tbuckley/cabot-search huggingface dataset:
Relationship of Extraluminal Tubular Deposition of Ferrocyanide to Peritubular Perfusion Rate in Cortical and Medullary Nephron Segments of the Rat Kidney
Authors: J. B. Coelho, K. C. H. Chien, S. R. Stella, S. E. Bradley
Journal: Circulation Research (1971)

Ferrocyanide can be precipitated in the kidney and retained in microdissected tubules. By means of 14 C-ferrocyanide it is possible to measure nephron glomerular filtration rate, but radioactivity is also detected in tubular segments beyond the reach of filtered ferrocyanide. The present study evaluated this radioactivity with the assumptions that it derives from peritubular capillary and vasa recta blood and that it may be proportional to the perfusion rate to single tubular segments. The findings rule out axial streaming of filtrate and transtubular diffusion of filtered ferrocyanide as factors and therefore point to an extraluminal deposition of ferrocyanide diffusing out of peritubular capillary and vasa recta blood. It was also found that the extraluminal tubular radioactivity is not affected by processing of the tissue, that it decreases from cortex to outer medulla to inner medulla, and that distal convoluted tubules have a greater radioactivity per unit length than the thick ascending limbs at the same level. A comparison with data obtained by others using a method to estimate intrarenal blood flow distribution lends support to the assumption that extraluminal tubular radioactivity is proportional to the capillary perfusion rate to single tubular segments.
Inhibitory effect of aerosol WP871 on SRS‐A mediated bronchoconstriction in the guinea pig <i>in vivo</i>
Authors: K. Kurashima, M. Fujimura, M. Saito, S. Sakamoto, Y. Miyake, K. Nishi, T. Matsuda
Journal: Allergy (1990)

Slow-reacting substance of anaphylaxis (SRS-A) is an important factor mediating bronchoconstriction in asthma. We developed a guinea pig model for SRS-A mediated bronchoconstriction induced by antigen inhalation. Using this model, we investigated the effect of inhaled WP871, a new anti-allergic drug, on bronchoconstriction. Aerosol WP871 (0.01 and 0.033%) to some extent inhibited the antigen-induced bronchoconstriction in a dose-dependent fashion, but high-dose WP871 (0.1%) inhalation itself produced a non-specific bronchoconstriction. However, aerosol WP871 (0.033%) showed no inhibitory effect on bronchoconstriction caused by direct inhalation of leukotriene C4, a component of SRS-A. These findings indicate that aerosol WP871 does not antagonize SRS-A, but inhibits synthesis and/or release of SRS-A and has some non-specific bronchoconstrictive effect in high concentration.
Detection of Micrometastases in Pelvic Lymph Nodes in Patients Undergoing Radical Cystectomy for Focally Invasive Bladder Cancer by Real-time Reverse Transcriptase-PCR for Cytokeratin 19 and Uroplakin II
Authors: Toshifumi Kurahashi, Isao Hara, Nobutoshi Oka, Sadao Kamidono, Hiroshi Eto, Hideaki Miyake
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical cystectomy for bladder cancer. Experimental Design: We included 40 patients with locally invasive bladder cancer who underwent radical cystectomy and pelvic lymphadenectomy. Expression of cytokeratin 19 (CK19), uroplakin II (UP II), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in 760 lymph nodes were assessed by a fully quantitative real-time reverse transcription-PCR (RT-PCR) assay. The quantification value of CK19 or UP II mRNA was described as each value relative to GAPDH mRNA. In this study, we regarded specimen in which either CK19 or UP II mRNA was positive as “presence of micrometastasis.” Results: Routine pathologic examinations detected tumor cells in 29 lymph nodes from six patients. Real-time RT-PCR identified positive expression of CK19 and UP II mRNAs in 49 lymph nodes from 10 patients and 98 lymph nodes from 16 patients, respectively. Of 633 lymph nodes from 34 patients with no pathologic evidence of nodal involvement, 13 nodes from five patients and 58 nodes from 10 patients were diagnosed as positive for CK19 and UP II mRNAs expression, respectively, by real-time RT-PCR. Presence of micrometastases was significantly associated with other conventional prognostic variables, including pathologic stage and microvascular invasion. Disease recurrence was occurred in eight patients, among whom four patients were negative for lymph node metastasis by routine pathologic examination and diagnosed as having micrometastasis by real-time RT-PCR assay. Furthermore, cause-specific survival rate in patients without micrometastasis was significantly higher than that in those with micrometastasis, irrespective of the presence of pathologic-positive nodes. Conclusions: Approximately 30% of locally invasive bladder cancer shed cancer cells to pelvic lymph nodes, and disease recurrence after radical cystectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.
Acute Radiation Skin Toxicity Associated With BRAF Inhibitors
Authors: Trish Pulvirenti, Angela Hong, Arthur Clements, Dion Forstner, Andrew Suchowersky, Alex Guminski, Catriona McNeil, Peter Hersey, Gerald Fogarty, Richard Kefford, Georgina V. Long, Wei Wang
Journal: Journal of Clinical Oncology (2014)
Exercise enhances creativity independently of mood
Authors: Hannah Steinberg, Elizabeth A Sykes, Tim Moss, Susan Lowery, Nick LeBoutillier, Alison Dewey
Journal: British Journal of Sports Medicine (1997)

Objectives It has been widely accepted in the literature that various forms of physical exercise, even in a single session, enhance positive mood. It has also been shown that physical exercise may sometimes enhance creative thinking, but the evidence is inconclusive. Positive moods can favour creative thinking, but the opposite has also been reported and these relations are unclear. There is a large anecdotal literature suggesting that creative people sometimes use bodily movement to help overcome “blocks”. The aim of this study was to establish whether post-exercise creative thinking was attributable to improved mood. Methods The responses of 63 participants to an exercise (aerobic workout or aerobic dance) and a “neutral” video watching condition were compared. Mood was measured using an adjective list, and creative thinking was tested by three measures of the Torrance test. Results Analysis of variance showed a large and significant increase in positive mood after exercise (P&lt;0.001) and a significant decrease in positive mood after video watching (P&lt;0.001). A significant increase between the creative thinking scores of the two conditions was found on the flexibility (variety of responses) measure (P&lt;0.05). A multifactorial analysis of all data failed to show a significant covariance of creative thinking with the two measures of mood (P&gt;0.05). Conclusions These results suggest that mood and creativity were improved by physical exercise independently of each other.
Is first-line single-agent mitoxantrone in the treatment ofhigh-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial
Authors: E. Heidemann, H. Stoeger, R. Souchon, W.-D. Hirschmann, H. Bodenstein, C. Oberhoff, J.T. Fischer, M. Schulze, M. Clemens, R. Andreesen, M. Mahlke, M. König, A. Scharl, K. Fehnle, M. Kaufmann
Journal: Annals of Oncology (2002)
Atrial natriuretic factor and renin-aldosterone in volume regulation of patients with cirrhosis†
Authors: Alexander L. Gerbes, Heinrich Wernze, Rainer M. Arendt, Angelika Riedel, Tilman Sauerbruch, Gustav Paumgartner
Journal: Hepatology (1989)

The role of the atrial natriuretic factor and of the main counteracting sodium-retaining principle, the renin-aldosterone system, in acute volume regulation of cirrhosis of the liver has been investigated. Central volume stimulation was achieved in 21 patients with cirrhosis, 11 without and 10 with ascites, and 25 healthy controls by 1-hr head-out water immersion. Immersion prompted a highly significant (p less than 0.001) increase of atrial natriuretic factor plasma concentrations in cirrhotic patients without ascites from 8.5 +/- 1.3 fmoles per ml to 16.5 +/- 2.6 fmoles per ml, comparable to the stimulation in control subjects (6.0 +/- 0.6 fmoles per ml to 13.6 +/- 2.6 fmoles per ml). In cirrhotic patients with ascites, atrial natriuretic factor increase (from 7.7 +/- 1.3 fmoles per ml to 11.4 +/- 2.3 fmoles per ml) was blunted (p less than 0.05). Plasma renin activity and plasma aldosterone concentration were elevated in cirrhotic patients, especially in the presence of ascites. Following immersion, plasma renin activity and plasma aldosterone concentration were reduced similarly in all groups. Water immersion induced a more pronounced natriuresis and diuresis in control subjects than in cirrhotic patients. Neither atrial natriuretic factor nor plasma renin activity nor plasma aldosterone concentration alone correlated to sodium excretion. However, atrial natriuretic factor to plasma aldosterone concentration ratios were closely correlated to basal and stimulated natriuresis in cirrhotic patients, particularly in those with ascites. These data suggest that atrial natriuretic factor and the renin-aldosterone system influence volume regulation in patients with cirrhosis.
Targets of Drug Action
Authors: A.S.V. Burgen
Journal: The Annual Review of Pharmacology and Toxicology (2000)

This article considers early work from the author’s laboratory on muscarinic receptor specificity, subtypes, and conformational variability, with the use of nuclear magnetic resonance in pharmacology and the conformational variants of dihydrofolate reductase and general questions of receptors. It also considers some current approaches to drug development and receptor function, particularly as influenced by increasing knowledge of three-dimensional structure of receptors.
Effect of budesonide and montelukast in asthmatic children exposed to relevant allergens
Authors: D. Peroni, A. Bodini, M. Miraglia Del Giudice, A. Loiacono, E. Baraldi, A. L. Boner, G. Piacentini
Journal: Allergy (2005)

Background: Montelukast has been shown to be effective in controlling the increase in exhaled NO in asthmatic children re‐exposed to house dust mite (HDM). This study compared the effect of low dose inhaled budesonide and oral montelukast in preventing the expected relapse of airway inflammation and reactivity in a group of 24 mild asthmatic children allergic to HDM after a brief period of exposure to relevant allergens. Methods: Lung function, bronchial hyperresponsiveness (BHR) to methacholine (PC 20 ), fractional exhaled nitric oxide (FeNO) levels and sputum eosinophilia were evaluated. Results: Pulmonary function remained stable. The BHR was unchanged after exposure in the group treated with budesonide, whereas a significant increase ( P = 0.028) was observed in the patients receiving montelukast. No significant difference was observed in FeNO levels after exposure to mite antigen in the two groups. In both the groups of asthmatic children we observed a significant increase in sputum eosinophil % after the exposure to mite antigen. Conclusions: The significant increase in BHR level observed in the group of children receiving montelukast suggests a more comprehensive effect as disease controller by inhaled steroids than by leukotriene antagonist in allergic asthmatic children re‐exposed to relevant allergens.
THU0151 Effects of tofacitinib (CP-690,550), an oral janus kinase inhibitor, or adalimumab on patient reported outcomes in a phase 3 study of active rheumatoid arthritis:
Authors: R.F. van Vollenhoven, G. Wallenstein, E.B. Lee, R. Fleischmann, S.H. Zwillich, D. Gruben, T. Koncz, J. Bradley, B. Wilkinson, V. Strand
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tofacitinib (CP-690,550) is a novel, oral Janus kinase (JAK) inhibitor being investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis (RA). <h3>Objectives</h3> To compare the effects of tofacitinib 5 and 10 mg twice daily (BID), and active control adalimumab, with placebo (PBO) on patient reported outcomes (PROs) in patients (pts) with active RA and an inadequate response to methotrexate (MTX). <h3>Methods</h3> Pts in this 12-month (Mo), phase 3, randomised control trial (RCT) with RA (≥6 TJC/SJC; ESR &gt;28 mm/h or CRP &gt;7 mg/L) and prior MTX failure were randomised (4:4:4:1:1) to 5 treatment sequences: tofacitinib 5 mg or 10 mg BID; adalimumab 40 mg subcutaneous (SC) injections once every two weeks (Q2W); PBO advanced to tofacitinib 5 mg BID; and PBO advanced to tofacitinib 10 mg BID, all with MTX. Pts on PBO with &lt;20% improvement in TJC and SJC after 3 months were blindly advanced to tofacitinib 5 or 10 mg BID at that time, and all other PBO pts after 6 months. We analysed changes from Baseline to Mo 6 based on the Full Analysis Set (all pts who received ≥1 dose of study drug) using a mixed-effect longitudinal model for the following PROs (secondary endpoints): PtGA [VAS]; pain (VAS); physical function (HAQ-DI); HR-QoL (SF-36); fatigue (FACIT-F), and sleep (MOS Sleep Scale). <h3>Results</h3> At Mo 6, treatment with tofacitinib 5 and 10 mg BID, and adalimumab 40 mg Q2W, resulted in statistically significant improvements from baseline vs placebo in all PROs (see Table): <h3>Conclusions</h3> In this phase 3 RCT in pts with RA with incomplete responses to MTX, the efficacy of tofacitinib 5 or 10 mg BID in improving PROs was significantly superior to placebo and numerically similar to adalimumab. <h3>Disclosure of Interest</h3> R. van Vollenhoven Consultant for: Pfizer Inc, G. Wallenstein Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. B. Lee Consultant for: Pfizer Inc, R. Fleischmann Consultant for: Pfizer Inc, S. Zwillich Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Koncz Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Bradley Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, B. Wilkinson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, V. Strand Consultant for: Pfizer Inc
Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism
Authors: Marta Yanina Pepino, Ondrej Kuda, Dmitri Samovski, Nada A. Abumrad
Journal: Annual Review of Nutrition (2014)

CD36 (cluster of differentiation 36) is a scavenger receptor that functions in high-affinity tissue uptake of long-chain fatty acids (FAs) and contributes under excessive fat supply to lipid accumulation and metabolic dysfunction. This review describes recent evidence regarding the CD36 FA binding site and a potential mechanism for FA transfer. It also presents the view that CD36 and FA signaling coordinate fat utilization, a view that is based on newly identified CD36 actions that involve oral fat perception, intestinal fat absorption, secretion of the peptides cholecystokinin and secretin, regulation of hepatic lipoprotein output, activation of beta oxidation by muscle, and regulation of the production of the FA-derived bioactive eicosanoids. Thus abnormalities of fat metabolism and the associated pathology might involve dysfunction of CD36-mediated signal transduction in addition to the changes in FA uptake.
Breast Carcinoma–Associated Fibroblasts and Their Counterparts Display Neoplastic-Specific Changes
Authors: Nahed M. Hawsawi, Hazem Ghebeh, Siti-Faujiah Hendrayani, Asma Tulbah, Maha Al-Eid, Taher Al-Tweigeri, Dahish Ajarim, Ayodele Alaiya, Said Dermime, Abdelilah Aboussekhra
Journal: Cancer Research (2008)

Abstract It has become clear that the initiation and progression of carcinomas depend not only on alterations in epithelial cells, but also on changes in their microenvironment. To identify these changes, we have undertaken cellular and molecular characterization of carcinoma-associated fibroblasts (CAF) and their tumor counterpart fibroblasts (TCF) isolated from 12 breast cancer patients. Normal breast fibroblasts (NBF) from plastic surgery were used as normal control. We present evidence that both CAFs and TCFs are myofibroblasts and show tumor-associated features. Indeed, the p53/p21 response pathway to γ-rays was defective in 70% CAFs, whereas it was normal in all the TCF and NBF cells. In addition, the basal levels of the p53 and p21 proteins were significantly low in 83% of CAFs and modulated in the majority of TCFs compared with NBFs. Interestingly, both TCFs and CAFs expressed high levels of the cancer marker survivin and consequently exhibited high resistance to cisplatin and UV light. Moreover, most CAFs were positive for the proliferation marker Ki-67 and exhibited high proliferation rate compared with NBFs and TCFs. However, proliferating cell nuclear antigen was highly expressed in both CAFs and TCFs. Using the two-dimensional gel electrophoresis technique, we have also shown that CAF, TCF, and NBF cells present different proteome profiles, with many proteins differentially expressed between these cells. Taken together these results indicate that different genetic alterations can occur in breast CAFs and their corresponding adjacent counterparts, showing the important role that stroma could play in breast carcinogenesis and treatment. [Cancer Res 2008;68(8):2717–25]
Evidence of Genetic Diversity Underlying Rh D−, Weak D (Du), and Partial D Phenotypes as Determined by Multiplex Polymerase Chain Reaction Analysis of the RHD Gene
Authors: Neil D. Avent, Peter G. Martin, Sylvia S. Armstrong-Fisher, Wendy Liu, Kirstin M. Finning, Deborah Maddocks, Stanislaw J. Urbaniak
Journal: Blood (1997)
Virulence factors or ancestral origin of<i>Helicobacter pylori</i>: which is a better predictor of gastric cancer risk?
Authors: Seiji Shiota, Osamu Matsunari, Masahide Watada, Yoshio Yamaoka
Journal: Gut (2011)

We have read the recently published article by de Sablet et al with great interest. The article is well structured and has important findings about the ancestral origin of Helicobacter pylori , which can be used as a predictor of gastric cancer risk.1 de Sablet et al performed multi-locus sequence typing (MLST) to determine phylogeographic variation, which was significantly associated with the different histopathological scores and the prevalence of gastric cancer in the specific regions that they studied. However, we think that the study by de Sablet et al has several limitations.

First, there …
Predictors of 2-Year Outcome for Patients With Borderline Personality Disorder
Authors: John G. Gunderson, Maria T. Daversa, Carlos M. Grilo, Thomas H. McGlashan, Mary C. Zanarini, M. Tracie Shea, Andrew E. Skodol, Shirley Yen, Charles A. Sanislow, Donna S. Bender, Ingrid R. Dyck, Leslie C. Morey, Robert L. Stout
Journal: American Journal of Psychiatry (2006)

Objective: The primary purpose of this report was to investigate whether characteristics of subjects with borderline personality disorder observed at baseline can predict variations in outcome at the 2-year follow-up. Method: Hypothesized predictor variables were selected from prior studies. The patients (N=160) were recruited from the four clinical sites of the Collaborative Longitudinal Personality Disorders Study. Patients were assessed at baseline and at 6, 12, and 24 months with the Structured Clinical Interview for DSM-IV Axis I Disorders; the Diagnostic Interview for DSM-IV Personality Disorders, a modified version of that instrument; the Longitudinal Interval Follow-Up Evaluation; and the Childhood Experiences Questionnaire–Revised. Univariate Pearson's correlation coefficients were calculated on the primary predictor variables, and with two forward stepwise regression models, outcome was assessed with global functioning and number of borderline personality disorder criteria. Results: The authors' most significant results confirm prior findings that more severe baseline psychopathology (i.e., higher levels of borderline personality disorder criteria and functional disability) and a history of childhood trauma predict a poor outcome. A new finding suggests that the quality of current relationships of patients with borderline personality disorder have prognostic significance. Conclusions: Clinicians can estimate 2-year prognosis for patients with borderline personality disorder by evaluating level of severity of psychopathology, childhood trauma, and current relationships.
B Lineage–specific Regulation of V(D)J Recombinase Activity Is Established in Common Lymphoid Progenitors
Authors: Lisa Borghesi, Lih-Yun Hsu, Juli P. Miller, Michael Anderson, Leonard Herzenberg, Leonore Herzenberg, Mark S. Schlissel, David Allman, Rachel M. Gerstein
Journal: The Journal of Experimental Medicine (2004)

Expression of V(D)J recombinase activity in developing lymphocytes is absolutely required for initiation of V(D)J recombination at antigen receptor loci. However, little is known about when during hematopoietic development the V(D)J recombinase is first active, nor is it known what elements activate the recombinase in multipotent hematopoietic progenitors. Using mice that express a fluorescent transgenic V(D)J recombination reporter, we show that the V(D)J recombinase is active as early as common lymphoid progenitors (CLPs) but not in the upstream progenitors that retain myeloid lineage potential. Evidence of this recombinase activity is detectable in all four progeny lineages (B, T, and NK, and DC), and rag2 levels are the highest in progenitor subsets immediately downstream of the CLP. By single cell PCR, we demonstrate that V(D)J rearrangements are detectable at IgH loci in approximately 5% of splenic natural killer cells. Finally, we show that recombinase activity in CLPs is largely controlled by the Erag enhancer. As activity of the Erag enhancer is restricted to the B cell lineage, this provides the first molecular evidence for establishment of a lineage-specific transcription program in multipotent progenitors.
STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS
Authors: K. Landsteiner, John Jacobs
Journal: The Journal of Experimental Medicine (1935)

Experiments on the sensitization of guinea pigs with simple chemical compounds are described. Positive effects were obtained by the administration of small quantities, namely fractions of milligrams, with 1:2:4 chlorodinitrobenzene, p-nitrosodimethylaniline, 1:2:4 trinitrobenzene, picryl chloride, four dichlorodinitrobenzenes, and a number of other aromatic compounds. Several substances chemically similar to those enumerated gave negative results. The first named compound is known to produce hypersensitiveness in human beings, a large number of cases having been observed in factory workers. The mechanism of these effects is discussed.