tbuckley/cabot-search huggingface dataset:
Non-Insulin-Dependent Diabetes Mellitus and Hypertriglyceridemia Impair Lipoprotein Metabolism in Chronic Hemodialysis Patients
Authors: THOMAS QUASCHNING, MICHAEL SCHÖMIG, MARKUS KELLER, JOACHIM THIERY, MATTHIAS NAUCK, PETER SCHOLLMEYER, CHRISTOPH WANNER, ANNETTE KRÄMER-GUTH
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Patients with diabetes mellitus undergoing chronic hemodialysis treatment have the worst outcome on dialysis due to an increased rate of cardiovascular complications. Nearly all patients present with dyslipidemia, a prominent vascular risk factor, probably responsible for the high rate of vascular injury. Since both uremia and diabetes predispose to hypertriglyceridemia, the present study was conducted to investigate the influence of diabetes mellitus and/or hypertriglyceridemia on lipoprotein metabolism in hemodialysis patients. LDL was isolated and characterized from hyper- and normotriglyceridemic diabetic and nondiabetic hemodialysis patients ( n = 40; 10 in each group); also, LDL-receptor-dependent uptake and intracellular cholesterol metabolism were studied in HepG2 cells. In addition, scavenger-receptor-mediated uptake was examined in mouse peritoneal macrophages. LDL isolated from nondiabetic normotriglyceridemic hemodialysis patients exhibited impaired cellular uptake via the LDL receptor. Additionally, intracellular sterol synthesis was less inhibited and cholesterol esterification was reduced compared with LDL from healthy control subjects. Reduction of catabolic capacities was more marked in hemodialysis patients who were either diabetic or hypertriglyceridemic and even more pronounced in patients presenting with a combination of both diabetes and hypertriglyceridemia. Hypertriglyceridemic and diabetic patients showed reduced lipase activity and increased LDL oxidation. Furthermore, they accumulated a fraction of small, dense LDL, and LDL was predominantly taken up via the scavenger-receptor pathway in peritoneal macrophages. This study elucidates the distinct influence of diabetes and/or hypertriglyceridemia in hemodialysis patients on cellular LDL metabolism via specific and nonspecific metabolic pathways. Furthermore, it underscores the cumulative impact of these pathologic entities on impairment of lipoprotein metabolism and increase of cardiovascular risk.
H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity.
Authors: J L Casanova, J C Cerottini, M Matthes, A Necker, H Gournier, C Barra, C Widmann, H R MacDonald, F Lemonnier, B Malissen
Journal: The Journal of Experimental Medicine (1992)

We previously showed that H-2Kd-restricted cytotoxic T lymphocyte (CTL) clones specific for a single nonapeptide derived from the Plasmodium berghei circumsporozoite (PbCS) protein displayed T cell receptors (TCRs) of highly diverse primary structure. We have now analyzed the TCR repertoire of CTLs that recognize a peptide derived from the human class I major histocompatibility complex (MHC) molecule HLA-Cw3 in association with the same murine class I MHC molecule H-2Kd. We first sequenced the TCR alpha and beta genes of the CTL clone Cw3/1.1 and, based on this genomic analysis, the TCR alpha and beta cDNA junctional regions of 23 independent H-2Kd-restricted CTL clones specific for HLA-Cw3. The results show that the TCR chains display very limited heterogeneity, both in terms of V alpha, J alpha, V beta, and J beta segments, and in terms of length and sequence of the CDR3 alpha and beta loops. The TCR repertoire used in vivo was then analyzed by harvesting CTL populations from the peritoneal cavity of immune mice. The peritoneal exudate lymphocytes (PELs) displayed HLA-Cw3-specific cytolytic activity in the absence of any stimulation in vitro. Remarkably, most of these freshly isolated PELs expressed TCRs that shared the same structural features as those from HLA-Cw3-reactive CTL clones. Thus, our results show that a peptide from HLA-Cw3 presented by H-2Kd selects CTLs that bear TCRs of very limited diversity in vivo. When taken together with the high diversity of the TCRs specific for the PbCS peptide, these findings suggest that natural tolerance to self peptides presented by class I MHC molecules may substantially reduce the size of the TCR repertoire of CTLs specific for antigenic peptides homologous to self.
Non-small cell lung cancer cells survived ionizing radiation treatment display cancer stem cell and epithelial-mesenchymal transition phenotypes
Authors: Roberto Gomez-Casal, Chitralekha Bhattacharya, Nandita Ganesh, Lisa Bailey, Per Basse, Michael Gibson, Michael Epperly, Vera Levina
Journal: Molecular Cancer (2013)

Abstract Ionizing radiation (IR) is used for patients diagnosed with unresectable non small cell lung cancer (NSCLC), however radiotherapy remains largely palliative due to radioresistance. Cancer stem cells (CSCs), as well as epithelial-mesenchymal transition (EMT), may contribute to drug and radiation resistance mechanisms in solid tumors. Here we investigated the molecular phenotype of A549 and H460 NSCLC cells that survived treatment with IR (5Gy) and are growing as floating tumor spheres and cells that are maintained in a monolayer after irradiation. Non-irradiated and irradiated cells were collected after one week, seeded onto ultra low attachment plates and propagated as tumor spheres. Bulk NSCLC cells which survived radiation and grew in spheres express cancer stem cell surface and embryonic stem cell markers and are able to self-renew, and generate differentiated progeny. These cells also have a mesenchymal phenotype. Particularly, the radiation survived sphere cells express significantly higher levels of CSC markers (CD24 and CD44), nuclear β-catenin and EMT markers (Snail1, Vimentin, and N-cadherin) than non-irradiated lung tumor sphere cells. Upregulated levels of Oct-4, Sox2 and beta-catenin were detected in H460 cells maintained in a monolayer after irradiation, but not in radiation survived adherent A459 cells. PDGFR-beta was upregulated in radiation survived sphere cells and in radiation survived adherent cells in both A549 and H460 cell lines. Combining IR treatment with axitinib or dasatinib, inhibitors with anti-PDFGR activity, potentiates the efficacy of NSCLC radiotherapy in vitro . Our findings suggest that radiation survived cells have a complex phenotype combining the properties of CSCs and EMT. CD44, SNAIL and PDGFR-beta are dramatically upregulated in radiation survived cells and might be considered as markers of radiotherapy response in NSCLC.
Nonlymphoblastic lymphoma in children--histology and stage-related response to therapy: a Pediatric Oncology Group study.
Authors: E V Hvizdala, C Berard, T Callihan, J Falletta, H Sabio, J J Shuster, M Sullivan, M D Wharam
Journal: Journal of Clinical Oncology (1991)

From May 1979 to March 1983, 93 eligible patients with nonlymphoblastic lymphoma (NLBL) were treated by members of the Pediatric Oncology Group (POG) with Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, prednisone, cyclophosphamide, and mercaptopurine (ACOP+); CNS prophylaxis with intrathecal (IT) methotrexate, hydrocortisone, and cranial irradiation (2,400 rads), and radiation therapy to the primary disease were administered in stages I and II, and to residual disease in stages III and IV. Duration of treatment was 2 years for stages I, II, and III and 3 years for stage IV disease. Of the 93 patients entered onto the study, 47 had diffuse small noncleaved-cell lymphoma (DSNCL), 38 had diffuse large-cell lymphoma (DLCL), and eight had other histologies. Localized disease (stages I and II) was present in 51 patients, and 42 had advanced (stages III and IV) disease. The study confirmed previously reported importance of stage with a 4-year event-free survival (EFS) of 78% (SE +/- 7%) for patients with localized disease as compared with 44% (SE +/- 9%) in patients with advanced disease (P less than or equal to .001). In localized disease, seven of 11 adverse events occurred in patients who were off therapy and more than 30 months after the initial diagnosis (relapse, three; second malignancy, two; death in remission, two). Large-cell histology proved to be an important prognostic factor in patients with stages III and IV disease with EFS at 4 years of 67% (SE +/- 11%) for DLCL versus 17% (SE +/- 11%) for DSNCL (P less than or equal to .001). We conclude that it is important to distinguish histologically between small noncleaved-cell and large-cell types of NLBL as a basis for further controlled clinical trials.
Persons With Chronic Conditions
Authors: Catherine Hoffman
Journal: JAMA (1996)

To determine (1) the number and proportion of Americans living with chronic conditions, and (2) the magnitude of their costs, including direct costs (annual personal health expenditures) and indirect costs to society (lost productivity due to chronic conditions and premature death).Analysis of the 1987 National Medical Expenditure Survey for prevalence and direct health care costs; indirect costs based on the 1990 National Health Interview Survey and Vital Statistics of the United States.US population.For the estimate of prevalence and direct costs, the National Medical Expenditure Survey sample of persons who reported health conditions associated with (1) use of health services or supplies or (2) periods of disability.None.The number of persons with chronic conditions, their annual direct health care costs, and indirect costs from lost productivity and premature deaths.In 1987, 90 million Americans were living with chronic conditions, 39 million of whom were living with more than 1 chronic condition. Over 45% of noninstitutionalized Americans have 1 or more chronic conditions and their direct health care costs account for three fourths of US health care expenditures. Total costs projected to 1990 for people with chronic conditions amounted to $659 billion--$425 billion for direct health care costs and $234 billion in indirect costs.The prevalence and costs of chronic conditions as a whole have rarely been estimated. Because the number of persons with limitations due to chronic conditions is more regularly reported in the literature, the total prevalence of chronic conditions has perhaps been minimized. The majority of persons with chronic conditions are not disabled, nor are they elderly. Chronic conditions affect all ages. Because persons with chronic conditions have greater health needs at any age, their costs are disproportionately high.
The Moral Duty to Buy Health Insurance
Authors: Tina Rulli, Ezekiel J. Emanuel, David Wendler
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Polymorphisms of interleukin-10 and its receptor and lung function in COPD
Authors: J-Q. He, K. Shumansky, X. Zhang, J. E. Connett, N. R. Anthonisen, A. J. Sandford
Journal: European Respiratory Journal (2007)

Interleukin (IL)-10 is a type-2 T-helper cell cytokine with a broad spectrum of anti-inflammatory actions. Inflammation plays an important role in the pathogenesis of chronic obstructive pulmonary disease. It was hypothesised that single nucleotide polymorphisms (SNPs) of the genes encoding IL-10 (<i>IL10</i>) and the α subunit of its receptor (<i>IL10RA</i>) are associated with changes in, or value of, forced expiratory volume in one second (FEV<sub>1</sub>) in smoking-induced chronic obstructive pulmonary disease. In total, eleven SNPs of <i>IL10</i> and <i>IL10RA</i> were studied in 586 White subjects, selected from continuous smokers followed for 5 yrs in the Lung Health Study, who showed the fastest (n = 280) and slowest (n = 306) decline in FEV<sub>1</sub>. These 11 SNPs were also studied in 1,072 participants exhibiting the lowest (n = 538) and highest (n = 534) baseline FEV<sub>1</sub> at the beginning of the Lung Health Study. No association was found in the primary analyses. Although a subgroup analysis showed that the IL-10 3368A allele was associated with a fast decline in FEV<sub>1</sub>, the association did not pass correction for multiple comparisons. No gene–gene interaction of <i>IL10</i> with <i>IL10RA</i> was found. There was no association of polymorphisms of the genes encoding interleukin-10 and the α subunit of its receptor with the rate of decline in, or value of, forced expiratory volume in one second in smoking-induced chronic obstructive pulmonary disease.
Genetic variation and gene expression in antioxidant related enzymes and risk of COPD: a systematic review
Authors: A R Bentley, P Emrani, P A Cassano
Journal: Thorax (2008)

<h3>Background:</h3> Observational epidemiological studies of dietary antioxidant intake, serum antioxidant concentration and lung outcomes suggest that lower levels of antioxidant defences are associated with decreased lung function. Another approach to understanding the role of oxidant/antioxidant imbalance in the risk of chronic obstructive pulmonary disease (COPD) is to investigate the role of genetic variation in antioxidant enzymes, and indeed family based studies suggest a heritable component to lung disease. Many studies of the genes encoding antioxidant enzymes have considered COPD or COPD related outcomes, and a systematic review is needed to summarise the evidence to date, and to provide insights for further research. <h3>Methods:</h3> Genetic association studies of antioxidant enzymes and COPD/COPD related traits, and comparative gene expression studies with disease or smoking as the exposure were systematically identified and reviewed. Antioxidant enzymes considered included enzymes involved in glutathione metabolism, in the thioredoxin system, superoxide dismutases (SOD) and catalase. <h3>Results:</h3> A total of 29 genetic association and 15 comparative gene expression studies met the inclusion criteria. The strongest and most consistent effects were in the genes <i>GCL</i>, <i>GSTM1</i>, <i>GSTP1</i> and <i>SOD3</i>. This review also highlights the lack of studies for genes of interest, particularly <i>GSR</i>, <i>GGT</i> and those related to <i>TXN</i>. There were limited opportunities to evaluate the contribution of a gene to disease risk through synthesis of results from different study designs, as the majority of studies considered either association of sequence variants with disease or effect of disease on gene expression. <h3>Conclusion:</h3> Network driven approaches that consider potential interaction between and among genes, smoke exposure and antioxidant intake are needed to fully characterise the role of oxidant/antioxidant balance in pathogenesis.
Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis
Authors: Mei-Tsz Su, Sheng-Hsiang Lin, Yi-Chi Chen
Journal: Human Reproduction Update (2011)

Angiogenesis and an adequate blood supply are critical for several steps in human early pregnancy. Some studies have reported angiogenesis- and vasoconstriction-related genes are associated with recurrent pregnancy loss (RPL), but their sample size was limited. This study was conducted to investigate the genetic association between these angiogenesis- and vasoconstriction-related genes and idiopathic RPL, using meta-analyses. A systematic review of the published literature from MEDLINE and EMBASE databases was conducted and investigations of an angiogenesis- and vasoconstriction-related gene polymorphism in RPL reported more than three times were selected. Aggregating data from eligible studies were integrated into meta-analyses by means of random effects models. Of 185 potentially relevant studies, 18 case–control studies comprising a total of 2397 RPL patients and 1760 controls were included into the meta-analyses. Among these genetic association studies were 4 reports of vascular endothelial growth factor (VEGF) (−1154G>A) polymorphisms, 4 reports of p53 (codon72) and 10 reports of endothelial nitric oxide synthase (eNOS) (B/A, Glu298Asp) with RPL. The integrated results showed that VEGF (−1154G>A), p53 (codon 72) and eNOS (Glu298Asp) polymorphisms were significantly associated with RPL, and their summary odd ratios [95% confidence interval (CI)] were 1.51 (1.13–2.03), 1.84(1.07–3.16) and 1.37 (1.11–1.69), respectively. The summary odd ratio of the eNOS (B/A) polymorphism in RPL was 1.15 (0.94–1.41), and failed to show significance at meta-analysis. Meta-analyses of available data showed significant associations between the VEGF (−1154G>A), p53 (codon72) and eNOS (Glu298Asp) polymorphisms and idiopathic RPL. These angiogenesis- and vasoconstriction-related genes jointly confer higher susceptibility to idiopathic RPL.
Some epidermolysis bullosa acquisita sera react with epitopes within the triple-helical collagenous domain as indicated by immunoelectron microscopy
Authors: N. Ishii, M. Yoshida, A. Ishida-Yamamoto, A. Fritsch, S. Elfert, L. Bruckner-Tuderman, T. Hashimoto
Journal: British Journal of Dermatology (2008)

Epidermolysis bullosa acquisita (EBA) autoantibodies recognize epitopes predominantly within the N-terminal noncollagenous (NC)-1 domain of type VII collagen. Recently, some EBA cases with reactivity to other domains, i.e. the triple-helical (T-H) collagenous domain and the NC-2 domain, have been reported.To investigate the ultrastructural localization of epitopes for sera from five patients with EBA that were unreactive by immunoblotting with the NC-1, NC-2 and collagenous domains of type VII collagen.Immunogold postembedding indirect immunoelectron microscopy was performed using normal human skin and type VII collagen-deficient skin as substrates.Postembedding indirect immunoelectron microscopy revealed that the five EBA sera showed immunoreactivity in the dermis, mainly located 0-400 nm below the lamina densa. IgG labelling was not observed in type VII collagen-deficient skin from a patient with recessive dystrophic epidermolysis bullosa. The distribution histogram found in this study was different from those of sera that reacted with the NC-1 and/or NC-2 domains, and was similar to those of sera reacting with the T-H collagenous domain.Our results suggest that epitopes within the T-H collagenous domain of type VII collagen are recognized by IgG antibodies from some EBA sera. These antibodies appear to be found in patients with inflammatory-type EBA.
Dipyridamole Selectively Inhibits Inflammatory Gene Expression in Platelet–Monocyte Aggregates
Authors: Andrew S. Weyrich, Melvin M. Denis, Jennifer R. Kuhlmann-Eyre, Eliott D. Spencer, Dan A. Dixon, Gopal K. Marathe, Tom M. McIntyre, Guy A. Zimmerman, Stephen M. Prescott
Journal: Circulation (2005)

Background— Drugs that simultaneously decrease platelet function and inflammation may improve the treatment of cardiovascular disorders. Here, we determined whether dipyridamole and aspirin, a combination therapy used to prevent recurrent stroke, regulates gene expression in platelet–monocyte inflammatory model systems. Methods and Results— Human platelets and monocytes were pretreated with dipyridamole, aspirin, or both inhibitors. The cells were stimulated with thrombin or activated by adhesion to collagen, and gene expression was measured in the target monocytes. Thrombin-stimulated platelets increased monocyte chemotactic protein-1 (MCP-1) expression by monocytes. Dipyridamole but not aspirin attenuated nuclear translocation of NF-κB and blocked the synthesis of MCP-1 at the transcriptional level. Dipyridamole delayed maximal synthesis of interleukin-8 but did not alter cyclooxygenase-2 accumulation. Adherence to collagen and platelets also increased the expression of matrix metalloproteinase-9 (MMP-9) in monocytes, a response that was inhibited by dipyridamole. In this case, however, dipyridamole did not block transcription or distribution of MMP-9 mRNA to actively translating polysomes, indicating that it regulates the expression of MMP-9 protein at a postinitiation stage of translation. Dipyridamole also blocked MCP-1 and MMP-9 generated by lipopolysaccharide-treated monocytes, indicating that at least part of its inhibitory action is unrelated to its antiplatelet properties. Conclusions— These results indicate that dipyridamole has selective antiinflammatory properties that may contribute to its actions in the secondary prevention of stroke.
Persistency of response to omalizumab therapy in severe allergic (IgE-mediated) asthma
Authors: J. Bousquet, Z. Siergiejko, E. Świebocka, M. Humbert, K. F. Rabe, N. Smith, J. Leo, C. Peckitt, R. Maykut, G. Peachey
Journal: Allergy (2011)

The physician's global evaluation of treatment effectiveness (GETE) at 16 weeks has been shown to be the most effective assessment of response to omalizumab (XOLAIR®). This randomized, open-label, parallel-group study evaluated the persistency of treatment responder classification in patients receiving omalizumab added to optimized asthma therapy (OAT).Patients (12-75 years, n = 400) with severe allergic asthma, uncontrolled despite Global Initiative for Asthma 2004 Step 4 therapy, received OAT and omalizumab (n = 272) or OAT (n = 128) for 32 weeks. Response or nonresponse was evaluated at Weeks 16 and 32. Response was defined as an investigator's (physician's) GETE rating of excellent or good; nonresponse was defined as a rating of moderate, poor or worsening.Three hundred and forty-nine patients had GETE ratings available at Weeks 16 and 32 (omalizumab n = 258, OAT n = 91). Omalizumab responders of about 171/187 (91.4%)and 44/71 (62.0%) omalizumab nonresponders at Week 16 persisted as responders or nonresponders at Week 32. The investigator's GETE at Week 16 predicted persistency of response or nonresponse to omalizumab at Week 32 for 83.3% (215/258) of patients. OAT patients showed a lower persistency of response (18/28 [64.3%]) and a higher persistency of nonresponse (57/63 [90.5%]) than omalizumab patients. Excellent and good GETE ratings in omalizumab-treated patients were reflected by improvements in exacerbation rates (P < 0.001), severe exacerbation rates (P = 0.023), hospitalizations (P = 0.003), total emergency visits (P = 0.026) and Asthma Control Questionnaire overall score (P < 0.001).Response to omalizumab, as assessed by a physician's GETE at 16 weeks, is an effective predictor of continuing persistent response to omalizumab for the majority of patients.