tbuckley/cabot-search huggingface dataset:
Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN-γ during the isolation of the Antarctic winter
Authors: William T. Shearer, Bang-Ning Lee, Stanley G. Cron, Howard M. Rosenblatt, E.O'Brian Smith, Desmond J. Lugg, Peter M. Nickolls, Robert M. Sharp, Karl Rollings, James M. Reuben
Journal: Journal of Allergy and Clinical Immunology (2002)
Hemostatic complications of angiogenesis inhibitors in cancer patients
Authors: Francesca Elice, Jack Jacoub, Frederick R. Rickles, Anna Falanga, Francesco Rodeghiero
Journal: American Journal of Hematology (2008)

Tumor vasculature and tumor-associated neo-angiogenesis have recently become major targets for rational drug design of antineoplastic agents. Five such agents with angiogenesis inhibiting activity (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib) have already obtained US Food and Drug Administration approval for clinical use and many others have entered clinical trials. Vascular complications, including venous or arterial thromboembolism and hemorrhage, have emerged as relevant toxicities in several clinical trials with angiogenesis inhibitors. Given the well-known interplay between the blood clotting system, angiogenesis, and tumor growth, a better understanding of the impact of these new drugs on overall hemostatic balance is required. In this brief overview, we discuss the incidence of hemostatic complications, the likely pathogenetic mechanisms involved, and the critical need to establish in randomized clinical trials the usefulness of thrombosis prophylaxis to prevent these complications. Careful documentation of hemostatic complications during treatment with each of the new antiangiogenic drugs is warranted. Further studies are urgently required to better define the causal association of these new agents with hemostatic complications and to establish the best prophylactic strategy.
Dental Erosion and Acid Reflux Disease
Authors: Patrick L. Schroeder
Journal: Annals of Internal Medicine (1995)

To determine the relation between gastroesophageal reflux disease and dental erosion using ambulatory 24-hour esophageal pH testing.Cross-sectional observational study.Tertiary referral center.The dental group consisted of 12 patients with idiopathic dental erosion who were identified by dentists and screened for gastroesophageal reflux disease using 24-hour pH testing. The gastroenterology group consisted of 30 patients who had 24-hour pH testing in the esophageal laboratory and who were referred for dental evaluation (10 did not have reflux, 10 had distal reflux, and 10 had proximal reflux).24-hour esophageal pH monitoring using a pH probe in the distal and proximal esophagus. Complete dental examination with particular attention to the presence and severity of dental erosion; plaque; gingival damage; and decayed, missing, and filled teeth. Analysis of saliva for pH, flow rates, buffering capacity, and calcium and phosphorus levels. Standardized questionnaire to ascertain possible causes of dental erosion and presence of reflux symptoms.Ten of the 12 patients in the dental group (83% [95% CI, 52% to 98%]) had gastroesophageal reflux on esophageal pH monitoring. Nine had distal and 7 had proximal reflux. Seven had reflux in the upright position only, 1 had reflux in the supine position only, and 2 had both upright and supine reflux. No saliva abnormalities were found. Ten patients had typical symptoms of gastroesophageal reflux, but dietary or mechanical problems that may have been causing dental erosion were not identified. In the gastroenterology group, upright reflux was seen in 5 of the 10 patients with distal reflux and in all 10 patients with proximal reflux. In addition, 40% of patients in the gastroenterology group (12 of 30) had dental erosion (4 of the 10 with distal reflux [40%], 7 of the 10 with proximal reflux [70%], and only 1 of the 10 without reflux [10%]; P = 0.02 for those with reflux compared with those without reflux). The cumulative dental erosion score correlated with proximal upright reflux when all 24 study patients with erosion were analyzed (r = 0.55 [P < 0.01]); this correlation was even stronger in the subgroup of 12 patients with abnormal amounts of proximal upright reflux (r = 0.84 [P = 0.001]).Dental erosion is a common finding in patients with gastroesophageal reflux disease and should be considered an atypical manifestation of this disease.
Abstract 4965: Metformin has an anticancer effect by repressing TWIST/N-cadherin signaling.
Authors: Ge Rongbin, Zongwei Wang, Aria F. Olumi
Journal: Cancer Research (2013)

Abstract Introduction and Objective. Metformin, one of the most commonly used medications for treatment of type 2 diabetes, has emerged as a potential anticancer agent. The molecular mechanisms associated with the anti-cancer effect of metformin are poorly understood. We demonstrate, for the first time, that metformin inhibits prostate cancer proliferation through suppression of TWIST/N-cadherin signaling pathway. Methods. RT–PCR, Western blot, immunofluorescence assays and confocal microscopy were applied to evaluate protein expression level. MTS assay and FACS analysis were applied to determine cellular proliferation. N-cadherin and TWIST-1 expression vectors were transfected into PC3 prostate cancer cells to establish stable cells with over-expression of N-cadherin and TWIST-1, respectively. Metformin-resistant prostate cancer cells were established by exposure to higher concentrations (10mM) of metformin over 4 weeks. Results. Treatment with metformin (5mM) inhibited proliferation in three different types of cancer cells (PC3-prostate cancer cells; T24-bladder cancer cells and 786-O- kidney cancer cells). Metformin treatment suppressed expression of N-cadherin in all cell types. Similar findings were observed by confocal microscopy. In contrast to N-cadherin, expression of E-cadherin was not affected by metformin. Metformin-mediated repression of N-cadherin was dose and time- dependent in prostate cancer cells. PC3 prostate cancer cells with stable over-expression of N-cadherin became resistant to metformin-mediated inhibition. Stable PC3 prostate cancer cells, after selection for metformin, became resistant to metformin-mediated inhibition, and the metformin-resistant cancer cells had slightly higher baseline level of N-cadherin. In addition, in the metformin-resistant cells, N-cadherin levels were unchanged after treatment with metformin. The expression of AKT and AP-1, the downstream molecules of N-cadherin, closely correlated with expression of N-cadherin after treatment with metformin. Moreover, we also found that metformin inhibited expression of TWIST-1, a transcriptional activator of N-cadherin. Similar findings were observed by confocal microscopy. PC3 prostate cancer cells with stable over-expression of TWIST-1 became resistant to metformin-mediated inhibition. Conclusions. We demonstrate that Metformin's anti-cancer therapeutic effect may be mediated through repression of the TWIST/N-cadherin signaling pathway. Citation Format: Ge Rongbin, Zongwei Wang, Aria F. Olumi. Metformin has an anticancer effect by repressing TWIST/N-cadherin signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4965. doi:10.1158/1538-7445.AM2013-4965 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Increased sensitivity of the thyroid in iodine-depleted rats to the goitrogenic effects of thyrotropin
Authors: George A. Bray
Journal: Journal of Clinical Investigation (1968)

The present studies demonstrate that iodine depletion increases the sensitivity of the thyroid to the goitrogenic effects of thyrotropin. Iodine depletion was induced by feeding rats a low iodine diet containing propylthiouracil for 10-14 days before hypophysectomy. Accumulation of iodine in the thyroid after hypophysectomy was prevented by continuing the antithyroid drugs in the diet. Doses of thyrotropin as low as 3 mU/100 g of body weight per day produced significant thyroid enlargement in 3-7 days in iodine-depleted rats. Adding propylthiouracil or perchlorate to the diet during treatment with thyrotropin did not reduce or augment the goitrogenic response to thyrotropin in iodine-depleted rats. Increasing the level of circulating iodide also did not reduce the goitrogenic response to thyrotropin. The increased sensitivity of the iodine-depleted thyroid gland may provide an explanation for the development of thyroid enlargement without requiring an increased level of circulating thyrotropin.
The differential effects of age on the association of KLOTHO gene polymorphisms with coronary artery disease
Authors: Eun-Jung Rhee, Ki-Won Oh, Won-Young Lee, Se-Yeon Kim, Chan-Hee Jung, Byung-Jin Kim, Ki-Chul Sung, Bum-Su Kim, Jin-Ho Kang, Man-Ho Lee, Sun-Woo Kim, Jung-Roe Park
Journal: Metabolism (2006)
Patient selection may affect gene therapy success. Dominant negative effects observed for ornithine transcarbamylase in mouse and human hepatocytes.
Authors: M A Morsy, J Z Zhao, T T Ngo, A W Warman, W E O'Brien, F L Graham, C T Caskey
Journal: Journal of Clinical Investigation (1996)

We have achieved significant improvement of ornithine transcarbamylase deficiency (OTCD) in a mouse model through adenoviral-mediated gene transfer of the human ornithine transcarbamylase cDNA. Substantial reduction in orotic aciduria was observed within 24 h of treatment. Metabolic correction was later associated with phenotypic correction and moderate increase in enzymatic activity. In an effort to identify the level of gene expression required to achieve wild-type levels of enzyme activity we uncovered a dominant negative effect of the endogenous mutant protein on the activity of the delivered recombinant wild-type protein. This phenomenon is relevant to homomultimeric protein defects such as OTCD, represent a challenging category of disorders for gene therapy. Thus, although our findings indicate that adenoviral-mediated gene transfer may have potential as a short-term treatment for OTCD in humans and may be effective especially during catabolic crisis, the observations in this study suggest that careful patient selection based on mutation class may be essential for initial OTCD gene therapy trials, and perhaps, for other homomultimeric enzyme deficiencies being considered as gene therapy targets.
The Small Office Laboratory in the Cycle of Laboratory Medicine: Reinventing the Magic Black Box
Authors: George F. Stevenson
Journal: JAMA (1985)

About 1920, many physicians began to lose interest in operating a clinical laboratory, primarily because of the complexities of the shaking machine and the reagents used to perform tests for syphilis. Thus, the clinical pathologist appeared (according to some unkind wits they were another complication of syphilis) as the physician with the interest, time, and skill to master the rapidly increasing complexities of the medical laboratory. In the early 1930s the American Society for the Control of Cancer recommended that there should be at least one pathologist in each state, "thoroughly competent to recognize malignancy." Thus, the surgeons gradually stopped doing their own surgical pathology, though an unrelenting few did not relinquish this activity to the anatomic pathologist until the 1950s. If you started practicing hospital laboratory medicine in the 50s, you will recall your long-term campaign to get the hospital to buy its first spectrophotometer costing several hundred dollars.
Bilirubin kinetics in intact rats and isolated perfused liver. Evidence for hepatic deconjugation of bilirubin glucuronides.
Authors: J Gollan, L Hammaker, V Licko, R Schmid
Journal: Journal of Clinical Investigation (1981)

Most previous compartmental models describing bilirubin transport and metabolism in the liver have been validated solely by analysis of the plasma disappearance of radiolabeled bilirubin in human subjects. We now have determined the transport kinetics of a bilirubin tracer pulse by analysis of plasma, liver, and bile radioactivity data from 30 intact rats. Plasma [3H]bilirubin disappearance was best described by the sum of three exponentials, and a six-compartment model, derived by simulation analysis, was necessary and adequate to describe all experimental data. Examination of the injected radiolabeled bilirubin by extraction with hexadecyltrimethylammonium bromide and thin-layer chromatography revealed that 6.6% (mean) of the original pigment had been degraded to labeled nonbilirubin derivatives during preparation of the tracer dose. This material exhibited a significantly longer half-life (mean 50.6 min) of the plasma terminal exponential than that of authentic radiobilirubin (20.6 min). In isolated perfused rat liver, the kinetics of [3H]bilirubin in perfusate and bile readily fitted the proposed model. Compatibility of the model with the data obtained, both in the isolated liver and in vivo, required that a fraction of bilirubin conjugated in the liver be deconjugated and returned to the plasma. Deconjugation of bilirubin glucuronides was evaluated directly by infusion of bilirubin monoglucuronides, containing 14C in the glucuronosyl group, into rats with an external bile fistula. Since metabolic degradation of hydrolyzed 14C-labeled glucuronic acid yields 14CO2, this was measured in expired air. Whereas 86% of the administered labeled pigment was recovered in bile, 7% of the label appeared in 14CO2. These findings directly validate a portion of the proposed kinetic model and suggest that hepatic deconjugation of a small fraction of bilirubin glucuronides is a physiological event. Deconjugation may also account, at least in part, for the presence of increased concentrations of unconjugated bilirubin in the plasma of patients with cholestasis.
Retired paediatrician found guilty of rapes and indecent assaults in 1970s and 1980s
Authors: C. Dyer
Journal: BMJ (2015)

A former consultant paediatrician has been found guilty of sexually assaulting and raping girls in the 1970s and 1980s at Stoke Mandeville Hospital, Buckinghamshire, where he worked as a specialist in growth and neurological disorders.

Michael Salmon, 80, was convicted at Reading Crown Court of nine indecent assaults and two rapes against six girls at the hospital between 1973 and 1988. His victims were aged between 12 and …
Incidence of additional genetic changes in the TEL and AML1 genes in DCOG and COALL-treated t(12;21)-positive pediatric ALL, and their relation with drug sensitivity and clinical outcome
Authors: W A G Stams, H B Beverloo, M L den Boer, R X de Menezes, R L Stigter, E van Drunen, N L Ramakers-van-Woerden, A H Loonen, E R van Wering, G E Janka-Schaub, R Pieters
Journal: Leukemia (2006)
SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS LEVELS ARE ASSOCIATED WITH ASYMMETRIC DIMETHYLARGININE AND LOW-GRADE INFLAMMATION IN ESSENTIAL HYPERTENSION
Authors: K. Dimitriadis, K. Tsioufis, M. Poulakis, L. Lioni, D. Flessas, K. Kintis, A. Kasiakogias, C. Stefanadis
Journal: Journal of the American College of Cardiology (2011)
Haemolytic-uraemic syndrome: clinical experience of an outbreak in the West Midlands.
Authors: C M Taylor, R H White, M H Winterborn, B Rowe
Journal: BMJ (1986)

In 1982-3, 35 children from the West Midlands developed the haemolytic-uraemic syndrome. This was a higher incidence than expected and included an epidemic localised to the Wolverhampton area in July 1983 which comprised 11 cases in two weeks. Twenty three children were treated with dialysis, of whom three died. Six patients developed chronic renal failure, four of them from Wolverhampton. Extrarenal manifestations included neurological sequelae in four, two of whom also developed insulin dependent diabetes mellitus and chronic renal failure. Cardiomyopathy occurred in one child, who also had chronic renal failure. The outcome of these 35 patients was not predictable from prognostic criteria derived from previous experience in Britain. This, together with the high prevalence of extrarenal disease and the geographical localisation of the 1983 outbreak, suggested an aetiological agent new to the region. Faeces from 10 patients were examined for verotoxin producing Escherichia coli, and positive strains of serotype O157.H7 were found in three patients during the Wolverhampton outbreak.
Human Colon Microbiota Transform Polycyclic Aromatic Hydrocarbons to Estrogenic Metabolites
Authors: Tom Van de Wiele, Lynn Vanhaecke, Charlotte Boeckaert, Kerry Peru, John Headley, Willy Verstraete, Steven Siciliano
Journal: Environmental Health Perspectives (2004)

Ingestion is an important exposure route for polycyclic aromatic hydrocarbons (PAHs) to enter the human body. Although the formation of hazardous PAH metabolites by human biotransformation enzymes is well documented, nothing is known about the PAH transformation potency of human intestinal microbiota. Using a gastrointestinal simulator, we show that human intestinal microbiota can also bioactivate PAHs, more in particular to estrogenic metabolites. PAH compounds are not estrogenic, and indeed, stomach and small intestine digestions of 62.5 nmol naphthalene, phenanthrene, pyrene, and benzo(a)pyrene showed no estrogenic effects in the human estrogen receptor bioassay. In contrast, colon digests of these PAH compounds displayed estrogenicity, equivalent to 0.31, 2.14, 2.70, and 1.48 nmol 17α-ethynylestradiol (EE2), respectively. Inactivating the colon microbiota eliminated these estrogenic effects. Liquid chromatography–mass spectrometry analysis confirmed the microbial PAH transformation by the detection of PAH metabolites 1-hydroxypyrene and 7-hydroxybenzo(a)pyrene in colon digests of pyrene and benzo(a)pyrene. Furthermore, we show that colon digests of a PAH-contaminated soil (simulated ingestion dose of 5 g/day) displayed estrogenic activity equivalent to 0.58 nmol EE2, whereas stomach or small intestine digests did not. Although the matrix in which PAHs are ingested may result in lower exposure concentrations in the gut, our results imply that the PAH bioactivation potency of colon microbiota is not eliminated by the presence of soil. Moreover, because PAH toxicity is also linked to estrogenicity of the compounds, the PAH bioactivation potency of colon microbiota suggests that current risk assessment may underestimate the risk from ingested PAHs.
Endogenous Circadian Rhythm in Vasovagal Response to Head-Up Tilt
Authors: Kun Hu, Frank A.J.L. Scheer, Michael Laker, Carolina Smales, Steven A. Shea
Journal: Circulation (2011)

Background— The incidence of syncope exhibits a daily pattern with more occurrences in the morning, possibly as a result of influences from the endogenous circadian system and/or the daily pattern of behavioral/emotional stimuli. This study tested the hypothesis that the circadian system modulates cardiovascular responses to postural stress, leading to increased susceptibility to syncope at specific times of day. Methods and Results— Twelve subjects underwent a 13-day in-laboratory protocol in which subjects' sleep-wake cycles were adjusted to 20 hours for 12 cycles. A 15-minute tilt-table test (60° head-up) was performed ≈4.5 hours after scheduled awakening in each cycle so that 12 tests in each subject were distributed evenly across the circadian cycle. Of 144 tests, signs/symptoms of presyncope were observed in 21 tests in 6 subjects. These presyncope events displayed a clear circadian rhythm ( P =0.028) with almost all cases (17/21) occurring in the half of the circadian cycle corresponding to the biological night (10:30 pm to 10:30 am ). Significant circadian rhythms were also observed in hemodynamic and autonomic function markers (blood pressure, heart rate, epinephrine, norepinephrine, and indices of cardiac vagal tone) that may underlie the circadian rhythm of presyncope susceptibility. Conclusions— The circadian system affects cardiovascular responses to postural stress, resulting in greater susceptibility to presyncope during the night. This finding suggests that night-shift workers and people with disrupted sleep at night may have greater risk of syncope as a result of their exposure to postural stress during the biological night.
Dopamine as a Novel Antioxidative Agent for Rat Vascular Smooth Muscle Cells Through Dopamine D <sub>1</sub> -Like Receptors
Authors: Kenichi Yasunari, Masakazu Kohno, Hiroaki Kano, Mieko Minami, Junichi Yoshikawa
Journal: Circulation (2000)

Background —To elucidate the roles of vascular D 1 -like receptors in atherosclerosis, the effects of the specific D 1 -like agonists on platelet-derived growth factor (PDGF)-BB–mediated oxidative stress in vascular smooth muscle cells (VSMCs) were studied. Methods and Results —Immunohistochemical studies demonstrated the coexistence of D 1A and D 1B dopamine receptors in VSMCs. Western blotting revealed a band of ≈70 kDa for D 1A and D 1B dopamine receptors. VSMCs stimulated by PDGF-BB exhibited increased oxidative stress directly measured by flow cytometry. These effects were prevented by dopamine, SKF 38393, or YM 435, and this prevention was reversed by Sch 23390. These effects were blocked by a specific protein kinase A (PKA) inhibitor, N -(2-[ p -bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H 89). The PDGF-BB–mediated increase in oxidative stress of VSMCs was significantly suppressed by the indirect phospholipase D (PLD) inhibitor suramin or the specific protein kinase C (PKC) inhibitor calphostin C. Both antisense but neither sense nor scrambled oligonucleotides to D 1A and D 1B receptors inhibited dopamine-induced suppression of increase in oxidative stress of VSMCs induced by PDGF-BB. Conclusions —These findings suggest that vascular D 1 -like receptors (D 1A and D 1B receptors) inhibit any increase in oxidative stress of VSMCs, possibly through activation of PKA and suppression of PLD and PKC.
TCTAP A-009 The Efficacy of Everolimus-eluting Stent (EES) Implantation in Patients with ST-elevation Myocardial Infarction: Outcomes of 2-year Clinical Follow-up
Authors: Hideki Yano, Shigeo Horinaka, Mayuko Ishikawa, Toshihiko Ishimitsu
Journal: Journal of the American College of Cardiology (2014)
COMPOSITE NATURE OF VITAMIN B
Authors: G. W. McCoy
Journal: JAMA (1928)

ABSTRACT To the Editor: —In The Journal, Dec. 31, 1927, p. 2277, you published a letter correcting an erroneous impression conveyed by an editorial in The Journal, Dec. 10, 1927, p. 2044, as to priority in respect to the composite nature of vitamin B.Your editorial, as well as the paper of Chick and Roscoe (Biochem. J.21:698, 1927) on which it was based, overlooked earlier work done at the Hygienic Laboratory by Smith and Hendrick (Pub. Health Rep.41:201-207 [Feb. 5] 1926), in which it was conclusively shown that dried brewers' yeast contains some growth-promoting factor essential in nutrition other than vitamin B, and that the unknown factor was thermostable.
Genetic Polymorphisms of NAT2, CYP2C9, CYP2C19, CYP2D6 and CYP2E1, and Antituberculosis Drugs Induced Maculopapular Eruption
Authors: S. Kim, S. Kim, J. Moon, T. Kim, J. Sohn, H. Yoon, D. Shin, S. Park, Y. Jee
Journal: Journal of Allergy and Clinical Immunology (2010)