tbuckley/cabot-search huggingface dataset:
Prevalence, Diagnosis, and Treatment of Impaired Fasting Glucose and Impaired Glucose Tolerance in Nondiabetic U.S. Adults
Authors: Amrita Karve, Rodney A. Hayward
Journal: Diabetes Care (2010)

OBJECTIVE To estimate the rates of prevalence, diagnosis, and treatment of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS A representative sample of the U.S. population (the National Health and Nutrition Examination Survey [NHANES]) from 2005–2006 including 1,547 nondiabetic adults (&amp;gt;18 years of age) without a history of myocardial infarction was assessed to determine the proportion of adults who met the criteria for IFG/IGT, and the proportion of IFG/IGT subjects who: 1) reported receiving a diagnosis from their physicians; 2) were prescribed lifestyle modification or an antihyperglycemic agent; and 3) were currently on therapy. We used multivariable regression analysis to identify predictors of diagnosis and treatment. RESULTS Of the 1,547 subjects, 34.6% (CI 30.3–38.9%) had pre-diabetes; 19.4% had IFG only; 5.4% had IGT only, and 9.8% had both IFG and IGT. Only 4.8% of those with pre-diabetes reported having received a formal diagnosis from their physicians. No subjects with pre-diabetes received oral antihyperglycemics, and the rates of recommendation for exercise or diet were 31.7% and 33.5%, respectively. Among the 47.7% pre-diabetic subjects who exercised, 49.4% reported exercising for at least 30 min daily. CONCLUSIONS Three years after a major clinical trial demonstrated that interventions could greatly reduce progression from IFG/IGT to type 2 diabetes, the majority of the U.S. population with IFG/IGT was undiagnosed and untreated with interventions. Whether this is due to physicians being unaware of the evidence, unconvinced by the evidence, or clinical inertia is unclear.
Tenascin-W Is a Novel Marker for Activated Tumor Stroma in Low-grade Human Breast Cancer and Influences Cell Behavior
Authors: Martin Degen, Florence Brellier, Renate Kain, Christian Ruiz, Luigi Terracciano, Gertraud Orend, Ruth Chiquet-Ehrismann
Journal: Cancer Research (2007)

Abstract This is the first report about human tenascin-W, the fourth and final member of the extracellular matrix protein family of tenascins. Sixty-three human breast tumor extracts were analyzed by Western blotting for the presence of tenascin-W and compared with tenascin-C, an established marker of tumor stroma. Interestingly, we found tenascin-W expression in the majority of the tumor tissues, but no detectable expression in the normal mammary parenchyma. Eighty-one percent of the breast tumor samples were tenascin-W positive and 86% showed expression of tenascin-C. However, tenascin-W and tenascin-C amounts varied greatly between tumors and some contained either tenascin-W or tenascin-C exclusively, indicating independent mechanisms regulating their expression. Although there was no difference between high- or low-grade tumors with respect to the presence of tenascin-C, tenascin-W was more prominent in low-grade tumors. For 42 of the breast cancer tissues, a frozen tumor microarray was available to confirm the Western blot data by immunohistochemistry. Similar to tenascin-C, tenascin-W was detected in the tumor stroma. Fibroblasts adhered to tenascin-W in a β1 integrin–dependent manner and spread with a distinctive morphology under conditions where they remained round on tenascin-C. CHOB2 cells expressing αvβ1 or α4β1 integrins were able to spread on tenascin-W. Furthermore, addition of tenascin-W to the culture medium increased migration of breast cancer cells toward a fibronectin substratum in vitro. These data imply that tenascin-W expression in the activated tumor stroma facilitates tumorigenesis by supporting the migratory behavior of breast cancer cells. [Cancer Res 2007;67(19):9169–79]
Using C-Arm X-Ray Imaging to Guide Local Reporter Probe Delivery for Tracking Stem Cell Engraftment
Authors: Dorota A Kedziorek, Meiyappan Solaiyappan, Piotr Walczak, Tina Ehtiati, Yingli Fu, Jeff W M Bulte, Steven M Shea, Alexander Brost, Frank K Wacker, Dara L Kraitchman
Journal: Theranostics (2013)

Poor cell survival and difficulties with visualization of cell delivery are major problems with current cell transplantation methods.To protect cells from early destruction, microencapsulation methods have been developed.The addition of a contrast agent to the microcapsule also could enable tracking by MR, ultrasound, and X-ray imaging.However, determining the cell viability within the microcapsule still remains an issue.Reporter gene imaging provides a way to determine cell viability, but delivery of the reporter probe by systemic injection may be hindered in ischemic diseases.In the present study, mesenchymal stem cells (MSCs) were transfected with triple fusion reporter gene containing red fluorescent protein, truncated thymidine kinase (SPECT/PET reporter) and firefly luciferase (bioluminescence reporter).Transfected cells were microencapsulated in either unlabeled or perfluorooctylbromide (PFOB) impregnated alginate.The addition of PFOB provided radiopacity to enable visualization of the microcapsules by X-ray imaging.Before intramuscular transplantation in rabbit thigh muscle, the microcapsules were incubated with D-luciferin, and bioluminescence imaging (BLI) was performed immediately.Twenty-four and forty-eight hours post transplantation, c-arm CT was used to target the luciferin to the X-ray-visible microcapsules for BLI cell viability assessment, rather than systemic reporter probe injections.Not only was the bioluminescent signal emission from the PFOB-encapsulated MSCs confirmed as compared to non-encapsulated, naked MSCs, but over 90% of injection sites of PFOB-encapsulated MSCs were visible on c-arm CT.The latter aided in successful targeting of the reporter probe to injection sites using conventional X-ray imaging to determine cell viability at 1-2 days post transplantation.Blind luciferin injections to the approximate location of unlabeled microcapsules resulted in successful BLI signal detection in only 18% of injections.In conclusion, reporter gene probes can be more precisely targeted using c-arm CT for in vivo transplant viability assessment, thereby avoiding large and costly systemic injections of a reporter probe.
Secondary Gain in Long-Term Hemodialysis Patients
Authors: DANIEL A. DANSAK
Journal: American Journal of Psychiatry (1972)

Patients on long-term hemodialysis are subjected to many psychological and social stresses. However, through the mechanism of secondary gain, such patients may obtain certain gratifications that they refuse to relinquish. The author presents two case reports that demonstrate various secondary gains and discusses the complications they presented to a hemodialysis unit.
Induction of murine peritoneal gamma/delta T cells and their role in resistance to bacterial infection.
Authors: M J Skeen, H K Ziegler
Journal: The Journal of Experimental Medicine (1993)

Previous studies have reported an association of gamma/delta T cells with microbial infection in both human lesions and murine infectious disease models. In this study we provide a comprehensive analysis of the conditions under which the induction of gamma/delta T cells occurs at a site of infection. We found a site-specific induction of gamma/delta T cells after the injection of Listeria monocytogenes in the peritoneal cavity of C3H mice. No changes were seen in the splenic or lymph node populations after these injections. Both the proportion and the absolute number of gamma/delta T cells increased in the peritoneal cavity. Additionally, when peritoneal T cells from Listeria-immune mice were restimulated in vitro, the induced gamma/delta T cells exhibited a greater expansion potential than the alpha/beta T cells. Neither the induced gamma/delta T cells nor those from normal mice expressed CD4 or CD8 on the cell surface. Thy-1 was expressed on only 29% of normal peritoneal gamma/delta T cells, but after intraperitoneal Listeria injection 65% of induced gamma/delta T cells expressed. Thy-1, Pgp-1 and CD45R expression on both normal and induced gamma/delta T cells was consistent with an activation phenotype. Significant increases in peritoneal gamma/delta T cells were not seen until 5-7 d after Listeria injection. The proportion of the CD3+ population expressing the gamma/delta T cell receptor remained elevated for 6-7 wk, while the absolute numbers of peritoneal gamma/delta T cells declined gradually over this time period, reflecting a decrease in both the number of lymphocytes and the percentage of these that were CD3+. Peak numbers of gamma/delta T cells were seen at day 10 with live microbes such as Listeria. A variety of microbes, toxins, mitogens, antigens, cytokines, and nonspecific inflammatory agents were evaluated for their ability to induce gamma/delta T cells in the peritoneal cavity. Both Gram-positive and Gram-negative bacteria as well as Mycobacteria were able to induce gamma/delta T cells that showed increased in vitro expansion potential. An exotoxin from a Gram-positive organism, listeriolysin-o, and the lipopolysaccharide (LPS) endotoxin from a Gram-negative organism were also effective. gamma/delta T cell responses to LPS were under lps gene control. Peak numbers of gamma/delta T cells were observed at day 3 after injection with exotoxins and endotoxins. Modifications that abrogated the virulence of a bacterial strain also eliminated the inductive effect for gamma/delta T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
GRAFT-VS.-HOST REACTIONS IN RECIPROCAL HYBRID MICE
Authors: Herbert C. Morse, Michael R. Harrison, Richard Asofsky
Journal: The Journal of Experimental Medicine (1974)

Spleen cells from BALB/c and C57BL/6 mice were tested for their reactivity against reciprocal hybrid tissues ((BALB/c x C57BL/6) F(1) and (C57BL/6 x BALB/c) F(1)) in three assay systems: the mixed lymphocyte reaction (MLR); the Simonsen spleen-weight graft-vs.-host (GVH) assay; and a GVH mortality assay. It was shown that both F(1)'s serve as equally effective stimulators of parental cells in the MLR. In the spleen-weight assay, BALB/c and C57BL/6 cells were equally active in a given host, but greater splenomegaly was observed in (BALB/c x C57BL/6) F(1) hosts regardless of the donor strain. By contrast, BALB/c cells were much less lethal than C57BL/6 cells in (BALB/c x C57BL/6) F(1) hosts than in (C57BL/6 x BALB/c) F(1) hosts, and to a lesser degree C57BL/6 cells were less lethal than BALB/c cells in (C57BL/6 x BALB/c) F(1) hosts. The possibility that modifying substances may differentially alter reactivity of parental lymphocytes and that considerations other than genotype determine the outcome of a GVH reaction are discussed in detail.
Agonist Anti-GITR Antibody Enhances Vaccine-Induced CD8+ T-Cell Responses and Tumor Immunity
Authors: Adam D. Cohen, Adi Diab, Miguel-Angel Perales, Jedd D. Wolchok, Gabrielle Rizzuto, Taha Merghoub, Deonka Huggins, Cailian Liu, Mary Jo Turk, Nicholas P. Restifo, Shimon Sakaguchi, Alan N. Houghton
Journal: Cancer Research (2006)

Abstract Immunization of mice with plasmids encoding xenogeneic orthologues of tumor differentiation antigens can break immune ignorance and tolerance to self and induce protective tumor immunity. We sought to improve on this strategy by combining xenogeneic DNA vaccination with an agonist anti–glucocorticoid-induced tumor necrosis factor receptor family–related gene (GITR) monoclonal antibody (mAb), DTA-1, which has been shown previously both to costimulate activated effector CD4+ and CD8+ T cells and to inhibit the suppressive activity of CD4+CD25+ regulatory T cells. We found that ligation of GITR with DTA-1 just before the second, but not the first, of 3 weekly DNA immunizations enhanced primary CD8+ T-cell responses against the melanoma differentiation antigens gp100 and tyrosinase-related protein 2/dopachrome tautomerase and increased protection from a lethal challenge with B16 melanoma. This improved tumor immunity was associated with a modest increase in focal autoimmunity, manifested as autoimmune hypopigmentation. DTA-1 administration on this schedule also led to prolonged persistence of the antigen-specific CD8+ T cells as well as to an enhanced recall CD8+ T-cell response to a booster vaccination given 4 weeks after the primary immunization series. Giving the anti-GITR mAb both during primary immunization and at the time of booster vaccination increased the recall response even further. Finally, this effect on vaccine-induced CD8+ T-cell responses was partially independent of CD4+ T cells (both helper and regulatory), consistent with a direct costimulatory effect on the effector CD8+ cells themselves. (Cancer Res 2006; 66(9); 4904-12)
Progeria: a cell culture study on aging
Authors: B. Shannon Danes
Journal: Journal of Clinical Investigation (1971)

Progeria is an autosomal recessive disorder showing precocious senility. The cultured skin fibroblast from both the homozygous affected individual and the heterozygous parents can be distinguished from normals by decreased cell growth in culture. Mitotic activity, DNA synthesis, and cloning efficiency are markedly reduced.
Glycine in the Treatment of Gout
Authors: F. Wrigley
Journal: Annals of the Rheumatic Diseases (1950)

The use of glycine and salicylate in the treatment of gout has now become fairly well established.This paper is to suggest a reconsideration of this form of therapy.Quick (1934), writing on " Uric Acid in Clinical Medicine ", says: " Of prime importance is the observation that under standardized and fixed conditions, the rate of uric acid excretion tends to be constant, is uninfluenced by the volume of urine, and is independent of the concentration of uric acid in the blood."The rate of uric acid excretion seems, therefore, dependent upon a metabolic process.Unlike creatinine, which is promptly excreted when fed, uric acid ingestion does not increase the hourly output.Quick then lists substances which increase and * 0008 g. of salicylic acid as acetylsalicylic acid excreted during the first hour.t 0 014 g. of salicylic acid as acetylsalicylic acid excreted during the first hour.38
Brain loading in concussive head impacts: implications for injury prevention
Authors: D Patton, A McIntosh, S Kleiven
Journal: British Journal of Sports Medicine (2011)

Background Concussion is a prominent injury risk in sport, but the mechanisms that cause concussion are unclear. An important debate centres on the roles of angular and linear head acceleration in the mechanism of concussion. Resolving this debate is a prerequisite for developing injury prevention methods. Objective To estimate the brain loading patterns in a case series of concussive and no-injury head impacts. To assess the relative affects of linear and angular acceleration on brain loading and injury. Design Biomechanical analysis of head impacts using the validated KTH human head finite element model to analyse brain loading patterns in reconstructed head impacts. Setting Professional male unhelmeted contact football. Participants Biomechanical data from a previous case series study of 40 male football players (concussed and no-injury). Main outcome measurements Maximum principle strain, a predictor of injury, was measured in discrete brain locations. Results The highest maximum principle strains were recorded in both the white and grey matter of the cerebrum. Strains in all brain regions were similar across all three grades of concussion (Cantu Revised Concussion Grading Guidelines), but lower (33–47%) for no-injury cases. Concussion was most correlated with strains in the brainstem and thalamus. Angular, rather than linear, resultant accelerations correlated higher to strains in all regions of the brain. Angular accelerations in the coronal plane and linear accelerations directed inferiorly had the greatest correlation to concussion and loss of consciousness. For linear accelerations, those directed laterally and inferiorly were most correlated with strain. Angular accelerations in the coronal plane correlated highly with strains in the brainstem, thalamus, and midbrain. Angular accelerations in the transverse plane correlated highly with strains in the cerebrum and corpus callosum. Conclusion Brain loading differences were observed between concussion and no-injury cases. Angular acceleration may play a more important role in the mechanism of concussion than linear acceleration.
Standardised methodology of sputum induction and processing
Authors: R. Djukanovic, P.J. Sterk, J.V. Fahy, F.E. Hargreave 
Journal: European Respiratory Journal (2002)

Research into the pathogenetic mechanisms and clinical monitoring of inammatory diseases of any system is complete only if it involves the study of both the underlying pathological features and the physio- logical consequences that result from what are always complex inammatory processes. Respiratory dis- eases, including those of the airways, are no exception in this respect. It is, therefore, not surprising that the development over the last 25 years of techniques enabling the study of inammatory processes in the airways has revolutionised understanding of the commonest pulmonary diseases, asthma and chronic obstructive pulmonary disease (COPD). Airways inammation is now an established feature and a central consideration of any treatment strategy for both of these conditions. Most of the initial observations made in asthma, documenting the involvement of eosinophils, mast cells, T-cells and more recently structural cells, ® broblasts, endothelial cells and epithelial cells, were made in studies using ® breoptic bronchoscopy in
Exposure to ultraviolet-B and risk of developing rheumatoid arthritis among women in the Nurses’ Health Study
Authors: Elizabeth V Arkema, Jaime E Hart, Kimberly A Bertrand, Francine Laden, Francine Grodstein, Bernard A Rosner, Elizabeth W Karlson, Karen H Costenbader
Journal: Annals of the Rheumatic Diseases (2013)

To examine the association between ultraviolet-B (UV-B) light exposure and rheumatoid arthritis (RA) risk among women in two large prospective cohort studies, the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII).A total of 106 368 women from NHS, aged 30-55 years in 1976, and 115 561 women from NHSII, aged 25-42 in 1989, were included in the analysis. We identified women with incident RA from the start of each cohort until 2008 (NHS) and 2009 (NHSII). Cumulative average UV-B flux, a composite measure of ambient UV exposure based on latitude, altitude and cloud cover, was estimated according to state of residence and categorised as low, medium or high. Estimates of UV-B at birth and age 15 years were also examined. We used multivariable-adjusted Cox proportional hazards models to estimate HR and 95% CI.1314 incident RA cases were identified in total. Among NHS participants, higher cumulative average UV-B exposure was associated with decreased RA risk; those in the highest versus lowest category had a 21% decreased RA risk (HR (95% CI); 0.79 (0.66 to 0.94)). UV-B was not associated with RA risk among younger women in NHSII (1.12 (0.87 to 1.44)). Results were similar for UV-B at birth and at age 15.These results suggest that ambient UV-B exposure is associated with a lower RA risk in NHS, but not NHSII. Differences in sun-protective behaviours (eg, greater use of sun block in younger generations) may explain the disparate results.
The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses
Authors: Natalie J. Serkova, Theodore J. Standiford, Kathleen A. Stringer
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Metabolomics, a science of systems biology, is the global assessment of endogenous metabolites within a biologic system and represents a "snapshot" reading of gene function, enzyme activity, and the physiological landscape. Metabolite detection, either individual or grouped as a metabolomic profile, is usually performed in cells, tissues, or biofluids by either nuclear magnetic resonance spectroscopy or mass spectrometry followed by sophisticated multivariate data analysis. Because loss of metabolic homeostasis is common in critical illness, the metabolome could have many applications, including biomarker and drug target identification. Metabolomics could also significantly advance our understanding of the complex pathophysiology of acute illnesses, such as sepsis and acute lung injury/acute respiratory distress syndrome. Despite this potential, the clinical community is largely unfamiliar with the field of metabolomics, including the methodologies involved, technical challenges, and, most importantly, clinical uses. Although there is evidence of successful preclinical applications, the clinical usefulness and application of metabolomics in critical illness is just beginning to emerge, the advancement of which hinges on linking metabolite data to known and validated clinically relevant indices. In addition, other important aspects, such as patient selection, sample collection, and processing, as well as the needed multivariate data analysis, have to be taken into consideration before this innovative approach to biomarker discovery can become a reliable tool in the intensive care unit. The purpose of this review is to begin to familiarize clinicians with the field of metabolomics and its application for biomarker discovery in critical illnesses such as sepsis.
Androgenic Control of Transforming Growth Factor-β Signaling in Prostate Epithelial Cells through Transcriptional Suppression of Transforming Growth Factor-β Receptor II
Authors: Kyung Song, Hui Wang, Tracy L. Krebs, Seong-Jin Kim, David Danielpour
Journal: Cancer Research (2008)

Abstract The androgen receptor cross-talks with transforming growth factor-β (TGF-β) through mechanisms that remain poorly understood. Here we provide strong evidence that 5α-dihydrotestosterone (DHT) intercepts the ability of prostate epithelial cells to undergo TGF-β–induced apoptosis, and present a new model for this androgenic effect. We report that DHT decreases the level of TGF-β receptor II (TβRII) through a transcriptional mechanism, leading to suppression of the ability of TGF-β to down-regulate expression of Bcl-xL and cyclin Ds, activate caspase-3, and induce apoptosis. Promoter analysis, DNA pulldown, and electrophoretic mobility shift assays support that transcriptional down-regulation of TβRII by DHT occurs through Sp1/Sp3 response elements, with the binding of Sp1 to the TβRII promoter being suppressed by DHT, largely driven by loss of Sp1 protein and/or activity. These results provide fresh insight on the mechanism of growth control by androgens and the progression of prostate cancer to androgen independence. [Cancer Res 2008;68(19):8173–82]