tbuckley/cabot-search huggingface dataset:
Understanding the High Prevalence of Diabetes in U.S. South Asians Compared With Four Racial/Ethnic Groups: The MASALA and MESA Studies
Authors: Alka M. Kanaya, David Herrington, Eric Vittinghoff, Susan K. Ewing, Kiang Liu, Michael J. Blaha, Swapna S. Dave, Fareeha Qureshi, Namratha R. Kandula
Journal: Diabetes Care (2014)

OBJECTIVE We compared South Asians with four other racial/ethnic groups in the U.S. to determine whether sociodemographic, lifestyle, or metabolic factors could explain the higher diabetes prevalence and whether insulin resistance and β-cell dysfunction occurred at younger ages and/or lower adiposity levels compared with other groups. RESEARCH DESIGN AND METHODS We performed a cross-sectional analysis of two community-based cohorts, the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study and the Multi-Ethnic Study of Atherosclerosis (MESA); all participants had no known cardiovascular disease and were between 44 and 84 years of age. We compared 799 South Asians with 2,611 whites, 1,879 African Americans, 1,493 Latinos, and 801 Chinese Americans. Type 2 diabetes was classified by fasting plasma glucose ≥126 mg/dL or use of a diabetes medication. Insulin resistance was estimated by the homeostasis model assessment (HOMA) and β-cell function was measured by the HOMA-β model. RESULTS South Asians had significantly higher age-adjusted prevalence of diabetes (23%) than the MESA ethnic groups (6% in whites, 18% in African Americans, 17% in Latinos, and 13% in Chinese Americans). This difference increased further after adjustment for potential confounders. HOMA of insulin resistance (HOMA-IR) levels were significantly higher and HOMA-β levels were lower among South Asians compared with all other racial/ethnic groups after adjustment for age and adiposity. CONCLUSIONS The higher prevalence of diabetes in South Asians is not explained by traditionally measured risk factors. South Asians may have lower β-cell function and an inability to compensate adequately for higher glucose levels from insulin resistance.
Waldenström macroglobulinemia: A review of therapy
Authors: Morie A. Gertz
Journal: American Journal of Hematology (2005)

Waldenström macroglobulinemia is a rare monoclonal gammopathy-associated lymphoplasmacytic lymphoma. Its incidence is only 4 per million per year. This review contains the known published literature specifically on the available management tools for Waldenström macroglobulinemia and is designed to assist clinicians in making management decisions for patients with this uncommon disorder.
Viral immunosuppression: disabling the guards
Authors: Marco Colonna
Journal: Journal of Clinical Investigation (2004)

When facing an immune response, viruses can either attempt to elude them or confront them. A new report demonstrates that a lymphocytic choriomeningitis virus (LCMV) strain can suppress immune responses by targeting both development and activation of DCs. Ironically, type I IFN released in response to LCMV infection contributes to the blockade of DC development. The discovery of these immunosuppressive mechanisms provides new perspectives for the therapy of chronic infections associated with immunosuppression.
Kringle 5 of Human Plasminogen Induces Apoptosis of Endothelial and Tumor Cells through Surface-Expressed Glucose-Regulated Protein 78
Authors: Don J. Davidson, Catherine Haskell, Sandy Majest, Abdullah Kherzai, David A. Egan, Karl A. Walter, Andrew Schneider, Earl F. Gubbins, Larry Solomon, Zhebo Chen, Rick Lesniewski, Jack Henkin
Journal: Cancer Research (2005)

Kringle 5 (K5) of human plasminogen has been shown to inhibit angiogenesis by inducing the apoptosis of proliferating endothelial cells. Peptide regions around the lysine-binding pocket of K5 largely mediate these effects, particularly the peptide PRKLYDY, which we show to compete with K5 for the binding to endothelial cells. The cell surface binding site for K5 that mediates these effects has not been defined previously. Here, we report that glucose-regulated protein 78, exposed on cell surfaces of proliferating endothelial cells as well as on stressed tumor cells, plays a key role in the antiangiogenic and antitumor activity of K5. We also report that recombinant K5-induced apoptosis of stressed HT1080 fibrosarcoma cells involves enhanced activity of caspase-7, consistent with the disruption of glucose-regulated protein 78-procaspase-7 complexes. These results establish recombinant K5 as an inhibitor of a stress response pathway, which leads to both endothelial and tumor cell apoptosis.
Risk of haematopoietic cancer in patients with inflammatory bowel disease
Authors: J Askling
Journal: Gut (2005)

Evidence is presented that a protein having immunological properties identical with those of a chromogranin purified from chromaffin granules (obtained from bovine adrenal medullae) is present in granules isolated from bovine splenic nerve. The possibility that chromogranin plays a role in noradrenaline storage in splenic nerve granules as well as in chromaffin granules is discussed.
Scaffold-Based Three-Dimensional Human Fibroblast Culture Provides a Structural Matrix That Supports Angiogenesis in Infarcted Heart Tissue
Authors: Robert S. Kellar, Lee K. Landeen, Benjamin R. Shepherd, Gail K. Naughton, Anthony Ratcliffe, Stuart K. Williams
Journal: Circulation (2001)

We have developed techniques to implant angiogenic patches onto the epicardium over regions of infarcted cardiac tissue to stimulate revascularization of the damaged tissue. These experiments used a scaffold-based 3D human dermal fibroblast culture (3DFC) as an epicardial patch. The 3DFC contains viable cells that secrete angiogenic growth factors and has previously been shown to stimulate angiogenic activity. The hypothesis tested was that a viable 3DFC cardiac patch would stimulate an angiogenic response within an area of infarcted cardiac tissue.A coronary occlusion of a branch of the left anterior descending coronary artery was performed by thermal ligation in severe combined immunodeficient mice. 3DFCs with or without viable cells were sized to the damaged area, implanted in replicate mice onto the epicardium at the site of tissue injury, and compared with animals that received infarct surgery but no implant. Fourteen and 30 days after surgery, hearts were exposed and photographed, and tissue samples were prepared for histology and cytochemistry. Fourteen and 30 days after surgery, the damaged myocardium receiving viable 3DFC exhibited a significantly greater angiogenic response (including arterioles, venules, and capillaries) than nonviable and untreated control groups.In this animal model, viable 3DFC stimulates angiogenesis within a region of cardiac infarction and can augment a repair response in damaged tissue. Therefore, a potential use for 3DFC is the repair of myocardial tissue damaged by infarction.
Defective immunoregulation in primary biliary cirrhosis: CD4+, Leu–8+ T cells have abnormal activation and suppressor functionin vitro
Authors: Takeaki Suou, Maria P. Civeira, Marjorie E. Kanof, Ricardo Moreno-Otero, Anthony E. Jones, Stephen P. James
Journal: Hepatology (1989)

To determine whether abnormalities of lymphocyte function in primary biliary cirrhosis are due to altered function of immunoregulatory T cell subpopulations, phenotypic and functional characteristics of CD4+ T cells were examined. The proportion of CD4+ T cells expressing the Leu-8 and CD45R antigens was normal in patients with primary biliary cirrhosis. The capacity of CD4+, Leu-8-T cells to provide helper function for pokeweed mitogen-stimulated immunoglobulin synthesis by B cells in vitro was similar in patients and controls. However, in contrast to normal individuals and patients with other liver diseases, CD4+, Leu-8+ T cells from six of 10 patients with primary biliary cirrhosis did not suppress, but enhanced immunoglobulin synthesis. Whereas treatment of CD4+ T cells from normal individuals with anti-Leu-8 monoclonal antibody enhanced their suppressor function, similar treatment of CD4+ T cells from patients with primary biliary cirrhosis did not increase their suppressor function. To determine whether the abnormal regulatory function of CD4+, Leu-8+ T cells was due to a defect of cell activation, the proliferative response of CD4+ T cell subpopulations to mitogenic stimulation was examined. The proliferative responses of CD4+, Leu-8-T cells from patients with primary biliary cirrhosis and controls were similar, but the proliferative responses of CD4+, Leu-8+ T cells from patients with primary biliary cirrhosis were lower than those of control cells. Since the CD4+, Leu-8+ T cell population plays a role in suppressing immunoglobulin synthesis and is contained within the autoreactive T cell population, the abnormal function of this T cell subpopulation in some patients with primary biliary cirrhosis may play a role in defective immunoregulation found in this disease.
Identifying adventure travellers at risk of developing exacerbations of asthma
Authors: A Bhowmik
Journal: Thorax (2003)

▴ Golan Y, Onn A, Villa Y, et al . Asthma in adventure travelers: a prospective study evaluating the occurrence and risk factors for acute exacerbations. Arch Intern Med2002;162:2421–6 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] This Israeli study followed up 180 mild to moderate asthmatics (mean age 23.9 years, 50% female) who were travelling to developing countries for, on average, 4 months. History, examination and spirometric tests were … [1]: {openurl}?query=rft.jtitle%253DArchives%2Bof%2BInternal%2BMedicine%26rft.stitle%253DArch%2BIntern%2BMed%26rft.issn%253D0003-9926%26rft.aulast%253DGolan%26rft.auinit1%253DY.%26rft.volume%253D162%26rft.issue%253D21%26rft.spage%253D2421%26rft.epage%253D2426%26rft.atitle%253DAsthma%2Bin%2BAdventure%2BTravelers%253A%2BA%2BProspective%2BStudy%2BEvaluating%2Bthe%2BOccurrence%2Band%2BRisk%2BFactors%2Bfor%2BAcute%2BExacerbations%26rft_id%253Dinfo%253Adoi%252F10.1001%252Farchinte.162.21.2421%26rft_id%253Dinfo%253Apmid%252F12437400%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/archinte.162.21.2421&link_type=DOI [3]: /lookup/external-ref?access_num=12437400&link_type=MED&atom=%2Fthoraxjnl%2F58%2F3%2F221.atom [4]: /lookup/external-ref?access_num=000179471700004&link_type=ISI
Notch-Dependent Cell Cycle Arrest Is Associated With Downregulation of Minichromosome Maintenance Proteins
Authors: Michela Noseda, Kyle Niessen, Graeme McLean, Linda Chang, Aly Karsan
Journal: Circulation Research (2005)

Perturbation of the Notch signaling pathway has been implicated in the pathogenesis of human cardiovascular diseases, and animal models have confirmed the requirement of Notch during cardiovascular development. We recently demonstrated that Notch activation delays S-phase entry and contributes to endothelial contact inhibition. Minichromosome maintenance (MCM) proteins, components of the prereplicative complex (pre-RC), are essential for DNA replication. Here, we report that Notch-mediated cell cycle arrest is associated with downregulation of MCM2 and MCM6 in endothelial cells and human fibroblasts. Downregulation of MCM proteins is also observed on activation of C promoter binding factor (CBF1) and is mediated by inhibition of Rb phosphorylation, as demonstrated using a constitutively active Rb mutant. Although the effects of the Notch pathway are cell-type specific and context-dependent, in cell types where Notch has an antiproliferative effect, downregulation of MCM proteins may be a common mechanism to inhibit DNA replication.
Low-dose FSH therapy for anovulatory infertility associated with polycystic ovary syndrome: rational, results, reflections refinements
Authors: R Homburg
Journal: Human Reproduction Update (1999)

Low-dose follicle stimulating hormone (FSH) regimens for induction of ovulation for women with polycystic ovaries have succeeded in reducing the rate of ovarian hyperstimulation syndrome (OHSS) almost to nil and the rate of multiple pregnancies to a minimum of 6%. This has been achieved by reaching, but not exceeding, the threshold level of FSH, starting with a daily dose of 75 IU for 14 days, using small incremental dose rises where necessary, and inducing uniovulation in 70% of cycles. Conception rates are as good, if not better, than those achieved with conventional therapy. The miscarriage rate is still relatively high (20-25%) and obese women fare worse. Serum oestradiol concentrations and the number of large and intermediate follicles on the day of human chorionic gonadotrophin administration are much lower, in parallel with lower serum FSH concentrations. Inhibin values increase with the rise in serum FSH concentrations but those of luteinizing hormone decrease steadily throughout the follicular phase. New data using recombinant hFSH (rhFSH), rather than urinary gonadotrophin as the ovarian stimulant, demonstrate that treatment time is shortened. However, the ideal regimen has still to be formulated.
Integrating Evolutionary and Functional Tests of Adaptive Hypotheses: A Case Study of Altitudinal Differentiation in Hemoglobin Function in an Andean Sparrow, Zonotrichia capensis
Authors: Zachary A. Cheviron, Chandrasekhar Natarajan, Joana Projecto-Garcia, Douglas K. Eddy, Jennifer Jones, Matthew D. Carling, Christopher C. Witt, Hideaki Moriyama, Roy E. Weber, Angela Fago, Jay F. Storz
Journal: Molecular Biology and Evolution (2014)

In air-breathing vertebrates, the physiologically optimal blood-O2 affinity is jointly determined by the prevailing partial pressure of atmospheric O2, the efficacy of pulmonary O2 transfer, and internal metabolic demands. Consequently, genetic variation in the oxygenation properties of hemoglobin (Hb) may be subject to spatially varying selection in species with broad elevational distributions. Here we report the results of a combined functional and evolutionary analysis of Hb polymorphism in the rufous-collared sparrow (Zonotrichia capensis), a species that is continuously distributed across a steep elevational gradient on the Pacific slope of the Peruvian Andes. We integrated a population genomic analysis that included all postnatally expressed Hb genes with functional studies of naturally occurring Hb variants, as well as recombinant Hb (rHb) mutants that were engineered through site-directed mutagenesis. We identified three clinally varying amino acid polymorphisms: Two in the αA-globin gene, which encodes the α-chain subunits of the major HbA isoform, and one in the αD-globin gene, which encodes the α-chain subunits of the minor HbD isoform. We then constructed and experimentally tested single- and double-mutant rHbs representing each of the alternative αA-globin genotypes that predominate at different elevations. Although the locus-specific patterns of altitudinal differentiation suggested a history of spatially varying selection acting on Hb polymorphism, the experimental tests demonstrated that the observed amino acid mutations have no discernible effect on respiratory properties of the HbA or HbD isoforms. These results highlight the importance of experimentally validating the hypothesized effects of genetic changes in protein function to avoid the pitfalls of adaptive storytelling.
Bcl11b is required for differentiation and survival of αβ T lymphocytes
Authors: Yuichi Wakabayashi, Hisami Watanabe, Jun Inoue, Naoki Takeda, Jun Sakata, Yukio Mishima, Jiro Hitomi, Takashi Yamamoto, Masanori Utsuyama, Ohtsura Niwa, Shinichi Aizawa, Ryo Kominami
Journal: Nature Immunology (2003)
Supported discharge shortens hospital stay in patients hospitalized because of an exacerbation of COPD
Authors: E. Sala, L. Alegre, M. Carrera, M. Ibars, F.J. Orriols, M.L. Blanco, F. Cárceles, S. Bertran, F. Mata, I. Font, A.G.N. Agustí
Journal: European Respiratory Journal (2001)

This prospective, controlled, but not formally randomized study investigates the feasibility and efficiency of an alternative to standard hospitalization for patients with exacerbated chronic obstructive pulmonary disease (COPD), based upon supported discharge with nurse supervision at home. Over a 12-month period, emergency physicians, not directly involved in the study, admitted 205 patients with exacerbated COPD to the authors' respiratory unit. Patients were included in the supported discharge group (n=105) if they voluntarily chose to participate in the programme and lived in the city of Palma de Mallorca (where adequate home support could be provided). Patients not fulfilling these criteria (mainly residents outside the city) served as controls (n=100). Inpatient treatment was standardized in all patients and included oxygen therapy, bronchodilators, antibiotics and steroids. Both groups were comparable in terms of age (mean±sd: 70±10 versus 65±11 yr for supported discharge and control group, respectively), severity of airflow obstruction (forced expiratory volume in one second 45±18% reference versus 46±19% ref.), comorbidity and socioeconomic status. Length of hospital stay (LOS) in the supported discharge group was shorter (5.9±2.8 versus 8.0±5.1 days, p&lt;0.001). After discharge, a respiratory nurse visited supported discharge patients at home during 7.3±3.8 days. Only one patient (1%) required hospital readmission during this period of time. The reduced LOS resulted in a lower utilization of hospital beds at any given point in time throughout the study period. Within the framework and potential limitations of this study, the results indicate that the supported discharge programme in Spain: 1) allows a significant reduction in the length of hospital stay of patients hospitalized because of an exacerbation of chronic obstructive pulmonary disease; 2) does not result in an inappropriately increased rate of hospital readmissions; and 3) reduces the utilization of hospital resources.
Genetic Engineering for Skeletal Regenerative Medicine
Authors: Charles A. Gersbach, Jennifer E. Phillips, Andrés J. García
Journal: Annual Review of Biomedical Engineering (2007)

The clinical challenges of skeletal regenerative medicine have motivated significant advances in cellular and tissue engineering in recent years. In particular, advances in molecular biology have provided the tools necessary for the design of gene-based strategies for skeletal tissue repair. Consequently, genetic engineering has emerged as a promising method to address the need for sustained and robust cellular differentiation and extracellular matrix production. As a result, gene therapy has been established as a conventional approach to enhance cellular activities for skeletal tissue repair. Recent literature clearly demonstrates that genetic engineering is a principal factor in constructing effective methods for tissue engineering approaches to bone, cartilage, and connective tissue regeneration. This review highlights this literature, including advances in the development of efficacious gene carriers, novel cell sources, successful delivery strategies, and optimal target genes. The current status of the field and the challenges impeding the clinical realization of these approaches are also discussed.
Clinical selection of melanocytic lesions for dermoscopy decreases the identification of suspicious lesions in comparison with dermoscopy without clinical preselection
Authors: S. Seidenari, C. Longo, F. Giusti, G. Pellacani
Journal: British Journal of Dermatology (2006)

Journal Article Clinical selection of melanocytic lesions for dermoscopy decreases the identification of suspicious lesions in comparison with dermoscopy without clinical preselection Get access S. Seidenari, S. Seidenari Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy Stefania Seidenari. E‐mail: seidenari.stefania@unimo.it Search for other works by this author on: Oxford Academic Google Scholar C. Longo, C. Longo Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy Search for other works by this author on: Oxford Academic Google Scholar F. Giusti, F. Giusti Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy Search for other works by this author on: Oxford Academic Google Scholar G. Pellacani G. Pellacani Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 5, 1 May 2006, Pages 873–879, https://doi.org/10.1111/j.1365-2133.2006.07165.x Published: 01 May 2006 Article history Accepted: 03 November 2005 Published: 01 May 2006
High expression of FOXP3 in primary melanoma is associated with tumour progression
Authors: A.L. Gerber, A. Münst, C. Schlapbach, M. Shafighi, D. Kiermeir, R. Hüsler, R.E. Hunger
Journal: British Journal of Dermatology (2013)

The antitumour immune response plays an important role in the prognosis of melanoma. High numbers of circulating regulatory T cells have been associated with rapid disease progression.To assess the influence of forkhead box protein (FOXP)3, CD1a and langerin expression on the prognosis of primary melanoma.We analysed 185 primary melanomas by immunohistochemical staining for expression of the regulatory T-cell marker FOXP3 and the dendritic cell markers langerin and CD1a, and correlated marker expression with clinical outcome.Disease-free survival and overall survival were significantly longer in patients expressing low levels of FOXP3 in the primary melanoma, whereas they were associated with high expression of CD1a. The negative prognostic value of FOXP3 expression was independent of the Breslow tumour thickness. Langerin expression did not correlate with the clinical outcome.High expression of FOXP3 in the primary melanoma may be used as an additional independent prognostic marker for early tumour progression in patients with melanoma.