tbuckley/cabot-search huggingface dataset:
Studies on the mechanisms of food-stimulated gastric acid secretion in normal human subjects.
Authors: C T Richardson, J H Walsh, M I Hicks, J S Fordtran
Journal: Journal of Clinical Investigation (1976)

Liquid test meals were infused into the stomach and acid secretion was measured by intragastric titration at pH 5.0 Acid secretion after 500 or 750-ml sodium chloride meals was two to three times higher than basal secretion rates and was equivalent to 25-30% of the peak acid output in response to histamine. Since these meals did not cause a rise in serum gastrin concentration, it is assumed that they stimulate acid secretion by causing distention of the body and fundus of the stomach. Compared with this distention stimulus, glucose meals had no effect on acid secretion and fat-inhibited acid secretion; however, both glucose and fat caused an increase in serum gastrin concentration. Amino acids caused a much greater increase in serum gastrin concentration and enhanced acid secretion above that noted with distention alone. In contrast, albumin did not enhance the serum gastrin concentration or stimulate acid secretion to a statistically significant extent. There was a close correlation between the rise in serum gastrin concentration and rate of acid secretion after different test meals when average results for each test meal were plotted. However, there was a poor correlation between acid secretion and serum gastrin concentration when the responses of the individual subjects with a given test meal were compared. Our interpretations are: (a) Distention is an important stimulant of the acid-secretory response to a meal, and this is not mediated by gastrin release. (b) Gastrin is one but probably not the only mediator of the chemical phase of acid secretion, i.e., acid secretion noted with amino acids that cannot be explained by distention. (c) Glucose and fat also release gastrin; however, with glucose the rise in serum gastrin is too small and too transient to enhance acid secretion, and fat probably releases unmeasured inhibitors that overwhelm the effect of gastrin on acid secretion. (d) Albumin is not a stimulant of acid secretion.
Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity
Authors: Sevvandi Senadheera, Youngsoo Kim, T. Hilton Grayson, Sianne Toemoe, Mikhail Y. Kochukov, Joel Abramowitz, Gary D. Housley, Rebecca L. Bertrand, Preet S. Chadha, Paul P. Bertrand, Timothy V. Murphy, Marianne Tare, Lutz Birnbaumer, Sean P. Marrelli, Shaun L. Sandow
Journal: Cardiovascular Research (2012)

AimsMicrodomain signalling mechanisms underlie key aspects of artery function and the modulation of intracellular calcium, with transient receptor potential (TRP) channels playing an integral role. This study determines the distribution and role of TRP canonical type 3 (C3) channels in the control of endothelium-derived hyperpolarization (EDH)-mediated vasodilator tone in rat mesenteric artery.
Patient acceptability of a new fragrance-free sulfacetamide/sulfur cleanser
Authors: Karl R. Beutner, Shawna Lemke, Janusz Czernielewski
Journal: Journal of the American Academy of Dermatology (2004)

The objective of this study was to evaluate the patient acceptability of a 10% sodium sulfacetamide and 5% sulfur cleanser in patients with mild-to-severe rosacea. This was a single-center, open-label, 4-week study involving 34 enrolled patients (31 of whom completed all visits). All patients were prescribed (metronidazole gel 0.75%) to be used twice daily after washing with the sulfacetamide/sulfur cleanser. The investigator's assessment of product tolerability involved a 4-point scale to evaluate dryness, scaling, pruritis, and stinging/burning. Patients were asked to assess various skin sensations after product use (eg, "feels soft/smooth') on a 6-point scale. In addition, the investigators performed an inflammatory lesion count and assessed erythema severity and global rosacea severity. Investigator assessment of product tolerability showed that the average score for each potential adverse effect decreased over the course of the study. Patient evaluation demonstrated that the average score for each subjective assessment decreased from or remained similar to baseline at the week 4 visit. There was a numerical trend toward improvement in disease-state evaluations (lesion counts, erythema severity score, and global rosacea severity score) over the course of the study.
Electroanatomic Substrate of Idiopathic Left Ventricular Tachycardia
Authors: Feifan Ouyang, Riccardo Cappato, Sabine Ernst, Masahiko Goya, Marius Volkmer, Joachim Hebe, Matthias Antz, Thomas Vogtmann, Anselm Schaumann, Parwis Fotuhi, Martin Hoffmann-Riem, Karl-Heinz Kuck
Journal: Circulation (2002)

Background — An abnormal potential (retroPP) from the left posterior Purkinje network has been demonstrated during sinus rhythm (SR) in some patients with idiopathic left ventricular tachycardia (ILVT). We hypothesized that this potential can specifically be identified and be a critical substrate for ILVT. Methods and Results — In 9 patients with ILVT and 6 control patients who underwent mapping of the left ventricle during SR using 3-dimensional electroanatomic mapping, an area with retroPP was found within the posterior Purkinje fiber network only in patients with ILVT. The earliest and latest retroPP was 185.4±57.4 and 465.2±37.3 ms after Purkinje potential; in the other patient with ILVT, an entire left ventricle mapping demonstrated a slow conduction area and passive retrograde activation along the posterior fascicle during ILVT. ILVT was noninducible in 3 patients after SR mapping. Diastolic potentials critical for ILVT during ILVT coincided with the earliest retroPP during SR in 7 patients. Mechanical termination of ILVT occurred in 5 patients. A single radiofrequency pulse was applied at the site with mechanical translation in 5 patients and the site with diastolic potential in 2 patients, and 3 radiofrequency pulses were delivered to the site with the earliest retroPP in the other 3 patients without inducible ILVT after SR mapping. No ILVT was inducible during control stimulation, and none recurred during follow-up of 9.1±5.1 months. Conclusion — In patients with ILVT, abnormal retroPP within the posterior Purkinje fiber network is a common finding. The earliest retroPP critical for ILVT substrate can be used for guiding successful ablation.
Selected genetic factors associated with male infertility
Authors: T. Huynh
Journal: Human Reproduction Update (2002)

Studies into the mechanisms underlying spermatogenesis, the process by which spermatogonia undergo meiosis to become spermatozoa, have identified a number of genetic determinants of male infertility. Indeed, a more comprehensive knowledge of the genetic regulation of spermatogenesis has alleviated the dependence on the use of idiopathic infertility as a classification for sterile men for whom a cause for their infertility is unknown, as genetic factors become more accountable for this phenotype. This review focuses on selected areas implicated in male infertility including: (i) autosomal and sex chromosomal abnormalities; (ii) genetic disorders associated with impaired gonadotrophin secretion or action; (iii) microdeletions within regions of the Y-chromosome containing candidate gene families for spermatogenesis; (iv) the genetic nexus between cystic fibrosis and congenital bilateral absence of the vas deferens; and (v) insights into human infertility as gleaned from animal studies into mechanisms involving the Bcl-2 family of apoptosis regulators and the interaction between the c-kit encoded tyrosine kinase receptor and its ligand, stem cell factor. As significant advances continue to further knowledge of the genetic basis of male infertility, such as those leading to an understanding of the aforementioned areas, greater progress can be made to rectify or at least ameliorate social stigmas associated with sterility.
New insight into the enhanced effect of pegylated interferon-α
Authors: Hiromi Abe, Nelson C. Hayes, Kazuaki Chayama
Journal: Hepatology (2014)

Abstract The use of pegylated interferon-α (pegIFN-α) has replaced unmodified recombinant IFN-α for the treatment of chronic viral hepatitis. While the superior antiviral efficacy of pegIFN-α is generally attributed to improved pharmacokinetic properties, the pharmacodynamic effects of pegIFN-α in the liver have not been studied. Here, we analyzed pegIFN-α-induced signaling and gene regulation in paired liver biopsies obtained prior to treatment and during the first week following pegIFN-α injection in 18 patients with chronic hepatitis C. Despite sustained high concentrations of pegIFN-α in serum, the Jak/STAT pathway was activated in hepatocytes only on the first day after pegIFN-α administration. Evaluation of liver biopsies revealed that pegIFN-α induces hundreds of genes that can be classified into four clusters based on different temporal expression profiles. In all clusters, gene transcription was mainly driven by IFN-stimulated gene factor 3 (ISGF3). Compared with conventional IFN-α therapy, pegIFN-α induced a broader spectrum of gene expression, including many genes involved in cellular immunity. IFN-induced secondary transcription factors did not result in additional waves of gene expression. Our data indicate that the superior antiviral efficacy of pegIFN-α is not the result of prolonged Jak/STAT pathway activation in hepatocytes, but rather is due to induction of additional genes that are involved in cellular immune responses.
Gastrointestinal and Mesenteric Hemodynamic Patterns in Neurogenic Hypertensive Rabbits
Authors: NATALIE ALEXANDER, VINCENT DeQUATTRO
Journal: Circulation Research (1974)

Patterns of blood flow and vascular resistance in the component tissues of the splanchnic region of sinoaortic denervated (SAD) hypertensive rabbits were compared with those of normotensive sham-operated rabbits using previously described methods. SAD rabbits with high total splanchnic resistance showed significant elevations in resistance in all parts of the gastrointestinal tract and mesentery, but the magnitude of the changes compared with values for sham-operated rabbits varied from one area to another, ranging from increases of 34% in the cecum-appendix to 77% in the stomach and jejunum. Blood flow was reduced 22-42% in some areas and less in others. An aboral gradient of mean blood flow was found between and within the small and large intestines in both groups. Intestinal flow pattern differences were found in individual rabbits. We concluded that activation of the sympathetic nervous system by sinoaortic denervation exerted a variable, unpredictable degree of vasoconstrictor tone on different parts of the splanchnic bed which reflected the net result of vascular smooth muscle response to neurogenic and local regulatory factors.
Reporting Trends and Outcomes in ST-Segment–Elevation Myocardial Infarction National Hospital Quality Assessment Programs
Authors: James M. McCabe, Kevin F. Kennedy, Andrew C. Eisenhauer, Howard M. Waldman, Elizabeth A. Mort, Eugene Pomerantsev, Frederic S. Resnic, Robert W. Yeh
Journal: Circulation (2013)

Background— For patients who undergo primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction, the door-to-balloon time is an important performance measure reported to the Centers for Medicare &amp; Medicaid Services (CMS) and tied to hospital quality assessment and reimbursement. We sought to assess the use and impact of exclusion criteria associated with the CMS measure of door-to-balloon time in primary PCI. Methods and Results— All primary PCI-eligible patients at 3 Massachusetts hospitals (Brigham and Women’s, Massachusetts General, and North Shore Medical Center) were evaluated for CMS reporting status. Rates of CMS reporting exclusion were the primary end points of interest. Key secondary end points were between-group differences in patient characteristics, door-to-balloon times, and 1-year mortality rates. From 2005 to 2011, 26% (408) of the 1548 primary PCI cases were excluded from CMS reporting. This percentage increased over the study period from 13.9% in 2005 to 36.7% in the first 3 quarters of 2011 ( P &lt;0.001). The most frequent cause of exclusion was for a diagnostic dilemma such as a nondiagnostic initial ECG, accounting for 31.2% of excluded patients. Although 95% of CMS-reported cases met door-to-balloon time goals in 2011, this was true of only 61% of CMS-excluded cases and consequently 82.6% of all primary PCI cases performed that year. The 1-year mortality for CMS-excluded patients was double that of CMS-included patients (13.5% versus 6.6%; P &lt;0.001). Conclusions— More than a quarter of patients who underwent primary PCI were excluded from hospital quality reports collected by CMS, and this percentage has grown substantially over time. These findings may have significant implications for our understanding of process improvement in primary PCI and mechanisms for reimbursement through Medicare.
Correlation between in vivo transmembrane action potential durations and activation-recovery intervals from electrograms. Effects of interventions that alter repolarization time.
Authors: C W Haws, R L Lux
Journal: Circulation (1990)

Classic cable theory was used to analyze the relation between the activation-recovery interval measured from unipolar electrograms and transmembrane action potential duration. Theoretic analysis demonstrated that the temporal derivative of the extracellular potential is proportional to a spatial weighting of the third temporal derivative of the transmembrane action potentials along a cable with uniform propagation in a homogeneous medium. Thus, the activation-recovery interval, measured as the interval between times of minimum derivative (Vmin) of the QRS and maximum derivative (Vmax) of the T wave, should be related to action potential duration, measured as the interval between times of Vmax of the upstroke and Vmin of the downstroke of the transmembrane action potential. This relation was examined experimentally in 12 anesthetized dogs. Unipolar electrograms and transmembrane action potentials were recorded simultaneously from sites within 2 mm of each other during control states, cardiac sympathetic nerve stimulation, localized epicardial warming, and graded reductions in myocardial perfusion. The heart was paced from several sites. There was close correlation between activation-recovery interval and action potential duration measurements taken during cardiac sympathetic nerve stimulation and local epicardial warming (r = 0.96 and 0.99 for cardiac sympathetic nerve stimulation and warming, respectively). In five animals in which coronary perfusion pressure was gradually lowered, the variables correlated closely over a range of values from 62 to 212 msec (r = 0.98). However, although the overall correlation was good and mean differences between activation-recovery interval and action potential duration were small, in individual cases there were differences up to 24 msec.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment of Patients With Low-Grade B-Cell Lymphoma With the Combination of Chimeric Anti-CD20 Monoclonal Antibody and CHOP Chemotherapy
Authors: M. S. Czuczman, A. J. Grillo-López, C. A. White, M. Saleh, L. Gordon, A. F. LoBuglio, C. Jonas, D. Klippenstein, B. Dallaire, C. Varns
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody, Rituxan (Rituximab, IDEC-C2B8; IDEC Pharmaceuticals Corporation, San Diego, CA), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. PATIENTS AND METHODS: Forty patients with low-grade or follicular B-cell non–Hodgkin's lymphoma received six infusions of Rituxan (375 mg/m 2 per dose) in combination with six doses of CHOP chemotherapy. RESULTS: The overall response rate was 95% (38 of 40 patients). Twenty-two patients experienced a complete response (55%), 16 patients had a partial response (40%), and two patients, who received no treatment, were classified as nonresponders. Medians for duration of response and time to progression had not been reached after a median observation time of 29 + months. Twenty-eight of 38 assessable patients (74%) continued in remission during this median follow-up period. The most frequent adverse events attributable to CHOP were alopecia (38 patients), neutropenia (31 patients), and fever (23 patients). The most frequent events attributed to Rituxan were fever and chills, observed primarily with the first infusion. No quantifiable immune response to the chimeric antibody was detected. In a subset of 18 patients, the bcl-2 [t(14;18)] translocation was positive in eight patients; seven of these patients had complete remissions and converted to polymerase chain reaction (PCR) negativity by completion of therapy. CONCLUSION: This is the first report demonstrating the safety and efficacy of Rituxan anti-CD20 chimeric antibody in combination with standard-dose systemic chemotherapy in the treatment of indolent B-cell lymphoma. The clinical responses suggest an additive therapeutic benefit for the combination with no significant added toxicity. The conversion of bcl-2 from positive to negative by PCR in blood and/or marrow suggests possible clearing of minimal residual disease not previously demonstrated by CHOP chemotherapy alone.
Novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis<i>in vivo</i>
Authors: Vikash Reebye, Pål Saetrom, Paul J. Mintz, Kai-Wen Huang, Piotr Swiderski, Ling Peng, Cheng Liu, Xiaoxuan Liu, Steen Lindkaer-Jensen, Dimitris Zacharoulis, Nikolaos Kostomitsopoulos, Noriyuki Kasahara, Joanna P. Nicholls, Long R. Jiao, Madhava Pai, Duncan R. Spalding, Malkhaz Mizandari, Tinatin Chikovani, Mohamed M. Emara, Abdelali Haoudi, Donald A. Tomalia, John J. Rossi, Nagy A. Habib
Journal: Hepatology (2013)

Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here we show an innovative RNA-based targeted approach to enhance endogenous albumin production while reducing liver tumor burden. We designed short-activating RNAs (saRNA) to enhance expression of C/EBPα (CCAAT/enhancer-binding protein-α), a transcriptional regulator and activator of albumin gene expression. Increased levels of both C/EBPα and albumin mRNA in addition to a 3-fold increase in albumin secretion and 50% decrease in cell proliferation was observed in C/EBPα-saRNA transfected HepG2 cells. Intravenous injection of C/EBPα-saRNA in a cirrhotic rat model with multifocal liver tumors increased circulating serum albumin by over 30%, showing evidence of improved liver function. Tumor burden decreased by 80% (P = 0.003) with a 40% reduction in a marker of preneoplastic transformation. Since C/EBPα has known antiproliferative activities by way of retinoblastoma, p21, and cyclins, we used messenger RNA (mRNA) expression liver cancer-specific microarray in C/EBPα-saRNA-transfected HepG2 cells to confirm down-regulation of genes strongly enriched for negative regulation of apoptosis, angiogenesis, and metastasis. Up-regulated genes were enriched for tumor suppressors and positive regulators of cell differentiation. A quantitative polymerase chain reaction (PCR) and western blot analysis of C/EBPα-saRNA-transfected cells suggested that in addition to the known antiproliferative targets of C/EBPα, we also observed suppression of interleukin (IL)6R, c-Myc, and reduced STAT3 phosphorylation.A novel injectable saRNA-oligonucleotide that enhances C/EBPα expression successfully reduces tumor burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model.
Outpatient Geriatric Psychiatry in an Urban Ghetto with Nonprofessional Workers
Authors: SHELDON ZIMBERG
Journal: American Journal of Psychiatry (1969)

After establishing a group therapy program for geriatric outpatients, the author found that: 1) relatively brief socialization opportunities can provide these patients with a significant degree of support; 2) small doses of medication can provide rapid and effective control of psychotic symptoms; 3) an intensive case-finding approach is necessary to reach many elderly patients; and 4) non-professional workers can provide a great deal of meaningful service.
Aspects of the effect of metiamide on pentagastrin-stimulated and basal gastric secretion of acid and pepsin in man.
Authors: B Thjodleifsson, K G Wormsley
Journal: Gut (1975)

This study has examined the inhibition produced by metiamide on the gastric secretion of acid and pepsin in 13 patients with duodenal and three with gastric ulcer. The effect of metiamide on the response to a range of doses of pentagastrin in three normal individuals was determined, as was the interaction of metiamide and atropine on prolonged basal secretion. Metiamide inhibited the secretion of acid more than pepsin and the gastric secretion of patients with gastric ulcer more than duodenal ulcer. Metiamide inhibited both the maximal secretory response attainable with pentagastrin and decreased the sensitivity to pentagastrin. Atropine augmented and prolonged the action of metiamide.
Developmentally Regulated Extinction of Ly-49 Receptor Expression Permits Maturation and Selection of NK1.1+ T Cells
Authors: H. Robson MacDonald, Rosemary K. Lees, Werner Held
Journal: The Journal of Experimental Medicine (1998)

Clonally distributed inhibitory receptors negatively regulate natural killer (NK) cell function via specific interactions with allelic forms of major histocompatibility complex (MHC) class I molecules. In the mouse, the Ly-49 family of inhibitory receptors is found not only on NK cells but also on a minor (NK1.1+) T cell subset. Using Ly-49 transgenic mice, we show here that the development of NK1.1+ T cells, in contrast to NK or conventional T cells, is impaired when their Ly-49 receptors engage self-MHC class I molecules. Impaired NK1.1+ T cell development in transgenic mice is associated with a failure to select the appropriate CD1-reactive T cell receptor repertoire. In normal mice, NK1.1+ T cell maturation is accompanied by extinction of Ly-49 receptor expression. Collectively, our data imply that developmentally regulated extinction of inhibitory MHC-specific receptors is required for normal NK1.1+ T cell maturation and selection.
Brief Communication: Morphologic Evidence Suggestive of Host-Tumor Cell Interactions In Vivo in Human Cancer Patients2
Authors: D. Sulitzeanu, Y. Gorsky, S. Paglin, D. Weiss
Journal: JNCI Journal of the National Cancer Institute (1974)

Pleural and ascites effusions of patients with malignant diseases contain occasional clusters of a central malignant cell surrounded by various types of Iymphoreticular cells. These clusters may be a manifestation of the immune reactivity of the patient against the tumor