tbuckley/cabot-search huggingface dataset:
Matrix Gla Protein Species and Risk of Cardiovascular Events in Type 2 Diabetic Patients
Authors: Geertje W. Dalmeijer, Yvonne T. van der Schouw, Elke J. Magdeleyns, Cees Vermeer, W.M. Monique Verschuren, Jolanda M.A. Boer, Joline W.J. Beulens
Journal: Diabetes Care (2013)

OBJECTIVE To investigate the relationship of circulating matrix Gla protein (MGP) species with incident cardiovascular disease (CVD) or coronary heart disease (CHD) in type 2 diabetic patients. RESEARCH DESIGN AND METHODS EPIC-NL is a prospective cohort study among 40,011 Dutch men and women. At baseline (1993–1997), 518 participants were known to have type 2 diabetes. MGP levels were measured by ELISA techniques in baseline plasma samples. The incidence of fatal and nonfatal CVD and CVD subtypes—CHD, peripheral arterial disease (PAD), heart failure, and stroke—were obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs), adjusted for sex, waist-to-hip ratio, physical activity, and history of CVD. RESULTS During a median 11.2 years of follow-up, 160 cases of CVD were documented. Higher circulating desphospho-uncarboxylated MGP (dp-ucMGP) levels were significantly associated with higher risk of CVD, with an HR per SD (HRSD) of 1.21 (95% CI 1.06–1.38), PAD (HRSD 1.32 [95% CI 1.07–1.65]), and heart failure (HRSD 1.75 [95% CI 1.42–2.17]) after adjustment. Higher circulating dp-ucMGP levels were not related to risk of CHD (HRSD 1.12 [95% CI 0.94–1.34]) or stroke (HRSD 1.05 [95% CI 0.73–1.49]). Circulating desphospho-carboxylated MGP and circulating total-uncarboxylated MGP levels were not associated with CVD or CVD subtypes. CONCLUSIONS High dp-ucMGP levels were associated with increased CVD risk among type 2 diabetic patients, especially with the subtypes PAD and heart failure, while other MGP species were not related to CVD risk. These results suggest that a poor vitamin K status is associated with increased CVD risk.
HIV-1 Infection Impairs the Bronchoalveolar T-Cell Response to Mycobacteria
Authors: Barbara Kalsdorf, Thomas J. Scriba, Kathryn Wood, Cheryl L. Day, Keertan Dheda, Rodney Dawson, Willem A. Hanekom, Christoph Lange, Robert J. Wilkinson
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The risk of developing active tuberculosis in persons with latent Mycobacterium tuberculosis infection is substantially increased shortly after HIV-1 seroconversion. Immune responses in the lung are important to restrict the growth of M. tuberculosis to prevent the development of disease.To investigate innate and adaptive immune responses to M. tuberculosis in bronchoalveolar lavage from HIV-1-infected persons without active tuberculosis.Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, HIV-1-uninfected (n = 21) and HIV-1-infected (n = 15) adults. Growth of M. tuberculosis was assessed in monocytes and alveolar macrophages. Cytokine expression by mycobacteria-specific CD4 and CD8 T cells was measured by intracellular cytokine staining or IFN-gamma ELISpot.Mycobacterial growth in monocytes or alveolar macrophages from HIV-1-infected and -uninfected persons did not differ. Total CD4 T-cell frequencies in BAL were lower in HIV-1-infected than in HIV-1-uninfected persons (P < 0.001). Mycobacteria (bacillus Calmette-Guérin)-specific CD4 T-cell responses in BAL were severely impaired: Frequencies of cells expressing IFN-gamma or tumor necrosis factor (TNF)-alpha, as well as polyfunctional cells, expressing IFN-gamma, TNF-alpha, and IL-2 together, were lower in HIV-1-infected persons than in uninfected controls (P < 0.01 for all).In addition to a total CD4 T-cell deficit, the function of mycobacteria-specific CD4 T cells is significantly impaired in the lung of HIV-1-infected persons, which may account for the HIV-1-associated elevated risk for developing tuberculosis.
The human immunoglobulin V(H) gene repertoire is genetically controlled and unaltered by chronic autoimmune stimulation.
Authors: H Kohsaka, D A Carson, L Z Rassenti, W E Ollier, P P Chen, T J Kipps, N Miyasaka
Journal: Journal of Clinical Investigation (1996)

The factors controlling immunoglobulin (Ig) gene repertoire formation are poorly understood. Studies on monozygotic twins have helped discern the contributions of genetic versus environmental factors on expressed traits. In the present experiments, we applied a novel anchored PCR-ELISA system to compare the heavy chain V gene (V(H)) subgroup repertoires of mu and gamma expressing B lymphocytes from ten pairs of adult monozygotic twins, including eight pairs who are concordant or discordant for rheumatoid arthritis. The results disclosed that the relative expression of each Ig V(H) gene subgroup is not precisely proportional to its relative genomic size. The monozygotic twins had more similar IgM V(H) gene repertoires than did unrelated subjects. Moreover, monozygotic twins who are discordant for RA also use highly similar IgM V(H) gene-subgroup repertoires. Finally, the V(H) gene repertoire remained stable over time. Collectively, these data reveal that genetic factors predominantly control V(H) gene repertoire formation.
Decreased Bone Mineral Density in Adults Born with Very Low Birth Weight: A Cohort Study
Authors: Petteri Hovi, Sture Andersson, Anna-Liisa Järvenpää, Johan G. Eriksson, Sonja Strang-Karlsson, Eero Kajantie, Outi Mäkitie
Journal: PLoS Medicine (2009)

Background Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood. Methods and Findings The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28–0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34–0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults' shorter height and lower self-reported exercise intensity. Conclusions Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention. Please see later in the article for the Editors' Summary
Improving care for patients with idiopathic pulmonary fibrosis (IPF) in the UK: a round table discussion
Authors: David R Thickett, Clare Kendall, Lisa G Spencer, Nick Screaton, William A Wallace, Hilary Pinnock, Julia Bott, Lucy Pigram, Sarah Watson, Ann B Millar
Journal: Thorax (2014)

This article is the result of a round table discussion held at BMA House. Its purpose is to outline the challenges facing both patients and doctors in managing idiopathic pulmonary fibrosis. A number of recommendations for service development and research have been identified.
Is the Asthma Quality of Life Questionnaire a Useful Measure for Low-income Asthmatics?
Authors: NANCY KLINE LEIDY, KITTY S. CHAN, CECELIA COUGHLIN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The purpose of this study was to evaluate the reliability and validity of the Asthma Quality of Life Questionnaire (AQLQ) in a population-based sample of low-income adults with asthma. A total of 112 subjects (46 African American, 66 Caucasian; mean age = 33 ± 9 yr; 26% male) were recruited from the Baltimore County, Maryland and Atlanta, Georgia metropolitan areas. Internal consistency reliability (Cronbach's α ) was high for the overall scale (0.96); 2-wk reproducibility (intraclass correlation, ICC) was 0.82 (n = 38). Overall score was significantly correlated with FEV1 percentage of predicted (r = 0.20), and the Asthma Disease Severity Scale (r = − 0.38). Correlations between overall score and the SF-36 Physical Component Summary (r = 0.49), SF-36 Mental Component Summary (r = 0.37), Cantril's Ladder (r = 0.23), and the Health Utilities Index (r = 0.22) supported the validity of the AQLQ in this sample. Comparison of reliability and validity estimates across racial groups found few substantive differences. Internal consistency, reproducibility, and validity estimates found in this sample were consistent with those of a reliable and valid measure and were comparable to those found in other populations. These results suggest the AQLQ is a useful indicator of health- related quality of life in low-income asthmatics.
Dermatitis induced by first-generation hepatitis C virus protease inhibitors
Authors: V. Descamps, F. Fiszenson-Albala
Journal: British Journal of Dermatology (2015)

Journal Article Dermatitis induced by first‐generation hepatitis C virus protease inhibitors Get access V. Descamps, V. Descamps Department of Dermatology Bichat Claude Bernard Hospital 46 rue Henri Huchard 75877 Paris Cedex 18 France E‐mail: vincent.descamps@bch.aphp.fr Search for other works by this author on: Oxford Academic Google Scholar F. Fiszenson‐Albala F. Fiszenson‐Albala Department of Dermatology Bichat Claude Bernard Hospital 46 rue Henri Huchard 75877 Paris Cedex 18 France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 1, 1 July 2015, Pages 311–312, https://doi.org/10.1111/bjd.13694 Published: 01 July 2015
The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)
Authors: A. Richard Green, Annis O. Mechan, J. Martin Elliott, Esther O'Shea, M. Isabel Colado
Journal: Pharmacological Reviews (2003)

The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug among young people, particularly those involved in the dance culture. MDMA produces an acute, rapid enhancement in the release of both serotonin (5-HT) and dopamine from nerve endings in the brains of experimental animals. It produces increased locomotor activity and the serotonin behavioral syndrome in rats. Crucially, it produces dose-dependent hyperthermia that is potentially fatal in rodents, primates, and humans. Some recovery of 5-HT stores can be seen within 24 h of MDMA administration. However, cerebral 5-HT concentrations then decline due to specific neurotoxic damage to 5-HT nerve endings in the forebrain. This neurodegeneration, which has been demonstrated both biochemically and histologically, lasts for months in rats and years in primates. In general, other neurotransmitters appear unaffected. In contrast, MDMA produces a selective long-term loss of dopamine nerve endings in mice. Studies on the mechanisms involved in the neurotoxicity in both rats and mice implicate the formation of tissue-damaging free radicals. Increased free radical formation may result from the further breakdown of MDMA metabolic products. Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. There is also some evidence for long-term physiological and psychological changes occurring in human recreational users. However, such evidence is complicated by the lack of knowledge of doses ingested and the fact that many subjects studied are or have been poly-drug users.
Cytokine Signaling and Hematopoietic Homeostasis Are Disrupted in <i>Lnk</i>-deficient Mice
Authors: Laura Velazquez, Alec M. Cheng, Heather E. Fleming, Caren Furlonger, Shirly Vesely, Alan Bernstein, Christopher J. Paige, Tony Pawson
Journal: The Journal of Experimental Medicine (2002)

The adaptor protein Lnk, and the closely related proteins APS and SH2B, form a subfamily of SH2 domain-containing proteins implicated in growth factor, cytokine, and immunoreceptor signaling. To elucidate the physiological function of Lnk, we derived Lnk-deficient mice. Lnk(-/-) mice are viable, but display marked changes in the hematopoietic compartment, including splenomegaly and abnormal lymphoid and myeloid homeostasis. The in vitro proliferative capacity and absolute numbers of hematopoietic progenitors from Lnk(-/-) mice are greatly increased, in part due to hypersensitivity to several cytokines. Moreover, an increased synergy between stem cell factor and either interleukin (IL)-3 or IL-7 was observed in Lnk(-/-) cells. Furthermore, Lnk inactivation causes abnormal modulation of IL-3 and stem cell factor-mediated signaling pathways. Consistent with these results, we also show that Lnk is highly expressed in multipotent cells and committed precursors in the erythroid, megakaryocyte, and myeloid lineages. These data implicate Lnk as playing an important role in hematopoiesis and in the regulation of growth factor and cytokine receptor-mediated signaling.
From catastrophe to complexity: a novel model of integrative central neural regulation of effort and fatigue during exercise in humans
Authors: T D Noakes, A St Clair Gibson, E V Lambert
Journal: British Journal of Sports Medicine (2004)

It is a popular belief that exercise performance is limited by metabolic changes in the exercising muscles, so called peripheral fatigue. Exercise terminates when there is a catastrophic failure of homoeostasis in the exercising muscles. A revolutionary theory is presented that proposes that exercise performance is regulated by the central nervous system specifically to ensure that catastrophic physiological failure does not occur during normal exercise in humans.
Urban particle-induced apoptosis and phenotype shifts in human alveolar macrophages.
Authors: A Holian, R F Hamilton, M T Morandi, S D Brown, L Li
Journal: Environmental Health Perspectives (1998)

Epidemiological studies report a small but positive association between short-term increases in airborne particulate matter and small increases in morbidity and mortality from respiratory and cardiovascular disease in urban areas. However, the lack of a mechanistic explanation to link particle exposure and human health effects makes it difficult to validate the human health effects. The present study tested the hypothesis that urban particles could cause apoptosis of human alveolar macrophages(AM) and a shift of their phenotypes to a higher immune active state, which would provide a mechanism to explain an inflammatory response. Freshly isolated human AM were incubated for 24 hr with urban particles (#1648 and #1649), Mount Saint Helen's ash (MSH), and residual oil fly ash (ROFA).Cell viability was assessed by trypan blue exclusion and apoptosis was demonstrated by morphology, cell death ELISA, and DNA ladder formation. Additionally, AM were characterized according to RFD1(+) (immune stimulatory macrophages) and RFD1(+)7(+) (suppressor macrophages) phenotypes by flow cytometry. ROFA particles caused AM necrosis at concentrations as low as 10 microg/ml, urban particles had no effect except at 200 microg/ml, and MSH had no effect at 200 microg/ml. ROFA (25 microg/ml) and particles #1648 or #1649 (100 microg/ml) caused apoptosis of AM by all three criteria, but 200 microg/ml MSH had no effect. Finally, 25 microg/ml ROFA and 100 microg/ml particles #1648 or #1649 up regulated the expression of the RFD1(+) AM phenotype, while only ROFA decreased the RFD1(+)7(+) phenotype. Consequently, ROFA and urban particles can induce apoptosis of human AM and increase the ratio of AM phenotypes toward a higher immune active state (i.e., increased RFD1(+):RFD1(+)7(+) ratio). Ifurban particles cause similar changes in vivo, this could result in lung inflammation and possible increased pulmonary and cardiovascular disease.
From Myeloma Precursor Disease to Multiple Myeloma: New Diagnostic Concepts and Opportunities for Early Intervention
Authors: Ola Landgren, Robert A. Kyle, S. Vincent Rajkumar
Journal: Clinical Cancer Research (2011)

Abstract Since monoclonal gammopathy of undetermined significance (MGUS) was first described more than 30 years ago, the definition of the entity has evolved. Today, 3 distinct clinical MGUS subtypes have been defined: non–immunoglobulin M (IgM; IgG or IgA) MGUS, IgM MGUS, and light chain MGUS. Each clinical MGUS subtype is characterized by unique intermediate stages and progression events. Although we now have strong evidence that multiple myeloma is consistently preceded by a precursor state at the molecular level, there is urgent need to better understand mechanisms that regulate transformation from precursor to full-blown multiple myeloma. In the future, if such knowledge was available, it would allow clinicians to define high-risk and low-risk precursor patients for a more tailored clinical management. Also, it would provide insights on the individual patient's disease biology, which, in turn, can be used for targeted and more individualized treatment strategies. On the basis of current clinical guidelines, patients diagnosed with MGUS and smoldering myeloma should not be treated outside of clinical trials. In the near future, it seems reasonable to believe that high-risk precursor patients will likely become candidates for early treatment strategies. In this review, we discuss novel insights from recent studies and propose future directions of relevance for clinical management and research studies. Clin Cancer Res; 17(6); 1243–52. ©2011 AACR.
Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma
Authors: K.H. Cohn, F. Wang, L.G. Patterson, M.R. Arnold, J. Weimar, W.B. Solomon, J.G. Feldman, F. DeSoto-LaPaix, A.T. Levy, A. Leone, P.S. Steeg
Journal: The Lancet (1991)
Clinical and genetic characterization of classical forms of familial adenomatous polyposis: a Spanish population study
Authors: B. Rivera, S. González, E. Sánchez-Tomé, I. Blanco, F. Mercadillo, R. Letón, J. Benítez, M. Robledo, G. Capellá, M. Urioste
Journal: Annals of Oncology (2010)
Differential regulation of the p70 S6 kinase pathway by interferon α (IFNα) and imatinib mesylate (STI571) in chronic myelogenous leukemia cells
Authors: Simrit Parmar, Jessica Smith, Antonella Sassano, Shahab Uddin, Efstratios Katsoulidis, Beata Majchrzak, Suman Kambhampati, Elizabeth A. Eklund, Martin S. Tallman, Eleanor N. Fish, Leonidas C. Platanias
Journal: Blood (2005)
Micronodules and emphysema in coal mine dust or silica exposure: relation with lung function
Authors: PA Gevenois, G Sergent, V De Maertelaer, F Gouat, JC Yernault, P De Vuyst
Journal: European Respiratory Journal (1998)

The aim of this study was to investigate the respective effects of micronodules and pulmonary emphysema, detected by computed tomography (CT), on lung function in workers exposed to silica and coal mine dust. Eighty-three subjects exposed to silica (n=35) or to coal mine dust (n=48), without progressive massive fibrosis, were investigated by high-resolution and conventional CT scans to detect micronodules and to quantify pulmonary emphysema by measuring the relative area of the lung with attenuation values lower than -950 Hounsfield units. Sixty-six (54.5%) subjects had evidence of micronodules on CT scans. Smokers had micronodules more rarely than nonsmokers. Significant correlations were found between the forced expiratory volume in one second (FEV(1); % predicted) (r=-0.41, p<0.001), FEV1/vital capacity (VC) (r=-0.61, p<0.001), diffusing capacity of the lung for carbon monoxide (DL,CO) (r=-0.36, p<0.001) and the extent of emphysema. No difference was demonstrated in the linear relationships between the extent of emphysema and the pulmonary function according to the type of exposure or the presence of micronodules on CT scans. This study suggests that micronodules detected by computed tomography have no influence, by themselves, on pulmonary function and that they should only be considered as a marker of exposure.
Eosinophilic differentiation of the human promyelocytic leukemia cell line, HL-60.
Authors: S A Fischkoff, A Pollak, G J Gleich, J R Testa, S Misawa, T J Reber
Journal: The Journal of Experimental Medicine (1984)

HL-60 promyelocytic leukemia cells differentiated to eosinophils and eosinophilic precursors when cultured under mildly alkaline conditions (pH 7.6-7.8) for 7 d without refeeding. New cytoplasmic granules appeared blue in the least mature cells and red in the most mature cells when stained with Wright-Giemsa. The granules also stained with Luxol-fast-blue, a characteristic of eosinophil granules. Furthermore, most cells contained the eosinophil major basic protein (MBP); the Charcot-Leyden Crystal (CLC) protein (lysophospholipase), eosinophil peroxidase, acid phosphatase, and arylsulfatase were also detected in a portion of these cells. The eosinophil major basic protein was found in a high proportion of undifferentiated cells, and thus may be constituitively produced. By examining finely banded chromosomes, translocation break points were demonstrated at q22 on one chromosome 16 and at q23 on the other homologue; abnormalities in this region of the long arm of 16 are a characteristic finding in the recently described syndrome of acute myelomonocytic leukemia (AMMoL) with abnormal bone marrow eosinophils. In common with the bone marrow eosinophils in these patients, the HL-60 eosinophil granules contained chloroacetate esterase and periodic-acid Schiff (PAS) reactive material; crystalloid inclusions were rare. Therefore, the HL-60 cell line appears to be an in vitro model for eosinophilopoiesis and may be specially suited for the study of the abnormal eosinophils seen in certain malignant conditions.
Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group.
Authors: S Klahr, J A Breyer, G J Beck, V W Dennis, J A Hartman, D Roth, T I Steinman, S R Wang, M E Yamamoto
Journal: Journal of the American Society of Nephrology (1995)

In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of 200 study participants with autosomal dominant polycystic kidney disease (ADPKD) was conducted to determine the effect of lowering protein intake and blood pressure on the rate of decline in GFR. The rate of decline was faster in participants with ADPKD than in persons with other diagnoses, reflecting, in part, faster disease progression in the ADPKD group. Baseline characteristics that predicted a faster rate of decline in GFR in persons with ADPKD were greater serum creatinine (independent of GFR), greater urinary protein excretion, higher mean arterial pressure (MAP), and younger age. In patients with initial GFR values between 25 and 55 mL/min per 1.73 m2, neither assignment to a low-protein diet group nor assignment to a low blood pressure group significantly reduced the rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was not related to achieved protein intake or MAP. In participants with GFR values between 13 and 24 mL/min per 1.73 m2, assignment to the low MAP group led to a somewhat more rapid decline in GFR. However, the more rapid decline in GFR did not appear to be due to a detrimental effect of low blood pressure or the antihypertensive agents used to reach the low blood pressure goal. Lower protein intake, but not prescription of the keto acid-amino acid supplement, was marginally associated with a slower progression of renal disease.