tbuckley/cabot-search huggingface dataset:
Altered Hierarchy of Protective Responses Against Severe Hypoglycemia in Normal Aging in Healthy Men
Authors: Krystyna Matyka, Mark Evans, Jill Lomas, Iain Cranston, Ian Macdonald, Stephane A Amiel
Journal: Diabetes Care (1997)

OBJECTIVE To investigate the effect of normal aging on the protective responses against hypoglycemia, in view of the fact that type II diabetes is primarily a disease of aging, and its treatment is associated with risk of hypoglycemia with cognitive impairment. RESEARCH DESIGN AND METHODS Plasma glucose was lowered stepwise from 5 to 2.4 mmol/l and restored by manipulation of an infusion of 20% glucose during 220-min intravenous infusion of 1.5 mU · kg−1 · min−1 soluble insulin in 14 men; 7 were aged 60–70 years and the other 7 were 22–26 years. Changes in neurohumoral responses, subjective awareness, and choice reaction time were assessed. RESULTS Hormonal responses were similar in the two groups, but symptoms began earlier in the younger men (at a plasma glucose of 3.6 ± 0.1 vs. 3.0 ± 0.2 mmol/l, P = 0.02) and were more intense (P = 0.03). Four-choice reaction time, a measure of psychomotor coordination, deteriorated earlier in the older men (at a plasma glucose of 3.0 ± 0.1 vs. 2.6 ± 0.1 mmol/l, P = 0.07) and to a greater degree. The difference between the glucose level for subjective awareness of hypoglycemia and the onset of cognitive dysfunction was lost in the older men (0.0 ± 0.2 vs. 0.8 ± 0.1 mmol/l, P &amp;lt; 0.007). CONCLUSIONS Older men are prone to more severe cognitive impairment during hypoglycemia than younger men and are less likely to experience prior warning symptoms if blood glucose falls. This effect of normal aging may contribute to the risk of severe hypoglycemia in older diabetic patients treated with sulfonylureas and insulin.
Tumor Necrosis Factor-α–Induced AT <sub>1</sub> Receptor Upregulation Enhances Angiotensin II–Mediated Cardiac Fibroblast Responses That Favor Fibrosis
Authors: JianFeng Peng, Devorah Gurantz, Van Tran, Randy T. Cowling, Barry H. Greenberg
Journal: Circulation Research (2002)

Extracellular matrix (ECM) remodeling after myocardial infarction (MI) is an important determinant of cardiac function. Tumor necrosis factor-α (TNF-α) and angiotensin (Ang) II levels increase after MI and both factors affect fibroblast functions. The type 1 (AT 1 ) receptor that mediates most Ang II effects is upregulated after MI in cardiac fibroblasts, and there is evidence that this is caused by TNF-α. We sought to determine if TNF-α–induced AT 1 receptor upregulation alters fibroblast responsiveness to Ang II and if this effect differs from direct TNF-α effects on fibroblast functions. In cultured neonatal rat cardiac fibroblasts, TNF-α reduced cellular [ 3 H]-proline incorporation, increased matrix metalloproteinase-2 (MMP-2) activity and protein, and increased TIMP-1 protein levels. In cardiac fibroblasts with TNF-α–induced AT 1 receptor upregulation, Ang II–stimulated [ 3 H]proline incorporation and TIMP-1 protein production was approximately 2-fold greater than in nonpretreated fibroblasts. Angiotensin II reduced MMP-2 activity and protein level only in TNF-α–pretreated fibroblasts. Angiotensin II effects were inhibited by selective AT 1 (but not AT 2 ) receptor blockers. Thus, TNF-α–induced AT 1 receptor upregulation enhances Ang II–mediated functions that favor fibrosis. These effects are mostly directionally opposite of direct TNF-α effects on cardiac fibroblasts. Recognition of multifaceted TNF-α effects provides new insights into post-MI ECM remodeling.
Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA.
Authors: S Ikeyama, M Koyama, M Yamaoko, R Sasada, M Miyake
Journal: The Journal of Experimental Medicine (1993)

Previously we showed that motility-related protein (MRP-1) is an antigen recognized by monoclonal antibody (mAb) M31-15 inhibiting cell motility and that the sequence of MRP-1 coincides with that of CD9. In the present study, plasmid was constructed in which human MRP-1/CD9 cDNA is expressed under the control of the Abelson murine leukemia virus promoter sequence. The expression plasmid for MRP-1/CD9 was introduced into Chinese hamster ovary cells, human lung adenocarcinoma cell line MAC10 (MRP-1 positive), and human myeloma cell line ARH77 (MRP-1 negative). All of the MRP-1/CD9 (over)expressing clones obtained from these transfected cells showed suppressed cell motility (penetration and phagokinetic track assays) depending on the degree of expression of MRP-1/CD9. Overexpression of MRP-1/CD9 by MAC10 cells resulted in the suppression of cell motility (maximally 73%) associated with considerable inhibition of the cell growth (maximally 48%). However, the inhibition of the growth of MAC10 cells by mAb M31-15 was < 17% at an antibody concentration of 1-5 micrograms/ml, which inhibits cell motility by > 90%. These results suggest that MRP-1/CD9 directly regulates cell motility and may also affect cell growth. Effects on metastasis by the expression of MRP-1 CD9 were investigated with mouse melanoma BL6 cells-BALB/c nu/nu mouse system. Metastatic potential of all transformants expressing MRP-1/CD9 was lower than that of parent BL6 cells.
N-acetylcysteine (NAC) and liver warm ischemia reperfusion injury: Alterations to bile composition demonstrated by proton nuclear magnetic resonance spectroscopy (MRS)
Authors: T.S. Hafez, G.K. Glantzounis, I.J. Cox, H. Sheth, W. Yang, A.M. Seifalian, B. Fuller, B.R. Davidson
Journal: Journal of Hepatology (2003)
Base rates, experience, and the big picture
Authors: Stephen E. Edgell, Robert M. Roe, Clayton H. Dodd
Journal: Behavioral and Brain Sciences (1996)

Abstract The important question is how people process probabilistic information, not whether they process it in accordance with a normative model that we never should have expected them to be capable of following. Experience is not the cure, as widely thought, to problems with utilizing base rate information.
Metabolic Approaches to Cancer Cachexia
Authors: David H. Lawson, Ann Richmond, Daniel W. Nixon, Daniel Rudman
Journal: Annual Review of Nutrition (1982)

OVERVIEW OF CANCER CACHEXIA Introduction   . Prevalence of Clinical Cancer Cachexia   . Relationship of Protein-Calorie Undernutrition to Survival in Cancer Patients   . Postulated Mechanisms for the Development of Cancer Cachexia   . METABOLIC ABNORMALITIES IN CANCER SUBJECTS ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Metabolic Characteristics of Cancer Cells   . Altered Metabolism of Host Cells: the Divergent Behavior of Liver and Muscle   . Altered Metabolism of Host at the Whole Organism Level   . CONCLUSIONS .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   . . . . . . . . . . . . . . . . . . . . . . . . .   .
Immunological mechanisms of sublingual immunotherapy
Authors: C. A. Akdis, I. B. Barlan, N. Bahceciler, M. Akdis
Journal: Allergy (2006)

Administration of allergen‐specific immunotherapy by the oral route, sublingual immunotherapy (SLIT), has been shown to be effective, with an improved safety profile compared with subcutaneous administration. However, the precise mechanisms underlying the induction of immune tolerance by SLIT remain unclear. Contact of the allergen with the antigen‐presenting cells in oral mucosa is likely to be critical. Mucosal Langerhans cells can capture the allergen and transport it to local lymph nodes, which may favour the induction of T lymphocytes that suppress the allergic response. In addition, the production of blocking IgG4 antibodies and the involvement of mucosal B cells appear to play a role. There is a growing evidence to support the role of regulatory T cells in controlling the development of asthma and allergic disease. Nevertheless, there remains a lack of firm evidence that SLIT induces regulatory T cells, although preliminary in vitro data suggest that SLIT may increase interleukin‐10, which has a clear role in suppressing the allergic immune response. Further studies are required to determine the involvement of regulatory T cells, the role of different dendritic cell subsets, mucosal B cells as well as the potential use of adjuvants during SLIT.
Pancreas Transplantation for Type 2 Diabetes at U.S. Transplant Centers
Authors: Amy L. Friedman, Eli A. Friedman
Journal: Diabetes Care (2002)

Pancreas transplantation, the most effective method of normalizing glucose control in type 1 diabetes, is not commonly used in type 2 diabetes, although patient and graft survival rates are equivalent (1). We conducted a mail survey of American transplant programs on 15 September 2000 characterizing the approach to pancreas transplantation in type 2 diabetic end-stage renal disease (ESRD) patients.

A total of 44 (30.3%) centers responded. The mean center-specific cumulative volume was 70 ± 227 cases (0–1,300), with a total of 6,014 procedures. The collective experience of 872 cases in 1999 represents 71% of the 1,237 …
Oral cancer overexpressed 1 (ORAOV1) regulates cell cycle and apoptosis in cervical cancer HeLa cells
Authors: Lu Jiang, Xin Zeng, Zhi Wang, Ning Ji, Yu Zhou, Xianting Liu, Qianming Chen
Journal: Molecular Cancer (2010)

Abstract Background Oral Cancer Overexpressed 1 (ORAOV1) is a candidate protooncogene locating on 11q13. Recent studies show that ORAOV1 acts as a primary driving force behind 11q13 gene amplification and plays a functional role in the tumorigenesis in a variety of human squamous cell carcinomas (SCCs). According to the results of molecular cytogenetic methods, 11q13 was characterized to be a high-level and recurrent amplification chromosomal site in cervical cancers. Up till now, the role of ORAOV1 in cervical cancer is unknown. The purpose of this study is to elucidate the function of ORAOV1 in cervical cancer cell growth by studying its roles in HeLa cells using small interfering RNA. Results Functional analyses revealed that ORAOV1 was involved in the regulation of HeLa cell growth through its effect on cell cycle and apoptosis. Silence of ORAOV1 in HeLa cells downregulated the expression of Cyclin A, Cyclin B1 and Cdc2, and led to a distinct S cell cycle arrest. Moreover, knockdown of ORAOV1 expression activated both extrinsic and intrinsic apoptotic pathways and led to apoptosis in HeLa cells through its effect on the expression of several apoptosis related proteins such as P53, Bcl-2, Caspase-3, Caspase-8, Caspase-9 and cytochrome c. Interestingly, the expression of Cyclin D1, a pivotal gene for cervical cancer tumorigenesis, was also found to be reduced in ORAOV1 silenced HeLa cells. Conclusion Our findings indicate that ORAOV1 has an important role in regulating cell growth of cervical cancer HeLa cells through regulating the cell cycle and apoptosis. Thus, it may be a crucial protooncogene and a novel candidate therapeutic target for cervical cancer.
Choline magnesium trisalicylate in patients with aspirin-induced asthma
Authors: A Szczeklik, E Nizankowska, R Dworski
Journal: European Respiratory Journal (1990)

Treatment of inflammatory diseases of asthmatics can be a serious problem since some patients show intolerance to aspirin and other non-steroidal, anti-inflammatory drugs that are cyclooxygenase inhibitors. Salicylates were believed to be well tolerated, but recent reports have demonstrated that diflunisal and salicylsalicylic acid can precipitate asthma attacks in aspirin-intolerant patients. This study was designed to determine the tolerance of choline magnesium trisalicylate (CMT), a nonacetylated salicylate with potent analgesic and anti-inflammatory activity, in 23 asthmatics with aspirin hypersensitivity confirmed by oral challenge. The study consisted of three phases: 1) patients received increasing doses (50-1,500 mg) of CMT under a single-blind protocol; 2) patients received either a placebo or CMT challenge in a double-blind, randomized, cross-over design; 3) patients received CMT at daily 3,000 mg doses for 1 week. Throughout the study, pulmonary function tests, peak nasal inspiratory flow, and serum salicylate and thromboxane B2 (TXB2) levels were monitored. Results showed no airway obstruction, nasal congestion or rhinorrhea after CMT. There was no significant decrease in serum TXB2 levels, indicating the absence of cyclooxygenase inhibition with CMT. We conclude that choline magnesium trisalicylate is a safe drug for treatment of different anti-inflammatory disorders in asthmatics with aspirin hypersensitivity.
The Burden of Disease and the Changing Task of Medicine
Authors: David S. Jones, Scott H. Podolsky, Jeremy A. Greene
Journal: New England Journal of Medicine (2012)

At first glance, the inaugural 1812 issue of the New England Journal of Medicine and Surgery seems reassuringly familiar: a review of angina pectoris, articles on infant diarrhea and burns.The apparent similarity to today's Journal, however, obscures a fundamental discontinuity.Disease has changed since 1812.People have different diseases, doctors hold different ideas about those diseases, and diseases carry different meanings in society.To understand the material and conceptual transformations of disease over the past 200 years, one must explore the inextricably social nature of disease.Disease is always generated, experienced, defined, and ameliorated within a social world.Patients need notions of disease that explicate their suffering.Doctors need theories of etiology and pathophysiology that account for the burden of disease and inform therapeutic practice.Policymakers need realistic understandings of determinants of disease and medicine's impact in order to design systems that foster health.The history of disease offers crucial insights into the intersections of these interests and the ways they can inform medical practice and health policy. Epidemiologic transitions
Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (Macaca fascicularis)
Authors: Alex D Greenwood, Michelle Vincendeau, Ann-Christin Schmädicke, Judith Montag, Wolfgang Seifarth, Dirk Motzkus
Journal: Molecular Neurodegeneration (2011)

Abstract Background Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results Cynomolgus macaques ( Macaca fasicularis ) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2) RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2) Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration.
Risks for Incident Human Papillomavirus Infection and Low-Grade Squamous Intraepithelial Lesion Development in Young Females
Authors: Anna-Barbara Moscicki
Journal: JAMA (2001)

OW-GRADE SQUAMOUS INTRAepithelial lesions (LSILs) are relatively common manifestations of cervical human papillomavirus (HPV) infections.][5] Some researchers suggest that all HPV infections result in pathologic changes of LSIL at some point in the natural history of infection; however, the discrepancy between rates of infection with HPV and development of LSIL is quite striking, even in adolescent and young women in whom the prevalence of both is high.7][8] Differences in the length of HPV and LSIL persistence do not completely explain the observed discordance because re-
High prevalence of anti-CD74 antibodies specific for the HLA class II-associated invariant chain peptide (CLIP) in patients with axial spondyloarthritis: Table 1
Authors: X Baraliakos, N Baerlecken, T Witte, F Heldmann, J Braun
Journal: Annals of the Rheumatic Diseases (2013)

The pathogenesis of axial spondyloarthritis (axSpA) is still unclear. There is a strong association with HLA-B27 and other genes. Recently, anti-CD74 antibodies with specificity to a class II-associated invariant chain peptide (anti-CLIP-ABs) were found in axSpA patients. We examined the prevalence, sensitivity and specificity of anti-CLIP-ABs in axSpA in comparison with controls.Sera of axSpA and non-SpA patients were analysed for IgG-antibodies against CD74 by ELISA with specificity for CLIP developed in cooperation with AESKU Diagnostics (Germany). A cut-off of ≥4 SDs of arbitrary units (AU) from mean serum levels was used to differentiate the results. The laboratory workers were completely blinded for clinical data.We analysed 145 sera from 94 axSpA and 51 non-SpA patients. AxSpA patients were more often male and younger. HLA-B27 status was available in 72 patients. Anti-CLIP-ABs were detected in 85.1% in axSpA but in only 7.8% in non-SpA patients (p≤0.0001). AxSpA patients showed higher levels of anti-CLIP-ABs versus non-SpA: mean 14.5 versus 0.8 AU (p≤0.0001). The sensitivity of anti-CLIP-ABs for diagnosing axSpA was 85.1%, specificity 92.2%, likelihood ratio (LR) LR+ was 10.8 and LR- was 0.08. Anti-CLIP-ABs and HLA-B27 were positive in 87.5% patients with axSpA, but only 14.9% were anti-CLIP-negative, while 23.6% were HLA-B27-negative.Anti-CLIP antibodies were strongly associated with axSpA. The LR for confirming axSpA by using anti-CLIP was even higher than by using HLA-B27. More studies using this promising new method in patients with non-radiographic axial SpA or peripheral SpA are needed to establish its usefulness in clinical practice.
T cell priming versus T cell tolerance induced by synthetic peptides.
Authors: P Aichele, K Brduscha-Riem, R M Zinkernagel, H Hengartner, H Pircher
Journal: The Journal of Experimental Medicine (1995)

It is well known that synthetic peptides are able to both induce and tolerize T cells. We have examined the parameters leading either to priming or tolerance of CD8+ cytotoxic T lymphocytes (CTL) in vivo with a major histocompatibility complex class I (H-2 Db) binding peptide derived from the glycoprotein (GP aa33-41) of lymphocytic choriomeningitis virus (LCMV). By varying dose, route, and frequency of LCMV GP peptide application, we found that a single local subcutaneous injection of 50-500 micrograms peptide emulsified in incomplete Freund's adjuvant protected mice against LCMV infection, whereas repetitive and systemic intraperitoneal application of the same dose caused tolerance of LCMV-specific CTL. The peptide-induced tolerance was transient in euthymic mice but permanent in thymectomized mice. These findings are relevant for a selective use of peptides as a therapeutic approach: peptide-induced priming of T cells for vaccination and peptide-mediated T cell tolerance for intervention in immunopathologies and autoimmune diseases.
Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity
Authors: Masayuki Ito, Takuma Maruyama, Naotoshi Saito, Satoru Koganei, Kazuo Yamamoto, Naoki Matsumoto
Journal: The Journal of Experimental Medicine (2006)

Killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor expressed on subsets of natural killer (NK) cells and T cells, for which no endogenous ligands are known. Here, we show that KLRG1 binds three of the classical cadherins (E-, N-, and R-), which are ubiquitously expressed in vertebrates and mediate cell–cell adhesion by homotypic or heterotypic interactions. By expression cloning using the mouse KLRG1 tetramer as a probe, we identified human E-cadherin as a xenogeneic ligand. We also identified a syngeneic interaction between mouse KLRG1 and mouse E-cadherin. Furthermore, we show that KLRG1 binds N- and R-cadherins. Finally, we demonstrate that E-cadherin binding of KLRG1 prevents the lysis of E-cadherin–expressing targets by KLRG1+ NK cells. These results suggest that KLRG1 ligation by E-, N-, or R-cadherins may regulate the cytotoxicity of killer cells to prevent damage to tissues expressing the cadherins.
A case of generalized psoriasiform and pustular eruption induced by infliximab: evidence for skin-homing Th17 in the pathogenesis
Authors: Y. Teraki, S. Tanaka, K. Hitomi, S. Izaki
Journal: British Journal of Dermatology (2010)

Journal Article A case of generalized psoriasiform and pustular eruption induced by infliximab: evidence for skin‐homing Th17 in the pathogenesis Get access Y. Teraki, Y. Teraki Department of Dermatology, Saitama Medical University, Saitama Medical Center, 1981 Kamoda, Kawagoe, Saitama 350‐8550, Japan E‐mail: teraki@saitama‐med.ac.jp Search for other works by this author on: Oxford Academic Google Scholar S. Tanaka, S. Tanaka Department of Dermatology, Saitama Medical University, Saitama Medical Center, 1981 Kamoda, Kawagoe, Saitama 350‐8550, Japan E‐mail: teraki@saitama‐med.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Hitomi, K. Hitomi Department of Dermatology, Saitama Medical University, Saitama Medical Center, 1981 Kamoda, Kawagoe, Saitama 350‐8550, Japan E‐mail: teraki@saitama‐med.ac.jp Search for other works by this author on: Oxford Academic Google Scholar S. Izaki S. Izaki Department of Dermatology, Saitama Medical University, Saitama Medical Center, 1981 Kamoda, Kawagoe, Saitama 350‐8550, Japan E‐mail: teraki@saitama‐med.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 6, 1 December 2010, Pages 1347–1351, https://doi.org/10.1111/j.1365-2133.2010.10002.x Published: 01 December 2010