tbuckley/cabot-search huggingface dataset:
NFAT Transcription Factors Are Critical Survival Factors That Inhibit Cardiomyocyte Apoptosis During Phenylephrine Stimulation In Vitro
Authors: William T. Pu, Qing Ma, Seigo Izumo
Journal: Circulation Research (2003)

Biomechanical stress on the heart results in activation of numerous signaling cascades, leading to cardiomyocyte hypertrophy, apoptosis, and ultimately, heart failure. The Ca2+-dependent phosphatase calcineurin is an essential mediator of cardiac hypertrophy, and in most but not all studies, calcineurin inhibition attenuated cardiac hypertrophy in vivo. However, calcineurin inhibition has been reported to have adverse effects on cardiac remodeling and cardiomyocyte apoptosis. Calcineurin regulates the activity of a number of downstream targets, including the transcription factors NFAT, MEF2, and NF-kappaB, and the apoptotic factor Bad. To evaluate the contribution of NFAT activation by calcineurin to cardiomyocyte responses to hypertrophic stimulation, we used adenovirus to express VIVIT, a selective peptide inhibitor of calcineurin-mediated NFAT activation. We found that selective NFAT inhibition during phenylephrine stimulation inhibited hypertrophy but resulted in increased cardiomyocyte apoptosis. In contrast, nonselective inhibition of calcineurin by cyclosporin A did not cause cardiomyocyte apoptosis after phenylephrine stimulation. Cyclosporin A suppressed the effect of VIVIT on cardiomyocyte apoptosis. These results demonstrate that during phenylephrine stimulation calcineurin activates both pro- and antiapoptotic pathways in cardiomyocytes, and that NFAT activity is a critical component of the antiapoptotic pathway that regulates whether the outcome of calcineurin activation is cardiomyocyte apoptosis or survival.
Induction and reversal of cardiac phenotype of human hypertrophic cardiomyopathy mutation cardiac troponin T-Q92 in switch on–switch off bigenic mice
Authors: Silvia Lutucuta, Natalia Tsybouleva, Masukuni Ishiyama, Gilberto DeFreitas, Lei Wei, Blase Carabello, A.J. Marian
Journal: Journal of the American College of Cardiology (2004)
Sclerotherapy of Bleeding Oesophageal Varices by Means of Endoscopy
Authors: K. Paquet, E. Oberhammer
Journal: Endoscopy (1978)

From 1.1.1969 up to 1.11.1977, 640 patients with hemorrhage from gastro-oesophageal varices were managed by sclerotherapy of the oesophageal wall. In 90 % this method succeeded in stopping hemorrhage or preventing a new bleeding during the next four months. Only 43 patients of the total number were treated because of impending hemorrhage under precise indications. After two or three sessions of sclerotherapy the interval of control can be extended up to one years without new danger of hemorrhage. Overall mortality was 14.5 %; main causes of death were liver coma, uncontrollable hemorrhage, mediastinitis and pyothorax. – If liver function improves, a porto-systemic-shunt is performed whenever possible. – 416 = 65 % of the patients are still alive; 50 % longer than one year up to eigth years. Thus sclerotherapy seems to be the method of choice in uncurable massive hemorrhage from varicosities from the oesophagus. It is indicated in patients with decompensated liver function, and whenever a shunt procedure is anatomically or clinically impossible or not advisable, too.
Why don't L2 learners end up with uniform and perfect linguistic competence?
Authors: Ping Li
Journal: Behavioral and Brain Sciences (1996)

Abstract Children in a given linguistic environment all uniformly acquire their target language, but adult learners of L2 do not. UG accounts for children's uniform linguistic behavior, but it cannot serve a similar role in accounting for adult learners' linguistic behavior. I argue that Epstein etal.'s study does not answer the question of why L2 learners end up with nonuniform and imperfect linguistic competence in learning a second language.
Systemic lupus erythematosus complicating complement type 2 deficiency: successful treatment with fresh frozen plasma
Authors: M.J. HUDSON-PEACOCK, S.A. JOSEPH, J. COX, C.S. MUNRO, N.B. SIMPSON
Journal: British Journal of Dermatology (1997)

We report a man who presented in 1981 at the age of 30 with cutaneous lupus erythematosus (LE), which was resistant to a range of treatments over the subsequent 11 years. In 1991 he suffered fits, dysphasia and agitated depression, and in 1992 a severe septicaemic illness. Systemic LE was diagnosed, and investigation showed homozygous complement type 2 deficiency (C2d). Over a period of 30 months he has received 6 weekly fresh frozen plasma. Since starting this treatment his cutaneous disease has resolved and his depression, verbal fluency and psychomotor scores improved. We have not observed any adverse effects to this treatment and suggest it should be considered in similar patients.
Inhibition of gastric secretion and motility by simulated upper gastrointestinal haemorrhage: a response to facilitate haemostasis?
Authors: G M Fullarton, E J Boyd, G P Crean, K Buchanan, K E McColl
Journal: Gut (1989)

As gastric acid and pepsin inhibit blood coagulation and platelet aggregation it is surprising that most upper GI haemorrhages stop spontaneously. To investigate this paradox we have studied acid and pepsin secretion, gastric motility and GI hormones after simulated upper GI haemorrhage. In seven healthy volunteers intraduodenal infusion of 160 ml autologous blood decreased pentagastrin stimulated submaximal acid secretion (mmol/h) from 30.0 (3.2) (mean (SE] in the hour preceding infusion to 21.4 (3.7) in the hour following infusion (p less than 0.02), representing a mean reduction in acid output of 30%. Pepsin output (mg/h) was also decreased from 207.5 (67.7) (mean (SE] in the hour preceding blood infusion to 135.7 (54.7) in the hour after infusion (p less than 0.02) representing a mean reduction in pepsin output of 43%. In six volunteers gastric emptying of a liquid meal was delayed after intraduodenal blood infusion compared with intubation alone with the emptying time (min) to half volume (t 1/2) being prolonged at 75.0 (8.2) (mean (SE] after blood infusion compared with 35.5 (6.6) after intubation alone (p less than 0.02). Plasma GIP concentrations (ng/l) increased to peak levels of 127.9 (62.7) (mean (SE] after intraduodenal blood infusion compared with the pre-infusion value of 58.3 (2.3) (p less than 0.02). These changes may represent protective physiological responses to facilitate haemostasis.
Alterations of the Endogenous Surfactant System in Septic Adult Rats
Authors: JARET MALLOY, LYNDA McCAIG, RUUD VELDHUIZEN, LI-JUAN YAO, MARIAMMA JOSEPH, JEFF WHITSETT, JIM LEWIS
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Sepsis is the most common factor leading to the acute respiratory distress syndrome (ARDS) and is associated with the highest mortality rate. It has been suggested that the pulmonary surfactant system is altered and contributes to the lung dysfunction associated with ARDS. The objective of this study was to characterize the lung injury, specifically the endogenous surfactant system in septic adult rats. Sepsis was induced in male Sprague-Dawley rats by cecal ligation and perforation and resulted in significant increases in heart rates, respiratory rates, and lactate levels along with positive blood cultures in septic animals compared with a sham control group. Two distinct septic groups were developed, a septic group and a sepsis with lung injury (septic + LI) group. The septic group had no significant differences in oxygenation compared with the sham group, whereas the septic + LI group had significantly lower PaO2 and higher A-a gradient values compared to both the sham and septic groups. The total surfactant pool size was significantly lower in the septic + LI group compared with the sham group. The small surfactant aggregate to large surfactant aggregate ratio was significantly lower in the septic group and was further reduced in the septic + LI group. There were also significantly higher levels of surfactant protein A (SP-A) in both septic and septic + LI groups compared to the sham group. These results demonstrated that the endogenous surfactant system was altered in systemic sepsis without lung dysfunction and is further altered when a lung injury is present.
The Joy of Uncircumcising: Restore Your Birthright and Maximize Sexual Pleasure
Authors: William J. Cromie
Journal: JAMA (1993)

<b>Say No to Circumcision: 40 Compelling Reasons Why You Should Respect His Birthright and Keep Your Son Whole</b>, by Thomas J. Ritter, various pagination, with illus, paper $10.95, ISBN 0-9630482-0-1, Aptos, Calif, Hourglass Book Publishing, 1992. The debate on elective circumcision of infants continues, with growing numbers of lay and medical persons dismissing the procedure as unnecessary. These two books, however, add a new dimension to the argument against routine circumcision. Apparently there are literally thousands of men who feel personally "victimized and mutilated" by the fact that they were circumcised against their will. The books list no fewer than 12 organizations whose purpose is to educate the public on the issue of elective circumcision and provide support and information for men having difficulty accepting their denuded penises. <i>Say No to Circumcision</i>is, to my knowledge, the first anticircumcision book written by a physician. Dr Ritter is a surgeon whose
Hormone Replacement and Breast Cancer
Authors: Hans-Olov Adami
Journal: JAMA (1995)

Ever since replacement hormones were introduced some 30 years ago, there has been concern regarding a possible adverse effect on breast cancer risk. More than 30 epidemiological studies have explored the relationship between exogenous hormones and breast cancer. Most of them were of case-control design,<sup>1-3</sup>while seven were prospective cohort studies.<sup>4-10</sup>Despite several attempts to summarize available evidence in overviews<sup>1</sup>and through meta-analyses,<sup>2,3</sup>there is still considerable uncertainty as to whether replacement hormones increase breast cancer risk. However, some recent studies indicate that long-term intake of conjugated estrogens or estradiol compounds is associated with a moderate risk increase.<sup>6,8,11-13</sup>The remaining controversy might be viewed as a shortcoming of the epidemiological method, ie, inability to clarify the role of a potential cause of breast cancer. According to a rival and more optimistic interpretation, the absence of unequivocal evidence for a risk-increasing effect of replacement hormones indicates
Control of the T Follicular Helper–Germinal Center B-Cell Axis by CD8 <sup>+</sup> Regulatory T Cells Limits Atherosclerosis and Tertiary Lymphoid Organ Development
Authors: Marc Clement, Kevin Guedj, Francesco Andreata, Marion Morvan, Laetitia Bey, Jamila Khallou-Laschet, Anh-Thu Gaston, Sandrine Delbosc, Jean-Marc Alsac, Patrick Bruneval, Catherine Deschildre, Marie Le Borgne, Yves Castier, Hye-Jung Kim, Harvey Cantor, Jean-Baptiste Michel, Giuseppina Caligiuri, Antonino Nicoletti
Journal: Circulation (2015)

Background— The atheromodulating activity of B cells during the development of atherosclerosis is well documented, but the mechanisms by which these cells are regulated have not been investigated. Methods and Results— Here, we analyzed the contribution of Qa-1–restricted CD8 + regulatory T cells to the control of the T follicular helper–germinal center B-cell axis during atherogenesis. Genetic disruption of CD8 + regulatory T cell function in atherosclerosis-prone apolipoprotein E knockout mice resulted in overactivation of this axis in secondary lymphoid organs, led to the increased development of tertiary lymphoid organs in the aorta, and enhanced disease development. In contrast, restoring control of the T follicular helper–germinal center B-cell axis by blocking the ICOS-ICOSL pathway reduced the development of atherosclerosis and the formation of tertiary lymphoid organs. Moreover, analyses of human atherosclerotic aneurysmal arteries by flow cytometry, gene expression analysis, and immunofluorescence confirmed the presence of T follicular helper cells within tertiary lymphoid organs. Conclusions— This study is the first to demonstrate that the T follicular helper–germinal center B-cell axis is proatherogenic and that CD8 + regulatory T cells control the germinal center reaction in both secondary and tertiary lymphoid organs. Therefore, disrupting this axis represents an innovative therapeutic approach.
Contact sensitivity to azobenzenearsonate and its inhibition after interaction of sensitized cells with antigen-conjugated cells.
Authors: W R Thomas, F I Smith, I D Walker, J F Miller
Journal: The Journal of Experimental Medicine (1981)

Painting mice on the skin with the diazonium salt of p-arsanilic acid elicited two types of T cell activity. One was restricted by the I region of the major histocompatibility complex and was responsible for the transfer of azobenzenearsonate (ABA) sensitivity to naive mice. The other was H-2K restricted and could be demonstrated by its ability to interact specifically with ABA-coupled cells in vitro and to inhibit nonspecifically the transfer of sensitivity by cells sensitized either to ABA or to another antigen. Free antigen, or antibody directed against the cross-reactive idiotype on the anti-ABA antibodies of A/J mice, could inhibit the H-2K-restricted suppressive activity induced in the ABA immune A/J cells.
Randomised trial comparing buprenorphine and diamorphine for chest pain in suspected myocardial infarction.
Authors: M J Hayes, A R Fraser, J R Hampton
Journal: BMJ (1979)

Buprenorphine, a new powerful analgesic agent, was used to treat chest pain in patients with suspected myocardial infarction. Initial studies showed no significant changes in systemic or pulmonary artery blood pressure or in heart rate after intravenous buprenorphine. Sublingual buprenorphine also appeared effective in relieving pain, but its onset of action was considerably delayed compared with the intravenous route. A randomised double-blind controlled trial of equivalent doses of buprenorphine and diamorphine showed no significant difference between the drugs in terms of pain relief and duration of action. The occurrence of nausea, vomiting, and other side effects was similar in the two groups. The onset of action of buprenorphine was slightly but significantly slower than that of diamorphine. Since buprenorphine seems to be comparable with diamorphine in action and is not a controlled drug, it may prove useful in both general and hospital practice.
Serum Vaccine Antibody Concentrations in Children Exposed to Perfluorinated Compounds
Authors: Philippe Grandjean, Elisabeth Wreford Andersen, Esben Budtz-Jørgensen, Flemming Nielsen, Kåre Mølbak, Pal Weihe, Carsten Heilmann
Journal: JAMA (2012)

<h3>Context</h3>Perfluorinated compounds (PFCs) have emerged as important food contaminants. They cause immune suppression in a rodent model at serum concentrations similar to those occurring in the US population, but adverse health effects of PFC exposure are poorly understood.<h3>Objective</h3>To determine whether PFC exposure is associated with antibody response to childhood vaccinations.<h3>Design, Setting, and Participants</h3>Prospective study of a birth cohort from the National Hospital in the Faroe Islands. A total of 656 consecutive singleton births were recruited during 1997-2000, and 587 participated in follow-up through 2008.<h3>Main Outcome Measures</h3>Serum antibody concentrations against tetanus and diphtheria toxoids at ages 5 and 7 years.<h3>Results</h3>Similar to results of prior studies in the United States, the PFCs with the highest serum concentrations were perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Among PFCs in maternal pregnancy serum, PFOS showed the strongest negative correlations with antibody concentrations at age 5 years, for which a 2-fold greater concentration of exposure was associated with a difference of −39% (95% CI, −55% to −17%) in the diphtheria antibody concentration. PFCs in the child's serum at age 5 years showed uniformly negative associations with antibody levels, especially at age 7 years, except that the tetanus antibody level following PFOS exposure was not statistically significant. In a structural equation model, a 2-fold greater concentration of major PFCs in child serum was associated with a difference of −49% (95% CI, −67% to −23%) in the overall antibody concentration. A 2-fold increase in PFOS and PFOA concentrations at age 5 years was associated with odds ratios between 2.38 (95% CI, 0.89 to 6.35) and 4.20 (95% CI, 1.54 to 11.44) for falling below a clinically protective level of 0.1 IU/mL for tetanus and diphtheria antibodies at age 7 years.<h3>Conclusion</h3>Elevated exposures to PFCs were associated with reduced humoral immune response to routine childhood immunizations in children aged 5 and 7 years.
Endocarditis Due to Serratia Marcescens
Authors: John D. Denney, Donald Kaye, Jack W. C. Hagstrom
Journal: New England Journal of Medicine (1967)

THREE cases of bacterial endocarditis produced by Serratia marcescens have been reported.1 2 3 This paper describes an additional case.Case ReportM.R., a 59-year-old woman, was transferred to the New York Hospital because of bacteremia of 1 month's duration. Two months before transfer, many teeth had been extracted. One month later she was admitted to another hospital because of fever (temperature of 104°F.) and shaking chills. S. marcescens was isolated from 4 blood cultures, and she was treated with penicillin, streptomycin and chloramphenicol. During 1 month of therapy there was no clinical response and blood cultures remained positive for S. marcescens . . .
The Validity of 99mTc-Pyridoxylideneglutamate (P.G.) Cholescintigraphy as a Diagnostic Test for Cholecystitis
Authors: ROBERT C. STADALNIK, JESS F. KRAUS, NATHANIEL M. MATOLO, KENNETH A. KROHN
Journal: Clinical Nuclear Medicine (1978)

The purpose of this investigation was to determine the diagnostic value (validity) of technetium-99mpyridoxylideneglutamate cholescintigraphy (99mTc- PGC) in patients with and without cholecystitis and to compare its validity to those of oral cholecystography (OC) and ultrasonography (US). 99mTc-PGC was applied to 50 patients with acute, subacute, and/or chronic cholecystitis with cystic duct obstruction proven histologically and operatively, and also to 27 non-diseased volunteers and 43 patients with right upper quadrant abdominal pain who subsequently were proven free of gallbladder disease. In addition, 38 patients had OC, and 31 had US performed. The results shows that the sensitivity and specificity of 99mTc-PGC were 100%. Whereas for OC the sensitivity was 87%, specificity was 100%. For US the sensitivity was 70%, and specificity was 93%. The repeatability of 99mTc-PGC, OC, and US were 100%, 94% and 81% respectively. These data show that 99mTc-pyridoxylideneglutamate cholescintigraphy is a valid diagnostic tool in the evaluation of patients with cholecystitis, and is also safe and simple.
Arterial pressure and heart rate responses to calcium channel blockers administered in the brainstem in rats.
Authors: S Higuchi, A Takeshita, N Ito, T Imaizumi, H Matsuguchi, M Nakamura
Journal: Circulation Research (1985)

The study examined the possibility that organic calcium channel blockers alter autonomic nervous system function by acting on brainstem neurons. Intracisternal administration of diltiazem or verapamil produced dose-related decreases in arterial pressure and heart rate. Diltiazem administered by drop on the dorsal surface of the brainstem at the obex or microinjected directly into the nucleus tractus solitarius also decreased arterial pressure and heart rate. The responses were absent or markedly attenuated in rats previously treated with 6-hydroxydopamine or with bilateral electrolytic lesions of the nucleus tractus solitarius but were preserved in rats treated with atropine or with sham nucleus tractus solitarius lesions. Nifedipine or ethylene glycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid administered on the dorsal surface of the brainstem at the obex decreased arterial pressure and heart rate. Vehicle, acid saline, or sucrose solution failed to alter arterial pressure or heart rate. These results suggest that organic calcium channel blockers produce excitation of the nucleus tractus solitarius neurons, directly or indirectly, which results in the withdrawal of sympathetic nervous activity and in the decrease in arterial pressure and heart rate. The results suggest that calcium ion plays an important role in maintaining integral function of neurons in the brainstem, particularly in the nucleus tractus solitarius.
Colon Cancer, Version 3.2014
Authors: Al B. Benson, Alan P. Venook, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Moon J. Fenton, Charles S. Fuchs, Jean L. Grem, Steven Hunt, Ahmed Kamel, Lucille A. Leong, Edward Lin, Wells Messersmith, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Kristina M. Gregory, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2014)

The NCCN Guidelines for Colon Cancer address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease,and survivorship. This portion of the guidelines focuses on the use of systemic therapy in metastatic disease. The management of metastatic colorectal cancer involves a continuum of care in which patients are exposed sequentially to a variety of active agents, either in combinations or as single agents. Choice of therapy is based on the goals of treatment, the type and timing of prior therapy, the different efficacy and toxicity profiles of the drugs, the mutational status of the tumor, and patient preference.
Primary Amoebic Meningoencephalitis in Britain
Authors: J. Apley, S. K. R. Clarke, A. P. C. H. Roome, S. A. Sandry, G. Saygi, B. Silk, D. C. Warhurst
Journal: BMJ (1970)

Meningoencephalitis proved to be due to an amoeba (Naegleria) has been diagnosed in Great Britain for the first time. The first patient (a boy of 2) survived longer than any previously recorded cases, but in spite of early diagnosis and treatment he died 15 days after the onset of meningeal symptoms. Two other children who were exposed to the same possible source of infection (a warm, muddy puddle) had similar symptoms and developed mild meningitis. A naegleria was isolated from the cerebrospinal fluid of one of them. Both recovered after treatment with amphotericin.
Early assessment of coronary artery bypass graft patency by high dose dipyridamole echocardiography
Authors: Angelo S. Bongo, Leonardo Bolognese, Gianni Sarasso, Carmelo Cernigliaro, Donatella Aralda, Andrea Campi, Cristina Piccinino, Antonietta Carfora, Lidia Rossi, Paolo Rossi
Journal: Journal of the American College of Cardiology (1991)