tbuckley/cabot-search huggingface dataset:
Human intrahepatic biliary epithelial cells proliferate in vitro in response to human hepatocyte growth factor.
Authors: R Joplin, T Hishida, H Tsubouchi, Y Daikuhara, R Ayres, J M Neuberger, A J Strain
Journal: Journal of Clinical Investigation (1992)

In previous studies, intrahepatic human biliary epithelial cells (BEC) were isolated in high purity. However, these cells demonstrated only limited growth responses. Here we report that human BEC proliferate in response to human hepatocyte growth factor (hHGF), retain BEC-specific phenotype, and can be serially passaged. BEC showed dose-dependent growth in response to 0.01-100 ng/ml hHGF. The maximum S-phase labeling index reached 40% with half-maximal stimulation at 1 ng/ml. The response of cells from normal and primary biliary cirrhotic liver to hHGF was similar. Cultures were immunostained with specific antibodies and then processed for [3H]thymidine autoradiography. Proliferating cells expressed BEC-specific markers (HEA125 and CK-19), but were negative for desmin and factor VIII-related antigen. Occasional vimentin-positive cells were observed, but these were nonproliferative. In conclusion, cells responding to hHGF were clearly BEC in origin. The observation that HGF is mitogenic for BEC as well as hepatocytes has important implications. First, greater yields of intrahepatic BEC are available for subsequent studies of the pathogenesis and etiology of diseases of the biliary epithelium. Secondly, some means of regulating the cellular response to HGF in vivo must operate, in that HGF levels rise early after partial hepatectomy and yet BEC proliferate 24 h later than hepatocytes.
Patient Assessment of Bowel Function During and After Pelvic Radiotherapy: Results of a Prospective Phase III North Central Cancer Treatment Group Clinical Trial
Authors: Michael G. Haddock, Jeff A. Sloan, John W. Bollinger, Gamini Soori, Preston D. Steen, James A. Martenson
Journal: Journal of Clinical Oncology (2007)

Purpose To evaluate patient assessment of long-term effect of pelvic radiotherapy on bowel function. Patients and Methods As part of a prospective randomized trial evaluating the impact of sucralfate on bowel function in patients receiving pelvic radiotherapy, patient-assessed bowel function data were collected during radiotherapy and again at 4 weeks and 1 year after completion of radiotherapy. Results The number of bowel movements per day increased up to week 4 and then slowly decreased. At 1 year, the mean number of bowel movements per day had increased from 1.75 to 2.09 and the median from 1 to 2. All measures of adverse bowel function worsened during radiotherapy. Frequency of bowel movements and symptoms of frequency, nocturnal bowel movements, cramping, and bleeding returned close to baseline values by 1 year. Symptoms of urgency, clustering, and measures of incontinence were all persistent at 1 year. The mean increase in bowel function score at 1 year was 0.74 (range, −5 to 7). Conclusion Pelvic radiotherapy is associated with a slight increase in bowel movement frequency and decrease in several patient-reported measures of adverse bowel function. Several measures of adverse function persisted at 1 year.
Effects of corticosteroids on mouse hepatitis virus infection.
Authors: D V Datta, K J Isselbacher
Journal: Gut (1969)

METHODSMICE Swiss-Webster male weanling mice (21 days), weighing 8 to 10 g and free from Eperythrozoon coc- coides, were used.A standard diet was fed and the animals were fasted overnight before bleeding or sacrifice.In all experiments 20 to 30 mice were bled at each point in time unless otherwise stated.A similar number of animals were used for mortality experiments.
Mechanisms of Vasorelaxation Induced by Troglitazone, a Novel Antidiabetic Drug, in the Porcine Coronary Artery
Authors: Junya Kawasaki, Katsuya Hirano, Junji Nishimura, Masatoshi Fujishima, Hideo Kanaide
Journal: Circulation (1998)

Background —Troglitazone (TRO), a novel antidiabetic drug, has been reported to decrease blood pressure and relax vascular strips. The mechanism of relaxation induced by TRO was determined in terms of Ca 2+ signaling in smooth muscle cells. Methods and Results —Front-surface fluorometry and fura 2–loaded medial strips of porcine coronary artery were used to examine the effects of TRO on cytosolic Ca 2+ concentrations ([Ca 2+ ] i ) and contractions. The sustained contraction induced by 100 nmol/L U46619 was similar to that induced by 60 mmol/L K + depolarization (60K + ). TRO concentration dependently decreased [Ca 2+ ] i and the force of these contractions. The concentration of TRO required to induce 50% inhibition of U46619-induced force (2.9 μmol/L) was significantly lower than that required in the case of 60K + -induced force (7.3 μmol/L). Replacing extracellular Ca 2+ with Mn 2+ gradually quenched fluorescence at 360 nm excitation. This decline was accelerated by 100 nmol/L U46619 and 30K + to a similar extent, indicating a similar activation of Ca 2+ influx. TRO completely inhibited U46619-activated influx but partly inhibited depolarization-activated influx. Cumulative applications of extracellular Ca 2+ during stimulations with U46619 or 118K + induced stepwise increases in [Ca 2+ ] i and force. TRO shifted the [Ca 2+ ] i -force relation to the right during both stimulations. Conclusions —TRO relaxes coronary artery by decreasing [Ca 2+ ] i and Ca 2+ sensitivity of contractile apparatus. Inhibition of Ca 2+ influx was important in decreasing [Ca 2+ ] i . TRO more effectively inhibits receptor-operated Ca 2+ influx than voltage-operated Ca 2+ channels.
An Unusual Case of Secondary Diabetes due to Surreptitious Nasal Steroid Use
Authors: Sophie Brochier, Orsalia Alexopoulou, Dominique Maiter, Martin Buysschaert
Journal: Diabetes Care (2005)

A 54-year-old woman with no family or personal history of diabetes was referred for assessment of fasting hyperglycemia (7.6 mmol/l) and asthenia. Medical history included recurrent stomatopharyngeal candidiasis, rectal ulcerations because of abuse of analgesic suppositories, depression, and chronic sinusitis. On physical examination, she had facial plethora, diffuse bruises, cutaneous fragility, normal weight, and mildly elevated blood pressure (140/90 mmHg). An oral glucose tolerance test (OGTT) showed a 120-min plasma glucose value of 16.2 mmol/l. Homeostasis model assessment suggested decreased insulin sensitivity (67%) with …
Can Coronary Blood Flow Velocity Pattern After Primary Percutaneous Transluminal Coronary Angiography Predict Recovery of Regional Left Ventricular Function in Patients With Acute Myocardial Infarction?
Authors: Takahiro Kawamoto, Kiyoshi Yoshida, Takashi Akasaka, Takeshi Hozumi, Tsutomu Takagi, Shuichiro Kaji, Yoshiaki Ueda
Journal: Circulation (1999)

Background —In the era of primary percutaneous transluminal coronary angioplasty (PTCA), it is important to judge whether myocardium within acute ischemic injury is viable. This study sought to investigate parameters derived from the coronary blood flow velocity spectrum immediately after primary PTCA in patients with acute myocardial infarction and to elucidate the clinical value of coronary blood flow measurement in predicting myocardial viability. Methods and Results —Using a Doppler guidewire, we measured coronary blood flow velocity after successful completion of primary PTCA in 23 consecutive patients with acute anterior myocardial infarction. Regional wall motion was analyzed to estimate anterior wall motion score index (A-WMSI) by echocardiography before PTCA and 1 month after the onset of symptoms. Average systolic peak velocity (ASV) and deceleration time of diastolic flow velocity (DDT) significantly correlated to 1-month A-WMSI ( r =−0.54, P =0.007 and r =−0.62, P =0.002, respectively), and optimal cutoff values to predict viable myocardium (defined as 1-month A-WMSI ≤2.0) were 6.5 cm/s for ASV and 600 ms for DDT (sensitivity=0.79, specificity=0.89 and sensitivity=0.86, specificity=0.89, respectively). ASV and DDT also correlated weakly to the change in A-WMSI ( r =0.46, P =0.03 and r =0.49, P =0.02, respectively). Conclusions —Low ASV and rapid DDT of coronary blood flow spectrum immediately after primary PTCA reflects a greater degree of microvascular damage in the risk area. Analysis of coronary blood flow spectrum immediately after primary PTCA by use of a Doppler guidewire is useful in predicting recovery of regional left ventricular function.
Lifetime Cancer Risks of <i>PTEN</i> Mutation Carriers—Letter
Authors: Molly S. Daniels, Thereasa Rich, Scott Weissman, Robert Pilarski
Journal: Clinical Cancer Research (2012)

We read with interest the recent article by Tan and colleagues (1), summarizing their experience in germline PTEN genetic testing. There is certainly a need for information about lifetime cancer risks for individuals with deleterious PTEN mutations and the authors' data set will be helpful in defining this phenotype. However, the very high lifetime cancer risks they reported are not consistent with our clinical impressions of the PTEN patients and families we work with, and we believe that the data presented are subject to a strong ascertainment bias that would significantly overestimate cancer risk, therefore calling into question the reported lifetime cancer risks as well as the cancer screening recommendations derived therein. Specifically, 80% (295 of 368) of the PTEN-positive patients included in this report were recruited for the study on the basis of clinical criteria that included personal history of breast, endometrial, thyroid, and renal cancer (2). Because participants were selected on the basis of having cancer, they of course have a higher incidence of cancer than the chosen comparison group (general population SEER data). This does not prove, however, to what extent the observed cancers are actually due to the presence of the PTEN mutation. In addition, there is referral bias likely in favor of having personal and family history of cancer, given that study participants were recruited from cancer genetics clinics. Simply noting the possibility of ascertainment bias without adjusting data analysis to account for it, as the authors have done, is not sufficient. Multiple strategies for overcoming ascertainment bias in assessing lifetime cancer risk for hereditary cancer predisposition syndromes can be used (3, 4). As a preliminary step, the authors could separately report what cancers have developed over how many years of follow-up in the 73 study participants who were identified through predictive genetic testing after a family member enrolled in the study and therefore would not be subject to the same ascertainment bias as the probands. In addition, the authors report both truncating and nontruncating mutations (including promoter mutations) as deleterious. Because nontruncating and promoter mutations do not always disrupt gene function, the authors should report the data supporting the classification of nontruncating and promoter mutations as deleterious as per generally accepted standards (5). For these reasons, we believe that it is premature to recommend changes in clinical practice based on these data. We eagerly await the publication of additional data further elucidating the PTEN-positive phenotype.See the Response, p. 4214No potential conflicts of interest were disclosed.
A modified Wingate test for measuring anaerobic work of the upper body in junior rowers.
Authors: Y Koutedakis, N C Sharp
Journal: British Journal of Sports Medicine (1986)

Eight elite junior oarsmen (ER) and sixteen club level rowers (CR) were tested for upper body strength (trunk, arms) and for mean, peak and minimum power outputs using the Double-Arm Anaerobic Work Test (DAAWT). This test is a modified version of the original Wingate test whereby athletes can be tested using trunk and both arms simultaneously. Multiple Discriminant Analysis was used to determine if the DAAWT variables alone were sensitive enough to discriminate between the two groups. Additionally, Pearson's correlation coefficients and ANOVA were employed. Results indicate that mean power and power difference expressed in absolute values (Watts) could successfully classify junior oarsmen into appropriate groups (91.8%, P less than 0.001). In addition, there was a fairly high correlation (r = 0.81) between mean power and strength in the ER. The strongest ER demonstrated the least fatigue while highly significant differences between the groups in most of the other variables examined have also been demonstrated.
Asteroids in the blood
Authors: I. Bohm
Journal: Gut (2010)

During transarterial embolisation of a patient with hepatocellular carcinoma (HCC), a medical student learnt during his bedside teaching lesson that haematogenous metastasis may occur in cases with HCC. After this interventional procedure the medical student saw the catheter that had been used. This prompted him to use microscopy to analyse a …
Treatment of obstructive sleep apnoea leads to improved microvascular endothelial function in the systemic circulation
Authors: J L Lattimore
Journal: Thorax (2006)

<b>Background:</b> Obstructive sleep apnoea (OSA) is a common and potentially reversible cause of systemic hypertension. The mechanisms whereby OSA leads to hypertension and the effects of treatment on arterial function, however, are not well established. Microvascular arterial endothelial and smooth muscle function was assessed in subjects with OSA before and after treatment with continuous positive airways pressure (CPAP). <b>Methods:</b> Ten subjects of mean (SE) age 49 (8) years with at least moderately severe OSA had detailed forearm vascular reactivity studies before and after 3 months of CPAP treatment. The systemic circulation was assessed by measuring brachial artery pressure, flow and resistance responses to intra-arterial infusions of acetylcholine (ACh; an endothelium dependent vasodilator), sodium nitroprusside (SNP; an endothelium independent vasodilator), l-NMMA (a nitric oxide (NO) antagonist), and l-arginine (the substrate for NO). <b>Results:</b> Before CPAP, ACh and SNP infusions increased forearm blood flow in a dose dependent manner (p&lt;0.01). After CPAP, endothelium dependent dilation to ACh was significantly increased (434 (23)% of baseline after CPAP <i>v</i> 278 (20)% before CPAP, p&lt;0.001), whereas SNP induced dilation was unchanged. Resting NO production was higher after CPAP, evidenced by a significantly greater reduction in basal flow by l-NMMA (p = 0.05). l-Arginine reversed the effect of l-NMMA in all cases. <b>Conclusion:</b> In patients with OSA, treatment with CPAP improves baseline endothelial NO release and stimulates endothelium dependent vasorelaxation in the systemic circulation. This is a potential mechanism for improving systemic and vascular function in patients with OSA treated with CPAP.
Abstract 3469: The effect of TGF-beta on matrix metalloproteinase-2, 9, and 13 expression and secrection in human prostate cancer cells
Authors: Yang Cao, Clement J. Bolton, Shafiq A. Khan
Journal: Cancer Research (2014)

Abstract Matrix metalloproteinases (MMPs) are major critical molecules assisting tumor cells during metastasis. The production of MMPs by prostatic epithelial and/or neighboring stromal cells plays an important role in the penetration of extracellular matrix barriers in normal or neoplastic growth. Activation of MMP-13 is critical in the MMP cascade and MMP-2 and -9 are important in tumor metastasis. Transforming growth factor (TGF)-beta has been reported to exert growth inhibitory activity in normal epithelial cells whereas it induces cell proliferation and invasive phenotypes in advanced carcinomas. In this study, we investigated the role of TGF-β1 and TGF-β3 in MMP expression and secretion in prostate cancer cell line PC-3 and prostatic epithelial cell line RWPE-1. Treatment with 1ng/ml of TGF-β1 and TGF-β3 enhanced MMP-9 expression in both cell lines but showed no significant effect on MMP-2 expression. TGF-β1 and TGF-β3 increased MMP-13 expression in PC-3 cells at 8 hr but decreased its expression in RWPE-1 cells. As examined in conditioned medium (CM) by zymography, TGF-β1 and TGF-β3 increased the secretion of pro-MMP-9 and its active form at different time points in PC-3cells. However, they inhibited pro-MMP-2 and no active MMP-2 activity was detected in the same CM. On the other hand, both TGF-β1 and TGF-β3 increased pro-MMP-9 and pro-MMP-2 in RWPE-1 cells. TGF-β3 is more potent that TGF-β1. TGF-β3 also increased active MMP-2 after 18 hr. MMP-9 siRNA abolished TGF-β induced invasion in PC-3 cells but MMP-13 siRNA didn’t affect PC3 cell migration. Our results suggest that TGF-β1 and TGF-β3 have stimulatory effects on MMP-9 secretion in both PC-3 and RWPE-1cells and similar effect on MMP-2 secretion in RWPE-1 cells. However, they have inhibitory effect on MMP-2 secretion in PC-3 cells. MMP-9 is essential for TGF-β effects on cell migration. TGF-β has opposite effect on MMP-13 expression in the two cell lines and MMP-13 is not required for cell migration. Citation Format: Yang Cao, Clement J. Bolton, Shafiq A. Khan. The effect of TGF-beta on matrix metalloproteinase-2, 9, and 13 expression and secrection in human prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3469. doi:10.1158/1538-7445.AM2014-3469
The predictive value of fluctuations in IgM and IgG class anti-dsDNA antibodies for relapses in systemic lupus erythematosus. A prospective long term observation
Authors: H. Bootsma, P. E Spronk, E. J T. Borg, E. J Hummel, G. de Boer, P. C Limburg, C. G M Kallenberg
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> This study investigated the predictive value of rises in IgM class antibodies against double stranded DNA (anti-dsDNA) for ensuing relapses in systemic lupus erythematosus (SLE) in comparison with rises in IgG class antibodies. In addition, it was analysed whether rises in IgM class anti-dsDNA were associated with specific clinical manifestations of SLE. <h3>METHODS</h3> Thirty four of a cohort of 72 SLE patients who were positive for IgM class anti-dsDNA at the start of the study or at the time of a relapse were analysed monthly for class specific anti-dsDNA levels during a median observation period of 19.6 months. Disease activity was scored according to the SLE Disease Activity Index. Anti-dsDNA were measured by IgM and IgG class enzyme linked immunosorbent assay (ELISA) and by Farr assay. <h3>RESULTS</h3> During the study 18 of 34 patients experienced 26 relapses. Twenty two (85%) of the relapses were accompanied by a positive test for IgM class anti-dsDNA by ELISA, 23 (89%) were positive for IgG class anti-dsDNA by ELISA, and 25 (96%) were positive by Farr assay. Patients with rises in IgG class anti-dsDNA by ELISA or in anti-dsDNA by Farr assay had a significantly higher cumulative risk for relapses than patients without those increases (p=0.04 and p=0.03, respectively). This was not the case for rises in IgM class anti-dsDNA (p=0.16). Moreover, a rise in IgM class anti-dsDNA before a relapse was not associated, expressed in terms of odds ratios, with specific clinical manifestations of SLE. <h3>CONCLUSION</h3> Relapses of SLE are frequently accompanied by IgM class anti-dsDNA. Rises of IgM class anti-dsDNA, in contrast with rises in IgG class anti-dsDNA, are not a sensitive tool for predicting a relapse and are not associated with specific clinical manifestations of SLE.
Effects of a serotonin 5-HT4 receptor antagonist SB-207266 on gastrointestinal motor and sensory function in humans
Authors: A E Bharucha
Journal: Gut (2000)

<h3>BACKGROUND</h3> Serotonin 5-HT<sub>4</sub> receptors are located on enteric cholinergic neurones and may regulate peristalsis. 5-HT<sub>4</sub> receptors on primary afferent neurones have been postulated to modulate visceral sensation. While 5-HT<sub>4</sub> agonists are used as prokinetic agents, the physiological role of 5-HT<sub>4</sub> receptors in the human gut is unknown. <h3>AIMS</h3> Our aim was to characterise the role of 5-HT<sub>4</sub> receptors in regulating gastrointestinal motor and sensory function in healthy subjects under baseline and stimulated conditions with a 5-HT<sub>4</sub> receptor antagonist. <h3>METHODS</h3> Part A compared the effects of placebo to four doses of a 5-HT<sub>4</sub>receptor antagonist (SB-207266) on the cisapride mediated increase in plasma aldosterone (a 5-HT<sub>4</sub> mediated response) and orocaecal transit in 18 subjects. In part B, 52 healthy subjects received placebo, or 0.05, 0.5, or 5 mg of SB-207266 for 10–12 days; gastric, small bowel, and colonic transit were measured by scintigraphy on days 7–9, and fasting and postprandial colonic motor function, compliance, and sensation during distensions were assessed on day 12. <h3>RESULTS</h3> Part A: 0.5, 5, and 20 mg doses of SB-207266 had significant and quantitatively similar effects, antagonising the cisapride mediated increase in plasma aldosterone and acceleration of orocaecal transit. Part B: SB-207266 tended to delay colonic transit (geometric centre of isotope at 24 (p=0.06) and 48 hours (p=0.08)), but did not have dose related effects on transit, fasting or postprandial colonic motor activity, compliance, or sensation. <h3>CONCLUSION</h3> 5-HT<sub>4</sub>receptors are involved in the regulation of cisapride stimulated orocaecal transit; SB 207266 tends to modulate colonic transit but not sensory functions or compliance in healthy human subjects.
The Epidemiology of Autism Spectrum Disorders
Authors: Craig J. Newschaffer, Lisa A. Croen, Julie Daniels, Ellen Giarelli, Judith K. Grether, Susan E. Levy, David S. Mandell, Lisa A. Miller, Jennifer Pinto-Martin, Judy Reaven, Ann M. Reynolds, Catherine E. Rice, Diana Schendel, Gayle C. Windham
Journal: Annual Review of Public Health (2007)

Autism spectrum disorders (ASDs) are complex, lifelong, neurodevelopmental conditions of largely unknown cause. They are much more common than previously believed, second in frequency only to mental retardation among the serious developmental disorders. Although a heritable component has been demonstrated in ASD etiology, putative risk genes have yet to be identified. Environmental risk factors may also play a role, perhaps via complex gene-environment interactions, but no specific exposures with significant population effects are known. A number of endogenous biomarkers associated with autism risk have been investigated, and these may help identify significant biologic pathways that, in turn, will aid in the discovery of specific genes and exposures. Future epidemiologic research should focus on expanding population-based descriptive data on ASDs, exploring candidate risk factors in large well-designed studies incorporating both genetic and environmental exposure data and addressing possible etiologic heterogeneity in studies that can stratify case groups and consider alternate endophenotypes.