tbuckley/cabot-search huggingface dataset:
Serum urate and its relationship with alcoholic beverage intake in men and women: findings from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort
Authors: Angelo L Gaffo, Jeffrey M Roseman, David R Jacobs, Cora E Lewis, James M Shikany, Ted R Mikuls, Pauline E Jolly, Kenneth G Saag
Journal: Annals of the Rheumatic Diseases (2010)

Objective To investigate if beer, liquor (spirits), wine and total alcohol intakes have different associations with serum urate (SU) concentrations at different ages in a cohort of young men and women. Methods Data from 3123 participants at baseline and follow-up at 20 years were used, with balanced proportions of Caucasians and African Americans. The relationships of SU with categories of beer, liquor, wine and total alcohol intake referent to no intake were examined in sex-specific, cross-sectional analyses. Results Mean age (SD) at the beginning of follow-up was 25.1 (3.6) years. Compared with non-drinkers, significant associations between higher SU concentrations and greater beer intake were observed among men and women, with more pronounced and consistent associations for women. An association between greater liquor intake and higher SU concentrations was only seen for men at the year 20 evaluation. Wine intake was not associated with SU in either sex and total alcohol was associated with higher SU concentrations in both men and women. The magnitude of the associations between alcoholic beverages intake and SU was modest (≤0.03 mg/dl/alcoholic beverage serving). Conclusion An association between higher SU concentrations and greater beer intake was consistent and pronounced among women, but also present in men. Despite the small magnitude of the increases in SU associated with alcohol intake, clinical implications in conditions such as cardiovascular disease and gout in young adults who are moderate and heavy drinkers cannot be ruled out.
Bleomycin induces pleural and subpleural fibrosis in the presence of carbon particles
Authors: N. Decologne, G. Wettstein, M. Kolb, P. Margetts, C. Garrido, P. Camus, P. Bonniaud
Journal: European Respiratory Journal (2009)

The pathological changes in idiopathic pulmonary fibrosis (IPF) typically start in subpleural lung regions, a feature that is currently not explained. IPF, as well as bleomycin-induced lung fibrosis, are more common in smokers. We hypothesised that carbon particles, which are major components of cigarette smoke that are transported to alveoli and pleural surface, might be involved in the development of subpleural fibrosis through interaction with pleural mesothelial cells. Carbon particles were administered to mice in combination with bleomycin through intratracheal and/or intrapleural injection and fibrosis was assessed using histomorphometry. Carbon administered to the chest cavity caused severe pleural fibrosis in the presence of bleomycin, whereas bleomycin alone had no fibrogenic effect. The pleural response was associated with progressive fibrosis in subpleural regions, similar to IPF in humans. Matrix accumulation within this area evolved through mesothelial-fibroblastoid transformation, where mesothelial cells acquire myofibroblast characteristics. In contrast, carbon did not exaggerate bleomycin-induced pulmonary fibrosis after combined intratracheal administration. This represents a novel approach to induce a robust experimental model of pleural fibrosis. It also suggests that carbon particles might be involved as a cofactor in the initiation and/or progression of (subpleural) pulmonary and pleural fibrosis. Mesothelial cells appear to be critical contributors to this fibrotic process.
Accelerated Neutrophil Apoptosis in Mice Lacking A1-a, a Subtype of the <i>bcl-2</i>–related A1 Gene
Authors: Azumi Hamasaki, Fujiro Sendo, Keiko Nakayama, Noriko Ishida, Izumi Negishi, Kei-ichi Nakayama, Shigetsugu Hatakeyama
Journal: The Journal of Experimental Medicine (1998)

To elucidate the role of A1, a new member of the Bcl-2 family of apoptosis regulators active in hematopoietic cell apoptosis, we established mice lacking A1-a, a subtype of the A1 gene in mice (A1-a−/− mice). Spontaneous apoptosis of peripheral blood neutrophils of A1-a−/− mice was enhanced compared with that of either wild-type mice or heterozygous mutants (A1-a+/− mice). Neutrophil apoptosis inhibition induced by lipopolysaccharide treatment in vitro or transendothelial migration in vivo observed in wild-type mice was abolished in both A1-a−/− and A1-a+/− animals. On the other hand, the extent of tumor necrosis factor α–induced acceleration of neutrophil apoptosis did not differ among A1-a−/−, A1-a+/−, and wild-type mice. The descending order of A1 mRNA expression was wild-type, A1-a+/−, and A1-a−/−. Taken together, these results suggest that A1 is involved in inhibition of certain types of neutrophil apoptosis.
Adapalene-benzoyl peroxide, a fixed-dose combination for the treatment of acne vulgaris: Results of a multicenter, randomized double-blind, controlled study
Authors: Diane M. Thiboutot, Jonathan Weiss, Alicia Bucko, Lawrence Eichenfield, Terry Jones, Scott Clark, Yin Liu, Michael Graeber, Sewon Kang
Journal: Journal of the American Academy of Dermatology (2007)
PreproEndothelin-1 Expression in Human Mesangial Cells
Authors: MARCO FOSCHI, ANDREY SOROKIN, PHILLIP PRATT, ANN MCGINTY, GIORGIO LA VILLA, FRANCO FRANCHI, MICHAEL J. DUNN
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Endothelin-1 (ET-1) has been implicated in the pathogenesis of renal inflammation. This study investigated the mechanisms underlying the synergistic upregulation of preproET-1 gene expression in human mesangial cells after co-stimulation with thrombin and tumor necrosis factor α (TNFα). Whereas thrombin induced a moderate upregulation of preproET-1 mRNA, co-stimulation with TNFα resulted in a strong and protracted upregulation of this mRNA species. Thrombin+TNFα-induced upregulation of preproET-1 expression was found to require p38 mitogen-activated protein kinase and protein kinases C, whereas activation of extracellular signal-regulated kinase, c-Jun-N-terminal kinase, or intracellular Ca2+ release were not required. Actinomycin D chase experiments suggested that enhanced stability of preproET-1 mRNA did not account for the increase in transcript levels. PreproET-1 promoter analysis demonstrated that the 5′-flanking region of preproET-1 encompassed positive regulatory elements engaged by thrombin. Negative modulation of thrombin-induced activation exerted by the distal 5′ portion of preproET-1 promoter (-4.4 kbp to 204 bp) was overcome by co-stimulation with TNFα, providing a possible mechanism underlying the synergistic upregulation of preproET-1 expression by these two agonists. In conclusion, human mesangial cell expression of preproET-1 may be increased potently in the presence of two common proinflammatory mediators, thereby providing a potential mechanism for ET-1 production in inflammatory renal disease.
EXPERIMENTS ON THE CULTIVATION OF SO CALLED TRACHOMA BODIES
Authors: Hideyo Noguchi, Martin Cohen
Journal: The Journal of Experimental Medicine (1913)

1. An organism was isolated and studied in pure cultures from cases of conjunctivitis accompanied by the so called trachoma body inclusions, as well as from a case of old trachoma without inclusions. 2. This organism was not found in the cultures made from other forms of conjunctivitis in which the inclusions were absent. 3. The organism presents the morphological features characteristic of so called trachoma bodies. It undergoes an early transformation, during which the forms known as initial bodies appear, and a later change, during which forms resembling elementary granules arise, while certain intermediate forms between these occur simultaneously. 4. No definite cell inclusions could be produced in monkeys by inoculating pure cultures of the organism. 5. The cultivation of this organism from a case of trachoma without the cell inclusions, together with the previously ascertained fact that the inclusions can be produced in suitable animals by inoculating such material directly from a human case, suggests the possibility of the organism being still present in such cases of trachoma, although not in the form of cell inclusions. 6. The facts presented justify the statement that by a suitable method an organism resembling the various important stages of the trachoma bodies and totally distinct from the gonococcus has been obtained in a living condition, capable of indefinite cultivation from cases of human trachoma and inclusion conjunctivitis. Whether the organism and trachoma bodies are identical cannot be positively stated at present. But the way is now opened to determine this point, as well as the specificity of the trachoma bodies.
A comparison of simultaneous measurements of systolic function in the baboon by electromagnetic flowmeter and high frame rate ECG-gated blood pool scintigraphy.
Authors: M V Green, H G Ostrow, R N Scott, M A Douglas, J J Bailey, G S Johnston
Journal: Circulation (1979)

Left ventricular (LV) systolic timing and relative volume variations were simultaneously measured by electromagnetic flowmeter (EMF) and high frame rate ECG-gated blood pool scintigraphy in five baboons. No significant differences (p greater than 0.1, paired t test) were observed in the time (from R wave) to peak aortic flow (maximum LV ejection rate), time to cessation of aortic flow (end-systole) or in the duration of aortic flow (LV ejection time). A small (approximately 15 msec) but significant systematic difference (p less than 0.02) was noted in the time to onset of aortic flow. The shape of each scintigraphic time-activity curve during systole was compared to an equivalent curve synthesized from 10 EMF flow profiles obtained in the same baboon. Comparison of these paired curves over systolic ejection yielded an average correlation or r = 0.95 (range 0.90--0.99). The ratio of peak flow to stroke volume determined from these data did not differ significantly (p greater than 0.05). In the baboon, quantitative high temporal resolution ECG-gated scintigraphy appears to reflect closely the detailed timing and relative magnitude variation of LV volume during the entire period of systolic ejection. We conclude that the assumptions underlying the scintigraphic method are valid in the baboon during the ejection interval.
Continuous Positive Airway Pressure Treatment Improves Pulmonary Hemodynamics in Patients with Obstructive Sleep Apnea
Authors: DIMITAR SAJKOV, TINGTING WANG, NICHOLAS A. SAUNDERS, ALEXANDRA J. BUNE, R. DOUGLAS McEVOY
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Daytime pulmonary hypertension (PH) is relatively common in obstructive sleep apnea (OSA) and is thought to be associated with pulmonary vascular remodeling (PRm). The extent to which PH is reversible with treatment is uncertain. To study this, we measured pulmonary hemodynamics (Doppler echocardiography) in 20 patients with OSA (apnea–hypopnea index [AHI] 48.6 ± 5.2/h, mean ± SEM) before and after 1 and 4 mo of CPAP treatment (compliance 4.7 ± 0.5 h/night). Patients had normal lung function, and no cardiac disease or systemic hypertension. Doppler studies were performed at three levels of inspired oxygen concentration (11%, 21%, and 50%) and during incremental increases in pulmonary blood flow (10, 20, and 30 μ g/kg/min dobutamine infusions). Treatment resulted in a decrease in pulmonary artery pressure (Ppa, 16.8 ± 1.2 mm Hg before CPAP versus 13.9 ± 0.6 mm Hg after 4 mo CPAP, p < 0.05) and total pulmonary vascular resistance (231.1 ± 19.6 versus 186.4 ± 12.3 dyn · s · cm− 5, p < 0.05). The greatest treatment effects occurred in the five patients who were pulmonary hypertensive at baseline. The pulmonary vascular response to hypoxia decreased after CPAP (ΔPpa/ΔSaO2 10.0 ± 1.6 mm Hg before versus 6.3 ± 0.8 mm Hg after 4 mo CPAP, p < 0.05). The curve of Ppa versus cardiac output (Q˙), derived from the incremental dobutamine infusion, shifted downward in a parallel fashion during treatment. Systemic diastolic blood pressure also fell significantly. Improvements in pulmonary hemodynamics were not attributable to changes in left ventricular diastolic function or Pa O2 . We conclude that CPAP treatment reduces Ppa and hypoxic pulmonary vascular reactivity in OSA and speculate that this may be due to improved pulmonary endothelial function.
Approaches to Treatment of Type 2 Diabetes
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2008)

Perspectives on the News commentaries are part of a free monthly CME activity. The Mount Sinai School of Medicine, New York, New York, designates this activity for 2.0 AMA PRA Category 1 credits. If you wish to participate, review this article and visit www.diabetes.procampus.net to complete a posttest and receive a certificate. The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. 

This article is based on presentations at the Metropolitan Diabetes Society on 11 December 2007 in New York, New York, and at the American Diabetes Association's 55th Annual Advanced Postgraduate Course, held 1–3 February 2008 in San Francisco, California (these lectures are available online at http://professional.diabetes.org), summarizing a number of somewhat divergent views recently expressed by different speakers on aspects type 2 diabetes treatment.

At the American Diabetes Association (ADA) Postgraduate Course, Ralph DeFronzo (San Antonio, TX) reviewed the mechanisms of action and utility of various antidiabetic drugs, suggesting that sulfonylureas “are very unlikely to create a durable decline in A1C,” based on understanding of the physiology. Studies with glimepiride (1) and glipizide (2) show falls in fasting glucose of 40–50 mg/dl and in A1C by 1.5%—with monotherapy controlling 25–30% of patients—which he characterized as “a very good effect, initially.” However, DeFronzo said that “after the first 6–12 months the A1C starts to rise progressively.” Sulfonylurea-induced insulin secretion increases portal insulin levels, suppressing hepatic glucose production and lowering fasting glucose to a greater extent than postprandial glucose. In the UK Prospective Diabetes Study (UKPDS), sulfonylureas and insulin reduced microvascular risk by 37%, but myocardial infarction, stroke, and congestive health failure decreased by 14, 12, and 16% (none of the latter decreases reaching statistical significance) (3), leading DeFronzo to contend that “there is no evidence …
A Common 8q24 Variant in Prostate and Breast Cancer from a Large Nested Case-Control Study
Authors: Fredrick R. Schumacher, Heather Spencer Feigelson, David G. Cox, Christopher A. Haiman, Demetrius Albanes, Julie Buring, Eugenia E. Calle, Stephen J. Chanock, Graham A. Colditz, W. Ryan Diver, Alison M. Dunning, Matthew L. Freedman, John M. Gaziano, Edward Giovannucci, Sue E. Hankinson, Richard B. Hayes, Brian E. Henderson, Robert N. Hoover, Rudolf Kaaks, Timothy Key, Laurence N. Kolonel, Peter Kraft, Loic Le Marchand, Jing Ma, Malcolm C. Pike, Elio Riboli, Meir J. Stampfer, Daniel O. Stram, Gilles Thomas, Michael J. Thun, Ruth Travis, Jarmo Virtamo, Gerald Andriole, Edward Gelmann, Walter C. Willett, David J. Hunter
Journal: Cancer Research (2007)

Abstract Two recent studies independently identified polymorphisms in the 8q24 region, including a single nucleotide polymorphism (rs1447295), strongly associated with prostate cancer risk. Here, we replicate the overall association in a large nested case-control study from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium using 6,637 prostate cancer cases and 7,361 matched controls. We also examine whether this polymorphism is associated with breast cancer among 2,604 Caucasian breast cancer cases and 3,118 matched controls. The rs1447295 marker was strongly associated with prostate cancer among Caucasians (P = 1.23 × 10−13). When we exclude the Multiethnic Cohort samples, previously reported by Freedman et al., the association remains highly significant (P = 8.64 × 10−13). Compared with wild-type homozygotes, carriers with one copy of the minor allele had an ORAC = 1.34 (99% confidence intervals, 1.19–1.50) and carriers with two copies of the minor allele had an ORAA = 1.86 (99% confidence intervals, 1.30–2.67). Among African Americans, the genotype association was statistically significant in men diagnosed with prostate cancer at an early age (P = 0.011) and nonsignificant for those diagnosed at a later age (P = 0.924). This difference in risk by age at diagnosis was not present among Caucasians. We found no statistically significant difference in risk when tumors were classified by Gleason score, stage, or mortality. We found no association between rs1447295 and breast cancer risk (P = 0.590). Although the gene responsible has yet to be identified, the validation of this marker in this large sample of prostate cancer cases leaves little room for the possibility of a false-positive result. [Cancer Res 2007;67(7):2951–6]
Polyclonal antibodies to quantitate cis-diamminedichloroplatinum(II)--DNA adducts in cancer patients and animal models.
Authors: M C Poirier, E Reed, L A Zwelling, R F Ozols, C L Litterst, S H Yuspa
Journal: Environmental Health Perspectives (1985)

cis-Diamminedichloroplatinum (II) (cis-DDP), the antitumor drug, is cytotoxic in vitro primarily by binding to DNA and disrupting its normal functions. We have studied cis-DDP modification of DNA in nucleated peripheral blood cells (buffy coat cells) of testicular and ovarian cancer patients receiving cis-DDP chemotherapy, and of untreated controls. Using a highly sensitive enzyme-linked immunosorbent assay (ELISA) with an antiserum specific for the bidentate intrastrand N7-deoxyguanosine adduct, blood cell DNA was assayed at multiple times during courses of cis-DDP treatment. A total of 138 samples were analyzed from 54 individuals. Of these, all samples from 18 untreated controls were negative, while 44 out of 120 samples from cis-DDP patients were positive. Testicular and ovarian cancer patients receiving chemotherapy on the first course, and given cis-DDP in 21- or 28-day cycles (five days of drug infusion followed by two or three drug-free weeks) accumulated cis-DDP-DNA adducts in blood cell DNA as a function of dose. Patients receiving their first course of cis-DDP on 56-day cycles and those given high doses of this drug after failing other chemotherapy showed much slower adduct accumulation than patients receiving their first course on 21- or 28-day cycles. Adduct accumulation, in positive patients, occurred both as a function of total cumulative dose and with increasing cycle number, suggesting that adduct removal took at least a month in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of rare germline copy number variations over-represented in five human cancer types
Authors: Richard W Park, Tae-Min Kim, Simon Kasif, Peter J Park
Journal: Molecular Cancer (2015)

Copy number variations (CNVs) are increasingly recognized as significant disease susceptibility markers in many complex disorders including cancer. The availability of a large number of chromosomal copy number profiles in both malignant and normal tissues in cancer patients presents an opportunity to characterize not only somatic alterations but also germline CNVs, which may confer increased risk for cancer. We explored the germline CNVs in five cancer cohorts from the Cancer Genome Atlas (TCGA) consisting of 351 brain, 336 breast, 342 colorectal, 370 renal, and 314 ovarian cancers, genotyped on Affymetrix SNP6.0 arrays. Comparing these to ~3000 normal controls from another study, our case–control association study revealed 39 genomic loci (9 brain, 3 breast, 4 colorectal, 11 renal, and 12 ovarian cancers) as potential candidates of tumor susceptibility loci. Many of these loci are new and in some cases are associated with a substantial increase in disease risk. The majority of the observed loci do not overlap with coding sequences; however, several observed genomic loci overlap with known cancer genes including RET in brain cancers, ERBB2 in renal cell carcinomas, and DCC in ovarian cancers, all of which have not been previously associated with germline changes in cancer. This large-scale genome-wide association study for CNVs across multiple cancer types identified several novel rare germline CNVs as cancer predisposing genomic loci. These loci can potentially serve as clinically useful markers conferring increased cancer risk.
Baroreceptor reflex effects on transient and steady-state hemodynamics of salt-loading hypertension in dogs.
Authors: A W Cowley, A C Guyton
Journal: Circulation Research (1975)

Intact dogs were compared with barorecptor-denervated dogs to determine the extent to which the baroreceptor reflexes delay the onset and offset transients and alter the final steady-state levels of salt-loading hypertension. Two months after their renal mass had been reduced to about one-third of normal, hypertension was produced in both groups of dogs by continuous intravenous infusion of isotonic saline (190 ml/kg day-1). Major hemodynamic variables were recorded continuously 24 hours/day throughout the experimental period. Both groups of dogs had similar control 24-hour arterial blood pressure values: intact dogs averaged 112 plus or minus 4.1 (SE) mm Hg, and denervated dogs averaged 110 plus or minus 4.3 mm Hg. Both groups reached the same average plateau of elevated arterial blood pressure: intact dogs averaged 142 plus or minus 4.8 mm Hg, and denervated dogs averaged 142 plus or minus 8.7 mm Hg. After the start of salt loading, the denervated dogs reached their plateau level of arterial blood pressure in an average of 8 hours compared with nearly 24 hours for the intact dogs. Cardiac output also rose more rapidly in the denervated dogs and reached a maximum elevation of 26% above the control level in an average of 7.4 hours compared with a maximum elevation of 40% above control in the intact dogs in 18 hours. Total peripheral resistance fell below the control level during the entire first day of infusion in the intact dogs but was somewhat elevated in the denervated dogs. When the saline infusion stopped, arterial blood pressure in both groups returned to control levels within 24 hours. The results indicate that the major action of the baroreceptor reflexes on the onset of salt-loading hypertension is to slow the development of hypertension by modifying the total peripheral resistance; the final steady-state level of hypertension is unaffected by the baroreceptor reflexes.
CLINICAL OUTCOME OF ENDOMYOCARDIAL BYOPSY PROVEN TRANSTHRETIN (ATTR) CARDIAC AMYLOIDOSIS IN COMPARISON TO IMMUNOGLOBULIN LIGHT CHAIN (AL) AMYLODOSIS
Authors: Takuya Nakahashi, Takeshi Arita, Masashi Iwabuchi, Masakiyo Nobuyoshi
Journal: Journal of the American College of Cardiology (2012)