tbuckley/cabot-search huggingface dataset:
Somatostatin reduces gastric mucosal blood flow in normal subjects but not in patients with cirrhosis of the liver.
Authors: A Sonnenberg, C West
Journal: Gut (1983)

The effects of 1 and 4 micrograms/kg/h somatostatin on pentagastrin-stimulated gastric mucosal blood flow and acid secretion were investigated in 12 normal subjects and in 12 patients with cirrhosis of the liver. Each dose of somatostatin was given intravenously to six normal subjects and to six patients. Gastric mucosal blood flow was measured by the neutral red clearance of the stomach. Pentagastrin at a dose of 0.67 micrograms/kg/h stimulated acid secretion less in patients with cirrhosis of the liver than in normal subjects. In normal subjects 1 micrograms/kg/h somatostatin induced a parallel decline of gastric mucosal blood flow and gastric secretion; with 4 micrograms/kg/h somatostatin mucosal blood flow was inhibited more than gastric secretion. In patients with cirrhosis of the liver gastric mucosal blood flow remained unaffected by both doses of somatostatin, while acid secretion was slightly decreased. It is concluded that somatostatin can affect gastric mucosal blood flow independently of acid secretion. Somatostatin may be ineffective in the treatment of gastric haemorrhage in patients with cirrhosis of the liver.
Combined analysis of the ORCHID and OCAY studies: does eradication of Helicobacter pylori lead to sustained improvement in functional dyspepsia symptoms?
Authors: S J O Veldhuyzen van Zanten, N J Talley, A L Blum, E Bolling-Sternevald, M Sundin, O Junghard
Journal: Gut (2002)

Currently, one of the most important unresolved questions concerning <i>Helicobacter pylori</i> is whether eradication of the organism leads to a sustained improvement in symptoms in patients diagnosed with functional (non-ulcer) dyspepsia. Recently, two very similar studies, the ORCHID and OCAY studies, have been completed and the combined results of these two multicentre, multinational, randomised, double blind, controlled clinical trials are reviewed.
FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection
Authors: Lisa M. Johansen, Jennifer M. Brannan, Sue E. Delos, Charles J. Shoemaker, Andrea Stossel, Calli Lear, Benjamin G. Hoffstrom, Lisa Evans DeWald, Kathryn L. Schornberg, Corinne Scully, Joseph Lehár, Lisa E. Hensley, Judith M. White, Gene G. Olinger
Journal: Science Translational Medicine (2013)

Clomiphene and toremifene inhibit Ebola virus infection.
Surgical Treatment of Atrial Fibrillation Using Argon-Based Cryoablation During Concomitant Cardiac Procedures
Authors: Charles A. Mack, Federico Milla, Wilson Ko, Leonard N. Girardi, Leonard Y. Lee, Anthony J. Tortolani, Justin Mascitelli, Karl H. Krieger, O. Wayne Isom
Journal: Circulation (2005)

Background— The development of ablative energy sources has simplified the surgical treatment of atrial fibrillation (AF) during concomitant cardiac procedures. We report our results using argon-based endocardial cryoablation for the treatment of AF in patients undergoing concomitant cardiac procedures. Methods and Results— Sixty-three patients with AF who were undergoing concomitant cardiac procedures had the same left atrial endocardial lesion set using a flexible argon-based cryoablative device. Mean age was 65.1±1.3 years. Sixty-two percent had permanent AF, whereas 38% had paroxysmal AF. Mean duration of AF was 30.5±4.8 months. Mean left atrial diameter was 5.5±0.1 cm. Mean ejection fraction was 45±1.4%. All endocardial lesions were performed for 1 minute once tissue temperature reached −40°C. Follow-up echocardiograms were obtained to determine freedom from AF. Kaplan-Meier analysis demonstrated an 88.5% freedom from AF rate at 12 months. Ablation time was 16.8±0.6 minutes. There were no in-hospital deaths and no strokes. Twelve patients (19%) required postoperative permanent pacemaker placement. Conclusions— Cryoablation using this flexible argon-based device for the treatment of AF during concomitant cardiac procedures was safe and effective, with 88.5% of patients free from AF at 12 months.
Hypoxia Inducible Factor 1 Mediates Hypoxia-Induced TRPC Expression and Elevated Intracellular Ca <sup>2+</sup> in Pulmonary Arterial Smooth Muscle Cells
Authors: Jian Wang, Letitia Weigand, Wenju Lu, J.T. Sylvester, Gregg L. Semenza, Larissa A. Shimoda
Journal: Circulation Research (2006)

Chronic hypoxia (CH) causes pulmonary vasoconstriction because of increased pulmonary arterial smooth muscle cell (PASMC) contraction and proliferation. We previously demonstrated that intracellular Ca(2+) concentration ([Ca(2+)](i)) was elevated in PASMCs from chronically hypoxic rats because of Ca(2+) influx through pathways other than L-type Ca(2+) channels and that development of hypoxic pulmonary hypertension required full expression of the transcription factor hypoxia inducible factor 1 (HIF-1). In this study, we examined the effect of CH on the activity and expression of store-operated Ca(2+) channels (SOCCs) and the regulation of these channels by HIF-1. Capacitative Ca(2+) entry (CCE) was enhanced in PASMCs from intrapulmonary arteries of rats exposed to CH (10% O(2); 21 days), and exposure to Ca(2+)-free extracellular solution or SOCC antagonists (SKF96365 or NiCl(2)) decreased resting [Ca(2+)](i) in these cells. Expression of TRPC1 and TRPC6, but not TRPC4, mRNA and protein was increased in PASMCs from rats and wild-type mice exposed to CH, in PASMCs from normoxic animals cultured under hypoxic conditions (4% O(2); 60 hours), and in PASMCs in which HIF-1 was overexpressed under nonhypoxic conditions. Hypoxia-induced increases in basal [Ca(2+)](i) and TRPC expression were absent in mice partially deficient for HIF-1. These results suggest that increased TRPC expression, leading to enhanced CCE through SOCCs, may contribute to hypoxic pulmonary hypertension by facilitating Ca(2+) influx and increasing basal [Ca(2+)](i) in PASMCs and that this response is mediated by HIF-1.
Intermediate End Point for Prostate Cancer-Specific Mortality Following Salvage Hormonal Therapy for Prostate-Specific Antigen Failure
Authors: Anthony V D'Amico, Judd W Moul, Peter R Carroll, Kerri Cote, Leon Sun, Deborah Lubeck, Andrew A Renshaw, Marian Loffredo, Ming-Hui Chen
Journal: JNCI Journal of the National Cancer Institute (2004)

Whether the prostate-specific antigen (PSA) response to salvage hormonal therapy can act as an intermediate end point for prostate cancer-specific mortality (PCSM) remains unclear. Therefore, we evaluated whether PSA response, defined as the absolute value of the ratio of the rate of PSA change after salvage hormonal therapy to the rate of PSA change before salvage therapy, is associated with the time to PCSM following salvage hormonal therapy.A single-institution and two pooled multi-institution databases containing baseline, treatment, and follow-up information on men who received salvage hormonal therapy for PSA failure following surgery or radiation therapy from January 1, 1988, to January 1, 2002, formed the study (n = 199) and validation cohorts (n = 1255), respectively. The ability of PSA response and its constituents (i.e., pre-salvage hormonal therapy PSA slope and post-salvage hormonal therapy PSA slope) to predict time to PCSM following salvage hormonal therapy was assessed using Cox regression analysis. For illustrative purposes, PSA response was analyzed as a dichotomous variable with a breakpoint for the ratio of PSA response of 1. All statistical tests were two-sided.PSA response was statistically significantly associated with time to PCSM following salvage hormonal therapy in both the study (P(Cox) =.0014) and validation (P(Cox)<.001) cohorts; however, its constituents were not (pre-salvage hormonal therapy PSA slope: P(Cox-study) =.97, P(Cox-validation) =.57; post-salvage hormonal therapy PSA slope: P(Cox-study) =.27, P(Cox-validation) =.31). Patients with a PSA response that was less than or equal to 1 had a statistically significantly shorter time to PCSM than patients with a PSA response of greater than 1 in both the study (hazard ratio [HR] = 3.6, 95% confidence interval [CI] = 1.3 to 10.3; P(Cox) =.01) and validation (HR = 12.8, 95% CI = 6.2 to 26.3; P(Cox)<.001) cohorts.The PSA response to salvage hormonal therapy can serve as an intermediate end point for PCSM in patients with a rising PSA level following surgery or radiation therapy.
Kaplan–Meier failure estimate for metachronous colorectal cancer risk is clinically relevant
Authors: Mark A Jenkins, Lyle C Gurrin, Susan Parry, Aung Ko Win
Journal: Gut (2011)

Renehan1 argues that we inappropriately used the Kaplan–Meier method to estimate the risk of metachronous colorectal cancer, and instead recommends a competing risk analysis.2 While we agree that a competing risk analysis is a valid technique, we claim that the Kaplan–Meier estimate is also valid, and in this setting more appropriate.

We have reported the cumulative risk of metachronous colorectal cancer following segmental surgery for a first colon cancer for carriers of mutations in mismatch repair genes.3 Using …
Linking hypothetical knowledge patterns to disease molecular signatures for biomarker discovery in Alzheimer’s disease
Authors: Ashutosh Malhotra, Erfan Younesi, Shweta Bagewadi, Martin Hofmann-Apitius
Journal: Genome Medicine (2014)

A number of compelling candidate Alzheimer's biomarkers remain buried within the literature. Indeed, there should be a systematic effort towards gathering this information through approaches that mine publicly available data and substantiate supporting evidence through disease modeling methods. In the presented work, we demonstrate that an integrative gray zone mining approach can be used as a way to tackle this challenge successfully.The methodology presented in this work combines semantic information retrieval and experimental data through context-specific modeling of molecular interactions underlying stages in Alzheimer's disease (AD). Information about putative, highly speculative AD biomarkers was harvested from the literature using a semantic framework and was put into a functional context through disease- and stage-specific models. Staging models of AD were further validated for their functional relevance and novel biomarker candidates were predicted at the mechanistic level.Three interaction models were built representing three stages of AD, namely mild, moderate, and severe stages. Integrated analysis of these models using various arrays of evidence gathered from experimental data and published knowledge resources led to identification of four candidate biomarkers in the mild stage. Mode of action of these candidates was further reasoned in the mechanistic context of models by chains of arguments. Accordingly, we propose that some of these 'emerging' potential biomarker candidates have a reasonable mechanistic explanation and deserve to be investigated in more detail.Systematic exploration of derived hypothetical knowledge leads to generation of a coherent overview on emerging knowledge niches. Integrative analysis of this knowledge in the context of disease mechanism is a promising approach towards identification of candidate biomarkers taking into consideration the complex etiology of disease. The added value of this strategy becomes apparent particularly in the area of biomarker discovery for neurodegenerative diseases where predictive biomarkers are desperately needed.
Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen.
Authors: Y Sharabi, D H Sachs
Journal: The Journal of Experimental Medicine (1989)

The use of allogeneic bone marrow transplantation as a means of inducing donor-specific tolerance across MHC barriers could provide an immunologically specific conditioning regimen for organ transplantation. However, a major limitation to this approach is the toxicity of whole body irradiation as currently used to abrogate host resistance and permit marrow engraftment. The present study describes methodology for abrogating host resistance and permitting marrow engraftment without lethal irradiation. Our preparative protocol involves administration of anti-CD4 and anti-CD8 mAbs in vivo, 300-rad WBI, 700-rad thymic irradiation, and unmanipulated fully MHC-disparate bone marrow. B10 mice prepared by this regimen developed stable mixed lymphohematopoetic chimerism without any clinical evidence of graft-vs.-host disease. Engraftment was accompanied by induction of specific tolerance to donor skin grafts (B10.D2), while third-party skin grafts (B10.BR) were promptly rejected. Mice treated with the complete regimen without bone marrow transplantation appeared healthy and enjoyed long-term survival. This study therefore demonstrates that stable mixed chimerism with donor-specific tolerance can be induced across an MHC barrier after a nonlethal preparative regimen, without clinical GVHD and without the risk of aplasia.
C5A Anaphylatoxin and Its Seven Transmembrane-Segment Receptor
Authors: C Gerard, N P Gerard
Journal: Annual Review of Immunology (1994)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Risk Analysis of Pneumonitis in Taxane Therapy After Chemoradiotherapy (Crt) for Patient with Esophageal Cancer
Authors: Yoshihiro Kishida, Takahiro Tsushima, Satoshi Hamauchi, Akiko Todaka, Tomoya Yokota, Nozomu Machida, Kentaro Yamazaki, Akira Fukutomi, Yusuke Onozawa, Hirofumi Yasui
Journal: Annals of Oncology (2014)
Status of myocardial antioxidants in ischemia–reperfusion injury
Authors: N Dhalla
Journal: Cardiovascular Research (2000)

Background: Myocardial ischemia–reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Injury of myocardium due to ischemia–reperfusion includes cardiac contractile dysfunction, arrhythmias as well as irreversible myocyte damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart. Observations: An increase in the formation of reactive oxygen species during ischemia–reperfusion and the adverse effects of oxyradicals on myocardium have now been well established by both direct and indirect measurements. Although several experimental studies as well as clinical trials have demonstrated the cardioprotective effects of antioxidants, some studies have failed to substantiate the results. Nonetheless, it is becoming evident that some of the endogenous antioxidants such as glutathione peroxidase, superoxide dismutase, and catalase act as a primary defense mechanism whereas the others including vitamin E may play a secondary role for attenuating the ischemia–reperfusion injury. The importance of various endogenous antioxidants in suppressing oxidative stress is evident from the depression in their activities and the inhibition of cardiac alterations which they produce during ischemia–reperfusion injury. The effects of an antioxidant thiol containing compound, N-acetylcysteine, and ischemic preconditioning were shown to be similar in preventing changes in the ischemic-reperfused hearts. Conclusions: The available evidence support the role of oxidative stress in ischemia–reperfusion injury and emphasize the importance of antioxidant mechanisms in cardioprotection.
Effects of salt depletion on the kidney
Authors: I E Stillman, M Brezis, S N Heyman, F H Epstein, K Spokes, S Rosen
Journal: Journal of the American Society of Nephrology (1994)

Previous studies have shown that salt depletion enhances the susceptibility of the kidney to nephrotoxins (amphotericin, cyclosporine, and contrast). To study the renal response to salt depletion, Sprague-Dawley rats were fed a sodium-deficient diet (N = 12) with pair-fed controls (N = 13) for 4 wk. In addition, rats from each group underwent 24-h water deprivation studies (N = 9; four salt deprived, five normal). Plastic 1-micron horizontal sections of mid-inner stripe were examined, and cross-sectional areas of the medullary thick ascending limb (mTAL) were analyzed. The mTAL of the salt-deprived rats were smaller (P = 0.04) and showed greater variance in size (P = 0.02) than control (618 +/- 106 versus 693 +/- 50 microns2). However, mean glomerular and collecting duct cross-sectional areas were unaffected by salt intake. Cross-sectional areas of long- and short-loop mTAL were significantly different, regardless of group (518 +/- 78 versus 732 +/- 92 microns2). Maximal urinary concentrating ability was found to correlate with mTAL cross-sectional area (r = 0.85; P = 0.004) and with long-loop mTAL size (r = 0.77; P = 0.016). However, it did not significantly correlate with short loop mTAL size (r = 0.53; P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)
Time-Dependent Autoregulation of Renal Blood Flow in Conscious Rats
Authors: BERT FLEMMING, NICOLE ARENZ, ERDMANN SEELIGER, THOMAS WRONSKI, KATHARINA STEER, PONTUS B. PERSSON
Journal: Journal of the American Society of Nephrology (2001)

Response of renal vasculature to changes in renal perfusion pressure (RPP) involves mechanisms with different frequency characteristics. Autoregulation of renal blood flow is mediated by a rapid myogenic response and a slower tubuloglomerular feedback mechanism. In 25 male conscious rats, ramp-shaped changes in RPP were induced to quantify dynamic properties of autoregulation. Decremental RPP ramps immediately followed by incremental ramps were made for four different rates of change, ranging from 0.118 to 1.056 mmHg/s. Renal blood flow and cortical and medullary fluxes were assessed, and the corresponding relative conductance values were calculated continuously. During RPP decrements, conductance increased. With increasing rate of change of RPP decrements, maximum conductance increased from 10% to 80%, as compared with control. This response, which indicates the magnitude of autoregulation, was more pronounced in cortical versus medullary vasculature. Pressure at maximum conductance decreased with increasing rate of change of RPP decrements from 88 to 72 mmHg. During RPP increments, dependence of maximum conductance changes on the rate of change was enhanced (-20 to 110% of control). Thus, a hysteresis-like asymmetry between RPP decrements and increments, a resetting of autoregulation, was observed, which in direction and magnitude depended on the rate of change and duration of RPP changes. In conclusion, renal vascular responses to changes in RPP are highly dependent on the dynamics of the error signal. Furthermore, the method presented allows differentiated stimulation of various static and dynamic components of pressure-flow relationship and, thus, a direct assessment of the magnitudes and operating pressure range of active mechanisms of pressure-flow relationships.
Skeletal muscle response to exercise training in congestive heart failure.
Authors: J R Minotti, E C Johnson, T L Hudson, G Zuroske, G Murata, E Fukushima, T G Cagle, T W Chick, B M Massie, M V Icenogle
Journal: Journal of Clinical Investigation (1990)

To examine the ability of the skeletal muscle of congestive heart failure (CHF) patients to adapt to chronic exercise, five patients performed localized nondominant wrist flexor training for 28 d. Inorganic phosphate (Pi) and phosphocreatine (PCr) were monitored by magnetic resonance spectroscopy in both forearms at rest and during submaximal wrist flexion exercise at 6, 12, 24, and 36 J.min-1 before and after exercise training. Simultaneous measurements of limb blood flow were made by plethysmography at 12, 24, and 36 J.min-1. Forearm muscle mass and endurance were measured by magnetic resonance imaging and wrist flexion exercise before and after training. The Pi/PCr ratio and pH were calculated from the measured Pi and PCr. Exercise cardiac output, heart rate, plasma norepinephrine, and lactate measured during training were not elevated above resting values, confirming that training was localized to the forearm flexor muscles. After training, muscle bioenergetics, as assessed by the slope of the regression line relating Pi/PCr to submaximal workloads, were improved in the trained forearm of each patient, although muscle mass, limb blood flow, and pH were unchanged. Forearm endurance increased by greater than 260% after training. In the dominant untrained forearm, none of the measured indices were affected. We conclude that localized forearm exercise training in CHF patients improves muscle energetics at submaximal workloads in the trained muscle, an effect which is independent of muscle mass, limb blood flow, or a central cardiovascular response during training. These findings indicate that peripheral muscle metabolic and functional abnormalities in CHF can be improved without altering cardiac performance.
The usefulness of transient elastography, acoustic-radiation-force impulse elastography, and real-time elastography for the evaluation of liver fibrosis
Authors: Jong Ho Chung, Hyung Su Ahn, Sang Gyune Kim, Yun Nah Lee, Young Seok Kim, Soung Won Jeong, Jae Young Jang, Sae Hwan Lee, Hong Soo Kim, Boo Sung Kim
Journal: Clinical and Molecular Hepatology (2013)

Several noninvasive methods have recently been developed for the evaluation of liver fibrosis. The accuracy of transient elastography (TE), acoustic-radiation-force impulse (ARFI) elastography, and real-time elastography (RTE) in predicting liver fibrosis were evaluated. Seventy-four patients who had undergone a liver biopsy within the previous 6 months were submitted to evaluation with TE, ARFI, and RTE on the same day. THERE WERE SIGNIFICANT CORRELATIONS BETWEEN FIBROSIS STAGE AND LIVER STIFFNESS MEASUREMENT (LSM) USING THE THREE TESTED METHODS: TE, r(2)=0.272, P=0.0002; ARFI, r(2)=0.225, P=0.0017; and RTE, r(2)=0.228, P=0.0015. The areas under the receiver operating characteristic curves (AUROC) for the diagnosis of significant fibrosis (≥F2, Metavir stage) by TE, ARFI, RTE, TE/platelet count (PLT), velocity of shear wave (Vs)/PLT, and elasticity score (Es)/PLT were 0.727, 0.715, 0.507, 0.876, 0.874, and 0.811, respectively. The AUROC for the diagnosis of cirrhosis by TE, ARFI, RTE, TE/PLT, Vs/PLT, and Es/PLT were 0.786, 0.807, 0.767, 0.836, 0.819, and 0.838, respectively. Comparisons of AUROC between all LSMs for predicting significant fibrosis (≥F2) produced the following results: TE vs. RTE, P=0.0069; ARFI vs. RTE, P=0.0277; and TE vs. ARFI, P=0.8836. Applying PLT, the ability of each LSM to predict fibrosis stage significantly increased: TE/PLT vs. TE, P=0.0004; Vs/PLT vs. ARFI, P=0.0022; and Es/PLT vs. RTE, P<0.0001. However, the ability to predict cirrhosis was not enhanced, combining LSM and PLT. TE and ARFI may be better methods for predicting significant liver fibrosis than RTE. This predictive ability increased significantly when accounting for platelet count. However, all of the measures had comparable efficacies for predicting cirrhosis.