hyperplasia and hypersecretion of insulin might occur early in the pathogenesis of this disease.

Devedjian, Jean-Christophe; George, Monica; Casellas, Alba; Pujol, Anna; Visa, Joana; Pelegrin, Mireia; Gros, Laurent; Bosch, Fatima



Factor Analysis Study on Sexual Responses in Women with Type 2 Diabetes Mellitus.  


AIMS: This study compared the components of sexual responses between Malaysian women with Type 2 diabetes mellitus and those without the disease. METHODS: This cross-sectional study measured sexual responses by using the validated Malay version of Female Sexual Function Index. A factor analysis with varimax rotation method was employed using principal component analysis to explore the correlation structure of the different domains of sexual responses between the two groups. Components of sexual responses were obtained using Kaiser's criteria and compared between those in the diabetic and non-diabetic groups. RESULTS: A total of 353 women (178 with diabetes and 175 without diabetes) were recruited. Three components of sexual responses emerged from the analysis in the study and control groups. Sexual pain was found to form a component together with lubrication and orgasm domains among the women with diabetes, unlike those without diabetes, where pain stood on its own. Sexual desire and arousal formed one component and satisfaction formed another in both groups. CONCLUSIONS: The domains in the sexual responses of Malaysian women were highly overlapping. It is concluded that the presence of pain as part of lubrication and orgasm component in women with diabetes indicates the importance of intact genital sensation, even though an adverse type of sensation, for vaginal congestion and orgasm to occur in this group of women. PMID:23375262

Ismail, Adibah Hanim; Bau, Rawa; Sidi, Hatta; Guan, Ng Chong; Naing, Lin; Jaafar, Nik Ruzyanei Nik; Razali, Rosdinom; Das, Srijit; Midin, Marhani



Type beta transforming growth factor controls the adipogenic differentiation of 3T3 fibroblasts.  


Differentiating mouse 3T3-L1 preadipocytes have been used as a model system to study the ability of type beta transforming growth factor (TGF-beta) to modulate cell development. We find that TGF-beta inhibits potently (ID50 approximately equal to 25 pM) the adipogenic conversion of 3T3-L1 cells. Inhibition is observed only when cells are exposed to TGF-beta before they become committed to differentiation. Even a transient (4 hr) exposure to TGF-beta immediately before the commitment point is sufficient to prevent differentiation. This point coincides with the time point immediately preceding the onset of coordinate expression of differentiation-specific proteins in 3T3-L1 cells. TGF-beta interacts with cell surface receptors in 3T3-L1 cells that have structural and binding properties similar to TGF-beta receptors in other cell types in which TGF-beta acts as a growth activator or a growth inhibitor. However, TGF-beta does not markedly alter differentiation-related mitosis in 3T3-L1 cells. The action of TGF-beta on 3T3-L1 cells does not involve changes in cAMP or prostaglandin E levels. These results suggest that TGF-beta is a unique modulator of adipogenic differentiation of fibroblasts. PMID:3001708

Ignotz, R A; Massagué, J



Equine antitoxin use and other factors that predict outcome in type A foodborne botulism.  


The use of trivalent equine antitoxin in treating foodborne botulism has not been adequately assessed. One hundred thirty-two cases of type A foodborne botulism reported to the Centers for Disease Control in the period from 1973 to 1980 are reviewed to evaluate the effect of antitoxin therapy and other factors on the outcomes of patients with botulism. The fatality rates were higher in patients over 60 years old and in those who were index patients (the first or only patient in an outbreak). The clinical course was longer in patients over 60 years old, patients whose incubation period was less than 36 hours, and index patients. Patients who had received trivalent equine antitoxin had a lower fatality rate and a shorter course than those who did not receive antitoxin, even after controlling for age and incubation period. Patients who received antitoxin in the first 24 hours after onset had a shorter course but about the same fatality rate as those who received antitoxin later. These results suggest that trivalent antitoxin has a beneficial effect on survival and shortens the course of patients with type A botulism. PMID:6720725

Tacket, C O; Shandera, W X; Mann, J M; Hargrett, N T; Blake, P A



Effects of two types of cobra venom factor on porcine complement activation and pulmonary artery pressure.  

PubMed Central

Autologous porcine plasma that has been incubated with cuprophan haemodialysis membranes causes pulmonary hypertension and peripheral leucopenia following reinfusion into swine. These effects appear to be mediated by biologically active fragments of C3 and C5 that are generated as a consequence of ex vivo activation of complement. Putatively, C5a induces the leucopenia; however, the specific contributions of products of C3 and C5 activation to the pulmonary vasoconstriction have not been elucidated. In the present study, the effects of in vivo infusion of two different types of cobra venom factor (CVF) on peripheral leucocyte count and pulmonary artery pressure in the swine are reported. The CVF from Naja n. naja (CVF(TN)) was shown to activate both porcine C3 and C5, whereas the CVF from Naja h. haje (CVF(NH)) activated only C3. Both types of CVF produced pulmonary hypertension. Significant peripheral leucopenia, however, was observed only with CVF(TN). These results suggest that activation products of C3 contribute to the pulmonary hypertension but not to the peripheral leucopenia observed during haemodialysis using dialysis membranes that activate complement.

Cheung, A K; Parker, C J; Wilcox, L



Tumor necrosis factor alpha inducing spatial interactions between calcium-sensing receptor and L-type voltage-dependent calcium channel.  


The temporal and spatial regulation of intracellular calcium concentration ([Ca(2+)](i)) is very crucial for maintaining calcium ion homeostasis within cells, and consequently in the regulation of cellular functions such as beta cell replication and differentiation, insulin secretion, and apoptosis. Calcium ion regulatory proteins playing major roles in these processes include L-type voltage-dependent calcium channels (L-type VDCCs) and calcium-sensing receptors (CaRs). Tumor necrosis factor alpha (TNF-alpha), a cytokine, is widely known to activate nuclear factor-kappa B (NF-kappaB) transcription in beta cells. Confocal fluorescence imaging data suggest increased co-localization of CaRs with L-type VDCCs upon treatment of beta cells with TNF-alpha, thereby indicating increased membrane-delimited spatial interactions between these two membrane proteins. PMID:19120320

Parkash, Jai



Railing Type Bridge Lighting.  

National Technical Information Service (NTIS)

Tests were conducted on five types of low mounted railing type lighting fixtures to determine whether it was feasible to use this method of lighting for a particular interchange in the Albany area. Factors investigated included: spacing and mounting heigh...

J. G. F. Hiss J. R. Lambert



Insulin-like growth factor-I attenuates the inhibitory effect of type I collagen through ?1 integrin receptor  

Microsoft Academic Search

Extracellular matrix and growth factors are the crucial factors that regulate healing and regenerating processes in human periodontal ligament cells. The purpose of this study was to examine the effects of type I collagen and insulin-like growth factor-I (IGF-I) on osteopontin (OPN) expression. The data showed that OPN expression was significantly decreased when cells were cultured on collagen-coated plates. Addition

Niraporn Chutivongse; Piyamas Sumrejkanchanakij; Tussanee Yongchaitrakul; Prasit Pavasant



Different Responses to Gefitinib in Lung Adenocarcinoma Coexpressing Mutant and Wild-Type Epidermal Growth Factor Receptor Genes  

Microsoft Academic Search

Response to gefitinib is strongly associated with the status of the epidermal growth factor receptor gene. Here we report the different treatment responses in a case of lung adenocar- cinoma coexpressing mutant-type gene in the primary lung mass and a wild-type gene in the metastatic bone lesions. This case demonstrated that at least two strains of tumor cells were present

Wen-Chi Chou; Shiu-Feng Huang; Kun-Yang Yeh; Hung-Ming Wang; Mei-Ying Liu; Jia-Juan Hsieh; Yun-Chung Cheung; John Wen-Cheng Chang


Predominant Intracellular Localization of the Type I Transforming Growth Factor-? Receptor and Increased Nuclear Accumulation after Growth Arrest  

Microsoft Academic Search

Transforming growth factor-? (TGF-?) signaling requires the functional interaction of two distinct receptors, type I (RI) and type II (RII), at the cell surface. Exposure of cells to TGF-? results in receptor internalization and down-regulation (Zwaagstra et al., 1999, Exp. Cell Res. 252, 352–362); however, little is known about the subsequent fate of RI or RII. In this study the

John C. Zwaagstra; Alain Guimond; Maureen D. O'Connor-McCourt



Type 1 Fimbriae, a Colonization Factor of Uropathogenic Escherichia coli, Are Controlled by the Metabolic Sensor CRP-cAMP  

Microsoft Academic Search

Type 1 fimbriae are a crucial factor for the virulence of uropathogenic Escherichia coli during the first steps of infection by mediating adhesion to epithelial cells. They are also required for the consequent colonization of the tissues and for invasion of the uroepithelium. Here, we studied the role of the specialized signal transduction system CRP-cAMP in the regulation of type

Claudia M. Müller; Anna Ĺberg; Jurate Straseviçiene; Levente Em?dy; Bernt Eric Uhlin; Carlos Balsalobre



Screen media time usage of 12–16 year-old Spanish school adolescents: Effects of personal and socioeconomic factors, season and type of day  

Microsoft Academic Search

This study examined screen media time usage (SMTU) and its association with personal and socioeconomic factors, as well as the effect of season and type of day, in a Spanish sample of 12–16 year-old school adolescents (N=323). The research design was a cross-sectional survey, in which an interviewer-administered recall questionnaire was used. Statistical analyses included repeated measures analyses of variance,

José Devís-Devís; Carmen Peiró-Velert; Vicente J. Beltrán-Carrillo; José Manuel Tomás



Photolithographically defined deposition of attachment factors as a versatile method for patterning the growth of different cell types in culture.  


Spatially defined growth of cells in culture is a useful model for studies ranging from the characterization of cellular motility to the analysis of network behaviour in structurally defined ensembles of excitable cells. Current methodological approaches for obtaining patterned growth include sophisticated modifications of surface chemistry, stamping techniques and microfluidics. The implementation of most of these techniques requires the availability of highly specialized apparatus and some of the methods are specific for certain cell types and/or substrate materials. The goal of the present study was to develop a cell-patterning technique that can be implemented by any laboratory working with cell culture and that is highly adaptable in terms of cell types and substrate materials. The method is based on a photolithographic process that permits the patterned deposition of attachment factors of choice on surfaces previously coated with agar with a spatial resolution (maximal deviation from a straight line) of +/-3 micro m. Because agar efficiently prevents cell adhesion, patterned growth obtained with this technique displays virtually no off-pattern cell attachment. The method permitted the patterning of cardiomyocytes, fibroblasts and HeLa cells on either glass substrates or polymer-coated materials with a spatial resolution of a few micrometers. PMID:12690471

Rohr, Stephan; Flückiger-Labrada, Regula; Kucera, Jan P



The type 2 vascular endothelial growth factor receptor recruits insulin receptor substrate-1 in its signalling pathway.  

PubMed Central

Vascular endothelial growth factor (VEGF) isoforms exert their biological effects through receptors that possess intrinsic tyrosine kinase activity. Whether VEGF binding to its receptors recruits insulin receptor substrate (IRS) family of docking proteins to the receptor is not known. Following incubation of mouse kidney proximal tubular epithelial cells with VEGF, we observed an increase in tyrosine phosphorylation of several proteins, including one of approximately 200 kDa, suggesting possible regulation of phosphorylation of IRS proteins. VEGF augmented tyrosine phosphorylation of IRS-1 in kidney epithelial cells and rat heart endothelial cells in a time-dependent manner. In the epithelial cells, association of IRS-1 with type 2 VEGF receptor was promoted by VEGF. VEGF also increased association of IRS-1 with the p85 regulatory subunit of phosphoinositide 3-kinase (PI 3-kinase), and PI 3-kinase activity in IRS-1 immunoprecipitates was increased in VEGF-treated cells. Incubation of epithelial cells with antisense IRS-1 oligonucleotide, but not sense oligonucleotide, reduced expression of the protein and VEGF-induced PI 3-kinase activity in IRS-1 immunoprecipitates. Additionally, VEGF-induced protein synthesis was also impaired by antisense but not sense IRS-1 oligonucleotide. These data provide the first evidence that binding of VEGF to its type 2 receptor promotes association of IRS-1 with the receptor complex. This association may account for some of the increase in VEGF-induced PI 3-kinase activity, and the increase in de novo protein synthesis seen in renal epithelial cells.

Senthil, Duraisamy; Ghosh Choudhury, Goutam; Bhandari, Basant K; Kasinath, Balakuntalam S



The quality of different types of child care at 10 and 18 months: a comparison between types and factors related to quality  

Microsoft Academic Search

The quality of care offered in four different types of non?parental child care to 307 infants at 10 months old and 331 infants at 18 months old was compared and factors associated with higher quality were identified. Observed quality was lowest in nurseries at each age point, except that at 18 months they offered more learning activities. There were few

Penelope Leach; Jacqueline Barnes; Kathy Sylva; Alan Stein



The Quality of Different Types of Child Care at 10 and 18 Months: A Comparison between Types and Factors Related to Quality  

ERIC Educational Resources Information Center

The quality of care offered in four different types of non-parental child care to 307 infants at 10 months old and 331 infants at 18 months old was compared and factors associated with higher quality were identified. Observed quality was lowest in nurseries at each age point, except that at 18 months they offered more learning activities. There…

Leach, Penelope; Barnes, Jacqueline; Malmberg, Lars-Erik; Sylva, Kathy; Stein, Alan



Prevalence and risk factors for vaginal Candida colonization in women with type 1 and type 2 diabetes  

PubMed Central

Background Diabetes mellitus increases the rate of vaginal colonization and infection with Candida species Methods We surveyed women with diabetes receiving care at either an urban or suburban diabetes clinic to examine the relationship between vaginal Candida colonization, diabetes type and duration, and HbA1c level. 101 participants completed the self-administered questionnaire and self-collected a vaginal swab for Candida culture. Candida colonization was similar by age and race. Results Type 1 diabetics were three times as likely as type 2 diabetics to be colonized with any Candida species (OR = 3.4; 95% CI: 1.03, 11.41; p = 0.04); even after adjusting for abnormal HbA1c, which had an independent effect (OR = 1.4; 95% CI: 1.04, 1.76; p = 0.02). Recent antibiotic use (OR = 4.5; 95% CI: 1.18, 16.79; p = 0.03), lifetime history of chlamydia (OR = 5.8; 95% CI: 1.09, 30.54; p = 0.04), and performing oral sex during the past 2 weeks (OR = 4.9; 95% CI:0.84, 28.27; p = 0.08) were also associated with Candida carriage after adjusting for diabetic type and abnormal HbA1c. C. albicans was isolated from the majority of colonized type 1 participants (56%), while C. glabrata was the most common isolate among colonized type 2 participants (54%). Conclusions Improving glucose control and possibly modifying sexual behavior may reduce risk of Candida colonization, and potentially symptomatic infection, among women with diabetes.

de Leon, Ella M; Jacober, Scott J; Sobel, Jack D; Foxman, Betsy



[Case-control study on the risk factors of type 2 diabetes of Dong nationality in Western Hunan].  


Objective: To explore the risk factors of type 2 diabetes mellitus (T2DM) of Dong nationality in Western Hunan, and to provide a scientific basis for the prevention and treatment of T2DM in the district. Methods: In the case-control study, the subjects were divided into a T2DM group, an impaired glucose regulation (IGR) group and a normal glucose tolerance (NGT) group through oral glucose tolerance test (OGTT). A questionnaire survey was conducted, and physical measurements and the detection of blood glucose, blood lipids and serum insulin were done. Results: Univariate analysis found significant difference in age, fasting insulin (FINS), HOMA insulin resistance index (HOMA-IRI), HOMA ?-cell function index (HOMA-?C), trigalloyl glycerol (TG), high density lipoprotein cholesterol (HDL-C), systolic blood pressure, and diastolic blood pressure in the glucose metabolism among different groups (P<0.05). Body mass index (BMI), waist/hip ratio (WHR), family history of diabetes, number of physical activities per week, dinner taste, fat and protein-rich foods, fresh vegetables and fruits intake were associated with T2DM. Multifactor non-conditional ordinal logistic regression indicated that age was the risk factor of T2DM and IGR. Compared with the group whose age was?50, the odds ratios of the groups of 5070 were 1.85, 2.83 and 2.64 respectively, P<0.05. The risk of suffering from diabetes of the overweighted or obese people was 2.13 times that of a normal BMI group, P<0.01. The other influencing factors included WHR (OR=2.06), family history of diabetes (OR=11.36), and fat and protein-rich foods (OR=1.90). Conclusion: The main influencing factors of T2DM of Dong nationality in Western Hunan include age, BMI, WHR, family history of diabetes, fat and protein-rich foods. We must strengthen the health eduation of T2DM of Dong nationality in Western Hunan to reduce the risk of T2DM. PMID:24164874

Liu, Liya; Chen, Lizhang; Dai, Jinxiong; Chen, Jiaxiong; Liang, Ying; Pei, Tingli; Huang, Yongbin



Association between vascular endothelial growth factor and hypertension in children and adolescents type I diabetes mellitus  

PubMed Central

The aim of the study was to analyse the relationship between the serum level of vascular endothelial growth factor (VEGF) and the incidence of hypertension (HT) in children and adolescents with type I diabetes mellitus (T1DM). One hundred and five patients with T1DM were enrolled in the study. The control group consisted of 30 healthy controls. All the T1DM patients were subjected to biochemical analyses, ophthalmologic examination and 24-h blood pressure monitoring. Besides, all the patients and healthy controls had serum VEGF levels measured with the use of the ELISA methodology. The essence of our research is that patients with T1DM and HT and with microalbuminuria (MA) and diabetic retinopathy (DR) (MA/DR) are characterized by a significantly higher level of VEGF (340.23±93.22?pg?ml–1) in blood serum in comparison with the group of T1DM patients without HT and MA/DR (183.6±96.6?pg?ml–1) and with healthy controls (145.32±75.58?pg?ml–1). In addition, the VEGF level was significantly higher in T1DM patients, who presented all three complications, that is HT, retinopathy and MA in comparison with T1DM patients without HT, but with MA/DR (P=0.036). On the other hand, no statistically significant differences (P=0.19) were noted in the level of VEGF in serum between T1DM patients without HT and MA/DR and the healthy control group. At a further stage of analysis, using the method of multiple regression, it was shown that systolic pressure, HbA1c and duration of disease are independent factors influencing the concentration of VEGF. Summarizing, the measurement of VEGF serum levels allows for the identification of groups of patients who have the highest risk of HT and, subsequently, progression of vascular complications.

Zorena, K; Mysliwska, J; Mysliwiec, M; Rybarczyk-Kapturska, K; Malinowska, E; Wisniewski, P; Raczynska, K



Etiopathogenesis of type 1 diabetes mellitus: prognostic factors for the evolution of residual ? cell function  

PubMed Central

Type 1A diabetes mellitus (T1ADM) is a progressive autoimmune disease mediated by T lymphocytes with destruction of beta cells. Up to now, we do not have precise methods to assess the beta cell mass, "in vivo" or "ex-vivo". The studies about its genetic susceptibility show strong association with class II antigens of the HLA system (particularly DQ). Others genetics associations are weaker and depend on the population studied. A combination of precipitating events may occur at the beginning of the disease. There is a silent loss of immune-mediated beta cells mass which velocity has an inverse relation with the age, but it is influenced by genetic and metabolic factors. We can predict the development of the disease primarily through the determination of four biochemically islet auto antibodies against antigens like insulin, GAD65, IA2 and Znt8. Beta cell destruction is chronically progressive but at clinical diagnosis of the disease a reserve of these cells still functioning. The goal of secondary disease prevention is halt the autoimmune attack on beta cells by redirecting or dampening the immune system. It is remains one of the foremost therapeutic goals in the T1ADM. Glycemic intensive control and immunotherapeutic agents may preserve beta-cell function in newly diagnosed patients with T1ADM. It may be assessed through C-peptide values, which are important for glycemic stability and for the prevention of chronic complications of this disease. This article will summarize the etiopathogenesis mechanisms of this disease and the factors can influence on residual C-peptide and the strategies to it preservation.



Wild Type p53 Transcriptionally Represses the SALL2 Transcription Factor under Genotoxic Stress  

PubMed Central

SALL2- a member of the Spalt gene family- is a poorly characterized transcription factor found deregulated in various cancers, which suggests it plays a role in the disease. We previously identified SALL2 as a novel interacting protein of neurotrophin receptors and showed that it plays a role in neuronal function, which does not necessarily explain why or how SALL2 is deregulated in cancer. Previous evidences indicate that SALL2 gene is regulated by the WT1 and AP4 transcription factors. Here, we identified SALL2 as a novel downstream target of the p53 tumor suppressor protein. Bioinformatic analysis of the SALL2 gene revealed several putative p53 half sites along the promoter region. Either overexpression of wild-type p53 or induction of the endogenous p53 by the genotoxic agent doxorubicin repressed SALL2 promoter activity in various cell lines. However R175H, R249S, and R248W p53 mutants, frequently found in the tumors of cancer patients, were unable to repress SALL2 promoter activity, suggesting that p53 specific binding to DNA is important for the regulation of SALL2. Electrophoretic mobility shift assay demonstrated binding of p53 to one of the identified p53 half sites in the Sall2 promoter, and chromatin immunoprecipitation analysis confirmed in vivo interaction of p53 with the promoter region of Sall2 containing this half site. Importantly, by using a p53ERTAM knockin model expressing a variant of p53 that is completely dependent on 4-hydroxy-tamoxifen for its activity, we show that p53 activation diminished SALL2 RNA and protein levels during genotoxic cellular stress in primary mouse embryo fibroblasts (MEFs) and radiosensitive tissues in vivo. Thus, our finding indicates that p53 represses SALL2 expression in a context-specific manner, adding knowledge to the understanding of SALL2 gene regulation, and to a potential mechanism for its deregulation in cancer.

Farkas, Carlos; Martins, Carla P.; Escobar, David; Hepp, Matias I.; Donner, David B.; Castro, Ariel F.; Evan, Gerard; Gutierrez, Jose L.; Warren, Robert; Pincheira, Roxana



[Fetal weight at weight as predisposing risk factor for type 2 diabetes in adulthood].  


When the fetus growth in an unfavorable intrauterine environment, this process has implications in the adult life, that predisposes to suffer metabolic abnormalities as obesity, hypertension and non-insulin dependent diabetes mellitus. The unfavorable intrauterine environment includes the pregnancy with diabetes mellitus, pregnancy with gestational diabetes, and pregnancy with maternal undernutrition. Multiple epidemiological studies developed in North America and Europe appear to broadly confirm the association of the low birth weight in babies borne at term, with the glucose metabolism impairments in the adult life. An implication of metabolic impairments on high birth weight for the gestational age has been founded. This alteration could start when there are changes in nutritional habits in migrate populations, having number and function of the pancreatic islets altered, maybe because during fetal life they were faced to blood fluid decreased, and nutrients also decrease as well as the differentiation of cells was modified, as an important intent for fetal survival. The prevalence of type 2 diabetes has been reported in 13 to 25% for low birth weight. On the other hand, maternal hyperglycemia leads to beta-cell hyperplasia in the fetus, by a constant stimulus over the insulin production which stimulates the use of glucose as nutrients, leading to the increase in fetal weight and determining genetic changes. In overnutrition conditions, the prevalence of type 2 diabetes has been reported of 8 to 18%. Growth of tissues has critical periods at different times and intrauterine environment can be one mechanism for may permanently changes in pancreas structure and hormonal secretion patterns. Thus, the hypothesis that autoprotective fetal changes during the intrauterine life occur, took place, specially during the critical period of development, leaves to permanent changes called "programmed changes", including an endocrine disturbance of pancreatic functions, appearing in adult life. Further molecular studies of pancreatic islets are necessary in order to determine the mechanisms for lifelong changes and insulin metabolism due to intrauterine growth. PMID:11816527

Hernández Valencia, M; Zárate, A



Reproductive factors and specific histological types of breast cancer: prospective study and meta-analysis  

PubMed Central

Little is known about how reproductive factors affect the risk of breast cancers of different histology. In an analysis of prospective data on 1.2 million middle-aged UK women, we used proportional hazards models to estimate the relative risks of six histological types in relation to menarche, childbearing and menopause. During 8.7 million person-years of follow-up, 17?923 ductal, 3332 lobular, 1062 tubular, 944 mixed ductal lobular, 330 mucinous and 117 medullary cancers were diagnosed. The effect of both age at menarche and age at first birth was greatest for lobular tumours; relative risks per 5-year increase in age at menarche for ductal, lobular, and tubular cancers were 0.93 (0.87–0.99), 0.65 (0.56–0.76), and 0.75 (0.57–0.98), respectively (P-value for heterogeneity=0.0001); and the relative risks per 5-year increase in age at first birth were 1.10 (1.07–1.12), 1.23 (1.17–1.29), and 1.13 (1.03–1.23), respectively (P-value for heterogeneity=0.0006). Increasing parity reduced the risk of each tumour type, except medullary cancers, but the reduction in risk was greater for mucinous cancers than for any other subtype considered (P<0.05 for comparison with each other subtype in turn). The effect of menopause did not vary significantly by tumour histology. Meta-analysis of published results on the effects of age at menarche and age at first birth on ductal and lobular cancers were in keeping with our findings.

Reeves, G K; Pirie, K; Green, J; Bull, D; Beral, V



Wild-type p53 attenuates cancer cell motility by inducing growth differentiation factor-15 expression.  


A major function of the p53 tumor suppressor is the regulation of the cell cycle and apoptosis. In addition to its well-documented functions in malignant cancer cells, p53 can also regulate cell migration and invasion, which contribute to metastasis. Growth differentiation factor-15 (GDF-15), a member of the TGF-? superfamily, has been shown to be a downstream target of p53 and is associated with diverse human diseases and cancer progression. In this study, we examined the potential role of GDF-15 in p53-regulated cancer cell motility. We show that overexpression of wild-type p53 in two highly invasive p53-null human cancer cell lines, SKOV3 and PC3, attenuated cell migration and the movement through Matrigel. Using wild-type p53 and DNA-binding-deficient p53 mutants, we found that the transcriptional activity of p53 is required in the induction of GDF-15 expression. Cell movement through uncoated and Matrigel-coated transwell decreased in response to treatment with recombinant GDF-15, whereas the cell proliferation was not affected by GDF-15 treatment. Moreover, the induction of GDF-15 expression and secretion by p53 and the reduction in cell movement through Matrigel were diminished by treatment with GDF-15 small interfering RNA. This study demonstrates a mechanism by which p53 attenuates cancer cell motility through GDF-15 expression. In addition, our results indicate that GDF-15 mediates the functions of p53 by autocrine/paracrine action. PMID:21586550

Cheng, Jung-Chien; Chang, Hsun-Ming; Leung, Peter C K




PubMed Central

Reactivity of factor IXa with basic pancreatic trypsin inhibitor is enhanced by low molecular weight heparin (enoxaparin). Previous studies by us have suggested that this effect involves allosteric modulation of factor IXa. We examined the reactivity of factor IXa with several isolated Kunitz-type inhibitor domains; basic pancreatic trypsin inhibitor, the Kunitz inhibitor domain of Protease Nexin-2 and the first two inhibitor domains of tissue factor pathway inhibitor. We find that enhancement of factor IXa reactivity by enoxaparin is greatest for basic pancreatic trypsin inhibitor (>10-fold), followed by the second tissue factor pathway inhibitor domain (1.7-fold) and the Kunitz inhibitor domain of Protease Nexin-2 (1.4-fold). Modeling studies of factor IXa with basic pancreatic trypsin inhibitor suggest that binding of this inhibitor is sterically hindered by the 99-loop of factor IXa, specifically residue K98. Slow-binding kinetic studies support the formation of a weak initial enzyme-inhibitor complex between factor IXa and basic pancreatic trypsin inhibitor that is facilitated by enoxaparin binding. Mutation of K98 to A in factor IXa results in enhanced reactivity with all inhibitors examined, while almost completely abrogating the enhancing effects of enoxaparin. The results implicate K98 and the 99-loop of factor IXa in defining enzyme inhibitor specificity. More importantly, these results demonstrate the ability of factor IXa to be allosterically modulated by occupation of the heparin-binding exosite.

Neuenschwander, Pierre F.; Williamson, Stephen R.; Nalian, Armen; Baker-Deadmond, Kimberly J.



Cholinergic Abnormalities, Endosomal Alterations and Up-Regulation of Nerve Growth Factor Signaling in Niemann-Pick Type C Disease  

PubMed Central

Background Neurotrophins and their receptors regulate several aspects of the developing and mature nervous system, including neuronal morphology and survival. Neurotrophin receptors are active in signaling endosomes, which are organelles that propagate neurotrophin signaling along neuronal processes. Defects in the Npc1 gene are associated with the accumulation of cholesterol and lipids in late endosomes and lysosomes, leading to neurodegeneration and Niemann-Pick type C (NPC) disease. The aim of this work was to assess whether the endosomal and lysosomal alterations observed in NPC disease disrupt neurotrophin signaling. As models, we used i) NPC1-deficient mice to evaluate the central cholinergic septo-hippocampal pathway and its response to nerve growth factor (NGF) after axotomy and ii) PC12 cells treated with U18666A, a pharmacological cellular model of NPC, stimulated with NGF. Results NPC1-deficient cholinergic cells respond to NGF after axotomy and exhibit increased levels of choline acetyl transferase (ChAT), whose gene is under the control of NGF signaling, compared to wild type cholinergic neurons. This finding was correlated with increased ChAT and phosphorylated Akt in basal forebrain homogenates. In addition, we found that cholinergic neurons from NPC1-deficient mice had disrupted neuronal morphology, suggesting early signs of neurodegeneration. Consistently, PC12 cells treated with U18666A presented a clear NPC cellular phenotype with a prominent endocytic dysfunction that includes an increased size of TrkA-containing endosomes and reduced recycling of the receptor. This result correlates with increased sensitivity to NGF, and, in particular, with up-regulation of the Akt and PLC-? signaling pathways, increased neurite extension, increased phosphorylation of tau protein and cell death when PC12 cells are differentiated and treated with U18666A. Conclusions Our results suggest that the NPC cellular phenotype causes neuronal dysfunction through the abnormal up-regulation of survival pathways, which causes the perturbation of signaling cascades and anomalous phosphorylation of the cytoskeleton.



Epidemiological characteristics and risk factors of diabetic retinopathy in type 2 diabetes mellitus in Shandong Peninsula of China  

PubMed Central

AIM To determine the epidemiological characteristics and estimate the risk factors of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) in Shandong Peninsula of China. METHODS The cases of T2DM admitted to Affiliated Hospital of Medical College of Qingdao University, Shandong Province, China, from January 2006 to December 2010 were retrospectively reviewed. The epidemiological characteristics of DR were estimated. The cases were divided into two groups according to degrees of retinopathy: non-DR group and DR group. Logistic regression analysis was used to study the related risk factors of DR. RESULTS The prevalence of DR in patients with T2DM was 25.08% (834/3326). There was significant difference between the average age for men (59.08±15.43 years) and for women (62.92±18.19 years, P=0.0021). The majority of DR occurred in women (female: male ratio=1.76:1, P<0.0001). The incidence rate of DR in urban (489/834) was higher than that in rural area (345/834, P<0.0001). In 834 DR patients, the mean duration of T2DM was 8.90±4.15 years (range: 0-16 years); 440 people (52.76%) had received varying degrees of health education about prevention and primary care of DM; and 473 people (56.71%) suffered from other DM complications confirmed at the same time. In addition, the incidence rate of monocular (551/3326) and binocular retinopathy (283/3326) were statistically different (P<0.0001). Factors associated (P<0.05) with the presence of DR included old age, lower health educational level, intraocular surgery history, longer duration of T2DM, accompanying with other DM complications, no standard treatment procedure, lower body mass index (BMI) and higher fasting plasma glucose (FPG), glycated hemoglobin A1C (HbA1C), urine albumin (UA), total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C). The risk factors (P<0.05) independently associated with the presence of DR were: longer duration of T2DM, lower health educational level, higher FPG, higher UA, lower BMI and higher TC. CONCLUSION DR is highly prevalent in the patients with T2DM in Shandong Peninsula of China. Besides blood glucose, many factors are associated with the present and development of DR.

Du, Zhao-Dong; Hu, Li-Ting; Zhao, Gui-Qiu; Ma, Yan; Zhou, Zhan-Yu; Jiang, Tao



40 CFR Table C-2 to Subpart C of... - Default CH4 and N2O Emission Factors for Various Types of Fuel  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Default CH4 and N2O Emission Factors for Various Types of Fuel...98âDefault CH4 and N2 O Emission Factors for Various Types of Fuel Fuel type Default CH4 emission factor (kg CH4 /mmBtu)...



Regulation of type II transforming-growth-factor-beta receptors by protein kinase C iota.  

PubMed Central

TGF-beta (transforming growth factor-beta) is implicated in the pathogenesis of diabetic nephropathy. We previously demonstrated that up-regulation of type II TGF-beta receptor (TbetaRII) induced by high glucose might contribute to distal tubular hypertrophy [Yang, Guh, Yang, Lai, Tsai, Hung, Chang and Chuang (1998) J. Am. Soc. Nephrol. 9, 182-193]. We have elucidated the mechanism by using cultured Madin-Darby canine kidney cells. Enhancer assay and electrophoretic-mobility-shift assay were used to estimate the involvement of transcription factors. Western blotting and an in vitro kinase assay were used to evaluate the level and activity of protein kinase. We showed that glucose (100-900 mg/dl) induced an increase in mRNA level and promoter activity of TbetaRII (note: 'mg/dl' are the units commonly used in diabetes studies). The promoter region -209 to -177 appeared to contribute to positive transactivation of TbetaRII promoter by comparing five TbetaRII-promoter-CAT (chloramphenicol acetyl-transferase) plasmids. Moreover, the transcription factor AP-1 (activator protein 1) was significantly activated and specifically binds to TbetaRII promoter (-209 to -177). More importantly, we found that atypical PKC iota might be pivotal for high glucose-induced increase in both AP-1 binding and TbetaRII promoter activity. First, high glucose induced cytosolic translocation, activation and autophosphorylation of PKC iota. Secondly, antisense PKC iota expression plasmids attenuated high-glucose-induced increase in AP-1 binding and TbetaRII promoter activity; moreover, sense PKC iota expression plasmids enhanced these instead. Finally, we showed that antisense PKC iota expression plasmids might partly attenuate a high-glucose/TGF-beta1-induced increase in fibronectin. We conclude that PKC iota might mediate high-glucose-induced increase in TbetaRII promoter activity. In addition, antisense PKC iota expression plasmid effectively suppressed up-regulation of TbetaRII and fibronectin in hyperglycaemic distal-tubule cells.

Chuang, Lea-Yea; Guh, Jinn-Yuh; Liu, Shu-Fen; Hung, Min-Yuan; Liao, Tung-Nan; Chiang, Tai-An; Huang, Jau-Shyang; Huang, Yu-Lun; Lin, Chi-Fong; Yang, Yu-Lin



Genotype Score in Addition to Common Risk Factors for Prediction of Type 2 Diabetes  

PubMed Central

BACKGROUND Multiple genetic loci have been convincingly associated with the risk of type 2 diabetes mellitus. We tested the hypothesis that knowledge of these loci allows better prediction of risk than knowledge of common phenotypic risk factors alone. METHODS We genotyped single-nucleotide polymorphisms (SNPs) at 18 loci associated with diabetes in 2377 participants of the Framingham Offspring Study. We created a genotype score from the number of risk alleles and used logistic regression to generate C statistics indicating the extent to which the genotype score can discriminate the risk of diabetes when used alone and in addition to clinical risk factors. RESULTS There were 255 new cases of diabetes during 28 years of follow-up. The mean (±SD) genotype score was 17.7±2.7 among subjects in whom diabetes developed and 17.1±2.6 among those in whom diabetes did not develop (P<0.001). The sex-adjusted odds ratio for diabetes was 1.12 per risk allele (95% confidence interval, 1.07 to 1.17). The C statistic was 0.534 without the genotype score and 0.581 with the score (P=0.01). In a model adjusted for sex and self-reported family history of diabetes, the C statistic was 0.595 without the genotype score and 0.615 with the score (P=0.11). In a model adjusted for age, sex, family history, body-mass index, fasting glucose level, systolic blood pressure, high-density lipoprotein cholesterol level, and triglyceride level, the C statistic was 0.900 without the genotype score and 0.901 with the score (P=0.49). The genotype score resulted in the appropriate risk reclassification of, at most, 4% of the subjects. CONCLUSIONS A genotype score based on 18 risk alleles predicted new cases of diabetes in the community but provided only a slightly better prediction of risk than knowledge of common risk factors alone.

Meigs, James B.; Shrader, Peter; Sullivan, Lisa M.; McAteer, Jarred B.; Fox, Caroline S.; Dupuis, Josee; Manning, Alisa K.; Florez, Jose C.; Wilson, Peter W.F.; D'Agostino, Ralph B.; Cupples, L. Adrienne



Factor VIII-von Willebrand Factor Binding Defects in Autosomal Recessive von Willebrand Disease Type Normandy and in Mild Hemophilia A  

Microsoft Academic Search

This concise review is focused on genetic, molecular and clinical aspects of von Willebrand disease (VWD) type 2N and of mild hemophilia A due to mutations impairing FVIII-von Willebrand factor (VWF) interactions. Missense mutations in the VWF gene impairing the binding to FVIII do not impair the structure of VWF multimers nor the ability of VWF to aggregate platelets but

Marc Jacquemin



Immunohistochemical expression of vascular endothelial growth factor (VEGF) in different types of odontogenic cysts.  


The objective of the present study was to evaluate vascular endothelial growth factor (VEGF) expression in different types of odontogenic cysts. A total of 25 parakeratotic odontogenic keratocysts (POKCs), 16 orthokeratotic odontogenic keratocysts (OOKCs), and 28 follicular cysts (FCs) were evaluated semiquantitatively for immunohistochemical analysis of VEGF in epithelial cells, endothelial cells of blood vessels, inflammatory cells and focally stromal cells. A significant different expression of VEGF in all cell components was found in keratocysts compared to FCs. The POKCs (80%) and OOKCs (68%) showed more than 50% VEGF positive epithelial cells, whereas the majority of FCs (71%) were either negative in the epithelium or showed less than 10% positive cells. Similarly, the POKCs (88%) and OOKCs (68%) showed more than 50% positive endothelial cells, whereas the FCs (75%) were either negative or showed less than 10% VEGF positive endothelial cells. The highest percentage of cases with score 2 positivity in the stromal cells was observed in POKCs (68%); OOKCs showed a score 2 positivity in 44%, score 1 in 31% and score 0 in 25%, whereas 68% of FCs showed a score 0, 25% a score 1 and only 7% of cases showed a score 2. No statistically significant differences were observed between POKCs and OOKCs in VEGF expression in the epithelial and endothelial cells, whereas the positivity score in stromal cells was significantly higher in POKCs compared to OOKCs. The present results can support the hypothesis that angiogenesis is an active mechanism in the invasive growth of the OKC. PMID:20563616

Rubini, Corrado; Artese, Luciano; Zizzi, Antonio; Fioroni, Massimiliano; Ascani, Giuliano; Goteri, Gaia; Stramazzotti, Daniela; Piccirilli, Marcello; Iezzi, Giovanna; Piattelli, Adriano



Action of platelet-activating factor on type 1 diabetic human platelets  

SciTech Connect

Platelets from patients with type 1 diabetes have exhibited more sensitivity to aggregation when compared with platelets from controls without diabetes after challenge with platelet-activating factor (PAF). The production of thromboxane B2 (TxB2) and 12-hydroxyeicosatetraenoic acid (12-HETE) and the release of 5-hydroxytryptamine (5HT) were increased when the platelets were challenged by PAF (5.0 x 10(-6) mol/L and 1.0 x 10(-6) mol/L). The production of TxB2 and 12-HETE and the release of 5HT were related to the irreversible biphasic aggregation profiles observed in the patients with diabetes. Inhibition of thromboxane A2 (TxA2) production by acetylsalicylic acid abolished the secondary wave of aggregation of platelets from patients with diabetes, changing an irreversible aggregation to a reversible one. Inhibition of both TxA2 and 12-HETE production by eicosatetraenoic acid did not contribute further to the inhibition caused by acetylsalicylic acid alone, indicating that 12-HETE was not involved in the secondary wave of aggregation. These data show that the increased aggregation observed in the platelets from the group with diabetes in response to PAF results in part from their higher production of TxA2 and release of 5HT.

Greco, N.J.; Arnold, J.H.; O'Dorisio, T.M.; Cataland, S.; Panganamala, R.V.



Mixed chimerism and growth factors augment ? cell regeneration and reverse late-stage type 1 diabetes.  


Type 1 diabetes (T1D) results from an autoimmune destruction of insulin-producing ? cells. Currently, islet transplantation is the only curative therapy for late-stage T1D, but the beneficial effect is limited in its duration, even under chronic immunosuppression, because of the chronic graft rejection mediated by both auto- and alloimmunity. Clinical islet transplantation is also restricted by a severe shortage of donor islets. Induction of mixed chimerism reverses autoimmunity, eliminates insulitis, and reverses new-onset but not late-stage disease in the nonobese diabetic (NOD) mouse model of T1D. Administration of gastrin and epidermal growth factor (EGF) also reverses new-onset but not late-stage T1D in this animal model. Here, we showed that combination therapy of induced mixed chimerism under a radiation-free nontoxic anti-CD3/CD8 conditioning regimen and administration of gastrin/EGF augments both ? cell neogenesis and replication, resulting in reversal of late-stage T1D in NOD mice. If successfully translated into humans, this combination therapy could replace islet transplantation as a long-term curative therapy for T1D. PMID:22572882

Wang, Miao; Racine, Jeremy J; Song, Xiaoping; Li, Xiaofan; Nair, Indu; Liu, Hongjun; Avakian-Mansoorian, Alina; Johnston, Heather F; Liu, Can; Shen, Christine; Atkinson, Mark; Todorov, Ivan; Kandeel, Fouad; Forman, Stephen; Wilson, Brian; Zeng, Defu



Type IV Longus Pilus of Enterotoxigenic Escherichia coli: Occurrence and Association with Toxin Types and Colonization Factors among Strains Isolated in Argentina  

PubMed Central

The longus type IV pilus structural gene (lngA) was sought among 217 clinical enterotoxigenic Escherichia coli (ETEC) strains isolated in Argentina. lngA was present in 20.7% of the isolates and was highly associated with ETEC producing heat-stable toxin and the most common colonization factors. The prevalence of longus among ETEC strains in Argentina was comparable to that of colonization factor antigen I (CFA/I), CFA/II, and CFA/IV in other regions of the world.

Pichel, Mariana G.; Binsztein, Norma; Qadri, Firdausi; Giron, Jorge A.



Factors associated with probability of personal digital assistant-based dietary self-monitoring in those with type 2 diabetes  

Microsoft Academic Search

Knowledge of factors associated with the use of technology could inform the design of technology-based behavioral interventions.\\u000a This study examined modifiable and nonmodifiable factors associated with technology-based self-monitoring. 123 participants\\u000a with type 2 diabetes self-monitored diet using a personal digital assistant in a 6-month behavioral intervention. Multinomial\\u000a logistic regression was used to examine probability of nonadherent and suboptimally adherent behavior

Mary Ann Sevick; Roslyn A. Stone; Susan Zickmund; Yuanyuan Wang; Mary Korytkowski; Lora E. Burke



Risk factors for coronary heart disease in type 1 diabetic patients in Europe : The EURODIAB Prospective Complications Study  

Microsoft Academic Search

OBJECTIVE—The goal of the study was to examine risk factors in the prediction of coronary heart disease (CHD) and differences in men and women in the EURODIAB Prospective Complications Study. RESEARCH DESIGN AND METHODS—Baseline risk factors and CHD at follow-up were assessed in 2,329 type 1 diabetic patients without prior CHD. CHD was defined as physician-diagnosed myocardial infarction, angina pectoris,

S. S. Soedamah-Muthu; N. Chaturvedi; M. Toeller; B. Ferriss; P. Reboldi; G. Michel; C. Manes; J. H. Fuller



Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type  

PubMed Central

Background: ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population. Methods: We used data from 2 Danish studies that followed members of the general public from 1977 through 2010. We obtained the genotype of 66 001 white participants for ABO blood type, factor V Leiden R506Q and prothrombin G20210A. We calculated hazard ratios (HRs) and population attributable risk. Our main outcome measures were venous thromboembolism and myocardial infarction. Results: The multivariable adjusted HR for venous thromboembolism was 1.4 (95% confidence interval [CI] 1.3–1.5) for non-O blood type (v. O blood type). For the factor V Leiden R506Q mutation, the adjusted HR was 2.2 (95% CI 2.0–2.5) for heterozygous participants and 7.0 (95%CI 4.8–10) for homozygous participants (v. participants without the mutation). For prothrombin G20210A, the adjusted HR was 1.5 (95%CI 1.2–1.9) for heterozygous participants and 11 (95% CI 2.8–44) for homozygous participants (v. participants without the mutation). When we combined ABO blood type and factor V Leiden R506Q or prothrombin G20210A genotype, there was a stepwise increase in the risk of venous thromboembolism (trend, p < 0.001). The population attributable risk of venous thromboembolism was 20% for ABO blood type, 10% for factor V Leiden R506Q and 1% for prothrombin G20210A. Multivariable adjusted HRs for myocardial infarction by genotypes did not differ from 1.0. Interpretation: ABO blood type had an additive effect on the risk of venous thromboembolism when combined with factor V Leiden R506Q and prothrombin G20210A mutations; blood type was the most important risk factor for venous thromboembolism in the general population.

Sode, Birgitte F.; Allin, Kristine H.; Dahl, Morten; Gyntelberg, Finn; Nordestgaard, B?rge G.



Assignment of human transforming growth factor-{beta} type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively  

SciTech Connect

Transforming growth factor-{Beta} (TGF-{beta}) is a multifunctional cytokine, known to modulate several tissue development and repair processes, including cell differentiation, cell cycle progression, cellular migration, adhesion, and extracellular matrix production. The TGF-{beta} receptors and cell surface binding proteins mediate the diverse effects of TGF-{beta}. An endothelial cell-specific TGF-{beta} binding protein, endoglin, is mutated in hereditary hemorrhagic telangiectasia type 1, an autosomal dominant disorder of vascular dysplasia. Mutations in other TGF-{beta} binding protein genes may also lead to disease. We have used PCR with a cell hybrid DNA panel, and fluorescence in situ chromosomal hybridization (FISH), to localize two other TGF-{beta} receptor genes. These are the TGF-{beta} type I and type II receptors (also known as ALK-5 and betaglycan, respectively). The corresponding gene loci are designated TGFBR1 and TGFBR3. 10 refs., 1 fig., 1 tab.

Johnson, D.W.; Qumsiyeh, M.; Marchuk, D.A. [Duke Univ., Durham, NC (United States); Benkhalifa, M. [Laboratoire Marcel Mercieux, Lyon (France)



Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis  

Microsoft Academic Search

Aims\\/hypothesis  Evidence strongly suggests that depression and type 2 diabetes are associated, but the direction of the association is still unclear. Depression may occur as a consequence of having diabetes, but may also be a risk factor for the onset of type 2 diabetes. This study examined the latter association by reviewing the literature and conducting a meta-analysis of longitudinal studies

M. J. Knol; J. W. R. Twisk; A. T. F. Beekman; R. J. Heine; F. J. Snoek; F. Pouwer



Load effects of Nola-type induction motor power-factor controllers on fuel-cell inverters  

SciTech Connect

This report covers tests performed on power inverters using Nola-type power factor controllers (PFC) and fractional horsepower single-phase induction motors as loading devices. The inverters were designed for integral operation with fuel cell power plants and represented four differential developmental designs ranging in power ratings from 1.5 kW to 5 kW. In addition, a 1000 VA commercial aircraft-type inverter was also tested. Results are presented and discussed.

Not Available



Improvement of lipid profile in Type 2 (non-insulin-dependent) diabetes mellitus by insulin-like growth factor I  

Microsoft Academic Search

Summary  Type 2 (non-insulin-dependent) diabetes mellitus is associated with increased glucose, insulin, total and VLDL-triglyceride, and often total and LDL-cholesterol levels which promote vascular disease. Recombinant human insulin-like growth factor-I which mimics many effects of insulin, decreased insulin, total and VLDL-triglyceride, and total and LDL-cholesterol levels in healthy man as well as glucose and insulin levels in Type 2 diabetic patients.

P. D. Zenobi; P. Holzmann; Y. Glatz; W. F. Riesen; E. R. Froesch



Evolution of ASABF ( Ascaris suum antibacterial factor)-type antimicrobial peptides in nematodes: Putative rearrangement of disulfide bonding patterns  

Microsoft Academic Search

ASABF (Ascaris suum antibacterial factor)-type antimicrobial peptides are defensin-like cysteine-rich peptides that are widely distributed in the phylum Nematoda. In known members of ASABF-type antimicrobial peptides, an array consisting of eight cysteine residues is completely conserved. In this study, we report a novel member ASABF-6Cys-?, which contains only six cysteine residues, in the pig round worm A. suum. The two

Masaomi Minaba; Satoshi Ueno; Ajitha Pillai; Yusuke Kato



A Comparison of Regression Prediction Accuracy on Several Types of Factor Scores.  

ERIC Educational Resources Information Center

Computer-based Monte Carlo methods compared the predictive accuracy upon replication of regression of five complete and four incomplete factor score estimation methods. Prediction on incomplete factor scores showed better double cross-validated prediction accuracy than on complete scores. The unique unit-weighted factor score was superior among…

Morris, John D.



Regulation of intestinal epithelial cell growth by transforming growth factor type. beta  

SciTech Connect

A nontransformed rat jejunal crypt cell line (IEC-6) expresses transforming growth factor type {beta}1 (TGF-{beta}1) mRNA, secretes latent {sup 125}I-labeled TGF-{beta}1 to specific, high-affinity cell surface receptors. IEC-6 cell growth is markedly inhibited by TGF-{beta}1 and TGF-{beta}2 with half-maximal inhibition occurring between 0.1 and 1.0 ng of TGF-{beta}1 per ml. TGF-{beta}1-mediated growth inhibition is not associated with the appearance of biochemical markers of enterocyte differentiation such as alkaline phosphatase expression and sucrase activity. TGF-{beta}1 increases steady-state levels of its own mRNA expression within 8 hr of treatment of rapidly growing IEC-6 cells. In freshly isolated rat jejunal enterocytes that are sequentially eluted from the crypt villus axis, TGF-{beta}1 mRNA expression is most abundant in terminally differentiated villus tip cells and least abundant in the less differentiated, mitotically active crypt cells. The authors conclude that TGF-{beta}1 is an autoregulated growth inhibitor in IEC-6 cells that potentially functions in an autocrine manner. In the rat jejunal epithelium, TGF-{beta}1 expression is most prominently localized to the villus tip--i.e., the region of the crypt villus unit that is characterized by the terminally differentiated phenotype. These data suggest that TGF-{beta}1 may function in coordination of the rapid cell turnover typical for the intestinal epithelium.

Barnard, J.A.; Beauchamp, R.D.; Coffey, R.J.; Moses, H.L. (Vanderbilt Univ. School of Medicine, Nashville, TN (USA))



Advanced glycation end products as environmental risk factors for the development of type 1 diabetes.  


The globally rising incidence of Type 1 diabetes (T1D) is no longer restricted to individuals with higher risk genotypes, but is now significantly increasing in a population with lower risk genotypes, likely as the result of environmental factors. In this review, we discuss the potential of advanced glycation end products (AGEs) as environmental contributors to the development of T1D. AGEs are nonenzymatically formed protein modifications found in the body, as well as, consumed in our daily diets. To date, many studies have provided evidence of AGE involvement in ? cell dysfunction, whether by AGE modification itself or via interaction with AGE receptors. The receptor for AGE (RAGE) and AGE-receptor-1 (AGE-R1) are of particular interest, given that studies have demonstrated the deleterious effects of RAGE modulation and the protection afforded by AGE-R1 in the context of diabetes. More interestingly, we have recently found that two RAGE polymorphism are predictive of T1D in humans while the third is protective. Moreover, soluble RAGE (sRAGE) levels (a circulating competitive inhibitor of RAGE) were greatly reduced at seroconversion to autoantibodies in both children on high risk of T1D background and in an animal model of autoiummune diabetes. Taken together with the fact that AGEs have also shown to be involved in immunomodulation, it is tempting to postulate that dietary AGEs, RAGE and even AGE-R1 could be working synergistically or independently to breach the tightly regulated immune system, providing a missing link in the development of T1D. PMID:22250649

Yap, Felicia Y T; Kantharidis, Phillip; Coughlan, Melinda T; Slattery, Robyn; Forbes, Josephine M



Orientation factor and number of fibers at failure plane in ring-type steel fiber reinforced concrete  

SciTech Connect

Considering the probabilistic distributions of fibers in ring-type steel fiber reinforced concrete, the orientation factor and the number of ring-type steel fibers crossing the failure plane were theoretically derived as a function of fiber geometry, specimen dimensions, and fiber volume fraction. A total number of 24 specimens were tested incorporating different fiber types, specimen geometry, and fiber volume fractions of 0.2% and 0.4%: 5 beams and 5 panels containing straight steel fibers; and 6 beams and 8 panels containing ring-type steel fibers. Measurements were made to assess the number of fibers at fractured surfaces of steel fiber reinforced concrete. The developed theoretical expressions reasonably predicted the orientation factor and the number of ring-type steel fibers at failure plane: the average and the standard deviation for the ratios of the test to theory were 1.03 and 0.26, respectively. Theoretical investigations and comparisons were made for the values of orientation factor and the number of fibers at failure plane for straight steel fibers and ring-type steel fibers.

Lee, C., E-mail: [School of Architecture and Building Science, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Kim, H. [School of Architecture and Building Science, Chung-Ang University, Seoul 156-756 (Korea, Republic of)



The barley ERF-type transcription factor HvRAF confers enhanced pathogen resistance and salt tolerance in Arabidopsis  

Microsoft Academic Search

We isolated HvRAF (Hordeum vulgare root abundant factor), a cDNA encoding a novel ethylene response factor (ERF)-type transcription factor, from young seedlings\\u000a of barley. In addition to the most highly conserved APETALA2\\/ERF DNA-binding domain, the encoded protein contained an N-terminal\\u000a MCGGAIL signature sequence, a putative nuclear localization sequence, and a C-terminal acidic transcription activation domain\\u000a containing a novel mammalian hemopexin

Jinwook Jung; So Youn Won; Seok Cheol Suh; HyeRan Kim; Rod Wing; Yeonhwa Jeong; Ingyu Hwang; Minkyun Kim



Physical factors influencing the blood glucose response to different breads in type II diabetic patients  

Microsoft Academic Search

Summary Blood glucose responses to test meals containing 75 g of different breads were compared in 103 type II diabetic patients under sulfonyl urea treatment. Nine breads differing in type of cereal, physical structure, and dietary fiber content were studied using pairwise intraindividual comparisons. It could be shown that the type of cereal and the fiber content had no significant

J. Arends; K. Ahrens; D. Liibke; B. Willms



Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes.  


New neurons and oligodendrocytes are continuously produced in the subventricular zone (SVZ) of adult mammalian brains. Under normal conditions, the SVZ primary precursors (type B1 cells) generate type C cells, most of which differentiate into neurons, with a small subpopulation giving rise to oligodendrocytes. Epidermal growth factor (EGF) signaling induces dramatic proliferation and migration of SVZ progenitors, a process that could have therapeutic applications. However, the fate of cells derived from adult neural stem cells after EGF stimulation remains unknown. Here, we specifically labeled SVZ B1 cells and followed their progeny after a 7-day intraventricular infusion of EGF. Cells derived from SVZ B1 cells invaded the parenchyma around the SVZ into the striatum, septum, corpus callosum, and fimbria-fornix. Most of these B1-derived cells gave rise to cells in the oligodendrocyte lineage, including local NG2+ progenitors, and pre-myelinating and myelinating oligodendrocytes. SVZ B1 cells also gave rise to a population of highly-branched S100beta+/glial fibrillary acidic protein (GFAP)+ cells in the striatum and septum, but no neuronal differentiation was observed. Interestingly, when demyelination was induced in the corpus callosum by a local injection of lysolecithin, an increased number of cells derived from SVZ B1 cells and stimulated to migrate and proliferate by EGF infusion differentiated into oligodendrocytes at the lesion site. This work indicates that EGF infusion can greatly expand the number of progenitors derived from the SVZ primary progenitors which migrate and differentiate into oligodendroglial cells. This expanded population could be used for the repair of white matter lesions. PMID:19544429

Gonzalez-Perez, Oscar; Romero-Rodriguez, Ricardo; Soriano-Navarro, Mario; Garcia-Verdugo, Jose Manuel; Alvarez-Buylla, Arturo



Two conserved regions within the tissue-type plasminogen activator gene promoter mediate regulation by brain-derived neurotrophic factor.  


Tissue-type plasminogen activator (t-PA) has recently been identified as a modulator of neuronal plasticity and can initiate conversion of the pro-form of brain-derived neurotrophic factor (BDNF) into its mature form. BDNF also increases t-PA gene expression implicating t-PA as a downstream effector of BDNF function. Here we demonstrate that BDNF-mediated induction of t-PA mRNA requires an increase in t-PA gene transcription. Reporter constructs harboring 9.5 kb of the human t-PA promoter conferred BDNF-responsiveness in transfected mouse primary cortical neurons. This regulation was recapitulated in HEK 293 cells coexpressing the TrkB neurotrophin receptor. t-PA promoter-deletion analysis revealed the presence of two BDNF-responsive domains, one located between -3.07 and -2.5 kb and the other within the proximal promoter. The upstream region was shown to confer BDNF responsiveness in a TrkB-dependent manner when attached to a heterologous promoter. We also identify homologous regions within the murine and bovine t-PA gene promoters and demonstrate that the equivalent upstream murine sequence functions as a BDNF-responsive enhancer when inserted 5' of the human proximal t-PA promoter. Hence, BDNF-mediated induction of t-PA transcription relies on conserved modular promoter elements including a novel upstream BDNF-responsive domain and the proximal t-PA gene promoter. PMID:17419735

Daniel, Philip B; Lux, Wolfram; Samson, Andre L; Schleuning, Wolf-Dieter; Niego, Be'eri; Weiss, Thomas W; Tjärnlund-Wolf, Anna; Medcalf, Robert L




NSDL National Science Digital Library

Test your factoring skills Factors and Multiples Jeopardy How much do you know about factoring and multiples? Play Jeopardy and find out! Prime Factoring Turkey Shoot Blast these turkeys using your factoring skills. Help the Professor Super save the planet by "cooking" the Giant Frozen Turkeys of Destruction. Math Lines 12 X-Factor Shoot the ball at the other factors to get a product of 12. You can also ...

Clark, Mr



Evaluating risk factors for endemic human Salmonella Enteritidis infections with different phage types in Ontario, Canada using multinomial logistic regression and a case-case study approach  

PubMed Central

Background Identifying risk factors for Salmonella Enteritidis (SE) infections in Ontario will assist public health authorities to design effective control and prevention programs to reduce the burden of SE infections. Our research objective was to identify risk factors for acquiring SE infections with various phage types (PT) in Ontario, Canada. We hypothesized that certain PTs (e.g., PT8 and PT13a) have specific risk factors for infection. Methods Our study included endemic SE cases with various PTs whose isolates were submitted to the Public Health Laboratory-Toronto from January 20th to August 12th, 2011. Cases were interviewed using a standardized questionnaire that included questions pertaining to demographics, travel history, clinical symptoms, contact with animals, and food exposures. A multinomial logistic regression method using the Generalized Linear Latent and Mixed Model procedure and a case-case study design were used to identify risk factors for acquiring SE infections with various PTs in Ontario, Canada. In the multinomial logistic regression model, the outcome variable had three categories representing human infections caused by SE PT8, PT13a, and all other SE PTs (i.e., non-PT8/non-PT13a) as a referent category to which the other two categories were compared. Results In the multivariable model, SE PT8 was positively associated with contact with dogs (OR=2.17, 95% CI 1.01-4.68) and negatively associated with pepper consumption (OR=0.35, 95% CI 0.13-0.94), after adjusting for age categories and gender, and using exposure periods and health regions as random effects to account for clustering. Conclusions Our study findings offer interesting hypotheses about the role of phage type-specific risk factors. Multinomial logistic regression analysis and the case-case study approach are novel methodologies to evaluate associations among SE infections with different PTs and various risk factors.



Common Variants of Hepatocyte Nuclear Factor 1? Are Associated With Type 2 Diabetes in a Chinese Population  

PubMed Central

OBJECTIVE Hepatocyte nuclear factor 1? (HNF1?) is a transcription factor that is critical for pancreatic cell formation and glucose homeostasis. Previous studies have reported that common variants of HNF1? were associated with type 2 diabetes in Caucasians and West Africans. However, analysis in the subjects from the Botnia study and Malmö Preventive Project produced conflicting results, and the role for HNF1? in type 2 diabetes susceptibility remains unclear. We therefore investigated common variants across the HNF1? gene in a Chinese population. RESEARCH DESIGN AND METHODS Fifteen tagging single nucleotide polymorphisms (SNPs) were analyzed for association with type 2 diabetes in subjects with type 2 diabetes (n = 1,859) and normal glucose regulation (n = 1,785). RESULTS Consistent with the initial study, we observed evidence that the risk G allele of rs4430796 in intron 2 was significantly associated with type 2 diabetes (odds ratio 1.16 [95% CI 1.05–1.29], P = 0.0035, empirical P = 0.0475). Furthermore, the at-risk G allele was associated with earlier age at diagnosis in the type 2 diabetic subjects (P = 0.0228). CONCLUSIONS The result of this study provides evidence that variants in the HNF1? region contribute to susceptibility to type 2 diabetes in the Chinese population.

Wang, Congrong; Hu, Cheng; Zhang, Rong; Bao, Yuqian; Ma, Xiaojing; Lu, Jingyi; Qin, Wen; Shao, Xinyu; Lu, Junxi; Xu, Jing; Lu, Huijuan; Xiang, Kunsan; Jia, Weiping



Cross-Sectional Versus Sequential Quality Indicators of Risk Factor Management in Patients with Type 2 Diabetes  

Microsoft Academic Search

Background: The fairness of quality assessment methods is under debate. Quality indicators incorporating the longitudinal nature of care have been advocated but their usefulness in comparison to more commonly used cross-sectional measures is not clear. Aims: To compare cross-sectional and sequential quality indicators for risk factor management in patients with type 2 diabetes. Methods: The study population consisted of 1912

Jaco Voorham; Petra Denig; Bruce H. R. Wolffenbuttel; Flora M. Haaijer-Ruskamp



Computer simulation of the correlation factors in vacancy-pair diffusion in mixed NaCl-type crystals  

Microsoft Academic Search

Monte Carlo computation of the correlation factors of ions and vacancies in a bound vacancy?pair mechanism has been extended to mixed NaCl-type crystals. Equations for the calculation of numerical values are proposed. The results make it possible to search for a vacancy-pair mechanism in mixed alkali halides and some oxide solid solutions.

R. Lindström



A synthetic peptide from transforming growth factor ? type III receptor inhibits liver fibrogenesis in rats with carbon tetrachloride liver injury  

Microsoft Academic Search

Transforming growth factor ?1 (TGF-?1) is a pleiotropic cytokine, which displays potent profibrogenic effects and is highly expressed in fibrotic livers. For this reason, development of TGF-?1 inhibitors might be of great importance to control liver fibrogenesis as well as other undesired side effects due to this cytokine. Potential peptide inhibitors of TGF-?1 (derived from TGF-?1 and from its type

Ignacio-José Ezquerro; Juan-José Lasarte; Javier Dotor; Inma Castilla-Cortázar; Matilde Bustos; Iván Peńuelas; Gemma Blanco; Carlos Rodr??guez; Mar??a del Carmen G. Lechuga; Patricia Greenwel; Marcos Rojkind; Jesús Prieto; Francisco Borrás-Cuesta



Tumour type and size are high risk factors for the syndrome of “cerebellar” mutism and subsequent dysarthria  

Microsoft Academic Search

OBJECTIVE“Cerebellar mutis” and subsequent dysarthria (MSD) is a documented complication of posterior fossa surgery in children. In this prospective study the following risk factors for MSD were assessed: type, size and site of the tumour; hydrocephalus at presentation and after surgery, cerebellar incision site, postoperative infection, and cerebellar swelling.METHODSIn a consecutive series of 42 children with a cerebellar tumour, speech

Coriene E Catsman-Berrevoets; Hugo R Van Dongen; Paul G H Mulder; Daniel Paz y Geuze; Philippe F Paquier; Maarten H Lequin



Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors  

ERIC Educational Resources Information Center

|Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40…

Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja