tbuckley/cabot-search huggingface dataset:
Regulatory T Cells: Mechanisms of Differentiation and Function
Authors: Steven Z. Josefowicz, Li-Fan Lu, Alexander Y. Rudensky
Journal: Annual Review of Immunology (2007)

The immune system has evolved to mount an effective defense against pathogens and to minimize deleterious immune-mediated inflammation caused by commensal microorganisms, immune responses against self and environmental antigens, and metabolic inflammatory disorders. Regulatory T (Treg) cell-mediated suppression serves as a vital mechanism of negative regulation of immune-mediated inflammation and features prominently in autoimmune and autoinflammatory disorders, allergy, acute and chronic infections, cancer, and metabolic inflammation. The discovery that Foxp3 is the transcription factor that specifies the Treg cell lineage facilitated recent progress in understanding the biology of regulatory T cells. In this review, we discuss cellular and molecular mechanisms in the differentiation and function of these cells.
Extra-articular Manifestations of Rheumatoid Arthritis
Authors: F. D. Hart
Journal: BMJ (1969)

Abstract   This paper only draws attention to some of the extra-articular manifestations of this extraordinary disease; or should it be diseases? The patient—and it has been estimated that about 5% of the population in the United Kingdom are affected — is sick in joints, body, and mind. I have not attempted in this review to discuss the last, but anxiety and depression play a large part at some time in almost all patients. Nor have I attempted to dig in the rich field of iatrogenic drug-induced disease; this is a large subject in itself, for few patients swallow so many drugs for so long as the rheumatoid sufferer. He who treats these patients has, indeed, to treat the whole man in every sense of the term.
Expression pattern of integrin adhesion molecules in endometriosis and human endometrium
Authors: P. Regidor
Journal: Human Reproduction Update (1998)

Integrins are cell adhesion molecules that undergo cell-specific dynamic changes during the normal menstrual cycle in the human endometrium. Here, using immunohistochemistry, we have investigated the expression pattern of the integrins alphav, alpha2beta1, alpha3beta1, alpha3, alpha6, beta1, beta2 and beta3 in the human ectopic endometrium of 30 patients and in nine cases in the corresponding eutopic endometrium. The biopsies were obtained during the early or late follicular phase (25 cases), during the corpus luteum phase (four cases) and in one case after 6 months' treatment with a gonadotrophin releasing hormone (GnRH) agonist. The integrin expression was independent of the ovarian steroid situation at the time of biopsy. The integrin alpha6 was expressed in all endometriotic and endometrium samples. The integrin alpha3 was absent in all endometrium tissues of patients with endometriosis. However, the corresponding endometriotic lesions re-expressed this adhesion molecule in 15 cases. No change in integrin beta3 expression pattern could be demonstrated in either endometriotic lesions or endometrium samples, regardless of the menstrual cycle phase. A correlation between serum oestradiol and progesterone concentrations and the expression of the investigated integrins was not observed, thus indicating that these two hormones play a minor role in the regulation of the cell adhesion molecules examined. Our investigation suggests that endometriosis is a dedifferentiated disease as it expressed different integrins in comparison with the eutopic endometrium, and independently of the hormonal situation. The ability of endometriotic tissues to express integrins may explain the high recurrence rates in patients with endometriosis, as these samples retain their adhesion potency after retrograde menstruation and are thus able to establish cell-cell and cell-matrix interactions with the surrounding peritoneum.
Medicolegal reports in asylum applications: a framework for addressing the practical and ethical challenges
Authors: Alexandra Pitman
Journal: Journal of the Royal Society of Medicine (2010)

Summary The clinical care of asylum-seekers may bring clinicians in contact with the immigration authorities. A request for a medicolegal report usually requires the responsible clinician to state their opinion on the risks involved in returning an applicant to their country of origin, taking into account their current condition, the treatments available in that country, and the risks involved in travel. This review draws on clinical experience and a review of the literature to describe the work involved in preparing a medical report requested by immigration authorities. Although the starting point chosen is the psychiatric report, the principles described apply to the preparation of immigration reports in any medical discipline.
Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the Pancreatic Cancer Cohort Consortium
Authors: Brian M. Wolpin, Peter Kraft, Myron Gross, Kathy Helzlsouer, H. Bas Bueno-de-Mesquita, Emily Steplowski, Rachael Z. Stolzenberg-Solomon, Alan A. Arslan, Eric J. Jacobs, Andrea LaCroix, Gloria Petersen, Wei Zheng, Demetrius Albanes, Naomi E. Allen, Laufey Amundadottir, Garnet Anderson, Marie-Christine Boutron-Ruault, Julie E. Buring, Federico Canzian, Stephen J. Chanock, Sandra Clipp, John Michael Gaziano, Edward L. Giovannucci, Göran Hallmans, Susan E. Hankinson, Robert N. Hoover, David J. Hunter, Amy Hutchinson, Kevin Jacobs, Charles Kooperberg, Shannon M. Lynch, Julie B. Mendelsohn, Dominique S. Michaud, Kim Overvad, Alpa V. Patel, Aleksandar Rajkovic, Maria-José Sanchéz, Xiao-Ou Shu, Nadia Slimani, Gilles Thomas, Geoffrey S. Tobias, Dimitrios Trichopoulos, Paolo Vineis, Jarmo Virtamo, Jean Wactawski-Wende, Kai Yu, Anne Zeleniuch-Jacquotte, Patricia Hartge, Charles S. Fuchs
Journal: Cancer Research (2010)

Abstract A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18–1.62], 1.47 (95% CI, 1.07–2.02), and 1.53 (95% CI, 1.21–1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13–1.58) and 1.61 (95% CI, 1.22–2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14–1.85) and 2.42 (1.28–4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03–3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk. Cancer Res; 70(3); 1015–23
The Molecular Descent of the Major Histocompatibility Complex
Authors: J Klein, Y Satta, C O'hUigin, N Takahata
Journal: Annual Review of Immunology (1993)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Role of the thymus in natural tolerance to an autologous protein antigen.
Authors: M Boguniewicz, G H Sunshine, Y Borel
Journal: The Journal of Experimental Medicine (1989)

C5-deficient mice grafted with thymus from C5-sufficient donors and immunized with C5 failed to make humoral antibody to C5, suggesting that the transfer of thymus had induced tolerance. Irradiated C5-deficient hosts repopulated with lymphoid cells from thymectomized C5-deficient mice grafted with C5-sufficient thymus also failed to respond to immunization with C5, thus showing that the state of tolerance can be adoptively transferred. These results demonstrate that natural tolerance to self-protein antigen is "learned" in the thymus.
Novel Approaches in Advancing the Treatment of Epithelial Ovarian Cancer: The Role of Angiogenesis Inhibition
Authors: Lainie Martin, Russell Schilder
Journal: Journal of Clinical Oncology (2007)

Despite an aggressive approach of surgical cytoreduction and adjuvant combination chemotherapy, ovarian cancer mortality remains a significant problem. We are entering a new era of cancer therapeutics in which targeted therapies offer the potential for improvement in long-term disease control with fewer toxicities. The greatest success of targeted therapy to date in the setting of epithelial ovarian carcinoma has come from angiogenesis inhibition. This review will focus on the role of angiogenesis in normal ovarian function as well as in ovarian carcinoma development and disease progression. Current knowledge about the molecular pathways involved in angiogenesis and various approaches to angiogenesis inhibition in the treatment of ovarian cancer are discussed. Current data regarding the role of bevacizumab and other novel agents in the treatment of ovarian carcinoma are summarized.
Pseudo-obstruction of the Large Bowel
Authors: H. Davies
Journal: BMJ (1970)

Nun= 47 that there was more evidence of obstructive respiratory disease in his sample of workers than among the workers exposed to similar products examined by ourselves.'On the other hand, the F.E.V./'V.C. ratio is not age standardized and differences in age struc- ture of the two populations might to some extent account for the difference.Also, a higher proportion of the workers in his sur- vey were sensitized to the B. subtilis derivatives than in our own series.Levels of enzyme concentration in air are not given, but exposure to higher levels for longer periods might account for the difference.-Iam, etc.,
Preoperative Proteinuria Predicts Adverse Renal Outcomes after Coronary Artery Bypass Grafting
Authors: Tao-Min Huang, Vin-Cent Wu, Guang-Huar Young, Yu-Feng Lin, Chih-Chung Shiao, Pei-Chen Wu, Wen-Yi Li, Hsi-Yu Yu, Fu-Chang Hu, Jou-Wei Lin, Yih-Sharng Chen, Yen-Hung Lin, Shoei-Shen Wang, Ron-Bin Hsu, Fan-Chi Chang, Nai-Kuan Chou, Tzong-Shinn Chu, Yu-Chang Yeh, Pi-Ru Tsai, Jenq-Wen Huang, Shuei-Liong Lin, Yung-Ming Chen, Wen-Je Ko, Kwan-Dun Wu
Journal: Journal of the American Society of Nephrology (2010)

Whether preoperative proteinuria associates with adverse renal outcomes after cardiac surgery is unknown. Here, we performed a secondary analysis of a prospectively enrolled cohort of adult patients undergoing coronary artery bypass grafting (CABG) at a medical center and its two affiliate hospitals between 2003 and 2007. We excluded patients with stage 5 CKD or those who received dialysis previously. We defined proteinuria, measured with a dipstick, as mild (trace to 1+) or heavy (2+ to 4+). Among a total of 1052 patients, cardiac surgery–associated acute kidney injury (CSA-AKI) developed in 183 (17.4%) patients and required renal replacement therapy (RRT) in 50 (4.8%) patients. In a multiple logistic regression model, mild and heavy proteinuria each associated with an increased odds of CSA-AKI, independent of CKD stage and the presence of diabetes mellitus (mild: OR 1.66, 95% CI 1.09 to 2.52; heavy: OR 2.30, 95% CI 1.35 to 3.90). Heavy proteinuria also associated with increased odds of postoperative RRT (OR 7.29, 95% CI 3.00 to 17.73). In summary, these data suggest that preoperative proteinuria is a predictor of CSA-AKI among patients undergoing CABG.
Estrogen Modulation of Endothelial Nitric Oxide Synthase
Authors: Ken L. Chambliss, Philip W. Shaul
Journal: Endocrine Reviews (2002)

Abstract Over the past decade, clinical and basic research has demonstrated that estrogen has a dramatic impact on the response to vascular injury and the development of atherosclerosis. Further work has indicated that this is at least partially mediated by an enhancement in nitric oxide (NO) production by the endothelial isoform of NO synthase (eNOS) due to increases in both eNOS expression and level of activation. The effects on eNOS abundance are primarily mediated at the level of gene transcription, and they are dependent on estrogen receptors (ERs), which classically serve as transcription factors, but they are independent of estrogen response element action. Estrogen also has potent nongenomic effects on eNOS activity mediated by a subpopulation of ERα localized to caveolae in endothelial cells, where they are coupled to eNOS in a functional signaling module. These observations, which emphasize dependence on cell surface-associated receptors, provide evidence for the existence of a steroid receptor fast-action complex, or SRFC, in caveolae. Estrogen binding to ERα on the SRFC in caveolae leads to Gαi activation, which mediates downstream events. The downstream signaling includes activation of tyrosine kinase-MAPK and Akt/protein kinase B signaling, stimulation of heat shock protein 90 binding to eNOS, and perturbation of the local calcium environment, leading to eNOS phosphorylation and calmodulin-mediated eNOS stimulation. These unique genomic and nongenomic processes are critical to the vasoprotective and atheroprotective characteristics of estrogen. In addition, they serve as excellent paradigms for further elucidation of novel mechanisms of steroid hormone action.
GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation
Authors: S Cai
Journal: Cardiovascular Research (2002)

Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide synthase (eNOS) activity. BH4 levels are regulated by de novo biosynthesis; the rate-limiting enzyme is GTP cyclohydrolase I (GTPCH). BH4 activates and promotes homodimerisation of purified eNOS protein, but the intracellular mechanisms underlying BH4-mediated eNOS regulation in endothelial cells remain less clear. We aimed to investigate the role of BH4 levels in intracellular eNOS regulation, by targeting the BH4 synthetic pathway as a novel strategy to modulate intracellular BH4 levels.We constructed a recombinant adenovirus, AdGCH, encoding human GTPCH. We infected human endothelial cells with AdGCH, investigated the changes in intracellular biopterin levels, and determined the effects on eNOS enzymatic activity, protein levels and dimerisation.GTPCH gene transfer in EAhy926 endothelial cells increased BH4 >10-fold compared with controls (cells alone or control adenovirus infection), and greatly enhanced NO production in a dose-dependent, eNOS-specific manner. We found that eNOS was principally monomeric in control cells, whereas GTPCH gene transfer resulted in a striking increase in eNOS homodimerisation. Furthermore, the total amounts of both native eNOS protein and a recombinant eNOS-GFP fusion protein were significantly increased following GTPCH gene transfer.These findings suggest that GTPCH gene transfer is a valid approach to increase BH4 levels in human endothelial cells, and provide new evidence for the relative importance of different mechanisms underlying BH4-mediated eNOS regulation in intact human endothelial cells. Additionally, these observations suggest that GTPCH may be a rational target to augment endothelial BH4 and normalise eNOS activity in endothelial dysfunction states.
The Delivery of Public Health Interventions via the Internet: Actualizing Their Potential
Authors: Gary G. Bennett, Russell E. Glasgow
Journal: Annual Review of Public Health (2009)

The Internet increasingly serves as a platform for the delivery of public health interventions. The efficacy of Internet interventions has been demonstrated across a wide range of conditions. Much more work remains, however, to enhance the potential for broad population dissemination of Internet interventions. In this article, we examine the effectiveness of Internet interventions, with particular attention to their dissemination potential. We discuss several considerations (characterizing reach rates, minimizing attrition, promoting Web site utilization, use of tailored messaging and social networking) that may improve the implementation of Internet interventions and their associated outcomes. We review factors that may influence the adoption of Internet interventions in a range of potential dissemination settings. Finally, we present several recommendations for future research that highlight the potential importance of better understanding intervention reach, developing consensus regarding Web site usage metrics, and more broadly integrating Web 2.0 functionality.
Mapping gene activity of Arabidopsis root hairs
Authors: Ping Lan, Wenfeng Li, Wen-Dar Lin, Simonetta Santi, Wolfgang Schmidt
Journal: Genome biology (2013)

Abstract Background Quantitative information on gene activity at single cell-type resolution is essential for the understanding of how cells work and interact. Root hairs, or trichoblasts, tubular-shaped outgrowths of specialized cells in the epidermis, represent an ideal model for cell fate acquisition and differentiation in plants. Results Here, we provide an atlas of gene and protein expression in Arabidopsis root hair cells, generated by paired-end RNA sequencing and LC/MS-MS analysis of protoplasts from plants containing a pEXP7-GFP reporter construct. In total, transcripts of 23,034 genes were detected in root hairs. High-resolution proteome analysis led to the reliable identification of 2,447 proteins, 129 of which were differentially expressed between root hairs and non-root hair tissue. Dissection of pre-mRNA splicing patterns showed that all types of alternative splicing were cell type-dependent, and less complex in EXP7 -expressing cells when compared to non-root hair cells. Intron retention was repressed in several transcripts functionally related to root hair morphogenesis, indicative of a cell type-specific control of gene expression by alternative splicing of pre-mRNA. Concordance between mRNA and protein expression was generally high, but in many cases mRNA expression was not predictive for protein abundance. Conclusions The integrated analysis shows that gene activity in root hairs is dictated by orchestrated, multilayered regulatory mechanisms that allow for a cell type-specific composition of functional components.
Demonstration of cooperative contribution of MET- and EGFR-mediated STAT3 phosphorylation to liver regeneration by exogenous suppressor of cytokine signalings
Authors: Ekihiro Seki, Yuichi Kondo, Yuji Iimuro, Tetsuji Naka, Gakuhei Son, Tadamitsu Kishimoto, Jiro Fujimoto, Hiroko Tsutsui, Kenji Nakanishi
Journal: Journal of Hepatology (2007)
Terminal deoxynucleotidyl transferase‐positive acute leukemias evolving from a myelodysplastic syndrome
Authors: E. Brusamolino, P. Isernia, E. P. Alessandrino, A. I. Scovassi, U. Bertazzoni, C. Bernasconi
Journal: American Journal of Hematology (1985)

Abstract We have analyzed the distribution of terminal deoxynucleotidyl transferase (TdT) in 30 patients with myelodysplastic syndromes (MDS), in connection with morphology, cytochemistry, and cytogenetics. All cases in preleukemic phase were strictly TdT‐negative. At variance, 4 (19%) of 21 cases with subsequent leukemia were TdT‐positive and showed a pure lymphoid (one case) or a mixed lymphoid‐myelomonocytic (three cases) morphology. The TdT enzymatic activity ranged from 2 to 21 U/10 8 cells and the percent of positive cells in the immunofluorescence test ranged from 10 to 80% of total. All cases were Philadelphia chromosome‐negative. The clonal origin of MDS from the pluripotent stem cell, capable of originating both a lymphoid and myeloid progeny, is further corroborated.
Autophagy and p62 in Cardiac Proteinopathy
Authors: Qingwen Zheng, Huabo Su, Mark J. Ranek, Xuejun Wang
Journal: Circulation Research (2011)

Recent studies suggest an important role of autophagy in protection against αB-crystallin-based (CryAB(R120G)) desmin-related cardiomyopathies (DRC), but this has not been demonstrated in a different model of cardiac proteinopathy. Mechanisms underlying the response of cardiomyocytes to proteotoxic stress remain incompletely understood.Our first objective was to determine whether and how the autophagic activity is changed in a mouse model of desminopathy. We also investigated the role of p62 in the protein quality control of cardiomyocytes.Using an autophagosome reporter and determining changes in LC3-II protein levels in response to lysosomal inhibition, we found significantly increased autophagic flux in mouse hearts with transgenic overexpression of a DRC-linked mutant desmin. Similarly, autophagic flux was increased in cultured neonatal rat ventricular myocytes (NRVMs) expressing a mutant desmin. Suppression of autophagy by 3-methyladenine increased, whereas enhancement of autophagy by rapamycin reduced the ability of a comparable level of mutant desmin overexpression to accumulate ubiquitinated proteins in NRVMs. Furthermore, p62 mRNA and protein expression was significantly up-regulated in cardiomyocytes by transgenic overexpression of the mutant desmin or CryAB(R120G) both in intact mice and in vitro. The p62 depletion impaired aggresome and autophagosome formation, exacerbated cell injury, and decreased cell viability in cultured NRVMs expressing the misfolded proteins.Autophagic flux is increased in desminopathic hearts, and as previously suggested in CryAB(R120G)-based DRC, this increased autophagic flux serves as an adaptive response to overexpression of misfolded proteins. The p62 is up-regulated in mouse proteinopathic hearts. The p62 promotes aggresome formation and autophagy activation and protects cardiomyocytes against proteotoxic stress.
Genetic variants in the prediction of rheumatoid arthritis
Authors: A. H. M. van der Helm-van Mil, R. E. M. Toes, T. W. J. Huizinga
Journal: Annals of the Rheumatic Diseases (2010)

To determine whether the currently known genetic risk factors for rheumatoid arthritis (RA) improve the prediction of the development of RA compared to prediction using clinical risk factors alone in patients with undifferentiated arthritis (UA).Five hundred and seventy early UA-patients included in the Leiden Early Arthritis Clinic cohort, previously used to derive a clinical prediction rule, were used to explore the additional value of genetic variants. The following genetic variants were assessed HLA-DRB1 shared epitope (SE) alleles, rs2476601 (PTPN22), rs108184088 (TRAF1-C5), rs7574865 (STAT4), rs3087243 (CTLA4), rs4810485 (CD40), rs1678542 (KIF5A-PIP4K2C), rs2812378 (CCL21), rs42041 (CDK6), rs4750316 (PRKCQ), rs6684865 (MMEL1-TNFRSF14), rs2004640 (IRF5), rs6920220 and rs10499194 (TNFAIP3-OLIG3), interactions between HLA-SE alleles and rs2476601 (PTPN22) and between HLA-SE alleles and smoking. The area under the receiver operator curve (AUC) was used as measure of the discriminative ability of the models.The AUC of a model consisting of genetic variants only was low, 0.536 (95% CI 0.48 to 0.59). The AUC of the model including genetic and clinical risk factors was not superior over the AUC of the clinical prediction rule (0.889, 95% CI 0.86 to 0.95 and 0.884, 95% CI 0.86 to 0.92).In a population at risk, information on currently known genetic risk factors for RA does not improve prediction of risk for RA compared to a prediction rule based on common clinical risk factors alone.
Hormonal contraception, vitamin A deficiency, and other risk factors for shedding of HIV-1 infected cells from the cervix and vagina
Authors: Sara B Mostad, Julie Overbaugh, Dana M DeVange, Mary J Welch, Bhavna Chohan, Kishorchandra Mandaliya, Patrick Nyange, Harold L Martin, Jeckoniah Ndinya-Achola, Job J Bwayo, Joan K Kreiss
Journal: The Lancet (1997)