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Sample records for mouse atrophic thymus

  1. Clonally Expanding Thymocytes Having Lineage Capability in Gamma-Ray-Induced Mouse Atrophic Thymus

    SciTech Connect

    Yamamoto, Takashi; Morita, Shin-ichi; Go, Rieka; Obata, Miki; Katsuragi, Yoshinori; Fujita, Yukari; Maeda, Yoshitaka; Yokoyama, Minesuke; Aoyagi, Yutaka; Ichikawa, Hitoshi; Mishima, Yukio; Kominami, Ryo

    2010-05-01

    Purpose: To characterize, in the setting of gamma-ray-induced atrophic thymus, probable prelymphoma cells showing clonal growth and changes in signaling, including DNA damage checkpoint. Methods and Materials: A total of 111 and 45 mouse atrophic thymuses at 40 and 80 days, respectively, after gamma-irradiation were analyzed with polymerase chain reaction for D-J rearrangements at the TCRbeta locus, flow cytometry for cell cycle, and Western blotting for the activation of DNA damage checkpoints. Results: Limited D-J rearrangement patterns distinct from normal thymus were detected at high frequencies (43 of 111 for 40-day thymus and 21 of 45 for 80-day thymus). Those clonally expanded thymocytes mostly consisted of CD4{sup +}CD8{sup +} double-positive cells, indicating the retention of lineage capability. They exhibited pausing at a late G1 phase of cell cycle progression but did not show the activation of DNA damage checkpoints such as gammaH2AX, Chk1/2, or p53. Of interest is that 17 of the 52 thymuses showing normal D-J rearrangement patterns at 40 days after irradiation showed allelic loss at the Bcl11b tumor suppressor locus, also indicating clonal expansion. Conclusion: The thymocytes of clonal growth detected resemble human chronic myeloid leukemia in possessing self-renewal and lineage capability, and therefore they can be a candidate of the lymphoma-initiating cells.

  2. Hedgehog Signalling in the Embryonic Mouse Thymus

    PubMed Central

    Saldaña, José Ignacio; Crompton, Tessa

    2016-01-01

    T cells develop in the thymus, which provides an essential environment for T cell fate specification, and for the differentiation of multipotent progenitor cells into major histocompatibility complex (MHC)-restricted, non-autoreactive T cells. Here we review the role of the Hedgehog signalling pathway in T cell development, thymic epithelial cell (TEC) development, and thymocyte–TEC cross-talk in the embryonic mouse thymus during the last week of gestation. PMID:27504268

  3. MicroRNA expression in the aging mouse thymus.

    PubMed

    Ye, Yaqiong; Li, Daotong; Ouyang, Dan; Deng, Li; Zhang, Yuan; Ma, Yongjiang; Li, Yugu

    2014-09-01

    MicroRNAs (miRNAs) have been implicated in the process of aging in many model organisms, such as Caenorhabditis elegans, and in many organs, such as the mouse lung and human epididymis. However, the role of miRNAs in the thymus tissues of the aging mouse remains unclear. To address this question, we investigated the miRNA expression profiles in the thymuses of 1-, 10- and 19-month-old mice using miRNA array and qRT-PCR assays. A total of 223 mouse miRNAs were screened, and the expression levels of those miRNAs exhibited gradual increases and decreases over the course of thymus aging. Fifty miRNAs in the 10-month-old thymus and 81 miRNAs in the 19-month-old thymus were defined as differentially expressed miRNAs (p<0.05) in comparison with their levels in the 1-month-old mouse, and approximately one-third of these miRNAs were grouped within 11 miRNA clusters. Each miRNA cluster contained 2 to 5 miRNA genes, and most of the cluster members displayed similar expression patterns, being either increased or decreased. In addition, Ingenuity Pathway Analysis (IPA) software and the IPA database were used to analyze the 12 miRNAs that exhibited significant expression changes, revealing that as many as 15 pathways may be involved. Thus, our current study determined the expression profiles of miRNAs in the mouse thymus during the process of aging. The results suggested that these miRNAs could become meaningful biomarkers for studying thymus aging and that the aging-related alternations in miRNA expression may be involved in the regulation of cell proliferation, apoptosis, development and carcinogenesis/tumorigenesis.

  4. Thymus

    MedlinePlus

    ... Cells, Tissues, & Membranes Cell Structure & Function Cell Structure Cell Function Body Tissues Epithelial Tissue Connective Tissue Muscle Tissue ... older adults it is quite small. The primary function of the thymus is ... called T-lymphocytes or T-cells. While in the thymus, the lymphocytes do not ...

  5. RNA synthesis in the thymus of the immunologically mature mouse

    PubMed Central

    Patt, D. J.; Cohen, E. P.

    1974-01-01

    RNA synthesis was investigated in the thymus glands of adult immunized mice. After the intraperitoneal injection of mice with sheep red blood cells (SRBC), the net synthesis of RNA in the gland increased. A small but consistent amount of the RNA synthesized was distinguished by RNA:DNA hybridizations from that found in the glands of mice not injected with antigen. The RNA formed after immunization did not appear by hybridization to be specific for different antigens since the species of RNA formed in the glands of mice injected with SRBC was indistinguishable from RNA formed in the thymuses of mice injected with chicken red blood cells. RNA synthesized in the thymus glands of mice pharmacologically `stressed' by the injections of hydrocortisone, however, was distinguishable from that formed in the glands of mice injected with antigen. PMID:4854183

  6. Alteration of T cell maturation and proliferation in the mouse thymus induced by serum factors from patients with ulcerative colitis.

    PubMed Central

    Watanabe, M; Aiso, S; Hibi, T; Watanabe, N; Iwao, Y; Yoshida, T; Asakura, H; Tsuru, S; Tsuchiya, M

    1987-01-01

    Recently it has been reported that patients with ulcerative colitis (UC) often have thymus abnormalities, although the precise mechanisms which induce those abnormalities remain unclear. We have examined the effect of serum fractions from patients with UC and other colonic diseases on mouse thymus to clarify the possible existence of factors which have thymus growth activity. These fractions were separated from sera of patients with UC by gel filtration and anion exchange high performance liquid chromatography. In mice given UC serum fractions; (i) remarkable increases in weight and total cell number of the thymus were observed from day 4 to day 9; (ii) a significant increase in the number of peanut agglutinin (PNA)+ thymus cells was demonstrated using flow cytometry on day 9; (iii) on quantitative analysis of surface antigens the percentage of Lyt-2+ thymus cells decreased and that of L3T4+ thymus cells increased remarkably on day 13; the number of bright Thy-1.2+ cells and of dull Lyt-1+ cells increased. In contrast, the serum fractions from patients with other colonic diseases and from normal persons caused little change in mouse thymus throughout the study. The results suggest that factors fractionated from the serum of patients with UC disturb intra-thymic T cell maturation and enhance the proliferation of thymus cells. PMID:3498579

  7. Ethanol extract of fermented soybean, Chungkookjang, inhibits the apoptosis of mouse spleen, and thymus cells.

    PubMed

    Kim, Han Bok; Lee, Hye Sung; Kim, Sook Jin; Yoo, Hyung Jae; Hwang, Jae Sung; Chen, Gang; Youn, Hyun Joo

    2007-06-01

    Apoptosis is a step of the cell cycle which is important in the regulation of immune cell populations. Chungkookjang is a Korean traditional fermented soybean containing microorganisms, enzymes, and bioactive compounds which was used in the treatment of mouse spleen as well as thymus cells (CH1-fermented soybean containing barley, wormwood, and sea tangle; CH2-fermented soybean) and was found to exhibit substantially reduced small DNA fragmentation. An MTT assay showed that the treatment of CH1 and CH2 into the mouse splenocytes and thymocytes sharply increased their survival. Moreover, a FACS analysis also showed that CH1 and CH2 are effective at suppressing the apoptosis of splenocytes and thymocytes. The fermented soybean isoflavone concentrations, which are implicated in lowering breast and prostate cancers, lowering the risk of cardiovascular diseases, and improving bone health, were determined using Capillary Electrophoresis-Electrochemical Detection (CE-ED). The amount of Daidzein in fermented soybean significantly increased by 44-fold dramatically, compared with those in unfermented soybean. In this study, we demonstrated that ethanol extracts of Chungkookjang promote the survival of the mouse spleen and thymus cells in culture by suppressing their apoptotic death. Future studies should investigate which genes are related to apoptosis of the immune cells.

  8. Inductive role of fibroblastic cell lines in development of the mouse thymus anlage in organ culture.

    PubMed

    Itoi, M; Amagai, T

    1998-01-10

    Previously, we have shown that embryonic day 12 thymus anlage cultured alone cannot develop into the mature organ but degenerates. In the present study, we investigated the cause of this insufficient organogenesis of embryonic day 12 thymus anlage in organ culture. We cocultured embryonic day 12 thymus anlages with various cell lines as pellets formed by centrifugation. In coculture with fibroblastic cell lines, but not with thymic epithelial cell lines, embryonic day 12 thymus anlages developed to support full T cell differentiation, and expressed mature stromal cell markers, Ia and Kb. By pellet culture of thymus anlages and fibroblastic cell lines transfected with a beta-galactosidase expression vector, we analyzed the distribution of added fibroblastic cells in pellets. The added fibroblastic cells constituted neither thymic capsule nor septa but disappeared after about 2 weeks in culture. Moreover, immunohistochemical studies indicated that added fibroblastic cells were adjacent to mesenchymal cells of thymus anlage. Our results strongly suggest that added fibroblastic cells support the development of the thymus anlage through interaction with its mesenchymal cells.

  9. Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse

    PubMed Central

    Chojnowski, Jena L.; Masuda, Kyoko; Trau, Heidi A.; Thomas, Kirk; Capecchi, Mario; Manley, Nancy R.

    2014-01-01

    Hoxa3 was the first Hox gene to be mutated by gene targeting in mice and is required for the development of multiple endoderm and neural crest cell (NCC)-derived structures in the pharyngeal region. Previous studies have shown that the Hoxa3 null mutant lacks third pharyngeal pouch derivatives, the thymus and parathyroids by E18.5, and organ-specific markers are absent or downregulated during initial organogenesis. Our current analysis of the Hoxa3 null mutant shows that organ-specific domains did undergo initial patterning, but the location and timing of key regional markers within the pouch, including Tbx1, Bmp4 and Fgf8, were altered. Expression of the parathyroid marker Gcm2 was initiated but was quickly downregulated and differentiation failed; by contrast, thymus markers were delayed but achieved normal levels, concurrent with complete loss through apoptosis. To determine the cell type-specific roles of Hoxa3 in third pharyngeal pouch development, we analyzed tissue-specific mutants using endoderm and/or NCC-specific Cre drivers. Simultaneous deletion with both drivers resulted in athymia at E18.5, similar to the null. By contrast, the individual tissue-specific Hoxa3 deletions resulted in small, ectopic thymi, although each had a unique phenotype. Hoxa3 was primarily required in NCCs for morphogenesis. In endoderm, Hoxa3 temporally regulated initiation of the thymus program and was required in a cell-autonomous manner for parathyroid differentiation. Furthermore, Hoxa3 was required for survival of third pharyngeal pouch-derived organs, but expression in either tissue was sufficient for this function. These data show that Hoxa3 has multiple complex and tissue-specific functions during patterning, differentiation and morphogenesis of the thymus and parathyroids. PMID:25249461

  10. Changes in mouse thymus and spleen after return from the STS-135 mission in space.

    PubMed

    Gridley, Daila S; Mao, Xiao Wen; Stodieck, Louis S; Ferguson, Virginia L; Bateman, Ted A; Moldovan, Maria; Cunningham, Christopher E; Jones, Tamako A; Slater, Jerry M; Pecaut, Michael J

    2013-01-01

    Our previous results with flight (FLT) mice showed abnormalities in thymuses and spleens that have potential to compromise immune defense mechanisms. In this study, the organs were further evaluated in C57BL/6 mice after Space Shuttle Atlantis returned from a 13-day mission. Thymuses and spleens were harvested from FLT mice and ground controls housed in similar animal enclosure modules (AEM). Organ and body mass, DNA fragmentation and expression of genes related to T cells and cancer were determined. Although significance was not obtained for thymus mass, DNA fragmentation was greater in the FLT group (P<0.01). Spleen mass alone and relative to body mass was significantly decreased in FLT mice (P<0.05). In FLT thymuses, 6/84 T cell-related genes were affected versus the AEM control group (P<0.05; up: IL10, Il18bp, Il18r1, Spp1; down: Ccl7, IL6); 15/84 cancer-related genes had altered expression (P<0.05; up: Casp8, FGFR2, Figf, Hgf, IGF1, Itga4, Ncam1, Pdgfa, Pik3r1, Serpinb2, Sykb; down: Cdc25a, E2F1, Mmp9, Myc). In the spleen, 8/84 cancer-related genes were affected in FLT mice compared to AEM controls (P<0.05; up: Cdkn2a; down: Birc5, Casp8, Ctnnb1, Map2k1, Mdm2, NFkB1, Pdgfa). Pathway analysis (apoptosis signaling and checkpoint regulation) was used to map relationships among the cancer-related genes. The results showed that a relatively short mission in space had a significant impact on both organs. The findings also indicate that immune system aberrations due to stressors associated with space travel should be included when estimating risk for pathologies such as cancer and infection and in designing appropriate countermeasures. Although this was the historic last flight of NASA's Space Shuttle Program, exploration of space will undoubtedly continue.

  11. Changes in mouse thymus and spleen after return from the STS-135 mission in space.

    PubMed

    Gridley, Daila S; Mao, Xiao Wen; Stodieck, Louis S; Ferguson, Virginia L; Bateman, Ted A; Moldovan, Maria; Cunningham, Christopher E; Jones, Tamako A; Slater, Jerry M; Pecaut, Michael J

    2013-01-01

    Our previous results with flight (FLT) mice showed abnormalities in thymuses and spleens that have potential to compromise immune defense mechanisms. In this study, the organs were further evaluated in C57BL/6 mice after Space Shuttle Atlantis returned from a 13-day mission. Thymuses and spleens were harvested from FLT mice and ground controls housed in similar animal enclosure modules (AEM). Organ and body mass, DNA fragmentation and expression of genes related to T cells and cancer were determined. Although significance was not obtained for thymus mass, DNA fragmentation was greater in the FLT group (P<0.01). Spleen mass alone and relative to body mass was significantly decreased in FLT mice (P<0.05). In FLT thymuses, 6/84 T cell-related genes were affected versus the AEM control group (P<0.05; up: IL10, Il18bp, Il18r1, Spp1; down: Ccl7, IL6); 15/84 cancer-related genes had altered expression (P<0.05; up: Casp8, FGFR2, Figf, Hgf, IGF1, Itga4, Ncam1, Pdgfa, Pik3r1, Serpinb2, Sykb; down: Cdc25a, E2F1, Mmp9, Myc). In the spleen, 8/84 cancer-related genes were affected in FLT mice compared to AEM controls (P<0.05; up: Cdkn2a; down: Birc5, Casp8, Ctnnb1, Map2k1, Mdm2, NFkB1, Pdgfa). Pathway analysis (apoptosis signaling and checkpoint regulation) was used to map relationships among the cancer-related genes. The results showed that a relatively short mission in space had a significant impact on both organs. The findings also indicate that immune system aberrations due to stressors associated with space travel should be included when estimating risk for pathologies such as cancer and infection and in designing appropriate countermeasures. Although this was the historic last flight of NASA's Space Shuttle Program, exploration of space will undoubtedly continue. PMID:24069384

  12. Changes in Mouse Thymus and Spleen after Return from the STS-135 Mission in Space

    PubMed Central

    Gridley, Daila S.; Mao, Xiao Wen; Stodieck, Louis S.; Ferguson, Virginia L.; Bateman, Ted A.; Moldovan, Maria; Cunningham, Christopher E.; Jones, Tamako A.; Slater, Jerry M.; Pecaut, Michael J.

    2013-01-01

    Our previous results with flight (FLT) mice showed abnormalities in thymuses and spleens that have potential to compromise immune defense mechanisms. In this study, the organs were further evaluated in C57BL/6 mice after Space Shuttle Atlantis returned from a 13-day mission. Thymuses and spleens were harvested from FLT mice and ground controls housed in similar animal enclosure modules (AEM). Organ and body mass, DNA fragmentation and expression of genes related to T cells and cancer were determined. Although significance was not obtained for thymus mass, DNA fragmentation was greater in the FLT group (P<0.01). Spleen mass alone and relative to body mass was significantly decreased in FLT mice (P<0.05). In FLT thymuses, 6/84 T cell-related genes were affected versus the AEM control group (P<0.05; up: IL10, Il18bp, Il18r1, Spp1; down: Ccl7, IL6); 15/84 cancer-related genes had altered expression (P<0.05; up: Casp8, FGFR2, Figf, Hgf, IGF1, Itga4, Ncam1, Pdgfa, Pik3r1, Serpinb2, Sykb; down: Cdc25a, E2F1, Mmp9, Myc). In the spleen, 8/84 cancer-related genes were affected in FLT mice compared to AEM controls (P<0.05; up: Cdkn2a; down: Birc5, Casp8, Ctnnb1, Map2k1, Mdm2, NFkB1, Pdgfa). Pathway analysis (apoptosis signaling and checkpoint regulation) was used to map relationships among the cancer–related genes. The results showed that a relatively short mission in space had a significant impact on both organs. The findings also indicate that immune system aberrations due to stressors associated with space travel should be included when estimating risk for pathologies such as cancer and infection and in designing appropriate countermeasures. Although this was the historic last flight of NASA’s Space Shuttle Program, exploration of space will undoubtedly continue. PMID:24069384

  13. Thymus Cancer

    MedlinePlus

    ... cell. These cells help protect you from infections. Cancer of the thymus is rare. You are more ... Sometimes there are no symptoms. Other times, thymus cancer can cause A cough that doesn't go ...

  14. Environmentally relevant concentrations of arsenite and monomethylarsonous acid inhibit IL-7/STAT5 cytokine signaling pathways in mouse CD3+CD4-CD8- double negative thymus cells.

    PubMed

    Xu, Huan; Lauer, Fredine T; Liu, Ke Jian; Hudson, Laurie G; Burchiel, Scott W

    2016-04-15

    Environmental arsenic exposure is a public health issue. Immunotoxicity induced by arsenic has been reported in humans and animal models. The purpose of this study was to evaluate mechanisms of As(+3) and MMA(+3) toxicity in mouse thymus cells. Because we know that MMA(+3) inhibits IL-7 signaling in mouse bone marrow pre-B cells, we studied the influence of As(+3) and MMA(+3) on T cell development in the thymus at the earliest stage of T cell development (CD4-CD8-, double negative, DN) which requires IL-7 dependent signaling. We found in a DN thymus cell line (D1) that a low concentration of MMA(+3) (50 nM) suppressed IL-7 dependent JAK1, 3 and STAT5 signaling. As(+3) suppressed STAT5 and JAK3 at higher concentrations (500 nM). Cell surface expression of the IL-7 receptor (CD127) was also suppressed by 50 nM MMA(+)3, but was increased by 500 NM As(+3), indicating possible differences in the mechanisms of action of these agents. A decrease in cyclin D1 protein expression was observed in D1 cells exposed to As(+3) at 500 nM and MMA(+3) starting at 50 nM, suggesting that arsenic at these environmentally-relevant doses suppresses early T cell development through the inhibition of IL-7 signaling pathway. PMID:26921788

  15. Environmentally relevant concentrations of arsenite and monomethylarsonous acid inhibit IL-7/STAT5 cytokine signaling pathways in mouse CD3+CD4-CD8- double negative thymus cells.

    PubMed

    Xu, Huan; Lauer, Fredine T; Liu, Ke Jian; Hudson, Laurie G; Burchiel, Scott W

    2016-04-15

    Environmental arsenic exposure is a public health issue. Immunotoxicity induced by arsenic has been reported in humans and animal models. The purpose of this study was to evaluate mechanisms of As(+3) and MMA(+3) toxicity in mouse thymus cells. Because we know that MMA(+3) inhibits IL-7 signaling in mouse bone marrow pre-B cells, we studied the influence of As(+3) and MMA(+3) on T cell development in the thymus at the earliest stage of T cell development (CD4-CD8-, double negative, DN) which requires IL-7 dependent signaling. We found in a DN thymus cell line (D1) that a low concentration of MMA(+3) (50 nM) suppressed IL-7 dependent JAK1, 3 and STAT5 signaling. As(+3) suppressed STAT5 and JAK3 at higher concentrations (500 nM). Cell surface expression of the IL-7 receptor (CD127) was also suppressed by 50 nM MMA(+)3, but was increased by 500 NM As(+3), indicating possible differences in the mechanisms of action of these agents. A decrease in cyclin D1 protein expression was observed in D1 cells exposed to As(+3) at 500 nM and MMA(+3) starting at 50 nM, suggesting that arsenic at these environmentally-relevant doses suppresses early T cell development through the inhibition of IL-7 signaling pathway.

  16. Atrophic Acne Scarring

    PubMed Central

    Graber, Emmy M.

    2015-01-01

    Background: Scarring is an unfortunate and frequent complication of acne, resulting in significant psychological distress for patients. Fortunately, numerous treatment options exist for acne scarring. Objectives: To extensively review the literature on treatment options for atrophic acne scarring. Materials and methods: A comprehensive literature search was conducted on the following topics: dermabrasion, subcision, punch techniques, chemical peels, tissue augmentation, and lasers. Results: The literature supports the use of various treatment modalities; superior results may be achieved when multiple modalities are combined for a multi-step approach to scarring. Conclusion: The safety and efficacy of various treatment devices for acne scarring is well established, but there is a paucity of split-face trials comparing modalities. PMID:25610524

  17. Thymus Gland Anatomy

    MedlinePlus

    ... historical Searches are case-insensitive Thymus Gland, Adult, Anatomy Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Thymus Gland, Adult, Anatomy Description: Anatomy of the thymus gland; drawing shows ...

  18. Rapid-high, syncytium-inducing isolates of human immunodeficiency virus type 1 induce cytopathicity in the human thymus of the SCID-hu mouse.

    PubMed Central

    Kaneshima, H; Su, L; Bonyhadi, M L; Connor, R I; Ho, D D; McCune, J M

    1994-01-01

    Clinical deterioration in human immunodeficiency virus type 1 (HIV-1) disease is associated with an increased viral burden in the peripheral blood and a loss of circulating CD4+ T cells. HIV-1 isolates obtained prior to this stage of disease often have a "slow-low," non-syncytium-inducing (NSI) phenotype, whereas those obtained afterwards are often characterized as "rapid-high" and syncytium inducing (SI). Paired NSI and SI isolates from two different patients were inoculated into the human thymus implants of SCID-hu mice. The two slow-low, NSI isolates replicated to minimal levels in the grafts and did not induce thymocyte depletion. In contrast, the two SI isolates from the same patients showed high levels of viral replication and induced a marked degree of thymocyte depletion, accompanied by evidence of programmed cell death. These observations reveal a correlation between the replicative and cytopathic patterns of HIV-1 isolates in vitro and in the SCID-hu mouse in vivo and provide direct evidence that the biological phenotype of HIV-1 switch may be a causal and not a derivative correlate of HIV-1 disease progression. PMID:7966610

  19. IGF-1 deficiency causes atrophic changes associated with upregulation of VGluT1 and downregulation of MEF2 transcription factors in the mouse cochlear nuclei.

    PubMed

    Fuentes-Santamaría, V; Alvarado, J C; Rodríguez-de la Rosa, L; Murillo-Cuesta, S; Contreras, J; Juiz, J M; Varela-Nieto, I

    2016-03-01

    Insulin-like growth factor 1 (IGF-1) is a neurotrophic protein that plays a crucial role in modulating neuronal function and synaptic plasticity in the adult brain. Mice lacking the Igf1 gene exhibit profound deafness and multiple anomalies in the inner ear and spiral ganglion. An issue that remains unknown is whether, in addition to these peripheral abnormalities, IGF-1 deficiency also results in structural changes along the central auditory pathway that may contribute to an imbalance between excitation and inhibition, which might be reflected in abnormal auditory brainstem responses (ABR). To assess such a possibility, we evaluated the morphological and physiological alterations in the cochlear nucleus complex of the adult mouse. The expression and distribution of the vesicular glutamate transporter 1 (VGluT1) and the vesicular inhibitory transporter (VGAT), which were used as specific markers for labeling excitatory and inhibitory terminals, and the involvement of the activity-dependent myocyte enhancer factor 2 (MEF2) transcription factors in regulating excitatory synapses were assessed in a 4-month-old mouse model of IGF-1 deficiency and neurosensorial deafness (Igf1 (-/-) homozygous null mice). The results demonstrate decreases in the cochlear nucleus area and cell size along with cell loss in the cochlear nuclei of the deficient mouse. Additionally, our results demonstrate that there is upregulation of VGluT1, but not VGAT, immunostaining and downregulation of MEF2 transcription factors together with increased wave II amplitude in the ABR recording. Our observations provide evidence of an abnormal neuronal cytoarchitecture in the cochlear nuclei of Igf1 (-/-) null mice and suggest that the increased efficacy of glutamatergic synapses might be mediated by MEF2 transcription factors.

  20. Expression of human cathepsin L or human cathepsin V in mouse thymus mediates positive selection of T helper cells in cathepsin L knock-out mice.

    PubMed

    Sevenich, Lisa; Hagemann, Sascha; Stoeckle, Christina; Tolosa, Eva; Peters, Christoph; Reinheckel, Thomas

    2010-11-01

    A genetic deficiency of the cysteine protease cathepsin L (Ctsl) in mice results in impaired positive selection of conventional CD4+ T helper cells as a result of an incomplete processing of the MHC class II associated invariant chain or incomplete proteolytic generation of positively selecting peptide ligands. The human genome encodes, in contrast to the mouse genome, for two cathepsin L proteases, namely cathepsin L (CTSL) and cathepsin V (CTSV; alternatively cathepsin L2). In the human thymic cortex, CTSV is the predominately expressed protease as compared to CTSL or other cysteine cathepsins. In order to analyze the functions of CTSL and CTSV in the positive selection of CD4+ T cells we employed Ctsl knock-out mice crossed either with transgenic mice expressing CTSL under the control of its genuine human promoter or with transgenic mice expressing CTSV under the control of the keratin 14 (K14) promoter, which drives expression to the cortical epithelium. Both human proteases are expressed in the thymus of the transgenic mice, and independent expression of both CTSL and CTSV rescues the reduced frequency of CD4+ T cells in Ctsl-deficient mice. Moreover, the expression of the human cathepsins does not change the number of CD4+CD25+Foxp3+ regulatory T cells, but the normalization of the frequency of conventional CD4+ T cell in the transgenic mice results in a rebalancing of conventional T cells and regulatory T cells. We conclude that the functional differences of CTSL and CTSV in vivo are not mainly determined by their inherent biochemical properties, but rather by their tissue specific expression pattern.

  1. Reconstituted Thymus Organ Culture.

    PubMed

    Deng, Zimu; Liu, Haifeng; Rui, Jinxiu; Liu, Xiaolong

    2016-01-01

    Reconstituted thymus organ culture is based on fetal thymus organ culture (FTOC). Purified thymocyte populations, from genetically modified mice or even from other species, are cultured in vitro with thymic lobes depleted of their endogenous thymocytes (by 2'-deoxyguanosine treatment) to form a new thymus. This potent and timesaving method is distinct from FTOC, which assesses development of unmodified thymic lobes, and reaggregate thymic organ culture, in which epithelial cells are separately purified before being aggregated with thymocytes.

  2. Organizing the thymus gland.

    PubMed

    Muñoz, Juan José; García-Ceca, Javier; Alfaro, David; Stimamiglio, Marco Augusto; Cejalvo, Teresa; Jiménez, Eva; Zapata, Agustín G

    2009-02-01

    Eph receptors and their ligands, ephrins, are molecules involved in the morphogenesis of numerous tissues, including the central nervous system in which they play a key role in determining cell positioning and tissue domains containing or excluding nerve fibers. Because common features have been suggested to occur in the microenvironmental organization of brain and thymus, a highly compartmentalized organ central for T cell differentiation, we examined the expression and possible role of Eph/ephrins in the biology of the thymus gland. We reviewed numerous in vivo and in vitro results that confirm a role for Eph and ephrins in the maturation of the thymic epithelial cell (TEC) network and T cell differentiation. Their possible involvement in different steps of early thymus organogenesis, including thymus primordium branching, lymphoid colonization, and thymocyte-TEC interactions, that determine the organization of a mature three-dimensional thymic epithelial network is also analyzed.

  3. Hemopoiesis in the Thymus

    PubMed Central

    Kendall, Marion D.

    1995-01-01

    The presence in the thymus of hemopoietic cells other than thymocytes has been known for many years, but the extent of the hemopoietic activity of the thymus and the possible functional implications have only recently begun to receive much attention. This review summarizes the literature in this field, especially in the light of current cytokine and thymic-factor knowledge, and includes clinical relevance where possible. PMID:8770555

  4. Evaluating evidence for atrophic scarring treatment modalities

    PubMed Central

    McGrouther, Duncan; Chakrabarty, Kaushik

    2014-01-01

    Summary Introduction Atrophic scars cause significant patient morbidity. Whilst there is evidence to guide treatment, there does not appear to be a systematic review to analyse the efficacy of treatment options. Objectives To retrieve all evidence relating to atrophic scar treatment and evaluate using the Clinical Evidence GRADE score in order to allow clinicians to make evidence-based treatment choices. Method Searches were performed in Medline, EMBASE, CINHL and Cochrane to identify all English studies published evaluating treatment of atrophic scars on adults excluding journal letters. Each study was allocated a GRADE score based on type of study, quality, dose response, consistency of results and significance of results. The end score allowed categorisation of evidence into high, moderate, low or very low quality. Results A total of 41 studies were retrieved from searches including randomised controlled trials, observational studies, retrospective analyses and case reports of which 7% were allocated a high-quality score, 10% a moderate score, 7% a low score and 75% a very low score. Treatment modalities included ablative laser therapy, non-ablative laser therapy, autologous fat transfer, dermabrasion, chemical peels, injectables, subcision, tretinoin iontophoresis and combination therapy. Conclusion There is a paucity of good-quality clinical evidence evaluating treatment modalities for atrophic scarring. Evidence supports efficacy of laser, surgery and peel therapy. Further biomolecular research is required to identify targeted treatment options and more randomised controlled trials would make the evidence base for atrophic scar treatment more robust. PMID:25352991

  5. Dynamics of thymus organogenesis and colonization in early human development

    PubMed Central

    Farley, Alison M.; Morris, Lucy X.; Vroegindeweij, Eric; Depreter, Marianne L. G.; Vaidya, Harsh; Stenhouse, Frances H.; Tomlinson, Simon R.; Anderson, Richard A.; Cupedo, Tom; Cornelissen, Jan J.; Blackburn, C. Clare

    2013-01-01

    The thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. Here we demonstrate, via spatial and temporal expression analyses, that the genetic mechanisms known to regulate mouse thymus organogenesis are conserved in humans. In addition, we provide molecular evidence that the human thymic epithelium derives solely from the third pharyngeal pouch, as in the mouse, in contrast to previous suggestions. Finally, we define the timing of onset of hematopoietic cell colonization and epithelial cell differentiation in the human thymic primordium, showing, unexpectedly, that the first colonizing hematopoietic cells are CD45+CD34int/-. Collectively, our data provide essential information for translation of principles established in the mouse to the human, and are of particular relevance to development of improved strategies for enhancing immune reconstitution in patients. PMID:23571219

  6. Effect of lithium salts on the microstructure of the thymus and on vitamin C content in some lymphatic organs, the liver and suprarenal glands in F1 mouse crosses (CBA x C57BL).

    PubMed

    Ficek, W; Lesniewska, J; Mrowca, D

    1993-01-01

    The administration of lithium chloride (LiCl) to mice by intraperitoneal injection caused involution in the thymus, both in the cortex and medulla. Lithium also considerably decreased vitamin C (ascorbic acid) content in all of the organs that were studied: thymus, lymph nodes, spleen, suprarenal glands, and liver.

  7. Microneedling Therapy for Atrophic Acne Scars

    PubMed Central

    Barakat, Manal; Awad, Sherif; Medhat, Walid; El-Fakahany, Hasan; Farag, Hanna

    2015-01-01

    Objective: Treatment of acne scarring is always a challenge. Microneedling therapy or percutaneous collagen induction is a new addition to the treatment modalities for such scars and has been reported to be simple and effective in atrophic acne scar treatment. The aim of this study is to evaluate the clinical effect and objectively quantify the histological changes of acne scarring in response to skin microneedling. Design: A prospective clinical study. Participants: Ten patients with different types of atrophic acne scars were subjected to three months of skin microneedling treatment (six sessions at two-week intervals). Measurements: Patients were photographed, and skin biopsies were obtained at baseline as well as one and three months from the start of treatment. Histometry for epidermal thickness and quantitative evaluation of total elastin; newly synthesized tropoelastin; collagen types I, III, and VII; and newly synthesized collagen were performed for all biopsies. Results: Compared to the baseline, patients’ evaluations revealed noticeable clinical improvement in atrophic post-acne scars in response to skin microneedling. There was a statistically significant increase (p<0.05) in the mean of collagen types I, III, and VII and newly synthesized collagen, while total elastin was significantly decreased (p<0.05) after the end of treatment. Conclusions: Multiple minimally invasive sessions of skin microneedling are an effective treatment for post-acne atrophic scars as it stimulates the repair processes with the advantage of being a relatively risk-free, in-office procedure with minimal patient recovery time. PMID:26203319

  8. Effective Treatments of Atrophic Acne Scars

    PubMed Central

    Zhou, Bingrong

    2015-01-01

    Atrophic scarring is often an unfortunate and permanent complication of acne vulgaris. It has high prevalence, significant impact on quality of life, and therapeutic challenge for dermatologists. The treatment of atrophic acne scars varies depending on the types of acne scars and the limitations of the treatment modalities in their ability to improve scars. Therefore, many options are available for the treatment of acne scarring, including chemical peeling, dermabrasion, laser treatment, punch techniques, fat transplantation, other tissue augmenting agents, needling, subcision, and combined therapy. Various modalities have been used to treat scars, but limited efficacy and problematic side effects have restricted their application. In order to optimally treat a patient’s scar, we need to consider which treatment offers the most satisfactory result. There are also promising procedures in the future, such as stem cell therapy. In this article, the authors review the different treatment options of atrophic acne scars. This may be useful for selecting the best therapeutic strategy, whether it be single or combined therapy, in the treatment of atrophic acne scars while reducing or avoiding the side effects and complications. PMID:26029333

  9. Plasma obestatin levels in men with chronic atrophic gastritis.

    PubMed

    Gao, Xin-Yuan; Kuang, Hong-Yu; Liu, Xiao-Min; Ma, Zhi-Bin; Nie, Hao-Jie; Guo, Hong

    2008-10-01

    Obestatin is a recently discovered active peptide isolated from the stomach. The purpose of the present study was to investigate the modification of plasma obestatin levels in men with chronic atrophic gastritis. Men older than 65 years undergoing upper gastrointestinal endoscopy were included. All patients with chronic atrophic gastritis underwent multiple biopsies. Fasting plasma obestatin and ghrelin levels were examined in 50 men with chronic atrophic gastritis and 50 healthy men. Plasma obestatin levels were significantly lower in patients with chronic atrophic gastritis than in healthy subjects. Plasma ghrelin levels and ghrelin to obestatin ratio was decreased in men with chronic atrophic gastritis. There was a significant relationship between atrophy and decreased obestatin. A negative correlation was found between circulating obestatin levels and body mass index (BMI) in healthy subjects, but not in patients with chronic atrophic gastritis. The data indicated that chronic atrophic gastritis influenced plasma obestatin levels as well as ghrelin to obestatin ratio in elderly men.

  10. Anatomy of the thymus gland.

    PubMed

    Safieddine, Najib; Keshavjee, Shaf

    2011-05-01

    In the case of the thymus gland, the most common indications for resection are myasthenia gravis or thymoma. The consistency and appearance of the thymus gland make it difficult at times to discern from mediastinal fatty tissues. Having a clear understanding of the anatomy and the relationship of the gland to adjacent structures is important.

  11. Atrophic rhinitis caused by Cedecea davisae with accompanying mucocele.

    PubMed

    Bayır, Ömer; Yıldırım, Gökçe Aksoy; Saylam, Güleser; Yüksel, Elvan; Özdek, Ali; Korkmaz, Mehmet Hakan

    2015-01-01

    Atrophic rhinitis is a chronic inflammatory disease characterized by progressive atrophy of nasal mucosa. Cedecea davisae, a rare pathogen, is a new member of Enterobacteriaceae family. In this article, we report a patient with atrophic rhinitis whose culture test revealed Cedecea davisae. The patient was operated due to accompanying posterior ethmoid mucocele. Levofloxacin and nasal irrigation were administered for two months. Significant improvement was observed in patient's complaints and nasal signs at postoperative sixth month. In conclusion, Cedecea davisae has been thought to cause atrophic rhinitis and mucocele in this patient. Patient recovered with simple treatment. These bacteria should be kept in mind as a causative agent for atrophic rhinitis.

  12. How to assess the severity of atrophic gastritis.

    PubMed

    Dai, Yan-Cheng; Tang, Zhi-Peng; Zhang, Ya-Li

    2011-04-01

    Atrophic gastritis, is the main consequence of long-standing Helicobacter pylori infection, and is linked to the development of gastric cancer. The severity of atrophic gastritis is related to the lifetime risk of gastric cancer development, especially in terms of its degree and extent of mucosal damage. Therefore, it is important for clinicians to assess the severity of atrophic gastritis, interfere with the disease progress, and reverse gastric mucosal atrophy. In the article, we demonstrated some methods (conventional endoscopy, modern endoscopic technology and noninvasive methods) that may help assess the severity of atrophic gastritis and select the reasonable treatment protocols.

  13. Pediatric atrophic rhinosinusitis: what can we do?

    PubMed

    Magalhães, Clara; Viana, Miguel; Alves, Valquíria; Nakamura, Roberto; Duarte, Delfim

    2015-05-01

    A 5-year-old female had history of chronic foul smelling nasal discharge. Rhinoscopy showed greenish crusts lining the nasal cavities and inferior turbinates were shriveled significantly. Nasal cavity cultures of crusts by swab revealed Klebsiella ozaenae making the diagnosis of primary atrophic rhinosinusitis. After several unsuccessful treatment, we have decided to try sulfamethoxazole-trimethoprim prophylaxis and 1 year later there was a complete clinical improvement. There are many medical therapies and surgical options described, but none of them showed effective at long term. We present antibiotic prophylaxis as a viable alternative for long term control of the disease. PMID:25799383

  14. An Atrophic Plaque with Arborizing Vessels

    PubMed Central

    Villarreal-Martinez, Alejandra; Chavez-Alvarez, Sonia; Herz-Ruelas, Maira; Miranda-Maldonado, Ivette; Vázquez-Martinez, Osvaldo

    2016-01-01

    Dermatofibromas are a common finding in the daily clinical practice. Most lesions are found incidentally or because patients seek medical attention due to the aspect of the lesion. Rare variants of dermatofibroma such as aneurismatic or atrophic dermatofibroma can be encountered simultaneously; thus, these combined features may raise the possibility of other diagnoses to be considered. By providing diverse clinical and dermoscopic examples of dermatofibromas, we may prevent misdiagnosing these lesions. This case illustrates how two rare variants of dermatofibroma can coexist. Clinical presentation of dermatofibromas may vary greatly, and it is essential for dermatologists to recognize them clinically and dermoscopically before obtaining histopathological diagnosis. PMID:27790113

  15. Overdenture locator attachments for atrophic mandible

    PubMed Central

    Mahajan, Neerja; Thakkur, Rahul K

    2013-01-01

    Implant-supported overdentures provide a good opportunity for dentists to improve oral health and quality-of-life of patients. Atrophic mandible poses a significant challenge to successful oral rehabilitation with dental implants. In this article, the fabrication of lower overdenture by two narrow platform implants is described with dual retentive, resilient, self-locating locator attachment system. The locator attachment system has the lowest profile in comparison with the ball and bar attachments and is versatile up to 40° of divergence between two implants. By using locators as attachments, we can meet functional, economic and social expectation of patients with ease and satisfaction. PMID:24403798

  16. Overdenture locator attachments for atrophic mandible.

    PubMed

    Mahajan, Neerja; Thakkur, Rahul K

    2013-10-01

    Implant-supported overdentures provide a good opportunity for dentists to improve oral health and quality-of-life of patients. Atrophic mandible poses a significant challenge to successful oral rehabilitation with dental implants. In this article, the fabrication of lower overdenture by two narrow platform implants is described with dual retentive, resilient, self-locating locator attachment system. The locator attachment system has the lowest profile in comparison with the ball and bar attachments and is versatile up to 40° of divergence between two implants. By using locators as attachments, we can meet functional, economic and social expectation of patients with ease and satisfaction.

  17. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors.

    PubMed

    Thiault, Nicolas; Darrigues, Julie; Adoue, Véronique; Gros, Marine; Binet, Bénédicte; Perals, Corine; Leobon, Bertrand; Fazilleau, Nicolas; Joffre, Olivier P; Robey, Ellen A; van Meerwijk, Joost P M; Romagnoli, Paola

    2015-06-01

    Most T lymphocytes, including regulatory T cells (Treg cells), differentiate in the thymus. The age-dependent involution of this organ leads to decreasing production of T cells. Here we found that the output of new Treg cells from the thymus decreased substantially more than that of conventional T cells. Peripheral mouse and human Treg cells recirculated back to the thymus, where they constituted a large proportion of the pool of Treg cells and displayed an activated and differentiated phenotype. In the thymus, the recirculating cells exerted their regulatory function by inhibiting interleukin 2 (IL-2)-dependent de novo differentiation of Treg cells. Thus, Treg cell development is controlled by a negative feedback loop in which mature progeny cells return to the thymus and restrain development of precursors of Treg cells.

  18. Management of the edentulous/atrophic mandibular fracture.

    PubMed

    Aziz, Shahid R; Najjar, Talib

    2009-03-01

    Edentulous or atrophic mandible fractures are rare and potentially problematic for the oral and maxillofacial surgeon. With the loss of teeth, atrophy of the alveolar bony apparatus ensues, creating a mandible more prone to fracture. This article describes the management of edentulous/atrophic mandibular fractures.

  19. Atrophic gastritis is associated with coronary artery disease.

    PubMed

    Senmaru, Takafumi; Fukui, Michiaki; Tanaka, Muhei; Kuroda, Masaaki; Yamazaki, Masahiro; Oda, Yohei; Naito, Yuji; Hasegawa, Goji; Toda, Hitoshi; Yoshikawa, Toshikazu; Nakamura, Naoto

    2012-07-01

    Atrophic gastritis is characterized by chronic inflammation of gastric mucosa by Helicobacter pylori infection and other factors. Helicobacter pylori infection has been linked to coronary artery disease. To our knowledge, however, no reports are available on the relationship between atrophic gastritis and coronary artery disease. In this study, we investigated the relationship between atrophic gastritis, which is diagnosed based on serum pepsinogen levels (pepsinogen I ≤ 70 ng/mL and pepsinogen I/II ratio ≤ 3.0), and the prevalence of coronary artery disease in general Japanese population. Among 2,633 study subjects, 531 subjects (20.2%) were diagnosed as atrophic gastritis. The prevalence of coronary artery disease was higher in the atrophic gastritis-positive group than that in the atrophic gastritis-negative group (5.8% vs 2.8%, p = 0.0005). Multiple logistic regression analysis demonstrated that atrophic gastritis was independently associated with coronary artery disease (odds ratio, 1.67; 95% confidence interval, 1.03-2.72), after adjustment for age, sex, obesity, hypertension, diabetes mellitus, dyslipidemia, hyperuricemia, and habits of smoking and drinking. These results suggest that atrophic gastritis is an independent risk factor for coronary artery disease. Chronic inflammation of gastric mucosa may be associated with the prevalence of coronary artery disease.

  20. The Functions of the Thymus

    PubMed Central

    Osoba, David

    1966-01-01

    In rodents the thymus performs at least two functions. It is a major site of lymphopoiesis in the embryo and newborn, with the resulting lymphocytes migrating from the thymus to seed the spleen, lymph nodes and other lymphoid organs. In addition, the thymus produces a hormone which has an immunotrophic effect, i.e. it endows cells having immunological potential with immunological competence. In some animals other organs, in addition to the thymus, are responsible for directing the normal development of the immunological system. These are the bursa of Fabricius in birds and the appendix in rabbits. In humans it has been postulated that the tonsillar tissues may play an analogous role. Animal experiments involving extirpation of the immunotrophic lymphoid tissues have led to a better understanding of immunological deficiency diseases in man. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:5324977

  1. Ectopic TBX1 suppresses thymic epithelial cell differentiation and proliferation during thymus organogenesis.

    PubMed

    Reeh, Kaitlin A G; Cardenas, Kim T; Bain, Virginia E; Liu, Zhijie; Laurent, Micheline; Manley, Nancy R; Richie, Ellen R

    2014-08-01

    The thymus and parathyroid glands arise from a shared endodermal primordium in the third pharyngeal pouch (3rd pp). Thymus fate is specified in the ventral 3rd pp between E9.5 and E11, whereas parathyroid fate is specified in the dorsal domain. The molecular mechanisms that specify fate and regulate thymus and parathyroid development are not fully delineated. Previous reports suggested that Tbx1 is required for thymus organogenesis because loss of Tbx1 in individuals with DiGeorge syndrome and in experimental Tbx1 deletion mutants is associated with thymus aplasia or hypoplasia. However, the thymus phenotype is likely to be secondary to defects in pharyngeal pouch formation. Furthermore, the absence of Tbx1 expression in the thymus-fated domain of the wild-type 3rd pp suggested that Tbx1 is instead a negative regulator of thymus organogenesis. To test this hypothesis, we generated a novel mouse strain in which expression of a conditional Tbx1 allele was ectopically activated in the thymus-fated domain of the 3rd pp. Ectopic Tbx1 expression severely repressed expression of Foxn1, a transcription factor that marks the thymus-fated domain and is required for differentiation and proliferation of thymic epithelial cell (TEC) progenitors. By contrast, ectopic Tbx1 did not alter the expression pattern of Gcm2, a transcription factor restricted to the parathyroid-fated domain and required for parathyroid development. Ectopic Tbx1 expression impaired TEC proliferation and arrested TEC differentiation at an early progenitor stage. The results support the hypothesis that Tbx1 negatively regulates TEC growth and differentiation, and that extinction of Tbx1 expression in 3rd pp endoderm is a prerequisite for thymus organogenesis.

  2. Ectopic TBX1 suppresses thymic epithelial cell differentiation and proliferation during thymus organogenesis

    PubMed Central

    Reeh, Kaitlin A. G.; Cardenas, Kim T.; Bain, Virginia E.; Liu, Zhijie; Laurent, Micheline; Manley, Nancy R.; Richie, Ellen R.

    2014-01-01

    The thymus and parathyroid glands arise from a shared endodermal primordium in the third pharyngeal pouch (3rd pp). Thymus fate is specified in the ventral 3rd pp between E9.5 and E11, whereas parathyroid fate is specified in the dorsal domain. The molecular mechanisms that specify fate and regulate thymus and parathyroid development are not fully delineated. Previous reports suggested that Tbx1 is required for thymus organogenesis because loss of Tbx1 in individuals with DiGeorge syndrome and in experimental Tbx1 deletion mutants is associated with thymus aplasia or hypoplasia. However, the thymus phenotype is likely to be secondary to defects in pharyngeal pouch formation. Furthermore, the absence of Tbx1 expression in the thymus-fated domain of the wild-type 3rd pp suggested that Tbx1 is instead a negative regulator of thymus organogenesis. To test this hypothesis, we generated a novel mouse strain in which expression of a conditional Tbx1 allele was ectopically activated in the thymus-fated domain of the 3rd pp. Ectopic Tbx1 expression severely repressed expression of Foxn1, a transcription factor that marks the thymus-fated domain and is required for differentiation and proliferation of thymic epithelial cell (TEC) progenitors. By contrast, ectopic Tbx1 did not alter the expression pattern of Gcm2, a transcription factor restricted to the parathyroid-fated domain and required for parathyroid development. Ectopic Tbx1 expression impaired TEC proliferation and arrested TEC differentiation at an early progenitor stage. The results support the hypothesis that Tbx1 negatively regulates TEC growth and differentiation, and that extinction of Tbx1 expression in 3rd pp endoderm is a prerequisite for thymus organogenesis. PMID:25053428

  3. Characterization of thymus atrophy in calves with subclinical BVD challenged with BHV-1.

    PubMed

    Romero-Palomo, F; Risalde, M A; Molina, V; Lauzi, S; Bautista, M J; Gómez-Villamandos, J C

    2015-05-15

    Since the thymus is a target organ for the bovine viral diarrhea virus (BVDV), our experiment aimed to understand its relationship with the immunosuppressive effect by studying the consequences of a previous infection with BVDV on the thymus of calves challenged with bovine herpesvirus 1.1 (BHV-1). For this purpose, 12 animals were inoculated intranasally with non-cytopathic BVDV-1; 12 days later, 10 of them were coinfected intranasally with BHV-1. These animals were euthanized in batches of two at 0, 1, 2, 4, 7 or 14 dpi with BHV-1. Another 10 calves were inoculated solely with BHV-1 and euthanized in batches of two at 1, 2, 4, 7 or 14 dpi with BHV-1; two uninoculated calves were used as negative controls. Thymus samples from these animals were processed for viral detection and histopathological, immunohistochemical, and ultrastructural studies focused on BVDV/BHV-1 antigens, cortex:medulla ratio, apoptosis (TUNEL and caspase-3), collagen deposition, and factor VIII endothelial detection. Our study revealed the immunohistochemical presence of BVDV antigen in all animals in the BVDV-infected group, unlike BHV-1 detection, which was observed in animals in both infection groups only by molecular techniques. BVDV-preinfected animals showed severe atrophic changes associated with reduced cortex:medulla ratio, higher presence of cortical apoptosis, and increased collagen deposition and vascularization. However, calves solely infected with BHV-1 did not show atrophic changes. These findings could affect not only the numbers of circulating and local mature T cells but also the T cell-mediated immunity, which seems to be impaired during infections with this virus, thus favoring pathogenic effects during secondary infections.

  4. Atrophic Vaginitis in Breast Cancer Survivors: A Difficult Survivorship Issue

    PubMed Central

    Lester, Joanne; Pahouja, Gaurav; Andersen, Barbara; Lustberg, Maryam

    2015-01-01

    Management of breast cancer includes systematic therapies including chemotherapy and endocrine therapy can lead to a variety of symptoms that can impair the quality of life of many breast cancer survivors. Atrophic vaginitis, caused by decreased levels of circulating estrogen to urinary and vaginal receptors, is commonly experienced by this group. Chemotherapy induced ovarian failure and endocrine therapies including aromatase inhibitors and selective estrogen receptor modulators can trigger the onset of atrophic vaginitis or exacerbate existing symptoms. Symptoms of atrophic vaginitis include vaginal dryness, dyspareunia, and irritation of genital skin, pruritus, burning, vaginal discharge, and soreness. The diagnosis of atrophic vaginitis is confirmed through patient-reported symptoms and gynecological examination of external structures, introitus, and vaginal mucosa. Lifestyle modifications can be helpful but are usually insufficient to significantly improve symptoms. Non-hormonal vaginal therapies may provide additional relief by increasing vaginal moisture and fluid. Systemic estrogen therapy is contraindicated in breast cancer survivors. Continued investigations of various treatments for atrophic vaginitis are necessary. Local estrogen-based therapies, DHEA, testosterone, and pH-balanced gels continue to be evaluated in ongoing studies. Definitive results are needed pertaining to the safety of topical estrogens in breast cancer survivors. PMID:25815692

  5. EA-1, a novel adhesion molecule involved in the homing of progenitor T lymphocytes to the thymus

    PubMed Central

    1991-01-01

    The mouse progenitor T lymphocyte (pro-T) cell line FTF1 binds in vitro to thymus blood vessels, the thymic capsule, and liver from newborn mice. A mAb, EA-1, raised against an embryonic mouse endothelial cell line, blocked adhesion. The antibody also interfered with pro-T cell adhesion to a thymus-derived mouse endothelial cell line; it had no effect on the adhesion of mature T lymphocytes and myeloid cells. The antigen recognized by EA-1 is located on the vascular endothelium of various mouse tissues and absent on pro-T cells. EA-1 antibody precipitates molecules with apparent molecular weights of 110,000, 140,000, 160,000, and 200,000. Immunoclearing and binding-inhibition studies with antibodies against known adhesion molecules suggest that the EA-1 antigen is a novel adhesion molecule involved in colonization of the embryonic thymus by T cell progenitors. PMID:1874787

  6. Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts

    PubMed Central

    Fan, Yong; Tajima, Asako; Goh, Saik Kia; Geng, Xuehui; Gualtierotti, Giulio; Grupillo, Maria; Coppola, Antonina; Bertera, Suzanne; Rudert, William A; Banerjee, Ipsita; Bottino, Rita; Trucco, Massimo

    2015-01-01

    One of the major obstacles in organ transplantation is to establish immune tolerance of allografts. Although immunosuppressive drugs can prevent graft rejection to a certain degree, their efficacies are limited, transient, and associated with severe side effects. Induction of thymic central tolerance to allografts remains challenging, largely because of the difficulty of maintaining donor thymic epithelial cells in vitro to allow successful bioengineering. Here, the authors show that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties. When transplanted into athymic nude mice, the bioengineered thymus organoids effectively promoted homing of lymphocyte progenitors and supported thymopoiesis. Nude mice transplanted with thymus organoids promptly rejected skin allografts and were able to mount antigen-specific humoral responses against ovalbumin on immunization. Notably, tolerance to skin allografts was achieved by transplanting thymus organoids constructed with either thymic epithelial cells coexpressing both syngeneic and allogenic major histocompatibility complexes, or mixtures of donor and recipient thymic epithelial cells. Our results demonstrate the technical feasibility of restoring thymic function with bioengineered thymus organoids and highlight the clinical implications of this thymus reconstruction technique in organ transplantation and regenerative medicine. PMID:25903472

  7. Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts.

    PubMed

    Fan, Yong; Tajima, Asako; Goh, Saik Kia; Geng, Xuehui; Gualtierotti, Giulio; Grupillo, Maria; Coppola, Antonina; Bertera, Suzanne; Rudert, William A; Banerjee, Ipsita; Bottino, Rita; Trucco, Massimo

    2015-07-01

    One of the major obstacles in organ transplantation is to establish immune tolerance of allografts. Although immunosuppressive drugs can prevent graft rejection to a certain degree, their efficacies are limited, transient, and associated with severe side effects. Induction of thymic central tolerance to allografts remains challenging, largely because of the difficulty of maintaining donor thymic epithelial cells in vitro to allow successful bioengineering. Here, the authors show that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties. When transplanted into athymic nude mice, the bioengineered thymus organoids effectively promoted homing of lymphocyte progenitors and supported thymopoiesis. Nude mice transplanted with thymus organoids promptly rejected skin allografts and were able to mount antigen-specific humoral responses against ovalbumin on immunization. Notably, tolerance to skin allografts was achieved by transplanting thymus organoids constructed with either thymic epithelial cells coexpressing both syngeneic and allogenic major histocompatibility complexes, or mixtures of donor and recipient thymic epithelial cells. Our results demonstrate the technical feasibility of restoring thymic function with bioengineered thymus organoids and highlight the clinical implications of this thymus reconstruction technique in organ transplantation and regenerative medicine.

  8. The thymus of the hairless rhino-j (hr/hr-j) mice

    PubMed Central

    SAN JOSE, I.; GARCÍA-SUÁREZ, O.; HANNESTAD, J.; CABO, R.; GAUNA, L.; REPRESA, J.; VEGA, J. A.

    2001-01-01

    The hairless (hr) gene is expressed in a large number of tissues, primarily the skin, and a mutation in the hr gene is responsible for the typical cutaneous phenotype of hairless mice. Mutant hr mouse strains show immune defects involving especially T cells and macrophages, as well as an age-related immunodeficiency and an accelerated atrophy of the thymus. These data suggest that the hr mutation causes a defect of this organ, although hr transcripts have not been detected in fetal or adult mice thymus. The present study analyses the thymus of young (3 mo) and adult (9 mo) homozygous hr-rh-j mice (a strain of hairless mice) by means of structural techniques and immunohistochemistry to selectively identify thymic epithelial cells, dendritic cells, and macrophages. There were structural alterations in the thymus of both young and adult rh-rh-j mice, which were more severe in older animals. These alterations consisted of relative cortical atrophy, enlargement of blood vessels, proliferation of perivascular connective tissue, and the appearance of cysts. hr-rh-j mice also showed a decrease in the number of epithelial and dendritic cells, and macrophages. Taken together, present results strongly suggest degeneration and accelerated age-dependent regression of the thymus in hr-rh-j mice, which could explain at least in part the immune defects reported in hairless mouse strains. PMID:11327202

  9. Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage.

    PubMed

    Itoi, M; Kawamoto, H; Katsura, Y; Amagai, T

    2001-09-01

    Thymic epithelial cells, which create a three-dimensionally organized meshwork structure peculiar to the thymus, develop from simple epithelia of the third pharyngeal pouch and cleft during organogenesis. We comparatively investigated the thymus anlages of normal and nude mice by immunohistochemical analysis with regard to epithelial organization and distribution of hematopoietic progenitor cells at early stages of organogenesis. Our results show that development of the mouse thymus anlage at early stages can be subdivided into at least two stages by the differences in epithelial organization, i.e. stratified epithelial stage on embryonic day (Ed) 11 and clustered epithelial stage on Ed12. At the former stage, hematopoietic progenitor cells are accumulated in the mesenchymal layer of the thymus anlage, and at the latter stage progenitor cells enter the epithelial cluster and proliferate. In nude mice, hematopoietic progenitor cells are found in the mesenchymal layer on Ed11.5, but they are not observed among epithelial cells on Ed12, even though epithelial cells form a cluster structure. The present results suggest that aberrant development of the nude mouse thymus anlage occurs at the clustered epithelial stage and that epithelial cells of the nude anlage lack the ability to induce the entrance of hematopoietic progenitor cells into the epithelial cluster.

  10. The thymus and rheumatology: should we care?

    PubMed Central

    Cosway, Emilie; Anderson, Graham; Garside, Paul; Prendergast, Catriona

    2016-01-01

    Purpose of review The purpose of this review is to discuss the mechanisms of central and peripheral tolerance in relation to T-cell mediated autoimmunity in rheumatoid arthritis (RA). Recent findings The well established association between major histocompatibility complex class II and RA has led us to understand that T cells, and the adaptive immune response, are important in the pathogenesis of disease. In order for autoimmune disease to develop, there is a breach of tolerance to self antigen and the mechanisms of both central and peripheral tolerance aim to prevent this. Here, we review evidence from mouse models indicating that alterations in T-cell receptor signalling thresholds during thymic selection may be linked to the escape of T cells that mediate autoimmune arthritis. In addition, we summarize the role of dendritic cells and Foxp3+ regulatory T cells in both peripheral and thymic tolerance, and highlight their relevance to what we know about the aetiology of RA. Summary Mechanisms of central tolerance in the thymus and peripheral tolerance are in place to control autoreactive T cells and to prevent the development of autoimmune disease. We anticipate that a better understanding of these mechanisms will lead to the development of better, antigen-specific therapeutics to restore tolerance. PMID:26751840

  11. Pediatric non-Helicobacter pylori atrophic gastritis: a case series.

    PubMed

    Pogoriler, Jennifer; Kamin, Daniel; Goldsmith, Jeffrey D

    2015-06-01

    Although autoimmune atrophic gastritis is classically a disease of elderly adults, recent studies have described the disease in younger adults, particularly in those with other autoimmune diseases and iron-deficiency anemia. Atrophic gastritis in pediatrics is a rare and possibly underdiagnosed entity that has been primarily reported as single-case reports. This retrospective study of atrophic gastritis not associated with Helicobacter pylori infection was performed to further expand the knowledge of clinical presentation, pathologic findings, and natural history of this disease in the pediatric population. Twelve patients with a histologic diagnosis of atrophic gastritis were identified, with an age range of 8 months to 18 years. Seven had other autoimmune diseases and/or immunodeficiency. Atrophy was confined to the oxyntic mucosa in 10 patients, with intramucosal inflammation in a diffuse or basal-predominant pattern. Active inflammation was present in 7 patients. Pseudopyloric, intestinal, or squamous/mucinous metaplasia was seen at initial biopsy or on follow-up in 8 patients, and enterochromaffin-like cell hyperplasia was seen in 5. One patient developed an adenocarcinoma during the follow-up period of 10 years. Two false-negative diagnoses were retrospectively identified. In the majority of cases, the possibility of atrophic gastritis was not raised by the submitting physician, and the endoscopic findings were not specific. Therefore, accurate diagnosis requires a high degree of suspicion on the part of the pathologist, and the diagnosis should be considered particularly in patients with a clinical history of other autoimmune diseases or iron-deficiency anemia.

  12. Correlations Among Endoscopic, Histologic and Serologic Diagnoses for the Assessment of Atrophic Gastritis

    PubMed Central

    Lee, Ju Yup; Kim, Nayoung; Lee, Hye Seung; Oh, Jane C.; Kwon, Yong Hwan; Choi, Yoon Jin; Yoon, Ki Chul; Hwang, Jae Jin; Lee, Hyun Joo; Lee, AeRa; Jeong, Yeonsang; Jo, Hyun Jin; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Lee, Dong Ho

    2014-01-01

    Background: Atrophic gastritis is a precancerous condition, which can be diagnosed by several methods. However, there is no consensus for the standard method. The aim of this study was to evaluate the correlations among endoscopic, histologic, and serologic findings for the diagnosis of atrophic gastritis. Methods: From March 2003 to August 2013, a total of 2,558 subjects were enrolled. Endoscopic atrophic gastritis was graded by Kimura-Takemoto classification and histological atrophic gastritis was assessed by updated Sydney system. Serological assessment of atrophic gastritis was based on serum pepsinogen test. Results: The serum pepsinogen I/II ratio showed a significant decreasing nature when the extent of atrophy increased (R2=0.837, P<0.001) and the cut-off value for distinguishing between presence and absence of endoscopic atrophic gastritis was 3.2. The serum pepsinogen I and pepsinogen I/II ratio were significantly lower when the histological atrophic gastritis progressed and the cut-off value was 3.0 for a diagnosis of histological atrophic gastritis. A significant correlation between endoscopic and histological atrophic gastritis was noted and the sensitivity and specificity of endoscopic diagnosis were 65.9% and 58.0% for antrum, 71.3% and 53.7% for corpus, respectively. Conclusions: The endoscopic, histological, and serological atrophic gastritis showed relatively good correlations. However, as these three methods have a limitation, a multifactorial assessment might be needed to ameliorate the diagnostic accuracy of atrophic gastritis. PMID:25337572

  13. Insights into the mechanisms of thymus involution and regeneration by modeling the glucocorticoid-induced perturbation of thymocyte populations dynamics.

    PubMed

    Moleriu, Radu Dumitru; Zaharie, Daniela; Moatar-Moleriu, Lavinia Cristina; Gruia, Alexandra Teodora; Mic, Ani Aurora; Mic, Felix Aurel

    2014-05-01

    T-cells develop in the thymus and based on CD4 and CD8 expressions there are four main thymocyte populations in a normal mouse thymus. Currently, there are several mathematical models that describe the dynamics of thymocyte populations in a normal thymus, but only a few of them model the transient perturbation of their homeostasis. Our aim is to model the perturbation in the dynamics of each thymocyte population which is induced by the administration of a glucocorticoid, i.e. dexamethasone. The proposed approach relies on extending a four compartment thymus model based on differential equations by adding perturbation terms either globally (at the level of each equation) or locally (at the level of proliferation, death, and transfer rates). By fitting the perturbed model with experimental data on mice thymi collected before and after the administration of dexamethasone, it was possible to estimate the relevant parameters using a population-based stochastic search method. The fitted model is further used to conduct a quantitative analysis on the differentiated impact of dexamethasone on each T-cell population and on proliferation, death, and transfer processes. The obtained quantitative information on the perturbation could be used to explore and modify the flow of thymocytes between thymus compartments in order to elucidate the mechanisms of thymus involution and its subsequent regeneration. Since glucocorticoids are raised in many pathological situations, such a model could be useful in evaluating the impact of diseases on thymocyte dynamics in the thymus.

  14. Study of the role of cytosolic phospholipase A2 alpha in eicosanoid generation and thymocyte maturation in the thymus.

    PubMed

    Rousseau, Matthieu; Naika, Gajendra S; Perron, Jean; Jacques, Frederic; Gelb, Michael H; Boilard, Eric

    2015-01-01

    The thymus is a primary lymphoid organ, home of maturation and selection of thymocytes for generation of functional T-cells. Multiple factors are involved throughout the different stages of the maturation process to tightly regulate T-cell production. The metabolism of arachidonic acid by cyclooxygenases, lipoxygenases and specific isomerases generates eicosanoids, lipid mediators capable of triggering cellular responses. In this study, we determined the profile of expression of the eicosanoids present in the mouse thymus at different stages of thymocyte development. As the group IVA cytosolic phospholipase A2 (cPLA2α) catalyzes the hydrolysis of phospholipids, thereby generating arachidonic acid, we further verified its contribution by including cPLA2α deficient mice to our investigations. We found that a vast array of eicosanoids is expressed in the thymus, which expression is substantially modulated through thymocyte development. The cPLA2α was dispensable in the generation of most eicosanoids in the thymus and consistently, the ablation of the cPLA2α gene in mouse thymus and the culture of thymuses from human newborns in presence of the cPLA2α inhibitor pyrrophenone did not impact thymocyte maturation. This study provides information on the eicosanoid repertoire present during thymocyte development and suggests that thymocyte maturation can occur independently of cPLA2α.

  15. A case of cholecystohepatic duct with atrophic common hepatic duct

    PubMed Central

    Schofield, A; Hankins, J

    2003-01-01

    Background Cholecystohepatic ducts are rare congenital variants of the biliary tree. Case outline An 81-year-old woman presented with biliary colic and elevated liver function tests. An ERCP demonstrated a common bile duct stone and stricture of the common hepatic duct. An operative cholangiogram demonstrated an atrophic common hepatic duct and retrograde filling of the gallbladder through a large cholecystoheptic duct. The patient had a cholecystectomy and reconstructive cholecystohepatic duct jejunostomy. Discussion This case demonstrates a rare congenital anomaly where the gallbladder fills retrograde during an intraoperative cholangiogram despite clipping of the cystic duct. The major path of biliary drainage was through a large cholecystoheptic duct similar to a gallbladder interposition; however, the common hepatic duct was still present but atrophic. This anomaly has not been described previously. PMID:18332999

  16. Combination Therapy in the Management of Atrophic Acne Scars

    PubMed Central

    Garg, Shilpa; Baveja, Sukriti

    2014-01-01

    Background: Atrophic acne scars are difficult to treat. The demand for less invasive but highly effective treatment for scars is growing. Objective: To assess the efficacy of combination therapy using subcision, microneedling and 15% trichloroacetic acid (TCA) peel in the management of atrophic scars. Materials and Methods: Fifty patients with atrophic acne scars were graded using Goodman and Baron Qualitative grading. After subcision, dermaroller and 15% TCA peel were performed alternatively at 2-weeks interval for a total of 6 sessions of each. Grading of acne scar photographs was done pretreatment and 1 month after last procedure. Patients own evaluation of improvement was assessed. Results: Out of 16 patients with Grade 4 scars, 10 (62.5%) patients improved to Grade 2 and 6 (37.5%) patients improved to Grade 3 scars. Out of 22 patients with Grade 3 scars, 5 (22.7%) patients were left with no scars, 2 (9.1%) patients improved to Grade 1and 15 (68.2%) patients improved to Grade 2. All 11 (100%) patients with Grade 2 scars were left with no scars. There was high level of patient satisfaction. Conclusion: This combination has shown good results in treating not only Grade 2 but also severe Grade 4 and 3 scars. PMID:24761094

  17. X-linked recessive atrophic macular degeneration from RPGR mutation.

    PubMed

    Ayyagari, Radha; Demirci, F Yesim; Liu, Jiafan; Bingham, Eve L; Stringham, Heather; Kakuk, Laura E; Boehnke, Michael; Gorin, Michael B; Richards, Julia E; Sieving, Paul A

    2002-08-01

    We mapped a new X-linked recessive atrophic macular degeneration locus to Xp21.1-p11.4 and show allelic involvement of the gene RPGR, which normally causes severe peripheral retinal degeneration leading to global blindness. Ten affected males whom we examined had primarily macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. One additional male showed extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) showed normal cone and rod responses in some affected males despite advanced macular degeneration, emphasizing the dissociation of atrophic macular degeneration from generalized cone degenerations, including X-linked cone dystrophy (COD1). The RPGR gene nonsense mutation G-->T at open reading frame (ORF)15+1164 cosegregated with the disease and may create a donor splice site. Identification of an RPGR mutation in atrophic maculardegeneration expands the phenotypic range associated with this gene and provides a new tool for the dissection of the relationship between clinically different retinal pathologies.

  18. Hematopoietic progenitor migration to the adult thymus

    PubMed Central

    Zlotoff, Daniel A.; Bhandoola, Avinash

    2010-01-01

    While most hematopoietic lineages develop in the bone marrow (BM), T cells uniquely complete their development in the specialized environment of the thymus. Hematopoietic stem cells with long-term self-renewal capacity are not present in the thymus. As a result, continuous T cell development requires that BM-derived progenitors be imported into the thymus throughout adult life. The process of thymic homing begins with the mobilization of progenitors out of the bone marrow, continues with their circulation in the bloodstream, and concludes with their settling in the thymus. This review will discuss each of these steps as they occur in the unirradiated and post-irradiation scenarios, focusing on the molecular mechanisms of regulation. Improved knowledge about these early steps in T cell generation may accelerate the development of new therapeutic options in patients with impaired T cell number or function. PMID:21251013

  19. Local glucocorticoid production in the thymus.

    PubMed

    Talaber, Gergely; Jondal, Mikael; Okret, Sam

    2015-11-01

    Besides generating immunocompetent T lymphocytes, the thymus is an established site of de novo extra-adrenal glucocorticoid (GC) production. Among the compartments of the thymus, both stromal thymic epithelial cells (TECs) and thymocytes secrete biologically active GCs. Locally produced GCs secreted by the various thymic cellular compartments have been suggested to have different impact on thymic homeostasis. TEC-derived GCs may regulate thymocyte differentiation whereas thymocyte-derived GCs might regulate age-dependent involution. However the full biological significance of thymic-derived GCs is still not fully understood. In this review, we summarize and describe recent advances in the understanding of local GC production in the thymus and immunoregulatory steroid production by peripheral T cells and highlight the possible role of local GCs for thymus function.

  20. [Neuropeptides, Cytokines and Thymus Peptides as Effectors of Interactions Between Thymus and Neuroendocrine System].

    PubMed

    Torkhovskaya, T I; Belova, O V; Zimina, I V; Kryuchkova, A V; Moskvina, S N; Bystrova, O V; Arion, V Ya; Sergienko, V I

    2015-01-01

    The review presents data on mutual influence of nervous system and thymus, realized through the neuroendocrine-immune interactions. The pres- ence of adrenergic and peptidergic nerves in thymus creates conditions for implementation of the effect of neuropeptides secreted by them. These neuropeptides induce activation of thymus cells receptors and influence on the main processes in thymus, including T-lymphocyte maturation, cytokine and hormones production. In turn, thymuspeptides and/or cytokines, controlled by them, enter the brain and exert influence on neuro- nalfunction, which creates the basis for changes of behavior and homeostasis maintenance in response to infection. Ageing and some infectious, autoimmune, neurodegenerative and cancer diseases are accompanied by distortion of interactions between thymus and central nervous system. Mechanisms of signaling pathways, which determine these interactions, are not revealed yet, and their understanding will promote the development of effective therapeutic strategies.

  1. Chronic atrophic gastritis in association with hair mercury level.

    PubMed

    Xue, Zeyun; Xue, Huiping; Jiang, Jianlan; Lin, Bing; Zeng, Si; Huang, Xiaoyun; An, Jianfu

    2014-11-01

    The objective of this study was to explore hair mercury level in association with chronic atrophic gastritis, a precancerous stage of gastric cancer (GC), and thus provide a brand new angle of view on the timely intervention of precancerous stage of GC. We recruited 149 healthy volunteers as controls and 152 patients suffering from chronic gastritis as cases. The controls denied upper gastrointestinal discomforts, and the cases were diagnosed as chronic superficial gastritis (n=68) or chronic atrophic gastritis (n=84). We utilized Mercury Automated Analyzer (NIC MA-3000) to detect hair mercury level of both healthy controls and cases of chronic gastritis. The statistic of measurement data was expressed as mean ± standard deviation, which was analyzed using Levene variance equality test and t test. Pearson correlation analysis was employed to determine associated factors affecting hair mercury levels, and multiple stepwise regression analysis was performed to deduce regression equations. Statistical significance is considered if p value is less than 0.05. The overall hair mercury level was 0.908949 ± 0.8844490 ng/g [mean ± standard deviation (SD)] in gastritis cases and 0.460198 ± 0.2712187 ng/g (mean±SD) in healthy controls; the former level was significantly higher than the latter one (p=0.000<0.01). The hair mercury level in chronic atrophic gastritis subgroup was 1.155220 ± 0.9470246 ng/g (mean ± SD) and that in chronic superficial gastritis subgroup was 0.604732 ± 0.6942509 ng/g (mean ± SD); the former level was significantly higher than the latter level (p<0.01). The hair mercury level in chronic superficial gastritis cases was significantly higher than that in healthy controls (p<0.05). The hair mercury level in chronic atrophic gastritis cases was significantly higher than that in healthy controls (p<0.01). Stratified analysis indicated that the hair mercury level in healthy controls with eating seafood was significantly higher than that in healthy

  2. Chronic atrophic gastritis in association with hair mercury level.

    PubMed

    Xue, Zeyun; Xue, Huiping; Jiang, Jianlan; Lin, Bing; Zeng, Si; Huang, Xiaoyun; An, Jianfu

    2014-11-01

    The objective of this study was to explore hair mercury level in association with chronic atrophic gastritis, a precancerous stage of gastric cancer (GC), and thus provide a brand new angle of view on the timely intervention of precancerous stage of GC. We recruited 149 healthy volunteers as controls and 152 patients suffering from chronic gastritis as cases. The controls denied upper gastrointestinal discomforts, and the cases were diagnosed as chronic superficial gastritis (n=68) or chronic atrophic gastritis (n=84). We utilized Mercury Automated Analyzer (NIC MA-3000) to detect hair mercury level of both healthy controls and cases of chronic gastritis. The statistic of measurement data was expressed as mean ± standard deviation, which was analyzed using Levene variance equality test and t test. Pearson correlation analysis was employed to determine associated factors affecting hair mercury levels, and multiple stepwise regression analysis was performed to deduce regression equations. Statistical significance is considered if p value is less than 0.05. The overall hair mercury level was 0.908949 ± 0.8844490 ng/g [mean ± standard deviation (SD)] in gastritis cases and 0.460198 ± 0.2712187 ng/g (mean±SD) in healthy controls; the former level was significantly higher than the latter one (p=0.000<0.01). The hair mercury level in chronic atrophic gastritis subgroup was 1.155220 ± 0.9470246 ng/g (mean ± SD) and that in chronic superficial gastritis subgroup was 0.604732 ± 0.6942509 ng/g (mean ± SD); the former level was significantly higher than the latter level (p<0.01). The hair mercury level in chronic superficial gastritis cases was significantly higher than that in healthy controls (p<0.05). The hair mercury level in chronic atrophic gastritis cases was significantly higher than that in healthy controls (p<0.01). Stratified analysis indicated that the hair mercury level in healthy controls with eating seafood was significantly higher than that in healthy

  3. Hollow dentures: treatment option for atrophic ridges. a clinical report.

    PubMed

    Caculo, Shweta Pandurang; Aras, Meena Ajay; Chitre, Vidya

    2013-04-01

    Severely atrophic ridges provide decreased retention, support, and stability and pose a clinical challenge to the success of complete denture prostheses. Extreme ridge resorption also increases the interridge distance. Restoration of the vertical dimension and esthetics thus demands increased height of the prosthesis and in turn leads to an increase in prosthesis weight. Reducing the weight of the denture enhances stability and retention and reduces further resorption of the jaw, thereby favoring the prognosis of the denture. This report describes the rehabilitation of an edentulous patient with resorbed maxillary and mandibular ridges and an increased interridge distance using simplified techniques of fabricating hollow dentures.

  4. A suggested mechanism for the pathogenesis of infectious atrophic rhinitis.

    PubMed

    Harris, D L; Switzer, W P; Harris, R A

    1971-10-01

    Boivin extracts of Bordetella bronchiseptica inhibited or uncoupled the energized processes of bovine heart and pig heart mitochondria. Energy-dependent accumulation of calcium phosphate by both types of mitochondria was markedly inhibited by the extracts. The thesis is advanced that Boivin extracts of B. bronchiseptica may contain the membrane-damaging component responsible for infectious atrophic rhinitis. The action of the extracts was decreased by heat but seemed rather insensitive to digestion by trypsin or extraction by lipid solvents. Attempts to resolve the active component from the extracts were unsuccessful.

  5. T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss.

    PubMed

    Furmanski, Anna L; O'Shaughnessy, Ryan F L; Saldana, Jose Ignacio; Blundell, Michael P; Thrasher, Adrian J; Sebire, Neil J; Davies, E Graham; Crompton, Tessa

    2013-05-01

    Here we present a mouse model for T-cell targeting of hair follicles, linking the pathogenesis of alopecia to that of depigmentation disorders. Clinically, thymus transplantation has been successfully used to treat T-cell immunodeficiency in congenital athymia, but is associated with autoimmunity. We established a mouse model of thymus transplantation by subcutaneously implanting human thymus tissue into athymic C57BL/6 nude mice. These xenografts supported mouse T-cell development. Surprisingly, we did not detect multiorgan autoimmune disease. However, in all transplanted mice, we noted a striking depigmentation and loss of hair follicles. Transfer of T cells from transplanted nudes to syngeneic black-coated RAG(-/-) recipients caused progressive, persistent coat-hair whitening, which preceded patchy hair loss in depigmented areas. Further transfer experiments revealed that these phenomena could be induced by CD4+ T cells alone. Immunofluorescent analysis suggested that Trp2+ melanocyte-lineage cells were decreased in depigmented hair follicles, and pathogenic T cells upregulated activation markers when exposed to C57BL/6 melanocytes in vitro, suggesting that these T cells are not tolerant to self-melanocyte antigens. Our data raise interesting questions about the mechanisms underlying tissue-specific tolerance to skin antigens. PMID:23303453

  6. T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss.

    PubMed

    Furmanski, Anna L; O'Shaughnessy, Ryan F L; Saldana, Jose Ignacio; Blundell, Michael P; Thrasher, Adrian J; Sebire, Neil J; Davies, E Graham; Crompton, Tessa

    2013-05-01

    Here we present a mouse model for T-cell targeting of hair follicles, linking the pathogenesis of alopecia to that of depigmentation disorders. Clinically, thymus transplantation has been successfully used to treat T-cell immunodeficiency in congenital athymia, but is associated with autoimmunity. We established a mouse model of thymus transplantation by subcutaneously implanting human thymus tissue into athymic C57BL/6 nude mice. These xenografts supported mouse T-cell development. Surprisingly, we did not detect multiorgan autoimmune disease. However, in all transplanted mice, we noted a striking depigmentation and loss of hair follicles. Transfer of T cells from transplanted nudes to syngeneic black-coated RAG(-/-) recipients caused progressive, persistent coat-hair whitening, which preceded patchy hair loss in depigmented areas. Further transfer experiments revealed that these phenomena could be induced by CD4+ T cells alone. Immunofluorescent analysis suggested that Trp2+ melanocyte-lineage cells were decreased in depigmented hair follicles, and pathogenic T cells upregulated activation markers when exposed to C57BL/6 melanocytes in vitro, suggesting that these T cells are not tolerant to self-melanocyte antigens. Our data raise interesting questions about the mechanisms underlying tissue-specific tolerance to skin antigens.

  7. ROLE OF THE THYMUS IN TOLERANCE

    PubMed Central

    Isaković, Katarina; Smith, Stanley B.; Waksman, Byron H.

    1965-01-01

    Rats thymectomized and irradiated as adults were restored to immunologic reactivity by grafts of normal adult rat thymus and bone marrow. Reactivity of the delayed (cellular) type and formation of mercaptoethanol-sensitive (MES) and mercaptoethanol-resistant (MER) antibody returned within 3 weeks, while Arthus reactivity remained subnormal till 9 weeks after irradiation and grafting. When the thymus donor was tolerant to BGG, the recipient showed specific non-reactivity to this antigen 3 weeks and, to a much lesser extent, 6 weeks after grafting. This non-reactivity affected delayed responses and MER antibody. No effect was noted on Arthus reactivity and a slight effect on MES antibody. Controls showed that the non-reactivity was not due to transfer of free antigen at the time of grafting. It was concluded that different source organs are responsible for different immune functions and that specific immunologic tolerance may be induced within such an organ as the thymus. PMID:4159035

  8. Angiogenic properties of adult human thymus fat.

    PubMed

    Salas, Julián; Montiel, Mercedes; Jiménez, Eugenio; Valenzuela, Miguel; Valderrama, José Francisco; Castillo, Rafael; González, Sergio; El Bekay, Rajaa

    2009-11-01

    The endogenous proangiogenic properties of adipose tissue are well recognized. Although the adult human thymus has long been known to degenerate into fat tissue, it has never been considered as a potential source of angiogenic factors. We have investigated the expression of diverse angiogenic factors, including vascular endothelial growth factor A and B, angiopoietin 1, and tyrosine-protein kinase receptor-2 (an angiopoietin receptor), and then analyzed their physiological role on endothelial cell migration and proliferation, two relevant events in angiogenesis. The detection of the gene and protein expression of the various proteins has been performed by immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction. We show, for the first time, that adult thymus fat produces a variety of angiogenic factors and induces the proliferation and migration of human umbilical cord endothelial cells. Based on these findings, we suggest that this fat has a potential angiogenic function that might affect thymic function and ongoing adipogenesis within the thymus.

  9. [Chronic atrophic gastritis and the risk of cancer].

    PubMed

    Gabrielli, F; Nemeth, A

    1990-10-15

    Chronic gastritis, which is frequent in subjects over 50 years old, is caused by the concurrence of predisposing and congenital conditions and exogenous harmful factors, in particular foods. In etiopathogenetic terms it is worth considering autoimmune diseases and duodenogastric back-flow separately. Lesions develop progressively from superficial gastritis to atrophic gastritis and finally to gastric atrophy; they are frequently found together with intestinal metaplasia, formed by areas of the epithelium with the morphological and histochemical characteristics of intestinal mucosa, which are the expression of a modified regeneration of the gastric wall. It is acknowledged that chronic atrophic gastritis is a precancerous phenomenon which is the majority of cases leads to the onset of intestinal cancer, passing through the stages of chronic gastritis, metaplasia and dysplasia. Identification of this lesion may therefore help to prevent cancer: diagnosis is essentially performed using endoscopy (together with histocytological tests and bioptic staining) and laboratory tests (enzyme and CEA assays in the gastric juices). Rather than prescribing generic medical therapy or surgical treatment, which is only possible in selected cases of alkaline gastritis, attention is focused on curing unhealthy habits and on an endoscopic follow-up (every 2 years in cases of gastritis, and more frequently in cases of metaplasia or dysplasia).

  10. Autoimmune atrophic gastritis--pathogenesis, pathology and management.

    PubMed

    Neumann, William L; Coss, Elizabeth; Rugge, Massimo; Genta, Robert M

    2013-09-01

    Autoimmune gastritis is a chronic progressive inflammatory condition that results in the replacement of the parietal cell mass by atrophic and metaplastic mucosa. A complex interaction of autoantibodies against the parietal cell proton pump and sensitized T cells progressively destroy the parietal cells, inducing hypochlorhydria and then achlorhydria, while autoantibodies against the intrinsic factor impair the absorption of vitamin B₁₂. The resulting cobalamin deficiency manifests with megaloblastic anaemia and neurological and systemic signs and symptoms collectively known as pernicious anaemia. Previously believed to be predominantly a disease of elderly women of Northern European ancestry, autoimmune gastritis has now been recognized in all populations and ethnic groups, but because of the complexity of the diagnosis no reliable prevalence data are available. For similar reasons, as well as the frequent and often unknown overlap with Helicobacter pylori infection, the risk of gastric cancer has not been adequately assessed in these patients. This Review summarizes the epidemiology, pathogenesis and pathological aspects of autoimmune metaplastic atrophic gastritis. We also provide practical advice for the diagnosis and management of patients with this disease. PMID:23774773

  11. Multimodal management of atrophic acne scarring in the aging face.

    PubMed

    O'Daniel, T Gerald

    2011-12-01

    Atrophic facial acne scarring is a widely prevalent condition that can have a negative impact on a patient's quality of life. The appearance of these scars is often worsened by the normal effects of aging. A number of options are available for the treatment of acne scarring, including chemical peeling, dermabrasion, ablative or nonablative laser resurfacing, dermal fillers, and surgical techniques such as subcision or punch excision. Depending on the type and extent of scarring, a multimodal approach is generally necessary to provide satisfactory results. Resurfacing techniques correct surface irregularities, long-lasting dermal fillers address the volume loss resulting from acne, and sub-superficial musculoaponeurotic system (SMAS) face-lift procedures counter the soft tissue laxity and ptosis associated with aging. This article briefly reviews the evolution of individual approaches to treating atrophic acne scarring, followed by case examples illustrating results that can be achieved using a multimodal approach. Representative cases from patients in their 30s, 40s, and 50s are presented. In the author's clinical practice, multimodal approaches incorporating fractionated laser, injectable poly-L: -lactic acid, and sub-SMAS face-lift procedures have achieved optimal aesthetic outcomes, high patient satisfaction, and durability of aesthetic effect over time. PMID:21491169

  12. Autoimmune atrophic gastritis--pathogenesis, pathology and management.

    PubMed

    Neumann, William L; Coss, Elizabeth; Rugge, Massimo; Genta, Robert M

    2013-09-01

    Autoimmune gastritis is a chronic progressive inflammatory condition that results in the replacement of the parietal cell mass by atrophic and metaplastic mucosa. A complex interaction of autoantibodies against the parietal cell proton pump and sensitized T cells progressively destroy the parietal cells, inducing hypochlorhydria and then achlorhydria, while autoantibodies against the intrinsic factor impair the absorption of vitamin B₁₂. The resulting cobalamin deficiency manifests with megaloblastic anaemia and neurological and systemic signs and symptoms collectively known as pernicious anaemia. Previously believed to be predominantly a disease of elderly women of Northern European ancestry, autoimmune gastritis has now been recognized in all populations and ethnic groups, but because of the complexity of the diagnosis no reliable prevalence data are available. For similar reasons, as well as the frequent and often unknown overlap with Helicobacter pylori infection, the risk of gastric cancer has not been adequately assessed in these patients. This Review summarizes the epidemiology, pathogenesis and pathological aspects of autoimmune metaplastic atrophic gastritis. We also provide practical advice for the diagnosis and management of patients with this disease.

  13. What's New in Research and Treatment for Thymus Cancer?

    MedlinePlus

    ... Next Topic Additional resources for thymus cancer What’s new in research and treatment for thymus cancer? There ... treating thymomas is still being explored. In addition, new treatments are being developed and tested. Researchers are ...

  14. Native fluorescence spectroscopy of thymus and fat tissues

    NASA Astrophysics Data System (ADS)

    Tang, Gui C.; Oz, Mehmet C.; Reid, V.; Steinglass, K.; Ginsberg, Mark D.; Jacobowitz, Larry; Alfano, Robert R.

    1993-08-01

    Fluorescence spectroscopy of the human thymus gland and surrounding mediastinal fat were measured to evaluate this approach in distinguishing between thymus and fat tissues during therapeutic surgery for myasthenia gravis disease.

  15. A case of malignant atrophic papulosis with cranial nerve and peripheral nerve impairment*

    PubMed Central

    Liu, Fang; Liu, Haibo; Zhang, Min; Yan, Wenliang; Sang, Hong

    2015-01-01

    Malignant atrophic papulosisis is a rare, multisystem obliterative vasculopathy of unknown etiology, occasionally involving the cranial nerve. We describe the first case of malignant atrophic papulosisis with cranial nerve and peripheral nerve involvement in China. A 47-year-old woman presented to our hospital with atrophic porcelain white papules over the trunk and extremities, numbness in the right calf, vision decrease and impaired movement of the right eye. She was diagnosed with malignant atrophic papulosisis, based on characteristic symptoms and histopathologic examination. The patient was treated with dipyridamole and aspirin for 9 months, but later died of gastrointestinal hemorrhage. We reviewed currently available case reports on cranial nerve involvement in malignant atrophic papulosisis and emphasized the importance of skin biopsy in diagnosing this disease. PMID:26312664

  16. A case of malignant atrophic papulosis with cranial nerve and peripheral nerve impairment.

    PubMed

    Liu, Fang; Liu, Haibo; Zhang, Min; Yan, Wenliang; Sang, Hong

    2015-01-01

    Malignant atrophic papulosisis is a rare, multisystem obliterative vasculopathy of unknown etiology, occasionally involving the cranial nerve. We describe the first case of malignant atrophic papulosisis with cranial nerve and peripheral nerve involvement in China. A 47-year-old woman presented to our hospital with atrophic porcelain white papules over the trunk and extremities, numbness in the right calf, vision decrease and impaired movement of the right eye. She was diagnosed with malignant atrophic papulosisis, based on characteristic symptoms and histopathologic examination. The patient was treated with dipyridamole and aspirin for 9 months, but later died of gastrointestinal hemorrhage. We reviewed currently available case reports on cranial nerve involvement in malignant atrophic papulosisis and emphasized the importance of skin biopsy in diagnosing this disease. PMID:26312664

  17. FOXN1 in thymus organogenesis and development

    PubMed Central

    Vaidya, Harsh Jayesh; Briones Leon, Alberto

    2016-01-01

    Development of the primary T‐cell repertoire takes place in the thymus. The linked processes of T‐cell differentiation and T‐cell repertoire selection each depend on interactions between thymocytes and thymic stromal cells; in particular, with the epithelial cells of the cortical and medullary thymic compartments (cortical and medullary thymic epithelial cells; cTECs and mTECs, respectively). The importance of the thymic epithelial cell lineage in these processes was revealed in part through analysis of nude (nu/nu) mice, which are congenitally hairless and athymic. The nude phenotype results from null mutation of the forkhead transcription factor FOXN1, which has emerged as a pivotal regulator both of thymus development and homeostasis. FOXN1 has been shown to play critical roles in thymus development, function, maintenance, and even regeneration, which positions it as a master regulator of thymic epithelial cell (TEC) differentiation. In this review, we discuss current understanding of the regulation and functions of FOXN1 throughout thymus ontogeny, from the earliest stages of organogenesis through homeostasis to age‐related involution, contextualising its significance through reference to other members of the wider Forkhead family. PMID:27378598

  18. TrkAIII expression in the thymus.

    PubMed

    Tacconelli, Antonella; Farina, Antonietta R; Cappabianca, Lucia; Cea, Gesilia; Panella, Sonia; Chioda, Antonella; Gallo, Rita; Cinque, Benedetta; Sferra, Roberta; Vetuschi, Antonella; Campese, Antonio Francesco; Screpanti, Isabella; Gulino, Alberto; Mackay, Andrew R

    2007-02-01

    The alternative TrkAIII splice variant is expressed by murine and human thymus. Alternative TrkAIII splicing predominates in postembryonic day E13 (E17 and E18), postnatal murine (3 week and 3 month) and human thymuses, with TrkAIII mRNA expressed by selected thymocyte subsets and thymic epithelial cells (TECs) and a 100 kDa immunoprecipitable TrkAIII-like protein detected in purified thymocyte and whole thymus extracts. FACS and immunohistochemical analysis indicate a non-cell surface localisation for the TrkAIII-like protein in cortical CD4+/CD8+ double positive and, to a lesser extent, single positive thymocyte subsets at the cortex/medulla boundary and in Hassle's corpuscles, reticular epithelial and dendritic cells of the thymic medulla. TrkA(I/II) expression, on the other hand, predominates in sub-capsular regions of the thymus. TrkAIII-like immunoreactivity at the cortex/medulla boundary associates with regions of thymocyte proliferation and not apoptosis. A potential role for thymic hypoxia in thymocyte alternative TrkAIII splicing is supported by reversal to TrkAI splicing by normoxic but not hypoxic culture and induction of Jurkat T cell alternative TrkAIII splicing by the hypoxia mimic CoCl2. In contrast, TEC expression of TrkAIII predominates in both normoxic and hypoxic culture conditions. The data support a potential role for TrkAIII in thymic development and function, of particular relevance to intermediate stage CD4+/CD8+ thymocyte subsets and TECs, which potentially reflects a reversible thymocyte and more permanent TEC adaptation to thymic environment. Since intracellular TrkAIII neither binds nor responds to NGF and can impede regular NGF/TrkA signalling (Tacconelli et al., Cancer Cell, 2004), its expression would be expected to provide an alternative and/or impediment to regular NGF/TrkA signalling within the developing and developed thymus of potential functional importance.

  19. [Characteristics of the pineal gland and thymus relationship in aging].

    PubMed

    Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M; Trofimov, A V; Sevost'ianova, N N

    2011-01-01

    The review presents the interference between thymus and pineal gland during their involution. The research data of thymus peptides influence on pineal gland and pineal peptides on thymus are summarized. Analysis of these data showed that pineal peptides (Epithalamin, Epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (Thymalin, Thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

  20. STUDIES ON THE DIFFERENTIATION OF THYMUS-DERIVED LYMPHOCYTES

    PubMed Central

    Owen, J. J. T.; Raff, M. C.

    1970-01-01

    The development pathway from embryonic thymus-stem cell to peripheral thymus-derived lymphocyte has been demonstrated using the alloantigens θ (theta) and TL as surface markers of cell differentiation. On the basis of cytotoxicity tests carried out on CBA.H or A embryo thymus cultured in diffusion chambers and on CBA.H embryo thymus grafts and peripheral lymphocytes derived from them in AKR hosts, it has been concluded that two differentiation stages take place during the maturation of thymus-derived cells, namely a first step from stem cell to thymocyte and a second step from thymocyte to peripheral lymphocyte. PMID:5511571

  1. Egress of mature murine regulatory T cells from the thymus requires RelA.

    PubMed

    Fukazawa, Taro; Hiraiwa, Noriko; Umemura, Takeshi; Mise-Omata, Setsuko; Obata, Yuichi; Doi, Takahiro

    2015-04-01

    The mechanism of egress of mature regulatory T cells (Tregs) from the thymus to the periphery remains enigmatic, as does the nature of those factors expressed in the thymic environment. In this study, we examined the fate of thymic Tregs in TNF-α/RelA double-knockout (TA-KO) mice, because TA-KO mice retain a Treg population in the thymus but have only a small Treg population at the periphery. Transplantation of whole TA-KO thymus to under the kidney capsule of Rag1-null mice failed to induce the production of donor-derived splenic Tregs expressing neuropilin-1, which is reported to be a marker of naturally occurring Tregs, indicating that TA-KO thymic Tregs either do not leave the thymus or are lost at the periphery. We next transplanted enriched TA-KO thymic Tregs to the peripheries of TA-KO mice and traced mouse survival. Transplantation of TA-KO thymic Tregs rescued the lethality in TA-KO mice, demonstrating that TA-KO thymic Tregs remained functional at the periphery. The TA-KO thymic Treg population had highly demethylated CpG motifs in the foxp3 locus, indicating that the cells were arrested at a late mature stage. Also, the population included a large subpopulation of Tregs expressing IL-7Rα, which is a possible marker of late-stage mature Tregs. Finally, TA-KO fetal liver chimeric mice developed a neuropilin-1(+) splenic Treg population from TA-KO cells, suggesting that Treg arrest was caused by a lack of RelA in the thymic environment. Taken together, these results suggest that egress of mature Tregs from the thymus depends on RelA in the thymic environment. PMID:25725099

  2. Egress of mature murine regulatory T cells from the thymus requires RelA.

    PubMed

    Fukazawa, Taro; Hiraiwa, Noriko; Umemura, Takeshi; Mise-Omata, Setsuko; Obata, Yuichi; Doi, Takahiro

    2015-04-01

    The mechanism of egress of mature regulatory T cells (Tregs) from the thymus to the periphery remains enigmatic, as does the nature of those factors expressed in the thymic environment. In this study, we examined the fate of thymic Tregs in TNF-α/RelA double-knockout (TA-KO) mice, because TA-KO mice retain a Treg population in the thymus but have only a small Treg population at the periphery. Transplantation of whole TA-KO thymus to under the kidney capsule of Rag1-null mice failed to induce the production of donor-derived splenic Tregs expressing neuropilin-1, which is reported to be a marker of naturally occurring Tregs, indicating that TA-KO thymic Tregs either do not leave the thymus or are lost at the periphery. We next transplanted enriched TA-KO thymic Tregs to the peripheries of TA-KO mice and traced mouse survival. Transplantation of TA-KO thymic Tregs rescued the lethality in TA-KO mice, demonstrating that TA-KO thymic Tregs remained functional at the periphery. The TA-KO thymic Treg population had highly demethylated CpG motifs in the foxp3 locus, indicating that the cells were arrested at a late mature stage. Also, the population included a large subpopulation of Tregs expressing IL-7Rα, which is a possible marker of late-stage mature Tregs. Finally, TA-KO fetal liver chimeric mice developed a neuropilin-1(+) splenic Treg population from TA-KO cells, suggesting that Treg arrest was caused by a lack of RelA in the thymic environment. Taken together, these results suggest that egress of mature Tregs from the thymus depends on RelA in the thymic environment.

  3. Identification and characterization of thymus LIM protein: targeted disruption reduces thymus cellularity.

    PubMed

    Kirchner, J; Forbush, K A; Bevan, M J

    2001-12-01

    We have identified a novel LIM gene encoding the thymus LIM protein (TLP), expressed specifically in the thymus in a subset of cortical epithelial cells. TLP was identified as a gene product which is upregulated in a thymus in which selection of T cells is occurring (Rag(-/-) OT-1) compared to its expression in a thymus in which selection is blocked at the CD4+ CD8+ stage of T-cell development (Rag(-/-) Tap(-/-) OT-1). TLP has an apparent molecular mass of 23 kDa and exists as two isomers (TLP-A and TLP-B), which are generated by alternative splicing of the message. The sequences of TLP-A and TLP-B are identical except for the C-terminal 19 or 20 amino acids. Based on protein sequence alignment, TLP is most closely related to the cysteine-rich proteins, a subclass of the family of LIM-only proteins. In both medullary and cortical thymic epithelial cell lines transduced with TLP, the protein localizes to the cytoplasm but does not appear to be strongly associated with actin. In immunohistochemical studies, TLP seems to be localized in a subset of epithelial cells in the cortex and is most abundant near the corticomedullary junction. We generated mice with a targeted disruption of the Tlp locus. In the absence of TLP, thymocyte development and thymus architecture appear to be normal but thymocyte cellularity is reduced by approximately 30%, with a proportional reduction in each subpopulation.

  4. Thymus epithelium induces tissue-specific tolerance

    PubMed Central

    1993-01-01

    Most current models of T cell development include a positive selection step in the thymus that occurs when T cells interact with thymic epithelium and a negative selection step after encounters with bone marrow-derived cells. We show here that developing T cells are tolerized when they recognize antigens expressed by thymic epithelium, that the tolerance is tissue specific, and that it can occur by deletion of the reactive T cells. PMID:8459209

  5. The mystery of the thymus gland.

    PubMed

    Liu, Daniel; Ellis, Harold

    2016-09-01

    The thymus is the last organ in the human body to have its mechanisms fully understood, having had its function fully delineated more than 50 years ago (Miller , Tissue Antigens 63:509-517). Prior to this, the thymus gland has had an interesting history with theories having included a role in fetal growth and development before becoming more sinisterly, a cause of sudden infant death in the late 19th century known as status lymphaticus (Paltauf , Wien Klin Wochenschr 2:877-881). Until Miller (, Lancet 278:748-749) eventually proved its primarily immunological role, the history of this mysterious gland has closely mirrored the history of medicine itself, troubling the minds of pathologists such as Virchow (, Ueber die Chlorose und die damit zusammenhängenden Anomalien im Gefässapparate, insbesondere über "Endocarditis puerperalis," vorgetragen in der Sitzung der Berliner Geburtshülflichen Gesellschaft vom 12) and Grawitz (, Deut Med Wochenschr 22:429-431), surgeons such as Astley Cooper (, The Anatomy of the Thymus Gland) and Keynes (1953, Ann R Coll Surg 12:88), and eminent medical epidemiologists such as Greenwood and Woods [, J Hyg (Lond) 26:305-326]. This article will hopefully be of interest therefore to both clinician and historian alike. Clin. Anat. 29:679-684, 2016. © 2016 Wiley Periodicals, Inc. PMID:27037529

  6. [A Case of Infantile Cervical Ectopic Thymus].

    PubMed

    Umehara, Tsuyoshi; Hakamada, Katsura; Oshima, Goro; Suzuki, Katsuyoshi; Iwanaga, Ken; Yamaguchi, Yuki; Arai, Hiroyuki; Hikida, Yumiko; Kita, Junya; Hayashi, Yasuhiro

    2015-05-01

    We report herein on a case of ectopic cervical thymus in a 5-year-old boy and the literature is reviewed. Swelling of the right neck was seen in the patient in his newborn period and it was diagnosed as cystic disease of the neck in a previous hospital at 4 months of age. Ultrasonography (US) and MRI revealed a cervical tumor consisting of a solid component in our hospital, and histopathologic examination showed no evidence of malignancy. The lesion revealed almost no change in size but showed a mosaic pattern on US, whereon the parents agreed to the removal of the tumor. Intraoperatively, the tumor could be easily dissected from the surrounding tissue and resected. The pathological diagnosis was normal thymic tissue. The postoperative course was uneventful and no complication or immunological disorders were seen. A cervical ectopic thymus is a congenital lesion that results from abnormal thymic migration during embryogenesis. Most patients are asymptomatic and the condition is found incidentally. Preoperative diagnosis of cervical ectopic thymus in children is rarely made, so surgical treatment is the definitive means of pathological diagnosis. This disease should be listed in the differential diagnosis for neck masses in children, and should be suspected when the mosaic pattern is detected in the lesion on US.

  7. The mystery of the thymus gland.

    PubMed

    Liu, Daniel; Ellis, Harold

    2016-09-01

    The thymus is the last organ in the human body to have its mechanisms fully understood, having had its function fully delineated more than 50 years ago (Miller , Tissue Antigens 63:509-517). Prior to this, the thymus gland has had an interesting history with theories having included a role in fetal growth and development before becoming more sinisterly, a cause of sudden infant death in the late 19th century known as status lymphaticus (Paltauf , Wien Klin Wochenschr 2:877-881). Until Miller (, Lancet 278:748-749) eventually proved its primarily immunological role, the history of this mysterious gland has closely mirrored the history of medicine itself, troubling the minds of pathologists such as Virchow (, Ueber die Chlorose und die damit zusammenhängenden Anomalien im Gefässapparate, insbesondere über "Endocarditis puerperalis," vorgetragen in der Sitzung der Berliner Geburtshülflichen Gesellschaft vom 12) and Grawitz (, Deut Med Wochenschr 22:429-431), surgeons such as Astley Cooper (, The Anatomy of the Thymus Gland) and Keynes (1953, Ann R Coll Surg 12:88), and eminent medical epidemiologists such as Greenwood and Woods [, J Hyg (Lond) 26:305-326]. This article will hopefully be of interest therefore to both clinician and historian alike. Clin. Anat. 29:679-684, 2016. © 2016 Wiley Periodicals, Inc.

  8. Horizontal Ridge Augmentation with Piezoelectric Hinge-Assisted Ridge Split Technique in the Atrophic Posterior Mandible

    PubMed Central

    Cha, Min-Sang; Lee, Ji-Hye; Lee, Sang-Woon; Cho, Lee-Ra; Huh, Yoon-Hyuk; Lee, You-Sun

    2014-01-01

    Onlay bone grafting, guided bone regeneration, and alveolar ridge split technique are considered reliable bone augmentation methods on the horizontally atrophic alveolar ridge. Among these techniques, alveolar ridge split procedures are technique-sensitive and difficult to perform in the posterior mandible. This case report describes successful implant placement with the use of piezoelectric hinge-assisted ridge split technique in an atrophic posterior mandible. PMID:27489822

  9. [Defining groups of patients with atrophic gastritis for endoscopic mucosal resection using mathematical modeling].

    PubMed

    Blashentseva, S A; Tiumikov, D K; Savchenkov, N N

    2014-01-01

    The article is devoted to the problem of diagnostics of atrophic gastritis. The main principles of morphological diagnostics are presented. The endoscopic findings are discussed. The authors had used the mathematical regression model to reveal groups of patients with some specific signs of atrophic gastritis, such as endoscopic sings, morphological and clinical signs. This model can be used to put a diagnosis and to look after the patients with metaplasia, dysplasia and early cancer.

  10. Comparison of transperitoneal laparoscopic nephrectomy outcomes in atrophic and hydronephrotic kidneys

    PubMed Central

    Gülpınar, Murat Tolga; Akçay, Muzaffer; Sancak, Eyüp Burak; Akbaş, Alpaslan; Tepeler, Abdulkadir; Reşorlu, Berkan; Armağan, Abdullah

    2015-01-01

    Objective To compare the results of transperitoneal laparoscopic nephrectomy in patients with atrophic and hydronephrotic kidneys. Material and methods Clinical data were collected from 35 patients who had undergone laparoscopic nephrectomies for atrophic or hydronephrotic non-functioning kidneys between January 2010 and March 2014. Comparative analysis was carried out between the two groups examining demographic characteristics, imaging modalities, etiology, operative times, port numbers, conversion to open surgery, complications, pre-and post-operative hemoglobin and creatinine values, transfusion rates and length of hospital stays. Results Laparoscopic nephrectomy was performed for atrophic kidneys in 20 (57%) patients and for hydronephrotic kidneys in 15 (42%) patients. In the atrophic group, 3 patients (15%) required transfusion because of bleeding but none of the patients required conversion to open surgery. In the hydronephrotic group one patient (6.6%) required transfusion and conversion to open surgery because of bleeding. Both of the groups were similar in terms of postoperative hospital stay but compared to the atrophic kidneys, hydronephrotic ones were associated with a longer total operative times (90.1 min vs. 73.6 min, p=0.03). Any serious complication (except for bleeding) and mortality were not encountered in both groups. Conclusion Laparoscopic nephrectomy is a safe and effective minimally invasive technique that can be used in atrophic and hydronephrotic non-functioning kidneys. PMID:26623146

  11. Current therapeutic developments in atrophic age-related macular degeneration.

    PubMed

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age-Related Eye Disease Study (AREDS) formulation, which has been demonstrated to slow down the progression of dry AMD. This review summarises recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem cell-based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  12. Current Therapeutic Development for Atrophic Age-related Macular Degeneration

    PubMed Central

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age Related Eye Disease Study (AREDS) formulation which has been demonstrated to slow down the progression of dry AMD. This review summarizes recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem-cell based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  13. MAFbx/Atrogin-1 is required for atrophic remodeling of the unloaded heart

    PubMed Central

    Baskin, Kedryn K.; Rodriguez, Meredith R.; Kansara, Seema; Chen, Wenhao; Carranza, Sylvia; Frazier, O. Howard; Glass, David J.; Taegtmeyer, Heinrich

    2014-01-01

    Background Mechanical unloading of the failing human heart induces profound cardiac changes resulting in the reversal of a distorted structure and function. In this process, cardiomyocytes break down unneeded proteins and replace those with new ones. The specificity of protein degradation via the ubiquitin proteasome system is regulated by ubiquitin ligases. Over-expressing the ubiquitin ligase MAFbx/Atrogin-1 in the heart inhibits the development of cardiac hypertrophy, but the role of MAFbx/Atrogin-1 in the unloaded heart is not known. Methods and Results Mechanical unloading, by heterotopic transplantation, decreased heart weight and cardiomyocyte cross-sectional area in wild type mouse hearts. Unexpectedly, MAFbx/Atrogin-1−/− hearts hypertrophied after transplantation (n=8–10). Proteasome activity and markers of autophagy were increased to the same extent in WT and MAFbx/Atrogin-1−/− hearts after transplantation (unloading). Calcineurin, a regulator of cardiac hypertrophy, was only upregulated in MAFbx/Atrogin-1−/− transplanted hearts, while the mTOR pathway was similarly activated in unloaded WT and MAFbx/Atrogin-1−/− hearts. MAFbx/Atrogin-1−/− cardiomyocytes exhibited increased calcineurin protein expression, NFAT transcriptional activity, and protein synthesis rates, while inhibition of calcineurin normalized NFAT activity and protein synthesis. Lastly, mechanical unloading of failing human hearts with a left ventricular assist device (n=18) also increased MAFbx/Atrogin-1 protein levels and expression of NFAT regulated genes. Conclusions MAFbx/Atrogin-1 is required for atrophic remodeling of the heart. During unloading, MAFbx/Atrogin-1 represses calcineurin-induced cardiac hypertrophy. Therefore, MAFbx/Atrogin-1 not only regulates protein degradation, but also reduces protein synthesis, exerting a dual role in regulating cardiac mass. PMID:24650875

  14. Multicongenic fate mapping quantification of dynamics of thymus colonization.

    PubMed

    Ziętara, Natalia; Łyszkiewicz, Marcin; Puchałka, Jacek; Witzlau, Katrin; Reinhardt, Annika; Förster, Reinhold; Pabst, Oliver; Prinz, Immo; Krueger, Andreas

    2015-09-21

    Postnatal T cell development depends on continuous colonization of the thymus by BM-derived T lineage progenitors. Both quantitative parameters and the mechanisms of thymus seeding remain poorly understood. Here, we determined the number of dedicated thymus-seeding progenitor niches (TSPNs) capable of supporting productive T cell development, turnover rates of niche occupancy, and feedback mechanisms. To this end, we established multicongenic fate mapping combined with mathematical modeling to quantitate individual events of thymus colonization. We applied this method to study thymus colonization in CCR7(-/-)CCR9(-/-) (DKO) mice, whose TSPNs are largely unoccupied. We showed that ∼160-200 TSPNs are present in the adult thymus and, on average, 10 of these TSPNs were open for recolonization at steady state. Preconditioning of wild-type mice revealed a similar number of TSPNs, indicating that preconditioning can generate space efficiently for transplanted T cell progenitors. To identify potential cellular feedback loops restricting thymus colonization, we performed serial transfer experiments. These experiments indicated that thymus seeding was directly restricted by the duration of niche occupancy rather than long-range effects, thus challenging current paradigms of thymus colonization. PMID:26347471

  15. Multicongenic fate mapping quantification of dynamics of thymus colonization

    PubMed Central

    Łyszkiewicz, Marcin; Puchałka, Jacek; Witzlau, Katrin; Reinhardt, Annika; Förster, Reinhold; Pabst, Oliver; Prinz, Immo

    2015-01-01

    Postnatal T cell development depends on continuous colonization of the thymus by BM-derived T lineage progenitors. Both quantitative parameters and the mechanisms of thymus seeding remain poorly understood. Here, we determined the number of dedicated thymus-seeding progenitor niches (TSPNs) capable of supporting productive T cell development, turnover rates of niche occupancy, and feedback mechanisms. To this end, we established multicongenic fate mapping combined with mathematical modeling to quantitate individual events of thymus colonization. We applied this method to study thymus colonization in CCR7−/−CCR9−/− (DKO) mice, whose TSPNs are largely unoccupied. We showed that ∼160–200 TSPNs are present in the adult thymus and, on average, 10 of these TSPNs were open for recolonization at steady state. Preconditioning of wild-type mice revealed a similar number of TSPNs, indicating that preconditioning can generate space efficiently for transplanted T cell progenitors. To identify potential cellular feedback loops restricting thymus colonization, we performed serial transfer experiments. These experiments indicated that thymus seeding was directly restricted by the duration of niche occupancy rather than long-range effects, thus challenging current paradigms of thymus colonization. PMID:26347471

  16. Multicongenic fate mapping quantification of dynamics of thymus colonization.

    PubMed

    Ziętara, Natalia; Łyszkiewicz, Marcin; Puchałka, Jacek; Witzlau, Katrin; Reinhardt, Annika; Förster, Reinhold; Pabst, Oliver; Prinz, Immo; Krueger, Andreas

    2015-09-21

    Postnatal T cell development depends on continuous colonization of the thymus by BM-derived T lineage progenitors. Both quantitative parameters and the mechanisms of thymus seeding remain poorly understood. Here, we determined the number of dedicated thymus-seeding progenitor niches (TSPNs) capable of supporting productive T cell development, turnover rates of niche occupancy, and feedback mechanisms. To this end, we established multicongenic fate mapping combined with mathematical modeling to quantitate individual events of thymus colonization. We applied this method to study thymus colonization in CCR7(-/-)CCR9(-/-) (DKO) mice, whose TSPNs are largely unoccupied. We showed that ∼160-200 TSPNs are present in the adult thymus and, on average, 10 of these TSPNs were open for recolonization at steady state. Preconditioning of wild-type mice revealed a similar number of TSPNs, indicating that preconditioning can generate space efficiently for transplanted T cell progenitors. To identify potential cellular feedback loops restricting thymus colonization, we performed serial transfer experiments. These experiments indicated that thymus seeding was directly restricted by the duration of niche occupancy rather than long-range effects, thus challenging current paradigms of thymus colonization.

  17. Distinct ribonuclease H activities in calf thymus.

    PubMed

    Büsen, W; Hausen, P

    1975-03-01

    Three enzymes with ribonuclease H activity are present in calf thymus. They have been separated on the basis of chromatographic behaviour and molecular weight. They are further distinguished from one another by their ionic requirements and sensitivity to the -SH reagent N-ethylmaleimide. Two of these enzymes are classified as ribonuclease H, the third is obtained in a fraction which possesses ribonuclease H activity but also degrades double-stranded RNA and poly(rA). No association between any of the enzymes and cellular DNA polymerases could be demonstrated.

  18. Differential Proteomics of Helicobacter pylori Associated with Autoimmune Atrophic Gastritis

    PubMed Central

    Repetto, Ombretta; Zanussi, Stefania; Casarotto, Mariateresa; Canzonieri, Vincenzo; De Paoli, Paolo; Cannizzaro, Renato; De Re, Valli

    2014-01-01

    Atrophic autoimmune gastritis (AAG) is a condition of chronic inflammation and atrophy of stomach mucosa, for which development can be partially triggered by the bacterial pathogen Helicobacter pylori (HP). HP can cause a variety of gastric diseases, such as duodenal ulcer (DU) or gastric cancer (GC). In this study, a comparative proteomic approach was used by two-dimensional fluorescence difference gel electrophoresis (DIGE) to identify differentially expressed proteins of HP strains isolated from patients with AAG, to identify markers of HP strain associated with AAG. Proteome profiles of HP isolated from GC or DU were used as a reference to compare proteomic levels. Proteomics analyses revealed 27 differentially expressed spots in AAG-associated HP in comparison with GC, whereas only 9 differential spots were found in AAG-associated HP profiles compared with DU. Proteins were identified after matrix-assisted laser desorption ionization (MALDI)-TOF and peptide mass fingerprinting. Some AAG-HP differential proteins were common between DU- and GC-HP (peroxiredoxin, heat shock protein 70 [HSP70], adenosine 5′-triphosphate [ATP] synthase subunit α, flagellin A). Our results presented here may suggest that comparative proteomes of HP isolated from AAG and DU share more common protein expression than GC and provide subsets of putative AAG-specific upregulated or downregulated proteins that could be proposed as putative markers of AAG-associated HP. Other comparative studies by two-dimensional maps integrated with functional genomics of candidate proteins will undoubtedly contribute to better decipher the biology of AAG-associated HP strains. PMID:24395566

  19. Parasympathetic innervation of the thymus: a histochemical and immunocytochemical study.

    PubMed Central

    Fatani, J A; Qayyum, M A; Mehta, L; Singh, U

    1986-01-01

    The presence of parasympathetic nerve supply to the thymus has been demonstrated by histochemical and immunocytochemical methods using antibodies against cholineacetyl transferase. Fine nerve fibres have been observed both in the thymic parenchyma and around the blood vessels. The role of the parasympathetic nerve supply to the thymus is briefly discussed. Images Fig. 1 Fig. 2 Fig. 3 PMID:3319996

  20. Decision-making algorithm in treatment of the atrophic mandible fractures*

    PubMed Central

    DE FEUDIS, F.; DE BENEDITTIS, M.; ANTONICELLI, V.; VITTORE, P.; CORTELAZZI, R.

    2014-01-01

    Aim Closed treatment of atrophic mandible fractures often results in malunion, pseudoarthrosis and pain. Open reduction and rigid internal fixation (ORIF) is still indicated for displaced atrophic mandible fractures. The Authors report a treatment protocol that allows to gain the best results using reconstruction plates, autologous bone grafting and free fibula flap reconstruction when necessary. Methods Retrospective analysis of 15 patients with atrophic mandible fractures who underwent treatment between 2007 and 2011. 7 cases did not receive any treatment because of their general condition, while the others 8 were surgically managed by external approach. In all cases load-bearing osteosynthesis plates with locking screws were used; in 2 of them contextual bone grafts were performed; in 1 case mandible reconstruction needed harvesting a free fibula flap. Results In 6 out of 8 cases complete functional and morphological restoration were obtained without any major complication. In 1 case suppurative infection and necrosis of the bone graft occurred, which made necessary its removing, leaving in situ only the reconstruction plate. In another case, during the first year after surgical treatment, atrophic mandible resorption occurred from one angle to the other, resulting in loss of the anchoring reconstruction plate. Conclusions ORIF is the gold standard procedure for the of atrophic mandible fractures, because it guarantees best morpho-functional outcomes and predictability. Nevertheless the Authors suggest contextual bone grafting in case of substance loss, or a poor quality bone or for dental implant surgery and free fibula flap in selected cases. PMID:24841687

  1. A discrete population of IFN λ-expressing BDCA3hi dendritic cells is present in human thymus.

    PubMed

    Martínez, Víctor G; Canseco, Noelia M; Hidalgo, Laura; Valencia, Jaris; Entrena, Ana; Fernández-Sevilla, Lidia M; Hernández-López, Carmen; Sacedón, Rosa; Vicente, Angeles; Varas, Alberto

    2015-08-01

    Human thymus contains two major subpopulations of dendritic cells (DCs), conventional DCs (cDCs) and plasmacytoid DCs (pDCs), which are mainly involved in central tolerance and also in protecting the thymus against infections. In blood and peripheral organs cDCs include the subpopulation of BDCA3(hi) DCs, considered as equivalents to mouse CD8α(+) DCs. In this study we describe in human thymus the presence of a discrete population of BDCA3(hi) DCs that, like their peripheral counterparts, express CD13, low-intermediate levels of CD11c, CLEC9A, high levels of XCR1, IRF8 and TLR3, and mostly lack the expression of CD11b, CD14 and TLR7. Thymic BDCA3(hi) DCs display immature features with a low expression of costimulatory molecules and HLA-DR, and a low allostimulatory capacity. Also, BDCA3(hi) DCs exhibit a strong response to TLR3 stimulation, producing high levels of interferon (IFN)-λ1 and CXCL10, which indicates that, similarly to thymic pDCs, BDCA3(hi) DCs can have an important role in thymus protection against viral infections.

  2. Innervation of the rat thymus gland.

    PubMed

    Kendall, M D; al-Shawaf, A A

    1991-03-01

    Current views from different laboratories on the innervation of the thymus gland are reviewed with particular reference to the rat. Noradrenergic nerve profiles of the sympathetic nervous system have been demonstrated in the subcapsular cortex, at the corticomedullary junction and in the cortex itself, and extremely sparsely in the medulla. By following beta-adrenergic receptor development in postnatal rats, it has been shown that there is a marked increase in density and morphological organization of the receptor in the medulla with the maturation of thymocyte function (monitored by measuring the proliferation response to concanavalin A) and a sexual dimorphism during the ontogeny of the receptor. Chemical sympathectomy of adult rats with 6-hydroxydopamine (6-OHDA) or guanethidine resulted in a loss of thymus weight, decreased cellularity, and increased apoptosis but a rise in the numbers of proliferating cells in the cortex. By contrast, proliferation of peripheral T cells was reduced after the use of 6-OHDA. Chemical sympathectomy also demonstrated that there were at least three nerve nets in the gland: noradrenergic neural profiles that were destroyed with both 6-OHDA and guanethidine, vasoactive intestinal polypeptide (VIP)-positive profiles that persisted, and AChE- and CGRP-positive profiles and cells that also persisted but had a different distribution to VIP-positive fibers. Some functional correlates of thymic innervation are discussed although the subject now needs to be further researched.

  3. Thymus and adrenal glands in elder abuse.

    PubMed

    Hayashi, Takahito; Bunai, Yasuo; Ago, Kazutoshi; Ago, Mihoko; Ogata, Mamoru

    2011-12-01

    Endogenous glucocorticoid-induced thymic involution is generally considered to be an important finding for determining child abuse. The present study investigated the weight of the thymus and the adrenal glands in elder abuse cases to identify a potential marker for elder abuse. There was no significant difference in the thymus and the adrenal weight between elder abuse and control cases. However, the elder abuse cases in which the duration of abuse was less than 3 months showed a significant increase in the adrenal weight in comparison to control cases. In such cases, histopathological findings showed a loss of intracellular light granules from the zona fasciculata, which might indicate a loss of cholesterol due to the overproduction of glucocorticoid. These results might imply that the elderly, who were maltreated for less than 3 months, were in the early phase of a long-term stress state during which stress-induced overproduction of glucocorticoid was observed in adrenal glands as indicated by Selye. Our results suggest that an increase in adrenal weight may be a potential marker for elder abuse of relatively short periods, especially less than a few months.

  4. Thymus in experimental carcinogenesis of the prostate gland.

    PubMed

    Borodin, Yu I; Lomshakov, A A; Astashov, V V; Kazakov, O V; Mayorov, A P; Larionov, P M

    2014-10-01

    We studied structural changes in the prostate gland, thymus, and lymph nodes in CBA mice after transplantation of Ehrlich ascites tumor cells into the prostate gland. On experimental day 5, the number of blood and lymph vessels decreased in the gland; the percentage of connective tissue elements and glandular tissue and the number of immunoblasts in the thymus increased. On day 18, the number of blood vessels in the tumor decreased; the width of the cortex and glandular tissue increased in the thymus, while the number of immunoblasts was reduced. On day 28, tumor infiltration and increased number of lymphatic vessels in its stroma were observed; parenchyma was reduced, and the area of the connective tissue increased in the thymus. These structural changes indicated the development of accidental involution of the thymus during carcinogenesis of the prostate. PMID:25339587

  5. Thymus in experimental carcinogenesis of the prostate gland.

    PubMed

    Borodin, Yu I; Lomshakov, A A; Astashov, V V; Kazakov, O V; Mayorov, A P; Larionov, P M

    2014-10-01

    We studied structural changes in the prostate gland, thymus, and lymph nodes in CBA mice after transplantation of Ehrlich ascites tumor cells into the prostate gland. On experimental day 5, the number of blood and lymph vessels decreased in the gland; the percentage of connective tissue elements and glandular tissue and the number of immunoblasts in the thymus increased. On day 18, the number of blood vessels in the tumor decreased; the width of the cortex and glandular tissue increased in the thymus, while the number of immunoblasts was reduced. On day 28, tumor infiltration and increased number of lymphatic vessels in its stroma were observed; parenchyma was reduced, and the area of the connective tissue increased in the thymus. These structural changes indicated the development of accidental involution of the thymus during carcinogenesis of the prostate.

  6. Determination of whether screening tests for chronic atrophic gastritis really has a positive predictive value.

    PubMed

    Di Paola, Flaviano; D'Angelo, Valentina; Tatangelo, Fabiana; Barchiesi, Vittoria; Rizzo, Marianna; Cantile, Monica; Botti, Gerardo; Cavalcanti, Ernesta

    2015-09-01

    Intestinal‑type gastric adenocarcinomas are preceded by precancerous lesions, which begin with chronic atrophic gastritis. Over the last few years, multiple serological screening techniques have been performed and commercialized for the diagnosis of chronic atrophic gastritis. In the present study, 123 patients were recruited at the International Cancer Institute 'G. Pascale' Foundation (Naples, Italy) to test commercial kits for the serological determination of chronic atrophic gastritis, supported by histological analysis, according to the International Group of Gastroenterologists 'Operative Link for Gastritis Assessment Staging System'. The results revealed a significant discrepancy between serological screening and histological evaluation in 10.6% of patients, which highlighted the dubious positive predictive value of commercial serological screening kits.

  7. Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63

    PubMed Central

    von Grabowiecki, Yannick; Abreu, Paula; Blanchard, Orphee; Palamiuc, Lavinia; Benosman, Samir; Mériaux, Sophie; Devignot, Véronique; Gross, Isabelle; Mellitzer, Georg; Gonzalez de Aguilar, José L; Gaiddon, Christian

    2016-01-01

    Mechanisms of muscle atrophy are complex and their understanding might help finding therapeutic solutions for pathologies such as amyotrophic lateral sclerosis (ALS). We meta-analyzed transcriptomic experiments of muscles of ALS patients and mouse models, uncovering a p53 deregulation as common denominator. We then characterized the induction of several p53 family members (p53, p63, p73) and a correlation between the levels of p53 family target genes and the severity of muscle atrophy in ALS patients and mice. In particular, we observed increased p63 protein levels in the fibers of atrophic muscles via denervation-dependent and -independent mechanisms. At a functional level, we demonstrated that TAp63 and p53 transactivate the promoter and increased the expression of Trim63 (MuRF1), an effector of muscle atrophy. Altogether, these results suggest a novel function for p63 as a contributor to muscular atrophic processes via the regulation of multiple genes, including the muscle atrophy gene Trim63. DOI: http://dx.doi.org/10.7554/eLife.10528.001 PMID:26919175

  8. Phosphorylation of insulin receptor substrate-1 serine 307 correlates with JNK activity in atrophic skeletal muscle

    NASA Technical Reports Server (NTRS)

    Hilder, Thomas L.; Tou, Janet C L.; Grindeland, Richard E.; Wade, Charles E.; Graves, Lee M.

    2003-01-01

    c-Jun NH(2)-terminal kinase (JNK) has been shown to negatively regulate insulin signaling through serine phosphorylation of residue 307 within the insulin receptor substrate-1 (IRS-1) in adipose and liver tissue. Using a rat hindlimb suspension model for muscle disuse atrophy, we found that JNK activity was significantly elevated in atrophic soleus muscle and that IRS-1 was phosphorylated on Ser(307) prior to the degradation of the IRS-1 protein. Moreover, we observed a corresponding reduction in Akt activity, providing biochemical evidence for the development of insulin resistance in atrophic skeletal muscle.

  9. Antigen-binding thymus-derived lymphocytes

    PubMed Central

    Hogg, Nancy M.; Greaves, M. F.

    1972-01-01

    Thymus-derived `rosette'-forming lymphocytes which have been separated from other SRBC-sensitive cells by means of cotton wool columns were examined for the presence of immunoglobulin. This was carried out by inhibition of rosette formation by anti-immunoglobulin sera. Inhibition was effected by a number of anti-IgM sera shown to contain antibodies with specificities directed towards the `hinge' region of the μ chain. No other heavy chain specific antisera were inhibitory. The ratio of rosette inhibition by anti-κ and anti-λ light chain sera varied during the course of the response to SRBC, the latter inhibiting by 89 per cent 3 days post-immunization. PMID:4113387

  10. Early development of the thymus in Xenopus laevis

    PubMed Central

    Lee, Young-Hoon; Williams, Allison; Hong, Chang-Soo; You, Youngjae; Senoo, Makoto; Saint-Jeannet, Jean-Pierre

    2012-01-01

    Background Although Xenopus laevis has been a model of choice for comparative and developmental studies of the immune system, little is known about organogenesis of the thymus, a primary lymphoid organ in vertebrates. Here we examined the expression of three transcription factors that have been functionally associated with pharyngeal gland development, gcm2, hoxa3 and foxn1, and evaluated the neural crest contribution to thymus development. Results In most species Hoxa3 is expressed in the third pharyngeal pouch endoderm where it directs thymus formation. In Xenopus, the thymus primordium is derived from the second pharyngeal pouch endoderm, which is hoxa3-negative, suggesting that a different mechanism regulates thymus formation in frogs. Unlike other species foxn1 is not detected in the epithelium of the pharyngeal pouch in Xenopus, rather, its expression is initiated as thymic epithelial cell starts to differentiate and express MHC class II molecules. Using transplantation experiments we show that while neural crest cells populate the thymus primordia, they are not required for the specification and initial development of this organ or for T cell differentiation in frogs. Conclusions These studies provide novel information on early thymus development in Xenopus, and highlight a number of features that distinguish Xenopus from other organisms. PMID:23172757

  11. Thymus involution in the acquired immunodeficiency syndrome.

    PubMed

    Grody, W W; Fligiel, S; Naeim, F

    1985-07-01

    Acquired immunodeficiency syndrome (AIDS) is a severe disorder of unknown etiology and pathogenesis, predominantly affecting homosexual males and other high-risk groups and characterized by profound alterations in T-lymphocyte function. The authors have examined thymus tissue from 14 patients who died of AIDS and compared the results with findings in five control groups: healthy age-matched controls, elderly individuals, patients with chronic or debilitating illnesses other than AIDS, infants with conditions causing "stress atrophy," and patients with myasthenia gravis. The AIDS group included 11 homosexual males, 1 Haitian, 1 homosexual who was also a drug abuser, and a 10-month-old infant believed to have contracted AIDS following blood transfusion. All the AIDS cases showed marked thymus involution with severe depletion of both lymphocytes and epithelial elements. The latter component consisted primarily of thin cords and nests of primitive-appearing epithelial cells that could be defined by positive immunohistochemical staining for keratin. Many cases showed a variable plasma cell infiltration, and the majority exhibited distinct vascular changes in the form of hyalinization and/or onion-skin patterns, primarily in the adventitia. Most striking of all was the marked paucity of Hassall's corpuscles; four patients had none at all, while in the other ten patients all the Hassall's corpuscles were calcified. These changes were far more extensive than those seen in any of the control groups, which retained most of their complement of Hassall's corpuscles even in the face of marked overall involution. The physiologic function of Hassall's corpuscles is not known, but recent immunohistochemical studies have implicated them in the synthesis of "facteur thymique serique" (FTS, thymulin) and other thymic hormones known to play a role in regulating T-helper and suppressor cell activity. It is conceivable that the extensive destruction of Hassall's corpuscles observed in

  12. Role of caspase-8 in thymus function

    PubMed Central

    Pozzesi, N; Fierabracci, A; Liberati, A M; Martelli, M P; Ayroldi, E; Riccardi, C; Delfino, D V

    2014-01-01

    The thymus is the primary organ responsible for de novo generation of immunocompetent T cells that have a diverse repertoire of antigen recognition. During the developmental process, 98% of thymocytes die by apoptosis. Thus apoptosis is a dominant process in the thymus and occurs through either death by neglect or negative selection or through induction by stress/aging. Caspase activation is an essential part of the general apoptosis mechanism, and data suggest that caspases may have a role in negative selection; however, it seems more probable that caspase-8 activation is involved in death by neglect, particularly in glucocorticoid-induced thymocyte apoptosis. Caspase-8 is active in double-positive (DP) thymocytes in vivo and can be activated in vitro in DP thymocytes by T-cell receptor (TCR) crosslinking to induce apoptosis. Caspase-8 is a proapoptotic member of the caspase family and is considered an initiator caspase, which is activated upon stimulation of a death receptor (e.g., Fas), recruitment of the adaptor molecule FADD, and recruitment and subsequent processing of procaspase-8. The main role of caspase-8 seems to be pro-apoptotic and, in this review, we will discuss about the involvement of caspase-8 in (1) TCR-triggered thymic apoptosis; (2) death receptor-mediated thymic apoptosis; and (3) glucocorticoid-induced thymic apoptosis. Regarding TCR triggering, caspase-8 is active in medullary, semi-mature heat-stable antigenhi (HAShi SP) thymocytes as a consequence of strong TCR stimulation. The death receptors Fas, FADD, and FLIP are involved upstream of caspase-8 activation in apoptosis; whereas, Bid and HDAC7 are involved downstream of caspase-8. Finally, caspase-8 is involved in glucocortocoid-induced thymocyte apoptosis through an activation loop with the protein GILZ. GILZ activates caspase-8, promoting GILZ sumoylation and its protection from proteasomal degradation. PMID:24270406

  13. Retropharyngeal thymus and parathyroid gland: a case report.

    PubMed

    Schramm, Jordan C; Perry, Deborah A; Sewell, Ryan K

    2014-01-01

    Cervical ectopic thymus occurs when thymic tissue arrests during its embryologic descent through the neck to the upper mediastinum. Most often it presents as an asymptomatic neck mass. Rarely does it present with airway compromise, particularly in neonates. A neonate presented with a retropharyngeal mass causing dynamic upper airway obstruction, mimicking a venolymphatic malformation. Ultimately this proved to be aberrant ectopic thymus with an associated parathyroid gland. While there have been isolated reports of thymus or parathyroid in the retropharyngeal space, none of the prior reports found both within the same patient.

  14. Complete Genome Sequence of Bordetella bronchiseptica S798, an Isolate from a Pig with Atrophic Rhinitis.

    PubMed

    Okada, Keisuke; Ogura, Yoshitoshi; Hayashi, Tetsuya; Abe, Akio; Kuwae, Asaomi; Horiguchi, Yasuhiko; Abe, Hiroyuki

    2014-01-01

    Bordetella bronchiseptica colonizes the respiratory tracts of a wide variety of mammals and causes a range of diseases, from lethal pneumonia to asymptomatic chronic infection. We report the complete genome sequence of Bordetella bronchiseptica strain S798, isolated from a pig with atrophic rhinitis in Japan. PMID:24831150

  15. Complete Genome Sequence of Bordetella bronchiseptica S798, an Isolate from a Pig with Atrophic Rhinitis.

    PubMed

    Okada, Keisuke; Ogura, Yoshitoshi; Hayashi, Tetsuya; Abe, Akio; Kuwae, Asaomi; Horiguchi, Yasuhiko; Abe, Hiroyuki

    2014-01-01

    Bordetella bronchiseptica colonizes the respiratory tracts of a wide variety of mammals and causes a range of diseases, from lethal pneumonia to asymptomatic chronic infection. We report the complete genome sequence of Bordetella bronchiseptica strain S798, isolated from a pig with atrophic rhinitis in Japan.

  16. Tolerance has its limits: how the thymus copes with infection

    PubMed Central

    Nunes-Alves, Cláudio; Nobrega, Claudia; Behar, Samuel M.; Correia-Neves, Margarida

    2013-01-01

    The thymus is required for T cell differentiation, a process that depends on which antigens are encountered by thymocytes, the environment surrounding the differentiating cells, and the thymic architecture. These features are altered by local infection of the thymus and by the inflammatory mediators that accompany systemic infection. Although once believed to be an immune privileged site, it is now known that anti-microbial responses are recruited to the thymus. Resolving infection in the thymus is important because chronic persistence of microbes impairs the differentiation of pathogen-specific T cells and diminishes resistance to infection. Understanding how these mechanisms contribute to disease susceptibility, particularly in infants with developing T cell repertoires, requires further investigation. PMID:23871487

  17. The discovery of the blood-thymus barrier.

    PubMed

    Ribatti, Domenico

    2015-12-01

    The blood-thymus barrier is a functional and selective barrier separating T-lymphocytes from blood and cortical capillaries in the cortex of the thymus. The existence of this barrier was proposed for the first in time in 1961 by Marshall and White, and demonstrated in 1963 by Clark and Weiss. The most clear morphological evidence concerning the existence of the blood-thymus barrier may be attributed to the collaborative work published in 1972 by two scientists, Morris Karnovsky and Elio Raviola. Raviola and Karnovsky, using peroxidase as a permeability tracer, demonstrated that the venules at the cortico-medullary junction are the site of leakage for blood antigens, while the capillaries draining the cortex are largely impermeable. Other permeability studies have confirmed the existence of a blood-thymus barrier, which allow the access to low molecular weight tracers, while most exclude high molecular weight particles.

  18. The effects of deoxynivalenol on gene expression in the murine thymus

    SciTech Connect

    Kol, Sandra W.M. van; Hendriksen, Peter J.M.; Loveren, Henk van; Peijnenburg, Ad

    2011-02-01

    Deoxynivalenol (DON) is a mycotoxin produced by several Fusarium species and is often detected in grains. Because of its high abundance, there has been a large interest in the effects of DON in animals and humans. DON is known to be immunosuppressive at high concentrations and immunostimulatory at low concentrations. The present study aimed to acquire insight into the modes of action of DON. For this, C57Bl6 mice were orally exposed to 5, 10, or 25 mg/kg bw DON for 3, 6, or 24 h and thymuses were subjected to genome-wide expression microarray analysis. Gene set enrichment analysis (GSEA) demonstrated that DON downregulated genes involved in proliferation, mitochondria, protein synthesis, and ribosomal proteins. Furthermore, GSEA showed a selective downregulation of genes highly expressed at the early precursor thymocytes stage. This indicates that early precursor thymocytes, particularly at the double-positive CD4+CD8+ stage, are more vulnerable to DON than very early or late precursor thymocytes. There was a large overlap of genes upregulated by DON with genes previously reported to be either upregulated during T cell activation or upregulated during negative selection of thymocytes that recognize 'self-antigens'. This indicates that DON induces cellular events that also occur after activation of the T cell receptor, for example, release of calcium from the endoplasmatic reticulum. This T cell activation in the thymus then evokes negative selection and depletion of thymocytes, which provides a plausible explanation for the high sensitivity of the thymus for DON exposure. The expression patterns of four genes indicative for some of the processes that were affected after DON treatment were confirmed using real-time PCR. Immunocytological experiments with primary mouse thymocytes demonstrated the translocation of NFAT from the cytoplasm into the nucleus upon exposure top DON, thus providing further evidence for the involvement of T cell activation.

  19. The Thymus: A Forgotten, But Very Important Organ.

    PubMed

    Zdrojewicz, Zygmunt; Pachura, Ewelina; Pachura, Paulina

    2016-01-01

    Medical science seems to be on the threshold of a revolution: It seems possible that in twenty years, doctors will be able to replace organs in the human body like parts in a car. This is thanks to the recent achievement of a team from the Medical Research Council Center for Regenerative Medicine in Edinburgh, Scotland - the group of researchers tried to regenerate the thymus gland in mice. The thymus gland is an essential organ for the development of the immune system, but very few people have any idea that it exists. In the literature and also in people's awareness, the fact is often that the thymus controls and harmonizes the entire immune system and the immune functioning of the organism. It is the primary donor of cells for the lymphatic system, much as bone marrow is the cell donor for the cardiovascular system. It is within the thymus that progenitor cells are created and then undergo maturation and differentiation into mature T cells. The thymus gland is located in the mediastinum, behind the sternum. It is composed of two identical lobes. Each lobe is divided into a central medulla and a peripheral cortex. The thymus is at its largest and most active during the neonatal and pre-adolescent periods. After this period the organ gradually disappears and is replaced by fat. In elderly individuals the thymus weighs 5 g. The aim of this work is to shed new light on this important immune defense organ, whose function is not confined to the destruction of nonfunctional T cells. PMID:27627572

  20. The Immunoendocrine Thymus as a Pacemaker of Lifespan.

    PubMed

    Csaba, György

    2016-06-01

    The thymus develops from an endocrine area of the foregut, and retains the ancient potencies of this region. However, later it is populated by bone marrow originated lymphatic elements and forms a combined organ, which is a central part of the immune system as well as an influential element of the endocrine orchestra. Thymus produces self-hormones (thymulin, thymosin, thymopentin, and thymus humoral factor), which are participating in the regulation of immune cell transformation and selection, and also synthesizes hormones similar to that of the other endocrine glands such as melatonin, neuropeptides, and insulin, which are transported by the immune cells to the sites of requests (packed transport). Thymic (epithelial and immune) cells also have receptors for hormones which regulate them. This combined organ, which is continuously changing from birth to senescence seems to be a pacemaker of life. This function is basically regulated by the selection of self-responsive thymocytes as their complete destruction helps the development (up to puberty) and their gradual release in case of weakened control (after puberty) causes the erosion of cells and intercellular material, named aging. This means that during aging, self-destructive and non-protective immune activities are manifested under the guidance of the involuting thymus, causing the continuous irritation of cells and organs. Possibly the pineal body is the main regulator of the pacemaker, the neonatal removal of which results in atrophy of thymus and wasting disease and its later corrosion causes the insufficiency of thymus. The co-involution of pineal and thymus could determine the aging and the time of death without external intervention; however, external factors can negatively influence both of them. PMID:27352969

  1. The Thymus: A Forgotten, But Very Important Organ.

    PubMed

    Zdrojewicz, Zygmunt; Pachura, Ewelina; Pachura, Paulina

    2016-01-01

    Medical science seems to be on the threshold of a revolution: It seems possible that in twenty years, doctors will be able to replace organs in the human body like parts in a car. This is thanks to the recent achievement of a team from the Medical Research Council Center for Regenerative Medicine in Edinburgh, Scotland - the group of researchers tried to regenerate the thymus gland in mice. The thymus gland is an essential organ for the development of the immune system, but very few people have any idea that it exists. In the literature and also in people's awareness, the fact is often that the thymus controls and harmonizes the entire immune system and the immune functioning of the organism. It is the primary donor of cells for the lymphatic system, much as bone marrow is the cell donor for the cardiovascular system. It is within the thymus that progenitor cells are created and then undergo maturation and differentiation into mature T cells. The thymus gland is located in the mediastinum, behind the sternum. It is composed of two identical lobes. Each lobe is divided into a central medulla and a peripheral cortex. The thymus is at its largest and most active during the neonatal and pre-adolescent periods. After this period the organ gradually disappears and is replaced by fat. In elderly individuals the thymus weighs 5 g. The aim of this work is to shed new light on this important immune defense organ, whose function is not confined to the destruction of nonfunctional T cells.

  2. An incidental solitary fibrous tumour in the retroperitoneum, coexisting with ipsilateral atrophic kidney.

    PubMed

    Savas, Murat; Ciftci, Halil; Ozgonul, Abdullah; Sogut, Ozgur; Guldur, Muhammet E

    2011-09-01

    Solitary fibrous tumour (SFT) is a relatively uncommon spindle-cell neoplasm that most commonly arises in the pleura, but which may also arise from other serosal surfaces outside the pleura. However, SFT is now known to affect various serosal surfaces including pericardium, peritoneum, retroperitoneum nasal and paranasal sinuses, thyroid, cavernous sinus or pituitary fossa. The histologic features of this lesion may create diagnostic confusion with a variety of other spindle-cell tumours. To the best our knowledge, no cases with SFT have been previously noted in the retroperitoneum coexisting with atrophic kidney. Herein, we report the unique association of a solitary fibrous tumour in the retroperitoneum coexisting with ipsilateral atrophic kidney in a 60-year-old man and define histopatological findings of this tumour.

  3. Severely Atrophic Human Muscle Fibers With Nuclear Misplacement Survive Many Years of Permanent Denervation.

    PubMed

    Carraro, Ugo; Kern, Helmut

    2016-06-13

    Likewise in rodents, after complete spinal cord injury (SCI) the lower motor neuron (LMN) denervated human muscle fibers lose completely the myofibrillar apparatus and the coil distribution of myonuclei that are relocated in groups (nuclear clumps) in the center of severely atrophic muscle fibers. Up to two years of LMN denervation the muscle fibers with nuclear clumps are very seldom, but in this cohort of patients the severely atrophic muscle fibers are frequent in muscle biopsies harvested three to six years after SCI. Indeed, the percentage increased to 27 ± 9% (p< 0.001), and then abruptly decreased from the 6th year onward, when fibrosis takes over to neurogenic muscle atrophy. Immunohistochemical analyses shown that nuclear misplacements occurred in both fast and slow muscle fibers. In conclusion, human muscle fibers survive permanent denervation much longer than generally accepted and relocation of nuclei is a general behavior in long term denervated muscle fibers. PMID:27478559

  4. Severely Atrophic Human Muscle Fibers With Nuclear Misplacement Survive Many Years of Permanent Denervation

    PubMed Central

    Carraro, Ugo; Kern, Helmut

    2016-01-01

    Likewise in rodents, after complete spinal cord injury (SCI) the lower motor neuron (LMN) denervated human muscle fibers lose completely the myofibrillar apparatus and the coil distribution of myonuclei that are relocated in groups (nuclear clumps) in the center of severely atrophic muscle fibers. Up to two years of LMN denervation the muscle fibers with nuclear clumps are very seldom, but in this cohort of patients the severely atrophic muscle fibers are frequent in muscle biopsies harvested three to six years after SCI. Indeed, the percentage increased to 27 ± 9% (p< 0.001), and then abruptly decreased from the 6th year onward, when fibrosis takes over to neurogenic muscle atrophy. Immunohistochemical analyses shown that nuclear misplacements occurred in both fast and slow muscle fibers. In conclusion, human muscle fibers survive permanent denervation much longer than generally accepted and relocation of nuclei is a general behavior in long term denervated muscle fibers. PMID:27478559

  5. Major motor atrophic patterns in the face and neck: CT evaluation

    SciTech Connect

    Harnsberger, H.R.; Dillon, W.P.

    1985-06-01

    Cranial nerve deficits from various pathologic processes of the head and neck may result in characteristic patterns of denervation muscular atrophy. Such atrophic patterns may be clues to the location and extent of the lesion, particularly when cranial nerves are involved early in the course of the disease process. Thirty-six patients with computed tomographic (CT) evidence of muscular atrophy secondary to pathologic conditions involving the motor division of cranial nerves were examined. Five characteristic denervation muscular atrophy patterns seen on CT scans were identified. Recognition of these atrophic patterns can prevent misinterpretation of their CT appearance and direct the CT examination to the course of the compromised cranial nerve from the brainstem to its peripheral innervation.

  6. Dendritic cells in hyperplastic thymuses from patients with myasthenia gravis.

    PubMed

    Nagane, Yuriko; Utsugisawa, Kimiaki; Obara, Daiji; Yamagata, Munehisa; Tohgi, Hideo

    2003-05-01

    To investigate the role of dendritic cells (DCs) in the hyperplastic myasthenia gravis (MG) thymus, we studied the frequency and distribution of three mature DC phenotypes (CD83(+)CD11c(+), CD86(+)CD11c(+), and HLA-DR(+)CD11c(+)) in samples from patients with MG whose symptoms dramatically improved following thymectomy and in non-MG control thymuses. In hyperplastic MG thymuses, mature DCs were much more numerous in nonmedullary areas, such as the subcapsular/outer cortex; around the germinal centers; and in extralobular connective tissue, particularly around blood vessels. Mature DCs strongly coexpressed CD44 and appeared to be components of a CD44-highly positive (CD44(high)) cell population migrating from the vascular system. Furthermore, in the hyperplastic MG thymus, the expression of secondary lymphoid-tissue chemokine (SLC) markedly increased especially around extralobular blood vessels, where the CD44(high) cell population accumulated. These findings suggest that DCs may migrate into the hyperplastic thymus from the vascular system via mechanisms that involve CD44 and SLC. DCs may present self-antigens, thereby promoting the priming and/or boosting of potentially autoreactive T cells against the acetylcholine receptor.

  7. Thymus and aging: morphological, radiological, and functional overview.

    PubMed

    Rezzani, Rita; Nardo, Lorenzo; Favero, Gaia; Peroni, Michele; Rodella, Luigi Fabrizio

    2014-02-01

    Aging is a continuous process that induces many alterations in the cytoarchitecture of different organs and systems both in humans and animals. Moreover, it is associated with increased susceptibility to infectious, autoimmune, and neoplastic processes. The thymus is a primary lymphoid organ responsible for the production of immunocompetent T cells and, with aging, it atrophies and declines in functions. Universality of thymic involution in all species possessing thymus, including human, indicates it as a long-standing evolutionary event. Although it is accepted that many factors contribute to age-associated thymic involution, little is known about the mechanisms involved in the process. The exact time point of the initiation is not well defined. To address the issue, we report the exact age of thymus throughout the review so that readers can have a nicely pictured synoptic view of the process. Focusing our attention on the different stages of the development of the thymus gland (natal, postnatal, adult, and old), we describe chronologically the morphological changes of the gland. We report that the thymic morphology and cell types are evolutionarily preserved in several vertebrate species. This finding is important in understanding the similar problems caused by senescence and other diseases. Another point that we considered very important is to indicate the assessment of the thymus through radiological images to highlight its variability in shape, size, and anatomical conformation.

  8. Thymus-autonomous T cell development in the absence of progenitor import.

    PubMed

    Martins, Vera C; Ruggiero, Eliana; Schlenner, Susan M; Madan, Vikas; Schmidt, Manfred; Fink, Pamela J; von Kalle, Christof; Rodewald, Hans-Reimer

    2012-07-30

    Thymus function is thought to depend on a steady supply of T cell progenitors from the bone marrow. The notion that the thymus lacks progenitors with self-renewal capacity is based on thymus transplantation experiments in which host-derived thymocytes replaced thymus-resident cells within 4 wk. Thymus grafting into T cell-deficient mice resulted in a wave of T cell export from the thymus, followed by colonization of the thymus by host-derived progenitors, and cessation of T cell development. Compound Rag2(-/-)γ(c)(-/-)Kit(W/Wv) mutants lack competitive hematopoietic stem cells (HSCs) and are devoid of T cell progenitors. In this study, using this strain as recipients for wild-type thymus grafts, we noticed thymus-autonomous T cell development lasting several months. However, we found no evidence for export of donor HSCs from thymus to bone marrow. A diverse T cell antigen receptor repertoire in progenitor-deprived thymus grafts implied that many thymocytes were capable of self-renewal. Although the process was most efficient in Rag2(-/-)γ(c)(-/-)Kit(W/Wv) hosts, γ(c)-mediated signals alone played a key role in the competition between thymus-resident and bone marrow-derived progenitors. Hence, the turnover of each generation of thymocytes is not only based on short life span but is also driven via expulsion of resident thymocytes by fresh progenitors entering the thymus.

  9. Rehabilitation of Edentulous Atrophic Anterior Mandible – The Role of Vertical Alveolar Distraction Osteogenesis

    PubMed Central

    Rao, Latha P; Sequiera, Joyce; Rao, B H Sripathi; Chandra, Jagadish; Rai, Gunachandra

    2014-01-01

    The rehabilitation of patients with edentulous alveolar ridge is always a challenge, more so in case of a long standing atrophic mandible. Mandible, the largest movable bone in the maxillofacial skeleton is associated with many soft tissue attachments which imparts dislodging forces to prosthesis. In addition to this, the rate of resorption of the mandibular ridge is four times that of the maxilla. These factors make the environment of the mandibular arch less favorable to complete denture stability and retention. An ideal solution would be to augment the atrophic alveolar ridge with native bone of the individual which shall eliminate the possible complications, associated with conventional ridge augmentation procedures. With advent of modern technology, and increased biological understanding, the principles of distraction osteogenesis are increasingly being applied to the craniofacial skeleton and have been found to be a viable option in augmenting the native alveolar bone in the mandible. Here the application of an indigenous stainless steel vertical alveolar distraction device to augment atrophic anterior mandibular ridge is assessed in six patients. PMID:25584344

  10. An Unusual Presentation of Pseudothrombotic Microangiopathy in a Patient with Autoimmune Atrophic Gastritis

    PubMed Central

    Nasnas, Roy

    2016-01-01

    Introduction. We hereby describe the case of a young female patient who presented with pseudothrombotic microangiopathy, as well as pancytopenia accompanied by autoimmune atrophic gastritis. Case Presentation. A 36-year-old Caucasian woman presented to the emergency department with fatigue and dyspnea on minimal exertion. Physical examination was unremarkable except for pallor and noninjected conjunctiva. Laboratory tests revealed high LDH and low hemoglobin, white blood cells, platelets, and haptoglobin. The peripheral blood smear showed schistocytes suggestive of pseudothrombotic microangiopathy. Low cobalamin level and hyperhomocysteinemia were also detected. Autoimmune atrophic gastritis was confirmed by gastric biopsy and positive anti-intrinsic factor antibodies. Vitamin B12 supplements were given which led to rapid recovery and normalization of blood parameters. Conclusion. This case highlights the importance and serves as a reminder to clinicians to rule out cobalamin deficiency and autoimmune atrophic gastritis in patients presenting with a picture suggestive of thrombotic thrombocytopenic purpura and pancytopenia, which was completely reversible after appropriate replacement therapy without recurring to unnecessary and invasive procedures such as plasma exchange. PMID:27018160

  11. [Atrophic gastritis as a pre-cancer gastric condition: a new view of the old problem].

    PubMed

    Kreĭmer, V D; Tiurin, V P; Kogan, E A; Khomiakova, I A

    2011-01-01

    The aim of the work was to study the relationship between structural changes in gastric mucosa affected by atrophic gastritis and inflammation associated with Hp infection. Endoscopic examination and NBI-visualization were used to assess distribution and severity of inflammation in 500 patients with different gastric pathologies. Histological material was studied to detect Hp. Structural changes of metaplastic type most frequently occurred in patients with atrophic gastritis (72 of 81, 88.9%), surface and erosive gastritis (13 or 3.5% and 16 or 14.3% respectively), p < 0.001. Hp infection and inflammatory-destructive changes showed no apparent trends. Mucosal changes characteristic of atrophy were only rarely accompanied by marked inflammation (14.8%) and were either mild (21%) or moderately severe (64.2%). It suggests that atrophy of gastric mucosa should be regarded as independent condition while the term atrophic gastritis should be used only in case of association between atrophy and inflammation confirmed by microscopic studies.

  12. [Peculiarities of relationship between atrophic gastritis and stomach cancer in the population of Eastern Siberia].

    PubMed

    Tsukanov, V V; Butorin, N N; Maady, A S; Shtygasheva, O V; Amel'chugova, O S; Tonkikh, Iu L; Bronnikova, E P

    2011-01-01

    The authors studied the prevalence of atrophic gastritis, H.pylori strains carrying the CagA gene, seeding and apoptosis indices of gastric mucosa in indigenous and newcomer residents of Evenkia. A total of 136 Evenks and 159 newcomers were examined using fibrogastroscopy and biopsy of antral gastric mucosa. Morphological study included light microscopy of hematoxylin and eosin-stained biopsies and their analysis using a visual-analog scale to reveal signs of inflammation, apoptosis, intestinal metaplasia and the degree of insemination by P. pylori. Urease and morphological tests were used to identify H. pylori and the TUNEL technique (Mebstain Apoptosis kit direct, France) to determine apoptosis index; serum anti-Helicobacter and CagA antibodies were detected by an immunoenzyme assay in 22 Evenks and 24 newcomers with chronic H. pylori-associated gastritis. The prevalence of atrophic gastritis in these groups was estimated at 13.2 and 23.9% respectively, seeding density 45.37 +/- 2.01 and 214 +/- 8.75 (p < 0.001). H. pylori strains carrying the CagA gene were identified in 59.6 and 43.6% of the newcomers and Evenks (p = 0.01), total apoptosis index in greater curvature mucosa was 4.99 +/- 0.23 and 3.19 +/- 0.28 (p < 0.01) respectively. These ethnic difference in the prevalence of atrophic gastritis appear to be attributable to different intensity of apoptosis in greater curvature mucosa.

  13. AMP-deaminase from thymus of patients with myasthenia gravis.

    PubMed

    Rybakowska, I; Szydłowska, M; Szrok, S; Bakuła, S; Kaletha, K

    2015-01-01

    Myasthenia gravis (MG) is characterized clinically by skeletal muscle fatigue following the excessive exercise. Interestingly most of MG patients manifest parallely also some abnormalities of the thymus.AMP-deaminase (AMPD) from human thymus was not a subject of studies up to now. In this paper, mRNA expression and some physico-chemical and immunological properties of AMPD purified from the thymus of MG patients were described. Experiments performed identified the liver isozyme (AMPD2) as the main isoform of AMPD expressed in this organ. The activity of AMPD found in this organ was higher than in other human non-(skeletal) muscle tissues indicating on role the enzyme may play in supplying of guanylates required for the intensive multiplication of thymocytes.

  14. ALTERED HISTOLOGY OF THE THYMUS AND SPLEEN IN CONTAMINANT-EXPOSED JUVENILE AMERICAN ALLIGATORS

    EPA Science Inventory

    Morphological difference in spleen and thymus are closely related to functional immune differences. Hormonal regulation of the immune system has been demonstrated in reptilian splenic and thymic tissue. Spleens and thymus were obtained from juvenile alligators at two reference si...

  15. Characterization and Angiogenic Potential of Human Neonatal and Infant Thymus Mesenchymal Stromal Cells

    PubMed Central

    Wang, Shuyun; Mundada, Lakshmi; Johnson, Sean; Wong, Joshua; Witt, Russell; Ohye, Richard G.

    2015-01-01

    Resident mesenchymal stromal cells (MSCs) are involved in angiogenesis during thymus regeneration. We have previously shown that MSCs can be isolated from enzymatically digested human neonatal and infant thymus tissue that is normally discarded during pediatric cardiac surgical procedures. In this paper, we demonstrate that thymus MSCs can also be isolated by explant culture of discarded thymus tissue and that these cells share many of the characteristics of bone marrow MSCs. Human neonatal thymus MSCs are clonogenic, demonstrate exponential growth in nearly 30 population doublings, have a characteristic surface marker profile, and express pluripotency genes. Furthermore, thymus MSCs have potent proangiogenic behavior in vitro with sprout formation and angiogenic growth factor production. Thymus MSCs promote neoangiogenesis and cooperate with endothelial cells to form functional human blood vessels in vivo. These characteristics make thymus MSCs a potential candidate for use as an angiogenic cell therapeutic agent and for vascularizing engineered tissues in vitro. PMID:25713463

  16. [Single mechanism of remodelling extracellular matrix in thymus and pineal gland at aging].

    PubMed

    Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M

    2011-01-01

    The expression of matrix metalloproteinase 2 and 9 in thymus and pineal gland has been verified. These data demonstrate single mechanism of remodelling extracellular matrix in thymus and pineal gland at aging.

  17. Characterization and angiogenic potential of human neonatal and infant thymus mesenchymal stromal cells.

    PubMed

    Wang, Shuyun; Mundada, Lakshmi; Johnson, Sean; Wong, Joshua; Witt, Russell; Ohye, Richard G; Si, Ming-Sing

    2015-04-01

    Resident mesenchymal stromal cells (MSCs) are involved in angiogenesis during thymus regeneration. We have previously shown that MSCs can be isolated from enzymatically digested human neonatal and infant thymus tissue that is normally discarded during pediatric cardiac surgical procedures. In this paper, we demonstrate that thymus MSCs can also be isolated by explant culture of discarded thymus tissue and that these cells share many of the characteristics of bone marrow MSCs. Human neonatal thymus MSCs are clonogenic, demonstrate exponential growth in nearly 30 population doublings, have a characteristic surface marker profile, and express pluripotency genes. Furthermore, thymus MSCs have potent proangiogenic behavior in vitro with sprout formation and angiogenic growth factor production. Thymus MSCs promote neoangiogenesis and cooperate with endothelial cells to form functional human blood vessels in vivo. These characteristics make thymus MSCs a potential candidate for use as an angiogenic cell therapeutic agent and for vascularizing engineered tissues in vitro.

  18. [Thymus Development in Early Ontogeny: A Comparative Aspect].

    PubMed

    Vasil'ev, K A; Polevshchikov, A V

    2015-01-01

    This review is dedicated to comparative analysis of the early stages of thymus ontogeny in fish, amphibians, and mammals. Morphological and molecular-genetic aspects of the formation of thymic stroma, colonization of this organ with T-cell progenitors, and interaction of different cell populations in the course of organogenesis are considered. Particular attention is given to the hematopoietic role of the thymus during embryogenesis and new data on the origin of T-cell progenitors. The hypothesis about the possible presence in the organ of a self-sustaining population of stem cells, formed regardless of fetal hematopoiesis areas, is discussed.

  19. Thymus organogenesis and development of the thymic stroma.

    PubMed

    Nowell, Craig S; Farley, Alison M; Blackburn, C Clare

    2007-01-01

    T-cell development occurs principally in the thymus. Here, immature progenitor cells are guided through the differentiation and selection steps required to generate a complex T-cell repertoire that is both self-tolerant and has propensity to bind self major histocompatibility complex. These processes depend on an array of functionally distinct epithelial cell types within the thymic stroma, which have a common developmental origin in the pharyngeal endoderm. Here, we describe the structural and phenotypic attributes of the thymic stroma, and review current cellular and molecular understanding of thymus organogenesis.

  20. Immunoproteomics of Helicobacter pylori infection in patients with atrophic body gastritis, a predisposing condition for gastric cancer.

    PubMed

    Lahner, Edith; Bernardini, Giulia; Possenti, Silvia; Renzone, Giovanni; Scaloni, Andrea; Santucci, Annalisa; Annibale, Bruno

    2011-02-01

    Atrophic body gastritis is considered an outcome of H. pylori infection at high risk for gastric cancer. Immunoproteomics has been used to detect H. pylori antigens, which may act as potential markers for neoplastic disease and may be used in specific serological tests. We used immunoproteome technology to identify H. pylori antigens, recognized by sera from patients with atrophic body gastritis. Here, we performed 2DE protein maps of H. pylori strain 10K, probed against single sera from 3 groups of H. pylori-positive patients (atrophic body gastritis; intestinal-type gastric cancer; peptic ulcer) and negative controls. Immunoreactive spots were identified by MALDI-TOF-MS. A total of 155 immunoreactive spots were detected corresponding to 14.1% of total spots detected in our reference map of H. pylori strain 10K. Sera from atrophic body gastritis (40.5±2%) and gastric cancer patients (25.9±1.8%) showed a significantly higher and stronger mean immunoreactivity versus H. pylori antigens compared to peptic ulcer patients (11.2±1.3%). The average intensity of immunoreactivity of sera from atrophic body gastritis and gastric cancer patients was significantly stronger compared to peptic ulcer patients. Sera from atrophic body gastritis and gastric cancer patients differentially recognized 17 H. pylori spots. Immunoproteome technology may discriminate between different H. pylori-related disease phenotypes showing a serological immunorecognition pattern common to patients with gastric cancer and atrophic body gastritis, its precursor condition. This tool may be promising for developing specific serological tests to identify patients with gastritis at high risk for gastric cancer, to be evaluated in prospective investigations.

  1. Central T cell tolerance: Identification of tissue-restricted autoantigens in the thymus HLA-DR peptidome.

    PubMed

    Alvarez, Iñaki; Collado, Javier A; Colobran, Roger; Carrascal, Montserrat; Ciudad, M Teresa; Canals, Françesc; James, Eddie A; Kwok, William W; Gärtner, Martina; Kyewski, Bruno; Pujol-Borrell, Ricardo; Jaraquemada, Dolores

    2015-06-01

    Promiscuous gene expression (pGE) of tissue-restricted self-antigens (TRA) in medullary thymic epithelial cells (mTECs) is in part driven by the Autoimmune Regulator gene (AIRE) and essential for self-tolerance. The link between AIRE functional mutations and multi-organ autoimmunity in human and mouse supports the role of pGE. Deep sequencing of the transcriptome revealed that mouse mTECs potentially transcribe an unprecedented range of >90% of all genes. Yet, it remains unclear to which extent these low-level transcripts are actually translated into proteins, processed and presented by thymic APCs to induce tolerance. To address this, we analyzed the HLA-DR-associated thymus peptidome. Within a large panel of peptides from abundant proteins, two TRA peptides were identified: prostate-specific semenogelin-1 (an autoantigen in autoimmune chronic prostatitis/chronic pelvic pain syndrome) and central nervous system-specific contactin-2 (an autoantigen in multiple sclerosis). Thymus expression of both genes was restricted to mTECs. SEMG1 expression was confined to mature HLA-DR(hi) mTECs of male and female donors and was AIRE-dependent, whereas CNTN2 was apparently AIRE-independent and was expressed by both populations of mTECs. Our findings establish a link between pGE, MHC-II peptide presentation and autoimmunity for bona fide human TRAs.

  2. Isolation and characterization of Thy 1 homologue from human thymus.

    PubMed

    Bonewald, L F; Goust, J M; Sade, R M; Wang, A C

    1985-01-01

    A 40 000 M.W. glycoprotein was isolated from human thymus. This molecule binds lentil lectin, reacts with an antiserum made against the p25 antigen (the human Thy 1 homologue) and possesses almost identical amino acid composition as the p25 antigen and its 40 000 M.W. dimer. PMID:2864756

  3. WNT signaling suppression in the senescent human thymus.

    PubMed

    Ferrando-Martínez, Sara; Ruiz-Mateos, Ezequiel; Dudakov, Jarrod A; Velardi, Enrico; Grillari, Johannes; Kreil, David P; Muñoz-Fernandez, M Ángeles; van den Brink, Marcel R M; Leal, Manuel

    2015-03-01

    Human thymus is completely developed in late fetal stages and its function peaks in newborns. After the first year of life, the thymus undergoes a progressive atrophy that dramatically decreases de novo T-lymphocyte maturation. Hormonal signaling and changes in the microRNA expression network are identified as underlying causes of human thymus involution. However, specific pathways involved in the age-related loss of thymic function remain unknown. In this study, we analyzed differential gene-expression profile and microRNA expression in elderly (70 years old) and young (less than 10 months old and 11 years old) human thymic samples. Our data have shown that WNT pathway deregulation through the overexpression of different inhibitors by the nonadipocytic component of the human thymus stimulates the age-related involution. These results are of particular interest because interference of WNT signaling has been demonstrated in both animal models and in vitro studies, with the three major hallmarks of thymic involution: (i) epithelial structure disruption, (ii) adipogenic process, and (iii) thymocyte development arrest. Thus, our results suggest that secreted inhibitors of the WNT pathway could be explored as a novel therapeutical target in the reversal of the age-related thymic involution.

  4. Differential transcript profiles of MHC class Ib(Qa-1, Qa-2, and Qa-10) and Aire genes during the ontogeny of thymus and other tissues.

    PubMed

    Melo-Lima, Breno Luiz; Evangelista, Adriane Feijó; de Magalhães, Danielle Aparecida Rosa; Passos, Geraldo Aleixo; Moreau, Philippe; Donadi, Eduardo Antonio

    2014-01-01

    Qa-2 and Qa-1 are murine nonclassical MHC class I molecules involved in the modulation of immune responses by interacting with T CD8(+) and NK cell inhibitory receptors. During thymic education, the Aire gene imposes the expression of thousands of tissue-related antigens in the thymic medulla, permitting the negative selection events. Aiming to characterize the transcriptional profiles of nonclassical MHC class I genes in spatial-temporal association with the Aire expression, we evaluated the gene expression of H2-Q7(Qa-2), H2-T23(Qa-1), H2-Q10(Qa-10), and Aire during fetal and postnatal development of thymus and other tissues. In the thymus, H2-Q7(Qa-2) transcripts were detected at high levels throughout development and were positively correlated with Aire expression during fetal ages. H2-Q7(Qa-2) and H2-T23(Qa-1) showed distinct expression patterns with gradual increasing levels according to age in most tissues analyzed. H2-Q10(Qa-10) was preferentially expressed by the liver. The Aire transcriptional profile showed increased levels during the fetal period and was detectable in postnatal ages in the thymus. Overall, nonclassical MHC class I genes started to be expressed early during the ontogeny. Their levels varied according to age, tissue, and mouse strain analyzed. This differential expression may contribute to the distinct patterns of mouse susceptibility/resistance to infectious and noninfectious disorders.

  5. [Influence of peptides from pineal gland on thymus function at aging].

    PubMed

    Lin'kova, N S; Poliakova, V O; Trofimov, A V; Sevost'ianova, N N; Kvetnoĭ, I M

    2010-01-01

    The interference between thymus and pineal gland during their involution is considered in this review. The research data about influence of thymus peptides on pineal gland and pineal peptides on thymus is summarized. Analysis of these data showed that pineal peptides (epithalamin, epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (thymalin, thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

  6. Myosin heavy chain composition in normal and atrophic equine laryngeal muscle.

    PubMed

    Adreani, C M; Li, Z B; Lehar, M; Southwood, L L; Habecker, P L; Flint, P W; Parente, E J

    2006-11-01

    The myosin heavy chain (MHC) composition of a given muscle determines the contractile properties and, therefore, the fiber type distribution of the muscle. MHC isoform expression in the laryngeal muscle is modulated by neural input and function, and it represents the cellular level changes that occur with denervation and reinnervation of skeletal muscle. The objective of this study was to evaluate the pattern of MHC isoform expression in laryngeal muscle harvested from normal cadavers and cadavers with naturally occurring left laryngeal hemiplegia secondary to recurrent laryngeal neuropathy. Left and right thyroarytenoideus (TA) and cricoarytenoideus dorsalis (CAD) were obtained from 7 horses affected with left-sided intrinsic laryngeal muscle atrophy and from 2 normal horses. Frozen sections were evaluated histologically for degree of atrophy and fiber type composition. MHC isoform expression was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of muscle protein. Histologic atrophy was seen in all atrophic muscles and some right-sided muscles of 3 affected horses, as well as the left TA of 1 normal horse. Fiber type grouping or loss of type I muscle fibers was observed in the left-sided laryngeal muscles in all but 1 affected horse, as well as in the right muscles of 2 affected horses, and the left TA of 1 normal horse. SDS-PAGE showed 2 bands corresponding to the type I and type IIB myosin isoforms in the CAD and TA of the 2 normal horses. Affected horses demonstrated a trend toward increased expression of the type IIB isoform and decreased expression of the type I isoform in atrophic muscles. This study confirmed the presence of histologic abnormalities in grossly normal equine laryngeal muscle, and it demonstrated an increased expression of type IIB MHC with a concurrent decreased expression of type I MHC in affected muscles. Evaluation of muscle fiber changes at the cellular level under denervated and reinnervated conditions

  7. Chemical composition, antibacterial and antioxidant activities of the essential oils from Thymus satureioides and Thymus pallidus.

    PubMed

    Ichrak, Ghalbane; Rim, Belaqziz; Loubna, Ait Said; Khalid, Oufdou; Abderrahmane, Romane; Said, El Messoussi

    2011-10-01

    This study was designed to examine the in vitro antibacterial and antioxidant activities of the essential oils (EOs) of Thymus satureioides (T.s) and T. pallidus (T.p). EOs were isolated by steam distillation and analyzed by capillary gas chromatography and gas chromatography coupled to mass spectrometry (GC-MS). The major constituents of the volatile fraction of T. satureioides were bomeol (29.5%), carvacrol (9.1%), and beta-caryophyllene (8.2%), while those of T. pallidus were camphor (29.8%), dihydrocarvone (17.6%), bomeol (7.6%) and camphene (7.5%). The essential oils were tested against a panel of Gram+ and Gram- bacteria by using agar diffusion and broth dilution methods. The data indicated that the Gram-positive Bacillus subtilis was the most sensitive strain producing an average inhibition zone of 51.7 mm. Furthermore, Pseudomonas aeruginosa, known as a resistant strain, was also sensitive. The samples were also subjected to screening for their possible antioxidant activity by using the 2,2-diphenyl-l-picrylhydrazyl (DPPH) assay. The IC50 values of the oil of T. satureioides and T. pallidus were 0.32 and 11.6 mg/mL, respectively. PMID:22164795

  8. Leucocyte migration inhibition test with two gastric antigens in pernicious anaemia and in simple atrophic gastritis.

    PubMed

    Fixa, B; Komárková, O; Nozicka, Z

    1979-02-01

    Leucocyte migration inhibition test was used for evaluation of cell-mediated immunity in patients with pernicious anaemia (PA) and simple atrophic gastritis (SAG). As antigens microsomal antigen from gastric mucosa of swine foetus and relatively pure hog intrinsic factor (IF) were used. Significant differences were found between PA and SAG with microsomal antigen, but not with IF. It was concluded, that the microsomal antigen might be more active than IF. This observation could contribute to explane the higher incidence of parietal cell antibody than that of IF antibody in PA patients.

  9. An atrophic plaque on the breast six years after breast reconstruction surgery.

    PubMed

    Khurana, Michele; Torbeck, Richard; Kauh, Young

    2016-01-01

    Necrobiosis lipoidica (NL) is a cutaneous disease entity that typically manifests as atrophic yellow plaques with telangiectasias on the anterior tibial region. Although NL is commonly associated with diabetes mellitus, the role of trauma in disease development is less commonly emphasized. The relationship between NL and the Köbner phenomenon has been established, as a few cases of NL occurring in surgical scars have been reported in the literature. We report the first case of NL occurring in a mastectomy scar on the breast in a non-diabetic female, and explore the relationship between NL, diabetes mellitus, and trauma. PMID:27617606

  10. [Collagenous colitis, IgA deficiency, Basedow's disease and atrophic gastritis].

    PubMed

    Pariente, E A; Chaumette, M T; Maître, F; Delchier, J C; Soulé, J C; Bader, J P

    1985-10-01

    In a 37-year-old woman with chronic watery diarrhea of three years duration, the diagnostic of collagenous colitis was established by optical and ultrastructural examination of rectal and colonic biopsies. No other cause of diarrhea could be found. Moreover, this patient had also selective IgA deficiency, Grave's disease and chronic atrophic gastritis of auto-immune type. Sequential treatments with loperamide, cholestyramine and antibiotics did not modified diarrhea which improved with salazosulfapyridine and betamethasone enemas. These observations suggest that collagenous colitis might be a part of the spectrum of enteropathies associated with immunoglobulin deficiencies. PMID:3840757

  11. Regulation of thymus-dependent and thymus-independent production of immunoglobulin G subclasses by Galpha12 and Galpha13

    PubMed Central

    Lee, Song Jin; Lee, Woo Hyung; Lee, Chang Ho; Kim, Sang Geon

    2008-01-01

    Background A previous study from this laboratory showed that Gα12 members participate in the production of inflammatory cytokines. In spite of the identification of B cell homeostasis responses regulated by Gα13, the functional roles of Gα12 members in the production of immunoglobulin (Ig) isotypes remained unknown. This study investigated whether Gα12 members are involved in the Ig isotype antibody production with the purpose of establishing their functions in thymus-dependent and thymus-independent humoral responses. Results Mice lacking Gα12 and/or Gα13 showed an impaired antigen-specific antibody production promoted by challenge(s) of ovalbumin or trinitrophenyl-lipopolysaccharide (TNP-LPS), used for thymus-dependent and thymus-independent stimuli, respectively. Homozygous knockout (KO) of Gα12 or double heterozygous KO of Gα12/Gα13 significantly reduced the antigen-specific total IgG level after multiple ovalbumin immunizations with decreases in the production of IgG1, IgG2a and IgG2b subclasses, as compared to wild type control. In contrast, IgM production was not decreased. Moreover, mice deficient in Gα12 or partially deficient in Gα13 or Gα12/Gα13 showed significantly low production of IgG2b in response to TNP-LPS. In TNP-LPS-injected mice, IgG1 and IgG2a productions were unaffected by the G protein KOs. Conclusion Our results demonstrate that both Gα12 and Gα13 are essentially involved in thymus-dependent and independent production of IgG subclasses, implying that the G-proteins contribute to the process of antigen-specific IgG antibody production. PMID:18620589

  12. Transcriptomic analysis supports similar functional roles for the two thymuses of the tammar wallaby

    PubMed Central

    2011-01-01

    Background The thymus plays a critical role in the development and maturation of T-cells. Humans have a single thoracic thymus and presence of a second thymus is considered an anomaly. However, many vertebrates have multiple thymuses. The tammar wallaby has two thymuses: a thoracic thymus (typically found in all mammals) and a dominant cervical thymus. Researchers have known about the presence of the two wallaby thymuses since the 1800s, but no genome-wide research has been carried out into possible functional differences between the two thymic tissues. Here, we used pyrosequencing to compare the transcriptomes of a cervical and thoracic thymus from a single 178 day old tammar wallaby. Results We show that both the tammar thoracic and the cervical thymuses displayed gene expression profiles consistent with roles in T-cell development. Both thymuses expressed genes that mediate distinct phases of T-cells differentiation, including the initial commitment of blood stem cells to the T-lineage, the generation of T-cell receptor diversity and development of thymic epithelial cells. Crucial immune genes, such as chemokines were also present. Comparable patterns of expression of non-coding RNAs were seen. 67 genes differentially expressed between the two thymuses were detected, and the possible significance of these results are discussed. Conclusion This is the first study comparing the transcriptomes of two thymuses from a single individual. Our finding supports that both thymuses are functionally equivalent and drive T-cell development. These results are an important first step in the understanding of the genetic processes that govern marsupial immunity, and also allow us to begin to trace the evolution of the mammalian immune system. PMID:21854594

  13. A study of cell-mediated immunity to gastric antigens in patients with atrophic type A and B gastritis.

    PubMed

    Kountouras, J; Raptopoulou-Gigi, M; Goulis, G

    1982-05-01

    The leucocyte migration in the presence of gastric antigens was studied in 10 patients with type A gastritis, 38 patients with type B gastritis (28 with atrophic and 10 with superficial gastritis) and 10 healthy controls. A positive leucocyte migration was found in a significant proportion of patients with both types of gastritis, whereas no difference between the two types was observed. These results indicate that cellular immunity is implicated in the aetiology of both types of gastritis, is of greater importance than auto-antibody production and is associated with the severity of the atrophic lesion.

  14. Visualization of nasal airflow patterns in a patient affected with atrophic rhinitis using particle image velocimetry

    NASA Astrophysics Data System (ADS)

    Garcia, G. J. M.; Mitchell, G.; Bailie, N.; Thornhill, D.; Watterson, J.; Kimbell, J. S.

    2007-10-01

    The relationship between airflow patterns in the nasal cavity and nasal function is poorly understood. This paper reports an experimental study of the interplay between symptoms and airflow patterns in a patient affected with atrophic rhinitis. This pathology is characterized by mucosal dryness, fetor, progressive atrophy of anatomical structures, a spacious nasal cavity, and a paradoxical sensation of nasal congestion. A physical replica of the patient's nasal geometry was made and particle image velocimetry (PIV) was used to visualize and measure the flow field. The nasal replica was based on computed tomography (CT) scans of the patient and was built in three steps: three-dimensional reconstruction of the CT scans; rapid prototyping of a cast; and sacrificial use of the cast to form a model of the nasal passage in clear silicone. Flow patterns were measured by running a water-glycerol mixture through the replica and evaluating the displacement of particles dispersed in the liquid using PIV. The water-glycerol flow rate used corresponded to an air flow rate representative of a human breathing at rest. The trajectory of the flow observed in the left passage of the nose (more affected by atrophic rhinitis) differed markedly from what is considered normal, and was consistent with patterns of epithelial damage observed in cases of the condition. The data are also useful for validation of computational fluid dynamics predictions.

  15. A two-short-implant-supported molar restoration in atrophic posterior maxilla: A finite element analysis

    PubMed Central

    2016-01-01

    PURPOSE The aim of this study was to investigate the stress distribution of 2-short implants (2SIs) installed in a severely atrophic maxillary molar site. MATERIALS AND METHODS Three different diameters of internal connection implants were modeled: narrow platform (NP), regular platform (RP), and wide platform (WP). The maxillary first molars were restored with one implant or two short implants. Three 2SI models (NP-oblique, NP-vertical, and NP-horizontal) and four single implant models (RP and WP in a centered or cantilevered position) were used. Axial and oblique loadings were applied on the occlusal surface of the crown. The von Mises stress values were measured at the bone-implant, peri-implant bone, and implant/abutment complex. RESULTS The highest stress distribution at the bone-implant interface and the peri-implant bone was noticed in the RP group, and the lowest stress distribution was observed in the 2SI groups. Cantilevered position showed unfavorable stress distribution with axial loading. 2SI types did not affect the stress distribution in oblique loading. The number and installation positions of the implant, rather than the bone level, influenced the stress distribution of 2SIs. The implant/abutment complex of WP presented the highest stress concentration while that of 2SIs showed the lowest stress concentration. CONCLUSION 2SIs may be useful for achieving stable stress distribution on the surrounding bone and implant-abutment complex in the atrophic posterior maxilla. PMID:27555900

  16. Calf thymus ribonuclease H IIa activity lacks ribonuclease H specificity.

    PubMed

    Vonwirth, H; Frank, P; Büsen, W

    1990-03-15

    Less purified fractions of ribonuclease H IIa activity of calf thymus display divalent cation-dependent ribonuclease H activity and divalent cation-independent ribonuclease activity. Because the ratio of the two enzyme activities does not change during successive chromatographic procedures, we suggest that ribonuclease H IIa activity is indeed able to degrade both ssRNA and the RNA moiety of RNA.DNA-hybrids. Ribonuclease H IIa activity can therefore be differentiated from calf thymus ribonuclease H I and H IIb by its lack of ribonuclease H specificity. The native molecular mass of ribonuclease H IIa activity is between 23 and 28 kDa. Under denaturing conditions a 23 kDa-protein band copurifies with the enzyme activity suggesting that this enzyme is monomeric.

  17. Thymus vulgaris essential oil: chemical composition and antimicrobial activity.

    PubMed

    Borugă, O; Jianu, C; Mişcă, C; Goleţ, I; Gruia, A T; Horhat, F G

    2014-01-01

    The study was designed to determine the chemical composition and antimicrobial properties of the essential oil of Thymus vulgaris cultivated in Romania. The essential oil was isolated in a yield of 1.25% by steam distillation from the aerial part of the plant and subsequently analyzed by GC-MS. The major components were p-cymene (8.41%), γ-terpinene (30.90%) and thymol (47.59%). Its antimicrobial activity was evaluated on 7 common food-related bacteria and fungus by using the disk diffusion method. The results demonstrate that the Thymus vulgaris essential oil tested possesses strong antimicrobial properties, and may in the future represent a new source of natural antiseptics with applications in the pharmaceutical and food industry. PMID:25870697

  18. Developing stratified epithelia: Lessons from the epidermis and thymus

    PubMed Central

    Roberts, Natalie; Horsley, Valerie

    2014-01-01

    Stratified squamous epithelial cells are found in a number of organs, including the skin epidermis and the thymus. The progenitor cells of the developing epidermis form a multilayered epithelium and appendages, like the hair follicle, to generate an essential barrier to protect against water loss and invasion of foreign pathogens. In contrast, the thymic epithelium forms a three-dimensional mesh of keratinocytes that are essential for positive and negative selection of self-restricted T cells. While these distinct stratified epithelial tissues derive from distinct embryonic germ layers, both tissues instruct immunity, and the epithelial differentiation programs and molecular mechanisms that control their development are remarkably similar. In this review, we aim to highlight some of the similarities between the thymus and the skin epidermis and its appendages during developmental specification. PMID:25176390

  19. Composition of the HLA-DR-associated human thymus peptidome.

    PubMed

    Collado, Javier A; Alvarez, Iñaki; Ciudad, M Teresa; Espinosa, Gabriel; Canals, Francesc; Pujol-Borrell, Ricardo; Carrascal, Montserrat; Abian, Joaquín; Jaraquemada, Dolores

    2013-09-01

    Major histocompatibility complex class II (MHC-II) molecules bind to and display antigenic peptides on the surface of antigen-presenting cells (APCs). In the absence of infection, MHC-II molecules on APCs present self-peptides and interact with CD4(+) T cells to maintain tolerance and homeostasis. In the thymus, self-peptides bind to MHC-II molecules expressed by defined populations of APCs specialised for the different steps of T-cell selection. Cortical epithelial cells present peptides for positive selection, whereas medullary epithelial cells and dendritic cells are responsible for peptide presentation for negative selection. However, few data are available on the peptides presented by MHC molecules in the thymus. Here, we apply mass spectrometry to analyse and identify MHC-II-associated peptides from five fresh human thymus samples. The data show a diverse self-peptide repertoire, mostly consisting of predicted MHC-II high binders. Despite technical limitations preventing single cell population analyses of peptides, these data constitute the first direct assessment of the HLA-II-bound peptidome and provide insight into how this peptidome is generated and how it drives T-cell repertoire formation.

  20. The inflatable thymus herniation of the normal mediastinal thymus: A case report and review of the literature.

    PubMed

    Stuut, Marijn; van Zwieten, Gusta; Straetmans, Jos M; Lacko, Martin; Stumpel, Constance T R M

    2016-04-01

    Anterior neck masses in young children can be a diagnostic challenge for otolaryngologists and radiologists. We present a rare case of herniation of normal mediastinal thymus in a four-year-old girl. Additional medical features as an inguinal hernia and trochlear nerve paresis raised the question whether there is a causal relationship or an association. A connective tissue disorder could not be diagnosed as possible causal factor to the abnormal movement of the mediastinal thymus. Awareness and recognition of this benign phenomenon is important in order to avoid unnecessary biopsy or surgery. Diagnosis can be confirmed by ultrasonography. Magnetic Resonance Imaging might be valuable in order to obtain more information about the extension of the mass. PMID:26968057

  1. Radiation effects on regeneration and T-cell-inducing function of the thymus

    SciTech Connect

    Hirokawa, K.; Sado, T.

    1984-04-01

    Radiation effects on regeneration and T-cell-inducing function of the thymus were studied in three sets of experiments. When TXB mice were grafted with 1-week-old thymus which had been previously irradiated at various doses, an exponential decrease was observed in the morphological regeneration of the thymus grafts and in their T-cell-inducing function at doses of 600 R and over, showing about 10% that of the control at 1500 R. When in situ thymus of adult mice was locally irradiated, the radiation effect on T-cell-inducing function was less pronounced as compared with the first experiment; i.e., about 40% of the control at 1797 R. When in situ thymus of 1-day-old newborn mice was locally irradiated, regeneration potential of 1-day-old newborn thymus was highly resistant to radiation exposure and no effect on immunological functions was observed even by local irradiation of 2000 R.

  2. Fatty infiltration of the thymus in response to illness in the pediatric population.

    PubMed

    Taweevisit, Mana; Anekpuritanang, Tauangtham; Thorner, Paul Scott

    2015-04-01

    Under physiologic stress, glucocorticoids contribute to thymic involution. While steroids enhance fatty infiltration, this change has not been well studied in the pediatric thymus during illness. Evaluation of 130 thymuses from fetuses, infants and children determined the frequency of thymic fatty infiltration to be low (25%), particularly in fetal thymus (4%). In most cases, fatty infiltration was focal. There was a significant correlation with duration of illness, but not with patient age, gestational age, or underlying disease. There was significantly less fatty infiltration in fetal thymus compared to post-natal thymus, for the same degree of thymic involution. Only seven cases showed diffuse thymic fatty infiltration; all were post-natal associated with an infectious etiology. In contrast, fetal cases of chorioamnionitis seldom showed fatty infiltration and only focally, implying the stress response of fetal thymus differs post-natal, possibly related to the timing of adipose tissue development and fetal glucocorticoid response to stress.

  3. Distinctive renal cell tumor simulating atrophic kidney with 2 types of microcalcifications. Report of 3 cases.

    PubMed

    Hes, Ondrej; de Souza, Tulio Geraldo; Pivovarcikova, Kristyna; Grossmann, Petr; Martinek, Petr; Kuroda, Naoto; Kacerovska, Denisa; Svajdler, Marian; Straka, Lubomir; Petersson, Fredrik; Hora, Milan; Michal, Michal

    2014-04-01

    We report 3 cases of primary renal cell tumor simulating atrophic kidney with distinct gross, morphologic, immunohistochemical, and molecular genetic features. The tumors were retrieved out of more than 17 000 renal tumors from the Plzen Tumor Registry. Tissues for light microscopy had been fixed, embedded, and stained with hematoxylin and eosin using routine procedures. The tumors were further analyzed using immunohistochemistry, array comparative genomic hybridization, and human androgen receptor. Analyses of VHL gene and loss of heterozygosity (LOH) 3p were also performed. The patients were 2 women and 1 man, with ages ranging from 29 to 35 years (mean, 31.3 years). Grossly, the neoplasms were encapsulated and round with largest diameter of 3.5 cm (mean, 3.2 cm). Follow-up available for all patients ranged from 2 to 14 years (mean, 8 years). No aggressive behavior was noted. Histologically, akin to atrophic (postpyelonephritic) kidney parenchyma, the tumors were composed of follicles of varying sizes that were filled by eosinophilic secretion. Rare areas contained collapsed follicles. Each follicle was endowed with a small capillary. The stroma was loose, inconspicuous, and focally fibrotic. Two types of calcifications were noted: typical psammoma bodies and amorphous dark-blue stained calcified deposits. Immunohistochemically, tumors were strongly positive for cytokeratins (OSCAR), CD10, and vimentin, with weak immunopositivity for CAM5.2 and AE1-AE3. WT1 and cathepsin K were weakly to moderately focally to diffusely positive. Tumors were negative for cytokeratin 20, carbonic anhydrase IX, parvalbumin, HMB45, TTF1, TFE3, chromogranin A, thyroglobulin, PAX8, and ALK. Only 1 case was suitable for molecular genetic analyses. No mutations were found in the VHL gene; no methylation of VHL promoter was noted. No numerical aberrations were found by array comparative genomic hybridization analysis. LOH for chromosome 3p was not detected. Analysis of clonality (human

  4. Distinctive renal cell tumor simulating atrophic kidney with 2 types of microcalcifications. Report of 3 cases.

    PubMed

    Hes, Ondrej; de Souza, Tulio Geraldo; Pivovarcikova, Kristyna; Grossmann, Petr; Martinek, Petr; Kuroda, Naoto; Kacerovska, Denisa; Svajdler, Marian; Straka, Lubomir; Petersson, Fredrik; Hora, Milan; Michal, Michal

    2014-04-01

    We report 3 cases of primary renal cell tumor simulating atrophic kidney with distinct gross, morphologic, immunohistochemical, and molecular genetic features. The tumors were retrieved out of more than 17 000 renal tumors from the Plzen Tumor Registry. Tissues for light microscopy had been fixed, embedded, and stained with hematoxylin and eosin using routine procedures. The tumors were further analyzed using immunohistochemistry, array comparative genomic hybridization, and human androgen receptor. Analyses of VHL gene and loss of heterozygosity (LOH) 3p were also performed. The patients were 2 women and 1 man, with ages ranging from 29 to 35 years (mean, 31.3 years). Grossly, the neoplasms were encapsulated and round with largest diameter of 3.5 cm (mean, 3.2 cm). Follow-up available for all patients ranged from 2 to 14 years (mean, 8 years). No aggressive behavior was noted. Histologically, akin to atrophic (postpyelonephritic) kidney parenchyma, the tumors were composed of follicles of varying sizes that were filled by eosinophilic secretion. Rare areas contained collapsed follicles. Each follicle was endowed with a small capillary. The stroma was loose, inconspicuous, and focally fibrotic. Two types of calcifications were noted: typical psammoma bodies and amorphous dark-blue stained calcified deposits. Immunohistochemically, tumors were strongly positive for cytokeratins (OSCAR), CD10, and vimentin, with weak immunopositivity for CAM5.2 and AE1-AE3. WT1 and cathepsin K were weakly to moderately focally to diffusely positive. Tumors were negative for cytokeratin 20, carbonic anhydrase IX, parvalbumin, HMB45, TTF1, TFE3, chromogranin A, thyroglobulin, PAX8, and ALK. Only 1 case was suitable for molecular genetic analyses. No mutations were found in the VHL gene; no methylation of VHL promoter was noted. No numerical aberrations were found by array comparative genomic hybridization analysis. LOH for chromosome 3p was not detected. Analysis of clonality (human

  5. Foxn1 is essential for vascularization of the murine thymus anlage.

    PubMed

    Mori, Kazuya; Itoi, Manami; Tsukamoto, Noriyuki; Amagai, Takashi

    2010-01-01

    We addressed whether vascularization of the thymus anlage depends on Foxn1 expression. In the thymus anlagen of wild-type mice, CD31(+) endothelial cells are initially observed between epithelial cells on embryonic day (Ed)12.5 and form luminal structure on Ed13. VEGF are produced in epithelial cells and mesenchymal cells which invaginate in the epithelial region of the anlagen on Ed13. However, in the nude thymus anlagen, neither CD31(+) cells nor VEGF producing mesenchymal cells is detected in the epithelial region. The present results indicate that Foxn1 dependent epithelial development is essential for vascularization of the thymus anlagen.

  6. Comparison of different laser systems in the treatment of hypertrophic and atrophic scars and keloids

    NASA Astrophysics Data System (ADS)

    Scharschmidt, D.; Algermissen, Bernd; Willms-Jones, J.-C.; Philipp, Carsten M.; Berlien, Hans-Peter

    1997-12-01

    Different laser systems and techniques are used for the treatment of hypertrophic scars, keloids and acne scars. Significant criteria in selecting a suitable laser system are the scar's vascularization, age and diameter. Flashlamp- pumped dye-lasers, CO2-lasers with scanner, Argon and Nd:YAG-lasers are used. Telangiectatic scars respond well to argon lasers, erythematous scars and keloids to dye-laser treatment. Using interstitial Nd:YAG-laser vaporization, scars with a cross-section over 1 cm can generally be reduced. For the treatment of atrophic and acne scars good cosmetic results are achieved with a CO2-laser/scanner system, which allows a precise ablation of the upper dermis with low risk of side-effects.

  7. Atrophic nerve fibers in regions of reduced MIBG uptake in doxorubicin cardiomyopathy

    SciTech Connect

    Takano, Hajime; Ozawa Hideyuki; Kobayashi, Isao

    1995-11-01

    A myocardial MIBG-SPECT examination was conducted 2 wk after doxorubicin chemotherapy on a 52-yr-old woman without cardiac symptoms. Despite normal {sup 201}Tl scintigraphy, reduced MIBG uptake was detected in the apical anterior, inferior and lateral segments of the left ventricle. The patient died of congestive heart failure due to doxorubicin-induced cardiomyopathy 10 mo later. At necropsy, the left ventricle was markedly dilated and the apical anterior, inferior and lateral walls were thin, stiff and whitish. Nerve fibers in the apical inferior wall were atrophic and markedly fibrotic where MIBG uptake was most reduced. Nerve fibers in the septum were normal where MIBG uptake had remained normal. The histologic findings correspond with the findings on the MIBG image. MIBG imaging may detect cardiac sympathetic denervation in doxorubicin-induced cardiomyopathy before cardiac symptoms are manifest and cardiac function deteriorates. 5 refs., 2 figs.

  8. Factors Modulating Recovery Rate after Intermittent Tetanic Fatigue in Atrophic Soleus

    NASA Astrophysics Data System (ADS)

    Li, Hui; Jiao, Bo; Yu, Zhibin

    2008-06-01

    To specify the factors modulating the recovery rate after intermittent tetanic fatigue in soleus, and to seek the reasons for the decrease of recovery rate in atrophic soleus, we observed the recovery time course of different types of fatigue in isolated muscle strips. A 10 % or 50 % decrease in maximal contraction tension of tetani was defined respectively as slight or moderate fatigue. Tetanic tension recovery rates after short-term and long-term of slight or moderate fatigue were observed, some pharmacological intervention were also used. The results showed that slight fatigue only induced an inhibition to myofibril, while moderate fatigue induced an inhibition in myofibril and sarcoplasmic reticulum Ca2+ release channels. There were significant decreases in all of the fatigue groups in one-week tail-suspended rats. These suggest that both slight and moderate fatigue inhibit the myofibrils and the sarcoplasmic reticulum Ca2+ release channels in one-week unloaded soleus.

  9. Time Course of Atrophic Remodeling: Effects of Exercise on Cardiac Morpology and Function

    NASA Technical Reports Server (NTRS)

    Scott, J. M.; Martin, D.; Caine, T.; Matz, T.; Ploutz-Snyder, L. L.

    2014-01-01

    Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. Exercise training is one intervention that has been shown to confer favorable improvements in LV mass and function during unloading. However, the format and intensity of exercise required to induce optimal cardiac improvements has not been investigated. PURPOSE: This randomized, controlled trial was designed to 1) comprehensively characterize the time course of unloading-induced morpho-functional remodeling, and 2) examine the effects of high intensity exercise training on cardiac structural and functional parameters during unloading. METHODS: Twenty six subjects completed 70 days of head down tilt bed rest (HDBR): 17 were randomized to exercise training (ExBR) and 9 remained sedentary. Exercise consisted of integrated high intensity, continuous, and resistance exercise. We assessed cardiac morphology (left ventricular mass; LVM) and function (speckle-tracking assessment of longitudinal, radial, and circumferential strain and twist) before (BR-2), during (BR7,21,31,70), and following (BR+0, +3) HDBR. Cardiorespiratory fitness (VO2max) was evaluated before (BR- 3), during (BR4,25,46,68) and following (BR+0) HDBR. RESULTS: Sedentary HDBR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain, and an increase in twist. ExBR mitigated decreases in LVM and function. Change in twist was significantly related to change in VO2max (R=0.68, p<0.01). CONCLUSIONS: Alterations in cardiac morphology and function begin early during unloading. High-intensity exercise attenuates atrophic morphological and functional remodeling.

  10. Mesenchymal stem cell implantation in atrophic nonunion of the long bones

    PubMed Central

    Phedy, P.; Kholinne, E.; Djaja, Y. P.; Kusnadi, Y.; Merlina, M.; Yulisa, N. D.

    2016-01-01

    Objectives To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone. Methods Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm3 (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm3 HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment. Results Post-operative pain evaluation showed no significant differences between the two groups. The treatment group demonstrated faster initial radiographic and functional improvements. Statistically significant differences in functional scores were present during the first (p = 0.002), second (p = 0.005) and third (p = 0.01) month. Both groups achieved similar outcomes by the end of one-year follow-up. No immunologic or neoplastic side effects were reported. Conclusions All cases of nonunion of a long bone presented in this study were successfully treated using autologous BM-MSCs. The combination of autologous BM-MSCs and HA granules is a safe method for treating nonunion. Patients treated with BM-MSCs had faster initial radiographic and functional improvements. By the end of 12 months, both groups had similar outcomes. Cite this article: H.D. Ismail, P. Phedy, E. Kholinne, Y. P. Djaja, Y. Kusnadi, M. Merlina, N. D. Yulisa. Mesenchymal stem cell implantation in atrophic nonunion of the long bones: A translational study. Bone Joint Res 2016;5:287–293. DOI: 10.1302/2046-3758.57.2000587. PMID:27412657

  11. Antioxidant and Anticholinesterase Potential of Six Thymus Species

    PubMed Central

    Kindl, Marija; Blažeković, Biljana; Bucar, Franz; Vladimir-Knežević, Sanda

    2015-01-01

    The present study aimed to evaluate antioxidant and acetylcholinesterase (AChE) inhibitory activities of the ethanolic extracts of six selected Thymus species growing in Croatia (T. longicaulis, T. praecox subsp. polytrichus, T. pulegioides, T. serpyllum subsp. serpyllum, T. striatus, and T. vulgaris). Antioxidant effectiveness was assessed using six different assays, in comparison with rosmarinic acid, luteolin, and reference antioxidants. All tested Thymus extracts possessed DPPH (IC50 = 3–6 μg/mL) and nitric oxide (IC50 = 70–177 μg/mL) free radical scavenging activities, strong reducing properties (IC50 = 11–15 μg/mL), ferrous ion chelating activity (IC50 = 126–389 μg/mL), ability to inhibit lipid peroxidation (IC50 = 34–80 μg/mL), and high total antioxidant capacities (238–294 mg AAE/g). AChE inhibitory activity was examined using Ellman's colorimetric method and all tested extracts showed anti-AChE activity in a dose dependent manner. The values of 10–28%, 23–39%, and 64–86% were obtained for tested concentrations of 0.25, 0.5, and 1 mg/mL, respectively. Additionally, the contents of total hydroxycinnamic derivatives, flavonoids, and tannins in dried plant samples were determined spectrophotometrically. Our results highlighted Thymus species as a rich source of natural antioxidants and AChE inhibitors that could be useful in preventing and treating Alzheimer's disease and other neurodegenerative disorders. PMID:26351513

  12. Monocyte chemoattractant protein 1 (MCP-1/CCL2) contributes to thymus atrophy in acute myeloid leukemia.

    PubMed

    Driss, Virginie; Quesnel, Bruno; Brinster, Carine

    2015-02-01

    Recent studies on acute myelogenous leukemia (AML) patients have revealed the existence of T-cell immunodeficiencies, characterized by peripheral T lymphocytes that are unable to interact with blasts, reduced thymic emigrants and oligoclonal restricted repertoires. These observations suggest that there is a profound thymic dysregulation, which is difficult to study in AML patients. Using the C1498 AML mouse model, we demonstrated that leukemia development was associated with thymus atrophy, which was defined by abnormal organ weight and reduced cellularity. In addition, we observed a dramatic loss of peripheral CD4(+) and CD8(+) T-cell numbers with increased frequencies of CD4(+) FoxP3(+) regulatory and activated/memory T cells. Investigating the mechanisms leading to this atrophy, we observed a significant accumulation of the monocyte chemoattractant protein 1 (MCP-1/CCL2) in thymi of leukemic mice. Treatment of AML-bearing animals with a blocking anti-CCL2 antibody revealed a lower tumor burden, augmented antileukemic T-cell responses, and improved survival rate compared to nontreated mice. These results were not observed when neutralization of CCL2 was performed in thymectomized mice. Altogether, we show that the CCL2 protein participates in thymic atrophy in AML mice, and this could have important implications for future immunotherapeutic strategies.

  13. Morphology and Immunohistochemical Phenotype of the Thymus in Secondary Immunodeficiency.

    PubMed

    Struchko, G Yu; Merkulova, L M; Moskvichev, E V; Kostrova, O Yu; Mikhailova, M N; Drandrova, E G

    2015-10-01

    The thymus of outbred male rats 5 months after splenectomy (experimental secondary immunodeficiency) was studied by common histological and immunohistochemical methods using monoclonal and polyclonal antibodies to CD3, CD30, CD68, synaptophysin, to S100, p53, bcl-2, and Ki-67 proteins. Removal of the spleen led to acute involution of the thymic parenchyma, which was replaced by the adipose tissue and was associated with restructuring of the thymopoietic and nonthymopoietic components of the gland, changes in cellular composition and antigenic phenotype of the lobular cortical and medullary matter, and by reduction of cell proliferation.

  14. HIV-Specific CD8+ T-Cell Immunity in Humanized Bone Marrow–Liver–Thymus Mice

    PubMed Central

    Dudek, Timothy E.; Allen, Todd M.

    2013-01-01

    CD8+ T-cell responses play a critical role in the control of human immunodeficiency virus (HIV) infection, and recent vaccine studies in nonhuman primates now demonstrate the ability of T cells to prevent the early dissemination of simian immunodeficiency virus and perhaps clear residual infection. Recent advances in humanized mouse models, in particular the humanized bone marrow–liver–thymus (BLT) mouse model, show promise in their ability not only to support sustained infection with HIV, but also to recapitulate human HIV-specific immunity. The availability of a small-animal model with which to study human-specific immune responses to HIV would greatly facilitate the elucidation of mechanisms of immune control, as well as accelerate the iterative testing of promising vaccine candidates. Here we discuss data from our recent study detailing the composition and efficacy of HIV-specific CD8+ T-cell responses in humanized BLT mice that was recently presented at a Harvard Center for AIDS Research symposium on humanized mouse models for HIV vaccine design. PMID:24151322

  15. Lymphotoxin β Receptor Controls T Cell Progenitor Entry to the Thymus.

    PubMed

    Lucas, Beth; James, Kieran D; Cosway, Emilie J; Parnell, Sonia M; Tumanov, Alexi V; Ware, Carl F; Jenkinson, William E; Anderson, Graham

    2016-10-01

    The recruitment of lymphoid progenitors to the thymus is essential to sustain T cell production throughout life. Importantly, it also limits T lineage regeneration following bone marrow transplantation, and so contributes to the secondary immunodeficiency that is caused by delayed immune reconstitution. Despite this significance, the mechanisms that control thymus colonization are poorly understood. In this study, we show that in both the steady-state and after bone marrow transplant, lymphotoxin β receptor (LTβR) controls entry of T cell progenitors to the thymus. We show that this requirement maps to thymic stroma, further underlining the key importance of this TNFR superfamily member in regulation of thymic microenvironments. Importantly, analysis of the requirement for LTβR in relationship to known regulators of thymus seeding suggests that it acts independently of its regulation of thymus-homing chemokines. Rather, we show that LTβR differentially regulates intrathymic expression of adhesion molecules known to play a role in T cell progenitor entry to the thymus. Finally, Ab-mediated in vivo LTβR stimulation following bone marrow transplant enhances initial thymus recovery and boosts donor-derived T cell numbers, which correlates with increased adhesion molecule expression by thymic stroma. Collectively, we reveal a novel link between LTβR and thymic stromal cells in thymus colonization, and highlight its potential as an immunotherapeutic target to boost T cell reconstitution after transplantation. PMID:27549174

  16. T cells generated in the absence of a thoracic thymus fail to establish homeostasis.

    PubMed

    Smolarchuk, Christa; Zhu, Lin Fu; Chan, William F N; Anderson, Colin C

    2014-08-01

    Cervical thymus mimics the thoracic thymus in supporting T-cell development and exists in a subset of mice and humans. Importantly, it remains unknown whether the cervical thymus can generate T cells that are self-tolerant in the complete absence of signals from the thoracic thymus. Using a fetal liver reconstitution model in thoracic thymectomized RAG(-/-) mice, we found that T cells could be generated without contribution from the thoracic thymus. However, these mice had decreased T cells, increased proportions of effector memory T cells and Treg phenotype cells, increased serum IgG1/2b, and increased frequency of T cells expressing IFN-γ, IL-17 or IL-10. Half of the mice that received a thoracic thymectomy and fetal liver cells, unlike sham surgery controls, developed substantial morbidity with age. Disease was associated with lymphopenia-driven activation rather than inherent defects in the cervical thymus, as both thoracic and cervical thymocytes could generate disease in lymphopenic recipients. Administration of the homeostatic cytokine IL-7 caused a rapid, transient increase in T-cell numbers and reduced the time to disease onset. Together the data suggests that the cervical thymus can function in the complete absence of the thoracic thymus; however, the T cells generated do not establish homeostasis.

  17. Lymphotoxin β Receptor Controls T Cell Progenitor Entry to the Thymus

    PubMed Central

    Lucas, Beth; James, Kieran D.; Cosway, Emilie J.; Parnell, Sonia M.; Tumanov, Alexi V.; Ware, Carl F.; Jenkinson, William E.

    2016-01-01

    The recruitment of lymphoid progenitors to the thymus is essential to sustain T cell production throughout life. Importantly, it also limits T lineage regeneration following bone marrow transplantation, and so contributes to the secondary immunodeficiency that is caused by delayed immune reconstitution. Despite this significance, the mechanisms that control thymus colonization are poorly understood. In this study, we show that in both the steady-state and after bone marrow transplant, lymphotoxin β receptor (LTβR) controls entry of T cell progenitors to the thymus. We show that this requirement maps to thymic stroma, further underlining the key importance of this TNFR superfamily member in regulation of thymic microenvironments. Importantly, analysis of the requirement for LTβR in relationship to known regulators of thymus seeding suggests that it acts independently of its regulation of thymus-homing chemokines. Rather, we show that LTβR differentially regulates intrathymic expression of adhesion molecules known to play a role in T cell progenitor entry to the thymus. Finally, Ab-mediated in vivo LTβR stimulation following bone marrow transplant enhances initial thymus recovery and boosts donor-derived T cell numbers, which correlates with increased adhesion molecule expression by thymic stroma. Collectively, we reveal a novel link between LTβR and thymic stromal cells in thymus colonization, and highlight its potential as an immunotherapeutic target to boost T cell reconstitution after transplantation. PMID:27549174

  18. Thymus recovery after intensive physical exercise under conditions of immunocorrection and without it.

    PubMed

    Sapin, M R; Tkachuk, M G

    2005-11-01

    Exogenous antioxidants, e.g. tocopherol, prevent undesirable changes in the thymus and accelerate its recovery after intensive physical exercise. Four weeks after the end of training (swimming) the general structure of the thymus and content of LPO products in rats treated with tocopherol corresponded to the control values, in contrast to animals receiving no correction.

  19. Failure of blood-thymus barrier as a mechanism of tumor and trophoblast escape.

    PubMed

    Bubanovic, I V

    2003-03-01

    A major process through which the immune system becomes tolerant to self-proteins involves the deletion of self-reactive clones in the thymus, but clonal deletion is not single mechanisms of thymic tolerance. There is now much evidence that intrathymic antigen expression results in anergy induction of T helper type-1 (Th1) clones in the periphery. Blood-thymus barrier is most important structure for prevention of unwanted penetration of antigens into the thymus. Impermeability of the barrier restrain induction of acquired thymic tolerance on unwanted antigens like microbes and tumor cells. Nevertheless, one of most important mechanism of tumor and trophoblast escape is in anergy of Th1 cells and in Th2 cells domination. Many mechanisms are included in disarrangement of Th1/Th2 balance in pregnancy and tumor bearers, but one of possibility is in failure of blood-thymus barrier. Possible consequences of blood-thymus barrier failure are trophoblast-specific or tumor-specific antigens penetrate into the thymus, deletion or anergy of antigen-specific clones and acquired thymic tolerance induction. Blood-thymus barrier is variable structure in anatomical and functional sense so that in certain condition foreign antigens probably can permeate across the barrier. Probability that some factors like hormones, cytokines, prostaglandine and neuromediators can affect blood-thymus barrier permeability and contribute in mechanisms of trophoblast and tumor escape is real but relatively unexplored.

  20. Noninvasive In Toto Imaging of the Thymus Reveals Heterogeneous Migratory Behavior of Developing T Cells.

    PubMed

    Bajoghli, Baubak; Kuri, Paola; Inoue, Daigo; Aghaallaei, Narges; Hanelt, Marleen; Thumberger, Thomas; Rauzi, Matteo; Wittbrodt, Joachim; Leptin, Maria

    2015-09-01

    The migration of developing T cells (thymocytes) between distinct thymic microenvironments is crucial for their development. Ex vivo studies of thymus tissue explants suggest two distinct migratory behaviors of thymocytes in the thymus. In the cortex, thymocytes exhibit a stochastic migration, whereas medullary thymocytes show confined migratory behavior. Thus far, it has been difficult to follow all thymocytes in an entire thymus and relate their differentiation steps to their migratory dynamics. To understand the spatial organization of the migratory behavior and development of thymocytes in a fully functional thymus, we developed transgenic reporter lines for the chemokine receptors ccr9a and ccr9b, as well as for rag2, and used them for noninvasive live imaging of the entire thymus in medaka (Oryzias latipes). We found that the expression of these two chemokine receptors in the medaka juvenile thymus defined two spatially distinct subpopulations of thymocytes. Landmark events of T cell development including proliferation, somatic recombination, and thymic selection can be mapped to subregions of the thymus. The migratory behavior of thymocytes within each of the subpopulations is equally heterogeneous, and specific migratory behaviors are not associated with particular domains in the thymus. During the period when thymocytes express rag2 their migratory behavior was more homogeneous. Therefore, the migratory behavior of thymocytes is partly correlated with their developmental stage rather than being defined by their spatial localization.

  1. Thymus medulla under construction: Time and space oddities.

    PubMed

    Alves, Nuno L; Ribeiro, Ana R

    2016-04-01

    The development of effective T-cell-based immunotherapies to treat infection, cancer, and autoimmunity should incorporate the ground rules that control differentiation of T cells in the thymus. Within the thymus, thymic epithelial cells (TECs) provide microenvironments supportive of the generation and selection of T cells that are responsive to pathogen-derived antigens, and yet tolerant to self-determinants. Defects in TEC differentiation cause syndromes that range from immunodeficiency to autoimmunity, which makes the study of TECs of fundamental and clinical importance to comprehend how immunity and tolerance are balanced. Critical to tolerance induction are medullary thymic epithelial cells (mTECs), which purge autoreactive T cells, or redirect them to a regulatory T-cell lineage. In this issue of the European Journal of Immunology, studies by Baik et al. and Mayer et al. [Eur. J. Immunol. 2016. 46: XXXX-XXXX and 46: XXXX-XXXX]) document novel spatial-temporal singularities in the lineage specification and maintenance of mTECs. While Baik et al. define a developmental checkpoint during mTEC specification in the embryo, Mayer et al. reveal that the generation and maintenance of the adult mTEC compartment is temporally controlled in vivo. The two reports described new developmentally related, but temporally distinct principles that underlie the homeostasis of the thymic medulla across life. PMID:26947141

  2. T cell receptor diversity in the human thymus.

    PubMed

    Vanhanen, Reetta; Heikkilä, Nelli; Aggarwal, Kunal; Hamm, David; Tarkkila, Heikki; Pätilä, Tommi; Jokiranta, T Sakari; Saramäki, Jari; Arstila, T Petteri

    2016-08-01

    A diverse T cell receptor (TCR) repertoire is essential for adaptive immune responses and is generated by somatic recombination of TCRα and TCRβ gene segments in the thymus. Previous estimates of the total TCR diversity have studied the circulating mature repertoire, identifying 1 to 3×10(6) unique TCRβ and 0.5×10(6) TCRα sequences. Here we provide the first estimate of the total TCR diversity generated in the human thymus, an organ which in principle can be sampled in its entirety. High-throughput sequencing of samples from four pediatric donors detected up to 10.3×10(6) unique TCRβ sequences and 3.7×10(6) TCRα sequences, the highest directly observed diversity so far for either chain. To obtain an estimate of the total diversity we then used three different estimators, preseq and DivE, which measure the saturation of rarefaction curves, and Chao2, which measures the size of the overlap between samples. Our results provide an estimate of a thymic repertoire consisting of 40 to 70×10(6) unique TCRβ sequences and 60 to 100×10(6) TCRα sequences. The thymic repertoire is thus extremely diverse. Moreover, extrapolation of the data and comparison with earlier estimates of peripheral diversity also suggest that the thymic repertoire is transient, with different clones produced at different times.

  3. Thymus medulla under construction: Time and space oddities.

    PubMed

    Alves, Nuno L; Ribeiro, Ana R

    2016-04-01

    The development of effective T-cell-based immunotherapies to treat infection, cancer, and autoimmunity should incorporate the ground rules that control differentiation of T cells in the thymus. Within the thymus, thymic epithelial cells (TECs) provide microenvironments supportive of the generation and selection of T cells that are responsive to pathogen-derived antigens, and yet tolerant to self-determinants. Defects in TEC differentiation cause syndromes that range from immunodeficiency to autoimmunity, which makes the study of TECs of fundamental and clinical importance to comprehend how immunity and tolerance are balanced. Critical to tolerance induction are medullary thymic epithelial cells (mTECs), which purge autoreactive T cells, or redirect them to a regulatory T-cell lineage. In this issue of the European Journal of Immunology, studies by Baik et al. and Mayer et al. [Eur. J. Immunol. 2016. 46: XXXX-XXXX and 46: XXXX-XXXX]) document novel spatial-temporal singularities in the lineage specification and maintenance of mTECs. While Baik et al. define a developmental checkpoint during mTEC specification in the embryo, Mayer et al. reveal that the generation and maintenance of the adult mTEC compartment is temporally controlled in vivo. The two reports described new developmentally related, but temporally distinct principles that underlie the homeostasis of the thymic medulla across life.

  4. Serological analysis and characterization of calf thymus ribonuclease H IIb.

    PubMed

    Vonwirth, H; Frank, P; Büsen, W

    1989-09-15

    Ribonuclease H IIb, which seems to play a physiological role during transcription, was purified from calf thymus tissue. A polyclonal antibody, raised against the most purified ribonuclease H IIb fraction, recognizes in crude extracts almost exclusively a 52-kDa protein band. By immunoaffinity chromatography and immunoprecipitation experiments, we are able to deplete enzyme extracts from the crossreacting 52-kDa protein band and from ribonuclease H IIb activity. Enzyme activity is eluted from the immunoaffinity matrix in association with a 52-kDa protein under denaturing conditions. Immunoaffinity chromatography enables us also to calculate a purification factor of around 20,000 from the crude extract. The native molecular mass for the enzyme of around 45 kDa, as determined by gel filtration, suggests that calf thymus ribonuclease H IIb is most probably monomeric. The enzyme possesses an isoelectric point of 7.0. It requires Mg2+ ions for activity, is inhibited by N-ethylmaleimide, and exhibits a pH optimum of 9.0-9.5. The enzyme releases oligoribonucleotides with 3'-OH and 5'-phosphate ends, probably in an exonucleolytical manner. The third largest subunit of yeast RNA polymerase A (I) displays ribonuclease H activity [Huet et al. (1976) Nature 261, 431-433]. We discuss our findings in the light of a possible association of ribonuclease H IIb and RNA polymerase A (I) in higher eukaryotes.

  5. Expression of pemphigus-autoantigen desmoglein 1 in human thymus.

    PubMed

    Mouquet, H; Berrih-Aknin, S; Bismuth, J; Joly, P; Gilbert, D; Tron, F

    2008-05-01

    Desmoglein (Dsg) 1 is a transmembrane glycoprotein of the desmosome allowing cell-cell adhesion between keratinocytes, whose expression is restricted to stratified squamous epithelia-like epidermis. Dsg1 is the target autoantigen of pathogenic autoantibodies produced by pemphigus foliaceus and 50% of pemphigus vulgaris patients in a Dsg1-specific T-cell-dependent pathway. Herewith, we show that mRNA of the DSG1 gene is present in normal human thymus and show by quantitative real-time polymerase chain reaction analysis that the expression of DSG1 transcript increases with age. Although immunoblot analysis on human thymus extracts using different anti-Dsg1 antibodies did not allow to detect the protein, we show by double-immunofluorescence assay that Dsg1 is expressed at protein level by CD19+ CD63+ cells located in the medulla. These data provide another illustration of the thymic expression of a tissue-specific autoantigen involved in an organ-specific autoimmune disease, which may participate in the tolerance acquisition and/or regulation of Dsg1-specific T cells.

  6. Genetic diversity and chemical polymorphism of some Thymus species.

    PubMed

    Rustaiee, Ali Reza; Yavari, Alireza; Nazeri, Vahideh; Shokrpour, Majid; Sefidkon, Fatemeh; Rasouli, Musa

    2013-06-01

    To ascertain whether there are chemical and genetic relationships among some Thymus species and also to determine correlation between these two sets of data, the essential-oil composition and genetic variability of six populations of Thymus including: T. daenensis ČELAK. (two populations), T. fallax FISCH. & C.A.MEY., T. fedtschenkoi RONNIGER, T. migricus KLOKOV & DES.-SHOST., and T. vulgaris L. were analyzed by GC and GC/MS, and also by randomly amplified polymorphic DNA (RAPD). Thus, 27 individuals were analyzed using 16 RAPD primers, which generated 264 polymorphic scorable bands and volatiles isolated by distillation extraction were subjected to GC and GC/MS analyses. The yields of oils ranged from 2.1 to 3.8% (v/w), and 34 components were identified, amounting to a total percentage of 97.8-99.9%. RAPD Markers allowed a perfect distinction between the different species based on their distinctive genetic background. However, they did not show identical clustering with the volatile-oil profiles. PMID:23776024

  7. Intermittent midline suprasternal neck mass caused by superior herniation of the thymus.

    PubMed

    Su, Siew Choo; Hess, Thomas; Whybourne, Annie; Chang, Anne B

    2015-03-01

    Neck masses in infants and children have a wide differential diagnosis. However, neck masses apparent only during raised intrathoracic pressure are rare with a limited number of causes, including superior herniation of the normal thymus, apical lung herniation, jugular phlebectasia and laryngocoele. These conditions can easily be differentiated from one another by imaging. We present an infant with intermittent suprasternal neck mass visible only during increased intrathoracic pressure, produced either by crying or straining. Diagnosis of superior herniation of the thymus into the neck was confirmed by ultrasonography with the characteristic sonographic appearances of the normal thymus as well as its shape, size and location. Ultrasonography should be the first imaging modality of choice. Management of superior herniation of the thymus into the neck should be conservative as the thymus naturally involutes with increasing age. Awareness of the differential diagnosis of neck swelling present only on Vasalva manoeuvre or increased intrathoracic pressure is important to prevent unnecessary tests, avoid radiation, biopsy and surgery.

  8. Pharmacological modulation of caspase-8 in thymus-related medical conditions.

    PubMed

    Pozzesi, Nicola; Fierabracci, Alessandra; Thuy, Trinh Thy; Martelli, Maria Paola; Liberati, Anna Marina; Ayroldi, Emira; Riccardi, Carlo; Delfino, Domenico V

    2014-10-01

    The thymus is a lymphoid organ that governs the development of a diverse T-cell repertoire capable of defending against nonself-antigens and avoiding autoimmunity. However, the thymus can also succumb to different diseases. Hypertrophic diseases, such as thymomas, are typically associated with impairment of negative selection, which leads to autoimmune disease, or disruption of positive selection, which results in immunodeficiency. Hypotrophic diseases of the thymus can manifest during acute infections, cancer, allogeneic bone marrow transplantation, or with aging. This condition leads to decreased immune function and can be treated by either replacing lost thymic tissue or by preventing thymic tissue death. Studies have demonstrated the critical role of caspase-8 in regulating apoptosis in the thymus. In this review, we discuss how pharmacological activation and inhibition of caspase-8 can be used to treat hypertrophic and hypotrophic diseases of the thymus, respectively, to improve its function.

  9. Contributory and exacerbating roles of gaseous ammonia and organic dust in the etiology of atrophic rhinitis.

    PubMed

    Hamilton, T D; Roe, J M; Hayes, C M; Jones, P; Pearson, G R; Webster, A J

    1999-03-01

    Pigs reared commercially indoors are exposed to air heavily contaminated with particulate and gaseous pollutants. Epidemiological surveys have shown an association between the levels of these pollutants and the severity of lesions associated with the upper respiratory tract disease of swine atrophic rhinitis. This study investigated the role of aerial pollutants in the etiology of atrophic rhinitis induced by Pasteurella multocida. Forty, 1-week-old Large White piglets were weaned and divided into eight groups designated A to H. The groups were housed in Rochester exposure chambers and continuously exposed to the following pollutants: ovalbumin (groups A and B), ammonia (groups C and D), ovalbumin plus ammonia (groups E and F), and unpolluted air (groups G and H). The concentrations of pollutants used were 20 mg m-3 total mass and 5 mg m-3 respirable mass for ovalbumin dust and 50 ppm for ammonia. One week after exposure commenced, the pigs in groups A, C, E, and G were infected with P. multocida type D by intranasal inoculation. After 4 weeks of exposure to pollutants, the pigs were killed and the extent of turbinate atrophy was assessed with a morphometric index (MI). Control pigs kept in clean air and not inoculated with P. multocida (group H) had normal turbinate morphology with a mean MI of 41.12% (standard deviation [SD], +/- 1. 59%). In contrast, exposure to pollutants in the absence of P. multocida (groups B, D, and F) induced mild turbinate atrophy with mean MIs of 49.65% (SD, +/-1.96%), 51.04% (SD, +/-2.06%), and 49.88% (SD, +/-3.51%), respectively. A similar level of atrophy was also evoked by inoculation with P. multocida in the absence of pollutants (group G), giving a mean MI of 50.77% (SD, +/-2.07%). However, when P. multocida inoculation was combined with pollutant exposure (groups A, C, and E) moderate to severe turbinate atrophy occurred with mean MIs of 64.93% (SD, +/-4.64%), 59.18% (SD, +/-2.79%), and 73.30% (SD, +/-3.19%), respectively. The

  10. [The application of helium-neon laser radiation for the combined treatment of the patients with atrophic rhinitis].

    PubMed

    Sharipov, R A; Sharipova, E R

    2012-01-01

    The objective of the present study was to improve the efficacy of the treatment of the patients presenting with atrophic rhinitis (ozena) of the upper respiratory tract by the application of helium-neon laser radiation. A total of 120 patients aged from 15 to 53 years were treated based at the Department of Otorhinolaryngology, G.G. Kuvatov Republican Clinical Hospital, Ufa. All these patients underwent routine clinical, roentgenological, microbiological, and rheographic examination. The method for the treatment of atrophic rhinitis is described; it includes the application of helium-neon laser radiation in combination with the administration of the purified preparation of liquid polyvalent Klebsiella bacteriophage. The positive results of the treatment by the proposed method were documented in 90% of the patients. PMID:23268248

  11. [Reasoning of the usage of multimicroelement drugs and monophytodrugs in complex treatment of patients with chronic atrophic gastritis].

    PubMed

    Molodovets', O B; Pozur, N Z; Havrysh, T Iu; Chaplyns'ka, N V; Zozuliak, N V; Iurak, M Z; Kulaiets', V M

    2014-01-01

    It was investigeted 126 patients with chronic atrophic gastritis, aged 19-73 years. Chronic inflammatory and degenerative processes of the gastric mucosa contributed to the destabilization of cell membranes. We found that patients with chronicatrophic gastritis have disturbances of lipid peroxidation and antioxidant defense, which is manifested by the accumulation of products of peroxidation and decreased activity of enzymes of antioxidant defense. Activation of lipid peroxidation, accompanied by increased levels of proinflammatory cytokines and deficiency of essential trace elements imbalance contributes antioxidant defense. After using basic therapy, it was no certain normalization of lipid peroxidation, antioxidant defense and restoration of microelement homeostasis in patients with chronic atrophic gastritis, which served as the justification for the development and testing of methods of treatment with the purpose of regulation of these processes.

  12. Serum OPN Expression for Identification of Gastric Cancer and Atrophic Gastritis and Its Influencing Factors

    PubMed Central

    Chen, Tiejun; Sun, Liping; He, Caiyun; Gong, Yuehua; Xu, Qian; Yuan, Yuan

    2014-01-01

    Background Most studies have found that osteopontin (OPN) expression level is related to the poor prognosis of gastric cancer. However, few studies have examined the relationship between OPN expression and gastric precancerous diseases, and the potential role of OPN in the formation and development of GC. We investigated the relationships between serum OPN levels and the risks of gastric cancer (GC) and its precancerous disease, to explore the diagnostic efficacy of serum OPN level for GC and atrophic gastritis and its influencing factors. Methods A total of 1,452 patients were enrolled, including 609 with mild superficial gastritis (SG), 594 with atrophic gastritis (AG) and 249 with GC. The levels of serum OPN and serum Helicobacter pylori IgG antibody were detected by enzyme-linked immunosorbent assay. Results Serum OPN levels increased from mild SG (1.99±1.91 ng/ml) to AG (2.37±2.27 ng/ml) to GC (5.94±4.52 ng/ml) (P≤0.002), along with increasing severity of gastric disease. OPN levels were significantly higher in patients with GC compared with the non-cancer population (2.17±2.10, P<0.0001). Serum OPN level was positively correlated with age and was higher in men than women, but was not correlated with H. pylori infection status. The area under the receiver operating characteristic curve was 0.805, the optimal cutoff was 2.56 ng/ml and the sensitivity and specificity were 74.3% and 71.8%, respectively, for the ability of serum OPN to discriminate GC. Conclusions Serum OPN expression was closely related to the risks of GC and AG, and it might be a useful marker for the discrimination of GC. OPN level was positively correlated with age and male sex, but was not affected by H. pylori infection, and it was promoted by smoking and drinking, in patients with mild SG. PMID:25479069

  13. Artificial neural networks in the recognition of the presence of thyroid disease in patients with atrophic body gastritis

    PubMed Central

    Lahner, Edith; Intraligi, Marco; Buscema, Massimo; Centanni, Marco; Vannella, Lucy; Grossi, Enzo; Annibale, Bruno

    2008-01-01

    AIM: To investigate the role of artificial neural networks in predicting the presence of thyroid disease in atrophic body gastritis patients. METHODS: A dataset of 29 input variables of 253 atrophic body gastritis patients was applied to artificial neural networks (ANNs) using a data optimisation procedure (standard ANNs, T&T-IS protocol, TWIST protocol). The target variable was the presence of thyroid disease. RESULTS: Standard ANNs obtained a mean accuracy of 64.4% with a sensitivity of 69% and a specificity of 59.8% in recognizing atrophic body gastritis patients with thyroid disease. The optimization procedures (T&T-IS and TWIST protocol) improved the performance of the recognition task yielding a mean accuracy, sensitivity and specificity of 74.7% and 75.8%, 78.8% and 81.8%, and 70.5% and 69.9%, respectively. The increase of sensitivity of the TWIST protocol was statistically significant compared to T&T-IS. CONCLUSION: This study suggests that artificial neural networks may be taken into consideration as a potential clinical decision-support tool for identifying ABG patients at risk for harbouring an unknown thyroid disease and thus requiring diagnostic work-up of their thyroid status. PMID:18203288

  14. Molecular Genotyping of Anisakis Larvae in Middle Eastern Japan and Endoscopic Evidence for Preferential Penetration of Normal over Atrophic Mucosa

    PubMed Central

    Arai, Toshio; Akao, Nobuaki; Seki, Takenori; Kumagai, Takashi; Ishikawa, Hirofumi; Ohta, Nobuo; Hirata, Nobuto; Nakaji, So; Yamauchi, Kenji; Hirai, Mitsuru; Shiratori, Toshiyasu; Kobayashi, Masayoshi; Fujii, Hiroyuki; Ishii, Eiji; Naito, Mikio; Saitoh, Shin-ichi; Yamaguchi, Toshikazu; Shibata, Nobumitsu; Shimo, Masamune; Tokiwa, Toshihiro

    2014-01-01

    Background Anisakiasis is a parasitic disease caused primarily by Anisakis spp. larvae in Asia and in Western countries. The aim of this study was to investigate the genotype of Anisakis larvae endoscopically removed from Middle Eastern Japanese patients and to determine whether mucosal atrophy affects the risk of penetration in gastric anisakiasis. Methods In this study, 57 larvae collected from 44 patients with anisakiasis (42 gastric and 2 colonic anisakiasis) were analyzed retrospectively. Genotyping was confirmed by restriction fragment length polymorphism (RFLP) analysis of ITS regions and by sequencing the mitochondrial small subunit (SSU) region. In the cases of gastric anisakiasis, correlation analyses were conducted between the frequency of larval penetration in normal/atrophic area and the manifestation of clinical symptoms. Results Nearly all larvae were A. simplex seusu stricto (s.s.) (99%), and one larva displayed a hybrid genotype. The A. simplex larvae penetrated normal mucosa more frequently than atrophic area (p = 0.005). Finally, patients with normal mucosa infection were more likely to exhibit clinical symptoms than those with atrophic mucosa infection (odds ratio, 6.96; 95% confidence interval, 1.52–31.8). Conclusions In Japan, A. simplex s.s. is the main etiological agent of human anisakiasis and tends to penetrate normal gastric mucosa. Careful endoscopic examination of normal gastric mucosa, particularly in the greater curvature of the stomach will improve the detection of Anisakis larvae. PMID:24586583

  15. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis

    PubMed Central

    Shen, Jian; Song, Ning; Williams, Christopher J.; Brown, Celeste J.; Yan, Zheng; Xu, Chen; Forney, Larry J.

    2016-01-01

    Atrophic vaginitis (AV) is common in postmenopausal women, but its causes are not well understood. The symptoms, which include vaginal itching, burning, dryness, irritation, and dyspareunia, can usually be alleviated by low doses of estrogen given orally or locally. Regrettably, the composition of vaginal bacterial communities in women with AV have not been fully characterized and little is known as to how these communities change over time in response to hormonal therapy. In the present intervention study we determined the response of vaginal bacterial communities in postmenopausal women with AV to low-dose estrogen therapy. The changes in community composition in response to hormonal therapy were rapid and typified by significant increases in the relative abundance of Lactobacillus spp. that were mirrored by a decreased relative abundance of Gardnerella. These changes were paralleled by a significant four-fold increase in serum estradiol levels and decreased vaginal pH, as well as nearly a two-fold increase in the Vaginal Maturation Index (VMI). The results suggest that after menopause a vaginal microbiota dominated by species of Lactobacillus may have a beneficial role in the maintenance of health and these findings that could lead to new strategies to protect postmenopausal women from AV. PMID:27103314

  16. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis.

    PubMed

    Shen, Jian; Song, Ning; Williams, Christopher J; Brown, Celeste J; Yan, Zheng; Xu, Chen; Forney, Larry J

    2016-01-01

    Atrophic vaginitis (AV) is common in postmenopausal women, but its causes are not well understood. The symptoms, which include vaginal itching, burning, dryness, irritation, and dyspareunia, can usually be alleviated by low doses of estrogen given orally or locally. Regrettably, the composition of vaginal bacterial communities in women with AV have not been fully characterized and little is known as to how these communities change over time in response to hormonal therapy. In the present intervention study we determined the response of vaginal bacterial communities in postmenopausal women with AV to low-dose estrogen therapy. The changes in community composition in response to hormonal therapy were rapid and typified by significant increases in the relative abundance of Lactobacillus spp. that were mirrored by a decreased relative abundance of Gardnerella. These changes were paralleled by a significant four-fold increase in serum estradiol levels and decreased vaginal pH, as well as nearly a two-fold increase in the Vaginal Maturation Index (VMI). The results suggest that after menopause a vaginal microbiota dominated by species of Lactobacillus may have a beneficial role in the maintenance of health and these findings that could lead to new strategies to protect postmenopausal women from AV.

  17. Are atrophic long-bone nonunions associated with low-grade infections?

    PubMed Central

    Dapunt, Ulrike; Spranger, Ole; Gantz, Simone; Burckhardt, Irene; Zimmermann, Stefan; Schmidmaier, Gerhard; Moghaddam, Arash

    2015-01-01

    Impaired fracture healing, especially when associated with bacterial infection, is a severe complication following long-bone fractures and requires special treatment. Because standard diagnostic techniques might provide falsely negative results, we evaluated the sonication method for detection of bacteria on implants of patients with fracture nonunions. A total of 49 patients with a nonunion (group NU) and, for comparison, 45 patients who had undergone routine removal of osteosynthetic material (group OM), were included in the study. Five different diagnostic methods (culture of tissue samples, culture of intraoperative swabs, histopathology of tissue samples, culture of sonication fluid, and 16S ribosomal DNA polymerase chain reaction of sonication fluid) were compared and related to clinical data. Among the diagnostic tests, culture of sonication fluid demonstrated by far the highest detection rate of bacteria (57%) in group NU, and rather unexpectedly 40% in group OM. Culture of sonication samples also revealed a broad spectrum of bacteria, in particular Propionibacterium spp. In conclusion, our results indicate that more bacteria can be detected on implants of patients with atrophic nonunions of long-bone fractures by means of the sonication procedure, which provides a valuable additional diagnostic tool to decide on a surgical procedure (eg, two-step procedure) and to further specify antimicrobial therapy. PMID:26719698

  18. Impaired translocation of GLUT4 results in insulin resistance of atrophic soleus muscle.

    PubMed

    Xu, Peng-Tao; Song, Zhen; Zhang, Wen-Cheng; Jiao, Bo; Yu, Zhi-Bin

    2015-01-01

    Whether or not the atrophic skeletal muscle induces insulin resistance and its mechanisms are not resolved now. The antigravity soleus muscle showed a progressive atrophy in 1-week, 2-week, and 4-week tail-suspended rats. Hyperinsulinemic-euglycemic clamp showed that the steady-state glucose infusion rate was lower in 4-week tail-suspended rats than that in the control rats. The glucose uptake rates under insulin- or contraction-stimulation were significantly decreased in 4-week unloaded soleus muscle. The key protein expressions of IRS-1, PI3K, and Akt on the insulin-dependent pathway and of AMPK, ERK, and p38 on the insulin-independent pathway were unchanged in unloaded soleus muscle. The unchanged phosphorylation of Akt and p38 suggested that the activity of two signal pathways was not altered in unloaded soleus muscle. The AS160 and GLUT4 expression on the common downstream pathway also was not changed in unloaded soleus muscle. But the GLUT4 translocation to sarcolemma was inhibited during insulin stimulation in unloaded soleus muscle. The above results suggest that hindlimb unloading in tail-suspended rat induces atrophy in antigravity soleus muscle. The impaired GLUT4 translocation to sarcolemma under insulin stimulation may mediate insulin resistance in unloaded soleus muscle and further affect the insulin sensitivity of whole body in tail-suspended rats.

  19. The Diagnostic Value of Gastrin-17 Detection in Atrophic Gastritis: A Meta-Analysis.

    PubMed

    Wang, Xu; Ling, Li; Li, Shanshan; Qin, Guiping; Cui, Wei; Li, Xiang; Ni, Hong

    2016-05-01

    A meta-analysis was performed to assess the diagnostic value of gastrin-17 (G-17) for the early detection of chronic atrophic gastritis (CAG).An extensive literature search was performed, with the aim of selecting publications that reported the accuracy of G-17 in predicting CAG, in the following databases: PubMed, Science Direct, Web of Science, Chinese Biological Medicine, Chinese National Knowledge Infrastructure, Wanfang, and VIP. To assess the diagnostic value of G-17, the following statistics were estimated and described: sensitivity, specificity, diagnostic odds ratios (DOR), summary receiver operating characteristic curves, area under the curve (AUC), and 95% confidence intervals (CIs).Thirteen studies that met the inclusion criteria were included in this meta-analysis, comprising 894 patients and 1950 controls. The pooled sensitivity and specificity of these studies were 0.48 (95% CI: 0.45-0.51) and 0.79 (95% CI: 0.77-0.81), respectively. The DOR was 5.93 (95% CI: 2.93-11.99), and the AUC was 0.82.G-17 may have potential diagnostic value because it has good specificity and a moderate DOR and AUC for CAG. However, more studies are needed to improve the sensitivity of this diagnostic tool in the future.

  20. Risk for gastric neoplasias in patients with chronic atrophic gastritis: A critical reappraisal

    PubMed Central

    Vannella, Lucy; Lahner, Edith; Annibale, Bruno

    2012-01-01

    Chronic atrophic gastritis (CAG) is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue (non-metaplastic atrophy) or by glandular structures inappropriate for location (metaplastic atrophy). Epidemiological data suggest that CAG is associated with two different types of tumors: Intestinal-type gastric cancer (GC) and type I gastric carcinoid (TIGC). The pathophysiological mechanisms which lead to the development of these gastric tumors are different. It is accepted that a multistep process initiating from Helicobacter pylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The TIGC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of TIGC. Thus, several events occur in the gastric mucosa before the development of intestinal-type GC and/or TIGC and these take several years. Knowledge of CAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors associated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias. PMID:22493541

  1. Review of Atrophic Gastritis and Intestinal Metaplasia as a Premalignant Lesion of Gastric Cancer

    PubMed Central

    Park, Yo Han; Kim, Nayoung

    2015-01-01

    Atrophic gastritis (AG) and intestinal metaplasia (IM) are the main precursor lesions of gastric cancer as the incidence of gastric cancer increases in the gastric mucosa involved with AG and IM. The prevalence of AG and IM vary depending on countries, even it represents diverse results in the same nation. Usually AG is antecedent of IM but the etiologies of AG and IM are not always the same. The sensitivity and specificity of diagnostic methods to detect AG and IM are different. Furthermore, the management strategy of AG and IM has not been established, yet. Helicobacter pylori infection has been proved as the most important cause of AG and IM. Thus the eradication of H. pylori is very important to prevent the progression to gastric cancer which is still placed in the high rank in morbidity and mortality among cancers. However, the reversibility of AG and IM by eradication of H. pylori which was assumed to be certain by meta-analysis is; however, controversial now. Therefore, the understanding and early diagnosis of AG and IM are very important, especially, in high incidence area of gastric cancer such as Republic of Korea. PMID:25853101

  2. [Multifocal gastric carcinoid associated with chronic type A atrophic gastritis. Analysis of 2 clinical cases].

    PubMed

    Moneghini, D; Fontana, M G; Villanacci, V; Salerni, B

    2001-01-01

    Gastric carcinoid is a rare disease, representing less than 1% of gastric tumours and 11-41% of all gastrointestinal carcinoids. The recent Solcia's classification distinguishes three subtypes of these neoplasms, which show specific clinical and pathological features. Type one arises in patients with chronic atrophic gastritis (CGA), achlorhydria, hypergastrinemia and consequent enterochromaffin-like cell hyperplasia and dysplasia. Type two is related to Zollinger Ellison syndrome and type three represents the sporadic kind. We report two cases of multifocal gastric carcinoid associated to CGA, one of them with pernicious anemia. Both patients had aspecific abdominal symptoms; the diagnosis was suspected by upper endoscopy and confirmed by histological examination. Patients were submitted to total gastrectomy. They are still alive six years after surgery, without signs or symptoms of recurrences. Treatment of these tumours is controversial, because of their uncertain biological and clinical behaviour. Some Authors propose a conservative strategy (only endoscopic surveillance or removal); others stress importance of surgery (antrectomy or gastric resection). We discuss and underline the role of surgical therapy and the relevance of radical approach.

  3. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis.

    PubMed

    Shen, Jian; Song, Ning; Williams, Christopher J; Brown, Celeste J; Yan, Zheng; Xu, Chen; Forney, Larry J

    2016-01-01

    Atrophic vaginitis (AV) is common in postmenopausal women, but its causes are not well understood. The symptoms, which include vaginal itching, burning, dryness, irritation, and dyspareunia, can usually be alleviated by low doses of estrogen given orally or locally. Regrettably, the composition of vaginal bacterial communities in women with AV have not been fully characterized and little is known as to how these communities change over time in response to hormonal therapy. In the present intervention study we determined the response of vaginal bacterial communities in postmenopausal women with AV to low-dose estrogen therapy. The changes in community composition in response to hormonal therapy were rapid and typified by significant increases in the relative abundance of Lactobacillus spp. that were mirrored by a decreased relative abundance of Gardnerella. These changes were paralleled by a significant four-fold increase in serum estradiol levels and decreased vaginal pH, as well as nearly a two-fold increase in the Vaginal Maturation Index (VMI). The results suggest that after menopause a vaginal microbiota dominated by species of Lactobacillus may have a beneficial role in the maintenance of health and these findings that could lead to new strategies to protect postmenopausal women from AV. PMID:27103314

  4. Treatment of atrophic maxilla with zygomatic implants in 29 consecutives patients

    PubMed Central

    Rodríguez-Chessa, Jaime G; Olate, Sergio; Netto, Henrique Duque; Shibli, Jamil; de Moraes, Márcio; Mazzonetto, Renato

    2014-01-01

    Atrophic maxilla is a common condition in older population; some treatments are proposed with bone reconstruction or zygomatic implant. Long-term follow up show the efficiencies of zygomatic implant but limited data are associated to consecutive patient. The aim of this study was to evaluate retrospectively the zygomatic implants performed consecutively in 29 patients. Data from clinical records of 29 patients treated with zygomatic implants were analyzed; were include patient with at least 10 month of prosthetic function. Four surgeons realized all surgeries using local anesthesia with a slot technique on local anesthesia; the variables analyzed were implant survival, complications, prosthetic load and satisfaction of patient; data collection was analyzed by descriptive statistic and chi-square test with p<0.05 for significance statistical. 67 zygomatic implants and 84 conventional implants were installed in patients between 35 and 69 year old being 18 (62%) female and 11 (38%) male.The main indication was the case of severe alveolar resorption in 21 cases (72.41%), followed by failures in maxillary reconstruction with bone graft in 4 (13.79%). The implant success was 79.1% and the immediate or delayed load was not associated to statistical difference (p=0.104). The main complication was the loss of osseointegration and mucositis. Analogue Visual Scale (AVS) for satisfaction show acceptable esthetic and function. Finally we conclude that zygomatic implant present adequate survivor and a good response of patient; important complication can be present in a learn curve for this surgery. PMID:24600500

  5. Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal.

    PubMed

    Vannella, Lucy; Lahner, Edith; Annibale, Bruno

    2012-03-28

    Chronic atrophic gastritis (CAG) is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue (non-metaplastic atrophy) or by glandular structures inappropriate for location (metaplastic atrophy). Epidemiological data suggest that CAG is associated with two different types of tumors: Intestinal-type gastric cancer (GC) and type I gastric carcinoid (TIGC). The pathophysiological mechanisms which lead to the development of these gastric tumors are different. It is accepted that a multistep process initiating from Helicobacter pylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The TIGC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of TIGC. Thus, several events occur in the gastric mucosa before the development of intestinal-type GC and/or TIGC and these take several years. Knowledge of CAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors associated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias.

  6. Occurrence, isolation and differentiation of Candida spp. and prevalence of variables associated to chronic atrophic candidiasis.

    PubMed

    Lund, Rafael Guerra; da Silva Nascente, Patrícia; Etges, Adriana; Ribeiro, Gladis Aver; Rosalen, Pedro Luiz; Del Pino, Francisco Augusto Burkert

    2010-05-01

    The purpose of this study was to survey the frequency of Candida spp. in patients with chronic atrophic candidiasis (CAC), to differentiate Candida species and to assess the prevalence of certain infection-associated variables to this disease. Patients with CAC and wearing partial or complete dentures were recruited. Data were obtained by means of a questionnaire with details involving identification of the subject, demographic characteristics, behaviour and medical history, clinical and mycological evaluation and identification of yeast. The sample collection was carried out in the palate or palate and tongue of the subjects using sterilised swabs. Data were submitted to statistical analyses using Fischer's test. Forty-three (53%) cases of CAC showed the presence of Candida albicans. Females (75.2%) wearing complete dentures (60.1%) for more than 10 years (58%) were risk factors to CAC development. It could be concluded that: (a) the results did not confirm a significant difference among patients with CAC concerning the presence or absence of Candida spp.; (b) the occurrence of Candida was negatively related to important factors associated to this opportunistic infection; and (c) mycological findings did not indicate that the variables investigated have a significant effect on oral infections by C. albicans or other Candida species.

  7. Laser Raman spectra of calf thymus chromatin and its constituents.

    PubMed Central

    Savoie, R; Jutier, J J; Alex, S; Nadeau, P; Lewis, P N

    1985-01-01

    Extensive Raman measurements have been made on calf thymus chromatin, core chromatin, the (H3,H4)/DNA complex, and isolated DNA. The results indicate that the alpha-helical content of the nucleosomal histones gradually increases as they form the heterocomplexes that lead to the formation of the octameric nucleosome core. The secondary structure of the latter is not modified as it binds to DNA. The spectra indicate that the DNA essentially retains its B conformation in nucleosomes, although slight changes probably occur in the ribose-phosphate backbone. No specific interactions between the nucleosomal histones and DNA can be established from the spectra, but histone H1 possibly interacts selectively with the thymine bases. PMID:3986278

  8. Effect of boric acid supplementation of ostrich water on the expression of Foxn1 in thymus.

    PubMed

    Xiao, Ke; Ansari, Abdur Rahman; Rehman, Zia Ur; Khaliq, Haseeb; Song, Hui; Tang, Juan; Wang, Jing; Wang, Wei; Sun, Peng-Peng; Zhong, Juming; Peng, Ke-Mei

    2015-11-01

    Foxn1 is essential for thymus development. The relationship between boric acid and thymus development, optimal dose of boric acid in ostrich diets, and the effects of boric acid on the expression of Foxn1 were investigated in the present study. Thirty healthy ostriches were randomly divided into six groups: Group I, II, III, IV, V, VI, and supplemented with boric acid at the concentration of 0 mg/L, 40 mg/L, 80 mg/L, 160 mg/L, 320 mg/L, 640 mg/L, respectively. The histological changes in thymus were observed by HE staining, and the expression of Foxn1 analyzed by immunohistochemistry and western blot. TUNEL method was used to label the apoptotic cells. Ostrich Foxn1 was sequenced by Race method. The results were as following: Apoptosis in ostrich thymus was closely related with boric acid concentrations. Low boric acid concentration inhibited apoptosis in thymus, but high boric acid concentration promoted apoptosis. Foxn1-positive cells were mainly distributed in thymic medulla and rarely in cortex. Foxn1 is closely related to thymus growth and development. The nucleotide sequence and the encoded protein of Foxn1 were 2736 bases and 654 amino acids in length. It is highly conserved as compared with other species. These results demonstrated that the appropriate boric acid supplementation in water would produce positive effects on the growth development of ostrich thymus by promoting Foxn1 expression, especially at 80 mg/L, and the microstructure of the thymus of ostrich fed 80 mg/L boric acid was well developed. The supplementation of high dose boron (>320 mg/L) damaged the microstructure of thymus and inhibited the immune function by inhibiting Foxn1 expression, particularly at 640 mg/L. The optimal dose of boric acid supplementation in ostrich diets is 80 mg/L boric acid. The genomic full-length of African ostrich Foxn1 was cloned for the first time in the study.

  9. Effect of boric acid supplementation of ostrich water on the expression of Foxn1 in thymus.

    PubMed

    Xiao, Ke; Ansari, Abdur Rahman; Rehman, Zia Ur; Khaliq, Haseeb; Song, Hui; Tang, Juan; Wang, Jing; Wang, Wei; Sun, Peng-Peng; Zhong, Juming; Peng, Ke-Mei

    2015-11-01

    Foxn1 is essential for thymus development. The relationship between boric acid and thymus development, optimal dose of boric acid in ostrich diets, and the effects of boric acid on the expression of Foxn1 were investigated in the present study. Thirty healthy ostriches were randomly divided into six groups: Group I, II, III, IV, V, VI, and supplemented with boric acid at the concentration of 0 mg/L, 40 mg/L, 80 mg/L, 160 mg/L, 320 mg/L, 640 mg/L, respectively. The histological changes in thymus were observed by HE staining, and the expression of Foxn1 analyzed by immunohistochemistry and western blot. TUNEL method was used to label the apoptotic cells. Ostrich Foxn1 was sequenced by Race method. The results were as following: Apoptosis in ostrich thymus was closely related with boric acid concentrations. Low boric acid concentration inhibited apoptosis in thymus, but high boric acid concentration promoted apoptosis. Foxn1-positive cells were mainly distributed in thymic medulla and rarely in cortex. Foxn1 is closely related to thymus growth and development. The nucleotide sequence and the encoded protein of Foxn1 were 2736 bases and 654 amino acids in length. It is highly conserved as compared with other species. These results demonstrated that the appropriate boric acid supplementation in water would produce positive effects on the growth development of ostrich thymus by promoting Foxn1 expression, especially at 80 mg/L, and the microstructure of the thymus of ostrich fed 80 mg/L boric acid was well developed. The supplementation of high dose boron (>320 mg/L) damaged the microstructure of thymus and inhibited the immune function by inhibiting Foxn1 expression, particularly at 640 mg/L. The optimal dose of boric acid supplementation in ostrich diets is 80 mg/L boric acid. The genomic full-length of African ostrich Foxn1 was cloned for the first time in the study. PMID:25665795

  10. Detection of UCP1 protein and measurements of dependent GDP-sensitive proton leak in non-phosphorylating thymus mitochondria.

    PubMed

    Clarke, Kieran J; Carroll, Audrey M; O'Brien, Gemma; Porter, Richard K

    2015-01-01

    Over several years we have provided evidence that uncoupling protein 1 (UCP1) is present in thymus mitochondria. We have demonstrated the conclusive evidence for the presence of UCP1 in thymus mitochondria and we have been able to demonstrate a GDP-sensitive UCP1-dependent proton leak in non-phosphorylating thymus mitochondria. In this chapter, we show how to detect UCP1 in mitochondria isolated from whole thymus using immunoblotting. We show how to measure GDP-sensitive UCP1-dependent oxygen consumption in non-phosphorylating thymus mitochondria and we show that increased reactive oxygen species production occurs on addition of GDP to non-phosphorylating thymus mitochondria. We conclude that reactive oxygen species production rate can be used as a surrogate for detecting UCP1 catalyzed proton leak activity in thymus mitochondria.

  11. Isolation and identification of a new thymic peptide from calf thymus.

    PubMed

    Qin, Xi-Ming; Duan, Ming-Xing; Deng, Bin; Liu, Xi-Cheng; Zhang, Qiang-Zhe; Liu, Zheng; He, Hong-Xuan

    2004-08-01

    Various thymic peptides (including thymulin, thymic humoral factor, thymopoietin, etc.) play important roles in the process of T cell maturation and development. We isolated a new peptide from calf thymus and named it thymus activity factor II (TAF-II). A yield of 0.92 mg of TAF-II was purified from 500 g calf thymus. Analysis by LC/MSD-Trap showed the amino acid sequence of this hexapeptide to be Glu-Ala-Lys-Ser-Gln-Gly-OH with molecular weight 618.5 daltons. We have also begun to investigate the influence of TAF-II.

  12. Thymus cell antigen 1 (Thy1, CD90) is expressed by lymphatic vessels and mediates cell adhesion to lymphatic endothelium.

    PubMed

    Jurisic, Giorgia; Iolyeva, Maria; Proulx, Steven T; Halin, Cornelia; Detmar, Michael

    2010-10-15

    The lymphatic vascular system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined by comparative transcriptional profiling studies of ex vivo isolated mouse intestinal lymphatic endothelial cells versus blood vascular endothelial cells, thymus cell antigen 1 (Thy1, CD90) was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative PCR, and at the protein level by FACS and immunofluorescence analyses. Thy1 was also strongly expressed by tumor-associated lymphatic vessels, as evaluated in a B16 melanoma footpad model in mice. Blockade of Thy1 inhibited tumor cell adhesion to cultured mouse lymphatic endothelial cells. Importantly, treatment of human dermal microvascular endothelial cells with tumor necrosis factor or phorbol 12-myristate 13-acetate resulted in Thy1 upregulation in podoplanin-expressing lymphatic endothelial cells, but not in podoplanin-negative blood vascular endothelial cells. Moreover, adhesion of human polymorphonuclear and mononuclear leukocytes to human lymphatic endothelial cells was Thy1-dependent. Together, these results identify Thy1 as a novel lymphatic vessel expressed gene and suggest its potential role in the cell adhesion processes required for tumor progression and inflammation.

  13. Effect of calf thymus extract and zinc supplementation on the cellular response of mice exposed to restraint stress.

    PubMed

    Obmińiska-Mrukowicz, B; Szczypka, M

    2005-01-01

    The studies were carried out on Balb/c mice exposed to restraint stress twice for 12 h at 24 h intervals. Prior to stress exposure, the mice were treated with calf thymus extract (TFX - Jelfa) i.p. at a dose of 10 mg/kg, ten times at 24 h intervals. TFX was used per se or with zinc ions interaction, by adding zinc ions (as sulfate salt) to drinking water at a dose of 72 microg/mouse per day. The results obtained show that restraint stress dramatically decreased the total number of thymocytes and splenocytes which is also accompanied by decreasing weight ratio of the thymus and spleen. The decreasing number of thymic and spleen cells corresponded to a diminishing percentage of immature, double-positive CD4+CD8+ thymocytes, mature single-positive CD4+ thymic cells and CD4+, CD8+ and CD19+ splenocytes. Changes in the number of thymic cells affect their activity, which is expressed as a decreased proliferative response of thymocytes stimulated in vitro with concanavalin A (Con A) and phytohaemagglutinin (PHA). Besides, exposure to the restraint stress decreased interleukin-1 (IL-1) production by murine intraperitoneal macrophages stimulated in vitro with lipopolisacharide (LPS) from E. coli. Previous treatment with TFX counteracted restraint stress-induced immunosuppression, which is expressed as partial normalisation of the total number of thymic and spleen cells, accelerated regeneration of these two lymphatic organs, shortned suppressive action of restraint stress on the percentage of immature CD4+CD8+ thymocytes and CD4+ splenocytes and in total normalisation of the CD4+ thymocytes and CD8+ splenocytes. TFX administered prior to restraint stress not only counteracted the suppresive effects of stress on the proliferative activity of thymic cells stimulated in vitro with Con A and PHA, but also augmented the proliferative response of these cells to two mitogens. The immunorestorative effect of TFX was augmented by zinc supplementation. PMID:15794467

  14. A strong association between thyrotropin receptor-blocking antibody-positive atrophic autoimmune thyroiditis and HLA-DR8 and HLA-DQB1 0302 in Koreans

    SciTech Connect

    Cho, Bo Youn; Chung, Jae Hoon; Lee, Hong Kyu; Koh, Chang-Soon; Lee, Jung-Bin ); Shong, Young Kee ); Han, Hoon ); Chang, Youn Bok )

    1993-09-01

    The authors investigated whether the associations between HLA alleles of patients with autoimmune hypothyroidism varied according to the presence or absence of TSH receptor-blocking antibody (TRBab). They analyzed the HLA-A, -B, -C, and -DR antigens by serotyping and the DQA1 and DQB1 genes using both enzymatic DNA amplification and sequence-specific oligonucleotide hybridizations. The patient population consisted of 47 Korean patients with atrophic autoimmune thyroiditis and 62 patients with goitrous autoimmune thyroiditis. The antigen frequency of HLA-DR8 was significantly increased in 23 atrophic autoimmune thyroiditis patients that were positive for TSH binding inhibitor immunoglobulin (TBII) compared to 136 controls [52% vs. 16%; x[sup 2] = 13.1; Pc (corrected P value) = 0.003]. This relative risk was 5.7; the etiological fraction was 0.43. HLA-DQB1*0302 was also increased in patients with TBII-positive atrophic autoimmune thyroiditis (24% vs. 7%; x[sup 2] = 11.2; Pc = 0.012; relative risk = 4.4; etiological fraction = 0.19). No specific DR antigens or DQB1 alleles were increased in either TBII-negative atrophic autoimmune thyroidities or goitrous autoimmune thyroiditis. A significant decrease in the frequency of HLA-DR6 antigen was observed in both TBII-positive atrophic antoimmune thyroiditis (0% vs. 32%; x[sup 2] = 8.4; Pc = 0.03) and goitrous autoimmune thyroiditis (0% vs. 32%; x[sup 2] = 23.2; Pc < 0.001) patients. The frequency of the HLC-Cwl antigen was significantly increased in all patient groups. The authors conclude that TRBab-positive atrophic autoimmune thyroiditis is immunogenetically different from both goitrous autoimmune thyroiditis and TRBab-negative atrophic autoimmune thyroiditis. It is possible that HLA-DR8 and/or DQB1*0302 may be related to the susceptibility genes involved in the production of TRBab in Koreans. 32 refs., 5 tabs.

  15. Myoid cell density in the thymus is reduced during mdx dystrophy and after muscle crush.

    PubMed

    Wong, A; Garrett, K L; Anderson, J E

    1999-01-01

    Thymic myoid cells share structural and behavioural features with cells of the skeletal muscle lineage: they express regulatory genes and contractile proteins, and they can form myofibers in culture. Historically, those features suggested that myoid cells could be precursors for muscle repair in addition to the satellite cells in muscle that are typically designated as the only muscle precursors. Muscles of the mutant mdx dystrophic mouse strain have a large demand for precursors, which is greatest at a young age. In the present study, immunostaining for troponin T was used to localize myoid cells. We tested the hypothesis that the myoid cell population changes when there is a demand for muscle precursors and that these changes would be anticipated if myoid cells have a role as myogenic precursors or stem cells in muscle. Chronic demands for muscle precursors in mdx dystrophic mice were accompanied by lower myoid cell density in comparison with density in two normal strains (C57BL10/ScSn and Swiss Webster). Acute demand for precursors was accompanied by a sharp decline in thymic myoid cell density within 2 days after a crush injury to one tibialis anterior muscle in normal but not dystrophic animals. To standardize the developmental age of the thymus, density was determined in all animals at 28 days of age. Given the current interest in nonmuscle sources of myogenic stem cells, these data suggest that changes in the density of thymic myoid cells may accompany acute and chronic demands for muscle precursors. Further experiments are required to determine whether thymic myoid cells are participants in distant muscle cell proliferation, new fiber formation, or the establishment of new stem cells in regenerated muscle.

  16. Reduced myotube diameter, atrophic signalling and elevated oxidative stress in cultured satellite cells from COPD patients.

    PubMed

    Pomiès, Pascal; Rodriguez, Julie; Blaquière, Marine; Sedraoui, Sami; Gouzi, Fares; Carnac, Gilles; Laoudj-Chenivesse, Dalila; Mercier, Jacques; Préfaut, Christian; Hayot, Maurice

    2015-01-01

    The mechanisms leading to skeletal limb muscle dysfunction in chronic obstructive pulmonary disease (COPD) have not been fully elucidated. Exhausted muscle regenerative capacity of satellite cells has been evocated, but the capacity of satellite cells to proliferate and differentiate properly remains unknown. Our objectives were to compare the characteristics of satellite cells derived from COPD patients and healthy individuals, in terms of proliferative and differentiation capacities, morphological phenotype and atrophy/hypertrophy signalling, and oxidative stress status. Therefore, we purified and cultivated satellite cells from progressively frozen vastus lateralis biopsies of eight COPD patients and eight healthy individuals. We examined proliferation parameters, differentiation capacities, myotube diameter, expression of atrophy/hypertrophy markers, oxidative stress damages, antioxidant enzyme expression and cell susceptibility to H2 O2 in cultured myoblasts and/or myotubes. Proliferation characteristics and commitment to terminal differentiation were similar in COPD patients and healthy individuals, despite impaired fusion capacities of COPD myotubes. Myotube diameter was smaller in COPD patients (P = 0.015), and was associated with a higher expression of myostatin (myoblasts: P = 0.083; myotubes: P = 0.050) and atrogin-1 (myoblasts: P = 0.050), and a decreased phospho-AKT/AKT ratio (myoblasts: P = 0.022). Protein carbonylation (myoblasts: P = 0.028; myotubes: P = 0.002) and lipid peroxidation (myotubes: P = 0.065) were higher in COPD cells, and COPD myoblasts were significantly more susceptible to oxidative stress. Thus, cultured satellite cells from COPD patients display characteristics of morphology, atrophic signalling and oxidative stress similar to those described in in vivo COPD skeletal limb muscles. We have therefore demonstrated that muscle alteration in COPD can be studied by classical in vitro cellular models.

  17. Helicobacter pylori Infection with Atrophic Gastritis Is an Independent Risk Factor for Advanced Colonic Neoplasm

    PubMed Central

    Lee, Ji Young; Park, Hye Won; Choi, Ji Young; Lee, Jong-Soo; Koo, Ja Eun; Chung, Eun Ju; Chang, Hye-Sook; Choe, Jaewon; Yang, Dong-Hoon; Myung, Seung-Jae; Jung, Hwoon-Yong; Yang, Suk-Kyun; Byeon, Jeong-Sik

    2016-01-01

    Background/Aims Helicobacter pylori is a major risk factor for atrophic gastritis (AG) and gastric cancer. The correlation between H. pylori, AG and colorectal neoplasm (CRN) has only been examined in a limited number of studies, and findings have been inconclusive. We aimed to investigate the association between H. pylori infection status, AG and advanced CRN. Methods This cross-sectional study investigated the relationship between the presence of serum anti-H. pylori IgG antibodies, AG, and advanced CRN in 6,351 consecutive asymptomatic subjects who underwent a screening colonoscopy. Results A total of 316 participants (5.0%) had advanced CRN. H. pylori seropositivity was 61.3%. In a univariate analysis, the presence of H. pylori infection was associated with advanced CRN (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17 to 1.91; p=0.001). H. pylori infection was associated with an increased risk of advanced CRN after adjusting for clinically relevant confounders (OR, 1.34; 95% CI, 1.04 to 1.72; p=0.023). H. pylori-related AG was significantly associated with the risk of advanced CRN (OR, 1.40; 95% CI, 1.03 to 1.91; p=0.030), whereas H. pylori infection without AG was not. Conclusions H. pylori infection increased the risk of advanced CRN, especially when it was combined with AG. Strict colonoscopy screening and surveillance may be warranted in those with H. pylori-positive AG. PMID:27458180

  18. Reduced myotube diameter, atrophic signalling and elevated oxidative stress in cultured satellite cells from COPD patients

    PubMed Central

    Pomiès, Pascal; Rodriguez, Julie; Blaquière, Marine; Sedraoui, Sami; Gouzi, Fares; Carnac, Gilles; Laoudj-Chenivesse, Dalila; Mercier, Jacques; Préfaut, Christian; Hayot, Maurice

    2015-01-01

    The mechanisms leading to skeletal limb muscle dysfunction in chronic obstructive pulmonary disease (COPD) have not been fully elucidated. Exhausted muscle regenerative capacity of satellite cells has been evocated, but the capacity of satellite cells to proliferate and differentiate properly remains unknown. Our objectives were to compare the characteristics of satellite cells derived from COPD patients and healthy individuals, in terms of proliferative and differentiation capacities, morphological phenotype and atrophy/hypertrophy signalling, and oxidative stress status. Therefore, we purified and cultivated satellite cells from progressively frozen vastus lateralis biopsies of eight COPD patients and eight healthy individuals. We examined proliferation parameters, differentiation capacities, myotube diameter, expression of atrophy/hypertrophy markers, oxidative stress damages, antioxidant enzyme expression and cell susceptibility to H2O2 in cultured myoblasts and/or myotubes. Proliferation characteristics and commitment to terminal differentiation were similar in COPD patients and healthy individuals, despite impaired fusion capacities of COPD myotubes. Myotube diameter was smaller in COPD patients (P = 0.015), and was associated with a higher expression of myostatin (myoblasts: P = 0.083; myotubes: P = 0.050) and atrogin-1 (myoblasts: P = 0.050), and a decreased phospho-AKT/AKT ratio (myoblasts: P = 0.022). Protein carbonylation (myoblasts: P = 0.028; myotubes: P = 0.002) and lipid peroxidation (myotubes: P = 0.065) were higher in COPD cells, and COPD myoblasts were significantly more susceptible to oxidative stress. Thus, cultured satellite cells from COPD patients display characteristics of morphology, atrophic signalling and oxidative stress similar to those described in in vivo COPD skeletal limb muscles. We have therefore demonstrated that muscle alteration in COPD can be studied by classical in vitro cellular models. PMID:25339614

  19. Evidence of Epstein-Barr Virus Association with Gastric Cancer and Non-Atrophic Gastritis

    PubMed Central

    Martínez-López, Juan L.E.; Torres, Javier; Camorlinga-Ponce, Margarita; Mantilla, Alejandra; Leal, Yelda A.; Fuentes-Pananá, Ezequiel M.

    2014-01-01

    Different lines of evidence support an association between Epstein-Barr virus (EBV) and gastric cancer (GC). The main understood risk factor to develop GC is infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory response critical for progression from gastritis to GC. The role of EBV in early inflammatory gastric lesions has been poorly studied. A recent study proposed a cutoff value of 2000 EBV particles to identify patients with increased chances of infection of the gastric epithelium, which may favor the inflammatory process. To better understand the role of EBV in cancer progression, we analyzed 75 samples of GC, 147 control samples of non-tumor gastric tissue derived from GC patients and 75 biopsies from patients with non-atrophic gastritis (NAG). A first-round PCR was used for EBV detection in tumor and non-tumor controls and a more sensitive nested PCR for gastritis samples; both PCRs had lower detection limits above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non-tumor controls and 8% of gastritis samples were found positive. An EBER1 in situ hybridization showed EBV infection of epithelial cells in GC and in a third of NAG samples, while in the other NAGs infection was restricted to the mononuclear cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns, while these rare patterns were not observed in EBV negative samples. Our results support a role for EBV in GC and early precursor lesions, either as directly oncogenic infecting epithelial cells or indirectly as an inflammatory trigger. PMID:24448220

  20. Autoimmune Metaplastic Atrophic Gastritis: Recognizing Precursor Lesions for Appropriate Patient Evaluation.

    PubMed

    Pittman, Meredith E; Voltaggio, Lysandra; Bhaijee, Feriyl; Robertson, Scott A; Montgomery, Elizabeth A

    2015-12-01

    Autoimmune metaplastic atrophic gastritis (AMAG) is a significant risk factor for pernicious anemia and gastric neoplasia. Still, the histologic features of AMAG are frequently overlooked, especially in the early stages of the disease. The purpose of our study, therefore, was to catalogue the progression of histologic changes that precede the development of AMAG in affected individuals. Over a 2-year period (2012 to 2014), the diagnosis of AMAG was rendered on material from 113 patients seen at Johns Hopkins Hospital (∼1.8% of "in house" gastric biopsies). Prior gastric body biopsies had been performed on 54 (48%) patients in the cohort, and the majority of these specimens had also shown AMAG. Eighteen of the previous biopsies, however, carried a diagnosis other than AMAG: 13 inactive chronic gastritis, 2 acute Helicobacter pylori gastritis, and 1 each of eosinophilic gastritis, iron pill gastritis, and proton-pump inhibitor-like effect. Upon review of these 18 biopsies, the most common histologic findings were heavy full-thickness or deep lamina propria chronic inflammation (12), inflammatory destruction of oxyntic glands (12), metaplasia (intestinal, pyloric, or pancreatic acinar) (10), prominent lamina propria eosinophils (8), and parietal cell pseudohypertrophy (4). At least 2 of these features were present in the majority (13, 72%) of the biopsies. In addition, 7 (58%) of these patients were also found to have another autoimmune or inflammatory disorder before the diagnosis of AMAG. Although subtle, histologic features of developing AMAG are identifiable in routine gastric body biopsies. When metaplasia, full-thickness chronic inflammation, and/or oxyntic destruction are seen, a note suggesting laboratory testing and/or close clinical follow-up in this subset of patients may be warranted.

  1. Evidence of Epstein-Barr virus association with gastric cancer and non-atrophic gastritis.

    PubMed

    Martínez-López, Juan L E; Torres, Javier; Camorlinga-Ponce, Margarita; Mantilla, Alejandra; Leal, Yelda A; Fuentes-Pananá, Ezequiel M

    2014-01-20

    Different lines of evidence support an association between Epstein-Barr virus (EBV) and gastric cancer (GC). The main understood risk factor to develop GC is infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory response critical for progression from gastritis to GC. The role of EBV in early inflammatory gastric lesions has been poorly studied. A recent study proposed a cutoff value of 2000 EBV particles to identify patients with increased chances of infection of the gastric epithelium, which may favor the inflammatory process. To better understand the role of EBV in cancer progression, we analyzed 75 samples of GC, 147 control samples of non-tumor gastric tissue derived from GC patients and 75 biopsies from patients with non-atrophic gastritis (NAG). A first-round PCR was used for EBV detection in tumor and non-tumor controls and a more sensitive nested PCR for gastritis samples; both PCRs had lower detection limits above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non-tumor controls and 8% of gastritis samples were found positive. An EBER1 in situ hybridization showed EBV infection of epithelial cells in GC and in a third of NAG samples, while in the other NAGs infection was restricted to the mononuclear cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns, while these rare patterns were not observed in EBV negative samples. Our results support a role for EBV in GC and early precursor lesions, either as directly oncogenic infecting epithelial cells or indirectly as an inflammatory trigger.

  2. Accuracy of GastroPanel for the diagnosis of atrophic gastritis

    PubMed Central

    Forné, Montserrat; Barrio, Jesus; De la Coba, Cristobal; González, Begoña; Rivera, Robin; Esteve, Maria; Fernandez-Bañares, Fernando; Madrigal, Beatriz; Gras-Miralles, Beatriz; Perez-Aisa, Angeles; Viver-Pi-Sunyer, Jose M.; Bory, Felipe; Rosinach, Merce; Loras, Carmen; Esteban, Carlos; Santolaria, Santos; Gomollon, Fernando; Valle, Julio; Gisbert, Javier P.

    2014-01-01

    Background It has been suggested that GastroPanel might be a useful tool for the diagnosis of chronic atrophic gastritis (CAG) measuring four biomarkers in blood: basal gastrin-17 (G17), pepsinogen I and II (PGI and PGII), and Helicobacter pylori antibodies. Aim To determine the accuracy of GastroPanel for the diagnosis of CAG. Methods This was a prospective, blinded, multicenter study that included dyspeptic patients. G17, PGI, and PGII were determined by enzyme immunoassays. Three antrum and two corpus biopsies were obtained for standard histological analysis and rapid urease test. Biopsies were analyzed by a single blinded expert pathologist. Results Ninety-one patients were included (77% women, mean age 44 years, 51% H. pylori positive, 17% with CAG). G17 was reduced in patients with antrum CAG (5.4 vs. 13.4 pmol/l; P<0.01) and increased in patients with corpus CAG (11 vs. 24 pmol/l; P<0.05), but its accuracy was only acceptable in the case of corpus localization [area under the receiver operating characteristic curve (AUC), 74%]; PGII difference was almost statistically significant only when testing for corpus atrophy (33 vs. 21 μg/l; P=0.05; AUC=72%). The PGI and PGI/PGII ratio showed no significant differences (AUCs were all unacceptably low). Helicobacter pylori antibody levels were higher in H. pylori-infected patients (251 vs. 109 EIU, P=0.01; AUC=70). The accuracy of GastroPanel for the diagnosis of CAG was as follows: sensitivity 50%; specificity 80%; positive 25% and negative 92% predictive values; and positive 2.4 and negative 0.6 likelihood ratios. Conclusion GastroPanel is not accurate enough for the diagnosis of CAG; thus, its systematic use in clinical practice cannot be recommended. PMID:25014624

  3. What Happens in the Thymus Does Not Stay in the Thymus: How T Cells Recycle the CD4+-CD8+ Lineage Commitment Transcriptional Circuitry To Control Their Function.

    PubMed

    Vacchio, Melanie S; Bosselut, Rémy

    2016-06-15

    MHC-restricted CD4(+) and CD8(+) T cells are at the core of most adaptive immune responses. Although these cells carry distinct functions, they arise from a common precursor during thymic differentiation, in a developmental sequence that matches CD4 and CD8 expression and functional potential with MHC restriction. Although the transcriptional control of CD4(+)-CD8(+) lineage choice in the thymus is now better understood, less was known about what maintains the CD4(+) and CD8(+) lineage integrity of mature T cells. In this review, we discuss the mechanisms that establish in the thymus, and maintain in postthymic cells, the separation of these lineages. We focus on recent studies that address the mechanisms of epigenetic control of Cd4 expression and emphasize how maintaining a transcriptional circuitry nucleated around Thpok and Runx proteins, the key architects of CD4(+)-CD8(+) lineage commitment in the thymus, is critical for CD4(+) T cell helper functions.

  4. Quest for the binding mode of tetrabromobisphenol A with Calf thymus DNA

    NASA Astrophysics Data System (ADS)

    Wang, Yan-Qing; Zhang, Hong-Mei; Cao, Jian

    2014-10-01

    The binding interaction of tetrabromobisphenol A with Calf thymus DNA was studied by multi-spectroscopic and molecular modeling methods. The UV-vis study revealed that an obvious interaction between tetrabromobisphenol A and Calf thymus DNA happened. The π-π∗ transitions and the electron cloud of tetrabromobisphenol A might be changed by entering the groove of Calf thymus DNA. From the fluorescence spectral and thermodynamics studies, it was concluded that the hydrogen bonds and hydrophobic force played a major role in the binding of tetrabromobisphenol A to Calf thymus DNA. The molecular modeling study showed that the possible sites of tetrabromobisphenol A in the groove of DNA. Circular dichroism study also depicted that tetrabromobisphenol A bond to DNA. These above results would further advance our knowledge on the molecular mechanism of the binding interactions of brominated flame-retardants with nucleic acid.

  5. [Morphogenesis of Human Fetal Thymus during Weeks 22-27 of Development].

    PubMed

    Kulida, L V; Peretyatko, L P; Nazarov, S B

    2015-01-01

    Distinctive features of human fetal thymus morphogenesis in early ontogeny in the case of uncomplicated pregnancy have been characterized. A steady increase of thymus dimensions and weight occurred concomitantly to differentiation of morphofunctional zones within the organ. Cell differentiation in the subcapsular and inner cortical zones of the thymus lobes was manifested as changes in parameters of expression of T-lymphocyte antigens CD1, CD2, and CD3 and ultrastructural features of reticuloepithelial cells (REC) type I and II forming a microenvironment for lymphocytes. RECs of the medullar zone formed a glomerular syncytium with desmosomal interepithelial contacts by week 22 of fetal development. Small lymphocytes predominated among thymocytes (66%). Hassall's corpuscles, the structural correlates of morphological and functional maturity, predominated in the fetal thymuses during developmental weeks 25-27.

  6. [Morphogenesis of Human Fetal Thymus during Weeks 22-27 of Development].

    PubMed

    Kulida, L V; Peretyatko, L P; Nazarov, S B

    2015-01-01

    Distinctive features of human fetal thymus morphogenesis in early ontogeny in the case of uncomplicated pregnancy have been characterized. A steady increase of thymus dimensions and weight occurred concomitantly to differentiation of morphofunctional zones within the organ. Cell differentiation in the subcapsular and inner cortical zones of the thymus lobes was manifested as changes in parameters of expression of T-lymphocyte antigens CD1, CD2, and CD3 and ultrastructural features of reticuloepithelial cells (REC) type I and II forming a microenvironment for lymphocytes. RECs of the medullar zone formed a glomerular syncytium with desmosomal interepithelial contacts by week 22 of fetal development. Small lymphocytes predominated among thymocytes (66%). Hassall's corpuscles, the structural correlates of morphological and functional maturity, predominated in the fetal thymuses during developmental weeks 25-27. PMID:26480484

  7. BDNF and its receptors in human myasthenic thymus: implications for cell fate in thymic pathology.

    PubMed

    Berzi, Angela; Ayata, C Korcan; Cavalcante, Paola; Falcone, Chiara; Candiago, Elisabetta; Motta, Teresio; Bernasconi, Pia; Hohlfeld, Reinhard; Mantegazza, Renato; Meinl, Edgar; Farina, Cinthia

    2008-07-15

    Here we show that in myasthenic thymus several cell types, including thymic epithelial cells (TEC) and immune cells, were the source and the target of the neurotrophic factor brain-derived growth factor (BDNF). Interestingly, many actively proliferating medullary thymocytes expressed the receptor TrkB in vivo in involuted thymus, while this population was lost in hyperplastic or neoplastic thymuses. Furthermore, in hyperplastic thymuses the robust coordinated expression of BDNF in the germinal centers together with the receptor p75NTR on all proliferating B cells strongly suggests that this factor regulates germinal center reaction. Finally, all TEC dying of apoptosis expressed BDNF receptors, indicating that this neurotrophin is involved in TEC turnover. In thymomas both BDNF production and receptor expression in TEC were strongly hindered. This may represent an attempt of tumour escape from cell death.

  8. Rhodiola rosea suppresses thymus T-lymphocyte apoptosis by downregulating tumor necrosis factor-α-induced protein 8-like-2 in septic rats

    PubMed Central

    LIU, MING-WEI; SU, MEI-XIAN; ZHANG, WEI; ZHANG, LIN-MING; WANG, YUN-HUI; QIAN, CHUAN-YUN

    2015-01-01

    In recent years, several studies have shown that Rhodiola rosea can enhance cellular immunity and humoral immune function in mice, and thus, it has become a research hotspot. However, its underlying mechanism of action has remained elusive. The present study investigated whether Rhodiola rosea was able to downregulate the expression of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2), thereby inhibiting the expression of apoptotic genes, attenuating T-lymphocyte apoptosis and improving immunity in septic mice. A mouse model of caecal ligation and puncture (CLP)-induced sepsis was established, and animals in the treatment group were pre-treated with an intraperitoneal injection of Rhodiola rosea extract, while animals in the control group and sham-operated group were injected with an equivalent amount of normal saline. TIPE2, B-cell lymphoma 2 (Bcl-2), Fas and Fas ligand (FasL) mRNA and protein levels in thymic T cells were determined using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. Furthermore, the thymus T-lymphocyte apoptosis rate, thymus T-lymphocyte count and thymus T-lymphocyte sub-sets were assessed using flow cytometry. Levels of T-helper cell type 1 (Th1) cytokines [Interleukin (IL)-2, IL-12 and interferon (IFN)-γ] and Th2 cytokines (IL-4 and IL-10) were determined using ELISA. The results showed that, compared to that in the CLP group, the expression of TIPE2, Fas and FasL in the treatment group was significantly decreased, while the expression of Bcl-2 was increased (P<0.05). The thymus lymphocyte count in the CLP group was significantly higher compared with that in the treatment group (P<0.05). Furthermore, the apoptotic rate of thymus T-lymphocytes in the treatment group was significantly lower than that in the CLP group (P<0.05). In addition, treatment with Rhodiola rosea rescued decreased in the counts of the CD3+ T and CD4+ T sub-sets of thymus T lymphocytes in the CLP group (P<0

  9. Rhodiola rosea suppresses thymus T-lymphocyte apoptosis by downregulating tumor necrosis factor-α-induced protein 8-like-2 in septic rats.

    PubMed

    Liu, Ming-Wei; Su, Mei-Xian; Zhang, Wei; Zhang, Lin-Ming; Wang, Yun-Hui; Qian, Chuan-Yun

    2015-08-01

    In recent years, several studies have shown that Rhodiola rosea can enhance cellular immunity and humoral immune function in mice, and thus, it has become a research hotspot. However, its underlying mechanism of action has remained elusive. The present study investigated whether Rhodiola rosea was able to downregulate the expression of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2), thereby inhibiting the expression of apoptotic genes, attenuating T-lymphocyte apoptosis and improving immunity in septic mice. A mouse model of caecal ligation and puncture (CLP)-induced sepsis was established, and animals in the treatment group were pre-treated with an intraperitoneal injection of Rhodiola rosea extract, while animals in the control group and sham-operated group were injected with an equivalent amount of normal saline. TIPE2, B-cell lymphoma 2 (Bcl-2), Fas and Fas ligand (FasL) mRNA and protein levels in thymic T cells were determined using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. Furthermore, the thymus T-lymphocyte apoptosis rate, thymus T-lymphocyte count and thymus T-lymphocyte sub-sets were assessed using flow cytometry. Levels of T-helper cell type 1 (Th1) cytokines [Interleukin (IL)-2, IL-12 and interferon (IFN)-γ] and Th2 cytokines (IL-4 and IL-10) were determined using ELISA. The results showed that, compared to that in the CLP group, the expression of TIPE2, Fas and FasL in the treatment group was significantly decreased, while the expression of Bcl-2 was increased (P<0.05). The thymus lymphocyte count in the CLP group was significantly higher compared with that in the treatment group (P<0.05). Furthermore, the apoptotic rate of thymus T-lymphocytes in the treatment group was significantly lower than that in the CLP group (P<0.05). In addition, treatment with Rhodiola rosea rescued decreased in the counts of the CD3(+) T and CD4(+) T sub-sets of thymus T lymphocytes in the CLP group

  10. Functional unity of the thymus and pineal gland and study of the mechanisms of aging.

    PubMed

    Polyakova, V O; Linkova, N S; Kvetnoy, I M; Khavinson, V Kh

    2011-09-01

    The data on the morphology and functions of the thymus and pineal gland in individuals of different age are analyzed and common mechanisms of involution of these organs during aging and the consequencies of this process are discussed. Based on the data on the molecular changes in the thymus and pineal gland during aging, the authors hypothesize the functional unity of these organs and their mutual complementarity in the maintenance of normal immune and endocrine status during aging.

  11. [The role of the pineal-thymus system in the regulation of autoimmunity, aging and lifespan].

    PubMed

    Csaba, György

    2016-07-01

    Thymus is an immunoendocrine organ, the hormones of which mainly influence its own lymphatic elements. It has a central role in the immune system, the neonatal removal causes the collapse of immune system and the whole organism. The thymic nurse cells select the bone marrow originated lymphocytes and destroy the autoreactive ones, while thymus originated Treg cells suppress the autoreactive cells in the periphery. The involution of the organ starts after birth, however, this truly happens in the end of puberty only, as before this it is overcompensated by developmental processes. From the end of adolescence the involution allows the life, proliferation and enhanced functioning of some autoreactive cells, which gradually wear down the cells and intercellular materials, causing the aging. The enhanced and mass function of autoreactive cells lead to the autoimmune diseases and natural death. This means that the involution of thymus is not a part of the organismic involution, but an originator of it, which is manifested in the lifespan-pacemaker function. Thus, aging can be conceptualized as a thymus-commanded slow autoimmune process. The neonatal removal of pineal gland leads to the complete destruction of the thymus and the crashing down of the immune system, as well as to wasting disease. The involution of the pineal and thymus runs parallel, because the two organs form a functional unit. It is probable that the pineal gland is responsible for the involution of thymus and also regulates its lifespan determining role. However, the data reviewed here do not prove the exclusive role of the pineal-thymus system in the regulation of aging and lifespan, but only call attention to such possibility. PMID:27346473

  12. [The role of the pineal-thymus system in the regulation of autoimmunity, aging and lifespan].

    PubMed

    Csaba, György

    2016-07-01

    Thymus is an immunoendocrine organ, the hormones of which mainly influence its own lymphatic elements. It has a central role in the immune system, the neonatal removal causes the collapse of immune system and the whole organism. The thymic nurse cells select the bone marrow originated lymphocytes and destroy the autoreactive ones, while thymus originated Treg cells suppress the autoreactive cells in the periphery. The involution of the organ starts after birth, however, this truly happens in the end of puberty only, as before this it is overcompensated by developmental processes. From the end of adolescence the involution allows the life, proliferation and enhanced functioning of some autoreactive cells, which gradually wear down the cells and intercellular materials, causing the aging. The enhanced and mass function of autoreactive cells lead to the autoimmune diseases and natural death. This means that the involution of thymus is not a part of the organismic involution, but an originator of it, which is manifested in the lifespan-pacemaker function. Thus, aging can be conceptualized as a thymus-commanded slow autoimmune process. The neonatal removal of pineal gland leads to the complete destruction of the thymus and the crashing down of the immune system, as well as to wasting disease. The involution of the pineal and thymus runs parallel, because the two organs form a functional unit. It is probable that the pineal gland is responsible for the involution of thymus and also regulates its lifespan determining role. However, the data reviewed here do not prove the exclusive role of the pineal-thymus system in the regulation of aging and lifespan, but only call attention to such possibility.

  13. Genome-wide analysis of single nucleotide polymorphisms in patients with atrophic age-related macular degeneration in oldest old Han Chinese.

    PubMed

    Zhou, T Q; Guan, H J; Hu, J Y

    2015-12-21

    The aim of this study was to identify disease-associated loci in oldest old Han Chinese with atrophic age-related macular degeneration (AMD). This genome-wide association study (GWAS) only included oldest old (≥95 years old) subjects in Rugao County, China. Thirty atrophic AMD patients and 47 age-matched non-AMD controls were enrolled. The study subjects underwent a complete ophthalmic examination. Genomic DNA was extracted from peripheral blood samples. Single nucleotide polymorphisms (SNPs) were scanned by Genome-Wide Human Mapping SNP 6.0 Arrays and GeneChip Scanner 3000 7G. The results were read and analyzed by the Affymetrix Genotyping Console software. We filtered out the SNPs with a no-call rate ≥10%, MAF P < 0.05, and HWE P < 0.001. The remaining 561,277 SNPs were included in the association analysis. We found that the following 2 SNPs had the highest association with atrophic AMD: rs7624556 (located on 3q24) and rs13119914 (located on 4q34.3). In conclusion, we identified two atrophic AMD-associated SNPs (rs7624556 and rs13119914) in an oldest old Han Chinese population. This finding may lead to new strategies for screening of atrophic AMD for Han Chinese.

  14. Protection against apoptosis in chicken bursa and thymus cells by phorbol ester in vitro

    SciTech Connect

    Asakawa, J.; Thorbecke, G.J. )

    1991-03-15

    Programmed suicide or apoptosis, due to activation of endogenous nucleases, occurs in immature CD4{sup {minus}}85{sup {minus}} mammalian thymus cells. Like the thymus, the bursa of Fabricius is a site of massive lymphopoiesis accompanied by cell death in vivo. In the present study the authors have, therefore, examined whether chicken bursa and thymus cells exhibit apoptosis. Bursa and thymus cells from SC chickens, 4-10 weeks of age, were incubated for 8-24 hrs with various reagents. Genomic DNA was isolated, electrophoresed in 3% Nusieve agarose gels, and examined for patterns of DNA fragmentation. A laddering of DNA in multiples of 200 base pairs, indicative of apoptosis, was observed with both bursa and thymus cells. These patterns of DNA fragmentation from bursa cells could be prevented by adding phorbol myristic acetate during culture and, more effectively, by PMA plus ionomycin, but not by ionomycin alone or by anti-{mu}. PMA did not affect the patterns of DNA fragmentation seen with spleen cells. Addition of the protein kinase C inhibitor staurosporin inhibited the preventive effect of PMA on apoptosis. PMA also greatly promoted the survival of bursa cells in culture, as assayed by percentage cell death and by {sup 3}H-thymidine incorporation. It is concluded that bursa and thymus cells from the chicken exhibit apoptosis. The data further suggest that protein kinase C activation protects apoptosis in cultured bursa cells.

  15. Dose-dependent Medicinal Effects of Thymus haussknechtii Velen Grown Wild in Turkey.

    PubMed

    Kılıçgün, Hasan; Korkmaz, Mustafa

    2016-01-01

    In this study, it was aimed to determine dose-dependent interactions between phenolic contents and antioxidant, antibacterial and antifungal effect mechanisms of the infusions of Thymus haussknechtii Velen, naturally grown in the Eastern Anatolia region of Turkey. Therefore, the infusions of Thymus haussknechtii were tested and the interactions between phenolic contents and antioxidant, antibacterial and antifungal effect mechanisms were determined by way of different antioxidant, antibacterial and antioxidant test systems. The concentrations of Thymus haussknechtii showed strong hydrogen peroxide scavenging activity and free radical scavenging activity [1,1-diphenyl-2-picryl-hydrazil (DPPH) % inhibition]. Also, it was seen that Thymus haussknechtii infusions possessed strong antibacterial and antifungal activity against different gram negative and positive bacteria and fungi. In this study, positive correlations between antioxidant, antibacterial, antifungal potency and the total phenolic content of Thymus haussknechtii were found. When the concentration differences were examined, it was seen that concentrations of 4% had the most strong antioxidant, antibacterial and antifungal activity. As a result, Thymus haussknechtii can be reliable antioxidant, antibacterial antifungal substance at concentrations of 4% when it is used as a supplement to therapeutic regimens and for medicinal purposes.

  16. Cloning of thyrotropin-releasing hormone precursor and receptor in rat thymus, adrenal gland, and testis.

    PubMed

    Montagne, J J; Ladram, A; Nicolas, P; Bulant, M

    1999-03-01

    TRH is a hypophysiotropic peptide that acts mainly via the hypothalamic-pituitary-thyroid axis, but TRH immunoreactivity is also detected in several peripheral tissues. PCR with two pairs of primers enabling amplification of three fragments of TRH complementary DNA (cDNA) was used to demonstrate local production of TRH. Products of the expected size were detected in the testis, adrenal gland, lymphoid organs, thymus, and spleen. The amplified cDNA fragments were cloned and sequenced to show that the TRH gene is expressed in the thymus, spleen, and adrenal gland. Competitive RT-PCR showed that the TRH messenger RNA content of the testis was about one third that of the hypothalamus, whereas the adrenal gland contained 2% and the thymus 6%. HPLC analysis of thymus and spleen extracts showed small amounts of TRH, with a particular processing pattern of pro-TRH in lymphoid organs. The expression of the TRH receptor gene in peripheral organs was investigated to determine whether TRH had an autocrine or a paracrine action. cDNA fragments that encompassed the coding region of the receptor were identified in the testis, adrenal gland and thymus. No signal was detected in the spleen. These findings indicate that TRH may have a biological activity in extrapituitary organs and may act locally in the testis, adrenal gland, and thymus.

  17. Dose-dependent Medicinal Effects of Thymus haussknechtii Velen Grown Wild in Turkey.

    PubMed

    Kılıçgün, Hasan; Korkmaz, Mustafa

    2016-01-01

    In this study, it was aimed to determine dose-dependent interactions between phenolic contents and antioxidant, antibacterial and antifungal effect mechanisms of the infusions of Thymus haussknechtii Velen, naturally grown in the Eastern Anatolia region of Turkey. Therefore, the infusions of Thymus haussknechtii were tested and the interactions between phenolic contents and antioxidant, antibacterial and antifungal effect mechanisms were determined by way of different antioxidant, antibacterial and antioxidant test systems. The concentrations of Thymus haussknechtii showed strong hydrogen peroxide scavenging activity and free radical scavenging activity [1,1-diphenyl-2-picryl-hydrazil (DPPH) % inhibition]. Also, it was seen that Thymus haussknechtii infusions possessed strong antibacterial and antifungal activity against different gram negative and positive bacteria and fungi. In this study, positive correlations between antioxidant, antibacterial, antifungal potency and the total phenolic content of Thymus haussknechtii were found. When the concentration differences were examined, it was seen that concentrations of 4% had the most strong antioxidant, antibacterial and antifungal activity. As a result, Thymus haussknechtii can be reliable antioxidant, antibacterial antifungal substance at concentrations of 4% when it is used as a supplement to therapeutic regimens and for medicinal purposes. PMID:26826832

  18. Normal Thymus in Adults: Appearance on CT and Associations with Age, Sex, BMI and Smoking

    PubMed Central

    Araki, Tetsuro; Nishino, Mizuki; Gao, Wei; Dupuis, Josée; Hunninghake, Gary M.; Murakami, Takamichi; Washko, George R.; O'Connor, George T.; Hatabu, Hiroto

    2016-01-01

    Objective To investigate the CT appearance and size of the thymus in associations with characteristics of participants. Materials and Methods 2540 supposedly healthy participants (mean age 58.9 years, 51% female) were evaluated for the CT appearance of thymic glands with four-point scores (according to the ratio of fat and soft tissue), size, and morphology. These were correlated with participants’ age, sex, BMI, and smoking history. Results Of 2540 participants, 1869 (74%) showed complete fatty replacement of the thymus (Score 0), 463 (18%) predominantly fatty attenuation (Score 1), 172 (7%) half fatty and half soft-tissue attenuation (Score 2), and 36 (1%) solid thymic gland with predominantly soft-tissue attenuation (Score 3). Female participants showed less fatty degeneration of the thymus with higher thymic scores within age 40-69 (P<0.001). Participants with lower thymic scores showed higher BMI (P<0.001) and were more likely to be former smokers (P<0.001) with higher pack-years (P=0.04). Conclusions Visual assessment with four-point thymic scores revealed a sex difference in the fatty degeneration of the thymus with age. Women show significantly higher thymic scores than men, suggesting less fat content of the thymus, during age 40-69. Cigarette smoking and high BMI are associated with advanced fatty replacement of the thymus. PMID:25925358

  19. Arachidonic acid accumulates in the stromal macrophages during thymus involution in diabetes.

    PubMed

    Gruia, Alexandra T; Barbu-Tudoran, Lucian; Mic, Ani A; Ordodi, Valentin L; Paunescu, Virgil; Mic, Felix A

    2011-07-01

    Diabetes is a debilitating disease with chronic evolution that affects many tissues and organs over its course. Thymus is an organ that is affected early after the onset of diabetes, gradually involuting until it loses most of its thymocyte populations. We show evidence of accumulating free fatty acids with generation of eicosanoids in the diabetic thymus and we present a possible mechanism for the involution of the organ during the disease. Young rats were injected with streptozotocin and their thymuses examined for cell death by flow cytometry and TUNEL reaction. Accumulation of lipids in the diabetic thymus was investigated by histology and electron microscopy. The identity and quantitation of accumulating lipids was done with gas chromatography-mass spectrometry and liquid chromatography. The expression and dynamics of the enzymes were monitored via immunohistochemistry. Diabetes causes thymus involution by elevating the thymocyte apoptosis. Exposure of thymocytes to elevated concentration of glucose causes apoptosis. After the onset of diabetes, there is a gradual accumulation of free fatty acids in the stromal macrophages including arachidonic acid, the substrate for eicosanoids. The eicosanoids do not cause thymocyte apoptosis but administration of a cyclooxygenase inhibitor reduces the staining for ED1, a macrophage marker whose intensity correlates with phagocytic activity. Diabetes causes thymus involution that is accompanied by accumulation of free fatty acids in the thymic macrophages. Excess glucose is able to induce thymocyte apoptosis but eicosanoids are involved in the chemoattraction of macrophage to remove the dead thymocytes.

  20. Computer-aided diagnostic method for classification of Alzheimer's disease with atrophic image features on MR images

    NASA Astrophysics Data System (ADS)

    Arimura, Hidetaka; Yoshiura, Takashi; Kumazawa, Seiji; Tanaka, Kazuhiro; Koga, Hiroshi; Mihara, Futoshi; Honda, Hiroshi; Sakai, Shuji; Toyofuku, Fukai; Higashida, Yoshiharu

    2008-03-01

    Our goal for this study was to attempt to develop a computer-aided diagnostic (CAD) method for classification of Alzheimer's disease (AD) with atrophic image features derived from specific anatomical regions in three-dimensional (3-D) T1-weighted magnetic resonance (MR) images. Specific regions related to the cerebral atrophy of AD were white matter and gray matter regions, and CSF regions in this study. Cerebral cortical gray matter regions were determined by extracting a brain and white matter regions based on a level set based method, whose speed function depended on gradient vectors in an original image and pixel values in grown regions. The CSF regions in cerebral sulci and lateral ventricles were extracted by wrapping the brain tightly with a zero level set determined from a level set function. Volumes of the specific regions and the cortical thickness were determined as atrophic image features. Average cortical thickness was calculated in 32 subregions, which were obtained by dividing each brain region. Finally, AD patients were classified by using a support vector machine, which was trained by the image features of AD and non-AD cases. We applied our CAD method to MR images of whole brains obtained from 29 clinically diagnosed AD cases and 25 non-AD cases. As a result, the area under a receiver operating characteristic (ROC) curve obtained by our computerized method was 0.901 based on a leave-one-out test in identification of AD cases among 54 cases including 8 AD patients at early stages. The accuracy for discrimination between 29 AD patients and 25 non-AD subjects was 0.840, which was determined at the point where the sensitivity was the same as the specificity on the ROC curve. This result showed that our CAD method based on atrophic image features may be promising for detecting AD patients by using 3-D MR images.

  1. Collagen induced arthritis (CIA) in mice features regulatory transcriptional network connecting major histocompatibility complex (MHC H2) with autoantigen genes in the thymus.

    PubMed

    Donate, Paula B; Fornari, Thaís A; Junta, Cristina M; Magalhães, Danielle A; Macedo, Cláudia; Cunha, Thiago M; Nguyen, Catherine; Cunha, Fernando Q; Passos, Geraldo A

    2011-05-01

    Considering that imbalance of central tolerance in the thymus contributes to aggressive autoimmunity, we compared the expression of peripheral tissue autoantigens (PTA) genes, which are involved in self-representation in the thymic stroma, of two mouse strains; DBA-1/J (MHC-H2(q)) susceptible and DBA-2/J (MHC-H2(d)) resistant to collagen induced arthritis (CIA). We evaluate whether these strains differ in their thymic gene expression, allowing identification of genes that might play a role in susceptibility/resistance to CIA. Microarray profiling showed that 1093 PTA genes were differentially modulated between collagen immunized DBA-1/J and DBA-2/J mice. These genes were assigned to 17 different tissues/organs, including joints/bone, characterizing the promiscuous gene expression (PGE), which is implicated in self-representation. Hierarchical clustering of microarray data and quantitative RT-PCR analysis showed that Aire (autoimmune regulator), an important regulator of the PGE process, Aire-dependent (insulin), Aire-independent (Col2A1 and Gad67), and other 22 joint/bone autoantigen genes were down-regulated in DBA-1/J compared with DBA-2/J in the thymus. Considering the importance of MHC-H2 in peptide-self presentation and autoimmunity susceptibility, we reconstructed transcriptional networks of both strains based on actual microarray data. The networks clearly demonstrated different MHC-H2 transcriptional interactions with PTAs genes. DBA-1/J strain featured MHC-H2 as a node influencing downstream genes. Differently, in DBA-2/J strain network MHC-H2 was exclusively self-regulated and does not control other genes. These findings provide evidence that CIA susceptibility in mice may be a reflex of a cascade-like transcriptional control connecting different genes to MHC-H2 in the thymus.

  2. Assessment of genetic and chemical variability in Thymus caramanicus.

    PubMed

    Hadian, Javad; Bigdeloo, Mahdi; Nazeri, Vahideh; Khadivi-Khub, Abdollah

    2014-05-01

    Thymus caramanicus is an endemic species grown in Iran with interesting pharmacological and biological properties. In the present work, essential oil compositions and inter-simple sequences repeat (ISSR) markers were used to estimate the relationships among and within seven populations of T. caramanicus, belonging to three provinces in Iran. The studied individuals were distinguished on the basis of ISSR markers and constituents of essential oil. A total of 127 band positions were produced by 12 ISSR primers, of which 105 were found polymorphic with 82.68% polymorphism. Genetic similarity values among individuals ranged between 0.15 and 0.82 which was indicative of a high level of genetic variation. On the basis of their genetic similarities, ISSR analysis allowed to group the samples into two main clusters. One of these included populations originated from Kerman and Isfahan provinces, and the other cluster consists of populations from Semnan province. Chemical compounds of essential oils were found variable in the various individuals and all samples were principally composed of phenolic constituents (carvacrol and/or thymol). As a consequence, the plants were classified into two major chemotypes including carvacrol and thymol/carvacrol. A relationship between genetic and chemical variability and geographic distribution has been observed in studied populations of T. caramanicus. PMID:24469732

  3. Activity of Thymus vulgaris essential oil against Anisakis larvae.

    PubMed

    Giarratana, F; Muscolino, D; Beninati, C; Giuffrida, A; Panebianco, A

    2014-07-01

    Anisakiasis is an important food-borne disease especially in countries with high fish consumption. The increase of cases of human disease and the virtual absence of effective treatments have prompted the research on new active compounds against Anisakis larvae. As well known, the disease is related to the consumption of raw or almost raw seafood products, but also marinated and/or salted fishery products, if the processing is insufficient to destroy nematode larvae can represent a risks for the consumers. In the light of the biocidal efficacy against different pathogens demonstrated for various essential oils, the aim of this work is to evaluate the effect of Thymus vulgaris essential oil (TEO) against anisakidae larvae. The TEO at 10% and 5% concentration in oil sunflower seeds, caused in vitro the death of all larvae within 14 h, with cuticle and intestinal wall damages. The results obtained showing a significant activity against Anisakis larvae, suggest further investigation on TEO as a larvicidal agent and on its potential use in the industrial marinating process.

  4. Chitosan microbeads for encapsulation of thyme (Thymus serpyllum L.) polyphenols.

    PubMed

    Trifković, Kata T; Milašinović, Nikola Z; Djordjević, Verica B; Krušić, Melina T Kalagasidis; Knežević-Jugović, Zorica D; Nedović, Viktor A; Bugarski, Branko M

    2014-10-13

    In this work chitosan microbeads were prepared by emulsion technique and loaded with thyme polyphenols by diffusion from an external aqueous solution of Thymus serpyllum L. The effects of concentrations of chitosan (1.5-3% (w/v)) and GA (glutaraldehyde) (0.1-0.4% (v/v)), as a crosslinking agent on the main properties of microbeads were assessed. The obtained microgel beads from ∼ 220 to ∼ 790 μm in diameter were exposed to controlled drying process at air (at 37 °C) after which they contracted to irregular shapes (∼ 70-230 μm). The loading of dried microbeads with polyphenols was achieved by swelling in the acidic medium. The swelling rate of microbeads decreased with the increase in GA concentration. Upon this rehydration, thyme polyphenols were effectively encapsulated (active load of 66-114 mg GAE g(beads)(-1)) and the microbeads recovered a spherical shape. Both, the increase in the amount of the crosslinking agent and the presence of polyphenols, contributed to a more pronounced surface roughness of microbeads. The release of encapsulated polyphenols in simulated gastrointestinal fluids was prolonged to 3h.

  5. Glandular Trichomes and Essential Oil of Thymus quinquecostatus

    PubMed Central

    Jia, Ping; Liu, Hanzhu; Gao, Ting; Xin, Hua

    2013-01-01

    The distribution and types of glandular trichomes and essential oil chemistry of Thymus quinquecostatus were studied. The glandular trichomes are distributed on the surface of stem, leaf, rachis, calyx and corolla, except petiole, pistil and stamen. Three morphologically distinct types of glandular trichomes are described. Peltate trichomes, consisting of a basal cell, a stalk cell and a 12-celled head, are distributed on the stem, leaf, corolla and outer side of calyx. Capitate trichomes, consisting of a unicellular base, a 1–2-celled stalk and a unicellular head, are distributed more diffusely than peltate ones, existing on stem, leaf, rachis and calyx. Digitiform trichomes are just distributed on the outer side of corolla, consisting of 1 basal cell, 3 stalk cells and 1 head cell. All three types of glandular trichomes can secrete essential oil, and in small capitate trichomes of rachis, all peltate trichomes and digitiform trichomes, essential oil is stored in a large subcuticular space, released by cuticle rupture, whereas, in other capitate trichomes, essential oil crosses the thin cuticle. The essential oil of T. quinquecostatus is yellow, and its content is highest in the growth period. 68 constituents were identified in the essential oils. The main constituent is linalool. PMID:24250266

  6. Chitosan microbeads for encapsulation of thyme (Thymus serpyllum L.) polyphenols.

    PubMed

    Trifković, Kata T; Milašinović, Nikola Z; Djordjević, Verica B; Krušić, Melina T Kalagasidis; Knežević-Jugović, Zorica D; Nedović, Viktor A; Bugarski, Branko M

    2014-10-13

    In this work chitosan microbeads were prepared by emulsion technique and loaded with thyme polyphenols by diffusion from an external aqueous solution of Thymus serpyllum L. The effects of concentrations of chitosan (1.5-3% (w/v)) and GA (glutaraldehyde) (0.1-0.4% (v/v)), as a crosslinking agent on the main properties of microbeads were assessed. The obtained microgel beads from ∼ 220 to ∼ 790 μm in diameter were exposed to controlled drying process at air (at 37 °C) after which they contracted to irregular shapes (∼ 70-230 μm). The loading of dried microbeads with polyphenols was achieved by swelling in the acidic medium. The swelling rate of microbeads decreased with the increase in GA concentration. Upon this rehydration, thyme polyphenols were effectively encapsulated (active load of 66-114 mg GAE g(beads)(-1)) and the microbeads recovered a spherical shape. Both, the increase in the amount of the crosslinking agent and the presence of polyphenols, contributed to a more pronounced surface roughness of microbeads. The release of encapsulated polyphenols in simulated gastrointestinal fluids was prolonged to 3h. PMID:25037430

  7. Thymus hyperplasia, differential diagnosis in the wheezing infant.

    PubMed

    Pedroza Meléndez, A; Larenas-Linnemann, D

    1997-01-01

    Thymus hyperplasia is not a rare condition in infancy, but it is generally considered not to cause any symptoms. We present here a series of 11 children seen at the National Institute of Pediatrics (NIP), Mexico-city, that do have respiratory symptoms secondary to the enlarged gland. Age of onset of the symptoms was median at birth, with age of first visit to the NIP of 6 months. Symptoms were respiratory crisis and various respiratory complaints. Five underwent thoracotomy and resection of the right pulmonary lobe was necessary in one, because of irreversible changes in the lung tissue due to chronic compression. In another patient thymic lobectomy was executed because extrinsic compression of the right upper bronchus resulted in recurrent atelectasia. The five biopsies taken during the intervention showed normal or hyperplastic or involutive thymic tissue without signs of malignancy. The evolution was positive in all the patients. In conclusion thymic hyperplasia must be taken into account in the evaluation of an infant with respiratory symptoms. PMID:9150833

  8. Association of nucleotide excision repair pathway gene polymorphisms with gastric cancer and atrophic gastritis risks.

    PubMed

    Liu, Jingwei; Sun, Liping; Xu, Qian; Tu, Huakang; He, Caiyun; Xing, Chengzhong; Yuan, Yuan

    2016-02-01

    Polymorphisms of NER genes could change NER ability, thereby altering individual susceptibility to GC. We systematically analyzed 39 SNPs of 8 key genes of NER pathway in 2686 subjects including 898 gastric cancer (GC), 851 atrophic gastritis (AG) and 937 controls (CON) in northern Chinese. SNP genotyping were performed using Sequenom MassARRAY platform. The results demonstrated that DDB2 rs830083 GG genotype was significantly associated with increased GC risk compared with wild-type CC (OR=2.32, P= 6.62 × 10-9); XPC rs2607775 CG genotype conferred a 1.73 increased odds of GC risk than non-cancer subjects compared with wild-type CC (OR=1.73, P= 3.04 × 10-4). The combined detection of these two polymorphisms demonstrated even higher GC risk (OR=3.05). Haplotype analysis suggested that DDB2 rs2029298-rs326222-rs3781619-rs830083 GTAG haplotype was significantly associated with disease risk in each step of CON→AG→GC development (AG vs. CON: OR=2.88, P= 7.51 × 10-7; GC vs. AG: OR=2.90, P=5.68 × 10-15; GC vs. CON: OR=8.42, P=2.22 × 10-15); DDB2 GTAC haplotype was associated with reduced risk of GC compared with CON (OR=0.63, P= 8.31 × 10-12). XPC rs1870134-rs2228000-rs2228001-rs2470352-rs2607775 GCAAG haplotype conferred increased risk of GC compared with AG (OR=1.88, P= 6.98 × 10-4). XPA rs2808668 and drinking, DDB2 rs326222, rs3781619, rs830083 and smoking demonstrated significant interactions in AG; XPC rs2607775 had significant interaction with smoking in GC. In conclusion, NER pathway polymorphisms especially in "damage incision" step were significantly associated with GC risk and had interactions with environment factors. The detection of NER pathway polymorphisms such as DDB2 and XPC might be applied in the prediction of GC risk and personalized prevention in the future. NER pathway polymorphisms especially in "damage incision" step were significantly associated with GC risk and had interactions with environment factors, which might be applied in the

  9. Atrophic gastritis: Risk factor for esophageal squamous cell carcinoma in a Latin-American population

    PubMed Central

    Almodova, Emiliano de Carvalho; de Oliveira, Walmar Kerche; Machado, Lucas Faria Abrahão; Grejo, Juliana Rigotto; da Cunha, Thiago Rabelo; Colaiacovo, Wagner; Ortolan, Erika Veruska Paiva

    2013-01-01

    AIM: To study the association between atrophic gastritis (AG) and esophageal squamous cell carcinoma (ESCC) in a Latin-America population. METHODS: A case-control study was performed at two reference Brazilian hospitals including patients diagnosed with advanced ESCC and dyspeptic patients who had been subjected to upper gastrointestinal endoscopy, with biopsies of the gastric antrum and body. All cases with ESCC were reviewed by a single pathologist, who applied standard criteria for the diagnosis of mucosal atrophy, intestinal metaplasia, and dysplasia, all classified as AG. The data on the patients’ age, sex, smoking status, and alcohol consumption were collected from clinical records, and any missing information was completed by telephone interview. The association between AG and ESCC was assessed by means of univariate and multiple conditional logistic regressions. RESULTS: Most patients were male, and the median age was 59 years (range: 37-79 years) in both the ESCC and control groups. Univariate analysis showed that an intake of ethanol greater than 32 g/d was an independent risk factor that increased the odds of ESCC 7.57 times (P = 0.014); upon multiple analysis, alcohol intake of ethanol greater than 32 g/d exhibited a risk of 4.54 (P = 0.081), as adjusted for AG and smoking. Smoking was shown to be an independent risk factor that increased the odds of ESCC 14.55 times (P = 0.011) for individuals who smoked 0 to 51 packs/year and 21.40 times (P = 0.006) for those who smoked more than 51 packs/year. Upon multiple analyses, those who smoked up to 51 packs/year exhibited a risk of 7.85 (P = 0.058), and those who smoked more than 51 packs/ year had a risk 11.57 times higher (P = 0.04), as adjusted for AG and alcohol consumption. AG proved to be a risk factor that increased the odds of ESCC 5.33 times (95%CI: 1.55-18.30, P = 0.008) according to the results of univariate conditional logistic regression. CONCLUSION: There was an association by univariate

  10. Influence of human myasthenia gravis thymus on the differentiation of human cord blood stem cells in SCID mice.

    PubMed

    Li, Qian Ru; Liu, Ping Ping; Xuan, Xiao Yan; Guan, Sha Sha; Du, Ying; Gao, Feng; Zhang, Qing Yong

    2014-02-01

    The normal thymus contributes to T lymphocytes differentiation and induction of tolerance to self-antigens. Myasthenia gravis (MG) is characterized by abnormal thymic hyperplasia. To assess the potential influence of MG-thymus on the differentiation of T lymphocytes differentiation, we used the MG-thymus transplanted severe combined immunodeficiency (SCID) mice model to evaluate the human cord blood stem cells differentiation. Thymus fragments from MG patient and human cord blood stem cells were transplanted into SCID mice successively. SCID mice were observed to develop sustained human T lymphocytes and a functional anti-tumor immune. The levels of various T cell subsets in SCID mice with MG-thymus were different from that of control group. Among that, the frequency of CD4(+)CD25(+) T cells was significant lower in SCID mice with MG-thymus. The deficiency of CD4(+)CD25(+) T cells seens to contribute to the pathogenesis of MG.

  11. The SCID-hu mouse as a model for HIV-1 infection.

    PubMed

    Aldrovandi, G M; Feuer, G; Gao, L; Jamieson, B; Kristeva, M; Chen, I S; Zack, J A

    1993-06-24

    During normal fetal ontogeny, one of the first organs to harbour CD4-positive cells is the thymus. This organ could therefore be one of the earliest targets infected by human immunodeficiency virus type 1 (HIV-1) in utero. HIV-1-infected cells and pathological abnormalities of the thymus have been seen in HIV-1-infected adults and children, and in some fetuses aborted from infected women. Studies of HIV-1 pathogenesis have been hampered by lack of a suitable animal model system. Here we use the SCID-hu mouse as a model to investigate the effect of virus infection on human tissue. The mouse is homozygous for the severe combined immunodeficiency (SCID) defect. The model is constructed by implanting human fetal liver and thymus under the mouse kidney capsule. A conjoint human organ develops, which allows normal maturation of human thymocytes. After direct inoculation of HIV-1 into these implants, we observed severe depletion of human CD4-bearing cells within a few weeks of infection. This correlated with increasing virus load in the implants. Thus the SCID-hu mouse may be a useful in vivo system for the study of HIV-1-induced pathology.

  12. [Overview of clinical study on traditional Chinese medicine invigorating spleen and stomach, promoting blood circulation and remove blood stasis in treatment of chronic atrophic gastritis].

    PubMed

    Liu, Ming; Liu, Zhen

    2012-11-01

    In recent years, traditional Chinese medicines invigorating spleen and stomach, promoting blood circulation and removing blood stasis have made fruitful achievements in the treatment of chronic atrophic gastritis (CAG) and remarkable curative effects in eliminating clinical signs, enhancing the mucosal barrier, improving submucosal microcirculation, prompting submucosal atrophic glands and atypical hyperplasia reversal. This essay summarizes reports and literatures for clinical studies on CAG in recent years, and discusses its etiology, pathogenesis and clinical administration of traditional Chinese medicine and western medicine, in order to provide ideas and methods for CAG treatment with traditional Chinese medicines.

  13. An unusual case of atrophic mandible fracture in a patient with osteogenesis imperfecta and on oral bisphosphonate therapy: Case report

    PubMed Central

    Al-Osaimi, Abdulrahman; Samman, Mahmood; Al-Shakhs, Mohammad; Al-Suhaim, Faisal; Ramalingam, Sundar

    2014-01-01

    Fractures of severely atrophic (height < 10 mm) edentulous mandibles are infrequent and challenging to manage. Factors such as sclerotic bone and decreased vascularity combined with systemic diseases complicate the management of such fractures. Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of type I collagen metabolism. Patients with OI characteristically present with histories of long bone fractures, deformities, blue sclerae, and opalescent dentin. However, fractures of the facial skeleton are rare. Bisphosphonate therapy has been proven to effectively reduce the fracture risk in patients with OI. The purpose of this clinical report is to present an unusual case of spontaneous fracture of the atrophic mandible in a patient with OI. Despite open reduction and internal fixation (ORIF) with miniplate osteosynthesis, the patient developed a second fracture at a screw placement site distal to the first fracture. The patient was successfully treated with ORIF using locking reconstruction plates fixed in the symphyseal and angle regions. Bone healing following ORIF was normal, and no clinical sign of osteonecrosis as a result of bisphosphonate therapy was observed. Patients with OI can present with spontaneous fractures of already weakened mandibles. Although such fractures can be managed with care using established protocols, further research is required to examine the effects of concomitant medication, such as bisphosphonates. PMID:25408599

  14. Inlay osteotome sinus floor elevation with concentrated growth factor application and simultaneous short implant placement in severely atrophic maxilla.

    PubMed

    Chen, Yonghui; Cai, Zhiyu; Zheng, Dingguo; Lin, Pei; Cai, Yahua; Hong, Shuxin; Lai, Yiwei; Wu, Dong

    2016-01-01

    Sinus floor elevation with simultaneous implant placement in severely atrophic maxilla is challenging. The aim of this retrospective study was to evaluate the short-term performance of modified osteotome sinus floor elevation (OSFE) with concentrated growth factor (CGF) application and concurrent placement of a short implant in cases with residual bone height (RBH) of 2-4 mm. Twenty-five short implants were installed in 16 patients with mean RBH of 3.23 mm using modified OSFE with CGFs from January 2012 to April 2014. Postoperatively, the implants were clinically evaluated, and vertical bone gain (VBG) was measured using cone beam computed tomography. The mean duration of follow-up was 19.88 months (12-32 months). All the implants were stable with an overall survival rate of 100%. The mean VBG immediately after surgery was 9.21 mm. Six months later, significant reduction of alveolar bone height (2.90 ± 0.22 mm) was found (P < 0.05). During the second 6-month period, further alveolar bone resorption (0.14 ± 0.11 mm) was noted but without significance (P > 0.05). Within the limits of this study, modified OSFE with CGF application and simultaneous short implant placement could yield predictable clinical results for severely atrophic maxilla with RBH of 2-4 mm. PMID:27250556

  15. Inlay osteotome sinus floor elevation with concentrated growth factor application and simultaneous short implant placement in severely atrophic maxilla

    PubMed Central

    Chen, Yonghui; Cai, Zhiyu; Zheng, Dingguo; Lin, Pei; Cai, Yahua; Hong, Shuxin; Lai, Yiwei; Wu, Dong

    2016-01-01

    Sinus floor elevation with simultaneous implant placement in severely atrophic maxilla is challenging. The aim of this retrospective study was to evaluate the short-term performance of modified osteotome sinus floor elevation (OSFE) with concentrated growth factor (CGF) application and concurrent placement of a short implant in cases with residual bone height (RBH) of 2–4 mm. Twenty-five short implants were installed in 16 patients with mean RBH of 3.23 mm using modified OSFE with CGFs from January 2012 to April 2014. Postoperatively, the implants were clinically evaluated, and vertical bone gain (VBG) was measured using cone beam computed tomography. The mean duration of follow-up was 19.88 months (12–32 months). All the implants were stable with an overall survival rate of 100%. The mean VBG immediately after surgery was 9.21 mm. Six months later, significant reduction of alveolar bone height (2.90 ± 0.22 mm) was found (P < 0.05). During the second 6-month period, further alveolar bone resorption (0.14 ± 0.11 mm) was noted but without significance (P > 0.05). Within the limits of this study, modified OSFE with CGF application and simultaneous short implant placement could yield predictable clinical results for severely atrophic maxilla with RBH of 2–4 mm. PMID:27250556

  16. Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions.

    PubMed

    Liu, Zhijie; Farley, Alison; Chen, Lizhen; Kirby, Beth J; Kovacs, Christopher S; Blackburn, C Clare; Manley, Nancy R

    2010-01-01

    In mammals, parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the parathyroid glands were thought to be the only source of PTH, extra-parathyroid PTH production in the thymus, which shares a common origin with parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aparathyroid Gcm2⁻/⁻ mutants. However, the developmental ontogeny and cellular identity of these "thymic" PTH-expressing cells is unknown. We found that the lethality of aparathyroid Gcm2⁻/⁻ mutants was affected by genetic background without relation to serum PTH levels, suggesting a need to reconsider the physiological function of thymic PTH. We identified two sources of extra-parathyroid PTH in wild-type mice. Incomplete separation of the parathyroid and thymus organs during organogenesis resulted in misplaced, isolated parathyroid cells that were often attached to the thymus; this was the major source of thymic PTH in normal mice. Analysis of thymus and parathyroid organogenesis in human embryos showed a broadly similar result, indicating that these results may provide insight into human parathyroid development. In addition, medullary thymic epithelial cells (mTECs) express PTH in a Gcm2-independent manner that requires TEC differentiation and is consistent with expression as a self-antigen for negative selection. Genetic or surgical removal of the thymus indicated that thymus-derived PTH in Gcm2⁻/⁻ mutants did not provide auxiliary endocrine function. Our data show conclusively that the thymus does not serve as an auxiliary source of either serum PTH or parathyroid function. We further show that the normal process of parathyroid organogenesis in both mice and humans leads to the generation of multiple small parathyroid clusters in addition to the main parathyroid glands, that are the likely source of physiologically relevant "thymic

  17. Tetanic contraction induces enhancement of fatigability and sarcomeric damage in atrophic skeletal muscle and its underlying molecular mechanisms.

    PubMed

    Yu, Zhi-Bin

    2013-11-01

    Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigravity muscles of the lower limbs. Besides reducing astronauts' mobility in space and on returning to a gravity environment, the molecular mechanisms for the adaptation of skeletal muscle to unloading also play an important medical role in conditions such as disuse and paralysis. The tail-suspended rat model was used to simulate the effects of weightlessness on skeletal muscles and to induce muscle unloading in the rat hindlimb. Our series studies have shown that the maximum of twitch tension and the twitch duration decreased significantly in the atrophic soleus muscles, the maximal tension of high-frequency tetanic contraction was significantly reduced in 2-week unloaded soleus muscles, however, the fatigability of high-frequency tetanic contraction increased after one week of unloading. The maximal isometric tension of intermittent tetanic contraction at optimal stimulating frequency did not alter in 1- and 2-week unloaded soleus, but significantly decreased in 4-week unloaded soleus. The 1-week unloaded soleus, but not extensor digitorum longus (EDL), was more susceptible to fatigue during intermittent tetanic contraction than the synchronous controls. The changes in K+ channel characteristics may increase the fatigability during high-frequency tetanic contraction in atrophic soleus muscles. High fatigability of intermittent tetanic contraction may be involved in enhanced activity of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and switching from slow to fast isoform of myosin heavy chain, tropomyosin, troponin I and T subunit in atrophic soleus muscles. Unloaded soleus muscle also showed a decreased protein level of neuronal nitric oxide synthase (nNOS), and the reduction in nNOS-derived NO increased frequency of calcium sparks and elevated

  18. Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies.

    PubMed

    Shimbo, Miki; Kudo, Takashi; Hamada, Michito; Jeon, Hyojung; Imamura, Yuki; Asano, Keigo; Okada, Risa; Tsunakawa, Yuki; Mizuno, Seiya; Yagami, Ken-Ichi; Ishikawa, Chihiro; Li, Haiyan; Shiga, Takashi; Ishida, Junji; Hamada, Juri; Murata, Kazuya; Ishimaru, Tomohiro; Hashimoto, Misuzu; Fukamizu, Akiyoshi; Yamane, Mutsumi; Ikawa, Masahito; Morita, Hironobu; Shinohara, Masahiro; Asahara, Hiroshi; Akiyama, Taishin; Akiyama, Nobuko; Sasanuma, Hiroki; Yoshida, Nobuaki; Zhou, Rui; Wang, Ying-Ying; Ito, Taito; Kokubu, Yuko; Noguchi, Taka-Aki K; Ishimine, Hisako; Kurisaki, Akira; Shiba, Dai; Mizuno, Hiroyasu; Shirakawa, Masaki; Ito, Naoki; Takeda, Shin; Takahashi, Satoru

    2016-05-20

    The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module ("Kibo") on the International Space Station. The CBEF provides "space-based controls" by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments. PMID:26822934

  19. Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies

    PubMed Central

    Shimbo, Miki; Kudo, Takashi; Hamada, Michito; Jeon, Hyojung; Imamura, Yuki; Asano, Keigo; Okada, Risa; Tsunakawa, Yuki; Mizuno, Seiya; Yagami, Ken-ichi; Ishikawa, Chihiro; Li, Haiyan; Shiga, Takashi; Ishida, Junji; Hamada, Juri; Murata, Kazuya; Ishimaru, Tomohiro; Hashimoto, Misuzu; Fukamizu, Akiyoshi; Yamane, Mutsumi; Ikawa, Masahito; Morita, Hironobu; Shinohara, Masahiro; Asahara, Hiroshi; Akiyama, Taishin; Akiyama, Nobuko; Sasanuma, Hiroki; Yoshida, Nobuaki; Zhou, Rui; Wang, Ying-Ying; Ito, Taito; Kokubu, Yuko; Noguchi, Taka-aki K.; Ishimine, Hisako; Kurisaki, Akira; Shiba, Dai; Mizuno, Hiroyasu; Shirakawa, Masaki; Ito, Naoki; Takeda, Shin; Takahashi, Satoru

    2016-01-01

    The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module (“Kibo”) on the International Space Station. The CBEF provides “space-based controls” by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments. PMID:26822934

  20. Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies.

    PubMed

    Shimbo, Miki; Kudo, Takashi; Hamada, Michito; Jeon, Hyojung; Imamura, Yuki; Asano, Keigo; Okada, Risa; Tsunakawa, Yuki; Mizuno, Seiya; Yagami, Ken-Ichi; Ishikawa, Chihiro; Li, Haiyan; Shiga, Takashi; Ishida, Junji; Hamada, Juri; Murata, Kazuya; Ishimaru, Tomohiro; Hashimoto, Misuzu; Fukamizu, Akiyoshi; Yamane, Mutsumi; Ikawa, Masahito; Morita, Hironobu; Shinohara, Masahiro; Asahara, Hiroshi; Akiyama, Taishin; Akiyama, Nobuko; Sasanuma, Hiroki; Yoshida, Nobuaki; Zhou, Rui; Wang, Ying-Ying; Ito, Taito; Kokubu, Yuko; Noguchi, Taka-Aki K; Ishimine, Hisako; Kurisaki, Akira; Shiba, Dai; Mizuno, Hiroyasu; Shirakawa, Masaki; Ito, Naoki; Takeda, Shin; Takahashi, Satoru

    2016-05-20

    The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module ("Kibo") on the International Space Station. The CBEF provides "space-based controls" by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments.

  1. Trb2, a mouse homolog of tribbles, is dispensable for kidney and mouse development

    SciTech Connect

    Takasato, Minoru; Kobayashi, Chiyoko; Okabayashi, Koji; Kiyonari, Hiroshi; Oshima, Naoko; Asashima, Makoto; Nishinakamura, Ryuichi

    2008-09-05

    Glomeruli comprise an important filtering apparatus in the kidney and are derived from the metanephric mesenchyme. A nuclear protein, Sall1, is expressed in this mesenchyme, and we previously reported that Trb2, a mouse homolog of Drosophila tribbles, is expressed in the mesenchyme-derived tissues of the kidney by microarray analyses using Sall1-GFP knock-in mice. In the present report, we detected Trb2 expression in a variety of organs during gestation, including the kidneys, mesonephros, testes, heart, eyes, thymus, blood vessels, muscle, bones, tongue, spinal cord, and ganglions. In the developing kidney, Trb2 signals were detected in podocytes and the prospective mesangium of the glomeruli, as well as in ureteric bud tips. However, Trb2 mutant mice did not display any apparent phenotypes and no proteinuria was observed, indicating normal glomerular functions. These results suggest that Trb2 plays minimal roles during kidney and mouse development.

  2. Expression of somatostatin and cDNA cloning in the thymus of the African ostrich.

    PubMed

    Min, Chen; Min, He; Kemei, Peng; Ke, Xiao; Haibo, Huang; Daiyun, Zhu; Xinting, Zheng

    2014-01-01

    The thymus in addition to being a central lymphoid organ is also an endocrine organ which produces various neuropeptides that influence the function of this gland. Somatostatin is a neuropeptide that was isolated initially in the hypothalamus and which inhibits the release of growth hormone. The distribution of somatostatin-producing cells and the sequence of somatostatin have been determined in many species. In the present study, we investigated the expression of somatostatin in the thymus of the African ostrich and its sequence by reverse-transcriptase polymerase chain reaction and immunohistochemistry. The results showed that somatostatin mRNA was expressed in the thymus and somatostatin immunoreative cells were distributed in both the cortical and medullary regions of the thymus. Results of cDNA cloning revealed that the nucleotide sequence and the encoded protein of African ostrich somatostatin were 348 bases and 116 amino acids in length and that it is highly conserved to that of other reported species. These findings indicated that the somatostatin expressed in the thymus of ostrich might play an important role in the function of the gland. In addition, this research has provided novel molecular data allowing further study of somatostatin in the ostrich.

  3. Young, proliferative thymic epithelial cells engraft and function in aging thymuses

    PubMed Central

    Kim, Mi-Jeong; Miller, Christine M.; Shadrach, Jennifer L.; Wagers, Amy J.; Serwold, Thomas

    2015-01-01

    The thymus reaches its maximum size early in life and then begins to shrink, producing fewer T cells with increasing age. This thymic decline is thought to contribute to age-related T cell lymphopenias and hinder T cell recovery following bone marrow transplantation. While several cellular and molecular processes have been implicated in age-related thymic involution, their relative contributions are not known. Using heterochronic parabiosis, we observe that young circulating factors are not sufficient to drive regeneration of the aged thymus. In contrast, we find that resupplying young, engraftable thymic epithelial cells to a middle-aged or defective thymus leads to thymic growth and increased T cell production. Intrathymic transplantation and in vitro colony forming assays reveal that the engraftment and proliferative capacities of thymic epithelial cells diminish early in life, whereas the receptivity of the thymus to thymic epithelial cell engraftment remains relatively constant with age. These results support a model in which thymic growth and subsequent involution are driven by cell intrinsic changes in the proliferative capacity of thymic epithelial cells, and further show that young thymic epithelial cells can engraft and directly drive the growth of involuted thymuses. PMID:25870244

  4. Bendiocarbamate induced structural alterations in rabbit thymus after experimental peroral administration.

    PubMed

    Flesarova, Slavka; Lukac, Norbert; Danko, Jan; Massanyi, Peter

    2007-01-01

    In this study histological structure of rabbit thymus after bendiocarbamate (2,3-isopropyledene-dioxyphenyl methylcarbamate) administration was studied. Bendiocarbamate was perorally administered for 90 days. At Day 3, 10, 20, 30, 60, 90 morphometric analysis was realized. Quantitative evaluation showed that in the control group thymus cortex forms 57.94 +/- 7.10% and medulla 35.94+/- 7.38%. In almost all experimental groups significantly higher relative volume of cortex and lower relative volume of medulla was detected. Detail morphometric analysis found that the number of thymocytes per constant area and the diameter of tymocytes was decresed after bendiocarbamate administration. The number and diameter of reticular cells was not affected. Results of this study suggest negative effect of bendiocarbamate on the formation of thymus structures.

  5. Bilateral ectopic cervical thymus presenting as a neck mass: Ultrasound and magnetic resonance imaging.

    PubMed

    Tanrivermis Sayit, Asli; Elmali, Muzaffer; Hashimov, Jalal; Ceyhan Bilgici, Meltem; Dağdemir, Ayhan

    2016-09-01

    Ectopic cervical thymus (ECT) is a rare cause of neck mass in the pediatric age group. It is extremely uncommon in infants. Overall more than 100 cases have been reported in the literature, though fewer than 10% involved infants. Furthermore, ECT is usually unilateral and more frequently seen in men than in women. Ultrasound (US) is the preferred initial imaging modality, especially in pediatric neck masses given its wide availability, low cost and lack of radiation exposure. US can show the location, extension, and echotexture of the ECT. Magnetic resonance imaging (MRI) can be performed to verify the diagnosis and confirm communication between the ECT and the mediastinal thymus. Diffusion restriction can aid diagnosis when seen in a neck mass similar to that in the mediastinal thymus. Herein is described a case of bilateral ECT in a 2-month-old boy with associated US and MRI findings. PMID:27463062

  6. A critical overview on Thymus daenensis Celak.: phytochemical and pharmacological investigations.

    PubMed

    Zarshenas, Mohammad M; Krenn, Liselotte

    2015-03-01

    Thymus daenensis Celak. is an herb endemic to Iran belonging to the Lamiaceae family. Growing in many parts of Iran, the plant is extensively used in folk medicine. This review was performed to compile phytochemical and pharmacological data of T. daenensis. Databases such as PubMed, Scopus, Web of Science, ScienceDirect, Scientific Information Database, Embase, IranMedex and Google Scholar were searched for the terms "Thymus daenensis" and "Avishan-e-denaii" up to 1st January 2014. Following reported ethnopharmacological uses, various T. daenensis preparations have been investigated for antimicrobial, antioxidant, insecticidal and immunomodulatory effects in recent studies. Moreover, numerous studies have been published on the composition of the herb's essential oil, focusing either on environmental parameters or preparation methods. Due to its high concentration of thymol, the plant's essential oil possesses high antimicrobial activities on human pathogenic strains. However, comprehensive studies on the toxicity and teratogenicity as well as clinical efficacy of Thymus daenensis are missing.

  7. Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow.

    PubMed

    Yu, Vionnie W C; Saez, Borja; Cook, Colleen; Lotinun, Sutada; Pardo-Saganta, Ana; Wang, Ying-Hua; Lymperi, Stefania; Ferraro, Francesca; Raaijmakers, Marc H G P; Wu, Joy Y; Zhou, Lan; Rajagopal, Jayaraj; Kronenberg, Henry M; Baron, Roland; Scadden, David T

    2015-05-01

    Production of the cells that ultimately populate the thymus to generate α/β T cells has been controversial, and their molecular drivers remain undefined. Here, we report that specific deletion of bone-producing osteocalcin (Ocn)-expressing cells in vivo markedly reduces T-competent progenitors and thymus-homing receptor expression among bone marrow hematopoietic cells. Decreased intrathymic T cell precursors and decreased generation of mature T cells occurred despite normal thymic function. The Notch ligand DLL4 is abundantly expressed on bone marrow Ocn(+) cells, and selective depletion of DLL4 from these cells recapitulated the thymopoietic abnormality. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell-based adaptive immunity.

  8. Age-related changes in the thymus gland: CT-pathologic correlation

    SciTech Connect

    Moore, A.V.; Korobkin, M.; Olanow, W.; Heaston, D.K.; Ram, P.C.; Dunnick, N.R.; Silverman, P.M.

    1983-08-01

    Recent reports suggest that computed tomography (CT) is useful for thymoma detection in patients with myasthenia gravis. However, that usefulness may be conditioned by the state of the normal thymus. To examine this concept, the CT findings in 64 consecutive patients with histologic confirmation of thymic status after thymectomy or thymic biopsy during mediastinal exploration were reviewed. The normal thymus has a bilobed, arrowhead-shaped cross section at all ages, with gradual focal or diffuse fatty infiltration of the parenchyma usually occurring between 20 and 40 years of age. A thymoma is usually a spherical or oval mass, often producing a focal, distinct bulge in the adjacent pleural reflection. The differentiation of thymoma from normal thymus should be possible in most patients if age-related changes in the normal gland are appreciated.

  9. Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow

    PubMed Central

    Yu, Vionnie W.C.; Saez, Borja; Cook, Colleen; Lotinun, Sutada; Pardo-Saganta, Ana; Wang, Ying-Hua; Lymperi, Stefania; Ferraro, Francesca; Raaijmakers, Marc H.G.P.; Wu, Joy Y.; Zhou, Lan; Rajagopal, Jayaraj; Kronenberg, Henry M.; Baron, Roland

    2015-01-01

    Production of the cells that ultimately populate the thymus to generate α/β T cells has been controversial, and their molecular drivers remain undefined. Here, we report that specific deletion of bone-producing osteocalcin (Ocn)-expressing cells in vivo markedly reduces T-competent progenitors and thymus-homing receptor expression among bone marrow hematopoietic cells. Decreased intrathymic T cell precursors and decreased generation of mature T cells occurred despite normal thymic function. The Notch ligand DLL4 is abundantly expressed on bone marrow Ocn+ cells, and selective depletion of DLL4 from these cells recapitulated the thymopoietic abnormality. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell–based adaptive immunity. PMID:25918341

  10. Does acid suppression by antacids and H2 receptor antagonists increase the incidence of atrophic gastritis in patients with or without H. pylori gastritis?

    PubMed

    Carter, M; Katz, D L; Haque, S; DeLuca, V A

    1999-09-01

    Currently there is controversial evidence that suggests that the accepted incidence of atrophic gastritis of 1.2 to 3.3% in patients with Helicobacter pylori gastritis may be increased by the long-term suppression of acid by a proton pump inhibitor (omeprazole). The purpose of this study is to show whether lesser forms of acid suppression by antacids or H2 receptor antagonists may have an influence on the development of atrophic gastritis. The authors recently reported a study in which a cohort of 36 patients with symptoms of dyspepsia were followed clinically for a period of 7 to 19 years. In that report all subjects underwent upper endoscopy with two biopsy specimens each from the antrum and fundus, on at least two occasions, 7 to 19 years apart. A diagnosis of atrophic gastritis was based on the interpretation of these biopsies by two gastrointestinal pathologists. The presence of H. pylori colonization was determined by tissue sampling and by a campylobacter-like organisms test of the antrum. Of the 36 patients in the authors' previous report, 33 had adequate baseline and follow-up data on medications consumed throughout the period of the study. In their current report they now present the findings of a retrospective review in which they correlate the presence of atrophic gastritis with the sole use of antacids and H2 receptor antagonists throughout the period of the study. In the cohort of 33 patients evaluated from the previous report, the authors found that atrophic gastritis had developed in all 28 patients positive for H. pylori, and in none of the 5 patients negative for H. pylori (p < 0.0001). A retrospective analysis of this previously studied cohort of 33 patients revealed that the use of antacids and H2 receptor antagonists did not predict the development of atrophic gastritis in either H. pylori-negative or -positive subjects. In a retrospective analysis of a cohort of 33 patients followed for an average of 11.7 years, atrophic gastritis developed in

  11. The appearance of the thymus and the integrated evolution of adaptive immune and neuroendocrine systems.

    PubMed

    Geenen, V

    2012-01-01

    The immune system may be considered as a sensory organ able to respond to different kinds of danger signals that are not detected by nervous cells. The immune response is not autonomous but also regulated by the central and peripheral nervous system, as well as by neuropeptides, vitamin D and neuroendocrine axes such as the corticotrope, somatotrope, thyrotrope and gonadotrope axes. During evolution, the thymus emerged concomitantly with recombinase-dependent adaptive immunity as an'immune brain' or a'master class' highly specialized in the orchestration of central immunological self-tolerance. This was an absolute requirement for survival of species because of the high risk of autotoxicity inherent to the stochastic generation of extreme diversity characterizing this novel adaptive type of immune defenses against non-self. The thymus now appears to be an obligatory intersection for the integrated evolution of the major systems of cell-to-cell signalling, the nervous, endocrine and immune systems. The presentation of many self-peptides by thymic major histocompatibility complex (MHC) proteins is controlled by the autoimmune regulator (AIRE) gene/protein and is responsible for the clonal deletion of self-reactive T cells. In the same time, by still unexplained mechanisms, MHC presentation of the same self-peptides in the thymus promotes the generation of self-specific FOXP3+ CD4+CD25+ natural regulatory T cells (nTreg) that are able to inhibit in periphery self-reactive CD4+ and CD8+ T cells having escaped the thymus censorship. Moreover, a thymus dysfunction is more and more established as the primary event driving the development of organ-specific autoimmunity, which is the tribute paid, mainly by mankind, for the preservation of self against non-self. Our novel knowledge about thymus physiology and physiopathology already serves as the basis for the development of various innovative and efficient immunomodulating strategies in pharmacology. PMID:22897070

  12. Response of thymus lymphocytes to streptozotocin-induced diabetes and exogenous vitamin C administration in rats.

    PubMed

    Ozerkan, Dilşad; Ozsoy, Nesrin; Cebesoy, Suna

    2014-12-01

    Diabetes causes oxidative stress, which in turn generates excessive free radicals resulting in cellular damage. Vitamin C is an antioxidant that protects tissues and organs from oxidative stress. The thymus is one of the most important lymphoid organs, which regulates T-lymphocyte proliferation and maturation. The aim of this study is to investigate the protective effects of vitamin C on the thymus of streptozotocin (STZ)-induced diabetic rats. The mitotic activity and cell integrity of thymic lymphocytes were explored. Wistar Albino rats were divided into three groups: control (Group 1), STZ-diabetes (Group 2) and vitamin C-treated STZ-diabetics (Group 3). Rats received a single intraperitoneal injection of 45 mg/kg STZ to induce diabetes. Vitamin C (20 mg/kg) was administered intragastrically. Semithin and ultrathin sections were examined under a light or an electron microscope, respectively. Considerable numbers of mitotic lymphocytes were observed in the thymus of control rats. In the diabetic rats, however, numbers of mitotic lymphocytes decreased to ∼57% of controls, and cell division abnormalities were observed. Additionally, diabetic rats showed degeneration in the structure of the thymus including trabecular thickening, accumulation of lipid vacuoles, heterochromatic nuclei and loss of mitochondrial cristae. Degradation of medullar and cortical integrity was also detected. In the vitamin C-treated STZ-diabetic group, the structure of the thymus and mitotic activity of the lymphocytes were similar to the control group. These results suggest that vitamin C protects the thymus against injury caused by diabetes and restores thymocyte mitotic activity. PMID:25145646

  13. Response of thymus lymphocytes to streptozotocin-induced diabetes and exogenous vitamin C administration in rats.

    PubMed

    Ozerkan, Dilşad; Ozsoy, Nesrin; Cebesoy, Suna

    2014-12-01

    Diabetes causes oxidative stress, which in turn generates excessive free radicals resulting in cellular damage. Vitamin C is an antioxidant that protects tissues and organs from oxidative stress. The thymus is one of the most important lymphoid organs, which regulates T-lymphocyte proliferation and maturation. The aim of this study is to investigate the protective effects of vitamin C on the thymus of streptozotocin (STZ)-induced diabetic rats. The mitotic activity and cell integrity of thymic lymphocytes were explored. Wistar Albino rats were divided into three groups: control (Group 1), STZ-diabetes (Group 2) and vitamin C-treated STZ-diabetics (Group 3). Rats received a single intraperitoneal injection of 45 mg/kg STZ to induce diabetes. Vitamin C (20 mg/kg) was administered intragastrically. Semithin and ultrathin sections were examined under a light or an electron microscope, respectively. Considerable numbers of mitotic lymphocytes were observed in the thymus of control rats. In the diabetic rats, however, numbers of mitotic lymphocytes decreased to ∼57% of controls, and cell division abnormalities were observed. Additionally, diabetic rats showed degeneration in the structure of the thymus including trabecular thickening, accumulation of lipid vacuoles, heterochromatic nuclei and loss of mitochondrial cristae. Degradation of medullar and cortical integrity was also detected. In the vitamin C-treated STZ-diabetic group, the structure of the thymus and mitotic activity of the lymphocytes were similar to the control group. These results suggest that vitamin C protects the thymus against injury caused by diabetes and restores thymocyte mitotic activity.

  14. Transcriptional regulation of early T-cell development in the thymus.

    PubMed

    Seo, Wooseok; Taniuchi, Ichiro

    2016-03-01

    T-cell development occurs in multipotent progenitors arriving in the thymus, which provides a highly specialized microenvironment. Specification and sequential commitment processes to T cells begin in early thymic progenitors upon receiving thymus-specific environmental cues, resulting in the activation of the genetically programmed transcriptional cascade that includes turning on and off numerous transcription factors in a precise manner. Thus, early thymocyte differentiation has been an excellent model system to study cell differentiation processes. This review summarizes recent advances in our knowledge on thymic T-cell development from newly arrived multipotent T-cell progenitors to fully committed T-cell precursors, from the transcriptional regulation perspective. PMID:26763078

  15. [Expression of AIF and CGRP markers in pineal gland and thymus during aging].

    PubMed

    Lin'kova, N S; Katanugina, A S; Khavinson, V Kh

    2011-01-01

    We investigated the expression of AIF (apoptotic inducing factor) and CGRP (calcitonin gene related peptide) at autopsy material of pineal gland and thymus of people after 60 years old. The expression of AIF and CGRP was identified in both organs, but it did not change with age, which demonstrates the probable safety of functional activity of neuroimmunoendocrine system at aging. We found correlation between expression AIF and CGRP at pineal gland, but the correlation at thymus wasn't found. It is possible that pineal gland can express unidentified signal molecule controlling the expression of AIF and CGRP.

  16. Transcriptional regulation of early T-cell development in the thymus.

    PubMed

    Seo, Wooseok; Taniuchi, Ichiro

    2016-03-01

    T-cell development occurs in multipotent progenitors arriving in the thymus, which provides a highly specialized microenvironment. Specification and sequential commitment processes to T cells begin in early thymic progenitors upon receiving thymus-specific environmental cues, resulting in the activation of the genetically programmed transcriptional cascade that includes turning on and off numerous transcription factors in a precise manner. Thus, early thymocyte differentiation has been an excellent model system to study cell differentiation processes. This review summarizes recent advances in our knowledge on thymic T-cell development from newly arrived multipotent T-cell progenitors to fully committed T-cell precursors, from the transcriptional regulation perspective.

  17. Work flow for the prosthetic rehabilitation of atrophic patients with a minimal-intervention CAD/CAM approach.

    PubMed

    Ciocca, Leonardo; Ragazzini, Sara; Fantini, Massimiliano; Corinaldesi, Giuseppe; Scotti, Roberto

    2015-07-01

    The implant-supported fixed rehabilitation of patients with an atrophic edentulous crest remains a challenge if bone augmentation is not planned. A minimal intervention approach for bone regeneration is necessary to minimize the flap overextension needed to close the defect over the augmented bone. Prosthetically guided bone regeneration can determine the amount of bone augmentation necessary for definitive prosthetic fixed rehabilitation. The positions of the implants and prosthetic restoration were planned; a 0.3 mm thick titanium mesh was customized for bone augmentation by using computer-aided design and computer-aided manufacturing and rapid prototyped by laser sintering, and the definitive prosthetic rehabilitation was carried out according to the initial treatment plan. This resulted in minimal bone augmentation relative to the functional needs of the definitive prosthetic rehabilitation. PMID:25862269

  18. THE EFFECTS OF THYMUS AND OTHER LYMPHOID ORGANS ENCLOSED IN MILLIPORE DIFFUSION CHAMBERS ON NEONATALLY THYMECTOMIZED MICE

    PubMed Central

    Osoba, David

    1965-01-01

    When neonatally thymectomized CBA mice were implanted at 9 to 12 days of age with Millipore diffusion chambers (pore size, 0.1 µ) containing either syngeneic or allogeneic neonatal thymus, they were subsequently found to have the capacity to reject skin homografts and to form antibodies to sheep erythrocytes. In spite of displaying restored immune reactivity, thymectomized mice bearing thymus-filled diffusion chambers still had a lymphopenia and diminished numbers of small lymphocytes in their spleens, lymph nodes and Peyer's patches. Comparison of the lymphoid organs of these mice with those of the thymectomized control mice did not reveal any appreciable difference in the numbers of primary follicles or small lymphocytes. It is postulated that the thymus humoral factor induced immunological competence in lymphoid cells which had left the thymus prior to neonatal thymectomy. The paucity of circulating and tissue small lymphocytes in thymectomized animals, the immune reactivity of which was restored by thymus tissue in diffusion chambers, argues against the theory that the thymus humoral factor has a lymphocytosis-stimulating effect. There was no restoration of immune reactivity in those neonatally thymectomized mice which had been implanted with diffusion chambers containing neonatal or adult spleens, or adult lymph nodes. Thus, the competence-inducing factor is elaborated by the thymus but not by the spleen or lymph nodes. Allogeneic (C57Bl) neonatal thymus tissue, enclosed within diffusion chambers, had the capacity to restore the immune reactivity of totally thymectomized CBA mice, not only to skin homografts of a totally unrelated strain (Ak), but also to grafts isogeneic with the donor of the allogeneic thymus. Therefore, there is no strain barrier to the action of thymus humoral factor. To explain the apparent lack of full participation of thymus lymphocytes in immune reactions it is postulated that thymus lymphocytes are functionally immature in situ, and

  19. Decreased pool of mesenchymal stem cells is associated with altered chemokines serum levels in atrophic nonunion fractures.

    PubMed

    Mathieu, Myrielle; Rigutto, Sabrina; Ingels, Aude; Spruyt, Delphine; Stricwant, Nadia; Kharroubi, Ilham; Albarani, Valentina; Jayankura, Marc; Rasschaert, Joanne; Bastianelli, Enrico; Gangji, Valérie

    2013-04-01

    Nonunion fractures can cause severe dysfunction and are often difficult to treat mainly due to a poor understanding of their physiopathology. Although many aspects of impaired fracture healing have been extensively studied, little is known about the cellular and molecular mechanisms leading to atrophic nonunion. Therefore, the aim of the present study was to assess the pools and biological functions of bone marrow-derived mesenchymal stem cells (hMSCs) and circulating endothelial progenitor cells (EPCs) in atrophic nonunion patients compared to healthy subjects, and the systemic levels of growth factors involved in the recruitment, proliferation and differentiation of these cells. In nonunions, the pool of hMSCs was decreased and their proliferation delayed. However, once committed, hMSCs from nonunions were able to proliferate, differentiate into osteoblastic cells and mineralize in vitro as efficiently as hMSCs from healthy subjects. In parallel, we found altered serum levels of chemokines and growth factors involved in the chemotaxis and proliferation of hMSCs such as leptin, interleukin-6 (IL-6) and its soluble receptor, platelet-derived growth factor-BB (PDGF-BB), stem cell factor (SCF) and insulin-like growth factor-1 (IGF-1). Moreover, we showed that the number of EPCs and their regulating growth factors were not affected in nonunion patients. If nonunion is generally attributed to a vascular defect, our results also support a role for a systemic mesenchymal and osteogenic cell pool defect that might be related to alterations in systemic levels of factors implicated in their chemotaxis and proliferation. PMID:23318974

  20. Treatment of the edentulous atrophic maxilla using zygomatic implants: evaluation of survival rates over 5-10 years.

    PubMed

    Yates, J M; Brook, I M; Patel, R R; Wragg, P F; Atkins, S A; El-Awa, A; Bakri, I; Bolt, R

    2014-02-01

    The aim of this retrospective observational cohort study was to analyse and report the 5-10-year survival rates of endosseous zygomatic implants used in the rehabilitation of the atrophic maxilla. Forty-three consecutive zygomatic implant placements in 25 patients were evaluated over a 5-10-year period. All zygomatic implant surgery was carried out under general anaesthesia. Nobel Biocare zygomatic machined-surface implants were used, and placement was undertaken using the modified sinus slot method. The main outcome measures and determinants for success were survival of the restored implants and the proportion of originally planned prostheses delivered to patients. Of the 25 patients treated, 12 were male and 13 were female; 19 were non-smokers, and the mean age at time of surgery was 64 years. Patients were treatment-planned for implant-retained bridgework, a removable prosthesis retained by fixed cast gold or milled titanium beams, or magnet-retained removable prostheses. A combination of zygomatic and conventional implants was used in all but one patient. In this study it was shown that the overall success rate for zygomatic implants was 86%, with six of the implants either failing to integrate or requiring removal due to persistent infection associated with the maxillary sinus. All patients received their planned prosthesis, although in six cases the method of retention required modification. This study illustrates that zygomatic implants are a successful and important treatment option when trying to restore the atrophic maxilla, with the potential to avoid additional augmentation/grafting procedures and resulting in a high long-term success rate. PMID:24120903

  1. Vitamin C supplementation in relation to inflammation in individuals with atrophic gastritis: a randomised controlled trial in Japan.

    PubMed

    Ma, Enbo; Sasazuki, Shizuka; Sasaki, Satoshi; Tsubono, Yoshitaka; Okubo, Shunji; Tsugane, Shoichiro

    2013-03-28

    Evidence has shown that both C-reactive protein (CRP) and serum amyloid component A (SAA) are increased in individuals with gastritis and stomach cancer. Controlling the level of these biomarkers by inhibiting the gastric infection with high doses of ascorbic acid may reduce the risk of carcinogenesis. A population-based double-blind randomised controlled trial in a Japanese population with atrophic gastritis in an area of high stomach cancer incidence was conducted between 1995 and 2000. Daily doses of 50 or 500 mg vitamin C were given, and 120 and 124 participants completed the 5-year study, respectively. Although serum ascorbic acid was higher in the high-dosage group (1.73 (SD 0.46) μg/l) than in the low-dosage group (1.49 (SD 0.29) μg/l, P< 0.001), at the end of the study, no significant difference was observed for CRP between the low- and high-dosage groups (0.39 (95 % CI 0.04, 4.19) mg/l and 0.38 (95 % CI 0.03, 4.31) mg/l, respectively; P= 0.63) or for SAA between the low- and high-dosage groups (3.94 (95 % CI 1.04, 14.84) μg/ml and 3.85 (95 % CI 0.99, 14.92) μg/ml, respectively; P= 0.61). Vitamin C supplementation may not have a strong effect on reducing infections in individuals with atrophic gastritis.

  2. [Comparative study of histones from slime mold Physarum polycephalum and calf thymus].

    PubMed

    Tyrsin, Iu A; Krasheninnikov, I A; Tyrsina, E G

    1977-05-01

    The histones from slime mold Physarum polycephalum and calf thymus were characterized in terms of some physico-chemical properties. The molecular weights of six principal histone fractions of Ph. polycephalum were found to be the following: P1--22 700, P3--15 700, P4a--15 000, P4b--14 300, P5--12 800 and P6--10 500. Electrophoretically homogenous histone fractions H1, H2b and H4 of calf thymus and histones P1, P3, P4b and P6 of slime mold were obtained by gel-filtration on Acrylex P-60. These findings suggest that fractions P1, P4a, P4b, P5 and P6 of slime mold Ph. polycephalum are homologus with respect to the histone fractions H1, H3, H2b, H2a and H4 of calf thymus. Only fraction P3 has no corresponding fraction in the calf thymus histones; a fraction corresponding to histone P3 of slime mold was absent.

  3. CXCR4 expression during lymphopoiesis: implications for human immunodeficiency virus type 1 infection of the thymus.

    PubMed Central

    Kitchen, S G; Zack, J A

    1997-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection of the human thymus results in depletion of CD4-bearing thymocytes. This depletion is initially manifested in the immature CD4+/CD8+ thymocyte subset. To determine cellular factors involved in HIV infection in the thymus, we examined the expression of the recently identified viral coreceptor, CXCR4, on fresh human thymocytes and on human cells from SCID-hu (Thy/Liv) mice. CXCR4 is a member of the chemokine receptor family which is required along with CD4 for entry into the cell of syncytium-inducing (SI) HIV-1 strains. Our analyses show that CXCR4 expression is modulated during T-lymphoid differentiation such that immature thymocytes display an increased frequency and higher surface density of the coreceptor than do more mature cells. In addition, using an SI strain of HIV-1 which directs expression of a reporter protein on the surface of infected cells, we have found that the immature CD4+/CD8+ thymocytes that express the highest levels of both CD4 and CXCR4 are the cells that are preferentially infected and depleted by the virus in vitro. Thus, high levels of both primary receptor and coreceptor may allow efficient infection of the thymus by certain HIV-1 strains. This in part may explain the rapid disease progression seen in some HIV-infected children, where the thymus is actively involved in the production of new T lymphocytes. PMID:9261420

  4. IFN-α Is Constitutively Expressed in the Human Thymus, but Not in Peripheral Lymphoid Organs

    PubMed Central

    Colantonio, Arnaud D.; Epeldegui, Marta; Jesiak, Maria; Jachimowski, Loes; Blom, Bianca; Uittenbogaart, Christel H.

    2011-01-01

    Type I interferons have been typically studied for their effects in the context of bacterial or viral infections. However in this report, we provide evidence that Interferon-alpha (IFN-α) expressing cells are present in the thymus in the absence of infection. We show that pDC express the highest level of IFN-α and that MxA, which is exclusively expressed after engagement of the type I IFN receptor by IFN-α/β, is expressed in normal fetal and post-natal thymus, but not in the periphery. The highest level of MxA is expressed in mature thymocytes and pDC located in the medulla and at the cortico-medullary junction. The anti-microbial peptide LL-37, which is expressed in the thymus, when complexed with eukaryotic nucleic acids, induces the secretion of IFN-α by thymic pDC. This results in the upregulation of MxA expression in responsive thymocytes. We propose that the secretion of IFN-α in the thymus may function to regulate the rate of T cell development and modulate the requirements for the selection of developing T cells. PMID:21904619

  5. Transcriptional analysis of host responses to Marek's disease virus infection in chicken thymus.

    PubMed

    Hu, Xuming; Qin, Aijian; Xu, Wencai; Wu, Genghua; Li, Dan; Qian, Kun; Shao, Hongxia; Ye, Jianqiang

    2015-01-01

    Marek's disease virus (MDV) is a cell-associated alpha-herpesvirus that causes T-cell lymphomas and nervous disorders in chickens. Different from other lymphoid organs, the thymus is the site of T-cell maturation and differentiation. However, the transcriptional response to MDV infection in the chicken thymus is still not known. In this study, we performed genome-wide expression analysis in thymus tissues of RB1B-infected chickens at different time points to investigate the molecular mechanisms of MDV pathogenesis. The number of differentially expressed genes with 2-fold or higher changes (>2) are as follows: 1,250 genes (7 dpi), 834 genes (14 dpi), 1,958 genes (21 dpi), and 2,306 genes (28 dpi). Gene ontology enrichment analysis revealed that the upregulated genes were involved in immune and inflammatory response at 7 dpi; angiogenesis, cytoskeleton organization, cell adhesion, and signal transduction showed different expressions at 21 and 28 dpi. The expression pattern of 18 randomly selected genes was confirmed by real-time RT-PCR. Several differently expressed host genes associated with tumor development are discussed. We identified the global host-gene expression pattern in the thymus of chickens that responded to MDV infection. The present data may provide groundwork for future investigation in the biology and pathogenesis of MDV.

  6. Isolation, characterization and cardiac differentiation of human thymus tissue derived mesenchymal stromal cells.

    PubMed

    Lin, Ze Bang; Qian, Bo; Yang, Yu Zhong; Zhou, Kai; Sun, Jian; Mo, Xu Ming; Wu, Kai Hong

    2015-07-01

    Mesenchymal stromal cells (MSCs) are promising candidate donor cells for replacement of cardiomyocyte loss during ischemia and in vitro generation of myocardial tissue. We have successfully isolated MSCs from the discarded neonatal thymus gland during cardiac surgery. The thymus MSCs were characterized by cell-surface antigen expression. These cells have high ability for proliferation and are able to differentiate into osteoblasts and adipocytes in vitro. For cardiac differentiation, the cells were divided into 3 groups: untreated control; 5-azacytidine group and sequential exposure to 5-azacytidine, bone morphogenetic protein 4, and basic fibroblast growth factor. Thymus MSCs showed a fibrolast-like morphology and some differentiated cells increased in size, formed a ball-like appearance over time and spontaneously contracting cells were observed in sequential exposure group. Immunostaining studies, cardiac specific genes/protein expression confirmed the cardiomyocyte phenotype of the differentiated cells. These results demonstrate that thymus MSCs can be a promising cellular source for cardiac cell therapy and tissue engineering.

  7. Is there a possible single mediator in modulating neuroendocrine-thymus interaction in ageing?

    PubMed

    Mocchegiani, Eugenio; Malavolta, Marco; Costarelli, Laura; Giacconi, Robertina; Piacenza, Francesco; Lattanzio, Fabrizia; Basso, Andrea

    2013-02-01

    The restoration of the thymic functions and the thymic re-growth may be achieved in old mice by some endocrinological (melatonin) or nutritional interventions (arginine or zinc), suggesting that the thymic involution in old age is a phenomenon secondary to age-related alterations occurring in neuroendocrine-thymus interactions. The targets for the thymic restoration may be hormone receptors and cytokines, strictly related to the presence of two nutritional factors, such as arginine and zinc, which are in turn essential for the efficiency of neuroendocrine-immune network both in ontogeny and ageing. The effect of melatonin is largely due to the presence of its specific receptors on cell membrane of thymocytes and Thymic Epithelial Cells (TECs). TECs synthesize thymulin peptide that is required for T-cell differentiation and maturation within the thymus gland. In this context, the role of zinc is pivotal because it is involved, through "zinc finger motifs", in the gene expression of melatonin receptors, in cell proliferation, apoptosis and thymulin reactivation. Zinc is also required for the biological action of arginine, via Nitric Oxide pathway. Therefore, the beneficial effect of melatonin or arginine on neuroendocrine-thymus interaction in ageing can also occur via a better zinc pool redistribution within the body where the capability of the zinc-binding proteins Metallothioneins (MT) in zinc release has a key role. These findings suggest that zinc, via MT buffering, can be a single mediator in modulating neuroendocrine-thymus interaction in ageing.

  8. Cytotoxic effect of essential oil of thyme (Thymus broussonettii) on the IGR-OV1 tumor cells resistant to chemotherapy.

    PubMed

    Ait M'barek, L; Ait Mouse, H; Jaâfari, A; Aboufatima, R; Benharref, A; Kamal, M; Bénard, J; El Abbadi, N; Bensalah, M; Gamouh, A; Chait, A; Dalal, A; Zyad, A

    2007-11-01

    The anti-tumor effect of the Moroccan endemic thyme (Thymus broussonettii) essential oil (EOT) was investigated in vitro using the human ovarian adenocarcinoma IGR-OV1 parental cell line OV1/P and its chemoresistant counterparts OV1/adriamycin (OV1/ADR), OV1/vincristine (OV1/VCR), and OV1/cisplatin (OV1/CDDP). All of these cell lines elicited various degrees of sensitivity to the cytotoxic effect of EOT. The IC50 values (mean +/- SEM, v/v) were 0.40 +/- 0.02, 0.39 +/- 0.02, 0.94 +/- 0.05, and 0.65 +/- 0.03% for OV1/P, OV1/ADR, OV1/VCR, and OV1/CDDP, respectively. Using the DBA-2/P815 (H2d) mouse model, tumors were developed by subcutaneous grafting of tumor fragments of similar size obtained from P815 (murin mastocytoma cell line) injected in donor mouse. Interestingly, intra-tumoral injection of EOT significantly reduced solid tumor development. Indeed, by the 30th day of repeated EOT treatment, the tumor volumes of the animals were 2.00 +/- 0.27, 1.35 +/- 0.20, and 0.85 +/- 0.18 cm(3) after injection with 10, 30, or 50 microL per 72 h (six times), respectively, as opposed to 3.88 +/- 0.50 cm(3) for the control animals. This tumoricidal effect was associated with a marked decrease of mouse mortality. In fact, in these groups of mice, the recorded mortality by the 30th day of treatment was 30 +/- 4, 18 +/- 4, and 8 +/- 3%, respectively, while the control animals showed 75 +/- 10% of mortality. These data indicate that the EOT which contains carvacrol as the major component has an important in vitro cytotoxic activity against tumor cells resistant to chemotherapy as well as a significant antitumor effect in mice. However, our data do not distinguish between carvacrol and the other components of EOT as the active factor.

  9. Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity.

    PubMed

    Geenen, Vincent; Bodart, Gwennaëlle; Henry, Séverine; Michaux, Hélène; Dardenne, Olivier; Charlet-Renard, Chantal; Martens, Henri; Hober, Didier

    2013-01-01

    For centuries after its first description by Galen, the thymus was considered as only a vestigial endocrine organ until the discovery in 1961 by Jacques FAP Miller of its essential role in the development of T (thymo-dependent) lymphocytes. A unique thymus first appeared in cartilaginous fishes some 500 million years ago, at the same time or shortly after the emergence of the adaptive (acquired) immune system. The thymus may be compared to a small brain or a computer highly specialized in the orchestration of central immunological self-tolerance. This was a necessity for the survival of species, given the potent evolutionary pressure imposed by the high risk of autotoxicity inherent in the stochastic generation of the diversity of immune cell receptors that characterize the adaptive immune response. A new paradigm of "neuroendocrine self-peptides" has been proposed, together with the definition of "neuroendocrine self." Neuroendocrine self-peptides are secreted by thymic epithelial cells (TECs) not according to the classic model of neuroendocrine signaling, but are processed for presentation by, or in association with, the thymic major histocompatibility complex (MHC) proteins. The autoimmune regulator (AIRE) gene/protein controls the transcription of neuroendocrine genes in TECs. The presentation of self-peptides in the thymus is responsible for the clonal deletion of self-reactive T cells, which emerge during the random recombination of gene segments that encode variable parts of the T cell receptor for the antigen (TCR). At the same time, self-antigen presentation in the thymus generates regulatory T (Treg) cells that can inhibit, in the periphery, those self-reactive T cells that escaped negative selection in the thymus. Several arguments indicate that the origin of autoimmunity directed against neuroendocrine glands results primarily from a defect in the intrathymic programming of self-tolerance to neuroendocrine functions. This defect may be genetic or

  10. Sodium valproate effect on the structure of rat glandule thymus: Gender-related differences.

    PubMed

    Valančiūtė, Angelija; Mozuraitė, Raminta; Balnytė, Ingrida; Didžiapetrienė, Janina; Matusevičius, Paulius; Stakišaitis, Donatas

    2015-01-01

    Sodium valproate (VPA) was shown to inhibit cell growth mechanisms such as cell cycle arrest, proliferation suppression, increase of apoptosis. Many aspects of the contribution of the VPA pharmacological mechanisms and their significance in gender-related processes have not been investigated. In our study, we have tested hypothesis that the influence of VPA on thymus weight and structure might be gender-related. The thymus of Wistar rats of both genders aged 8 weeks was investigated in the following groups (n = 6 each): controls, treated with VPA, castrated male and female treated with VPA, and the castrated control of both genders. The thymus weight, structural changes and area of cortical and medullar parts of the gland in slides stained with hematoxylin and eosin and immunohistochemically were assessed. A comparison of thymus weight of castrated male and of castrated VPA-treated male rats showed a significant thymus weight loss after VPA treatment (0.66 ± 0.04 g vs. 0.43 ± 0.03 g, p < 0.05). The treatment with VPA caused an about 6-fold (0.39 ± 0.12 vs. 0.07 ± 0.03) increase of Hassall's corpuscles (HCs) numbers per 1mm(2) in male and more than 4-fold increase (0.46 ± 0.07 vs. 0.10 ± 0.04) in female rats. In castrated males and females, the HCs number was also increased, but this increase was statistically significant only in male animals vs. controls (0.46 ± 0.10 vs. 0.07 ± 0.03, p < 0.001 in males; 0.29 ± 0.13 vs. 0.10 ± 0.04, p > 0.05 in females). When castrated male and female rats were treated with VPA, further increase of HC numbers was found. In our study, VPA has inhibited the proliferative capacity of thymocytes by diminishing the thymus weight and inducing a differentiation of thymic medullar epithelial cells into HCs. The diminishing of the gl. thymus weight under the influence of VPA was significant in castrated male rats. The number of HCs increased in animals of both genders under the influence of VPA. Gender differences in HCs

  11. Insights on Foxn1 Biological Significance and Usages of the “Nude” Mouse in Studies of T-Lymphopoiesis

    PubMed Central

    Zhang, Zhijie; Burnley, Preston; Coder, Brandon; Su, Dong-Ming

    2012-01-01

    Mutation in the “nude” gene, i.e. the FoxN1 gene, induces a hairless phenotype and a rudimentary thymus gland in mice (nude mouse) and humans (T-cell related primary immunodeficiency). Conventional FoxN1 gene knockout and transgenic mouse models have been generated for studies of FoxN1 gene function related to skin and immune diseases, and for cancer models. It appeared that FoxN1's role was fully understood and the nude mouse model was fully utilized. However, in recent years, with the development of inducible gene knockout/knockin mouse models with the loxP-Cre(ERT) and diphtheria toxin receptor-induced cell abolished systems, it appears that the complete repertoire of FoxN1's roles and deep-going usage of nude mouse model in immune function studies have just begun. Here we summarize the research progress made by several recent works studying the role of FoxN1 in the thymus and utilizing nude and “second (conditional) nude” mouse models for studies of T-cell development and function. We also raise questions and propose further consideration of FoxN1 functions and utilizing this mouse model for immune function studies. PMID:23091413

  12. Composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation model of bone marrow transplantation.

    PubMed

    Bozkurt, Mehmet; Klimczak, Aleksandra; Nasir, Serdar; Zor, Fatih; Krokowicz, Lukasz; Siemionow, Maria

    2013-01-01

    Cellular and vascularized bone marrow cells have been used to induce donor-specific chimerism in various models of composite tissue allotransplantation. Although thymus transplantation has been reported in the literature, the effect of thymus transplantation on chimerism levels in vascularized bone containing composite tissue allotransplantation has not been reported. In this study, a new method for composite vascularized sternal bone marrow transplant model is descried that can be applied to augment chimerism after transplantation. A total of seven composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin transplantations were performed in two groups. The first group (n = 5) was designed as an allotransplantation group and the second group (n = 2) was designed as an isotransplantation group. Composite osseomusculocutaneous sternum, ribs, thymus, and pectoralis muscles allografts were harvested on the common carotid artery and external jugular vein and a heterotopic transplantation was performed to the inguinal region of the recipient rat. Cyclosporine A monotherapy was administered in order to prevent acute and chronic allograft rejection. Animals sacrificed when any sign of rejection occurred. The longest survival was 156 day post-transplant. Assessment of bone marrow cells within sternum bone component and flow cytometry analysis of donor-specific chimerism in the peripheral blood of recipients were evaluated. Our results showed that this composite allograft carried 7.5 × 10(6) of viable hematopoietic cells within the sternum component. At day 7 post-transplant chimerism was developed in T-cell population and mean level was assessed at 2.65% for RT1(n) /CD4 and at 1.0% for RT1(n) /CD8. In this study, a new osseomusculocutaneous sternum, ribs, thymus, pectoralis muscle, and skin allotransplantation model is reported which can be used to augment hematopoietic activity for chimerism induction after transplantation.

  13. Comparative effect of thymus vulgaris and ibuprofen on primary dysmenorrhea: A triple-blind clinical study

    PubMed Central

    Salmalian, Hajar; Saghebi, Roshanak; Moghadamnia, Ali Akbar; Bijani, Ali; Faramarzi, Mahbobeh; Nasiri Amiri, Fatemeh; Bakouei, Fatemeh; Behmanesh, Fereshte; Bekhradi, Reza

    2014-01-01

    Background: Dysmenorrhea is one of the most common medical problems in gynecology causing several problems in the personal and social life of women. This study was conducted to compare the effect of thymus vulgaris and ibuprofen on the treatment of primary dysmenorrhea Methods: This clinical study was conducted on 84 students of Babol University of Medical Sciences with primary dysmenorrhea. The students were randomly assigned to three groups receiving thymus vulgaris, ibuprofen and placebo. In all three groups, with the beginning of pain, 200 mg capsules and 25 drops of essential oil were given every 6 hours for two consecutive cycles. Pain intensity used the visual scale before and one hour after each dose for 48 hour after starting medication. The data were collected and analyzed. This study was registered in the Iranian Registry of Clinical Trial (www.irct.ir) with registration number ID: IRCT201101245683N1 Results: The mean age of participants was 20.5±1.8 years. Both thymus vulgaris and ibuprofen were effective to reduce the pain severity of dysmenorrhea. Before treatment, the mean pain intensity in thymus vulgaris, ibuprofen and placebo groups were 6.57±2.02, 5.30±2.23 and 6.18±1.78, respectively and after treatment decreased to 1.21±1.06, 1.48±1.62 and 3.54±2.26, respectively. Reduction of pain severity was not statistically significant between the two medications, however it was significant for each drug compared with placebo (p<0.001). Conclusion: The results suggest that thymus vulgaris as well as ibuprofen can be effective in reducing the severity of pain and spasm in primary dysmenorrhea. PMID:24778782

  14. The Effect of Root, Shoot and Seed Extracts of The Iranian Thymus L. (Family: Lamiaceae) Species on HIV-1 Replication and CD4 Expression

    PubMed Central

    Soleimani Farsani, Maryam; Behbahani, Mandana; Isfahani, Hamid Zarkesh

    2016-01-01

    Objective The genus Thymus L. is a cushion plant that was previously used for the treatment of bronchitis and rheumatism. The present investigation was carried out to study the effects of root, shoot, leaf and seed extracts of five Thymus species and subspecies on peripheral blood mononuclear cells (PBMCs) toxicity and HIV-1 replication. Materials and Methods In this experimental study, the activity of the Thymus extracts on HIV-1 replication and lymphocytes population were examined respectively using HIV-1 p24 Antigen kit and flow-cytometer. The Thymus species effect was investigated, including Thymus kotschyanus, Thymus vulgaris, Thymus carmanicus, Thymus daenensis subspecies lancifolius and Thymus daenensis subspecies daenensis. Results The effect of root methanol extracts of all species on PBMCs proliferation was significantly higher than the other extracts. The intensity of CD4, CD3 and CD45 were decreased in the presence of all root extracts. Although the average median fluorescence intensity (MFI) values of CD19 were increased in the cells treated with these extracts. All methanol extracts showed anti-HIV-1 activity at high concentrations (200 and 500 µg/ml). Anti-HIV-1 activity of Thymus daenensis subspecies daenensis was significantly more than the other species. Conclusion These results demonstrated that root extracts of Thymus species might be a good candidate to investigate anti-HIV infection in vivo. PMID:27540531

  15. Horizontal Resorption of Fresh-Frozen Corticocancellous Bone Blocks in the Reconstruction of the Atrophic Maxilla at 5 Months

    PubMed Central

    Pereira, Eugénio; Messias, Ana; Dias, Ricardo; Judas, Fernando; Salvoni, Alexander; Guerra, Fernando

    2015-01-01

    Background Reliable implant-supported rehabilitation of an alveolar ridge needs sufficient volume of bone. In order to achieve a prosthetic-driven positioning, bone graft techniques may be required. Purpose This prospective cohort study aims to clinically evaluate the amount of resorption of corticocancellous fresh-frozen allografts bone blocks used in the reconstruction of the severe atrophic maxilla. Materials and Methods Twenty-two partial and totally edentulous patients underwent bone augmentation procedures with fresh-frozen allogenous blocks from the iliac crest under local anesthesia. Implants were inserted into the grafted sites after a healing period of 5 months. Final fixed prosthesis was delivered ± 4 months later. Ridge width analysis and measurements were performed with a caliper before and after grafting and at implant insertion. Bone biopsies were performed in 16 patients. Results A total of 98 onlay block allografts were used in 22 patients with an initial mean alveolar ridge width of 3.41 ± 1.36 mm. Early exposure of blocks was observed in four situations and one of these completely resorbed. Mean horizontal bone gain was 3.63 ± 1.28 mm (p < .01). Mean buccal bone resorption between allograph placement and the reopening stage was 0.49 ± 0.54 mm, meaning approximately 7.1% (95% confidence interval: [5.6%, 8.6%]) of total ridge width loss during the integration period. One hundred thirty dental implants were placed with good primary stability (≥ 30 Ncm). Four implants presented early failure before the prosthetic delivery (96.7% implant survival). All patients were successfully rehabilitated. Histomorphometric analysis revealed 20.9 ± 5.8% of vital bone in close contact to the remaining grafted bone. A positive strong correlation (adjusted R2 = 0.44, p = .003) was found between healing time and vital bone percentage. Conclusions Augmentation procedures performed using fresh-frozen allografts from the

  16. [Mining analysis and experience summary for chronic atrophic gastritis cases treated by Professor LIU Feng-bin].

    PubMed

    Hou, Zheng-kun; Liu, Feng-bin; Li, Pei-wu; Zhuang, Kun-hai

    2015-06-01

    To summarize Professor LIU Feng-bin's clinical experience and theoretical thoughts on chronic atrophic gastritis (CAG), the study group designed a retrospective study on his case series and expert interview. First of all, the data of CAG patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine between 2009 and 2013, e. g. herbs, diseases, syndrome type, prescription amount and number of herbs, was collected and processed. The statistical description and binary logistic regression were used to determined the syndrome type, initial basic remedy and modification. During the statistics, a complete and sub-group analysis was performed simultaneously. After the expert interview, the syndrome type and medication were finalized. As a result, a total of 228 CAG patients aged at (50.30 ± 10.18) were collected, including 151 males (66.23%). Of them, the TCM diagnosis and syndrome type were extracted from the information of 157 patients, including 115 cases with gastric stuffiness, 23 cases with gastric pain, 19 missing cases, 2 cases with spleen-stomach weakness syndrome, 57 cases with spleen deficiency and dampness-heat syndrome, 18 cases with spleen-stomach disharmony syndrome, 23 cases with syndrome of liver depression syndrome, 21 cases with liver qi invading stomach syndrome and 26 qi and yin deficiency syndrome, respectively. All of the 228 patients used totally 104 herbs, while the subgroups with 157 patients used 94 herbs. The most frequently used 15 herbs used in each groups were analyzed to determine the initial basic remedy and modification. Subsequently, based on the information of the sub-groups with 157 patients, with the syndrome type as the dependent variable, the logistic regression analysis was made on the most frequently used 32 herbs, in order to determined the modification in herbs for different syndrome types. After experts reviewed and modified, they believed the main causes of CAG were dietary irregularities

  17. Effect of ERCC8 tagSNPs and their association with H. pylori infection, smoking, and alcohol consumption on gastric cancer and atrophic gastritis risk.

    PubMed

    Jing, Jing-Jing; Sun, Li-Ping; Xu, Qian; Yuan, Yuan

    2015-12-01

    Excision repair cross-complementing group 8 (ERCC8) plays a critical role in DNA repair. Genetic polymorphisms in ERCC8 may contribute to the risk of cancer development. We selected tag single nucleotide polymorphisms (tagSNPs) in Chinese patients from the HapMap database to investigate associations with gastric cancer and its precursors. Genomic DNA was extracted from 394 controls, 394 atrophic gastritis, and 394 gastric cancer cases in northern Chinese patients, and genotypes were identified using the Sequenom MassARRAY system. We found that the ERCC8 rs158572 GG+GA genotype showed a 1.651-fold (95 % confidence interval (CI) = 1.109-2.457, P = 0.013) increased risk of gastric cancer compared with the AA genotype, especially in diffuse type. Stratified analysis comparing the common genotype revealed significantly increased gastric cancer risk in males and individuals older than 50 years with rs158572 GA/GG/GG+GA genotypes, while individuals older than 50 years with rs158916 CT/CC+CT genotypes were less susceptible to atrophic gastritis. Haplotype analysis showed that the G-T haplotype was associated with increased risk of gastric cancer. Statistically significant interactions between the two ERCC8 tagSNPs and Helicobacter pylori infection were observed for gastric cancer and atrophic gastritis risk (P < 0.05). Smokers and drinkers with ERCC8 rs158572 GG+GA genotype were more susceptible to gastric cancer compared with non-smokers and non-drinkers homozygous for AA. Our findings suggested that ERCC8 rs158572 and rs158916, alone or together with environmental factors, might be associated with gastric cancer and atrophic gastritis susceptibility. Further validation of our results in larger populations along with additional studies evaluating the underlying molecular function is required.

  18. Effect of honey on antibody production against thymus-dependent and thymus-independent antigens in primary and secondary immune responses.

    PubMed

    Al-Waili, Noori S; Haq, Afruz

    2004-01-01

    The objective was to study the effect of natural pure honey on the antibody production against thymus-dependent antigen [sheep red blood cells (SRBCs)] and thymus-independent antigen (Escherichia coli) in mice. Forty-two mice (mean weight 28.33 +/- 3.44 g) were divided into two groups: group A (21 mice) fed regular diet and group B (21 mice) fed regular diet plus 0.8 g/kg of body weight/day of honey administered in four equally divided doses. Each animal was injected intraperitoneally with 0.1 mL of 5% SRBCs and 0.1 mL of killed E. coli. The same dose of both antigens was given after 17 days. At days 7 and 16 after primary immunization and at day 4 after secondary immunization, blood samples were collected from seven mice at each time interval from group A and group B to estimate antibody titer using the hemoaggulination test. At day 7 after primary immunization, the mean antibody titer against SRBCs was 9.14 +/- 3.02 in group A and 13.7 +/- 3.9 in group B (P < .05), while the mean antibody titer against E. coli was 14.8 +/- 8.5 in group A and 14.8 +/- 9.35 in group B. At day 16, the mean antibody titer against SRBCs was 13.71 +/- 3.9 in group A and 20 +/- 9.8 in group B, while the mean antibody titer against E. coli was 14.69 +/- 935 in group A and 26.67 +/- 8.26 in group B (P < .05). Four days after secondary immunization, the mean antibody titer against SRBCs was 13.33 +/- 4.62 in group A and 16 +/- 8.7 in group B, while the mean antibody titer against E. coli was 42.67 +/- 18.4 in group A and 69.33 +/- 31.4 in group B. It might be concluded that oral honey stimulates antibody production during primary and secondary immune responses against thymus-dependent and thymus-independent antigens. PMID:15671696

  19. Differences in estrogen and progesterone receptor expression in endometrial polyps and atrophic endometrium of postmenopausal women with and without exposure to tamoxifen

    PubMed Central

    LEÃO, ROGERIO BARROS FERREIRA; ANDRADE, LILIANA; VASSALO, JOSE; ANTUNES, ARMANDO; PINTO-NETO, AARÃO; COSTA-PAIVA, LUCIA

    2013-01-01

    Postmenopausal women who use tamoxifen present with an increased incidence of endometrial alterations, such as polyps and hyperplasia, in addition to a higher risk of malignant endometrial neoplasms. Among these endometrial changes, polyps are the most common, with a pathogenesis associated with hormonal influence. The objective of this study was to compare the expression of estrogen receptors (ERs) and progesterone receptors (PRs) in endometrial polyps from tamoxifen users with that in endometrial polyps and the atrophic endometrium of postmenopausal tamoxifen non-users. Among women undergoing surgical hysteroscopy, 84 tamoxifen users with benign endometrial polyps were selected. This group was compared to 84 samples of atrophic endometrium and to 252 benign polyps from postmenopausal women who were not treated with tamoxifen. The expression of ER/PR was assessed by immunohistochemical analysis, according to the percentage of stained cells, intensity of nuclear staining and final score. The polyps from tamoxifen users exhibited a higher expression of ER and PR in the glandular epithelium and stroma compared to the atrophic endometrium (P<0.0001). Compared to the polyps from women not treated with tamoxifen, tamoxifen users exhibited a higher PR expression in the epithelium (P=0.0014) and stroma (P=0.0056), with no difference in the expression of ER. In conclusion, endometrial polyps frequently exhibit an increase in ER expression, regardless of tamoxifen use. High levels of PR expression appear to be consistent with the estrogen agonist effects of tamoxifen. PMID:24649292

  20. [Relation between Helicobacter pylori and pathogenesis of chronic atrophic gastritis and the research of its prevention and treatment].

    PubMed

    Zhang, L; Yang, L W; Yang, L J

    1992-09-01

    The total detectable rate of Helicobacter pylori (HP) of 485 patients suffering from gastric diseases was 59.6%. The HP in gastric mucosa of chronic atrophic gastritis (CAG) patients was separated from the cell culture in vitro and transferred successively. The mice were perfused with exciccate alum, and the rabbits with aspirin to injure their gastric mucosa, then HP was perfused. Result showed that the change of experimental animals was identical with that of CAG patients by means of bacteriological and pathological examination. It revealed that HP was in agreement with Robert Koch's three principles about pathogenic bacteria. According to the bacterial infectious hypothesis of CAG, 53 Chinese medicinal herbs and prescriptions were investigated with bacteriostatic test. Panax notogenseng and Magnolia officinalis were discovered to be sensitive, Prunus mume and Corydalis yanhusuo were moderate sensitive, and Coptis chinensis and Rheum palmatum highly sensitive to HP. Decoction of Clearing up the Heat and Relieving the Blood Stasis and No.2 recipe of Huowei were used to treat 70 CAG patients with Stomach Heat Syndrome. The effective rate of gastroscopic examination was 85.7%, that of pathological study was 80%. In comparing with the group of Shanjiu Weitai, there was significant difference between the traditional Chinese medicine treated group and Shanjiu Weitai control group, the former being markedly better. PMID:1298465

  1. Bimaxillary protrusion with an atrophic alveolar defect: orthodontics, autogenous chin-block graft, soft tissue augmentation, and an implant.

    PubMed

    Chiu, Grace S C; Chang, Chris H N; Roberts, W Eugene

    2015-01-01

    Bimaxillary protrusion in a 28-year-old woman was complicated by multiple missing, restoratively compromised, or hopeless teeth. The maxillary right central incisor had a history of avulsion and replantation that subsequently evolved into generalized external root resorption with Class III mobility and severe loss of the supporting periodontium. This complex malocclusion had a discrepancy index of 21, and 8 additional points were scored for the atrophic dental implant site (maxillary right central incisor). The comprehensive treatment plan included extraction of 4 teeth (both maxillary first premolars, the maxillary right central incisor, and the mandibular right first molar), orthodontic closure of all spaces except for the future implant site (maxillary right central incisor), augmentation of the alveolar defect with an autogenous chin-block graft, enhancement of the gingival biotype with a connective tissue graft, and an implant-supported prosthesis. Orthodontists must understand the limitations of bone grafts. Augmented alveolar defects are slow to completely turn over to living bone, so they are usually good sites for implants but respond poorly to orthodontic space closure. However, postsurgical orthodontic treatment is often indicated to optimally finish the esthetic zone before placing the final prosthesis. The latter was effectively performed for this patient, resulting in a total treatment time of about 36 months for comprehensive interdisciplinary care. An excellent functional and esthetic result was achieved. PMID:25533077

  2. Use of 4 immediately loaded zygomatic fixtures for retreatment of atrophic edentulous maxilla after complications of maxillary reconstruction.

    PubMed

    Kuabara, Marcos Rikio; Ferreira, Edilson José; Gulinelli, Jéssica Lemos; Panzarini, Sônia Regina

    2010-05-01

    This article reports the 20-month clinical outcome of the use of 4 zygomatic implants with immediate occlusal loading and reverse planning for the retreatment of atrophic edentulous maxilla after failed rehabilitation with autogenous bone graft reconstruction and maxillary implants. The intraoral clinical examination revealed mispositioned and loosened implants underneath a maxillary complete denture. The panoramic radiograph showed 6 maxillary implants. One implant was displaced into the right maxillary sinus, and the implant anchored in the region of tooth 21 was fractured. The other implants presented peri-implant bone loss. The implants anchored in the regions of teeth 21 to 23 and 11 to 13 were first removed. After 2 months, the reverse planning started with placement of 4 zygomatic fixtures, removal of the implants migrated into the sinus cavity and anchored in the region of tooth 17, and installation of a fixed denture. After 20 months of follow-up, no painful symptoms, peri-implant inflammation or infection, implant instability, or bone resorption was observed. The outcomes of this case confirm that the zygoma can offer a predictable anchorage and support function for a fixed denture in severely resorbed maxillae.

  3. Single-stage implantation in the atrophic alveolar ridge of the mandible with the Norian skeletal repair system.

    PubMed

    Hölzle, Frank; Bauer, Florian; Kesting, Marco R; Mücke, Thomas; Deppe, Herbert; Wolff, Klaus-Dietrich; Swaid, Sami

    2011-10-01

    Dental implants have played a part in rehabilitation of the jaws for more than 40 years, but in some cases they alone are inadequate because of extreme alveolar resorption. Correction may necessitate a two-stage procedure with additional interventions. We have made a preliminary study of the use of the Norian skeletal repair system (SRS), a carbonated calcium phosphate bone cement used to augment the alveolar ridge as a single-stage procedure, with the placement of implants. Ten edentulous patients with insufficient vertical bone in the interforaminal area were treated. After a horizontal osteotomy and crestal mobilisation of the alveolar ridge, implants were placed through the crestal part and fixed in the basal part of the mandible. Norian SRS was used to fill the gap created. The prostheses were inserted 3 months later. Forty implants were inserted. The follow up period was 60 months, and no fractures or dislocations developed. One of the implants was lost and there was one wound dehiscence, but no surgical intervention or revision was necessary. Radiographs showed good consolidation of the bony structure in all cases. We have described a reliable, single-stage procedure for augmentation and implantation in a highly atrophic alveolar crest. A 98% survival is comparable with those of other techniques. Further clinical trials are necessary to replicate these promising results.

  4. Atrophic thyroid follicles and inner ear defects reminiscent of cochlear hypothyroidism in Slc26a4-related deafness.

    PubMed

    Dror, Amiel A; Lenz, Danielle R; Shivatzki, Shaked; Cohen, Keren; Ashur-Fabian, Osnat; Avraham, Karen B

    2014-08-01

    Thyroid hormone is essential for inner ear development and is required for auditory system maturation. Human mutations in SLC26A4 lead to a syndromic form of deafness with enlargement of the thyroid gland (Pendred syndrome) and non-syndromic deafness (DFNB4). We describe mice with an Slc26a4 mutation, Slc26a4 (loop/loop) , which are profoundly deaf but show a normal sized thyroid gland, mimicking non-syndromic clinical signs. Histological analysis of the thyroid gland revealed defective morphology, with a majority of atrophic microfollicles, while measurable thyroid hormone in blood serum was within the normal range. Characterization of the inner ear showed a spectrum of morphological and molecular defects consistent with inner ear pathology, as seen in hypothyroidism or disrupted thyroid hormone action. The pathological inner ear hallmarks included thicker tectorial membrane with reduced β-tectorin protein expression, the absence of BK channel expression of inner hair cells, and reduced inner ear bone calcification. Our study demonstrates that deafness in Slc26a4 (loop/loop) mice correlates with thyroid pathology, postulating that sub-clinical thyroid morphological defects may be present in some DFNB4 individuals with a normal sized thyroid gland. We propose that insufficient availability of thyroid hormone during inner ear development plays an important role in the mechanism underlying deafness as a result of SLC26A4 mutations.

  5. Immunogenicity and efficacy of three recombinant subunit Pasteurella multocida toxin vaccines against progressive atrophic rhinitis in pigs

    USGS Publications Warehouse

    Liao, Chih-Ming; Huang, Chienjin; Hsuan, Shih-Ling; Chen, Zeng-Weng; Lee, Wei-Cheng; Liu, Cheng-I; Winton, James R.; Chien, Maw-Sheng

    2006-01-01

    Three short fragments of recombinant subunit Pasteurella multocida toxin (rsPMT) were constructed for evaluation as candidate vaccines against progressive atrophic rhinitis (PAR) of swine. PMT-specific antibody secreting cells and evidence of cellular immunity were detected in rsPMT-immunized pigs following authentic PMT challenge or homologous antigen booster. Piglets immunized with rsPMT fragments containing either the N-terminal or the C-terminal portions of PMT developed high titers of neutralizing antibodies. Pregnant sows immunized with rsPMT had higher levels of maternal antibodies in their colostrum than did those immunized with a conventional PAR-toxoid vaccine. Offspring from rsPMT vaccinated sows had better survival after challenge with a five-fold lethal dose of authentic PMT and had better growth performance after challenge with a sublethal dose of toxin. Our findings indicate these non-toxic rsPMT proteins are attractive candidates for development of a subunit vaccine against PAR in pigs.

  6. Predictability of short implants (< 10 mm) as a treatment option for the rehabilitation of atrophic maxillae. A systematic review

    PubMed Central

    García-Sala-Bonmatí, Fernando; Martínez-González, Amparo; García-Dalmau, Carlos; Mañes-Ferrer, José-Félix; Brotons-Oliver, Alejandro

    2016-01-01

    Background Short implants (< 10 mm) are one of the treatment options available in cases of limited vertical bone. A purpose of this paper is to evaluate the predictability of short implants as an alternative to technically molthough such implants are now widely used, there is controversy regarding their clinical reliability. There complex treatments in patients with atrophic maxillae, based on a systematic review of the literature and the analysis of the implant survival rates, changes in peri-implant bone level, and associated complications. It is postulated that short implants offer clinical results similar to those of longer implants. Material and Methods A Medline-PubMed search was made covering the period between January 2004 and December 2014 (both included). Studies in English published in indexed journals, involving at least 20 implants and with a follow-up period of at least 12 months were considered. A manual search in four high impact journals was also conducted. Results A total of 37 studies meeting the inclusion criteria were included in this review. 9792 implants placed in over 5000 patients were analyzed. Conclusions Based on the results of this review, short implants are seen to offer clinical results in terms of survival, bone loss and complications similar to those of longer implants. Key words:Survival rate, clinical results, dental implants, oral implants, short implants, short lengt PMID:26946199

  7. A cross-reactive antigen of thymus and skin epithelial cells common with the polysaccharide of group A streptococci.

    PubMed Central

    Lyampert, I M; Beletskaya, L V; Borodiyuk, N A; Gnezditskaya, E V; Rassokhina, I I; Danilova, T A

    1976-01-01

    Investigation of antibodies to the specific determinant of streptococcal group A polysaccharide in indirect immunofluorescence experiments has revealed the existence of a cross-reactive antigen in the epithelial cells of the thymus and skin. This CR antigen is contained by the epithelial cells of man and animals of different species. It has been demonstrated in all the individuals studied including animals producing antibodies to the polysaccharide of Group A streptococci. The principal cause of autoimmune thymitis characteristic of rheumatic fever and other autoimmune processes is probably damage done to the thymus by autoantibodies resulting from immunization with microbial cross-reactive antigens shared by the thymus. Reaction of the autoantibodies with thymic antigens may affect the immunosuppressive function of the thymus and the maturation process of suppressor T cells. These events probably constitute the basic stage in the development of an autoimmune process. Images Figure 1 Figure 2 Figures 3-6 PMID:800402

  8. Expression of nerve growth factor is upregulated in the rat thymic epithelial cells during thymus regeneration following acute thymic involution.

    PubMed

    Lee, Hee-Woo; Kim, Sung-Min; Shim, Na-Ri; Bae, Soo-Kyung; Jung, Il-Gun; Kwak, Jong-Young; Kim, Bong-Seon; Kim, Jae-Bong; Moon, Jeon-Ok; Chung, Joo-Seop; Yoon, Sik

    2007-06-01

    Neuroimmune networks in the thymic microenvironment are thought to be involved in the regulation of T cell development. Nerve growth factor (NGF) is increasingly recognized as a potent immunomodulator, promoting "cross-talk" between various types of immune system cells. The present study describes the expression of NGF during thymus regeneration following acute involution induced by cyclophosphamide in the rat. Immunohistochemical stain demonstrated not only the presence of NGF but also its upregulated expression mainly in the subcapsular, paraseptal, and perivascular epithelial cells, and medullary epithelial cells including Hassall's corpuscles in both the normal and regenerating thymus. Biochemical data obtained using Western blot and RT-PCR supported these results and showed that thymic extracts contain NGF protein and mRNA, at higher levels during thymus regeneration. Thus, our results suggest that NGF expressed in these thymic epithelial cells plays a role in the T lymphopoiesis associated with thymus regeneration during recovery from acute thymic involution.

  9. Calf thymus DNA-binding ability study of anthocyanins from purple sweet potatoes ( Ipomoea batatas L.).

    PubMed

    Wang, Dan; Wang, Xirui; Zhang, Chao; Ma, Yue; Zhao, Xiaoyan

    2011-07-13

    A total of 10 anthocyanin compounds were identified from five purple sweet potato ( Ipomoea batatas L.) varieties, Qunzi, Zishu038, Ji18, Jingshu6, and Ziluolan, by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to assess their calf thymus DNA-binding ability in vitro. The interaction between anthocyanins and calf thymus DNA in Tris-HCl buffer solution (pH 6.9) was evaluated by fluorescence spectroscopy. Using ethidium bromide (EB) as a fluorescence probe, fluorescence quenching of the emission peak was seen in the DNA-EB system when anthocyanins were added, indicating that the anthocyanins bound with DNA. The acylated groups influenced the ability of the interaction with DNA. Anthocyanins from purple sweet potato with more acylated groups in sorphorose have a stronger binding ability with DNA.

  10. Calf thymus DNA-binding ability study of anthocyanins from purple sweet potatoes ( Ipomoea batatas L.).

    PubMed

    Wang, Dan; Wang, Xirui; Zhang, Chao; Ma, Yue; Zhao, Xiaoyan

    2011-07-13

    A total of 10 anthocyanin compounds were identified from five purple sweet potato ( Ipomoea batatas L.) varieties, Qunzi, Zishu038, Ji18, Jingshu6, and Ziluolan, by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to assess their calf thymus DNA-binding ability in vitro. The interaction between anthocyanins and calf thymus DNA in Tris-HCl buffer solution (pH 6.9) was evaluated by fluorescence spectroscopy. Using ethidium bromide (EB) as a fluorescence probe, fluorescence quenching of the emission peak was seen in the DNA-EB system when anthocyanins were added, indicating that the anthocyanins bound with DNA. The acylated groups influenced the ability of the interaction with DNA. Anthocyanins from purple sweet potato with more acylated groups in sorphorose have a stronger binding ability with DNA. PMID:21678894

  11. Influence of nandrolone decanoate on the repopulation of the thymus after total body irradiation of mice

    SciTech Connect

    Plum, J.; Huys, J.; De Scheerder, Y.; Dhont, E.; De Smedt, M.

    1982-10-01

    It has been reported that nandrolone decanoate is helpful in overcoming the neutropenic phase following irradiation. In the present study the influence of nandrolone decanoate on the thymus' cellularity after total body irradiation was investigated. In comparison with a placebo-treated group, mice receiving nandrolone decanoate showed a similar pattern of thymus repopulation, but a significantly lower number of thymocytes over the whole period of treatment was found. Nonirradiated mice also had a significantly lower number of thymocytes when treated with nandrolone decanoate. In addition, the number of circulating leukocytes was also evaluated over a period of 1 month after total body irradiation. On 11 of the 21 days investigated, a significantly higher number of leukocytes was found in the nandrolone decanoate-treated group. We conclude that the action of nandrolone decanoate was not clearly distinct from that of testosterone regarding either granulopoiesis or thymic involution.

  12. Antifungal activity of extracts of Rosmarinus officinalis and Thymus vulgaris against Aspergillus flavus and A. ochraceus.

    PubMed

    Centeno, S; Calvo, M A; Adelantado, C; Figueroa, S

    2010-05-01

    The antifungal activity of ethanolic extracts of Rosmarinus officinalis and Thymus vulgaris were tested against strains of Aspergillus flavus and A. ochraceus, since these two species are common contaminants of cereals and grains and are able to produce and accumulate mycotoxins. The methodology used is based on measuring the inhibition halos produced by discs impregnated with the extracts and establishing their Minimum Inhibitory Concentration (MIC) as well as the Minimum Fungicide Concentration (MFC). The results obtained suggest that the assayed extracts affect the proper development of A. flavus and A. ochraceus; leading to a lower MIC (1200 ppm) and MFC (2400 ppm) for T. vulgaris extract against A. ochraceus than against A. flavus. The results show, that the extracts of Rosmarinus officinalis and Thymus vulgaris used at low concentrations could have significant potential for the biological control of fungi in foodstuffs. PMID:20973400

  13. Expression, crystallization and structure elucidation of γ-terpinene synthase from Thymus vulgaris.

    PubMed

    Rudolph, Kristin; Parthier, Christoph; Egerer-Sieber, Claudia; Geiger, Daniel; Muller, Yves A; Kreis, Wolfgang; Müller-Uri, Frieder

    2016-01-01

    The biosynthesis of γ-terpinene, a precursor of the phenolic isomers thymol and carvacrol found in the essential oil from Thymus sp., is attributed to the activitiy of γ-terpinene synthase (TPS). Purified γ-terpinene synthase from T. vulgaris (TvTPS), the Thymus species that is the most widely spread and of the greatest economical importance, is able to catalyze the enzymatic conversion of geranyl diphosphate (GPP) to γ-terpinene. The crystal structure of recombinantly expressed and purified TvTPS is reported at 1.65 Å resolution, confirming the dimeric structure of the enzyme. The putative active site of TvTPS is deduced from its pronounced structural similarity to enzymes from other species of the Lamiaceae family involved in terpenoid biosynthesis: to (+)-bornyl diphosphate synthase and 1,8-cineole synthase from Salvia sp. and to (4S)-limonene synthase from Mentha spicata. PMID:26750479

  14. Plants belonging to the genus Thymus as antibacterial agents: from farm to pharmacy.

    PubMed

    Nabavi, Seyed Mohammad; Marchese, Anna; Izadi, Morteza; Curti, Valeria; Daglia, Maria; Nabavi, Seyed Fazel

    2015-04-15

    In traditional medicine, plants have been used since ancient times for the prevention and/or protection against infectious diseases. In recent years, the use of herbal medicines and food supplements containing botanical ingredients, as alternative therapy for infectious diseases, has been intensified due to their high content of antimicrobial agents such as polyphenols, i.e. flavonoids, tannins, and alkaloids. Plants from the genus Thymus are important medicinal herbs, which are known to contain antimicrobial agents, and are rich in different active substances such as thymol, carvacrol, p-cymene and terpinene. In this review, we summarise the available literature data about the in vitro antibacterial effects of the main plants belonging to the genus Thymus. We also provide information about cultivation, chemical composition of the essential oils obtained from these plants, and their use for medicinal purposes.

  15. Antifungal activity of chemically different essential oils from wild Tunisian Thymus spp.

    PubMed

    Maissa, Ben Jabeur; Walid, Hamada

    2015-01-01

    Essential oils isolated by using hydrodistillation from the aerial parts of Thymus algeriensis and Thymus capitatus Hoff. et Link. from different locations of Tunisia (Kef, Takelsa, Zaghouan, Fahs and Toukeber) were characterised. The chemical composition was analysed by using gas chromatography/mass spectrometry, the major component of T. capitatus from Kef and T. algeriensis was thymol while carvacrol was the main component of T. capitatus from Zaghouan, Fahs and Toukeber. The antifungal activity of the oils and some pure components was assessed by the in vitro assay against several fungi and oomycetes. T. capitatus (chemotype carvacrol) exhibited the strongest antifungal activity followed by T. capitatus (chemotype thymol) and T. algeriensis, indicating that carvacrol might have a stronger antifungal activity than thymol.

  16. Plants belonging to the genus Thymus as antibacterial agents: from farm to pharmacy.

    PubMed

    Nabavi, Seyed Mohammad; Marchese, Anna; Izadi, Morteza; Curti, Valeria; Daglia, Maria; Nabavi, Seyed Fazel

    2015-04-15

    In traditional medicine, plants have been used since ancient times for the prevention and/or protection against infectious diseases. In recent years, the use of herbal medicines and food supplements containing botanical ingredients, as alternative therapy for infectious diseases, has been intensified due to their high content of antimicrobial agents such as polyphenols, i.e. flavonoids, tannins, and alkaloids. Plants from the genus Thymus are important medicinal herbs, which are known to contain antimicrobial agents, and are rich in different active substances such as thymol, carvacrol, p-cymene and terpinene. In this review, we summarise the available literature data about the in vitro antibacterial effects of the main plants belonging to the genus Thymus. We also provide information about cultivation, chemical composition of the essential oils obtained from these plants, and their use for medicinal purposes. PMID:25466031

  17. Effects of Thymol and Carvacrol, Constituents of Thymus vulgaris L. Essential Oil, on the Inflammatory Response

    PubMed Central

    Fachini-Queiroz, Fernanda Carolina; Kummer, Raquel; Estevão-Silva, Camila Fernanda; Carvalho, Maria Dalva de Barros; Cunha, Joice Maria; Grespan, Renata; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

    2012-01-01

    Thyme (Thymus vulgaris L., Lamiaceae) is an aromatic and medicinal plant that has been used in folk medicine, phytopharmaceutical preparations, food preservatives, and as an aromatic ingredient. The effect of Thymus vulgaris essential oil (TEO) and its isolated constituents thymol and cavacrol (CVL) were studied in the following experimental models: ear edema, carrageenan-induced pleurisy, and chemotaxis in vitro. In the pleurisy model, TEO, CVL, and thymol significantly inhibited inflammatory edema. However, only TEO and CVL inhibited leukocyte migration. In the in vitro chemotaxis experiment, CVL inhibited leukocyte migration, whereas thymol exerted a potent chemoattractant effect. In the ear edema model, CVL (10 mg/ear), applied topically, reduced edema formation, exerting a topical anti-inflammatory effect. Thymol did not reduce edema formation but rather presented an irritative response, probably dependent on histamine and prostanoid release. Our data suggest that the antiinflammatory effects of TEO and CVL are attributable to the inhibition of inflammatory edema and leukocyte migration. PMID:22919415

  18. Non-intercalative, deoxyribose binding of boric acid to calf thymus DNA.

    PubMed

    Ozdemir, Ayse; Gursaclı, Refiye Tekiner; Tekinay, Turgay

    2014-05-01

    The present study characterizes the effects of the boric acid binding on calf thymus DNA (ct-DNA) by spectroscopic and calorimetric methods. UV-Vis absorbance spectroscopy, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), and Fourier transform infrared (FT-IR) spectroscopy were employed to characterize binding properties. Changes in the secondary structure of ct-DNA were determined by CD spectroscopy. Sizes and morphologies of boric acid-DNA complexes were determined by transmission electron microscopy (TEM). The kinetics of boric acid binding to calf thymus DNA (ct-DNA) was investigated by isothermal titration calorimetry (ITC). ITC results revealed that boric acid exhibits a moderate affinity to ct-DNA with a binding constant (K a) of 9.54 × 10(4) M(-1). FT-IR results revealed that boric acid binds to the deoxyribose sugar of DNA without disrupting the B-conformation at tested concentrations.

  19. Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency.

    PubMed

    Griffith, Ann V; Venables, Thomas; Shi, Jianjun; Farr, Andrew; van Remmen, Holly; Szweda, Luke; Fallahi, Mohammad; Rabinovitch, Peter; Petrie, Howard T

    2015-08-18

    T lymphocytes are essential mediators of immunity that are produced by the thymus in proportion to its size. The thymus atrophies rapidly with age, resulting in progressive diminution of new T cell production. This decreased output is compensated by duplication of existing T cells, but it results in gradual dominance by memory T cells and decreased ability to respond to new pathogens or vaccines. Here, we show that accelerated and irreversible thymic atrophy results from stromal deficiency in the reducing enzyme catalase, leading to increased damage by hydrogen peroxide generated by aerobic metabolism. Genetic complementation of catalase in stromal cells diminished atrophy, as did chemical antioxidants, thus providing a mechanistic link between antioxidants, metabolism, and normal immune function. We propose that irreversible thymic atrophy represents a conventional aging process that is accelerated by stromal catalase deficiency in the context of an intensely anabolic (lymphoid) environment.

  20. The subunit structure of calf thymus ribonuclease H i as revealed by immunological analysis.

    PubMed

    Büsen, W

    1982-06-25

    We have recently reported on the purification, subunit structure, and serological analysis of calf thymus ribonuclease H I and suggested a trimeric or tetrameric structure for the enzyme (Büsen, W., and Vogt, G. (1980) J. Biol. Chem. 255, 9434-9443). Continuation of our immunological analysis, using a protein blotting procedure for antigen detection and immunoaffinity chromatography, revealed that the native enzyme molecule is composed of polypeptides A and C with molecular weights of 31,600 and 24,800 respectively, in a molar ratio of 2 to 1. This is in accordance with a trimeric structure (A,A,C) for calf thymus ribonuclease H I. Polypeptides B and D, found in the most purified fraction, are shown to be generated during the early steps of the purification procedure, suggesting specific protein nicking which does not affect the native molecular weight of the enzyme.

  1. Intronic regulation of Aire expression by Jmjd6 for self-tolerance induction in the thymus

    PubMed Central

    Yanagihara, Toyoshi; Sanematsu, Fumiyuki; Sato, Tetsuya; Uruno, Takehito; Duan, Xuefeng; Tomino, Takahiro; Harada, Yosuke; Watanabe, Mayuki; Wang, Yuqing; Tanaka, Yoshihiko; Nakanishi, Yoichi; Suyama, Mikita; Yoshinori, Fukui

    2015-01-01

    The thymus has spatially distinct microenvironments, the cortex and the medulla, where the developing T-cells are selected to mature or die through the interaction with thymic stromal cells. To establish the immunological self in the thymus, medullary thymic epithelial cells (mTECs) express diverse sets of tissue-specific self-antigens (TSAs). This ectopic expression of TSAs largely depends on the transcriptional regulator Aire, yet the mechanism controlling Aire expression itself remains unknown. Here, we show that Jmjd6, a dioxygenase that catalyses lysyl hydroxylation of splicing regulatory proteins, is critical for Aire expression. Although Jmjd6 deficiency does not affect abundance of Aire transcript, the intron 2 of Aire gene is not effectively spliced out in the absence of Jmjd6, resulting in marked reduction of mature Aire protein in mTECs and spontaneous development of multi-organ autoimmunity in mice. These results highlight the importance of intronic regulation in controlling Aire protein expression. PMID:26531897

  2. Intronic regulation of Aire expression by Jmjd6 for self-tolerance induction in the thymus.

    PubMed

    Yanagihara, Toyoshi; Sanematsu, Fumiyuki; Sato, Tetsuya; Uruno, Takehito; Duan, Xuefeng; Tomino, Takahiro; Harada, Yosuke; Watanabe, Mayuki; Wang, Yuqing; Tanaka, Yoshihiko; Nakanishi, Yoichi; Suyama, Mikita; Yoshinori, Fukui

    2015-11-04

    The thymus has spatially distinct microenvironments, the cortex and the medulla, where the developing T-cells are selected to mature or die through the interaction with thymic stromal cells. To establish the immunological self in the thymus, medullary thymic epithelial cells (mTECs) express diverse sets of tissue-specific self-antigens (TSAs). This ectopic expression of TSAs largely depends on the transcriptional regulator Aire, yet the mechanism controlling Aire expression itself remains unknown. Here, we show that Jmjd6, a dioxygenase that catalyses lysyl hydroxylation of splicing regulatory proteins, is critical for Aire expression. Although Jmjd6 deficiency does not affect abundance of Aire transcript, the intron 2 of Aire gene is not effectively spliced out in the absence of Jmjd6, resulting in marked reduction of mature Aire protein in mTECs and spontaneous development of multi-organ autoimmunity in mice. These results highlight the importance of intronic regulation in controlling Aire protein expression.

  3. Binding of a new bisphenol analogue, bisphenol S to bovine serum albumin and calf thymus DNA.

    PubMed

    Wang, Yan-Qing; Zhang, Hong-Mei; Cao, Jian; Tang, Bo-Ping

    2014-09-01

    Interactions of bisphenol S, a new bisphenol analogue with bovine serum albumin and calf thymus DNA were investigated using different spectroscopic methods and molecular modeling calculation. According to the analysis of experimental and theoretical data, we concluded that hydrophobic interactions and hydrogen bonding primarily mediated the binding processes of bisphenol S with bovine serum albumin and DNA. In addition, the electrostatic force should not be excluded. Molecular modeling studies indicated that the binding site of bisphenol S to bovine serum albumin located in the subdomain IB, while bisphenol S was a groove binder of DNA. In addition, BPS did not obviously induce second structural changes of bovine serum albumin, but it induced a conformational change of calf thymus DNA.

  4. Antifungal activity of chemically different essential oils from wild Tunisian Thymus spp.

    PubMed

    Maissa, Ben Jabeur; Walid, Hamada

    2015-01-01

    Essential oils isolated by using hydrodistillation from the aerial parts of Thymus algeriensis and Thymus capitatus Hoff. et Link. from different locations of Tunisia (Kef, Takelsa, Zaghouan, Fahs and Toukeber) were characterised. The chemical composition was analysed by using gas chromatography/mass spectrometry, the major component of T. capitatus from Kef and T. algeriensis was thymol while carvacrol was the main component of T. capitatus from Zaghouan, Fahs and Toukeber. The antifungal activity of the oils and some pure components was assessed by the in vitro assay against several fungi and oomycetes. T. capitatus (chemotype carvacrol) exhibited the strongest antifungal activity followed by T. capitatus (chemotype thymol) and T. algeriensis, indicating that carvacrol might have a stronger antifungal activity than thymol. PMID:25484099

  5. Portuguese Thymbra and Thymus species volatiles: chemical composition and biological activities.

    PubMed

    Figueiredo, A C; Barroso, J G; Pedro, L G; Salgueiro, L; Miguel, M G; Faleiro, M L

    2008-01-01

    Thymbra capitata and Thymus species are commonly known in Portugal as thyme and they are currently used as culinary herbs, as well as for ornamental, aromatizing and traditional medicinal purposes. The present work reports on the state of the art on the information available on the taxonomy, ethnobotany, cell and molecular biology of the Portuguese representatives of these genera and on the chemotaxonomy and antibacterial, antifungal and antioxidant activities of their essential oils and other volatile-containing extracts. PMID:19075695

  6. Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous

    PubMed Central

    Langhi, Larissa G. P.; Andrade, Leonardo R.; Shimabukuro, Marilia Kimie; van Ewijk, Willem; Taub, Dennis D.; Borojevic, Radovan; de Mello Coelho, Valeria

    2015-01-01

    Intrathymic lipid-laden multilocular cells (LLMC) are known to express pro-inflammatory factors that might regulate functional activity of the thymus. However, the phenotype of age-associated intrathymic LLMC is still controversial. In this study, we evaluated LLMC density in the aging thymus and better characterized their distribution, ultrastructure and phenotype. Our results show an increased density of LLMC in the thymus from 03 to 24 months of age. Morphologically, intrathymic LLMC exhibit fibroblastoid fusiform, globular or stellate shapes and can be found in the subcapsular region as well as deeper in the parenchyma, including the perivascular area. Some parenchymal LLMC were like telocytes accumulating lipids. We identified lipid droplets with different electrondensities, lipofuscin granules and autolipophagosome-like structures, indicating heterogeneous lipid content in these cells. Autophagosome formation in intrathymic LLMC was confirmed by positive staining for beclin-1 and perilipin (PLIN), marker for lipid droplet-associated proteins. We also found LLMC in close apposition to thymic stromal cells, endothelial cells, mast cells and lymphocytes. Phenotypically, we identified intrathymic LLMC as preadipocytes (PLIN+PPARγ2+), brown adipocytes (PLIN+UCP1+), macrophages (PLIN+Iba-1+) or pericytes (PLIN+NG2+) but not epithelial cells (PLIN- panCK+). These data indicate that intrathymic LLMC are already present in the young thymus and their density significantly increases with age. We also suggest that LLMC, which are morphologically distinct, establish direct contact with lymphocytes and interact with stromal cells. Finally, we evidence that intrathymic LLMC correspond to not only one but to distinct cell types accumulating lipids. PMID:26509710

  7. A Tale from TGF-β Superfamily for Thymus Ontogeny and Function

    PubMed Central

    Jurberg, Arnon Dias; Vasconcelos-Fontes, Larissa; Cotta-de-Almeida, Vinícius

    2015-01-01

    Multiple signaling pathways control every aspect of cell behavior, organ formation, and tissue homeostasis throughout the lifespan of any individual. This review takes an ontogenetic view focused on the large superfamily of TGF-β/bone morphogenetic protein ligands to address thymus morphogenesis and function in T cell differentiation. Recent findings on a role of GDF11 for reversing aging-related phenotypes are also discussed. PMID:26441956

  8. A tour of the thymus: a review of thymic lesions with radiologic and pathologic correlation.

    PubMed

    Goldstein, Alan J; Oliva, Isabel; Honarpisheh, Hedieh; Rubinowitz, Ami

    2015-02-01

    The thymus is routinely encountered on cross-sectional imaging studies of the chest. It has a variable appearance, undergoes dynamic changes during periods of stress, and demonstrates numerous different pathologic lesions. Understanding the imaging characteristics of these different lesions facilitates accurate radiographic diagnosis and can prevent unnecessary follow-up imaging and intervention. This article will review normal thymic anatomy and development, thymic hyperplasia and associated medical conditions, and the imaging and pathologic features of various benign and malignant thymic lesions.

  9. Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous.

    PubMed

    Langhi, Larissa G P; Andrade, Leonardo R; Shimabukuro, Marilia Kimie; van Ewijk, Willem; Taub, Dennis D; Borojevic, Radovan; de Mello Coelho, Valeria

    2015-01-01

    Intrathymic lipid-laden multilocular cells (LLMC) are known to express pro-inflammatory factors that might regulate functional activity of the thymus. However, the phenotype of age-associated intrathymic LLMC is still controversial. In this study, we evaluated LLMC density in the aging thymus and better characterized their distribution, ultrastructure and phenotype. Our results show an increased density of LLMC in the thymus from 03 to 24 months of age. Morphologically, intrathymic LLMC exhibit fibroblastoid fusiform, globular or stellate shapes and can be found in the subcapsular region as well as deeper in the parenchyma, including the perivascular area. Some parenchymal LLMC were like telocytes accumulating lipids. We identified lipid droplets with different electrondensities, lipofuscin granules and autolipophagosome-like structures, indicating heterogeneous lipid content in these cells. Autophagosome formation in intrathymic LLMC was confirmed by positive staining for beclin-1 and perilipin (PLIN), marker for lipid droplet-associated proteins. We also found LLMC in close apposition to thymic stromal cells, endothelial cells, mast cells and lymphocytes. Phenotypically, we identified intrathymic LLMC as preadipocytes (PLIN+PPARγ2+), brown adipocytes (PLIN+UCP1+), macrophages (PLIN+Iba-1+) or pericytes (PLIN+NG2+) but not epithelial cells (PLIN- panCK+). These data indicate that intrathymic LLMC are already present in the young thymus and their density significantly increases with age. We also suggest that LLMC, which are morphologically distinct, establish direct contact with lymphocytes and interact with stromal cells. Finally, we evidence that intrathymic LLMC correspond to not only one but to distinct cell types accumulating lipids.

  10. Selenium Deficiency Downregulates Selenoproteins and Suppresses Immune Function in Chicken Thymus.

    PubMed

    Khoso, Pervez Ahmed; Yang, Zijiang; Liu, Chunpeng; Li, Shu

    2015-09-01

    Selenoproteins and selenium (Se) play important roles in the immune system. Selenoprotein expression in the immune system of mammals is sensitive to dietary Se levels; however, little is known about the expression of selenoproteins and their immune functions in the chicken thymus. We assessed selenoprotein gene expression and cytokine content in the chicken thymus in this study. The animals were randomly assigned to two groups as follows: the Se-deficient group (L group) was fed a diet containing 0.033 mg Se/Kg, and the control group was fed the same basal diet supplemented with Se at 0.15 mg/kg (sodium selenite). Real-time qPCR was used to investigate the expression level of selenoproteins on days 15, 25, 35, 45, and 55, and ELISA was used to evaluate the cytokine content on days 15, 35, and 55. The messenger RNA (mRNA) levels of Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, Dio3, GPx1, GPx2, GPx3, Gpx4, Sepp1, Selo, Sep15, Sepx1, Sels, Seli, Selu, Selh, and SPS2 were all significantly decreased (P < 0.05) in the L group compared to the control group. A significant decrease in IL-2, IL-10, IL-17, IL-1β, IFN-α, and IFN-β was observed in the L group, and there was also a significant increase in IL-6, IL-8, IFN-γ, and TNF-α in the L group. In summary, Se deficiency results in significant changes in the expression of selenoproteins, which may cause oxidative stress in the chicken thymus tissue. Moreover, immunological changes and immune stress may occur because of Se deficiency in the chicken thymus.

  11. [MORPHO-FUNCTIONAL CHANGES OF THYMUS TISSUES IN CHILDREN WITH CONGENITAL HEART DISEASE].

    PubMed

    Loginova, N P; Chetvertnykh, V A; Chemurziyeva, N V

    2016-01-01

    Biopsy specimens of the thymus were studied in children aged under 11 months (n = 77) with congenital heart defects and circulatory hypoxia of varying severity. Histological sections were stained with hematoxylin-eosin and Shubich's method (to demonstrate mast cells). The expression of Ki-67, CD3 and CD34 was assessed by immunohistochemistry. The ultrastructure of thymic tissues was also examined. It was found that the severity of hypoxia determined the morphological changes in the organ associated with a development of large complex of tissue reactions. A disruption of internal structure and a loss of integrity of epithelio-reticular cells and thymocytes were demonstrated in ultrathin sections. Thymocyte proliferation index (Ki-67) and thymocytopoiesis intensity (CD3+) were reduced in all the zones of the thymus. The degree of hypoxia affected the redistribution of CD3+ lymphocytes leading to their accumulation in the medulla. The processes of endogenous regeneration took place which involved the cells of fibroblastic line and progenitor cells (CD34+) together with active formation of new blood vessels. These findings suggest that the morphological changes identified in the tissues of the thymus are a manifestation of tissue adaptation to hypoxia of varying severity under conditions of endogenous regeneration, simultaneously reflecting the processes of substitution cytogenesis. PMID:27487665

  12. Development of the chick thymus microenvironment: a study by lectin histochemistry.

    PubMed Central

    Fernandez, J G; Sanchez, A J; Melcon, C; Chamorro, C A; Garcia, C; Paz, P

    1994-01-01

    The microenvironment of the chick thymus has been examined during development using lectin histochemistry. We have assayed WGA, Con A, RCA-I and TPA on thymic sections from 13, 15, 17 and 19 d chick embryos and 0, 5, 10 and 15 d chicks. All lectins were immunoperoxidase and colloidal gold-conjugated for transmission electron microscope observations. WGA labelled both the cortical and medullary thymic stroma at all the stages analysed. An intense reaction to WGA was observed in the subcortical region from stage 18 embryos to 5 d chicks. On the other hand, WGA did not stain medullary areas of the chick thymus. Con A lectin detected several cell clusters of stromal cells and thymocytes in cortical regions. These clusters could represent a lymphostromal complex with which Con A receptors are associated, probably in relation to cell adhesion. The residues detected by RCA were distributed both in stromal cells and thymocytes of the developing chick thymus. There was an increase of the reaction to RCA between the 19 d embryos and the 5 d chicks. This increase might be interpreted in terms of the secretion of thymic humoral factors at these stages. The thymic stromal cells stained with immunoperoxidase conjugated-TPA showed a reticular pattern in the medulla. There is a possibility that the fucosyl residues may be expressed in the Ia antigen as has previously been suggested in other species. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7512541

  13. A study of the chick thymus microenvironment during development: analysis by monoclonal antibodies against thymic epithelium.

    PubMed

    Paz, P; Sánchez, A; Melcón, C; Fernández, J G; Chamorro, C A

    1993-02-01

    The process of T-lymphocyte differentiation within the thymus involves a series of molecular interactions. In this work we have carried out an analysis of the chick thymus microenvironment in order to evaluate its heterogeneity during development. We have produced 11 monoclonal antibodies whose staining patterns detected by the immunoperoxidase technique allowed us to divide them into five groups. A first group (E19-E2, P0-E5, and P15-T1) binds to thymic medullary stroma showing a reticular pattern on medullary epithelial cells and whose significance would be related to thymic stromal secretion. The second group of monoclonal antibodies (P15-T3) stains thymic corpuscles of 10- and 15-day chicks. The third group of antibodies includes P0-E1, P0-E3, P5-A6, and P15-T2 whose staining pattern is both medullary and cortical. The fourth group (P10-HB1 and P10-HB2) binds to thymic stromal and cortical thymocytes, and the fifth group (P5-A1) is characterized by the staining of medullary vessels of 5-day chicks. These five groups of monoclonal antibodies corroborate the existence of an antigenic diversity of the chick thymus microenvironment. Their possible relationships with T-cell differentiation and stromal-thymocyte interactions are discussed.

  14. A critical overview on Thymus daenensis Celak.: phytochemical and pharmacological investigations.

    PubMed

    Zarshenas, Mohammad M; Krenn, Liselotte

    2015-03-01

    Thymus daenensis Celak. is an herb endemic to Iran belonging to the Lamiaceae family. Growing in many parts of Iran, the plant is extensively used in folk medicine. This review was performed to compile phytochemical and pharmacological data of T. daenensis. Databases such as PubMed, Scopus, Web of Science, ScienceDirect, Scientific Information Database, Embase, IranMedex and Google Scholar were searched for the terms "Thymus daenensis" and "Avishan-e-denaii" up to 1st January 2014. Following reported ethnopharmacological uses, various T. daenensis preparations have been investigated for antimicrobial, antioxidant, insecticidal and immunomodulatory effects in recent studies. Moreover, numerous studies have been published on the composition of the herb's essential oil, focusing either on environmental parameters or preparation methods. Due to its high concentration of thymol, the plant's essential oil possesses high antimicrobial activities on human pathogenic strains. However, comprehensive studies on the toxicity and teratogenicity as well as clinical efficacy of Thymus daenensis are missing. PMID:25797639

  15. Keratin 8 is required for the maintenance of architectural structure in thymus epithelium.

    PubMed

    Odaka, Chikako; Loranger, Anne; Takizawa, Kazuya; Ouellet, Michel; Tremblay, Michel J; Murata, Shigeo; Inoko, Akihito; Inagaki, Masaki; Marceau, Normand

    2013-01-01

    Keratins (Ks), the intermediate filament (IF) proteins of epithelia, are coordinately expressed as pairs in a cell-lineage and differentiation manner. Cortical thymic epithelial cells (cTECs) predominantly express the simple epithelium keratin 8/18 (K8/K18) pair, whereas medullary thymic epithelial cells (mTECs) express the stratified epithelium K5/K14 pair, with TECs exhibiting K5 and K8 at the cortico-medullary junction in mature thymus. In the work reported here, we used wild-type (WT) and K8-knockout (K8-null) mice to address the contribution of K8/K18 IFs in the maintenance of the thymic epithelial structure. K8-null thymus maintained the differential cell segregation at the cortex versus the medulla observed in WT thymus, and the distribution of immature thymocytes at the cortex. The K8/K18 loss did not affect thymocyte development. However, it massively perturbed the TEC morphology both at the cortex and the medulla, along with a prominent depletion of cTECs. Such tissue alterations coincided with an increase in apoptosis and a reduced expression of Albatross (Fas-binding factor-1), also known for its capacity to bind K8/18 IFs. In addition, the K8/K18 loss affected the distribution of K5/K14-positive mTECs, but not their differentiation status. Together, the results indicate that K8/K18 IFs constitute key promoters of the thymic epithelium integrity.

  16. Histological and cytological studies on the developing thymus of sharpsnout seabream, Diplodus puntazzo.

    PubMed

    Romano, N; Fanelli, M; Maria Del Papa, G; Scapigliati, G; Mastrolia, L

    1999-01-01

    The structure of the developing thymus of the marine teleost, Diplodus puntazzo, was studied by light and transmission electron microscopy. The first anlage of the thymus developed by d 20 postfertilisation (p.f.) as a group of undifferentiated cells dorsal to the epithelium of the branchial chamber. The organ increased significantly in size around d 51-66 p.f. and differentiation of cortex and medulla occurred concomitantly. On the basis of their localisation, 4 main types of epithelial cell were distinguished: (1) limiting, adjacent to the connective capsule; (2) medullary and cortical reticular cells; (3) nurse cells, located in the corticomedullary boundary; (4) Hassall-like corpuscles. The majority of medium to large blast-like lymphoid cells were localised in the medulla, while small lymphocytes were housed in the cortical region. These morphological features were maintained at later stages. However, in juveniles in the medulla we observed reticular epithelial cells with cysts and rare Hassall-like corpuscles. The study was designed to obtain more information concerning the histology of the developing thymus of sharpsnout seabream and give a concise description of the differentiation of epithelial cells and lymphoid cells in the thymic parenchyma. PMID:10227665

  17. Histological and cytological studies on the developing thymus of sharpsnout seabream, Diplodus puntazzo

    PubMed Central

    ROMANO, NICLA; FANELLI, MONICA; DEL PAPA, GIOVANNI MARIA; SCAPIGLIATI, GIUSEPPE; MASTROLIA, LUCIA

    1999-01-01

    The structure of the developing thymus of the marine teleost, Diplodus puntazzo, was studied by light and transmission electron microscopy. The first anlage of the thymus developed by d 20 postfertilisation (p.f.) as a group of undifferentiated cells dorsal to the epithelium of the branchial chamber. The organ increased significantly in size around d 51–66 p.f. and differentiation of cortex and medulla occurred concomitantly. On the basis of their localisation, 4 main types of epithelial cell were distinguished: (1) limiting, adjacent to the connective capsule; (2) medullary and cortical reticular cells; (3) nurse cells, located in the corticomedullary boundary; (4) Hassall-like corpuscles. The majority of medium to large blast-like lymphoid cells were localised in the medulla, while small lymphocytes were housed in the cortical region. These morphological features were maintained at later stages. However, in juveniles in the medulla we observed reticular epithelial cells with cysts and rare Hassall-like corpuscles. The study was designed to obtain more information concerning the histology of the developing thymus of sharpsnout seabream and give a concise description of the differentiation of epithelial cells and lymphoid cells in the thymic parenchyma. PMID:10227665

  18. [MORPHO-FUNCTIONAL CHANGES OF THYMUS TISSUES IN CHILDREN WITH CONGENITAL HEART DISEASE].

    PubMed

    Loginova, N P; Chetvertnykh, V A; Chemurziyeva, N V

    2016-01-01

    Biopsy specimens of the thymus were studied in children aged under 11 months (n = 77) with congenital heart defects and circulatory hypoxia of varying severity. Histological sections were stained with hematoxylin-eosin and Shubich's method (to demonstrate mast cells). The expression of Ki-67, CD3 and CD34 was assessed by immunohistochemistry. The ultrastructure of thymic tissues was also examined. It was found that the severity of hypoxia determined the morphological changes in the organ associated with a development of large complex of tissue reactions. A disruption of internal structure and a loss of integrity of epithelio-reticular cells and thymocytes were demonstrated in ultrathin sections. Thymocyte proliferation index (Ki-67) and thymocytopoiesis intensity (CD3+) were reduced in all the zones of the thymus. The degree of hypoxia affected the redistribution of CD3+ lymphocytes leading to their accumulation in the medulla. The processes of endogenous regeneration took place which involved the cells of fibroblastic line and progenitor cells (CD34+) together with active formation of new blood vessels. These findings suggest that the morphological changes identified in the tissues of the thymus are a manifestation of tissue adaptation to hypoxia of varying severity under conditions of endogenous regeneration, simultaneously reflecting the processes of substitution cytogenesis.

  19. Purification, subunit structure, and serologicai analysis of calf thymus ribonuclease H I.

    PubMed

    Büsen

    1980-10-10

    Calf thymus ribonuclease H I (for nomenclature, see Büsen, W., and Hausen, P. (1975) Eur. J. Biochem. 52, 179-190) has been purified to near homogeneity. The large scale purification procedure results in a 1,000-fold enrichment of enzyme protein over the crude extract. The enzyme has a molecular weight of about 80,000, and S value of about 5, and an isoelectric point of about 4.9 under nondenaturing conditions. The purified enzyme sample contains two forms of ribonuclease H I, possibly isozymes, named ribonuclease H I 1 and ribonuclease H I 2. They can be activated by Mn2+ or Mg2+ ions. The most highly purified fraction is composed of four polypeptides named A, B, C, and D with molecular weights of 31,6000, 26,6000, 24,800, and 24,300, respectively. Polypeptides A, C, and D are acidic, whereas Polypeptide B is basic. Each form consists of three polypeptides. Ribonuclease H I 1 and ribonuclease H I 2 have Polypeptides A and B in common and differ from each other in the third. The data are consistent with a trimeric (A, B, C/D) or tetrameric (A, B2, C/D) structure for calf thymus ribonuclease H I. When alkalisensitive supercoiled DNA molecules containing ribonucleotides covalently inserted in one of the DNA strands are used as substrate, the products of the reaction are relaxed circles; thus, ribonuclease H I has an endonucleolytic mode of action. The final preparation is free of ribonuclease, and also of endodeoxyribonuclease activity single- and double-stranded DNA. Rabbit antiserum raised against the most highly purified calf thymus ribonuclease H I specifically precipitates the Polypeptides A, B, C, and D and inhibits the Mn2+ - and Mg2+ -dependent enzyme activities to more than 90%. Whereas a typical monophasic neutralization curve is obtained with Mn2+ activation, the neutralization curve observed with Mg2+ is biphasic. These results and several other differences between the Mn2+ - and the Mg2+ -dependent activities of the ribonucleases H I seem best explained

  20. An Observational Study on Aberrant Methylation of Runx3 With the Prognosis in Chronic Atrophic Gastritis Patients

    PubMed Central

    Zhao, Chunna; Li, Ping; Zhang, Lili; Wang, Bei; Xiao, Lili; Guo, Feng; Wei, Yueguang

    2016-01-01

    Abstract The aim of this study is to discuss whether the methylation levels of Runx3 could be used as the early biomarker for predicting the prognosis in chronic atrophic gastritis (CAG) patients. A total of 200 subjects including 60 controls without CAG (Group 1), 70 patients with mild CAG (Group 2), and 70 patients with moderate and severe CAG (Group 3) were recruited for this cross-sectional investigation in the Department of Gastroenterology in Daqing Oilfield General Hospital from July 2013 to May 2014. The MlALDI-TOF-MS was used to measure the methylation levels of Runx3 in all of the subjects. Real-time quantitative reverse transcription polymerase chain reaction and western blotting were chosen to determine the expression levels of Runx3. The correlations between methylation levels of Runx3 among these CAG patients and their prognosis were shown by logistic regression models. The results demonstrated that the methylation levels of CpG13, CpG14, and CpG15 in Runx3 were higher in Group 3 than those in Groups 1 and 2 (P <0.05), whereas the mRNA and protein expression levels of Runx3 were lower in Group 3 than those in Groups 1 and 2 (P <0.05). There were significantly negative correlations between the methylation levels of Runx3 with its expression and the healing prognosis of CAG patients. In brief, this study proved that the hypermethylation modifications of CpG13, CpG14, and CpG15 in the promoter region of Runx3 could result in the down regulation of Runx3 expression to affect the prognosis of CAG. So the methylation levels of these CpG sites in Runx3 in the peripheral blood can be used as the biomarker for predicting the healing prognosis of CAG patients. PMID:27196446

  1. An Observational Study on Aberrant Methylation of Runx3 With the Prognosis in Chronic Atrophic Gastritis Patients.

    PubMed

    Zhao, Chunna; Li, Ping; Zhang, Lili; Wang, Bei; Xiao, Lili; Guo, Feng; Wei, Yueguang

    2016-05-01

    The aim of this study is to discuss whether the methylation levels of Runx3 could be used as the early biomarker for predicting the prognosis in chronic atrophic gastritis (CAG) patients. A total of 200 subjects including 60 controls without CAG (Group 1), 70 patients with mild CAG (Group 2), and 70 patients with moderate and severe CAG (Group 3) were recruited for this cross-sectional investigation in the Department of Gastroenterology in Daqing Oilfield General Hospital from July 2013 to May 2014. The MlALDI-TOF-MS was used to measure the methylation levels of Runx3 in all of the subjects. Real-time quantitative reverse transcription polymerase chain reaction and western blotting were chosen to determine the expression levels of Runx3. The correlations between methylation levels of Runx3 among these CAG patients and their prognosis were shown by logistic regression models. The results demonstrated that the methylation levels of CpG13, CpG14, and CpG15 in Runx3 were higher in Group 3 than those in Groups 1 and 2 (P <0.05), whereas the mRNA and protein expression levels of Runx3 were lower in Group 3 than those in Groups 1 and 2 (P <0.05). There were significantly negative correlations between the methylation levels of Runx3 with its expression and the healing prognosis of CAG patients. In brief, this study proved that the hypermethylation modifications of CpG13, CpG14, and CpG15 in the promoter region of Runx3 could result in the down regulation of Runx3 expression to affect the prognosis of CAG. So the methylation levels of these CpG sites in Runx3 in the peripheral blood can be used as the biomarker for predicting the healing prognosis of CAG patients. PMID:27196446

  2. Comparison of antibacterial activity of natural and hydroformylated essential oil of Thymus capitatus growing wild in north Sardinia with commercial Thymus essential oils.

    PubMed

    Usai, Marianna; Foddai, Marzia; Sechi, Barbara; Juliano, Claudia; Marchetti, Mauro

    2010-12-01

    Thymus capitatus growing wild in Sardinia showed different essential oil composition if grown surrounding Cagliari than in north Sardinia. Here we verify the composition and antimicrobial activity of the oil to make it suitable for the cosmetic and confectionery industries. With the aim of improving the scent and the antimicrobical activity of T. capitatus essential oil, a hydroformylation reaction was carried out to transform the unsaturated components of the oil into the corresponding aldehydes. The essential oil of T. capitatus exhibited a significant antibacterial activity (MIC 0.125-0.5 mg/mL), and was also found effective on C. albicans (MIC 0.125 mg/mL). After hydroformylation, several new irregular terpenoid aldehydes were detected. The perfume of the new terpenic-like aldehydes is very agreeable and, therefore, the acceptability of the aroma is remarkably improved, but the antimicrobial activity was not increased.

  3. Histologic changes in type A chronic atrophic gastritis indicating increased risk of neuroendocrine tumor development: the predictive role of dysplastic and severely hyperplastic enterochromaffin-like cell lesions.

    PubMed

    Vanoli, Alessandro; La Rosa, Stefano; Luinetti, Ombretta; Klersy, Catherine; Manca, Rachele; Alvisi, Costanza; Rossi, Sandro; Trespi, Erminio; Zangrandi, Adriano; Sessa, Fausto; Capella, Carlo; Solcia, Enrico

    2013-09-01

    The role of putative preneoplastic enterochromaffin-like cell lesions, either hyperplastic or dysplastic, in the genesis of type 1 enterochromaffin-like cell neuroendocrine tumors associated with type A chronic atrophic gastritis, their actual neoplastic risk, and their precise histogenetic mechanism deserve further clarification by specific histopathologic studies coupled with patient follow-up. A total of 100 patients with severe type A chronic atrophic gastritis, enterochromaffin-like cell hyperplasia, and antral G-cell hyperplasia were endoscopically and histologically followed up for a median of 90.1 months (total of 9118 person-months). Preneoplastic enterochromaffin-like cell lesions and newly developed neuroendocrine tumors were investigated histologically and histochemically, in parallel with enterochromaffin-like cell lesions found in nontumor mucosa of another 32 well-characterized and previously reported type 1 neuroendocrine tumors. Both neuroendocrine and nonneuroendocrine mucosa changes were analyzed and statistically evaluated. During follow-up, 7 of 100 patients developed neuroendocrine tumors: 5 were in a group of 20 cases with previous enterochromaffin-like cell dysplasia and 2 were among 80 cases showing only enterochromaffin-like cell hyperplasia throughout the study (hazard ratio, 20.7; P < .001). The severity of enterochromaffin-like cell hyperplasia at first biopsy, with special reference to linear hyperplasia with 6 chains or more per linear millimeter, also increased the risk of neuroendocrine tumor development during follow-up (hazard ratio, 13.0; P < .001). Enterochromaffin-like cell microinvasive dysplastic lesions arising at the epithelial renewal zone level, in connection with immature proliferating mucous-neck cells, were found to be linked to early intramucosal neuroendocrine tumor histogenesis. Both enterochromaffin-like cell dysplasia and severe hyperplasia indicate increased risk of neuroendocrine tumor development in type A

  4. Ablative non-fractional lasers for atrophic facial acne scars: a new modality of erbium:YAG laser resurfacing in Asians.

    PubMed

    Lee, Sang Ju; Kang, Jin Moon; Chung, Won Soon; Kim, Young Koo; Kim, Hei Sung

    2014-03-01

    Atrophic facial scars which commonly occur after inflammatory acne vulgaris can be extremely disturbing to patients both physically and psychologically. Treatment with fractional laser devices has become increasingly popular, but there has been disappointment in terms of effectiveness. The objective of this study was to assess the safety and efficacy of ablative full-face resurfacing on atrophic acne scars in the Korean population. A total of 22 patients, aged 25-44 years, underwent a new modality of resurfacing combining both short-pulsed and dual-mode erbium:yttrium-aluminum garnet (Er:YAG) laser. The patients had Fitzpatrick skin types ranging from III to V. Photographs were taken before and up to 6 months after treatment. Results were evaluated for the degree of clinical improvement and any adverse events. Degree of improvement was graded using a four-point scale: poor (1) = <25%, fair (2) = 25-50%, good (3) = 51-75%, and excellent (4) = >75%. Based on the blinded photo assessments by two independent reviewers, clinically and statistically significant mean improvement of 3.41 was observed (one-sample Wilcoxon signed rank test, P < 0.001). Complete wound healing occurred between 6 and 9 days. Erythema occurred in all patients and lasted longer than 3 months in two patients (9.1%). Postinflammatory hyperpigmentation occurred in ten patients (45.5%) and lasted longer than 3 months in one patient (4.5%). One patient experienced mild hypopigmentation (4.5%). Mild to moderate acne flare-up occurred in five patients (22.7%). No other adverse effects were observed. A new modality of Er:YAG laser resurfacing combining short-pulsed and dual-mode Er:YAG laser is a safe and very effective treatment modality for atrophic facial acne scars in Asians with darker skin tones.

  5. [Clinical use of flavonoid enriched biologically active food supplements in patients with chronic atrophic gastritis in combination with chronic cholecystitis or bile ducts dyskinesia].

    PubMed

    Tutel'ian, V A; Vasil'ev, A V; Kochetkov, A M; Pogozheva, A V; Lysikova, S L; Akol'zina, S E; Vorob'eva, L Sh

    2003-01-01

    60 patients with chronic atrophic gastritis and secretory insufficiency allied with chelicobacterial infection in combination with chronic unlithic cholecystitis or diskinesia of choledoch ways were explored with a view to study the efficiency of dietary cure including biologically active food supplements--flavonoids source. Fortification of the patients food intake with flavonoids-containing biologically active food supplements benefits mucous membrane of gastroduodenal zone that is evidenced in decrease of activity of pyloric chelicobacteriosis and resolvent and reparative effect, it also contributes to normalization of hepatobiliaric system condition and antioxidant status.

  6. Promoter polymorphisms in trefoil factor 2 and trefoil factor 3 genes and susceptibility to gastric cancer and atrophic gastritis among Chinese population.

    PubMed

    Xu, Qian; Chen, Mo-Ye; He, Cai-Yun; Sun, Li-Ping; Yuan, Yuan

    2013-10-15

    The polymorphisms in trefoil factor (TFF) gene family that protect gastrointestinal epithelium might influence individual vulnerability to gastric cancer (GC) and atrophic gastritis. We used the Sequenom MassARRAY platform to identify the genotypes of TFF2 rs3814896 and TFF3 rs9981660 polymorphisms in 478 GC patients, 652 atrophic gastritis patients, and 724 controls. For the TFF2 rs3814896 polymorphism, in the subgroup aged ≤ 50 years, we found that AG+GG genotypes were associated with a 0.746-fold decreased risk of atrophic gastritis [p=0.023, 95% confidence interval (CI)=0.580-0.960], a 0.626-fold decreased risk of GC (p=0.005, 95% CI=0.451-0.868), and a 0.663-fold decreased risk of diffuse-type GC (p=0.034, 95% CI=0.452-0.970) compared with the common AA genotype. For the TFF3 rs9981660 polymorphism, in the male subgroup, individuals with variant AG+AA genotype were associated with a 0.761-fold decreased risk of diffuse-type GC compared with the common GG genotype (p=0.043, 95% CI=0.584-0.992). Additionally, we found that in subjects aged ≤ 50 years compared with common AA genotype, TFF2 rs3814896 AG+GG genotypes were associated with increased TFF2 mRNA levels in the total gastric cancer specimens and in the diffuse-type gastric cancer specimens; and in males aged ≤ 50 years compared with common GG genotype, TFF3 rs9981660 AA+AG genotypes were associated with TFF3 mRNA levels in diffuse-type gastric cancer tissues and their corresponding non-cancerous tissues. To our knowledge, this is the first report of an association between the TFF2 rs3814896 AG+GG genotypes and decreased risks of GC, diffuse-type GC, and atrophic gastritis in younger people aged ≤ 50 years, and an association between TFF3 rs9981660 AG+AA genotype and decreased risk of diffuse-type GC in men. Moreover, we found that TFF2 rs3814896 AG+GG genotypes in people aged ≤ 50 years and TFF3 rs9981660 AG+AA genotypes in younger males with diffuse-type GC were associated with higher levels of

  7. Inflammation and Epstein-Barr Virus Infection Are Common Features of Myasthenia Gravis Thymus: Possible Roles in Pathogenesis

    PubMed Central

    Cavalcante, Paola; Maggi, Lorenzo; Colleoni, Lara; Caldara, Rosa; Motta, Teresio; Giardina, Carmelo; Antozzi, Carlo; Berrih-Aknin, Sonia; Bernasconi, Pia; Mantegazza, Renato

    2011-01-01

    The thymus plays a major role in myasthenia gravis (MG). Our recent finding of a persistent Epstein-Barr (EBV) virus infection in some MG thymuses, combined with data showing that the thymus is in a proinflammatory state in most patients, supports a viral contribution to the pathogenesis of MG. Aim of this study was to gain further evidence for intrathymic chronic inflammation and EBV infection in MG patients. Transcriptional profiling by low density array and real-time PCR showed overexpression of genes involved in inflammatory and immune response in MG thymuses. Real-time PCR for EBV genome, latent (EBER1, EBNA1, LMP1) and lytic (BZLF1) transcripts, and immunohistochemistry for LMP1 and BZLF1 proteins confirmed an active intrathymic EBV infection, further supporting the hypothesis that EBV might contribute to onset or perpetuation of the autoimmune response in MG. Altogether, our results support a role of inflammation and EBV infection as pathogenic features of MG thymus. PMID:21961056

  8. Induction of transplantation tolerance in mice across major histocompatibility barrier by using allogeneic thymus transplantation and total lymphoid irradiation

    SciTech Connect

    Waer, M.; Palathumpat, V.; Sobis, H.; Vandeputte, M. )

    1990-07-15

    The use of allogeneic thymus transplantation as a means of inducing tolerance across MHC barriers was investigated in thymectomized, total lymphoid irradiated BALB/c mice. In 90% of the animals long term outgrowth of histologically normal C57BL thymus grafts was observed. None of the latter animals was chimeric. All thymus graft-bearing mice showed specific nonresponsiveness for C57BL MHC Ag in mixed lymphocyte reaction and cell-mediated lympholysis. Spleen cells of the C57BL thymus-bearing mice were unable to induce lethal graft-vs-host disease in neonatal (BALB/c X C57BL) F1 mice but provoked a vigorous graft-vs-host disease reaction in (BALB/c x C3H) F1 neonates. Tolerant mice permanently accepted C57BL heart and pancreas grafts, but all rejected C3H grafts. Induction of tolerance of BALB/c pre-T cells through allogeneic thymus graft and/or specific suppressor cells seems to be involved. The present model offers new opportunities to study thymocyte maturation in a fully allogeneic environment and may yield applications for clinical organ transplantation.

  9. Selective Depletion of Eosinophils or Neutrophils in Mice Impacts the Efficiency of Apoptotic Cell Clearance in the Thymus

    PubMed Central

    Kim, Hye-Jung; Alonzo, Eric S.; Dorothee, Guillaume; Pollard, Jeffrey W.; Sant'Angelo, Derek B.

    2010-01-01

    Developing thymocytes undergo a rigorous selection process to ensure that the mature T cell population expresses a T cell receptor (TCR) repertoire that can functionally interact with major histocompatibility complexes (MHC). Over 90% of thymocytes fail this selection process and die. A small number of macrophages within the thymus are responsible for clearing the large number of dying thymocytes that must be continuously cleared. We studied the capacity of thymic macrophages to clear apoptotic cells under acute circumstances. This was done by synchronously inducing cell death in the thymus and then monitoring the clearance of apoptotic thymocytes. Interestingly, acute cell death was shown to recruit large numbers of CD11b+ cells into the thymus. In the absence of a minor CSF-1 dependent population of macrophages, the recruitment of these CD11b+ cells into the thymus was greatly reduced and the clearance of apoptotic cells was disrupted. To assess a possible role for the CD11b+ cells in the clearance of apoptotic cells, we analyzed mice deficient for eosinophils and mice with defective trafficking of neutrophils. Failure to attract either eosinophils or neutrophils to the thymus resulted in the impaired clearance of apoptotic cells. These results suggested that there is crosstalk between cells of the innate immune system that is necessary for maximizing the efficiency of apoptotic cell removal. PMID:20625428

  10. The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

    PubMed

    Collado, Javier A; Guitart, Carolina; Ciudad, M Teresa; Alvarez, Iñaki; Jaraquemada, Dolores

    2013-12-17

    T-cell tolerance to self-antigens is established in the thymus through the recognition by developing thymocytes of self-peptide-MHC complexes and induced and maintained in the periphery. Efficient negative selection of auto-reactive T cells in the thymus is dependent on the in situ expression of both ubiquitous and tissue-restricted self-antigens and on the presentation of derived peptides. Weak or inadequate intrathymic expression of self-antigens increases the risk to generate an autoimmune-prone T-cell repertoire. Indeed, even small changes of self-antigen expression in the thymus affect negative selection and increase the predisposition to autoimmunity. Together with other mechanisms, tolerance is maintained in the peripheral lymphoid organs via the recognition by mature T cells of a similar set of self-peptides in homeostatic conditions. However, non-lymphoid peripheral tissue, where organ-specific autoimmunity takes place, often have differential functional processes that may lead to the generation of epitopes that are absent or non-presented in the thymus. These putative differences between peptides presented by MHC molecules in the thymus and in peripheral tissues might be a major key to the initiation and maintenance of autoimmune conditions.

  11. The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

    PubMed Central

    Collado, Javier A.; Guitart, Carolina; Ciudad, M. Teresa; Alvarez, Iñaki; Jaraquemada, Dolores

    2013-01-01

    T-cell tolerance to self-antigens is established in the thymus through the recognition by developing thymocytes of self-peptide-MHC complexes and induced and maintained in the periphery. Efficient negative selection of auto-reactive T cells in the thymus is dependent on the in situ expression of both ubiquitous and tissue-restricted self-antigens and on the presentation of derived peptides. Weak or inadequate intrathymic expression of self-antigens increases the risk to generate an autoimmune-prone T-cell repertoire. Indeed, even small changes of self-antigen expression in the thymus affect negative selection and increase the predisposition to autoimmunity. Together with other mechanisms, tolerance is maintained in the peripheral lymphoid organs via the recognition by mature T cells of a similar set of self-peptides in homeostatic conditions. However, non-lymphoid peripheral tissue, where organ-specific autoimmunity takes place, often have differential functional processes that may lead to the generation of epitopes that are absent or non-presented in the thymus. These putative differences between peptides presented by MHC molecules in the thymus and in peripheral tissues might be a major key to the initiation and maintenance of autoimmune conditions. PMID:24381570

  12. Immunology in the clinic review series; focus on type 1 diabetes and viruses: enterovirus, thymus and type 1 diabetes pathogenesis

    PubMed Central

    Jaïdane, H; Sané, F; Hiar, R; Goffard, A; Gharbi, J; Geenen, V; Hober, D

    2012-01-01

    OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy. Thymus dysfunction, especially immune suppression, is frequently associated with various virus infections. Whether viruses may disturb the thymus function and play a role in the pathogenesis of autoimmune diseases is an open issue. Enteroviruses, especially Coxsackievirus B4 (CV-B4), have been largely suggested as potential inducers or aggravating factors of type 1 diabetes (T1D) pathogenesis in genetically predisposed individuals. Several pathogenic mechanisms of enterovirus-induced T1D have been suggested. One of these mechanisms is the impairment of central self-tolerance due to viral infections. Coxsackievirus-B4 is able to infect murine thymus in vitro and in vivo and to infect human thymus in vitro. Thymic epithelial cells and thymocytes are targets of infection with this virus, and several abnormalities, especially disturbance of maturation/differentiation processes, were observed. Altogether, these data suggest that CV-B infection of thymus may be involved in the pathogenesis of T1D. Further investigations are needed to explore this hypothesis. PMID:22385235

  13. Maternal Milk T Cells Drive Development of Transgenerational Th1 Immunity in Offspring Thymus

    PubMed Central

    Ghosh, Mrinal K.; Nguyen, Virginia; Muller, H. Konrad

    2016-01-01

    Using multiple murine foster-nursing protocols, thereby eliminating placental transfer and allowing a distinction between dam- and pup-derived cells, we show that foster nursing by an immunized dam results in development of CD8+ T cells in nonimmunized foster pups that are specific for Ags against which the foster dam was immunized (Mycobacterium tuberculosis or Candida albicans). We have dubbed this process “maternal educational immunity” to distinguish it from passive cellular immunity. Of the variety of maternal immune cells present in milk, only T cells were detected in pup tissues. Maternal T cells, a substantial percentage of which were CD4+MHC class II+, accumulated in the pup thymus and spleen during the nursing period. Further analysis of maternal cells in the pup thymus showed that a proportion was positive for maternal immunogen-specific MHC class II tetramers. To determine the outcome of Ag presentation in the thymus, the maternal or foster pup origin of immunogen-responding CD8+ cells in foster pup spleens was assessed. Whereas ∼10% were maternally derived in the first few weeks after weaning, all immunogen-responding CD8+ T cells were pup derived by 12 wk of age. Pup-derived immunogen-responsive CD8+ cells persisted until at least 1 y of age. Passive cellular immunity is well accepted and has been demonstrated in the human population. In this study, we show an arguably more important role for transferred immune cells: the direction of offspring T cell development. Harnessing maternal educational immunity through prepregnancy immunization programs has potential for improvement of infant immunity. PMID:27496970

  14. Maternal Milk T Cells Drive Development of Transgenerational Th1 Immunity in Offspring Thymus.

    PubMed

    Ghosh, Mrinal K; Nguyen, Virginia; Muller, H Konrad; Walker, Ameae M

    2016-09-15

    Using multiple murine foster-nursing protocols, thereby eliminating placental transfer and allowing a distinction between dam- and pup-derived cells, we show that foster nursing by an immunized dam results in development of CD8(+) T cells in nonimmunized foster pups that are specific for Ags against which the foster dam was immunized (Mycobacterium tuberculosis or Candida albicans). We have dubbed this process "maternal educational immunity" to distinguish it from passive cellular immunity. Of the variety of maternal immune cells present in milk, only T cells were detected in pup tissues. Maternal T cells, a substantial percentage of which were CD4(+)MHC class II(+), accumulated in the pup thymus and spleen during the nursing period. Further analysis of maternal cells in the pup thymus showed that a proportion was positive for maternal immunogen-specific MHC class II tetramers. To determine the outcome of Ag presentation in the thymus, the maternal or foster pup origin of immunogen-responding CD8(+) cells in foster pup spleens was assessed. Whereas ∼10% were maternally derived in the first few weeks after weaning, all immunogen-responding CD8(+) T cells were pup derived by 12 wk of age. Pup-derived immunogen-responsive CD8(+) cells persisted until at least 1 y of age. Passive cellular immunity is well accepted and has been demonstrated in the human population. In this study, we show an arguably more important role for transferred immune cells: the direction of offspring T cell development. Harnessing maternal educational immunity through prepregnancy immunization programs has potential for improvement of infant immunity. PMID:27496970

  15. How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?

    PubMed

    Michaux, Hélène; Martens, Henri; Jaïdane, Hela; Halouani, Aymen; Hober, Didier; Geenen, Vincent

    2015-01-01

    Through synthesis and presentation of neuroendocrine self-antigens by major histocompatibility complex proteins, thymic epithelial cells (TECs) play a crucial role in programing central immune self-tolerance to neuroendocrine functions. Insulin-like growth factor-2 (IGF-2) is the dominant gene/polypeptide of the insulin family that is expressed in TECs from different animal species and humans. Igf2 transcription is defective in the thymus of diabetes-prone bio-breeding rats, and tolerance to insulin is severely decreased in Igf2 (-/-) mice. For more than 15 years now, our group is investigating the hypothesis that, besides a pancreotropic action, infection by coxsackievirus B4 (CV-B4) could implicate the thymus as well, and interfere with the intrathymic programing of central tolerance to the insulin family and secondarily to insulin-secreting islet β cells. In this perspective, we have demonstrated that a productive infection of the thymus occurs after oral CV-B4 inoculation of mice. Moreover, our most recent data have demonstrated that CV-B4 infection of a murine medullary (m) TEC line induces a significant decrease in Igf2 expression and IGF-2 production. In these conditions, Igf1 expression was much less affected by CV-B4 infection, while Ins2 transcription was not detected in this cell line. Through the inhibition of Igf2 expression in TECs, CV-B4 infection could lead to a breakdown of central immune tolerance to the insulin family and promote an autoimmune response against insulin-secreting islet β cells. Our major research objective now is to understand the molecular mechanisms by which CV-B4 infection of TECs leads to a major decrease in Igf2 expression in these cells. PMID:26175734

  16. Molecular Structures of DNA-Dependent RNA Polymerases (II) from Calf Thymus and Rat Liver

    PubMed Central

    Weaver, R. F.; Blatti, S. P.; Rutter, W. J.

    1971-01-01

    DNA-dependent RNA polymerase II has been purified to high specific activity and apparent homogeneity from both calf thymus and rat liver. Two form II enzymes are present in rat-liver preparations, one with the molecular structure [(190,000)1(150,000)1(35,000)1(25,000)1], the other with a molecular structure of [(170,000)1(150,000)1(35,000)1(25,000)1] (molecular weights are within ±5% but the absolute values are approximate). Inclusion of a proteolytic inhibitor during the isolation procedure decreases the proportion of the molecule containing the 170,000 subunit. Calf-thymus RNA polymerase preparations typically exhibit four components on polyacrylamide gels that contain sodium dodecyl sulfate, with an apparent molecular structure of [(190,000)1(150,000)1(35,000)1(25,000)1]. In addition, some calf-thymus polymerase II preparations contain small quantities of the [(170,000)1(150,000)1(35,000)1(25,000)1] species; the quantity of this species may also be increased from less than 5% in the normal preparation to at least 40% in an “aged” preparation. Thus, the 170,000 subunit may be derived from the 190,000 subunit in both tissues. Until unequivocal evidence is obtained on this point, however, the possibility that the large subunits are unique species should not be eliminated. The general structural similarity of the eukaryotic RNA polymerase II with that of the prokaryotic polymerase suggests that the modes of action and regulation may be analogous. Images PMID:5289245

  17. Repopulation of the atrophied thymus in diabetic rats by insulin-like growth factor I.

    PubMed Central

    Binz, K; Joller, P; Froesch, P; Binz, H; Zapf, J; Froesch, E R

    1990-01-01

    Atrophy of the thymus is one of the consequences of severe insulin deficiency. We describe here that the weight and the architecture of the thymus of diabetic rats is restored towards normal not only by insulin but also by insulin-like growth factor I (IGF-I) treatment. In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia. We also investigated the in vivo effect of IGF-I on replication and differentiation of thymocytes from streptozotocin-induced diabetic rats. Thymocytes from diabetic rats incorporated less [3H]thymidine than did thymocytes from healthy rats. Insulin, as well as IGF-I treatment of diabetic rats increased [3H]thymidine incorporation by thymocytes. Flow cytometry of thymocytes labeled with monoclonal antibodies revealed a decreased expression of the Thy-1 antigen in diabetic rats compared with control rats. In addition, a major deficiency of thymocytes expressing simultaneously the W3/25 and the Ox8 antigens (corresponding to immature human CD4+/CD8+ thymocytes) was observed. These changes were restored towards normal by insulin as well as by IGF-I treatment. The antibody response to a T cell-dependent antigen (bovine serum albumin) was comparable in normal and diabetic rats. We conclude that IGF-I has important effects on the thymocyte number and the presence of CD4+/CD8+ immature cells in the thymus of diabetic rats despite persisting hyperglycemia. However, helper T-cell function for antibody production appears to be preserved even in the severely diabetic state. Images PMID:2187189

  18. The effect of measles on the thymus and other lymphoid tissues

    PubMed Central

    White, R. G.; Boyd, J. F.

    1973-01-01

    The histological changes in the thymus and other lymphoid tissues in cases of severe measles resulting in death during the acute phase or at sometime afterwards (from a presumably unrelated cause) have been surveyed and compared with cases of similar age and duration of illnesses other than measles which were admitted to the same infectious diseases hospital. Severe changes of aggregation and formation of large syncytia of thymocytes which progressed to cytoplasmic and nuclear destruction were observed early in the disease (at 4 days). These `giant-cells' failed to show either nuclear or cytoplasmic inclusion bodies. Such cases when seen at a later stage had total loss of thymic cortex. After measles the cortex of the thymus can be absent for at least 2 months. Thus no cortex was discernible in cases of post-measles death at 28 and 64 days; recovery of cortex was seen at 91 and 122 days. Other cases of severe systemic disease entering the same hospital also showed loss of thymic cortex from 6 days of illness. Thus, although measles-determined aggregative destruction of thymocytes can cause rapid loss of cortex, the final histological picture of the latter need not necessarily have been preceded by the same type of measles-dependent thymocyte destruction. Although thymocyte aggregation and secondary depletion were the most obvious histological result, a careful quantitation of the medulla and of HassalFs corpuscles showed a small decrease in both tissues in the acute phase. Cases recovering from measles showed a small decrease in the number of Hassall's corpuscles. Measles-specific changes were not found in lymphoid tissues other than the thymus of these cases. ImagesFig. 4Fig. 1Fig. 2Fig. 3Fig. 5 PMID:4701743

  19. The effects of wild thyme (Thymus serpyllum L.) essential oil components against ochratoxin-producing Aspergilli.

    PubMed

    Sokolić-Mihalak, Darja; Frece, Jadranka; Slavica, Anita; Delaš, Frane; Pavlović, Hrvoje; Markov, Ksenija

    2012-12-01

    The aim of this study was to determine the effects of the essential oil of Thymus serpyllum L. and of its components thymol and total phenols (total phenolic content, TPC) extracted from the plant on the growth and mycotoxin production of Aspergillus ochraceus, A. carbonarius, and A. niger. Minimal inhibitory concentration (MIC) determined for the essential oil and thymol, and selected concentration of the TPC extract inhibited fungal growth and ochratoxin A biosynthesis by more than 60 %, depending on the conditions and duration of incubation with the fungi. Essential oil showed the strongest inhibitory effect which may have been related to the synergistic or cumulative effects of its components. PMID:23334040

  20. The effects of wild thyme (Thymus serpyllum L.) essential oil components against ochratoxin-producing Aspergilli.

    PubMed

    Sokolić-Mihalak, Darja; Frece, Jadranka; Slavica, Anita; Delaš, Frane; Pavlović, Hrvoje; Markov, Ksenija

    2012-12-01

    The aim of this study was to determine the effects of the essential oil of Thymus serpyllum L. and of its components thymol and total phenols (total phenolic content, TPC) extracted from the plant on the growth and mycotoxin production of Aspergillus ochraceus, A. carbonarius, and A. niger. Minimal inhibitory concentration (MIC) determined for the essential oil and thymol, and selected concentration of the TPC extract inhibited fungal growth and ochratoxin A biosynthesis by more than 60 %, depending on the conditions and duration of incubation with the fungi. Essential oil showed the strongest inhibitory effect which may have been related to the synergistic or cumulative effects of its components.

  1. The capsule of Bacillus anthracis behaves as a thymus-independent type 2 antigen.

    PubMed

    Wang, Taia T; Lucas, Alexander H

    2004-09-01

    Bacillus anthracis elaborates a homopolymeric capsule composed of gamma-D-glutamic acid residues. Mice were immunized with formalin-fixed encapsulated B. anthracis bacilli, and the serum antibody response to a gamma-D-glutamyl capsular epitope was measured. Antiglutamyl antibodies were elicited in athymic BALB/c Nu/Nu, BALB/c Nu/+, and CBA/J mice but not in CBA/N xid mice. These response patterns define the capsule of B. anthracis as a thymus-independent type 2 antigen.

  2. Thymus and Myasthenia Gravis: what can we learn from DNA microarrays?

    PubMed

    Cizeron-Clairac, Géraldine; Le Panse, Rozen; Frenkian-Cuvelier, Mélinée; Meraouna, Amel; Truffault, Frédérique; Bismuth, Jacky; Mussot, Sacha; Kerlero de Rosbo, Nicole; Berrih-Aknin, Sonia

    2008-09-15

    This review is dedicated to John Newsom-Davis, who was an exceptional colleague and friend, always exchanging ideas with respect and consideration. We shall not forget his involvement and passion in search for the truth on the role of thymectomy in the management of Myasthenia Gravis (MG). In this short review, we shall summarize what we learnt from DNA microarrays applied to MG thymus. We shall focus on three main comparisons of the thymic transcriptomes: 1) highly hyperplastic MG patients versus non-MG adults; 2) corticosteroid-treated versus untreated seropositive MG patients; and 3) seronegative versus seropositive MG patients.

  3. [Effect of thymostimulin on endocrine thymus function in thyroidectomized rats during suppressive hormone therapy].

    PubMed

    Hrinevych, Iu Ia; Bendiuh, H D; Ostapenko, O M

    2003-01-01

    Due to disorders of hormonal balance in the organism, a decrease in thymic endocrine function occurred in rats after thyroidectomy. After removing the thyroid gland, we observed 1,3-2,2-fold decrease in the level of thymic hormone thymulin in the blood serum. When thyroxin was applied at a suppressive dose, endocrine function of the thymus did not restore. Injections of thymostimulin (Tp1) or its combination with thyroxin to thyroidectomized animals restored the level of thymulin up to the level in the intact rats due to effects of either injected preparation or induction of substances possessing thymosine-like activity.

  4. Transient infiltration of neutrophils into the thymus following whole-body X-ray irradiation in IL-10 knockout mice

    SciTech Connect

    Fujiwara, Hiroya; Yamazaki, Takahiro; Uzawa, Akiko; Nagata, Kisaburo; Kobayashi, Yoshiro

    2008-05-02

    IL-10 is known to suppress the inflammatory responses in a variety of experimental models. Because we previously found that whole-body X-irradiation causes massive apoptosis in the thymus and transient infiltration of neutrophils, in this study, we examined whether or not IL-10 is involved in the regulation of neutrophil infiltration upon whole-body X-ray irradiation using IL-10 knockout mice. Although IL-10 was induced in the thymus on whole-body X-ray irradiation, apoptosis of thymocytes, neutrophil infiltration, and MIP-2 and KC production in the thymus were not affected by an IL-10 deficiency. Coculturing of bone marrow-derived macrophages with late apoptotic cells caused MIP-2 production, which was also not affected by an IL-10 deficiency. These results suggest the uniqueness of the inflammatory response induced by whole-body X-ray irradiation, which does not seem to be regulated by IL-10.

  5. [Formation of spontaneous and immune rosettes by the cells of the thymus and other formations of the rabbit lymphoid system].

    PubMed

    Grinevich, Iu A

    1975-11-01

    Only T1--RFC (rosette-forming cells) are revealed in the thymus of nonimmunized rabbits. Their number is 2--2.5 times less than in the palatine tonsils, submaxillary lymph nodes and the spleen. T2--RFC are present in these lymphoid formations. There is an increase in the T1--RFC in the thymus after the intravenous immunization of rabbits with sheep erythrocytes. In other lymphoid formations the correlation of the population of cells of the thymus origin altered as a result of increase in the number of T2--RFC. B--RFC accumulated in considerable amounts. Dynamics of T2 and B--RFC accumulation in the lymphoid formations corresponded to the highest antibody titres in the rabbit blood. In the formation of primary immune response the amount of the T1 and T2-RFC in the formations of rabbit lymphoid system depended on the dose of the antigen. PMID:1221703

  6. The use of imaging technology in the assessment of the fetal inflammatory response syndrome-imaging of the fetal thymus.

    PubMed

    Sciaky-Tamir, Yael; Hershkovitz, Reli; Mazor, Moshe; Shelef, Ilan; Erez, Offer

    2015-05-01

    The fetal inflammatory response syndrome (FIRS) describes a state of extensive fetal multi organ involvement during chorioamnionitis, and is associated with grave implications on perinatal outcome. The syndrome has been linked to the preterm parturition syndrome and is associated with inflammation/infection processes in most of the fetal organs. The fetal thymus, a major organ in the developing immune system involutes during severe neonatal disease and has been shown to be smaller in fetuses with FIRS. Various methods for imaging of the fetal thymus and measurement are described. Currently the only method to diagnose FIRS prenatally is through amniocentesis. We suggest that women who are admitted with preterm labor with intact membranes and those with PPROM should have a detailed sonographic examination of the fetal thymus as a surrogate marker of fetal involvement in intrauterine infection/inflammation processes.

  7. Custom-Made Computer-Aided-Design/Computer-Aided-Manufacturing Biphasic Calcium-Phosphate Scaffold for Augmentation of an Atrophic Mandibular Anterior Ridge

    PubMed Central

    Mangano, Francesco Guido; van Noort, Ric; Apresyan, Samvel; Piattelli, Adriano; Macchi, Aldo

    2015-01-01

    This report documents the clinical, radiographic, and histologic outcome of a custom-made computer-aided-design/computer-aided-manufactured (CAD/CAM) scaffold used for the alveolar ridge augmentation of a severely atrophic anterior mandible. Computed tomographic (CT) images of an atrophic anterior mandible were acquired and modified into a 3-dimensional (3D) reconstruction model; this was transferred to a CAD program, where a custom-made scaffold was designed. CAM software generated a set of tool-paths for the manufacture of the scaffold on a computer-numerical-control milling machine into the exact shape of the 3D design. A custom-made scaffold was milled from a synthetic micromacroporous biphasic calcium phosphate (BCP) block. The scaffold closely matched the shape of the defect: this helped to reduce the time for the surgery and contributed to good healing. One year later, newly formed and well-integrated bone was clinically available, and two implants (AnyRidge, MegaGen, Gyeongbuk, South Korea) were placed. The histologic samples retrieved from the implant sites revealed compact mature bone undergoing remodelling, marrow spaces, and newly formed trabecular bone surrounded by residual BCP particles. This study demonstrates that custom-made scaffolds can be fabricated by combining CT scans and CAD/CAM techniques. Further studies on a larger sample of patients are needed to confirm these results. PMID:26064701

  8. The Prerequisites for Central Tolerance Induction against Citrullinated Proteins in the Mouse

    PubMed Central

    Engelmann, Robby; Biemelt, Andra; Cordshagen, Antje; Johl, Anja; Kuthning, Daniela; Müller-Hilke, Brigitte

    2016-01-01

    Objectives To assess the prerequisites for negative selection of peptidylcitrulline-specific T cells in the thymus. In detail, we here analyzed murine medullary thymic epithelial cells for the expression of peptidylarginine deiminases (PAD) and subsequent citrullination. Methods Medullary thymic epithelial cells were sorted, their mRNA was isolated and the expression of Pad genes was analyzed by quantitative PCR. Citrullination was detected by Western Blot in lysates of sorted medullary thymic epithelial cells and histologically by immunofluorescence of thymic thin sections. Results Pad2 and Pad4 are the main Pad isoforms expressed in mature medullary thymic epithelial cells of the mouse and their levels of expression are comparable to that of insulin (Ins2), another highly and promiscuously expressed protein in the thymus. Citrullination was detected in medullary thymic epithelial cells as shown by Western Blot and immunofluorescence. Conclusions Even though we here show that the murine thymus harbors the prerequisites for central tolerance to PAD and citrullinated peptides, it remains an open question whether the emergence of peptidylcitrulline-specific T cells and of autoantibodies recognizing citrullinated epitopes is caused by a failure of central or peripheral tolerance mechanisms. PMID:27362943

  9. Thymectomy Cures Diabetes Mellitus and Ameliorates Myasthenia Gravis in a Patient with Thymus Hyperplasia and Hyperthyroidism: Report of a Case.

    PubMed

    Feng, Shiyun; Zhang, Yao; Cui, Youbin; Chen, Yu

    2015-12-01

    Myasthenia gravis (MG) is a devastating autoimmune disease that involves the acetylcholine receptor (AchR) in the postsynaptic membrane of the neuromuscular junction. It is not uncommon for MG to accompany with other autoimmune diseases and complicate with multiple organ dysfunction. Here, we report on an 18-year-old female patient with a rare case of MG concomitant with thymus hyperplasia, diabetes mellitus, and hyperthyroidism. After full excision of the hyperplastic thymus gland, the patient's muscle weakness was greatly improved and her blood glucose level was restored to normal at the 6-month follow-up. PMID:26884666

  10. Effect of pesticide bendiocarbamate on distribution of acetylcholine- and butyrylcholine-positive nerves in rabbit's thymus

    PubMed Central

    Dorko, F.; Danko, J.; Flešárová, S.; Boroš, E.; Sobeková, A.

    2011-01-01

    Many pesticides used in agriculture have a negative effect on organisms. The group of hazardous pesticides includes the cholinesterase inhibitor bendiocarbamate. According to literature, bendiocarbamate has relatively low toxicity in mammals and vertebrates in general, since it does accumulate in their tissues and the cholinesterase activity returns to norm within 24 h after acute exposure. The present study focused on the influence of bendiocarbamate on rabbit thymus after its administration at a dose of 5 mg/kg body weight (BW) for the period of 3 months. The thymus was observed for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)-positive nerve fibers visualized by histochemical methods. Microscopic findings of BuChE - positive nerve fibers show the same density and the topography by the experimental and the control animals. On the other hand, AChE - positive nerve fibers in experimental animals after administration of bendiocarbamate is only poorly identified, suggesting that bendiocarbamate inhibits AChE but not BuChE. PMID:22297443

  11. Effect of pesticide bendiocarbamate on distribution of acetylcholine- and butyrylcholine-positive nerves in rabbit's thymus.

    PubMed

    Dorko, F; Danko, J; Flešárová, S; Boroš, E; Sobeková, A

    2011-10-19

    Many pesticides used in agriculture have a negative effect on organisms. The group of hazardous pesticides includes the cholinesterase inhibitor bendiocarbamate. According to literature, bendiocarbamate has relatively low toxicity in mammals and vertebrates in general, since it does accumulate in their tissues and the cholinesterase activity returns to norm within 24 h after acute exposure. The present study focused on the influence of bendiocarbamate on rabbit thymus after its administration at a dose of 5 mg/kg body weight (BW) for the period of 3 months. The thymus was observed for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)-positive nerve fibers visualized by histochemical methods. Microscopic findings of BuChE-positive nerve fibers show the same density and the topography by the experimental and the control animals. On the other hand, AChE-positive nerve fibers in experimental animals after administration of bendiocarbamate is only poorly identified, suggesting that bendiocarbamate inhibits AChE but not BuChE.

  12. Studies on Chemical Composition, Antimicrobial and Antioxidant Activities of Five Thymus vulgaris L. Essential Oils.

    PubMed

    Mancini, Emilia; Senatore, Federica; Del Monte, Donato; De Martino, Laura; Grulova, Daniela; Scognamiglio, Mariarosa; Snoussi, Mejdi; De Feo, Vincenzo

    2015-07-01

    This study is aimed at assessing the essential oil composition, total phenolic content, antimicrobial and antioxidant activities of Thymus vulgaris collected in five different area of the Campania Region, Southern Italy. The chemical composition of the essential oils was studied by GC-flame ionization detector (FID) and GC/MS; the biological activities were evaluated through determination of MIC and minimum bactericidal concentration (MBC) and evaluation of antioxidant activity. In total, 134 compounds were identified. The oils were mainly composed of phenolic compounds, and all oils belonged to the chemotype thymol. The antimicrobial activity of the five oils was assayed against ten bacterial strains. The oils showed different inhibitory activity against some Gram-positive pathogens. The total phenol content in the essential oils ranged from 77.6-165.1 mg gallic acid equivalents (GAE)/g. The results reported here may help to shed light on the complex chemotaxonomy of the genus Thymus. These oils could be used in many fields as natural preservatives of food and as nutraceuticals.

  13. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

    PubMed

    Paltsev, Michael A; Polyakova, Victoria O; Kvetnoy, Igor M; Anderson, George; Kvetnaia, Tatiana V; Linkova, Natalia S; Paltseva, Ekaterina M; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

    2016-03-15

    Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing.

  14. Essential oil composition and preliminary molecular study of four Hungarian Thymus species.

    PubMed

    Pluhár, Zsuzsanna; Kocsis, Marianna; Kuczmog, Anett; Csete, S; Simkó, Hella; Sárosi, Szilvia; Molnár, P; Horváth, Györgyi

    2012-03-01

    Chemical and genetic differences of twenty taxa belonging to four Thymus species were studied in order to determine whether molecular characters and essential oil components could be used as taxonomic markers and to examine the correlation between them. Plant samples, representing different taxa and geographic regions, were collected from experimentally grown populations. Essential oil samples were analysed by GC/MS and cluster analysis of volatile composition resulted in segregation of thymol chemotypes from sesquiterpenic ones. Thymol was characteristic for all the populations of Thymus glabrescens and T. pannonicus as well as for certain taxa belonging to T. praecox and T. pulegioides. Sesquiterpenes occurred in only two taxa of T. glabrescens, in each sample of T. praecox and in three taxa of T. pulegioides. Plant samples were analysed by random amplified polymorphic DNA (RAPD). The obtained dendrogram revealed high gene diversity. The 13 primers resulted 114 polymorphic RAPD bands, and the average percentage of polymorphism was 80.8%. The RAPD dendogram showed separation neither at interspecific nor at interpopulational levels. Therefore, further specific molecular studies involving more taxa are suggested. Partial correlation have been found between molecular and chemical assessments. PMID:22453802

  15. Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation.

    PubMed

    Figueiredo, Marta; Silva, Joana Clara; Santos, Ana Sofia; Proa, Vitor; Alcobia, Isabel; Zilhão, Rita; Cidadão, António; Neves, Hélia

    2016-10-15

    The avian thymus and parathyroids (T/PT) common primordium derives from the endoderm of the third and fourth pharyngeal pouches (3/4PP). The molecular mechanisms that govern T/PT development are not fully understood. Here we study the effects of Notch and Hedgehog (Hh) signalling modulation during common primordium development using in vitro, in vivo and in ovo approaches. The impairment of Notch activity reduced Foxn1/thymus-fated and Gcm2/Pth/parathyroid-fated domains in the 3/4PP and further compromised the development of the parathyroid glands. When Hh signalling was abolished, we observed a reduction in the Gata3/Gcm2- and Lfng-expression domains at the median/anterior and median/posterior territories of the pouches, respectively. In contrast, the Foxn1 expression-domain at the dorsal tip of the pouches expanded ventrally into the Lfng-expression domain. This study offers novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner. PMID:27544844

  16. Analgesic, anti-inflammatory and anti-pyretic activities of Thymus linearis.

    PubMed

    Qadir, Muhammad Imran; Parveen, Amna; Abbas, Khizar; Ali, Muhammad

    2016-03-01

    The present study was aimed to investigate the antipyretic, analgesic and anti-inflammatory activity of aqueous methanolic and n-hexane extract of Thymus linearis. For measuring analgesic activity, writhing test, hot plate method and formalin test were performed and abdominal writhing was induced by intra-peritoneal injection of 0.2 ml of 3% acetic acid. While in formalin test, pain was experimentally induced by injecting 25 μl of 2.5% formalin in left hind paw. In hot plate method, pain was induced thermally by keeping the animals on a hot plate with temperature of about 51°C. Anti-inflammatory activity was assessed by carrageenan induced mice paw edema. For determination of antipyretic activity, pyrexia was induced by subcutaneous injection of 15% yeast. The results showed that both the extracts had significant analgesic activity (p<0.05); anti-inflammatory activity (p<0.05) and anti-pyretic activity (p<0.05). Therefore, it was concluded from this study that the extracts of Thymus linearis may be used against pain, pyrexia and inflammation.

  17. Unravelling the complex antimicrobial interactions of essential oils--the case of Thymus vulgaris (thyme).

    PubMed

    Ahmad, Aijaz; van Vuuren, Sandy; Viljoen, Alvaro

    2014-03-06

    Thymus vulgaris has gained tremendous popularity as an ornamental, culinary herb and its use in phytotherapy is well established and supported in the literature. The objective of this study was to explore possible interactions between selected molecules within Thymus vulgaris essential oil (TvEO) to gain a better understanding of how this complex essential oil exerts its antimicrobial activity. Evaluation of the antimicrobial efficacy and interactions were assessed on the essential oil and volatile constituents against various pathogens. Interactions between molecules at various ratios were graphically observed through the construction of isobolograms. Gas chromatography-mass spectrometry (GC-MS) analysis revealed 22 compounds which collectively represent >95% of the oil composition. Based on their minimum inhibitory concentration (MIC) values, they were categorised into weak (≥4 mg mL⁻¹), moderate (2-4 mg mL⁻¹) and noteworthy active (≤2 mg mL⁻¹) compounds. For the combination study, 21% synergistic, 42% additive, 36% indifferent and 1% antagonistic interactions were observed. Most of the interactions were observed between the weak and highly active molecules, and interestingly, no synergistic interaction was observed between the highly active compounds. Synergistic and additive interactions between the strong and weaker antimicrobial constituents present in TvEO enhance the antimicrobial efficacy of this commercially important essential oil.

  18. Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation.

    PubMed

    Figueiredo, Marta; Silva, Joana Clara; Santos, Ana Sofia; Proa, Vitor; Alcobia, Isabel; Zilhão, Rita; Cidadão, António; Neves, Hélia

    2016-10-15

    The avian thymus and parathyroids (T/PT) common primordium derives from the endoderm of the third and fourth pharyngeal pouches (3/4PP). The molecular mechanisms that govern T/PT development are not fully understood. Here we study the effects of Notch and Hedgehog (Hh) signalling modulation during common primordium development using in vitro, in vivo and in ovo approaches. The impairment of Notch activity reduced Foxn1/thymus-fated and Gcm2/Pth/parathyroid-fated domains in the 3/4PP and further compromised the development of the parathyroid glands. When Hh signalling was abolished, we observed a reduction in the Gata3/Gcm2- and Lfng-expression domains at the median/anterior and median/posterior territories of the pouches, respectively. In contrast, the Foxn1 expression-domain at the dorsal tip of the pouches expanded ventrally into the Lfng-expression domain. This study offers novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner.

  19. Studies on Chemical Composition, Antimicrobial and Antioxidant Activities of Five Thymus vulgaris L. Essential Oils.

    PubMed

    Mancini, Emilia; Senatore, Federica; Del Monte, Donato; De Martino, Laura; Grulova, Daniela; Scognamiglio, Mariarosa; Snoussi, Mejdi; De Feo, Vincenzo

    2015-01-01

    This study is aimed at assessing the essential oil composition, total phenolic content, antimicrobial and antioxidant activities of Thymus vulgaris collected in five different area of the Campania Region, Southern Italy. The chemical composition of the essential oils was studied by GC-flame ionization detector (FID) and GC/MS; the biological activities were evaluated through determination of MIC and minimum bactericidal concentration (MBC) and evaluation of antioxidant activity. In total, 134 compounds were identified. The oils were mainly composed of phenolic compounds, and all oils belonged to the chemotype thymol. The antimicrobial activity of the five oils was assayed against ten bacterial strains. The oils showed different inhibitory activity against some Gram-positive pathogens. The total phenol content in the essential oils ranged from 77.6-165.1 mg gallic acid equivalents (GAE)/g. The results reported here may help to shed light on the complex chemotaxonomy of the genus Thymus. These oils could be used in many fields as natural preservatives of food and as nutraceuticals. PMID:26140436

  20. Interaction of a copper (II) complex containing an artificial sweetener (aspartame) with calf thymus DNA.

    PubMed

    Shahabadi, Nahid; Khodaei, Mohammad Mehdi; Kashanian, Soheila; Kheirdoosh, Fahimeh

    2014-01-01

    A copper (II) complex containing aspartame (APM) as ligand, Cu(APM)2Cl2⋅2H2O, was synthesized and characterized. In vitro binding interaction of this complex with native calf thymus DNA (CT-DNA) was studied at physiological pH. The interaction was studied using different methods: spectrophotometric, spectrofluorometric, competition experiment, circular dichroism (CD) and viscosimetric techniques. Hyperchromicity was observed in UV absorption band of Cu(APM)2Cl2⋅2H2O. A strong fluorescence quenching reaction of DNA to Cu(APM)2Cl2⋅2H2O was observed and the binding constants (Kf) and corresponding numbers of binding sites (n) were calculated at different temperatures. Thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS) were calculated to be+89.3 kJ mol(-1) and+379.3 J mol(-1) K(-1) according to Van't Hoff equation which indicated that reaction is predominantly entropically driven. Experimental results from spectroscopic methods were comparable and further supported by viscosity measurements. We suggest that Cu(APM)2Cl2⋅2H2O interacts with calf thymus DNA via a groove interaction mode with an intrinsic binding constant of 8×10+4 M(-1). Binding of this copper complex to DNA was found to be stronger compared to aspartame which was studied recently.

  1. Increased generation of Foxp3(+) regulatory T cells by manipulating antigen presentation in the thymus.

    PubMed

    Lin, Jiqiang; Yang, Lu; Silva, Hernandez Moura; Trzeciak, Alissa; Choi, Yongwon; Schwab, Susan R; Dustin, Michael L; Lafaille, Juan J

    2016-01-01

    Regulatory T-cell (Treg) selection in the thymus is essential to prevent autoimmune diseases. Although important rules for Treg selection have been established, there is controversy regarding the degree of self-reactivity displayed by T-cell receptors expressed by Treg cells. In this study we have developed a model of autoimmune skin inflammation, to determine key parameters in the generation of skin-reactive Treg cells in the thymus (tTreg). tTreg development is predominantly AIRE dependent, with an AIRE-independent component. Without the knowledge of antigen recognized by skin-reactive Treg cells, we are able to enhance skin-specific tTreg cell generation using three approaches. First, we increase medullary thymic epithelial cells by using mice lacking osteoprotegerin or by adding TRANCE (RANKL, Tnfsf11). Second, we inject intrathymically peripheral dendritic cells from skin-draining sites. Finally, we inject skin tissue lysates intrathymically. These findings have implications for enhancing the generation of organ-specific Treg cells in autoimmune diseases. PMID:26923114

  2. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

    PubMed

    Paltsev, Michael A; Polyakova, Victoria O; Kvetnoy, Igor M; Anderson, George; Kvetnaia, Tatiana V; Linkova, Natalia S; Paltseva, Ekaterina M; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

    2016-03-15

    Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing. PMID:26943046

  3. Split tolerance in nude mice transplanted with 2'-deoxyguanosine-treated allogeneic thymus lobes

    SciTech Connect

    Suzuki, G.; Moriyama, T.; Takeuchi, Y.; Kawase, Y.; Habu, S.

    1989-03-01

    To elucidate the acquisition of self tolerance in the thymus, full-allogeneic thymic chimeras were constructed. Athymic C3H and BALB/c nude mice were reconstituted with the thymic lobes of BALB/c and B10.BR fetuses, respectively, that were organ cultured for 5 days in the presence of 2'-deoxyguanosine. T cells in these chimeras were tolerized to the host MHC in both MLR and CTL assays. In contrast, T cells in the chimeras exhibited split tolerance for the thymic MHC haplotype. CTL specific for class I MHC of the thymic haplotype were generated not only from the peripheral T cells of the chimeras but also from thymocytes re-populated in the engrafted thymic lobes. However, T cells in these chimeras responded poorly to the class II MHC of the thymic haplotype in a standard MLR assay. In a syngeneic MLR culture upon stimulation with enriched APC of the thymic haplotype, only 22 to 48% of the responses were mediated by CD4+ cells, and proliferations of CD4- cells were prominent. There were no haplotype-specific suppressor cells detected which would cause the unresponsiveness to the thymic class II MHC. These results indicated that the thymic lobes treated with 2'-deoxyguanosine were defective in the ability to induce the transplantation tolerance for the class I MHC expressed on the thymus, although the same thymic lobes were able to induce the transplantation tolerance for the thymic class II MHC.

  4. Thymus Daenensis Extract and Essential Oils Effects on Morphine Withdrawal Signs in Mice

    PubMed Central

    Khodayar, Mohammad Javad; Taherzadeh, Esmaeil; Siahpoosh, Amir; Mansourzadeh, Zahra; Tabatabaei, Seyed Amir Hossein

    2014-01-01

    Background: Thymus species are well known medicinal plants which the previous studies suggested the involvement of the opioid system in them. Objectives: This study aimed to investigate the effects of methanolic extract and essential oil of aerial parts of Thymus daenensis (TD), an endemic aromatic medicinal plant of Iran, on morphine withdrawal syndrome in mice. Materials and Methods: Experiments were performed in two groups of five, each group treated with extracts or essential oils of TD. Dependency was induced by subcutaneous injection of morphine for three consecutive days. On the fourth day, the last dose of morphine was injected two hours prior to intraperitoneal injection of naloxone while the extract or essential oil of TD was administered 30 minutes before naloxone. A period of 20 minutes after naloxone injection was considered the critical period of the withdrawal syndrome. The number of jumps, standing, leaning, and the weight of stools were recorded as withdrawal signs. Results: The 200 mg/kg and 400 mg/kg doses of extract and all doses of essential oil decreased significantly the number of jumps, standing, leaning and the weight of stool. Administration of 100 mg/kg of extract only decreased the weight of stool and had no effect on the other factors. Conclusions: Extract and essential oil of TD attenuates morphine withdrawal behaviors in mice and may be useful in alleviating the signs and symptoms of opiate withdrawal syndrome in human. PMID:25237649

  5. T Cell/Histiocyte-Rich Large B Cell Lymphoma of the Thymus: A Diagnostic Pitfall

    PubMed Central

    Xu, Jie; Wu, Xiaojun; Reddy, Vishnu

    2016-01-01

    T cell/histiocyte-rich large B cell lymphoma (THRLBCL) is predominantly a nodal disease, with extranodal involvement, such as bone marrow, spleen, and liver. However, primary THRLBCL has never been reported in the thymus in the English literature. Here we report a case of THRLBCL presenting as mediastinal mass and lymphadenopathy. Based on the frozen section diagnosis of “thymoma,” a 12 cm mass was excised. A year later she developed multiple enlarged lymph nodes and pulmonary nodules. Consultant review of the excised mediastinal mass showed scattered large atypical cells that were CD20+ and PAX-5+ and negative for pan-cytokeratin, AE1, and AE3, compatible with THRLBCL and excluding thymoma. The excised lymph nodes were replaced by diffuse infiltrate of small CD3+ lymphocytes and histiocytes with intermingled large CD20+ B lymphoma cells scattered throughout the section. A diagnosis of THRLBCL was made in lymph node, similar to previous thymic lesion. A clonal rearrangement of immunoglobulin heavy chain (IGH) gene was detected, further supporting the diagnosis. This is the first reported case of THRLBCL in thymus. Correct recognition of this entity is critical, because of the difference in therapeutic impact on these patients. PMID:26904321

  6. Affinity maturation of lymphocyte receptors and positive selection of T cells in the thymus.

    PubMed

    Steele, E J; Rothenfluh, H S; Ada, G L; Blanden, R V

    1993-10-01

    In this review we have re-evaluated the dominant paradigm that TcR V genes do not somatically mutate. We highlight the many structural and functional similarities between Ig and TcR antigen-specific receptors on B and T cells. We have reviewed the factors influencing the somatic and germline evolution of IgV regions in B cells, have evaluated in detail various models which could be invoked to explain the pattern of variation in both transcribed and non-transcribed segments of germline IgV-gene DNA sequences, and applied this perspective to the TcR V beta and V alpha genes. Whilst specific TcRs recognize a complex of a short antigenic peptide bound to MHC Class I or II glycoprotein, and Ig receptors can recognize both oligopeptides and conformational determinants on undegraded polypeptides, they both employ heterodimer variable regions (Fabs) utilizing all three CDRs in epitope binding. We conclude that a plausible case can be made for the possibility that rearranged TcR V genes may undergo some type of somatic hypermutation process during T-cell development in the thymus (concurrent with or after the positive selection phase) thus allowing a repertoire of TvR alpha beta heterodimers to be both positively and negatively selected by the same set of ligands (self MHC + self peptide) in the thymus.

  7. Inhibitory effects of Iranian Thymus vulgaris extracts on in vitro growth of Entamoeba histolytica.

    PubMed

    Behnia, Maryam; Haghighi, Ali; Komeylizadeh, Hossein; Tabaei, Seyyed-Javadi Seyyed; Abadi, Alireza

    2008-09-01

    One of the most common drugs used against a wide variety of anaerobic protozoan parasites is metronidazole. However, this drug is mutagenic for bacteria and is a potent carcinogen for rodents. Thymus vulgaris is used for cough suppression and relief of dyspepsia. Also it has antibacterial and antifungal properties. The aim of this study was to investigate antiamebic effect of Thymus vulgaris against Entamoeba histolytica in comparison with metronidazole. One hundred gram air-dried T. vulgaris plant was obtained and macerated at 25 degrees C for 14 days using n-hexane and a mixture of ethanol and water. For essential oil isolation T. vulgaris was subjected to hydrodistillation using a clevenger-type apparatus for 3 hr. E. histolytica, HM-1: IMSS strain was used in all experiments. It was found that the minimal inhibitory concentration (MIC) for T. vulgaris hydroalcoholic, hexanic extracts, and the essential oil after 24 hr was 4 mg/mL, 4 mg/mL, and 0.7 mg/mL, respectively. After 48 hr the MIC for T. vulgaris hydroalcoholic and hexanic extracts was 3 and 3 mg/mL, respectively. Therefore, it can be concluded that the Iranian T. vulgaris is effective against the trophozoites of E. histolytica.

  8. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging

    PubMed Central

    Paltsev, Michael A.; Polyakova, Victoria O.; Kvetnoy, Igor M.; Anderson, George; Kvetnaia, Tatiana V.; Linkova, Natalia S.; Paltseva, Ekaterina M.; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

    2016-01-01

    Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin A); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing. PMID:26943046

  9. Analgesic, anti-inflammatory and anti-pyretic activities of Thymus linearis.

    PubMed

    Qadir, Muhammad Imran; Parveen, Amna; Abbas, Khizar; Ali, Muhammad

    2016-03-01

    The present study was aimed to investigate the antipyretic, analgesic and anti-inflammatory activity of aqueous methanolic and n-hexane extract of Thymus linearis. For measuring analgesic activity, writhing test, hot plate method and formalin test were performed and abdominal writhing was induced by intra-peritoneal injection of 0.2 ml of 3% acetic acid. While in formalin test, pain was experimentally induced by injecting 25 μl of 2.5% formalin in left hind paw. In hot plate method, pain was induced thermally by keeping the animals on a hot plate with temperature of about 51°C. Anti-inflammatory activity was assessed by carrageenan induced mice paw edema. For determination of antipyretic activity, pyrexia was induced by subcutaneous injection of 15% yeast. The results showed that both the extracts had significant analgesic activity (p<0.05); anti-inflammatory activity (p<0.05) and anti-pyretic activity (p<0.05). Therefore, it was concluded from this study that the extracts of Thymus linearis may be used against pain, pyrexia and inflammation. PMID:27087102

  10. A human postnatal lymphoid progenitor capable of circulating and seeding the thymus.

    PubMed

    Six, Emmanuelle M; Bonhomme, Delphine; Monteiro, Marta; Beldjord, Kheira; Jurkowska, Monika; Cordier-Garcia, Corinne; Garrigue, Alexandrine; Dal Cortivo, Liliane; Rocha, Benedita; Fischer, Alain; Cavazzana-Calvo, Marina; André-Schmutz, Isabelle

    2007-12-24

    Identification of a thymus-seeding progenitor originating from human bone marrow (BM) constitutes a key milestone in understanding the mechanisms of T cell development and provides new potential for correcting T cell deficiencies. We report the characterization of a novel lymphoid-restricted subset, which is part of the lineage-negative CD34(+)CD10(+) progenitor population and which is distinct from B cell-committed precursors (in view of the absence of CD24 expression). We demonstrate that these Lin(-)CD34(+)CD10(+)CD24(-) progenitors have a very low myeloid potential but can generate B, T, and natural killer lymphocytes and coexpress recombination activating gene 1, terminal deoxynucleotide transferase, PAX5, interleukin 7 receptor alpha, and CD3epsilon. These progenitors are present in the cord blood and in the BM but can also be found in the blood throughout life. Moreover, they belong to the most immature thymocyte population. Collectively, these findings unravel the existence of a postnatal lymphoid-polarized population that is capable of migrating from the BM to the thymus.

  11. Concentration of antioxidant polyphenols from Thymus capitatus extracts by membrane process technology.

    PubMed

    Achour, Sami; Khelifi, Eltaief; Attia, Yesmine; Ferjani, Ezzeddine; Noureddine Hellal, Ahmed

    2012-06-01

    Thymus capitatus is a Mediterranean plant characterized by its antioxidant polyphenols of which the most known are the carnosic and rosmarinic acids. In this way, this study aims to concentrate these acids by membrane processes. The thyme essential oil composition was established by capillary GC-MS and 27 components were identified representing 98.93%± 1.97% of total oils. The antioxidant test for permeate and retentate of methanolic and aqueous extract were determined using 3 types of membranes. The results showed that the synthetic NF membrane is able to trap and concentrate phenolic compounds in the retentate much better than the NF commercial and UF synthetic membrane. The results of the total phenolic content (TPC) showed a significant value of the polyphenol content present in the aqueous extract with 175.53 mg Gallic Acid Equivalents (GAE)/g of extract. The spectrum of the aqueous extract of Thymus capitatus showed the presence of 3 visible peaks, the 1st one at 217 nm corresponding to the carnosic acid, the 2nd one at 277 nm for essential oils, and the last one at 326 nm attributed to the rosmarinic acid. The commercial membrane NF-DK succeeded to concentrate rosmarinic acid and can be considered as a stage towards the concentration of this product with a high added value. PMID:22612548

  12. Evaluation of the antioxidant capacity and phenolic content of three Thymus species.

    PubMed

    Nickavar, Bahman; Esbati, Naser

    2012-06-01

    Thymus species are known to have significant amounts of phenolic and flavonoid compounds and exhibit strong antioxidant activities. This work was designed to evaluate the antioxidant activities of three endemic Iranian Thymus species (including T. daenensis, T. kotschyanus, and T. pubescens) in different test systems [namely DPPH() (2,2'-diphenyl-1-picrylhydrazyl), ABTS(+) [2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid], and linoleic acid/β-carotene bleaching assays] to determine the total phenolic and flavonoid contents of the species (assayed by colorimetric techniques) and to study the possible composition-activity relationship. All the tested plants exhibited concentration-dependent antioxidant and free radical scavenging activities. T. pubescens showed the highest free radical scavenging activities in both DPPH() and ABTS(+) methods, while T. daenensis and T. kotschyanus were the most active species in the β-carotene bleaching inhibition test. Alternatively, T. pubescens exhibited a significantly higher level of the total flavonoid content compared with those of the other species, while no significant statistically differences were found among the tested plants regarding the total phenolic content. In addition, significant correlations were found between the flavonoid content and DPPH()/ABTS(+) radical scavenging activities, but not between the β-carotene bleaching inhibition system and the flavonoid content. PMID:22682273

  13. Unravelling the complex antimicrobial interactions of essential oils--the case of Thymus vulgaris (thyme).

    PubMed

    Ahmad, Aijaz; van Vuuren, Sandy; Viljoen, Alvaro

    2014-01-01

    Thymus vulgaris has gained tremendous popularity as an ornamental, culinary herb and its use in phytotherapy is well established and supported in the literature. The objective of this study was to explore possible interactions between selected molecules within Thymus vulgaris essential oil (TvEO) to gain a better understanding of how this complex essential oil exerts its antimicrobial activity. Evaluation of the antimicrobial efficacy and interactions were assessed on the essential oil and volatile constituents against various pathogens. Interactions between molecules at various ratios were graphically observed through the construction of isobolograms. Gas chromatography-mass spectrometry (GC-MS) analysis revealed 22 compounds which collectively represent >95% of the oil composition. Based on their minimum inhibitory concentration (MIC) values, they were categorised into weak (≥4 mg mL⁻¹), moderate (2-4 mg mL⁻¹) and noteworthy active (≤2 mg mL⁻¹) compounds. For the combination study, 21% synergistic, 42% additive, 36% indifferent and 1% antagonistic interactions were observed. Most of the interactions were observed between the weak and highly active molecules, and interestingly, no synergistic interaction was observed between the highly active compounds. Synergistic and additive interactions between the strong and weaker antimicrobial constituents present in TvEO enhance the antimicrobial efficacy of this commercially important essential oil. PMID:24662066

  14. EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus.

    PubMed

    Alfaro, David; García-Ceca, Javier; Farias-de-Oliveira, Desio A; Terra-Granado, Eugenia; Montero-Herradón, Sara; Cotta-de-Almeida, Vinicius; Savino, Wilson; Zapata, Agustín

    2015-12-01

    Adult thymuses lacking either ephrin type B receptor 2 (EphB2) or EphB3, or expressing a truncated form of EphB2, the forward signal-deficient EphB2LacZ, have low numbers of early thymic progenitors (ETPs) and are colonized in vivo by reduced numbers of injected bone marrow (BM) lineage-negative (Lin(-)) cells. Hematopoietic progenitors from these EphB mutants showed decreased capacities to colonize wild type (WT) thymuses compared with WT precursors, with EphB2(-/-) cells exhibiting the greatest reduction. WT BM Lin(-) cells also showed decreased colonizing capacity into mutant thymuses. The reduction was also more severe in EphB2(-/-) host thymuses, with a less severe phenotype in the EphB2LacZ thymus. These results suggest a major function for forward signaling through EphB2 and, to a lesser extent, EphB3, in either colonizing progenitor cells or thymic stromal cells, for in vivo adult thymus recruitment. Furthermore, the altered expression of the molecules involved in thymic colonization that occurs in the mutant thymus correlates with the observed colonizing capacities of different mutant mice. Reduced production of CCL21 and CCL25 occurred in the thymus of the 3 EphB-deficient mice, but their expression, similar to that of P-selectin, on blood vessels, the method of entry of progenitor cells into the vascular thymus, only showed a significant reduction in EphB2(-/-) and EphB3(-/-) thymuses. Decreased migration into the EphB2(-/-) thymuses correlated also with reduced expression of both ephrinB1 and ephrinB2, without changes in the EphB2LacZ thymuses. In the EphB3(-/-) thymuses, only ephrinB1 expression appeared significantly diminished, confirming the relevance of forward signals mediated by the EphB2-ephrinB1 pair in cell recruitment into the adult thymus.

  15. Studies on rat and human thymus to demonstrate immunoreactivity of calcitonin gene-related peptide, tyrosine hydroxylase and neuropeptide Y

    PubMed Central

    KRANZ, ANDREA; KENDALL, MARION D.; VON GAUDECKER, BRITA

    1997-01-01

    The peptidergic and noradrenergic innervation of rat and human thymus was investigated by immunohistochemistry at the light and electron microscopical level (avidin-biotin-complex, sucrose-phosphate-glyoxylic-acid, and immunogold techniques). The distribution of noradrenergic neural profiles, and positive immunoreactivity for calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH) and neuropeptide Y (NPY) is described in female rats during ageing, and in human children. In the neonatal rat thymus, the arteries and septa are well supplied by fine varicose nerves. In older animals (2 wk–1 y) the number of septa and blood vessels increase and consequently also the innervation. No nerves were found in the cortex. Apart from the innervation of the septal areas, immunoreactivity for CGRP and TH was present in thymic cells. Except for the young rats (neonatal–14 d), all rats showed CGRP positivity in subcapsular/perivascular epithelial cells (type 1 cells). All rat thymuses also contained a few TH positive cells in the medulla, which could only be confirmed as epithelial cells (type 6 cells) in children. Type 1 cells in the human thymus were not CGRP positive, but as in the rat, there were similar TH positive cells in the medulla. It was concluded that in addition to nerves containing CGRP, noradrenaline or dopamine, epithelial cells also contain these transmitters. They could therefore act on different cells (compared with neural targets) in a paracrine manner. PMID:9419001

  16. Expression of T cell antigen receptor genes in the thymus of irradiated mice after bone marrow transplantation

    SciTech Connect

    Matsuzaki, G.; Yoshikai, Y.; Kishihara, K.; Nomoto, K.

    1988-01-15

    Sequential appearance of the expression of T cell antigen receptor genes was investigated in the thymus of irradiated mice at the early stage after transplantation of Thy-1 congeneic H-2 compatible allogeneic bone marrow cells. The first cells to repopulate the thymus on day 7 after bone marrow transplantation were intrathymic radioresistant T cell precursors, which expanded mainly to CD4+CD8+ host-type thymocytes by day 14. A high level of gamma gene expression but a much reduced level of alpha and beta gene expression were detected in the host-type thymocytes on day 7. During regeneration of these cells, gamma-chain messages fell to low level and alpha and beta mRNA levels increased. The thymus of the recipients began to be repopulated by donor-derived T cells about 2 wk after bone marrow transplantation and was almost completely replaced by the third week. An ordered expression of gamma then beta and alpha-chain gene transcript was also observed in the donor-type thymocytes at the early stage after bone marrow transplantation. The use of thymocytes at early stage in whole-body irradiated bone marrow chimera provides a pertinent source for investigating the molecular mechanism of T cell differentiation in adult thymus.

  17. A study on aromatic profiles of Thymus hyemalis and Spanish T. vulgaris essential oils at five physiological stages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Shrubs of clonal selections of Thymus hyemalis L. and Spanish T. vulgaris subsp. vulgaris were harvested at five phenological stages during the plant growing cycle: vegetative (VEG), floral (FL), floral-fructification (FL-FR), fructification (FR), and passed fructification (FR-pas). The volatile pro...

  18. The inhibitory effect of Thymus vulgaris extracts on the planktonic form and biofilm structures of six human pathogenic bacteria

    PubMed Central

    Mohsenipour, Zeinab; Hassanshahian, Mehdi

    2015-01-01

    Objective: Microorganisms are responsible for many problems in industry and medicine because of biofilm formation. Therefore, this study was aimed to examine the effect of Thymus vulgaris (T. vulgaris) extracts on the planktonic form and biofilm structures of six pathogenic bacteria. Materials and methods: Antimicrobial activities of the plant extracts against the planktonic form of the bacteria were determined using the disc diffusion method. MIC and MBC values were evaluated using macrobroth dilution technique. Anti-biofilm effects were assessed by microtiter plate method. Results: According to disc diffusion test (MIC and MBC), the ability of Thymus vulgaris (T. vulgaris ) extracts for inhibition of bacteria in planktonic form was confirmed. In dealing with biofilm structures, the inhibitory effect of the extracts was directly correlated to their concentration. Except for the inhibition of biofilm formation, efficacy of each extract was independent from type of solvent. Conclusion: According to the potential of Thymus vulgaris (T. vulgaris) extracts to inhibit the test bacteria in planktonic and biofilm form, it can be suggested that Thymus vulgaris (T. vulgaris) extracts can be applied as antimicrobial agents against the pathogenic bacteria particularly in biofilm forms. PMID:26442753

  19. [Changes of the thymus gland in patients operated for myasthenia in dependence on the blood grouping and Rh-factor].

    PubMed

    Peliukhovskiĭ, S V

    2006-02-01

    In 1974-2001 yrs there were examined 250 patients with various forms of myasthenia, of them in 95 (38%) the dependence of thymus gland changes from the blood grouping and Rh-factor presence was studied. The blood group in 39 (41%) of patients was A (II) Rh+ and in 22% - 0 (I).

  20. Influence of spaceflight on the production of interleukin-3 and interleukin-6 by rat spleen and thymus cells

    NASA Technical Reports Server (NTRS)

    Miller, Edwin S.; Koebel, D. Anne; Sonnefeld, Gerald

    1995-01-01

    Six adult male Sprague-Dawley rats were flown on the 7-day US space shuttle mission STS-54. After flight, the spleen and thymus from each animal were assayed for the capacity to secrete the cytokines interleukin-3 (IL-3) and IL-6. Spleen and thymus cells were incubated for 48 h in the presence of 5 microgram/ml of concanavalin A or 2 microgram/ml of bacterial lipopolysaccharide to stimulate the production of IL-3 and IL-6. IL-3 activity was measured using the IL-3/colony-stimulating-factor-dependent cell line 32D. IL-6 activity was measured using the IL-6-dependent cell line 7TD1. Spleen and thymus cells harvested from flown rats secreted significantly higher titers of biologically active IL-3 compared with ground control rats. Spaceflight significantly enhanced IL-6 production by thymus, but not spleen, cells. The results of this study demonstrate that spaceflight can enhance the production of certain cytokines by cells of the immune system.

  1. Exploration of binding of bisphenol A and its analogues with calf thymus DNA by optical spectroscopic and molecular docking methods.

    PubMed

    Wang, Yan-Qing; Zhang, Hong-Mei

    2015-08-01

    Bisphenol A and its analogues have carcinogenic potentials and toxicities. However, there are lacks of studies elucidating gene toxic interactions of bisphenols with DNA. In this work, the binding modes of five bisphenol compounds with calf thymus DNA were characterized. The multi-spectroscopic experimental results indicated that the fluorescence quenching of bisphenols by calf thymus DNA point to groove binding. The ultraviolet visible and circular dichroism spectral data displayed that bisphenols partly induced conformational changes of calf thymus DNA. In addition, the binding constants of bisphenol A, diphenolic acid, bisphenol AF, bisphenol AP, bisphenol fluorine with calf thymus DNA obtained from fluorescence emission spectra were 1.09×10(4), 3.65×10(4), 4.46×10(4), 1.69×10(4), 4.49×10(4)Lmol(-1) at 298.15K, which indicated that the multi-noncovalent binding forces were involved in the binding processes. In silico investigations indicated that DNA has the preferable binding sites binding with bisphenols by minor groove binding and electrons transfer from DNA bases to bisphenols occurred. In addition, the structural differences of these five bisphenols partly affected the binding ability of them with DNA.

  2. A comparative study of toluidine blue-mediated photodynamic therapy versus topical corticosteroids in the treatment of erosive-atrophic oral lichen planus: a randomized clinical controlled trial.

    PubMed

    Jajarm, Hasan Hoseinpour; Falaki, Farnaz; Sanatkhani, Majid; Ahmadzadeh, Meysam; Ahrari, Farzaneh; Shafaee, Hooman

    2015-07-01

    Recently, photodynamic therapy (PDT) has been suggested as a new treatment option that is free from side effects for erosive-atrophic oral lichen planus (OLP). The purpose of this study was to compare the effect of toluidine blue-mediated photodynamic therapy (TB-PDT) with local corticosteroids on treatment of erosive-atrophic OLP. In this randomized clinical trial, 25 patients with keratotic-atrophic-erosive oral lichen planus were allocated randomly into two groups. Group 1 (experimental): topical application of toluidine blue with micropipette was applied, and after 10 min, the patients were treated with a 630-nm GaAlAs laser (power density: 10 mW/cm(2)) during two visits. Group 2 (control) used mouthwash diluted with dexamethasone (tab 0/5 in 5 ml water) for 5 min, and then, it was spat out, and after 30 min, the mouth was rinsed with 30 drops of nystatin 100,000 units for 5 min and again spat out. Demographic data, type, and severity of the lesions and pain were recorded before and after treatment and then at the 1-month follow-up visit. Response rate was defined based on changes in intensity of the lesions and pain. In the experimental and control groups, sign scores of changes significantly reduced after treatment respectively (p = 0.021) and (p = 0.002), but between the two groups, no significant difference was observed (p = 0.72). In the experimental (p = 0.005) and control groups (p = 0.001), the intensity of lesions significantly reduced after treatment and there was a significant difference between the two groups (p = 0.001). The mean amount of improvement in pain was significantly greater in the control group compared with the experimental group (p < 0.001) (α = 0.05). Our study showed that TB-PDT with laser was effective in the management of OLP.

  3. Mouse Curve Biometrics

    SciTech Connect

    Schulz, Douglas A.

    2007-10-08

    A biometric system suitable for validating user identity using only mouse movements and no specialized equipment is presented. Mouse curves (mouse movements with little or no pause between them) are individually classied and used to develop classication histograms, which are representative of an individual's typical mouse use. These classication histograms can then be compared to validate identity. This classication approach is suitable for providing continuous identity validation during an entire user session.

  4. Building a Brainier Mouse.

    ERIC Educational Resources Information Center

    Tsien, Joe Z.

    2000-01-01

    Describes a genetic engineering project to build an intelligent mouse. Cites understanding the molecular basis of learning and memory as a very important step. Concludes that while science will never create a genius mouse that plays the stock market, it can turn a mouse into a quick learner with a better memory. (YDS)

  5. In-vitro assessment of antioxidant and antimicrobial activities of methanol extracts and essential oil of Thymus hirtus sp. algeriensis

    PubMed Central

    2014-01-01

    Background Owing to the complexity of the antioxidant materials and their mechanism of actions, it is obvious that no single testing method is capable of providing a comprehensive picture of the antioxidant profile. The essential oil of the Thymus specie may still possess other important activities in traditional medicine, it can be used in the treatment of fever and cough. This essential oil may also have an anticancer activity. Methods The essential oils aerial parts hydrodistilled from Thymus hirtus sp. algeriensis, were characterised by GC/MS analysis and the methanolic extracts were chemically characterized by HPLC method. The essence of thyme was evaluated for its antioxidant and antibacterial activity. Result The Terpinen-4-ol are the principal class of metabolites (33.34%) among which 1.8-cineole (19.96%) and camphor (19.20%) predominate. In this study, quantitative values of antioxidant activity of crude methanolic extracts of Thymus hirtus sp. algeriensis were investigated. The essential oils was screened for their antibacterial activity against six common pathogenic microorganisms (Escherichia coli, Pseudomonas aeruginosa, Salmonella enteridis, Staphylococcus aureus, Bacillus subtilis and Listeria monocytogenes) by well diffusion method and agar dilution method (MIC). All the essences were found to inhibit the growth of both gram (+) and gram (−) bacteria organisms tested. These activities were correlated with the presence of phenolic compounds in active fractions. HPLC confirmed presence of phenolic compounds in methanol extracts. Conclusion Methanol extracts and essential oils from aerial parts of Thymus hirtus sp. algeriensis, were examined for their potential as antioxidants. The technique for measuring antioxidant activity, which was developed using DPPH, ABTS and β-carotene bleaching, produced results as found in established literatures. The present results indicate clearly that methanol extracts and essential oils from Thymus hirtus sp

  6. Characterization of the mouse DAX-1 gene reveals evolutionary conservation of a unique amino-terminal motif and widespread expression in mouse tissue.

    PubMed

    Bae, D S; Schaefer, M L; Partan, B W; Muglia, L

    1996-09-01

    The human genetic disorder adrenal hypoplasia congenita with hypogonadotropic hypogonadism results from mutations in the recently isolated DAX-1 gene, a member of the nuclear hormone receptor superfamily. To study the role of DAX-1 in adrenal development and activation of the hypothalamic pituitary-gonadal axis, animal model systems will be essential. Here, we report the isolation and characterization of the mouse DAX-1 gene and its tissue-specific pattern of expression. The mouse DAX-1 gene codes for a 472-amino acid protein, with 75% overall nucleotide sequence homology to its human homolog. The 3.5 amino-terminal repeats of a unique motif with probable DNA-binding activity have been conserved between mouse and human, although highest conservation in the DAX-1 peptide exists in the carboxy-terminal ligand-binding domain. The DAX-1 gene remains X-linked in the mouse, consistent with its potential role in sex determination. We have developed a sensitive reverse transcription-PCR assay that detects DAX-1 messenger RNA in the central nervous system, pituitary, lung, heart, spleen, kidney, and thymus in addition to the adrenal and testis DAX-1 expression noted for the human DAX-1 gene. Future studies using mouse models of altered DAX-1 expression will be critical in defining the role of this factor in tissue- and development-specific gene regulation.

  7. Characterization of a subpopulation in neonatal thymus which suppress the graft-vs.-host reaction.

    PubMed

    Van Bekkum, D W; Knaan-Shanzer, S

    1983-05-01

    Thymus cells from neonatal and infant mice were found to have a high capacity to prevent mortality from acute graft-vs.-host disease as compared with spleen cells from stable radiation chimeras. This suppressive capacity of thymocytes decreases with age after birth as was demonstrated by semi-quantitative cell titrations. This suppressor activity is restricted to syngeneity of the graft-vs.-host disease-including cells. The thymic suppressor cells are Thy-1+ and Lyt-1+ and IgG- and IgM-. They do not agglutinate with peanut agglutinin and have a high electrophoretic mobility. In vitro irradiation experiments showed that the suppressor cells are radiation sensitive. These results are compared with the available information on cells suppressing delayed-type hypersensitivity reactions and those suppressing B cell responses.

  8. Synthesis and characterisation of platinum (II) salphen complex and its interaction with calf thymus DNA

    NASA Astrophysics Data System (ADS)

    Sukri, Shahratul Ain Mohd; Heng, Lee Yook; Karim, Nurul Huda Abd

    2014-09-01

    A platinum (II) salphen complex was synthesised by condensation reaction of 2,4-dihydroxylbenzaldehyde and o-phenylenediamine with potassium tetrachloroplatinate to obtain N,N'-Bis-4-(hydroxysalicylidene)-phenylenediamine-platinum (II). The structure of the complex was confirmed by 1H and 13C NMR spectroscopy, FTIR spectroscopy, CHN elemental analyses and ESI-MS spectrometry. The platinum (II) salphen complex with four donor atoms N2O2 from its salphen ligand coordinated to platinum (II) metal centre were determined. The binding mode and interaction of this complex with calf thymus DNA was determined by UV/Vis DNA titration and emission titration. The intercalation between the DNA bases by π-π stacking due to its square planar geometry and aromatic rings structures was proposed.

  9. A naproxen complex of dysprosium intercalates into calf thymus DNA base pairs

    NASA Astrophysics Data System (ADS)

    Yang, Mengsi; Jin, Jianhua; Xu, Guiqing; Cui, Fengling; Luo, Hongxia

    2014-01-01

    The binding mode and mechanism of dysprosium-naproxen complex (Dy-NAP) with calf thymus deoxyribonucleic acid (ctDNA) were studied using UV-vis and fluorescence spectra in physiological buffer (pH 7.4). The results showed that more than one type of quenching process occurred and the binding mode between Dy-NAP with ctDNA might be intercalation. In addition, ionic strength, iodide quenching and fluorescence polarization experiments corroborated the intercalation binding mode between Dy-NAP and ctDNA. The calculated thermodynamic parameters ΔG, ΔH and ΔS at different temperature demonstrated that hydrophobic interaction force played a major role in the binding process.

  10. Thymus catharinae Camarda essential oil: β-cyclodextrin inclusion complexes, evaluation of antimicrobial activity.

    PubMed

    Delogu, Giovanna; Juliano, Claudia Clelia Assunta; Usai, Marianna

    2016-09-01

    An efficient antimicrobial activity was evidenced in a complex β-cyclodextrin-essential oil of Thymus catharinae Camarda (carvacrol chemotype). The release of carvacrol with respect to the antimicrobial activity was calculated as function of time. The βCD-complex of the bioactive agent was obtained by a simple, efficient and non-expensive method without purification of the carvacrol chemotype essential oil. According to the starting stoichiometry of β-cyclodextrin with respect to carvacrol, two inclusion complexes were produced, 1:1 and 2:1, respectively. The results demonstrate that, although the antimicrobial activity of the essential oil of T. catharinae Camarda is remarkable but acts too quickly in some types of application, its inclusion in a bio-matrix allows a slower release and improves its effectiveness.

  11. Evidence for hydrated spermidine-calf thymus DNA toruses organized by circumferential DNA wrapping.

    PubMed Central

    Marx, K A; Ruben, G C

    1983-01-01

    In spermidine-condensed calf thymus DNA preparations, torus-shaped condensates were shown by transmission electron microscopy to exist under the hydrated conditions of the freeze fracture experiment. Using extremely low Pt metal deposition levels (9 A Pt/C) high-contrast replicas of the spermidine-DNA toruses were obtained that showed circumferential wrapping of single DNA double helix-size surface fibres. Stereoscopic analysis of high magnification stereomicrographs established some details of the three-dimensional organization of two DNA double helix sections winding circumferentially on the inner surface of one such torus. These measurements demonstrate the usefulness of stereoscopic analysis of these high macromolecular organization magnification. Measurements on a number of torus-shaped complexes (n = 16) yielded these average dimensions: inner circumference (1840 +/- 204 A) outer circumference (2800 +/- 222 A), torus ring thickness (143 +/- 18 A). These data support a continuous circumferential DNA-winding model of torus organization proposed by Marx & Reynolds. Images PMID:6835840

  12. Thymus as a target tissue of glucocorticoid action: what are the consequences of glucocorticoids thymectomy?

    PubMed

    Bjelaković, Gordana; Stojanovic, Ivana; Jevtovic-Stoimenov, Tatjana; Pavlović, Dusica; Kocić, Gordana; Kamenov, Borisav; Saranac, Ljiljana; Nikolić, Jelenka; Bjelaković, Bojko; Sokolović, Dusan; Basić, Jelena

    2009-01-01

    Glucocorticoids represent the most powerful endogenous anti-inflammatory and immunosuppressive effectors, interfering with virtually every step of immunoinflammatory responses. Glucocorticoids are often the most effective therapy in the prevention or suppression of inflammation and other immunologically mediated processes, but their use is limited by systemic side effects induced by the over-production of reactive oxygen species, causing dysregulation of physiological processes. The thymus is an organ with both endocrine and immune functions. Glucocorticoids induce thymocyte apoptosis, causing a profound reduction in thymic mass and volume and inducing hormonal thymectomy. The clinical aspects of glucocorticoid thymectomy are not under enough investigation. These unwanted systemic side effects may be the consequence of prolonged therapeutic application of glucocorticoids and prolonged or chronic activation of the hypothalamic-pituitary adrenal axis, which may lead to increased and prolonged secretion of glucocorticoids. This review will discuss the metabolic effects of glucocorticoids in the context of thymic physiology asthe primary sex hormone-responsive organ.

  13. Spectroscopic studies on the interaction of sodium benzoate, a food preservative, with calf thymus DNA.

    PubMed

    Zhang, Guowen; Ma, Yadi

    2013-11-01

    The interaction between sodium benzoate (SB) and calf thymus DNA in simulated physiological buffer (pH 7.4) using acridine orange (AO) dye as a fluorescence probe, was investigated by UV-Vis absorption, fluorescence and circular dichroism (CD) spectroscopy along with DNA melting studies and viscosity measurements. An expanded UV-Vis spectral data matrix was resolved by multivariate curve resolution-alternating least squares (MCR-ALS) approach. The equilibrium concentration profiles and the pure spectra for SB, DNA and DNA-SB complex from the high overlapping composite response were simultaneously obtained. The results indicated that SB could bind to DNA, and hydrophobic interactions and hydrogen bonds played a vital role in the binding process. Moreover, SB was able to quench the fluorescence of DNA-AO complex through a static procedure. The quenching observed was indicative of an intercalative mode of interaction between SB and DNA, which was supported by melting studies, viscosity measurements and CD analysis.

  14. Calf thymus DNA binding studies of the new neodymium-naproxen complex.

    PubMed

    Huo, Ruina; Xu, Guiqing; Jiang, Xiaoying; Ge, Yao; Xue, Zaikun; Cui, Fengling

    2012-05-01

    Fluorescence spectroscopy in combination with UV absorption spectroscopy was carried out to investigate the interaction between the neodymium-naproxen complex (Nd-NAP) and calf thymus DNA (ctDNA). The experimental results showed that Nd-NAP intercalated with the ctDNA base pairs. Analysis of fluorescence quenching data of Nd-NAP by ctDNA at different temperatures using a Stern-Volmer equation revealed that dynamic and static quenching occurred simultaneously. The binding constants and the number of binding sites at 293 and 310 K were obtained as 2.904 × 10(4) L mol(-1), 1.172 and 2.432 × 10(4) L mol(-1), 1.143, respectively. The thermodynamic parameters ΔG, ΔH, and ΔS calculated at different temperatures indicated that hydrogen bonding and van der Waals force were the main binding forces.

  15. Eph/Ephrins-Mediated Thymocyte–Thymic Epithelial Cell Interactions Control Numerous Processes of Thymus Biology

    PubMed Central

    García-Ceca, Javier; Alfaro, David; Montero-Herradón, Sara; Tobajas, Esther; Muñoz, Juan José; Zapata, Agustín G.

    2015-01-01

    Numerous studies emphasize the relevance of thymocyte–thymic epithelial cell (TECs) interactions for the functional maturation of intrathymic T lymphocytes. The tyrosine kinase receptors, Ephs (erythropoietin-producing hepatocyte kinases) and their ligands, ephrins (Eph receptor interaction proteins), are molecules known to be involved in the regulation of numerous biological systems in which cell-to-cell interactions are particularly relevant. In the last years, we and other authors have demonstrated the importance of these molecules in the thymic functions and the T-cell development. In the present report, we review data on the effects of Ephs and ephrins in the functional maturation of both thymic epithelial microenvironment and thymocyte maturation as well as on their role in the lymphoid progenitor recruitment into the thymus. PMID:26167166

  16. The role of mast cell in tissue morphogenesis. Thymus, duodenum, and mammary gland as examples.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2016-02-01

    Mast cells (MCs) are strategically located at host/environment interfaces like skin, airways, and gastro-intestinal and uro-genital tracts. MCs also populate connective tissues in association with blood and lymphatic vessels and nerves. MCs are absent in avascular tissues, such as mineralized bone, cartilage, and cornea. MCs have various functions and different functional subsets of MCs are encountered in different tissues. However, we do not' know exactly what is the physiological function of MC. Most of these functions are not essential for life, as various MC-deficient strains of mice and rats seems to have normal life spans. In this review article, we have reported and discussed the literature data concerning the role of MCs in tissue morphogenesis, and in particular their role in the development of thymus, duodenum, and mammary gland. PMID:26615957

  17. Synthesis and characterisation of platinum (II) salphen complex and its interaction with calf thymus DNA

    SciTech Connect

    Sukri, Shahratul Ain Mohd; Heng, Lee Yook; Karim, Nurul Huda Abd

    2014-09-03

    A platinum (II) salphen complex was synthesised by condensation reaction of 2,4-dihydroxylbenzaldehyde and o-phenylenediamine with potassium tetrachloroplatinate to obtain N,N′-Bis-4-(hydroxysalicylidene)-phenylenediamine-platinum (II). The structure of the complex was confirmed by {sup 1}H and {sup 13}C NMR spectroscopy, FTIR spectroscopy, CHN elemental analyses and ESI-MS spectrometry. The platinum (II) salphen complex with four donor atoms N{sub 2}O{sub 2} from its salphen ligand coordinated to platinum (II) metal centre were determined. The binding mode and interaction of this complex with calf thymus DNA was determined by UV/Vis DNA titration and emission titration. The intercalation between the DNA bases by π-π stacking due to its square planar geometry and aromatic rings structures was proposed.

  18. Histochemical Investigation and Kinds of Alkaloids in Leaves of Different Developmental Stages in Thymus quinquecostatus

    PubMed Central

    Jing, Haiting; Liu, Jing; Liu, Hanzhu; Xin, Hua

    2014-01-01

    Thymus quinquecostatus, with more medical value, is a kind of wild plants. In order to exploit and utilize this plant, we studied the species and locations of alkaloids in its leaves. In this paper, histochemical study of leaves at different developing stages was taken to localize the alkaloids. Meanwhile, the kinds and content of alkaloids in leaves were identified using GC-MS technique. It was found that there were two kinds of glandular trichomes, namely, peltate trichomes and capitate trichomes, on the surface of leaves, and their secretory cells could secrete alkaloids. Results showed that trichomes could secrete alkaloids as soon as the first pair of leaves formed, and there were altogether 18 kinds of alkaloids identified by GC-MS. Nearly all of these alkaloids of leaves at different developing stages were distinct from each other, except one, 3-methoxy-a-methyl-benzeneethanamine, persists at different developing stages with high concentration. PMID:25101324

  19. Anatomy and cytology of the thymus in juvenile Australian lungfish, Neoceratodus forsteri

    PubMed Central

    Mohammad, M G; Chilmonczyk, S; Birch, D; Aladaileh, S; Raftos, D; Joss, J

    2007-01-01

    The anatomy, histology and ultrastructure of the thymus of a dipnoan, the Australian lungfish, Neoceratodus forsteri, was studied by light and transmission electron microscopy. The thymic tissue showed clear demarcation into a cortex and medulla with ample vascularization. Large cells including foamy and giant multinucleated cells with periodic acid Schiff/Alcian blue positive staining properties were localized mainly in the medulla. The major cellular components were epithelial cells and lymphoid cells. The epithelial cells were classified by location and ultrastructure into six sub-populations: capsular cells, cortical and medullary reticular cells, perivascular endothelial cells, intermediate cells, nurse-like cells and Hassall-like corpuscles. Myoid cells were found mainly in the cortico-medullary boundary and medulla. Macrophages and secretory-like cells were also present. These findings will provide a base of knowledge about the cellular immune system of lungfish. PMID:17944863

  20. The role of mast cell in tissue morphogenesis. Thymus, duodenum, and mammary gland as examples.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2016-02-01

    Mast cells (MCs) are strategically located at host/environment interfaces like skin, airways, and gastro-intestinal and uro-genital tracts. MCs also populate connective tissues in association with blood and lymphatic vessels and nerves. MCs are absent in avascular tissues, such as mineralized bone, cartilage, and cornea. MCs have various functions and different functional subsets of MCs are encountered in different tissues. However, we do not' know exactly what is the physiological function of MC. Most of these functions are not essential for life, as various MC-deficient strains of mice and rats seems to have normal life spans. In this review article, we have reported and discussed the literature data concerning the role of MCs in tissue morphogenesis, and in particular their role in the development of thymus, duodenum, and mammary gland.

  1. Essential oils of Thymus leucospermus Hartvig, a Greek endemic rich in phenolic monoterpenes.

    PubMed

    Hanlidou, Effie; Lazari, Diamanto

    2013-01-01

    Thymus leucospermus Hartvig is a Greek endemic species of Section Teucrioides Jalas. The essential oils obtained from five populations growing wild in the National Park of Northern Pindhos (NW Greece) were studied. The oil content ranged between 1.1 and 2.0 mL per 100 g of dry plant weight. The oils were particularly rich in phenolic monoterpenes: they had a high thymol (64.7-92.0%) or carvacrol (93.4%) content, whereas in one of the oils considerable amount of both compounds was found (thymol 61.6% and carvacrol 26.4%). Our results show that T. leucospermus is a high-quality thyme species, with respect to both oil content and composition. PMID:23297716

  2. [Results of a quantitative cytological analysis of the thymus of rats exposed on biosatellites].

    PubMed

    Sushkov, F V; Rudneva, S B; Durnova, G N; Ponomareva, T F

    1983-01-01

    The mitotic activity, destruction and volume of nuclei of thymocytes were investigated on histological preparations of the thymus of rats flown onboard Cosmos-782 and Cosmos-936. The cytological data showed that immediately after touchdown large quantities of thymocytes of the cortical matter perished. The mitotic activity of the remaining undamaged thymocytes declined and returned to normal 9 hours after recovery. The rats that were centrifuged inflight (at 1 g) did not display a lower mitotic activity or noticeable destruction of thymocytes. Karyometric measurements demonstrated that the population of thymic lymphocytes was heterogeneous in the nuclear volume: it consisted of three peak classes of nuclear volumes. The variance curves of nuclear volumes of lymphocytes of the medullary matter were drastically shifted toward large numbers. An increase in the nuclei of thymocytes of the cortical matter in the flight rats was stable and persisted till R+25.

  3. In vitro reactions of glycidol with pyrimidine bases in calf thymus DNA.

    PubMed

    Segal, A; Solomon, J J; Mukai, F

    1990-01-01

    The 3-carbon epoxide glycidol (GLC) was reacted with dCyd and dThd at pH 7.0 to 7.5 and 37 degrees C for 10 h. The only product detected from the reaction with dCyd was 3-(2,3-dihydroxypropyl)-dUrd (3-DHP-dUrd) whose structure was established from UV spectra, isobutane chemical ionization (CI) mass spectra together with accurate mass measurements and synthesis of 3-DHP-dUrd from reactions of GLC with dUrd. Reaction of GLC with dThd gave a single product, 3-DHP-dThd, whose structure was established from UV spectra and CI mass spectra together with accurate mass measurements. The compounds, 3-DHP-dUrd and 3-DHP-dThd, were identified and quantitated following in vitro reaction of GLC with calf thymus DNA at pH 7.0 to 7.5 and 37 degrees C for 10 h. The amounts of 3-DHP-dUrd and 3-DHP-dThd formed were 10 and 1 nmol/mg DNA respectively. Alkylation at the N-3 position of Cyt resulted in a rapid hydrolytic deamination of Cyt to form a Ura adduct. This phenomena was previously reported by us following reaction of propylene oxide (PO) with dCyd and following in vitro reaction of PO with calf thymus DNA under identical conditions. The rapid hydrolytic deamination of Cyt to Ura may be a general occurrence following alkylation of N-3 of Cyt by 3-carbon epoxides and is postulated to be related to the presence of a C-2 hydroxyl group on the 3-carbon propyl side chain. The implications of this newly discovered lesion in DNA in terms of the mutagenicity of GLC (and PO) remain to be elucidated.

  4. Identification and characterization of a second isogene encoding γ-terpinene synthase in Thymus caespititius.

    PubMed

    Mendes, Marta D; Barroso, José G; Oliveira, M Margarida; Trindade, Helena

    2014-07-15

    Thymus caespititius Brot. is an Iberian endemic species, whose essential oils possess high polymorphism. They consist mostly of mono- and sesquiterpene, some of them with interest for the pharmaceutical and food industries. The search for terpene synthase genes was performed in three in vitro T. caespititius genotypes. For these plants, the expression of a previously described γ-terpinene synthase gene, Tctps2, was confirmed, occurring concomitantly with a new gene encoding an enzyme with similar activity, named Thymus caespititius terpene synthase 4 (Tctps4). The two isogenes were isolated and functionally characterized in the three plant genotypes. Alignment of the two Tctps revealed a transit peptide much shorter in Tctps4 than in Tctps2 (3-4 amino acids instead of 47). The Tctps4 open reading frame is shorter than Tctps2 (1665 bp versus 1794 bp). The amino acid sequence of both γ-terpinene synthases shared an 88% pairwise identity. The fact that T. caespititius carries two isogenes for γ-terpinene synthases, suggests gene duplication along the evolutionary process, followed by mutations leading to the differentiation of both genes. These mutations didn't compromise protein activity. A high accumulation of transcripts from both genes was found in shoots of in vitro plantlets, while in roots they could not be detected. Still, γ-terpinene levels in aerial parts were reduced, probably due to fast conversion into carvacrol and thymol, the main components from T. caespititius essential oils. This study is a contribution to the identification of terpene synthase genes in Lamiaceae.

  5. Clinicopathologic and DNA cytometric analysis of carcinoid tumors of the thymus.

    PubMed

    Goto, K; Kodama, T; Matsuno, Y; Yokose, T; Asamura, H; Kamiya, N; Shimosato, Y

    2001-10-01

    Twelve cases of carcinoid tumors of the thymus were reviewed in terms of clinicopathologic, histochemical, and immunohistochemical features and DNA ploidy patterns. The collective consisted of nine male and three female patients, aged 34 to 74 years, of whom five (42%) had symptoms. Eleven patients underwent surgical resection, and one with systemic metastases was autopsied. In the 11 resected patients, tumors had invaded surrounding structures in four cases, and mediastinal lymph node metastases were detected in six. Recurrence occurred in two of the resected patients (18%), and the 5-year survival rate was 82%. Histologically, all tumors showed an organoid growth pattern with delicate fibrovascular stroma. In addition, three tumors had unusual morphologic features such as combined features of carcinoid tumor and thymoma and solid growth pattern with occasional large tumor cells. Mitotic counts ranged from 1 to 14 per 10 high-power fields with a mean count of 4.9. Central necrosis within solid nests was observed in nine tumors. Classification of this series using the WHO histologic classification system resulted in categorization of all 12 tumors as atypical carcinoids. All tumors were positive for Grimelius staining and for cytokeratin. Immunohistochemical staining documented the presence of moderately to strongly positive neuroendocrine markers such as neuron-specific enolase, chromogranin A, synaptophysin, and neural cell adhesion molecule. No correlation between proliferative activity based on the Ki67 labeling index and prognosis or lymph node metastasis was found. Concerning DNA ploidy patterns, only one tumor with multiple lymph node metastases was considered to be aneuploid. In conclusion, although all of our cases were histologically classified as atypical carcinoid tumors of the thymus, most were diploid, and the patients enjoyed a relatively good prognosis.

  6. Thymus fat as an attractive source of angiogenic factors in elderly subjects with myocardial ischemia.

    PubMed

    Coín Aragüez, Leticia; Murri, Mora; Oliva Olivera, Wilfredo; Salas, Julian; Mayas, Maria Dolores; Delgado-Lista, Javier; Tinahones, Francisco; El Bekay, Rajaa

    2013-08-01

    Aging negatively affects angiogenesis which is found to be linked to declined vascular endothelial growth factor (VEGF) production. Adult human thymus degenerates into fat tissue (thymus adipose tissue (TAT)). Recently, we described that TAT from cardiomyopathy ischemic subjects has angiogenic properties. The goal of our study was to analyze whether aging could also impair angiogenic properties in TAT as in other adipose tissue such as subcutaneous (subcutaneous adipose tissue (SAT)). SAT and TAT specimens were obtained from 35 patients undergoing cardiac surgery, making these tissues readily available as a prime source of adipose tissue. Patients were separated into two age-dependent groups; middle-aged (n = 18) and elderly (n = 17). Angiogenic, endothelial, and adipogenic expression markers were analyzed in both tissues from each group and correlations were examined between these parameters and also with age. There were no significant differences in subjects from either group in clinical or biological variables. Angiogenic markers VEGF-A, B, C, and D and adipogenic parameters, peroxisome proliferator-activated receptors (PPARγ2), FABP4, and ADRP showed elevated expression levels in TAT from elderly patients compared to the middle-aged group, while in SAT, expression levels of these isoforms were significantly decreased in elderly patients. VEGF-R1, VEGF-R2, VEGF-R3, Thy1, CD31, CD29, and VLA1 showed increased levels in TAT from the elderly compared to the middle-aged, while in SAT these levels displayed a decline with aging. Also, in TAT, angiogenic and endothelial parameters exhibited strong positive correlations with age. TAT appears to be the most appropriate source of angiogenic and endothelial factors in elderly cardiomyopathy subjects compared to SAT.

  7. Composition of headspace volatiles and essential oils of three Thymus species.

    PubMed

    Stojanović, Gordana; Jovanović, Olga; Petrović, Goran; Mitić, Violeta; Jovanović, Vesna Stankov; Jovanović, Snežana

    2014-11-01

    Analysis of head space volatiles (HSV) and hydrodistilled essential oils (EO) of the above-ground parts of Thymus glabrescens Willd., T. praecox Opiz subsp. jankae (Celak.) Jalas (from two localities) and T. pulegoides L. was made by GC-FID and GC-MS. This is the first report on the headspace volatiles composition of T. glabrescens and T. pulegoides. The most abundant compound of T. glabrescens HSV was p-cymene (27.8%) followed by γ-terpinene (18.4%), while thymol (55.4%) and geraniol (10.5%) were the most abundant in the corresponding EO. T. praecox subsp. jankae EO from Serbia was characterized by (E)-caryophyllene (14.6%) and thymol (10.7%), which is substantially different from that of Bulgarian T. praecox subsp. jankae, which contained a-terpinyl acetate (20.1%) and linalool (17.7%) as its main components. The dominating components of the Serbian and Bulgarian T. praecox subsp. jankae HSV were α-pinene (29.4% and 18.6%, respectively), myrcene (12.1% and 23.2%, respectively), limonene (7.5% and 17.8%, respectively) and β-pinene (11.7% and 7.6%, respectively). Linalyl acetate predominated in T. pulegoides EO and HSV, representing 40.0% and 42.4% (respectively) of the total peak area. The chemical composition of the essential oils of the examined Thymus species could not be attributed to any particular recorded chemotype of T. glabrescens, T. praecox and T. pulegoides. PMID:25532293

  8. Efficacy of Punch Elevation Combined with Fractional Carbon Dioxide Laser Resurfacing in Facial Atrophic Acne Scarring: A Randomized Split-face Clinical Study

    PubMed Central

    Faghihi, Gita; Nouraei, Saeid; Asilian, Ali; Keyvan, Shima; Abtahi-Naeini, Bahareh; Rakhshanpour, Mehrdad; Nilforoushzadeh, Mohammad Ali; Hosseini, Sayed Mohsen

    2015-01-01

    Background: A number of treatments for reducing the appearance of acne scars are available, but general guidelines for optimizing acne scar treatment do not exist. The aim of this study was to compare the clinical effectiveness and side effects of fractional carbon dioxide (CO2) laser resurfacing combined with punch elevation with fractional CO2 laser resurfacing alone in the treatment of atrophic acne scars. Materials and Methods: Forty-two Iranian subjects (age range 18–55) with Fitzpatrick skin types III to IV and moderate to severe atrophic acne scars on both cheeks received randomized split-face treatments: One side received fractional CO2 laser treatment and the other received one session of punch elevation combined with two sessions of laser fractional CO2 laser treatment, separated by an interval of 1 month. Two dermatologists independently evaluated improvement in acne scars 4 and 16 weeks after the last treatment. Side effects were also recorded after each treatment. Results: The mean ± SD age of patients was 23.4 ± 2.6 years. Clinical improvement of facial acne scarring was assessed by two dermatologists blinded to treatment conditions. No significant difference in evaluation was observed 1 month after treatment (P = 0.56). Their evaluation found that fractional CO2 laser treatment combined with punch elevation had greater efficacy than that with fractional CO2 laser treatment alone, assessed 4 months after treatment (P = 0.02). Among all side effects, coagulated crust formation and pruritus at day 3 after fractional CO2 laser treatment was significant on both treatment sides (P < 0.05). Conclusion: Concurrent use of fractional laser skin resurfacing with punch elevation offers a safe and effective approach for the treatment of acne scarring. PMID:26538695

  9. A cell surface marker gene transferred with a retroviral vector into CD34+ cord blood cells is expressed by their T-cell progeny in the SCID-hu thymus.

    PubMed

    Champseix, C; Maréchal, V; Khazaal, I; Schwartz, O; Fournier, S; Schlegel, N; Dranoff, G; Danos, O; Blot, P; Vilmer, E; Heard, J M; Péault, B; Lehn, P

    1996-07-01

    Gene transduction into immature hematopoietic cells collected at birth from the umbilical cord could be useful for the treatment of genetic or acquired disorders of the hematopoietic system diagnosed during pregnancy. The SCID-hu mouse is a convenient model to investigate T-cell lineage gene therapy, since it allows replication of human intrathymic T-cell development. CD34+ cells isolated from cord blood were cocultured with CRIP MFG-murine CD2 (mCD2) cells that produce recombinant retroviruses encoding the mCD2 antigen, a cell surface marker easily detectable by flow cytometry. After 3 and 4 days in coculture, a mean of 19% and 39% human hematopoietic cells, respectively, expressed the mCD2 antigen. CD34+ cells cocultured for 4 days were used to reconstitute human fetal thymus implanted in SCID mice. Five to 10 weeks later, the mCD2 antigen was detected on approximately 10% of human thymocytes repopulating the thymic grafts in four of nine SCID mouse chimeras. Vector genomes were detected in graft cell DNA by Southern blot. Analysis of vector integration indicated that positive cells were of polyclonal origin in three animals and predominantly monoclonal in the other one. Our data show that foreign genes can be transduced into CD34+ cord blood cells endowed with T-cell differentiation potential, and suggest strategies for T-cell lineage gene therapy in the neonate.

  10. Stem-cell Based Engineered Immunity Against HIV Infection in the Humanized Mouse Model.

    PubMed

    Zhen, Anjie; Rezek, Valerie; Youn, Cindy; Rick, Jonathan; Lam, Brianna; Chang, Nelson; Zack, Jerome; Kamata, Masakazu; Kitchen, Scott

    2016-01-01

    With the rapid development of stem cell-based gene therapies against HIV, there is pressing requirement for an animal model to study the hematopoietic differentiation and immune function of the genetically modified cells. The humanized Bone-marrow/Liver/Thymus (BLT) mouse model allows for full reconstitution of a human immune system in the periphery, which includes T cells, B cells, NK cells and monocytes. The human thymic implant also allows for thymic selection of T cells in autologous thymic tissue. In addition to the study of HIV infection, the model stands as a powerful tool to study differentiation, development and functionality of cells derived from hematopoietic stem cells (HSCs). Here we outline the construction of humanized non-obese diabetic (NOD)-severe combined immunodeficient (SCID)-common gamma chain knockout (cγ(-/-))-Bone-marrow/Liver/Thymus (NSG-BLT) mice with HSCs transduced with CD4 chimeric antigen receptor (CD4CAR) lentivirus vector. We show that the CD4CAR HSCs can successfully differentiate into multiple lineages and have anti-HIV activity. The goal of the study is to demonstrate the use of NSG-BLT mouse model as an in vivo model for engineered immunity against HIV. It is worth noting that, because lentivirus and human tissue is used, experiments and surgeries should be performed in a Class II biosafety cabinet in a Biosafety Level 2 (BSL2) with special precautions (BSL2+) facility. PMID:27404517

  11. The mouse lymph node as an ectopic transplantation site for multiple tissues

    PubMed Central

    Komori, Junji; Boone, Lindsey; DeWard, Aaron; Hoppo, Toshitaka; Lagasse, Eric

    2012-01-01

    Cell-based therapy has been viewed as a promising alternative to organ transplantation, but cell transplantation aimed at organ repair is not always possible. Here, we show that the mouse lymph node can support the engraftment and growth of healthy cells from multiple tissues. Direct injection of hepatocytes into a single mouse lymph node generated enough ectopic liver mass to rescue survival of mice with lethal metabolic disease. Furthermore, thymuses transplanted into a lymph node of athymic nude mice generate a functional immune system capable of rejecting allogeneic and xenogeneic grafts. Finally, pancreatic islets injected into the lymph node of diabetic mice restore normal glucose control. Collectively, these results suggest the practical approach of targeting lymph nodes to restore, maintain or improve tissue and organ functions. PMID:23000933

  12. Absence of ductal hyper-keratinization in mouse age-related meibomian gland dysfunction (ARMGD).

    PubMed

    Parfitt, Geraint J; Xie, Yilu; Geyfman, Mikhail; Brown, Donald J; Jester, James V

    2013-11-01

    Meibomian gland dysfunction (MGD) is frequent with aging and is the primary cause of dry eye disease, the most prevalent ocular complaint. We used a novel 3-D reconstruction technique, immunofluorescent computed tomography (ICT), to characterize meibomian gland keratinization and cell proliferation in a mouse model of age-related meibomian gland dysfunction (ARMGD). To visualize the changes associated with ARMGD, 5-month and 2-year old mouse eyelids were 3-D reconstructed by ICT using antibodies to cytokeratin (CK) 1, 5 and 6 and the proliferation marker Ki67. We quantified total gland, ductal and lipid volume from the reconstructions, observing a dramatic decrease in old glands. In young glands, proliferative ductules suggest a potential site of acinar progenitors that were found to be largely absent in aged, atrophic glands. In the aged mouse, we observed an anterior migration of the mucocutaneous junction (MCJ) and an absence of hyper-keratinization with meibomian gland atrophy. Thus, we propose that changes in the MCJ and glandular atrophy through a loss of meibocyte progenitors are most likely responsible for ARMGD and not ductal hyper-keratinization and gland obstruction.

  13. Absence of ductal hyper-keratinization in Mouse age-related meibomian gland dysfunction (ARMGD)

    PubMed Central

    Parfitt, Geraint J.; Xie, Yilu; Geyfman, Mikhail; Brown, Donald J.; Jester, James V.

    2013-01-01

    Meibomian gland dysfunction (MGD) is frequent with aging and is the primary cause of dry eye disease, the most prevalent ocular complaint. We used a novel 3-D reconstruction technique, immunofluorescent computed tomography (ICT), to characterize meibomian gland keratinization and cell proliferation in a mouse model of age-related meibomian gland dysfunction (ARMGD). To visualize the changes associated with ARMGD, 5-month and 2-year old mouse eyelids were 3-D reconstructed by ICT using antibodies to cytokeratin (CK) 1, 5 and 6 and the proliferation marker Ki67. We quantified total gland, ductal and lipid volume from the reconstructions, observing a dramatic decrease in old glands. In young glands, proliferative ductules suggest a potential site of acinar progenitors that were found to be largely absent in aged, atrophic glands. In the aged mouse, we observed an anterior migration of the mucocutaneous junction (MCJ) and an absence of hyper-keratinization with meibomian gland atrophy. Thus, we propose that changes in the MCJ and glandular atrophy through a loss of meibocyte progenitors are most likely responsible for ARMGD and not ductal hyper-keratinization and gland obstruction. PMID:24259272

  14. Constitutive expression of genes encoding notch receptors and ligands in developing lymphocytes, nTreg cells and dendritic cells in the human thymus.

    PubMed

    Bento-de-Souza, Luciana; Victor, Jefferson R; Bento-de-Souza, Luiz C; Arrais-Santos, Magaly; Rangel-Santos, Andréia C; Pereira-Costa, Érica; Raniero-Fernandes, Elaine; Seixas-Duarte, Maria I; Oliveira-Filho, João B; Silva Duarte, Alberto J

    2016-01-01

    The thymus is the site of T cell maturation. Notch receptors (Notch1-4) and ligands (DLL1-3 and Jagged1-2) constitute one of several pathways involved in this process. Our data revealed differential constitutive expression of Notch genes and ligands in T lymphocytes and thymic dendritic cells (tDCs), suggesting their participation in human thymocyte maturation. nTreg analyses indicated that the Notch components function in parallel to promote maturation in the thymus. PMID:27504259

  15. Antioxidant and Antiproliferative Activities of the Essential Oils from Thymbra capitata and Thymus Species Grown in Portugal

    PubMed Central

    Miguel, Maria Graça; Gago, Custódia; Antunes, Maria Dulce; Megías, Cristina; Cortés-Giraldo, Isabel; Vioque, Javier; Lima, A. Sofia; Figueiredo, A. Cristina

    2015-01-01

    The antioxidant and antiproliferative activities of the essential oils from Thymbra capitata and Thymus species grown in Portugal were evaluated. Thymbra and Thymus essential oils were grouped into two clusters: Cluster I in which carvacrol, thymol, p-cymene, α-terpineol, and γ-terpinene dominated and Cluster II in which thymol and carvacrol were absent and the main constituent was linalool. The ability for scavenging ABTS•+ and peroxyl free radicals as well as for preventing the growth of THP-1 leukemia cells was better in essential oils with the highest contents of thymol and carvacrol. These results show the importance of these two terpene-phenolic compounds as antioxidants and cytotoxic agents against THP-1 cells. PMID:26229547

  16. Antibacterial, antioxidant and optical properties of edible starch-chitosan composite film containing Thymus kotschyanus essential oil

    PubMed Central

    Mehdizadeh, Tooraj; Tajik, Hossein; Razavi Rohani, Seyed Mehdi; Oromiehie, Abdol Rassol

    2012-01-01

    Thyme Essential oils (EO) with antimicrobial and antioxidant properties are widely used in pharmaceutical, cosmetic, and perfume industry. It is also used for flavoring and preservation of several foods. Nowadays, packaging research is receiving a considerable attention due to the development of eco-friendly materials made from natural polymers such as starch and chitosan. In this study Thymus kotschyanus EO concentrations ranging from 0 to 2.0%, incorporated in starch-chitosan composite (S-CH) film were used. Antimicrobial and antioxidant properties significantly increased with the incorporation of EO (p < 0.05). Incorporating EO, increased total color differences (DE), yellowness index (YI) and whiteness index (WI) which were significantly higher than control and its transparency was reduced. Our results pointed out that the incorporation of Thymus kotschyanus EO as a natural antibacterial agent has potential for using the developed film as an active packaging. PMID:25610564

  17. Antibacterial, antioxidant and optical properties of edible starch-chitosan composite film containing Thymus kotschyanus essential oil.

    PubMed

    Mehdizadeh, Tooraj; Tajik, Hossein; Razavi Rohani, Seyed Mehdi; Oromiehie, Abdol Rassol

    2012-01-01

    Thyme Essential oils (EO) with antimicrobial and antioxidant properties are widely used in pharmaceutical, cosmetic, and perfume industry. It is also used for flavoring and preservation of several foods. Nowadays, packaging research is receiving a considerable attention due to the development of eco-friendly materials made from natural polymers such as starch and chitosan. In this study Thymus kotschyanus EO concentrations ranging from 0 to 2.0%, incorporated in starch-chitosan composite (S-CH) film were used. Antimicrobial and antioxidant properties significantly increased with the incorporation of EO (p < 0.05). Incorporating EO, increased total color differences (DE), yellowness index (YI) and whiteness index (WI) which were significantly higher than control and its transparency was reduced. Our results pointed out that the incorporation of Thymus kotschyanus EO as a natural antibacterial agent has potential for using the developed film as an active packaging.

  18. Effect of infrared and X-ray radiation on thymus cells and the rate of growth of Ehrlich carcinoma.

    PubMed

    Dyukina, A R; Zaichkina, S I; Rozanova, O M; Aptikaeva, G F; Romanchenko, S P; Sorokina, S S

    2012-09-01

    We studied the effect of infrared light with a wavelength of 850 nm and modulated frequency of 101 Hz and X-ray radiation on the induction of cross-adaptive and radiation responses in the thymus and on the rate of tumor growth in mice in vivo. Preliminary exposure to infrared and X-ray radiation was shown to result in recovery in thymus weight after irradiation in a dose of 1.5 Gy and also inhibited the growth rate of Ehrlich carcinoma. These data attest to common mechanisms of the adaptive response induced by infrared and X-ray radiation in mice. Infrared light can be used as an adaptogen to adapt the animals to adverse factors.

  19. The transcription factor NR4A1 is essential for the development of a novel macrophage subset in the thymus

    PubMed Central

    Tacke, Robert; Hilgendorf, Ingo; Garner, Hannah; Waterborg, Claire; Park, Kiwon; Nowyhed, Heba; Hanna, Richard N.; Wu, Runpei; Swirski, Filip K.; Geissmann, Frederic; Hedrick, Catherine C.

    2015-01-01

    Tissue macrophages function to maintain homeostasis and regulate immune responses. While tissue macrophages derive from one of a small number of progenitor programs, the transcriptional requirements for site-specific macrophage subset development are more complex. We have identified a new tissue macrophage subset in the thymus and have discovered that its development is dependent on transcription factor NR4A1. Functionally, we find that NR4A1-dependent macrophages are critically important for clearance of apoptotic thymocytes. These macrophages are largely reduced or absent in mice lacking NR4A1, and Nr4a1-deficient mice have impaired thymocyte engulfment and clearance. Thus, NR4A1 functions as a master transcription factor for the development of this novel thymus-specific macrophage subset. PMID:26091486

  20. Comparative study of the topographic localization of NADPH diaphorase positive cells in the rabbit and pheasant thymuses.

    PubMed

    Dorko, F; Kluchová, D; Dorko, E; Danko, J; Svický, E; Pilipcinec, E; Kocisová, M; Sirotáková, M

    2002-01-01

    Nicotinamide adenine dinucleotide hydrogen phosphatediaphorase (NADPHd) histochemistry was used as a marker for nitric oxide synthase (NOS). In the rabbit thymus, NADPHd staining was observed between the capsule and corticomedullary junction in radially oriented blood vessels in the cortex. The outer surface of the thymic lobule and interlobular septa showed adipocytes clumped together. There was a high density of NADPHd positive cells in the medulla, without a sharp boundary in corticomedullary space. In addition to radially oriented blood vessels in the cortex, they were also found as solitary profiles with well stained walls in the medulla. Neuronal plexuses were localized in perivascular topography. In the pheasant thymus, NADPHd positive cells were present as clusters which were distributed in the medulla and the corticomedullar area. NADPHd positive nerve fibres were localized in perivascular topography.

  1. Antioxidant and Antiproliferative Activities of the Essential Oils from Thymbra capitata and Thymus Species Grown in Portugal.

    PubMed

    Miguel, Maria Graça; Gago, Custódia; Antunes, Maria Dulce; Megías, Cristina; Cortés-Giraldo, Isabel; Vioque, Javier; Lima, A Sofia; Figueiredo, A Cristina

    2015-01-01

    The antioxidant and antiproliferative activities of the essential oils from Thymbra capitata and Thymus species grown in Portugal were evaluated. Thymbra and Thymus essential oils were grouped into two clusters: Cluster I in which carvacrol, thymol, p-cymene, α-terpineol, and γ-terpinene dominated and Cluster II in which thymol and carvacrol were absent and the main constituent was linalool. The ability for scavenging ABTS(•+) and peroxyl free radicals as well as for preventing the growth of THP-1 leukemia cells was better in essential oils with the highest contents of thymol and carvacrol. These results show the importance of these two terpene-phenolic compounds as antioxidants and cytotoxic agents against THP-1 cells. PMID:26229547

  2. An encyclopedia of mouse DNA elements (Mouse ENCODE).

    PubMed

    Stamatoyannopoulos, John A; Snyder, Michael; Hardison, Ross; Ren, Bing; Gingeras, Thomas; Gilbert, David M; Groudine, Mark; Bender, Michael; Kaul, Rajinder; Canfield, Theresa; Giste, Erica; Johnson, Audra; Zhang, Mia; Balasundaram, Gayathri; Byron, Rachel; Roach, Vaughan; Sabo, Peter J; Sandstrom, Richard; Stehling, A Sandra; Thurman, Robert E; Weissman, Sherman M; Cayting, Philip; Hariharan, Manoj; Lian, Jin; Cheng, Yong; Landt, Stephen G; Ma, Zhihai; Wold, Barbara J; Dekker, Job; Crawford, Gregory E; Keller, Cheryl A; Wu, Weisheng; Morrissey, Christopher; Kumar, Swathi A; Mishra, Tejaswini; Jain, Deepti; Byrska-Bishop, Marta; Blankenberg, Daniel; Lajoie, Bryan R; Jain, Gaurav; Sanyal, Amartya; Chen, Kaun-Bei; Denas, Olgert; Taylor, James; Blobel, Gerd A; Weiss, Mitchell J; Pimkin, Max; Deng, Wulan; Marinov, Georgi K; Williams, Brian A; Fisher-Aylor, Katherine I; Desalvo, Gilberto; Kiralusha, Anthony; Trout, Diane; Amrhein, Henry; Mortazavi, Ali; Edsall, Lee; McCleary, David; Kuan, Samantha; Shen, Yin; Yue, Feng; Ye, Zhen; Davis, Carrie A; Zaleski, Chris; Jha, Sonali; Xue, Chenghai; Dobin, Alex; Lin, Wei; Fastuca, Meagan; Wang, Huaien; Guigo, Roderic; Djebali, Sarah; Lagarde, Julien; Ryba, Tyrone; Sasaki, Takayo; Malladi, Venkat S; Cline, Melissa S; Kirkup, Vanessa M; Learned, Katrina; Rosenbloom, Kate R; Kent, W James; Feingold, Elise A; Good, Peter J; Pazin, Michael; Lowdon, Rebecca F; Adams, Leslie B

    2012-08-13

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  3. Effect of a probiotic fermented milk on the thymus in Balb/c mice under non-severe protein-energy malnutrition.

    PubMed

    Núñez, Ivanna Novotny; Galdeano, Carolina Maldonado; Carmuega, Esteban; Weill, Ricardo; de Moreno de LeBlanc, Alejandra; Perdigón, Gabriela

    2013-08-28

    Protein–energy malnutrition (PEM) causes a significant impairment of the immune system, the thymus being one of the most affected organs. It has been demonstrated that the administration of probiotic fermented milk (PFM) recovered the intestinal barrier, histological alterations and mucosal and systemic immune functions in a non-severe malnutrition model using BALB/c mice. The aim of the present study was to evaluate, in the same model of malnutrition, the effect of a PFM added to a re-nutrition diet on the recovery of the thymus, analysing histological and functional alterations caused by malnutrition. Mice were undernourished and divided into three groups according to the dietary supplement received during re-nutrition: milk, PFM or its bacterial-free supernatant (BFS). They were compared with well-nourished and malnourished mice. PFM was the most effective re-nutrition supplement to improve the histology of the thymus, decreasing cellular apoptosis in this organ and recovering the percentage of CD4þ/CD82 single-positive thymocytes. Immature doublepositive thymocytes were increased in the malnourished control (MC). The production of different cytokines in the thymus was increased in mice given PFM, compared with the mice that received other dietary supplements and MC. Mice given the BFS presented an improvement in the thymus similar to those that received milk. We demonstrated the importance of the whole PFM supplementation on the histological and functional recovery of the thymus in a non-severe PEM model.

  4. Photophysical and photochemical studies of a novel amphiphilic zinc phthalocyanine and its interaction with calf thymus DNA

    NASA Astrophysics Data System (ADS)

    Yuan, Linxin; Gui, Li; Wang, Yue; Zhang, Quanquan; Zhou, Lin; Wei, Shaohua

    2016-04-01

    β-tetra (aminophenoxy) sulfonic substituted zinc phthalocyanines (SNZnPc), a novel amphiphilic zinc phthalocyanine (Pc), was synthesized. The photophysical, photochemical, and photobiology properties were studied. Results indicated that the synthesized SNZnPc has good amphiphilic property and high reactive oxygen species (ROSs) generation ability. Furthermore, SNZnPc has strong affinity to calf thymus DNA (CT-DNA) through intercalation ways and can effectively cleavage CT-DNA after irradiation by light with appropriate wavelength.

  5. Photophysical and photochemical studies of a novel amphiphilic zinc phthalocyanine and its interaction with calf thymus DNA.

    PubMed

    Yuan, Linxin; Gui, Li; Wang, Yue; Zhang, Quanquan; Zhou, Lin; Wei, Shaohua

    2016-04-01

    β-tetra (aminophenoxy) sulfonic substituted zinc phthalocyanines (SNZnPc), a novel amphiphilic zinc phthalocyanine (Pc), was synthesized. The photophysical, photochemical, and photobiology properties were studied. Results indicated that the synthesized SNZnPc has good amphiphilic property and high reactive oxygen species (ROSs) generation ability. Furthermore, SNZnPc has strong affinity to calf thymus DNA (CT-DNA) through intercalation ways and can effectively cleavage CT-DNA after irradiation by light with appropriate wavelength.

  6. Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus.

    PubMed

    Brugman, Martijn H; Wiekmeijer, Anna-Sophia; van Eggermond, Marja; Wolvers-Tettero, Ingrid; Langerak, Anton W; de Haas, Edwin F E; Bystrykh, Leonid V; van Rood, Jon J; de Haan, Gerald; Fibbe, Willem E; Staal, Frank J T

    2015-11-01

    The fate and numbers of hematopoietic stem cells (HSC) and their progeny that seed the thymus constitute a fundamental question with important clinical implications. HSC transplantation is often complicated by limited T-cell reconstitution, especially when HSC from umbilical cord blood are used. Attempts to improve immune reconstitution have until now been unsuccessful, underscoring the need for better insight into thymic reconstitution. Here we made use of the NOD-SCID-IL-2Rγ(-/-) xenograft model and lentiviral cellular barcoding of human HSCs to study T-cell development in the thymus at a clonal level. Barcoded HSCs showed robust (>80% human chimerism) and reproducible myeloid and lymphoid engraftment, with T cells arising 12 wk after transplantation. A very limited number of HSC clones (<10) repopulated the xenografted thymus, with further restriction of the number of clones during subsequent development. Nevertheless, T-cell receptor rearrangements were polyclonal and showed a diverse repertoire, demonstrating that a multitude of T-lymphocyte clones can develop from a single HSC clone. Our data imply that intrathymic clonal fitness is important during T-cell development. As a consequence, immune incompetence after HSC transplantation is not related to the transplantation of limited numbers of HSC but to intrathymic events.

  7. Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants.

    PubMed

    Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Silva, Filipi Nascimento; Costa, Luciano da Fontoura; Ferreira, Leandro Rodrigues; Furlanetto, Glaucio; Chacur, Paulo; Zerbini, Maria Claudia Nogueira; Carneiro-Sampaio, Magda

    2016-02-16

    Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue--obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT)--and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the "canonical" way of thymus functioning. Conversely, DS networks represent a "non-canonical" way, i.e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes. PMID:26848775

  8. Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus

    PubMed Central

    Brugman, Martijn H.; Wiekmeijer, Anna-Sophia; van Eggermond, Marja; Wolvers-Tettero, Ingrid; Langerak, Anton W.; de Haas, Edwin F. E.; Bystrykh, Leonid V.; van Rood, Jon J.; de Haan, Gerald; Fibbe, Willem E.; Staal, Frank J. T.

    2015-01-01

    The fate and numbers of hematopoietic stem cells (HSC) and their progeny that seed the thymus constitute a fundamental question with important clinical implications. HSC transplantation is often complicated by limited T-cell reconstitution, especially when HSC from umbilical cord blood are used. Attempts to improve immune reconstitution have until now been unsuccessful, underscoring the need for better insight into thymic reconstitution. Here we made use of the NOD-SCID-IL-2Rγ−/− xenograft model and lentiviral cellular barcoding of human HSCs to study T-cell development in the thymus at a clonal level. Barcoded HSCs showed robust (>80% human chimerism) and reproducible myeloid and lymphoid engraftment, with T cells arising 12 wk after transplantation. A very limited number of HSC clones (<10) repopulated the xenografted thymus, with further restriction of the number of clones during subsequent development. Nevertheless, T-cell receptor rearrangements were polyclonal and showed a diverse repertoire, demonstrating that a multitude of T-lymphocyte clones can develop from a single HSC clone. Our data imply that intrathymic clonal fitness is important during T-cell development. As a consequence, immune incompetence after HSC transplantation is not related to the transplantation of limited numbers of HSC but to intrathymic events. PMID:26483497

  9. Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants

    PubMed Central

    Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Silva, Filipi Nascimento; da Fontoura Costa, Luciano; Ferreira, Leandro Rodrigues; Furlanetto, Glaucio; Chacur, Paulo; Zerbini, Maria Claudia Nogueira; Carneiro-Sampaio, Magda

    2016-01-01

    Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue - obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT) - and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the “canonical” way of thymus functioning. Conversely, DS networks represent a “non-canonical” way, i.e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes. PMID:26848775

  10. Effects of partial decerebration and hypophyseal allograft in the thymus of chicken embryos: thymostimulin localization and enzymatic activities.

    PubMed

    Aita, M; Romano, N

    2006-01-01

    Changes in chicken embryo thymus after partial decerebration (including the hypophysis) and hypophyseal allograft were investigated. Chicken embryos were partially decerebrated at 36-40 hr of incubation and on day 12 received a hypophyseal allograft from 18-day-old donor embryos. The embryonic thymuses were collected on day 18 and examined with histological methods, tested for the anti-thymostimulin-like immune-reaction, and for histoenzymatic activities and compared with normal and sham-operated embryos at the same age. After partial decerebration, the thymic cortical and medullary compartments diminished markedly in size. Anti-thymostimulin, succinic dehydrogenase and ATPase enzymatic activities tested, yielded negative reactions. In partially decerebrated hypophyseal allografted embryos, the same thymic compartments improved and anti-thymostimulin-like immune-reaction and enzymatic activities partially recovered. These findings confirmed the key role of hypophysis in thymic ontogenic development and provided new information in metabolic enzymatic pathways and synthesis of a thymostimulin-like substance in the thymus.

  11. Seroepidemiology of gastritis in Japanese and Dutch working populations: evidence for the development of atrophic gastritis that is not related to Helicobacter pylori.

    PubMed Central

    Schlemper, R J; van der Werf, S D; Vandenbroucke, J P; Biemond, I; Lamers, C B

    1995-01-01

    Serological markers of gastritis, like pepsinogen A, pepsinogen C, gastrin, and Helicobacter pylori antibodies, can be used to explore the state of the gastric mucosa in populations with contrasting cancer risks. A decreasing pepsinogen A:C ratio and an increasing serum gastrin are known to reflect an increasing severity of atrophic corpus gastritis, which is a precursor of gastric cancer. In 723 subjects (without gastroduodenal surgery) from Japanese (n = 225) and Dutch (n = 498) working populations, which had a similar composition of age (mean 48 years), sex (male to female ratio 6:1), and type of occupation, fasting serum samples were analysed for IgG antibodies to H pylori, pepsinogen A, pepsinogen C, and gastrin in the same laboratory. H pylori infection was significantly more prevalent in the Japanese than in the Dutch (74.7% and 31.3%); as was a very low pepsinogen A, indicative of severe mucosal atrophy (4.4% and 1.6%). Among subjects with and without severe mucosal atrophy the H pylori seropositivity rate was similar. Between the Japanese and the Dutch there were significant differences in mean gastrin (31.8 and 13.4 pmol/l) and pepsinogen A:C ratio (1.7 and 2.9). These intercountry differences were as great for H pylori negative subjects (gastrin: 23.7 and 10.3 pmol/l, pepsinogen A:C ratio: 2.4 and 3.2) as for H pylori positive subjects (gastrin: 34.6 and 20.1 pmol/l, pepsinogen A:C ratio: 1.5 and 2.5). The intercountry difference in gastrin nearly disappeared after stratification into categories of pepsinogen A:C ratio. In conclusion, the intercountry differences in pepsinogen A:C ratio and gastrin reflect a higher prevalence of mild and severe mucosal atrophy of the corpus in the Japanese than in the Dutch, both among H pylori positive and negative subjects. Thus, these findings suggest that in the Japanese the development of atrophic gastritis is in part unrelated to H pylori. PMID:7557568

  12. Controversies concerning thymus-derived regulatory T cells: fundamental issues and a new perspective

    PubMed Central

    Ono, Masahiro; Tanaka, Reiko J

    2016-01-01

    Thymus-derived regulatory T cells (Tregs) are considered to be a distinct T-cell lineage that is genetically programmed and specialised for immunosuppression. This perspective is based on the key evidence that CD25+ Tregs emigrate to neonatal spleen a few days later than other T cells and that thymectomy of 3-day-old mice depletes Tregs only, causing autoimmune diseases. Although widely believed, the evidence has never been reproduced as originally reported, and some studies indicate that Tregs exist in neonates. Thus we examine the consequences of the controversial evidence, revisit the fundamental issues of Tregs and thereby reveal the overlooked relationship of T-cell activation and Foxp3-mediated control of the T-cell system. Here we provide a new model of Tregs and Foxp3, a feedback control perspective, which views Tregs as a component of the system that controls T-cell activation, rather than as a distinct genetically programmed lineage. This perspective provides new insights into the roles of self-reactivity, T cell–antigen-presenting cell interaction and T-cell activation in Foxp3-mediated immune regulation. PMID:26215792

  13. Characterization of interaction of calf thymus DNA with gefitinib: spectroscopic methods and molecular docking.

    PubMed

    Shi, Jie-Hua; Liu, Ting-Ting; Jiang, Min; Chen, Jun; Wang, Qi

    2015-06-01

    The binding interaction of gefitinib with calf thymus DNA (ct-DNA) under the simulated physiological pH condition was studied employing UV absorption, fluorescence, circular dichroism (CD), viscosity measurement and molecular docking methods. The experimental results revealed that gefitinib preferred to bind to the minor groove of ct-DNA with the binding constant (Kb) of 1.29 × 10(4)Lmol(-1) at 298K. Base on the signs and magnitudes of the enthalpy change (ΔH(0)=-60.4 kJ mol(-1)) and entropy change (ΔS(0)=-124.7 J mol(-1)K(-1)) in the binding process and the results of molecular docking, it can be concluded that the main interaction forces between gefitinib and ct-DNA in the binding process were van der Waals force and hydrogen bonding interaction. The results of CD experiments revealed that gefitinib did not disturb native B-conformation of ct-DNA. And, the significant change in the conformation of gefitinib in gefitinib-ct-DNA complex was observed from the molecular docking results and the change was close relation with the structure of B-DNA fragments, indicating that the flexibility of gefitinib molecule also plays an important role in the formation of the stable gefitinib-ct-DNA complex.

  14. Chemical composition and biological activity of the essential oil from Thymus lanceolatus.

    PubMed

    Khadir, Abdelmounaim; Sobeh, Mansour; Gad, Haidy A; Benbelaid, Fethi; Bendahou, Mourad; Peixoto, Herbenya; Sporer, Frank; Ashour, Mohamed L; Wink, Michael

    2016-01-01

    Thymus lanceolatus is a rare species, which grows wild in Algeria and Tunis. It is used traditionally as a drink and to flavor and preserve meat and poultry. The composition of the essential oil was determined by GLC/FID and GLC/MS. Forty-nine components were identified and quantified, accounting for 96.75% of the total detected components in the oil. The oxygenated monoterpenes (74.85%) constitute the major class of volatile secondary metabolites in the oil. Thymol was the most abundant constituent (69.61%) followed by γ-terpinene (8.38%). The antioxidant activity was evaluated using both diphenylpicrylhydrazyl (DPPH˙) reduction and 2-deoxyribose (2-DR) degradation prevention methods. The oil showed a very potent antioxidant activity with IC(50) values of 0.20 ± 0.07 and 4.96 ± 0.39 μg/mL for the DPPH˙ and 2-DR methods, respectively. The antimicrobial activity of the oil was assessed using the agar diffusion method, and the in vitro cytotoxicity on five different cancer cells was examined using the MTT assay. The oil revealed promising inhibitory activity against Gram positive bacteria, especially Bacillus subtilis and Streptococcus pyogenes with an MIC value of 62.5 μg/mL. Additionally, the highest cytotoxic activity was observed against the HL-60 cells with an IC(50) of 113.5 μg/mL. These results validate some of their traditional uses in food preservation. PMID:27155003

  15. Purification and biological activity of acidic polysaccharide from leaves of Thymus vulgaris L.

    PubMed

    Chun, H; Shin, D H; Hong, B S; Cho, H Y; Yang, H C

    2001-08-01

    Polysaccharides are involved in biological responses and can activate complement system, which plays an important role in primary host defense mechanisms. We investigated anticomplementary activities from spice plants and selected thyme (Thymus vulgaris L.) as a potent complementary activator. Acidic polysaccharide (TV-3-IIIA-IIa) purified from the hot-water extract of thyme leaves by DEAE-Toyopearl 650C, Butyl-Toyopearl 650M and Sepharose CL-6B column chromatography and preparative HPLC. The purified polysaccharide, TV-3-IIIA-IIa showed potent anticomplementary activity via classical and alternative pathway with the increase proportional to dosage. TV-3-IIIA-IIa seemed to be a homogenous polymer from the results of HPLC and its molecular mass was estimated as 180 kDa. TV-3-IIIA-IIa mainly consisted of galacturonic acid (44.8 mol%), glucuronic acid (16.7 mol%), arabinose (11.1 mol%), rhamnose (9.2 mol%), galactose (8.9 mol%) and small amounts of glucose, xylose, mannose and fucose. By methylation analysis and reactivity to beta-glucosyl Yariv reagent, TV-3-IIIA-IIa was assumed to contain small amounts of type II arabinogalactan and large amounts of pectin-like polysaccharides in the structure. Based upon these results, TV-3-IIIA-IIa was suggested to be a complement activator.

  16. Review of the touch preparation cytology of spindle epithelial tumor with thymus-like differentiation

    PubMed Central

    Yi, Kijong; Rehman, Abdul; Jang, Se Min; Paik, Seung Sam

    2016-01-01

    We experienced a case of spindle epithelial tumor with thymus-like differentiation (SETTLE) with touch preparation cytology performed during the intraoperative frozen section diagnosis in a 22-year-old woman. The tumor was partially encapsulated by fibrous capsule. It was a highly cellular biphasic tumor characterized by fasciculated spindle cells with streaming pattern and tubulopapillary epithelial component. The tumor cells were positive for cytokeratin, vimentin, c-kit, epithelial membrane antigen (EMA), and thyroid transcription factor-1 (TTF-1). However, the tumor cells were negative for thyroglobulin, calcitonin, CD99, S-100 protein, CD34, smooth muscle actin, HBME-1, and galectin-3. The reviewed touch smears showed tight clusters with high cellularity. Most cellular clusters showed papillary configuration. However, some clusters showed spindle cells with streaming pattern. The spindle tumor cells showed elongated and cigar-shaped nuclei. Although the incidence is very rare, SETLLE should be included in the differential diagnosis when a spindle cell neoplasm is encountered in touch preparation cytology in young patients with a thyroid mass. PMID:27011438

  17. Interaction of Bis-Zn(II) salphen complex with calf thymus-DNA

    NASA Astrophysics Data System (ADS)

    Yussof, Aida Mastura Binti Mohd; Karim, Nurul Huda Abd

    2014-09-01

    Metal salphen family has been extensively studied over the past few years and has been reported to be good DNA stabilizers due to its high binding affinity. Binding studies of metal complex with DNA are useful for understanding the interaction mechanism and to provide an insight about the application and design of a novel effective drug target to DNA. In this study, a bis-zinc (II) salphen metal complex derived from 4-methyl-2,6-diformylphenol and 1,2-diaminobenzene (H2L) via condensation reactions has been synthesised. The zinc(II) macrocyclic complex is characterised using standard spectroscopic and structural techniques such as 1H NMR spectroscopy and FTIR spectroscopy. The binding interaction between the synthesised metal complex with calf thymus-DNA (ct-DNA) has been investigated by preliminary UV/Vis DNA study. From the preliminary UV/Vis DNA study, it shows that Bis-Zn(II) salphen complex has interaction with ct-DNA.

  18. Studies on the interaction of apigenin with calf thymus DNA by spectroscopic methods

    NASA Astrophysics Data System (ADS)

    Zhang, Shufang; Sun, Xuejun; Kong, Rongmei; Xu, Mingming

    2015-02-01

    The interaction between apigenin and calf thymus deoxyribonucleic acid (ctDNA) in a pH 7.4 Tris-HCl buffer solution was investigated by UV-Vis spectroscopy, fluorescence spectroscopy, DNA melting techniques, and viscosity measurements. It was found that apigenin molecules could intercalate into the base pairs of DNA, forming a apigenin-DNA complex with a binding constant of K310K = 6.4 × 104 L mol-1. The thermodynamic parameters enthalpy change (ΔH), entropy change (ΔS) and Gibbs free energy (ΔG) were calculated to be 7.36 × 104 J mol-1, 329 J K-1 mol-1 and -2.84 × 104 J mol-1 at 310 K, respectively. Hydrophobic interaction was the predominant intermolecular force in stabilizing the apigenin-DNA complex. Thermal denaturation study suggested that the stabilization of the ctDNA helix was increased when the apigenin binding to ctDNA as indicated by the increase in thermal denaturation temperature of ctDNA at around 5.0 °C in the presence of apigenin. Spectroscopic techniques together with melting techniques and viscosity determination provided evidences of intercalation mode of binding for the interaction between apigenin and ctDNA.

  19. Interaction studies between biosynthesized silver nanoparticle with calf thymus DNA and cytotoxicity of silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Roy, Swarup; Sadhukhan, Ratan; Ghosh, Utpal; Das, Tapan Kumar

    2015-04-01

    The interaction of calf thymus DNA (CTDNA) with silver nanoparticles (SNP) has been investigated following spectroscopic studies, analysis of melting temperature (Tm) curves and hydrodynamic measurement. In spectrophotometric titration and thermal denaturation studies of CTDNA it was found that SNP can form a complex with double-helical DNA and the increasing value of Tm also supported the same. The association constant of SNP with DNA from UV-Vis study was found to be 4.1 × 103 L/mol. The fluorescence emission spectra of intercalated ethidium bromide (EB) with increasing concentration of SNP represented a significant reduction of EB intensity and quenching of EB fluorescence. The results of circular dichroism (CD) suggested that SNP can change the conformation of DNA. From spectroscopic, hydrodynamic, and DNA melting studies, SNP has been found to be a DNA groove binder possessing partial intercalating property. Cell cytotoxicity of SNP was compared with that of normal silver salt solution on HeLa cells. Our results show that SNP has less cytotoxicity compared to its normal salt solution and good cell staining property.

  20. Binding interaction between sorafenib and calf thymus DNA: Spectroscopic methodology, viscosity measurement and molecular docking

    NASA Astrophysics Data System (ADS)

    Shi, Jie-Hua; Chen, Jun; Wang, Jing; Zhu, Ying-Yao

    2015-02-01

    The binding interaction of sorafenib with calf thymus DNA (ct-DNA) was studied using UV-vis absorption spectroscopy, fluorescence emission spectroscopy, circular dichroism (CD), viscosity measurement and molecular docking methods. The experimental results revealed that there was obvious binding interaction between sorafenib and ct-DNA. The binding constant (Kb) of sorafenib with ct-DNA was 5.6 × 103 M-1 at 298 K. The enthalpy and entropy changes (ΔH0 and ΔS0) in the binding process of sorafenib with ct-DNA were -27.66 KJ mol-1 and -21.02 J mol-1 K-1, respectively, indicating that the main binding interaction forces were van der Waals force and hydrogen bonding. The docking results suggested that sorafenib preferred to bind on the minor groove of A-T rich DNA and the binding site of sorafenib was 4 base pairs long. The conformation change of sorafenib in the sorafenib-DNA complex was obviously observed and the change was close relation with the structure of DNA, implying that the flexibility of sorafenib molecule played an important role in the formation of the stable sorafenib-ct-DNA complex.

  1. Spectroscopic and molecular docking studies on the interaction of the drug olanzapine with calf thymus DNA

    NASA Astrophysics Data System (ADS)

    Shahabadi, Nahid; Bagheri, Somayeh

    2015-02-01

    The present study investigated the binding interaction between olanzapine and calf thymus DNA (ct-DNA) using emission, absorption, circular dichroism, viscosity measurements and molecular modeling. Thermodynamic parameters (ΔH < 0 and ΔS < 0) indicated that hydrogen bond and van der Waals play main roles in the binding of the drug to ct-DNA. Spectrophotometric studies of the interaction of olanzapine with DNA have shown that it could bind to ct-DNA (Kb = 2 × 103 M-1). The binding constant is comparable to standard groove binding drugs. Competitive fluorimetric studies with Hoechst 33258 have shown that olanzapine exhibits the ability to displace the DNA-bound Hoechst 33258 indicating that binds strongly in minor groove of DNA helix. Furthermore, the drug induces detectable changes in the CD spectrum of ct-DNA as well as changes in its viscosity. All of the experimental results prove that the groove binding must be predominant. The results obtained from experimental data were in good agreement with molecular modeling studies.

  2. Lipoplex-Mediated Deintercalation of Doxorubicin from Calf Thymus DNA-Doxorubicin Complex.

    PubMed

    Das, Anupam; Adhikari, Chandan; Chakraborty, Anjan

    2016-09-01

    In this paper, we report the lipoplex-mediated deintercalation of anticancer drug doxorubicin (DOX) from the DOX-DNA complex under controlled experimental conditions. We used three zwitterionic liposomes, namely, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC), which are widely different in their phase transition temperatures to form a lipoplex with calf thymus DNA in the presence of Ca(2+) ions. The study revealed that DPPC being in sol-gel phase was more effective in releasing the drug from the DOX-DNA complex compared with liposomes that remain in liquid crystalline phase (DMPC and POPC). The higher extent of drug release in the case of DPPC liposomes was attributed to the stronger lipoplex formation with DNA as compared with that of other liposomes. Owing to the relatively smaller head group area, the DPPC liposomes in their sol-gel phase can absorb a larger number of Ca(2+) ions and hence offer a strong electrostatic interaction with DNA. This interaction was confirmed by time-resolved anisotropy and circular dichroism spectroscopy. Apart from the electrostatic interaction, the possible hydrophobic interaction between the liposomes and DNA was also taken into account for the observed deintercalation. The successful uptake of drug molecules by liposomes from the drug-DNA complex in the post-release period was also confirmed using confocal laser scanning microscopy (CLSM). PMID:27465781

  3. Review of Ethnobotanical, Phytochemical, and Pharmacological Study of Thymus serpyllum L.

    PubMed Central

    Jarić, Snežana; Mitrović, Miroslava; Pavlović, Pavle

    2015-01-01

    Thymus serpyllum L. (wild thyme) is a perennial shrub, native to areas of northern and central Europe. Its aerial parts are most frequently used in ethnomedicine (mainly for treating illnesses and problems related to the respiratory and gastrointestinal systems), although recently its essential oils are becoming more popular as an important plant-derived product. The composition of these oils is affected by geographic region, the development stage of the plant, the harvest season, habitat, and climatic conditions. Wild thyme essential oil has an ever-growing number of uses in contemporary medicine due to its pharmacological properties: antioxidative, antimicrobial, and anticancerogenic activities. The antioxidative and antimicrobial properties of the essential oil are related to the synergistic and cumulative effect of its components. In terms of antitumor and cytotoxic activity, further research into the effects of essential oil is necessary, aimed at improving its cytotoxic effects, on the basis of which appropriate medicines can be formulated. Due to its pharmacological properties, the essential oil of wild thyme, a plant used in traditional medicine, represents an important natural resource for the pharmaceutical industry. In addition, it can be a source of natural antioxidants, nutritional supplements, or components of functional foods in the food industry. PMID:26265920

  4. Spectroscopic studies of the interaction between pirimicarb and calf thymus DNA

    NASA Astrophysics Data System (ADS)

    Zhang, Guowen; Hu, Xing; Pan, Junhui

    2011-02-01

    The interaction between pirimicarb and calf thymus DNA in physiological buffer (pH 7.4) was investigated with the use of Neutral Red (NR) dye as a spectral probe by UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopy, as well as viscosity measurements and DNA melting techniques. The results revealed that an intercalation binding should be the interaction mode of pirimicarb to DNA. CD spectra indicated that pirimicarb induced conformational changes of DNA. The binding constants of pirimicarb with DNA were obtained by the fluorescence quenching method. The thermodynamic parameters, enthalpy change (Δ Hθ) and entropy change (Δ Sθ) were calculated to be -52.13 ± 2.04 kJ mol -1 and -108.8 ± 6.72 J mol -1 K -1 according to the van't Hoff equation, which suggested that hydrogen bonds and van der Waals forces might play a major role in the binding of pirimicarb to DNA. Further, the alternative least squares (ALS) method was applied to resolve a complex two-way array of the absorption spectra data, which provided simultaneously the concentration information for the three reaction components, pirimicarb, NR and DNA-NR. This ALS analysis indicated that the intercalation of pirimicarb into the DNA by substituting for NR in the DNA-NR complex.

  5. Superior antibacterial activity of nanoemulsion of Thymus daenensis essential oil against E. coli.

    PubMed

    Moghimi, Roya; Ghaderi, Lida; Rafati, Hasan; Aliahmadi, Atousa; McClements, David Julian

    2016-03-01

    Natural preservatives are being extensively investigated for their potential industrial applications in foods and other products. In this work, an essential oil (Thymus daenensis) was formulated as a water-dispersible nanoemulsion (diameter=143nm) using high-intensity ultrasound. The antibacterial activity of the essential oil in both pure and nanoemulsion forms was measured against an important food-borne pathogen bacterium, Escherichia coli. Antibacterial activity was determined by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The antibacterial activity of the essential oil against E. coli was enhanced considerably when it was converted into a nanoemulsion, which was attributed to easier access of the essential oils to the bacterial cells. The mechanism of antibacterial activity was investigated by measuring potassium, protein, and nucleic acid leakage from the cells, and electron microscopy. Evaluation of the kinetics of microbial deactivation showed that the nanoemulsion killed all the bacteria in about 5min, whereas only a 1-log reduction was observed for pure essential oil. The nanoemulsion appeared to amplify the antibacterial activity of essential oils against E. coli by increasing their ability to disrupt cell membrane integrity.

  6. Thymus vulgaris (thyme) inhibits proliferation, adhesion, migration, and invasion of human colorectal cancer cells.

    PubMed

    Al-Menhali, Afnan; Al-Rumaihi, Aisha; Al-Mohammed, Hana; Al-Mazrooey, Hana; Al-Shamlan, Maryam; AlJassim, Meaad; Al-Korbi, Noof; Eid, Ali Hussein

    2015-01-01

    Colorectal cancer (CRC) remains one of the most common malignancies and a leading cause of cancer-related deaths. Its prognosis remains poor for patients with several grades of this disease. This underscores the need for alternative modalities, such as herbal medicines, to treat this disease. A commonly used plant that appears to be of high medicinal value is Thymus vulgaris L. However, the effects of this plant on the malignant behavior of human CRC cells remains poorly investigated. This study was undertaken to determine the anticancer efficacy of T. vulgaris extract (TVE) in CRC cells. Our results show that TVE inhibits proliferation in a concentration- and time-dependent fashion. This decreased proliferation was concomitant with increased apoptotic cell death as evidenced by increased caspase3/7 activity. Moreover, TVE also decreased adhesion to fibronectin in a concentration-dependent manner. The migratory and invasive capacities of HCT116 cells were significantly inhibited by TVE. Taken together, these data suggest that the TVE inhibits malignant phenotype of colon cancer cells. Therefore, T. vulgaris could have an anticancer effect and that some of its bioactive compounds may prove to be effective treatment modalities for human CRC.

  7. Antifungal properties and inhibitory effects upon aflatoxin production of Thymus vulgaris L. by Aspergillus flavus Link.

    PubMed

    Kohiyama, Cássia Yumie; Yamamoto Ribeiro, Milene Mayumi; Mossini, Simone Aparecida Galerani; Bando, Erika; Bomfim, Natália da Silva; Nerilo, Samuel Botião; Rocha, Gustavo Henrique Oliveira; Grespan, Renata; Mikcha, Jane Martha Graton; Machinski, Miguel

    2015-04-15

    The antifungal and antiaflatoxigenic properties of Thymus vulgaris essential oil (TEO) were evaluated upon Aspergillus flavus "in vitro". Suspension containing 10(6) of A. flavus were cultivated with TEO in concentrations ranging from 50 to 500 μg/mL. TEO reached minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) at 250 μg/mL. Inhibition of ergosterol biosynthesis was detected at a concentration of 100 μg/mL of TEO. Morphological evaluation performed by both light microscopy and scanning electron microscopy showed that antifungal activity of TEO could be detected starting at a concentration of 50 μg/mL and the fungicide effect at a concentration of 250 μg/mL. TEO completely inhibited production of both B1 and B2 aflatoxins (AFB1 and AFB2) at a concentration of 150 μg/mL. This way, fungal biomass development and aflatoxin production were dependent on TEO concentration. Therefore, TEO was capable of controlling the growth of A. flavus and its production of aflatoxins.

  8. Stereochemical mechanism of two sabinene hydrate synthases forming antipodal monoterpenes in thyme (Thymus vulgaris).

    PubMed

    Krause, Sandra T; Köllner, Tobias G; Asbach, Julia; Degenhardt, Jörg

    2013-01-15

    The essential oil of Thymus vulgaris consists of a complex blend of mono- and sesquiterpenes that provides the plant with its characteristic aromatic odor. Several chemotypes have been described for thyme. In this study, we identified two enzymes of the sabinene hydrate chemotype which are responsible for the biosynthesis of its major monoterpene alcohols, (1S,2R,4S)-(Z)-sabinene hydrate and (1S,2S,4R)-(E)-sabinene hydrate. Both TPS6 and TPS7 are multiproduct enzymes that formed 16 monoterpenes and thus cover almost the whole monoterpene spectrum of the chemotype. Although the product spectra of both enzymes are similar, they form opposing enantiomers of their chiral products. Incubation of the enzymes with the potential reaction intermediates revealed that the stereospecificity of TPS6 and TPS7 is determined by the formation of the first intermediate, linalyl diphosphate. Since TPS6 and TPS7 shared an amino acid sequence identity of 85%, a mutagenesis study was employed to identify the amino acids that determine the stereoselectivity. One amino acid position had a major influence on the stereochemistry of the formed products. Based on comparative models of TPS6 and TPS7 protein structures with the GPP substrate docked in the active site pocket, the influence of this amino acid residue on the reaction mechanism is discussed.

  9. Absorption spectroscopic probe to investigate the interaction between Nd(III) and calf-thymus DNA

    NASA Astrophysics Data System (ADS)

    Devi, Ch. Victory; Singh, N. Rajmuhon

    2011-03-01

    The interaction between Nd(III) and Calf Thymus DNA (CT-DNA) in physiological buffer (pH 7.4) has been studied using absorption spectroscopy involving 4f-4f transition spectra in different aquated organic solvents. Complexation with CT-DNA is indicated by the changes in absorption intensity following the subsequent changes in the oscillator strengths of different 4f-4f bands and Judd-Ofelt intensity ( Tλ) parameters. The other spectral parameters namely Slator-Condon ( Fk's), nephelauxetic effect ( β), bonding ( b1/2) and percent covalency ( δ) parameters are computed to correlate with the binding of Nd(III) with DNA. The absorption spectra of Nd(III) exhibited hyperchromism and red shift in the presence of DNA. The binding constant, Kb has been determined by absorption measurement. The relative viscosity of DNA decreased with the addition of Nd(III). Thermodynamic parameters have been calculated according to relevant absorption data and Van't Hoff equation. The characterisation of bonding mode has been studied in detail. The results suggested that the major interaction mode between Nd(III) and DNA was external electrostatic binding.

  10. Chemical composition, larvicidal action, and adult repellency of Thymus magnus against Aedes albopictus.

    PubMed

    Park, Young-Uk; Koo, Hyun-Na; Kim, Gil-Hah

    2012-09-01

    Thymus magnus, an endemic species, is found in the Republic of Korea. The volatile compounds extracted by SPME from T. magnus were investigated for their chemical composition and electrophysiological response against the Asian tiger mosquito, Aedes albopictus. The volatile compounds of T. magnus as determined by gas chromatography mass spectrometry were gamma-terpinene (33.0%), thymol (29.9%), beta-bisabolene (8.9%), p-cymene (8.3%), alpha-terpinene (5.0%), myrcene (4.7%), beta-caryophyllene (4.0%), alpha-thujene (2.7%), camphene (1.3%), carvacrol (1.2%), and alpha-pinene (1.1%). Among these candidates, thymol exhibited complete (100%) repellent activity against female Ae. albopictus, an effect that was confirmed through evaluating the electrophysiological response on the antenna of Ae. albopictus. The effectiveness of a binary 1:2 mixture of thymol and vanillin (0.05:0.1 microl per cm2) was found to be significantly more effective than thymol alone for a period of 120 min. In addition, thymol, alpha-terpinene, and carvacrol showed high larvicidal activity against on the third-stage larvae with LC50 values of 0.9 microl per 100 ml. PMID:23833899

  11. Study of the effect of extract of Thymus vulgaris on anxiety in male rats.

    PubMed

    Komaki, Alireza; Hoseini, Faeghe; Shahidi, Siamak; Baharlouei, Negar

    2016-07-01

    There is some evidence in traditional medicine for the effectiveness of Thymus vulgaris ( bǎi lǐ xiāng) in the treatment of anxiety in humans. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of extract of T. vulgaris on rat behavior in the EPM. In the present study, the data were obtained from male Wistar rats. Animals were divided into four groups: saline group and T. vulgaris groups (50 mg/kg, 100 mg/kg, and 200 mg/kg infusion for 7 days by feeding). During the test period, the total distance covered by animals, the number of open- and closed-arm entries, and the time spent in open and closed arms of the EPM were recorded. T. vulgaris increased open-arm exploration and open-arm entry in the EPM, whereas extract of this plant has no effects on the total distance covered by animals and the number of closed-arm entries. The results of the present experiment indicate that T. vulgaris may have an anxiolytic profile in rat behavior in the EPM test, which is not influenced by the locomotor activity. Further research is required to determine the mechanisms by which T. vulgaris extract exerts an anxiolytic effect in rats. PMID:27419090

  12. Superior antibacterial activity of nanoemulsion of Thymus daenensis essential oil against E. coli.

    PubMed

    Moghimi, Roya; Ghaderi, Lida; Rafati, Hasan; Aliahmadi, Atousa; McClements, David Julian

    2016-03-01

    Natural preservatives are being extensively investigated for their potential industrial applications in foods and other products. In this work, an essential oil (Thymus daenensis) was formulated as a water-dispersible nanoemulsion (diameter=143nm) using high-intensity ultrasound. The antibacterial activity of the essential oil in both pure and nanoemulsion forms was measured against an important food-borne pathogen bacterium, Escherichia coli. Antibacterial activity was determined by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The antibacterial activity of the essential oil against E. coli was enhanced considerably when it was converted into a nanoemulsion, which was attributed to easier access of the essential oils to the bacterial cells. The mechanism of antibacterial activity was investigated by measuring potassium, protein, and nucleic acid leakage from the cells, and electron microscopy. Evaluation of the kinetics of microbial deactivation showed that the nanoemulsion killed all the bacteria in about 5min, whereas only a 1-log reduction was observed for pure essential oil. The nanoemulsion appeared to amplify the antibacterial activity of essential oils against E. coli by increasing their ability to disrupt cell membrane integrity. PMID:26471573

  13. Characterization of murine BATF: a negative regulator of activator protein-1 activity in the thymus.

    PubMed

    Williams, K L; Nanda, I; Lyons, G E; Kuo, C T; Schmid, M; Leiden, J M; Kaplan, M H; Taparowsky, E J

    2001-05-01

    BATF belongs to the AP-1/ATF superfamily of transcription factors and forms heterodimers with Jun proteins to bind AP-1 consensus DNA. Unlike Fos/Jun heterodimers which stimulate gene transcription, BATF/Jun heterodimers are transcriptionally inert and inhibit biological processes that are associated with the overstimulation of AP-1 activity. Here, we describe the murine BATF cDNA and genomic clones and map the BATF locus to chromosome 12 D2-3. Using in situ hybridization of BATF mRNA, we show that BATF gene expression is highly restricted, with the most prominent signals detected in the thymus. BATF mRNA levels are regulated differentially during discrete stages of T cell development and are up-regulated following activation of T cells in the periphery. To demonstrate the impact of BATF on AP-1 activity in vivo, AP-1 luciferase reporter mice were crossed to transgenic mice overexpressing BATF exclusively in thymic T cells. Results show that elevated levels of BATF protein correlate with reduced transactivation by AP-1. Since the differential regulation of AP-1 activity is linked to key transitions in the developing immune system, our observations support a critical role for BATF in determining the overall level of AP-1 activity, and thus AP-1 target gene expression, in specific T cell subtypes.

  14. Application of PLE for the determination of essential oil components from Thymus vulgaris L.

    PubMed

    Dawidowicz, Andrzej L; Rado, Ewelina; Wianowska, Dorota; Mardarowicz, Marek; Gawdzik, Jan

    2008-08-15

    Essential plants, due to their long presence in human history, their status in culinary arts, their use in medicine and perfume manufacture, belong to frequently examined stock materials in scientific and industrial laboratories. Because of a large number of freshly cut, dried or frozen plant samples requiring the determination of essential oil amount and composition, a fast, safe, simple, efficient and highly automatic sample preparation method is needed. Five sample preparation methods (steam distillation, extraction in the Soxhlet apparatus, supercritical fluid extraction, solid phase microextraction and pressurized liquid extraction) used for the isolation of aroma-active components from Thymus vulgaris L. are compared in the paper. The methods are mainly discussed with regard to the recovery of components which typically exist in essential oil isolated by steam distillation. According to the obtained data, PLE is the most efficient sample preparation method in determining the essential oil from the thyme herb. Although co-extraction of non-volatile ingredients is the main drawback of this method, it is characterized by the highest yield of essential oil components and the shortest extraction time required. Moreover, the relative peak amounts of essential components revealed by PLE are comparable with those obtained by steam distillation, which is recognized as standard sample preparation method for the analysis of essential oils in aromatic plants.

  15. Interaction of coumarin with calf thymus DNA: deciphering the mode of binding by in vitro studies.

    PubMed

    Sarwar, Tarique; Rehman, Sayeed Ur; Husain, Mohammed Amir; Ishqi, Hassan Mubarak; Tabish, Mohammad

    2015-02-01

    DNA is the major target for a wide range of therapeutic substances. Thus, there has been considerable interest in the binding studies of small molecules with DNA. Interaction between small molecules and DNA provides a structural guideline in rational drug designing and in the synthesis of new and improved drugs with enhanced selective activity and greater clinical efficacy. Plant derived polyphenolic compounds have a large number of biological and pharmacological properties. Coumarin is a polyphenolic compound which has been extensively studied for its diverse pharmacological properties. However, its mode of interaction with DNA has not been elucidated. In the present study, we have attempted to ascertain the mode of binding of coumarin with calf thymus DNA (Ct-DNA) through various biophysical techniques. Analysis of UV-visible absorbance spectra and fluorescence spectra indicates the formation of complex between coumarin and Ct-DNA. Several other experiments such as effect of ionic strength, iodide induced quenching, competitive binding assay with ethidium bromide, acridine orange and Hoechst 33258 reflected that coumarin possibly binds to the minor groove of the Ct-DNA. These observations were further supported by CD spectral analysis, viscosity measurements, DNA melting studies and in silico molecular docking.

  16. Controversies concerning thymus-derived regulatory T cells: fundamental issues and a new perspective.

    PubMed

    Ono, Masahiro; Tanaka, Reiko J

    2016-01-01

    Thymus-derived regulatory T cells (Tregs) are considered to be a distinct T-cell lineage that is genetically programmed and specialised for immunosuppression. This perspective is based on the key evidence that CD25(+) Tregs emigrate to neonatal spleen a few days later than other T cells and that thymectomy of 3-day-old mice depletes Tregs only, causing autoimmune diseases. Although widely believed, the evidence has never been reproduced as originally reported, and some studies indicate that Tregs exist in neonates. Thus we examine the consequences of the controversial evidence, revisit the fundamental issues of Tregs and thereby reveal the overlooked relationship of T-cell activation and Foxp3-mediated control of the T-cell system. Here we provide a new model of Tregs and Foxp3, a feedback control perspective, which views Tregs as a component of the system that controls T-cell activation, rather than as a distinct genetically programmed lineage. This perspective provides new insights into the roles of self-reactivity, T cell-antigen-presenting cell interaction and T-cell activation in Foxp3-mediated immune regulation.

  17. Myocardial Ischemic Subject’s Thymus Fat: A Novel Source of Multipotent Stromal Cells

    PubMed Central

    Salas, Julián; Lhamyani, Said; Gentile, Adriana-Mariel; Sarria García, Esteban; Hmadcha, Abdelkrim; Zayed, Hatem; Vega-Rioja, Antonio; Tinahones, Francisco J.; El Bekay, Rajaa

    2015-01-01

    Objective Adipose Tissue Stromal Cells (ASCs) have important clinical applications in the regenerative medicine, cell replacement and gene therapies. Subcutaneous Adipose Tissue (SAT) is the most common source of these cells. The adult human thymus degenerates into adipose tissue (TAT). However, it has never been studied before as a source of stem cells. Material and Methods We performed a comparative characterization of TAT-ASCs and SAT-ASCs from myocardial ischemic subjects (n = 32) according to the age of the subjects. Results TAT-ASCs and SAT-ASCs showed similar features regarding their adherence, morphology and in their capacity to form CFU-F. Moreover, they have the capacity to differentiate into osteocyte and adipocyte lineages; and they present a surface marker profile corresponding with stem cells derived from AT; CD73+CD90+CD105+CD14-CD19-CD45-HLA-DR. Interestingly, and in opposition to SAT-ASCs, TAT-ASCs have CD14+CD34+CD133+CD45- cells. Moreover, TAT-ASCs from elderly subjects showed higher adipogenic and osteogenic capacities compared to middle aged subjects, indicating that, rather than impairing; aging seems to increase adipogenic and osteogenic capacities of TAT-ASCs. Conclusions This study describes the human TAT as a source of mesenchymal stem cells, which may have an enormous potential for regenerative medicine. PMID:26657132

  18. Cardiovascular malformations in DiGeorge syndrome (congenital absence of hypoplasia of the thymus).

    PubMed Central

    Moerman, P; Goddeeris, P; Lauwerijns, J; Van der Hauwaert, L G

    1980-01-01

    Partial or complete absence of the thymus (DiGeorge syndrome, III-IV pharyngeal pouch syndrome) is often associated with agenesis or hypoplasia of the parathyroid glands and, almost invariably, with cardiovascular malformations. The clinical and pathologcial findings in 10 cases proven at necropsy are presented. All patients presented with cardiac symptoms and signs in the first weeks of life and, with one exception, all died of a cardiac cause. Major cardiovascular malformations were found in all 10 cases. Four had, in association with a ventricular septal defect of the infundibular type, an interrupted aortic arch, which was left-sided in two and right-sided in two other cases. Four patients had truncus arteriosus type I, in two of them associated with a right-sided aortic arch. Two patients with tetralogy of Fallot had a right-sided aortic arch. Only two of the 10 had a normally developed left aortic arch. Aberrant subclavian arteries were found in five cases. From our observations and a survey of the previously published patients it appears that 90 per cent of the necropsy-proven cases of DiGeorge syndrome have cardiovascular malformations and that 95 per cent of these malformations can be classified as aortic arch anomalies, truncus ateriosus, or tetralogy of Fallot. Images PMID:7426208

  19. Influence of ultraviolet radiation on calf thymus DNA studied by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Tang, Yulong; Guo, Zhouyi

    2005-01-01

    In order to assess the mutagenic effects of ultraviolet (UV) and solar irradiation on DNA, Raman spectroscopy is used to investigate the structural changes of calf thymus DNA in aqueous solution after ultraviolet radiation. The damage to DNA induced by UV is usually carried out with a germicidal lamp, which mainly covers the region of UVC. For the sake of making a complete investigation of the damage to DNA by ultraviolet radiation, we use different intervals of UV (UVA, UVB and UVC) to conduct our experiments. Such UV radiation is obtained from a solar UV simulator (SS) made by us, which can be conveniently adjusted to different wavelengths and radiation intensities. From the comparison of the Raman spectra of DNA in aqueous solution before and after ultraviolet radiation, it can be inferred that the UV-C has a serious influence on the DNA molecular conformation and damages the hydrogen bonds and bases, UV-B only damages the DNA molecular structure to some extent while UV-A almost does not play an impact on the DNA molecular conformation. For all the three regions of UV, the damage increases with the elongation of irradiation time and is first observed in pyrimidine-dimer bases and deoxyribose. The experimental results also partly support the formation of several types of dimeric lesions between adjacent pyrimidine bases, most notably cyclobutane pyrimidine dimers (CPDs) and the Dewar valence isomers.

  20. Antifungal properties and inhibitory effects upon aflatoxin production of Thymus vulgaris L. by Aspergillus flavus Link.

    PubMed

    Kohiyama, Cássia Yumie; Yamamoto Ribeiro, Milene Mayumi; Mossini, Simone Aparecida Galerani; Bando, Erika; Bomfim, Natália da Silva; Nerilo, Samuel Botião; Rocha, Gustavo Henrique Oliveira; Grespan, Renata; Mikcha, Jane Martha Graton; Machinski, Miguel

    2015-04-15

    The antifungal and antiaflatoxigenic properties of Thymus vulgaris essential oil (TEO) were evaluated upon Aspergillus flavus "in vitro". Suspension containing 10(6) of A. flavus were cultivated with TEO in concentrations ranging from 50 to 500 μg/mL. TEO reached minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) at 250 μg/mL. Inhibition of ergosterol biosynthesis was detected at a concentration of 100 μg/mL of TEO. Morphological evaluation performed by both light microscopy and scanning electron microscopy showed that antifungal activity of TEO could be detected starting at a concentration of 50 μg/mL and the fungicide effect at a concentration of 250 μg/mL. TEO completely inhibited production of both B1 and B2 aflatoxins (AFB1 and AFB2) at a concentration of 150 μg/mL. This way, fungal biomass development and aflatoxin production were dependent on TEO concentration. Therefore, TEO was capable of controlling the growth of A. flavus and its production of aflatoxins. PMID:25466118

  1. Antibacterial, antioxidant and hypoglycaemic effects of Thymus capitatus (L.) Hoffmanns. et Link leaves' fractions.

    PubMed

    Iauk, Liliana; Acquaviva, Rosaria; Mastrojeni, Silvana; Amodeo, Andrea; Pugliese, Michela; Ragusa, Monica; Loizzo, Monica R; Menichini, Francesco; Tundis, Rosa

    2015-06-01

    The aim of this study was to examine the bioactivity of the methanol fraction (MF) and n-hexane fraction (HF) of Thymus capitatus leaves in relation to their constituents analysed by gas chromatography and gas chromatography-mass spectrometry. The effects of T. capitatus on the growth of pathogenic bacteria associated with respiratory diseases (13 gram-positive and 4 gram-negative) were determined using a microdilution method. The MF was particularly effective on Streptococcus pneumoniae and Moraxella catarrhalis. The antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), ferric-reducing antioxidant power and β-carotene bleaching assays. A strong activity using β-carotene bleaching test was observed with the MF (IC50 of 0.7 μg/mL after 30 min of incubation). In the hypoglycaemic test, a selective α-amylase inhibitory activity was detected with the HF begging the most active (IC50 of 422.5 μg/mL). T. capitatus may represent a source of natural bioactive compounds. PMID:25032744

  2. Interaction of dinuclear cadmium(II) 5-Cl-salicylaldehyde complexes with calf-thymus DNA.

    PubMed

    Ristovic, Maja Sumar; Zianna, Ariadni; Psomas, George; Hatzidimitriou, Antonios G; Coutouli-Argyropoulou, Evdoxia; Lalia-Kantouri, Maria

    2016-04-01

    Five dinuclear Cd(II) complexes with the anion of 5-Cl-salicylaldehyde (5-Cl-saloH) were synthesized in the absence or presence of the α-diimines: 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neoc) or 2,2'-dipyridylamine (dpamH) and characterized as [Cd(5-Cl-salo)2(CH3OH)]2 (1), [Cd(5-Cl-salo)2(bipy)]2 (2), [Cd(5-Cl-salo)2(phen)]2 (3), [Cd(5-Cl-salo)(neoc)(ONO2)]2 (4) and [Cd(5-Cl-salo)(dpamΗ)(ONO2)]2 (5). The complexes were characterized by spectroscopic techniques (IR, UV-vis, (1)H-NMR and (13)C-NMR), elemental analysis and molar conductivity measurements. The structures of four complexes (1-3 and 5) were determined by X-ray crystallography, providing all three possible coordination modes of the ligand 5-Cl-salicylaldehyde, i.e. bidentate or tridentate chelating and/or bridging mode. The complexes bind to calf-thymus (CT) DNA mainly by intercalation, as concluded by the viscosity measurements and present relatively high DNA-binding constants. The complexes exhibit significant ability to displace ethidium bromide (EB) from the EB-DNA complex, thus indirectly proving the intercalation as the most possible binding mode to CT DNA.

  3. Studies on the interaction of diacetylcurcumin with calf thymus-DNA

    NASA Astrophysics Data System (ADS)

    Sahoo, Bijaya Ketan; Ghosh, Kalyan Sundar; Bera, Rabindranath; Dasgupta, Swagata

    2008-07-01

    Ongoing research on curcumin and its structural derivatives are a subject of growing interest because of their demonstrated biological properties. Diacetylcurcumin (DAC), a synthetic derivative of natural non-toxic curcumin has been shown to affect a host of activities ranging from wound healing to life threatening diseases like AIDS, cancer etc. The interaction of diacetylcurcumin (DAC) with calf thymus-DNA (ct-DNA) has been investigated by spectroscopic and viscometric techniques. The fluorescence intensity of DAC was quenched by ct-DNA. The mean binding constant obtained from the spectroscopic techniques was 3.97 ± 0.31 × 10 5 M -1. Circular dichroism studies did not reveal any unwinding of the DNA helix on interaction with DAC, implying no conformational changes. The binding mode was analyzed by competitive binding between ethidium bromide (EB) and DAC for ct-DNA and also by viscometric studies. DAC was found to be a minor groove binder with a preference for the A-T region compared to the G-C region. This was substantiated by displacement studies with Hoechst 33258, a known minor groove binder. Docking studies were found to corroborate the experimental results.

  4. Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): is cytopathological diagnosis possible?

    PubMed

    Kloboves-Prevodnik, Veronika; Jazbec, Janez; Us-Krasovec, Marija; Lamovec, Janez

    2002-05-01

    Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare tumor of the thyroid gland which occurs predominantly in children, adolescents, and young adults. It usually presents as a painless neck or thyroid mass and only exceptionally as a diffusely enlarged thyroid gland, without metastatic disease at diagnosis. We report on the case of 12-yr-old girl who had diffusely enlarged thyroid gland for about 1 yr and was initially treated for thyroiditis. Fine-needle aspiration biopsy (FNAB) was performed 8 mo after the first admission. Cytological examination of smears showed unusual morphological features. FNAB smears were cellular, with dissociated cells, naked oval nuclei, aggregates, and groups. Three main cell types were observed: spindle, epithelioid, and epithelial. These cells were uniform, cytologically bland, with few mitotic figures. The distinction between these cells was not always unequivocal. In the background of the smears abundant red extracellular material in the form of fine, dust-like granules and irregular patches were present. It was also observed in some aggregates and groups of tumor cells. Spindle and epithelioid cells were immunocytochemically diffusely pan-cytokeratin-positive. In the differential diagnosis, medullary thyroid carcinoma and SETTLE were suggested. The final histological diagnosis was SETTLE. In cases of SETTLE presented as a diffuse thyromegaly the correct diagnosis may be delayed because clinically and ultrasonographically thyroiditis is suspected. To avoid such a delay, FNAB should be used preoperatively. It can provide specific cytological diagnosis based on morphological features and certain immunocytochemical characteristics of the tumor.

  5. Branchial Cleft-Like Cysts Involving 3 Different Organs: Thyroid Gland, Thymus, and Parotid Gland.

    PubMed

    Nakazawa, Tadao; Kondo, Tetsuo; Oishi, Naoki; Tahara, Ippei; Kasai, Kazunari; Inoue, Tomohiro; Mochizuki, Kunio; Katoh, Ryohei

    2015-10-01

    Branchial cleft cysts (BCCs) are also named lateral cervical cysts and widely acknowledged as being derived from embryonic remnants. Lymphoepithelial cysts (LECs) generally show microscopic features that are identical to those of BCCs, and rarely occur at unusual sites or organs.A case of multiple cysts arising in both lobes of the thyroid gland, thymus, and right parotid gland in a 41-year-old man is reported. Clinically, the patient presented with Hashimoto's thyroiditis for about 20 years and had past histories of idiopathic thrombocytopenic purpura and severe respiratory infection.This case is unusual in that multiple cysts arose synchronously and/or heterochronously and grew, increasing their sizes in these different organs. Microscopic examinations revealed that all of the cysts were composed of squamous epithelium, dense lymphoid tissue with germinal centers, and a fibrous capsule. These findings corresponded to those of BCCs or LECs. It is notable that the histopathological features were nearly the same in the individual organs. A review of the literature disclosed no previous such reported cases.The etiology is unknown. However, based upon the similar histopathological features of all the excised specimens, common immune and/or hematopoietic disorders may have contributed to their occurrence and development in association with putative genetic abnormalities.

  6. Branchial Cleft-Like Cysts Involving 3 Different Organs: Thyroid Gland, Thymus, and Parotid Gland.

    PubMed

    Nakazawa, Tadao; Kondo, Tetsuo; Oishi, Naoki; Tahara, Ippei; Kasai, Kazunari; Inoue, Tomohiro; Mochizuki, Kunio; Katoh, Ryohei

    2015-10-01

    Branchial cleft cysts (BCCs) are also named lateral cervical cysts and widely acknowledged as being derived from embryonic remnants. Lymphoepithelial cysts (LECs) generally show microscopic features that are identical to those of BCCs, and rarely occur at unusual sites or organs.A case of multiple cysts arising in both lobes of the thyroid gland, thymus, and right parotid gland in a 41-year-old man is reported. Clinically, the patient presented with Hashimoto's thyroiditis for about 20 years and had past histories of idiopathic thrombocytopenic purpura and severe respiratory infection.This case is unusual in that multiple cysts arose synchronously and/or heterochronously and grew, increasing their sizes in these different organs. Microscopic examinations revealed that all of the cysts were composed of squamous epithelium, dense lymphoid tissue with germinal centers, and a fibrous capsule. These findings corresponded to those of BCCs or LECs. It is notable that the histopathological features were nearly the same in the individual organs. A review of the literature disclosed no previous such reported cases.The etiology is unknown. However, based upon the similar histopathological features of all the excised specimens, common immune and/or hematopoietic disorders may have contributed to their occurrence and development in association with putative genetic abnormalities. PMID:26496296

  7. Characterization of interaction of calf thymus DNA with gefitinib: spectroscopic methods and molecular docking.

    PubMed

    Shi, Jie-Hua; Liu, Ting-Ting; Jiang, Min; Chen, Jun; Wang, Qi

    2015-06-01

    The binding interaction of gefitinib with calf thymus DNA (ct-DNA) under the simulated physiological pH condition was studied employing UV absorption, fluorescence, circular dichroism (CD), viscosity measurement and molecular docking methods. The experimental results revealed that gefitinib preferred to bind to the minor groove of ct-DNA with the binding constant (Kb) of 1.29 × 10(4)Lmol(-1) at 298K. Base on the signs and magnitudes of the enthalpy change (ΔH(0)=-60.4 kJ mol(-1)) and entropy change (ΔS(0)=-124.7 J mol(-1)K(-1)) in the binding process and the results of molecular docking, it can be concluded that the main interaction forces between gefitinib and ct-DNA in the binding process were van der Waals force and hydrogen bonding interaction. The results of CD experiments revealed that gefitinib did not disturb native B-conformation of ct-DNA. And, the significant change in the conformation of gefitinib in gefitinib-ct-DNA complex was observed from the molecular docking results and the change was close relation with the structure of B-DNA fragments, indicating that the flexibility of gefitinib molecule also plays an important role in the formation of the stable gefitinib-ct-DNA complex. PMID:25839749

  8. Changes in Structure and Histochemistry of Glandular Trichomes of Thymus quinquecostatus Celak

    PubMed Central

    Jia, Ping; Gao, Ting; Xin, Hua

    2012-01-01

    The types, morphology, distribution, structure, and development process of the glandular trichomes on the leaves of Thymus quinquecostatus Celak had been investigated in this study. Two different types of glandular trichomes were determined in detail, namely, capitate trichomes and peltate ones. Besides, there were distinct differences on morphology, distribution, structure, and development process between the two kinds of trichomes. As the peltate trichome stepping into senium stage, it caved in the epidermis integrally, which was different from the capitate one. The secretion of the capitate trichome contained essential oil, polyphenols, and flavonoids, while, in addition to these three components, the secretion of the peltate one also contained acid polysaccharides. A distinctive difference was also seen in the secretory pathway of the secretion between the two types of trichomes. The secretion of capitate one was extruded through the cuticle of the head cell, but the secretion of the peltate one kept accumulating in the subcuticular space of the head cells until it was released by cuticle rupture. PMID:22545009

  9. Binding characteristics of sodium saccharin with calf thymus DNA in vitro.

    PubMed

    Zhang, Guowen; Wang, Langhong; Zhou, Xiaoyue; Li, Yu; Gong, Deming

    2014-01-29

    The binding characteristics of sodium saccharin (SSA), an artificial sweetener, with calf thymus DNA (ctDNA) were investigated by multispectroscopic techniques, chemometrics, and molecular simulation. A combined fluorescence and UV-vis spectroscopic data matrix was resolved by the multivariate curve resolution-alternating least-squares (MCR-ALS) chemometrics algorithm. The MCR-ALS analysis extracted simultaneously the concentration profiles and spectra for the three components (SSA, ctDNA, and SSA-ctDNA complex) to quantitatively monitor the SSA-ctDNA interaction, which is difficult to perform by conventional spectroscopic approach. The binding mode of SSA to ctDNA was principally through groove binding as revealed by ctDNA melting temperature studies, viscosity measurements, and iodide and salt quenching effects. Analysis of the Fourier transform infrared and circular dichroism spectra as well as molecular docking indicated that SSA preferentially bound to the guanine base of ctDNA and led to a transformation from B-like DNA structure to A-like conformation. Moreover, gel electrophoresis results suggested that SSA did not induce any significant cleavage in plasmid DNA.

  10. Sebaceous lymphadenoma of the thymus: A clinicopathologic and immunohistochemical study of 2 cases.

    PubMed

    Weissferdt, Annikka; Kalhor, Neda; Moran, Cesar A

    2016-10-01

    Two cases of primary sebaceous lymphadenoma of the thymus are presented. The patients were a man and a woman 58 and 77 years old, respectively. The female patient had a history of breast carcinoma and on follow-up was identified to have an anterior mediastinal mass; the male patient did not have any history of malignancy, and the tumor was discovered during a chest radiographic evaluation when the patient presented with symptoms of fatigue, chest pain, and dyspnea. Histologically, both lesions were characterized by the presence of solid-cystic epithelial islands in a prominent lymphocytic background. The epithelial islands were haphazardly distributed in the form of small tubular structures with focal keratinization and groups of epithelial cells with clear cytoplasm, round nuclei and lack of mitotic activity in keeping with sebaceous cells. The presence of germinal centers in the lymphoid background was seen in both cases. Immunohistochemically, the epithelial component was positive for cytokeratin 8 (CAM5.2), cytokeratin 5/6, and for adipophilin in the sebaceous component. B- and T-cell markers were positive in the lymphoid component. Clinical follow-up in both patients showed that the 2 patients were well and alive 3 years after diagnosis. The cases herein presented expand the spectrum of salivary gland-type tumors in the mediastinum and raise awareness of lesions which are easily confused with other more common thymic tumors that have different prognosis and treatment implications. PMID:27374279

  11. Inhibitory action of oestrogen on calcium-induced mitosis in rat bone marrow and thymus.

    PubMed

    Smith, G R; Gurson, M L; Riddell, A J; Perris, A D

    1975-04-01

    In the male rat injections of CaCl-2 and MgCl-2 stimulated mitosis in bone marrow and thymus tissue. The magnesium salt was also mitogenic in the normal female, but calcium only exerted its mitogenic effect after ovariectomy. Oestradiol, but not progesterone replacement therpy abolished calcium-induced mitosis in the ovariectomized rat. The inability of calcium to stimulate cell division was also apparent in the thyroparathyroidectomized female rat, suggesting the oestradiol blockage did not operate via some indirect action on the calcium homeostatic hormones calcitonin or parathyroid hormone. When thymic lymphocytes derived from male or female rats were isolated and maintained in suspension, increased calcium or magnesium concentrations in the culture medium stimulated the entry of cells into mitosis. Addition of oestradiol to the culture medium abolished the mitogenic effect of increased calcium levels, but had no effect on magnesium-induced proliferation. These experiments suggested that oestradiol might act at the cell surface to prevent the influx of calcium but not magnesium ions into the interior of the cell and thus to block the sequence of biochemical events which led to the initiation of DNA synthesis and culminate in mitosis.

  12. Carboplatin interaction with calf-thymus DNA: A FTIR spectroscopic approach

    NASA Astrophysics Data System (ADS)

    Jangir, Deepak K.; Tyagi, Gunjan; Mehrotra, Ranjana; Kundu, Suman

    2010-04-01

    Carboplatin is a chemotherapeutic drug, used for the treatment of different types of cancers, particularly solid tumors. Carboplatin, like other platinum containing drugs, exerts its cytotoxic effect through DNA binding via cross-linking. It forms interstrand and intrastrand cross-linking with DNA. Intrastrand cross-linking is dominant and believed to be conferring antitumoral efficacy of the drug. This cross-linking results in alteration of DNA winding and bending, which hampers DNA replication and transcription and finally leads to cell death. In the present work, we studied the interaction of carboplatin with calf-thymus DNA in buffer solution under physiological conditions. Different concentrations of carboplatin were incubated with a constant DNA concentration to form carboplatin-DNA complexes. These complexes were studied with Fourier Transform Infrared (FTIR) spectroscopy and circular dichroism (CD) spectroscopy to understand the binding modes of carboplatin with DNA and its effect on DNA conformation. The results showed that carboplatin binds to DNA through direct interaction of platin-DNA bases (guanine, thymine, adenine and cytosine), with a small perturbation of phosphate group of DNA backbone, while DNA remains in the B-conformation. DNA aggregation was also observed at higher drug concentrations.

  13. Repellent and fumigant toxicity of essential oil from Thymus persicus against Tribolium castaneum and Callosobruchus maculatus.

    PubMed

    Moharramipour, S; Taghizadeh, A; Meshkatalsadat, M H; Talebi, A A; Fathipour, Y

    2008-01-01

    Repellent and insecticidal activity of the essential oil extracted from Thymus persicus (Roniger ex Reach. F.) Jalas was evaluated against two stored-product beetles Tribolium castaneum (Herbst) and Callosobruchus maculatus (F.). Dry flowering aerial parts of the plant were subjected to hydro distillation using a modified Clevenger-type apparatus. The repellent and fumigant toxicity were tested against 1-7 days old adult beetles at 27 +/- 1 degrees C and 65 +/- 5% RH in dark condition. The repellency on C. maculatus and T. castaneum at highest concentration (2 microL/mL acetone) was 82.40% and 70.40% respectively. Fumigation bioassays showed that C. maculatus adults were significantly more susceptible (LC50 = 2.39 microL/L air) to the essential oil than T. castaneum adults (LC50 = 234.42 microL/L air). It could be concluded that T. persicus may have potential for applications in management of stored-product pests because of its safety, strong repellency and fumigant toxicity. PMID:19226805

  14. Study on the Interaction between Isatin-β-Thiosemicarbazone and Calf Thymus DNA by Spectroscopic Techniques

    PubMed Central

    Pakravan, Parvaneh; Masoudian, Shahla

    2015-01-01

    The interaction between isatin-β-thiosemicarbazone (IBT) and calf thymus DNA (CT-DNA) was investigated in physiological buffer (pH 7.4) using Neutral Red (NR) dye as a spectral probe by UV–Vis absorption and fluorescence spectroscopy, as well as viscosity measurements. The IBT is stabilized by intercalation in the DNA (K [IBT –DNA] = 1.03×105 M−1), and displaces the NR dye from the NR–DNA complex. The binding constants Kf and number of binding sites (n≈1) of IBT with DNA were obtained by fluorescence quenching method at different temperatures. Furthermore, the enthalpy and entropy of the reaction between IBT and CT-DNA showed that the reaction is enthalpy-favored and entropy-disfavored. The changes in the base stacking of CT-DNA upon the binding of IBT are reflected in the circular dichroic (CD) spectral studies. The viscosity increase of CT-DNA solution is another evidence to indicate that, IBT is able to be intercalated in the DNA base pairs. PMID:25561917

  15. Binding studies of the antidiabetic drug, metformin to calf thymus DNA using multispectroscopic methods

    NASA Astrophysics Data System (ADS)

    Shahabadi, Nahid; Heidari, Leila

    2012-11-01

    Interaction between antidiabetic drug, Metformin and calf thymus DNA (CT-DNA) in (50 mM Tris-HCl) buffer were studied by UV-Visible absorption, fluorescence, CD spectroscopy and viscosity measurements. In fluorimetric studies, the enthalpy and entropy of the reaction between the drug and CT-DNA showed that the reaction is exothermic (ΔH = -35.4522 kJ mol-1; ΔS = -49.9523 J mol-1 K-1). The competitive binding studies showed that the drug could release Hoechst 33258 completely. The complex showed absorption hyperchromism in its UV-Vis spectrum with DNA. The calculated binding constant, Kb, obtained from UV-Vis absorption studies was 8.3 × 104 M-1. Moreover, the changes in the CD spectra in the presence of the drug show stabilization of the right-handed B form of CT-DNA. Finally, viscosity measurements revealed that the binding of the complex with CT-DNA could be surface binding, mainly due to groove binding.

  16. Multivariate optimization of hydrodistillation-headspace solvent microextraction of thymol and carvacrol from Thymus transcaspicus.

    PubMed

    Kiyanpour, Vahid; Fakhari, Ali Reza; Alizadeh, Reza; Asghari, Behvar; Jalali-Heravi, Mehdi

    2009-08-15

    In this paper multivariate response surface methodology (RSM) has been used for the optimization of hydrodistillation-headspace solvent microextraction (HD-HSME) of thymol and carvacrol in Thymus transcaspicus. Quantitative determination of compounds of interest was performed simultaneously using gas chromatography coupled with flame ionization detector (GC-FID). Parameters affecting the extraction efficiency were assessed and the optimized values were 5 min, 2 microL and 3 min for the extraction time, micro-drop volume and cooling time after extraction, respectively. The amounts of analyte extracted increased with plant weight. The calibration curves were linear in the ranges of 6.25-81.25 and 1.25-87.50 mg L(-1) for thymol and carvacrol, respectively. Limit of detection (LOD) for thymol and carvacrol was 1.87 and 0.23 mg L(-1), respectively. Within-day and between-day precisions for both analytes were calculated in three different concentrations and recoveries obtained were in the range of 89-101% and 95-116% for thymol and carvacrol, respectively. PMID:19576432

  17. Chemical composition and antioxidant and anticandidal activities of essential oils from different wild Moroccan Thymus species.

    PubMed

    Jamali, Chaima Alaoui; El Bouzidi, Laila; Bekkouche, Khalid; Lahcen, Hassani; Markouk, Mohammed; Wohlmuth, Hans; Leach, David; Abbad, Abdelaziz

    2012-06-01

    Samples of the aerial parts of Thymus broussonetii, T. ciliatus, T. leptobotrys, T. maroccanus, T. pallidus, T. satureioides, and T. serpyllum collected from different natural regions in southern and south-western Morocco were analyzed for their qualitative and quantitative essential oil profiles. In total, 46 compounds, representing more than 99% of the oils, were characterized. Monoterpenes, both hydrocarbons (12.9-58.0%) and oxygenated monoterpenes (38.8-81.1%), were the principal classes of compounds for most of the thyme species studied. Cluster analysis allowed the classification of the species into three main groups: a carvacrol group (Group I), comprising the species T. maroccanus and T. leptobotrys, a linalyl acetate and (E)-nerolidol group (Group II), represented by T. serpyllum, and a thymol and/or carvacrol, γ-terpinene, and p-cymene group (Group III), composed of T. satureioides, T. broussonetii, T. ciliatus, and T. pallidus. The essential oils were screened for their antioxidant and anticandidal activities. The data showed that the oils obtained from T. leptobotrys and T. maroccanus (carvacrol group) possessed the highest antioxidant activities as assessed by the determination of the DPPH free radical-scavenging ability and the ferric-reducing potential. The anticandidal assays indicated that the highest activity was noticed for the essential oil isolated from T. leptobotrys. PMID:22700236

  18. The MOUSE Squad

    ERIC Educational Resources Information Center

    Borja, Rhea R.

    2004-01-01

    This article presents a New York city after-school program started by MOUSE (Making Opportunities for Upgrading Schools and Education), a national nonprofit group that teaches students how to fix computers, and equips them with the communication and problem-solving skills to help them in the working world. The MOUSE program is part of a trend…

  19. Human thymus medullary epithelial cells promote regulatory T-cell generation by stimulating interleukin-2 production via ICOS ligand.

    PubMed

    Nazzal, D; Gradolatto, A; Truffault, F; Bismuth, J; Berrih-Aknin, S

    2014-09-11

    Natural thymic T regulatory (tTreg) cells maintain tolerance to self-antigen. These cells are generated in the thymus, but how this generation occurs is still controversial. Furthermore, the contribution of thymus epithelial cells to this process is still unclear, especially in humans. Using an exceptional panel of human thymic samples, we demonstrated that medullary thymus epithelial cells (mTECs) promote the generation of tTreg cells and favor their function. These effects were mediated through soluble factors and were mTEC specific since other cell types had no such effect. By evaluating the effects of mTECs on the absolute number of Treg cells and their state of proliferation or cell death, we conclude that mTECs promote the proliferation of newly generated CD25+ cells from CD4+CD25- cells and protect Treg cells from cell death. This observation implicates Bcl-2 and mitochondrial membrane potential changes, indicating that the intrinsic cell death pathway is involved in Treg protection by mTECs. Interestingly, when the mTECs were cultured directly with purified Treg cells, they were able to promote their phenotype but not their expansion, suggesting that CD4+CD25- cells have a role in the expansion process. To explore the mechanisms involved, several neutralizing antibodies were tested. The effects of mTECs on Treg cells were essentially due to interleukin (IL)-2 overproduction by thymus CD4+ T cells. We then searched for a soluble factor produced by mTECs able to increase IL-2 production by CD4+ cells and could identify the inducible T-cell costimulator ligand (ICOSL). Our data strongly suggest a « ménage à trois »: mTEC cells (via ICOSL) induce overproduction of IL-2 by CD25- T cells leading to the expansion of tTreg cells. Altogether, these results demonstrate for the first time a role of mTECs in promoting Treg cell expansion in the human thymus and implicate IL-2 and ICOSL in this process.

  20. Mouse genome database 2016.

    PubMed

    Bult, Carol J; Eppig, Janan T; Blake, Judith A; Kadin, James A; Richardson, Joel E

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data.