tbuckley/cabot-search huggingface dataset:
Physical and Functional Interaction Between Calcineurin and the Cardiac L-Type Ca <sup>2+</sup> Channel
Authors: Samvit Tandan, Yanggan Wang, Thomas T. Wang, Nan Jiang, Duane D. Hall, Johannes W. Hell, Xiang Luo, Beverly A. Rothermel, Joseph A. Hill
Journal: Circulation Research (2009)

The L-type Ca(2+) channel (LTCC) is the major mediator of Ca(2+) influx in cardiomyocytes, leading to both mechanical contraction and activation of signaling cascades. Among these Ca(2+)-activated cascades is calcineurin, a protein phosphatase that promotes hypertrophic growth of the heart. Coimmunoprecipitations from heart extracts and pulldowns using heterologously expressed proteins provided evidence for direct binding of calcineurin at both the N and C termini of alpha(1)1.2. At the C terminus, calcineurin bound specifically at amino acids 1943 to 1971, adjacent to a well-characterized protein kinase (PK)A/PKC/PKG phospho-acceptor site Ser1928. In vitro assays demonstrated that calcineurin can dephosphorylate alpha(1)1.2. Channel function was increased in voltage-clamp recordings of I(Ca,L) from cultured cardiomyocytes expressing constitutively active calcineurin, consistent with previous observations in cardiac hypertrophy in vivo. Conversely, acute suppression of calcineurin pharmacologically or with specific peptides decreased I(Ca,L). These data reveal direct physical interaction between the LTCC and calcineurin in heart. Furthermore, they demonstrate that calcineurin induces robust increases in I(Ca,L) and highlight calcineurin as a key modulator of pathological electrical remodeling in cardiac hypertrophy.
A Knotted Umbilical Cord.
Authors: Arthur MacNeal
Journal: JAMA (1896)

Berwyn, Ill., Jan. 16, 1896. <h3>To the Editor:</h3> —A rather unique case occurred in my obstetric practice at this place last week. Mrs. S., who was under my care and expected to be confined late in February, sent for me early the morning of January 10. Upon arriving at the house I found my patient in the midst of labor, regular pains, very frequent and severe. Examination revealed dilated os, breech presentation, no evidence of fetus being alive. A short time later delivery was accomplished. The fetus was dead. Stage of development was that of a seven-months' fetus. It weighed about three pounds, and gave evidence of having been dead some little time, as it was considerably macerated. Upon examination of the cord I found a tight knot about midway between fetus and placenta. This undoubtedly had caused fetal death, which precipitated labor. The mother had not felt life for
Percutaneous Mitral Valvuloplasty Versus Surgical Treatment in Mitral Stenosis With Severe Tricuspid Regurgitation
Authors: Hyun Song, Duk-Hyun Kang, Jeong Hoon Kim, Kyoung-Min Park, Jong-Min Song, Kee-Joon Choi, Myeong-Ki Hong, Cheol Hyun Chung, Jae-Kwan Song, Jae-Won Lee, Seong-Wook Park, Seung-Jung Park
Journal: Circulation (2007)

The persistence of significant tricuspid regurgitation (TR) after percutaneous mitral valvuloplasty (PMV) is known to be an independent predictor of adverse outcome in mitral stenosis (MS). However, it remains unclear whether mitral valve (MV) surgery combined with surgical correction of TR is the better treatment option than PMV in patients with severe MS and severe functional TR.We included a total of 92 consecutive patients (18 men, age 49+/-13 years) with severe MS and severe functional TR, who were potential candidates for PMV from 1997 to 2005, and the exclusion criteria were defined as the presence of left atrial thrombi, mitral regurgitation > or = grade 3, echo score > 10, and left ventricular ejection fraction (EF) < 35%. PMV was performed on 48 patients (PMV group), and MV surgery combined with tricuspid valve (TV) repair was performed on 44 patients (TVP group). The clinical events were defined as death, repeat surgical or percutaneous intervention, and readmission because of heart failure. There were no significant differences between the 2 groups in terms of gender, baseline EF, and baseline severity of pulmonary hypertension, but patients in the TVP group were older and had a higher echo score and a higher incidence of atrial fibrillation than those in the PMV group. During follow-up of 57+/-35 months, 2 deaths occurred in the TVP group, and there were 2 deaths, 7 cases of heart failure requiring surgical intervention in the PMV group. The difference of event rates between the 2 groups showed borderline significance (P=0.05), but no difference in mortality was observed. The estimated actuarial 7-year event-free survival rate was 77+/-8% in the PMV group and 95+/-3% in the TVP group. Severe TR was improved to mild or absent TR in 43 (98%) patients in the TVP group, and this was significantly higher than in the PMV group (22/48, 46%; P<0.001). In the TVP group, the right ventricle (RV) size was significantly decreased in 18 (90%) patients among 20 patients with preoperative significant RV enlargement. On stepwise multivariate logistic regression analysis, TVP group and baseline sinus rhythm were independent predictors for improvement of TR (P<0.001).TV repair combined with MV surgery was related to better clinical outcomes than PMV alone, and we recommend that this surgical option should be considered preferentially in severe MS with severe functional TR, especially if atrial fibrillation or enlarged RV is associated.
Chemoprevention of Intestinal Tumorigenesis in APCmin/+ Mice by Silibinin
Authors: Subapriya Rajamanickam, Balaiya Velmurugan, Manjinder Kaur, Rana P. Singh, Rajesh Agarwal
Journal: Cancer Research (2010)

Abstract Chemoprevention is a practical and translational approach to reduce the risk of various cancers including colorectal cancer (CRC), which is a major cause of cancer-related deaths in the United States. Accordingly, here we assessed chemopreventive efficacy and associated mechanisms of long-term silibinin feeding on spontaneous intestinal tumorigenesis in the APCmin/+ mice model. Six-week-old APCmin/+ mice were p.o. fed with vehicle control (0.5% carboxymethyl cellulose and 0.025% Tween 20 in distilled water) or 750 mg silibinin/kg body weight in vehicle for 5 d/wk for 13 weeks and then sacrificed. Silibinin feeding strongly prevented intestinal tumorigenesis in terms of polyp formation in proximal, middle, and distal portions of small intestine by 27% (P &amp;lt; 0.001), 34% (P &amp;lt; 0.001), and 49% (P &amp;lt; 0.001), respectively. In colon, we observed 55% (P &amp;lt; 0.01) reduction in number of polyps by silibinin treatment. In size distribution analysis, silibinin showed significant decrease in large-size polyps (&amp;gt;3 mm) by 66% (P &amp;lt; 0.01) and 88% (P &amp;lt; 0.001) in middle and distal portions of small intestine, respectively. More importantly, silibinin caused a complete suppression in &amp;gt;3 mm sized polyps and 92% reduction in &amp;gt;2 to 3 mm sized polyps in colon. Molecular analyses of polyps suggested that silibinin exerts its chemopreventive efficacy by inhibiting cell proliferation, inflammation, and angiogenesis; inducing apoptosis; decreasing β-catenin levels and transcriptional activity; and modulating the expression profile of cytokines. These results show for the first time the efficacy and associated mechanisms of long-term p.o. silibinin feeding against spontaneous intestinal tumorigenesis in the APCmin/+ mice model, suggesting its chemopreventive potential against intestinal cancers including CRC. Cancer Res; 70(6); 2368–78
Epidermal keratinocyte-derived basophil promoting activity. Role of interleukin 3 and soluble CD23.
Authors: A H Dalloul, M Arock, C Fourcade, J Y Béranger, P Jaffray, P Debré, M D Mossalayi
Journal: Journal of Clinical Investigation (1992)

Human epidermal keratinocytes (EK) secrete factors able to sustain the proliferation of early myeloid cells and, in particular, the generation of basophils. This activity was previously attributed to IL-3, although no definitive in situ demonstration of this cytokine was provided. In regard to the possible physiological relevance of these data, we investigated herein the nature of EK-derived factors responsible for basophil promotion. Our data show that EK-derived supernatants (EK-sup) contain IL-3 as well as soluble CD23 (sCD23), both known for their colony stimulating activity. Messenger RNA for IL-3 and CD23 were also detected in EK. Blocking experiments using specific neutralizing monoclonal antibodies (mAb) further indicate that EK-derived basophil promoting activity is mainly due to the presence of IL-3 and sCD23 in EK-sup. Furthermore, by contrast to IL-3, sCD23 secretion by EK is cortisone sensitive and highly enhanced by IL-4, suggesting distinct regulatory mechanisms for their production.
<i>In vivo</i> Knockdown of the Androgen Receptor Results in Growth Inhibition and Regression of Well-Established, Castration-Resistant Prostate Tumors
Authors: Robert Snoek, Helen Cheng, Katia Margiotti, Latif A. Wafa, Charmaine A. Wong, Erica Chan Wong, Ladan Fazli, Colleen C. Nelson, Martin E. Gleave, Paul S. Rennie
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Progression to the castration-resistant state is the incurable and lethal end stage of prostate cancer, and there is strong evidence that androgen receptor (AR) still plays a central role in this process. We hypothesize that knocking down AR will have a major effect on inhibiting growth of castration-resistant tumors. Experimental Design: Castration-resistant C4-2 human prostate cancer cells stably expressing a tetracycline-inducible AR-targeted short hairpin RNA (shRNA) were generated to directly test the effects of AR knockdown in C4-2 human prostate cancer cells and tumors. Results: In vitro expression of AR shRNA resulted in decreased levels of AR mRNA and protein, decreased expression of prostate-specific antigen (PSA), reduced activation of the PSA-luciferase reporter, and growth inhibition of C4-2 cells. Gene microarray analyses revealed that AR knockdown under hormone-deprived conditions resulted in activation of genes involved in apoptosis, cell cycle regulation, protein synthesis, and tumorigenesis. To ensure that tumors were truly castration-resistant in vivo, inducible AR shRNA expressing C4-2 tumors were grown in castrated mice to an average volume of 450 mm3. In all of the animals, serum PSA decreased, and in 50% of them, there was complete tumor regression and disappearance of serum PSA. Conclusions: Whereas castration is ineffective in castration-resistant prostate tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and frequently cause tumor regression. This study is the first direct evidence that knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors that have already progressed to the castration-resistant state.
Direct-current Shock in Treatment of Drug-resistant Cardiac Arrhythmias
Authors: L. McDonald, L. Resnekov, K. O'Brien
Journal: BMJ (1964)

ment of ventricular fibrillation at the time of cardiac operations, and has proved successful at other times (McDonald et al., 1963). Lown et al. (1962b) have described the use of directcurrent shock both experimentally and in the treatment of patients with atrial and ventricular arrhythmias (Lown et al., 1962a). The use of direct current enables the shock to be applied at a precise moment in the cardiac cycle, since the charge is activated by the R wave of the electrocardiogram and timed to occur synchronously with it. Thus undesirable-effects such as ventricular fibrillation are avoided ; ventricular fibrillation may theoretically occur if the shock enters the cardiac cycle during the phase of ventricular repolarization. Lown's  cardioverter,l the unit that was used in this work, consists of a capacitor of 16 microfarads which is charged by a variable D.C. transformer and discharges over 2.5 milliseconds across an inductance coil, and the resistance of the body, to give an underdamped impulse.
Quantitative ultrasonic analysis of myocardium in patients with thalassemia major and iron overload.
Authors: F Lattanzi, P Bellotti, E Picano, F Chiarella, A Mazzarisi, C Melevendi, G Forni, L Landini, A Distante, C Vecchio
Journal: Circulation (1993)

Patients with beta-thalassemia major present with severe anemia and need continuous transfusion therapy. The consequent iron overload leads to hemochromatosis. Initial cardiac dysfunction has been documented even in thalassemics without clinical manifestations of heart failure as well as by conventional echocardiographic-Doppler techniques. The purpose of this study was to assess the acoustic quantitative properties of myocardium in patients with iron overload.Thirty-eight patients with beta-thalassemia major, without clinical signs of cardiac failure, and 20 age- and sex-matched young controls were studied by echocardiography. An on-line analysis of the ultrasonic radiofrequency signal was performed to obtain quantitative operator-independent measurements of the integrated backscatter (IB) signal of the ventricular septum and the posterior wall. The integrated values of the radiofrequency signal were normalized for the pericardial interface and expressed in percent (IB%). Thalassemic patients had been receiving transfusion therapy for 16 +/- 5 years and had received 313 +/- 138 transfusion units; they all had received chelation treatment (desferroxiamine) for 9 +/- 2 years. Patients and controls showed comparable values of echocardiographically assessed percent fractional shortening (32 +/- 3% versus 36 +/- 4%, p = NS), whereas thalassemics showed higher values of left ventricular mass index (118 +/- 30 versus 98 +/- 15 g/m2, p < 0.05). The IB% values were higher in patients with thalassemia major than in controls for both septum (35 +/- 14% versus 21 +/- 6%, p < 0.001) and posterior wall (16 +/- 6% versus 11 +/- 3%, p < 0.001). In thalassemic patients, no significant correlation was found between the septum IB% value and hematological parameters, such as the total number of transfusions (r = 0.2, p = NS) or the mean ferritin value (r = 0.1, p = NS). No significant correlation was also found between the septum IB% value and the echocardiographically assessed left ventricular mass index (r = 0.2, p = NS).These data demonstrate that myocardial reflectivity is abnormally increased in patients with thalassemia major under transfusion treatment, probably due to myocardial iron deposits and/or secondary structural changes. These quantitatively assessed abnormalities in regional reflectivity can be detected when conventional echocardiographic parameters of systolic left ventricular function are undistinguishable from normal controls.
CHRONIC CATARRHAL GASTRITIS.
Authors: HENRY M. LYMAN
Journal: JAMA (1897)

I desire to call your attention, this morning, to a number of patients who belong to a large class that will confront you during the whole of your active career as medical practitioners. The first one is a young woman, 25 years of age, who had typhoid fever about a year ago. She had been employed as a shop girl for seven years previous to her illness, but had considered herself in good health till a month before the attack. She says that she was very ill for a period of five weeks and "took a lot of strong medicine." Instead of recovering her normal vigor she has remained thin and feeble. Her heart, lungs, kidneys, spleen, liver and reproductive organs appear to be healthy, but she complains of lack of appetite, epigastric distension, frequent eructation for several hours after eating and constipation of the bowels. She is listless, depressed
Sudden Infant Death
Authors: Irene Garrow
Journal: JAMA (1974)

ABSTRACT To the Editor.— Your MEDICAL NEWS item on the progress in the explanation of sudden death in infancy (226:1291, 1973) reveals that little has been added to the knowledge of this condition since the reports published by Dr. Werne and myself in 1947 and 1953.I doubt Dr. Bergman's conclusion that because children made no sound, a laryngeal constriction was present. Our 1953 article in the American Journal of Pathology was a review of 12 patients who had been observed dying, had no gross findings at autopsy, and in whom microscopic findings were identical to those found dead. In these cases, only one was reported to have screamed. The remaining infants were observed to be gasping or breathing heavily. The parents were very explicit as to the excursions of the chest that meant that air was being exhaled and inhaled with vigor. We always asked these questions because we wished
A Useful Pharmacopeia
Authors: N. S. Davis
Journal: JAMA (1913)

of the foramen for three reasons. 1.If the needle docs not enter the foramen it will be blocked by (he great wing of the sphenoid. 2. If is sometimes possible to follow the under surface of the great wing und feel one's way into the foramen.:i.When the fornincn is entered with the needle in the high» position, its point, niter passing through the ganglion, is blocked by the anterior surface of the petrous portion of the temporal bone.When the needle is introduced nt too low a point, and its direction is consequently .revertical than WOltld be necessary with a higher insertion, the needle, if inserted loo far, may pass over the petrous portion of the temporal bone into the superior petroBal sinus or brain.
Effects of salicylate on intestinal absorption: in vitro and in vivo studies with enterotoxigenic micro-organisms.
Authors: V Burke, M Gracey
Journal: Gut (1980)

This study was done to determine whether salicylate could affect alterations in intestinal absorption induced by preparations of enterotoxigenic micro-organisms. It was found in rats that salicylate increased intestinal monosaccharide uptake in vitro and reversed the inhibitory effects induced by cell-free preparations of Staphylococcus sp., Candida sp. and Klebsiella sp. In vivo, salicylates increased net water absorption in rat jejunum exposed to cell-free preparations of various micro-organisms. Increase in net fluid flux occurred after subcutaneous injection only with bacteria which stimulate adenylate cyclase activity. These observations suggest that the absorptive and anti-secretory effects of aspirin are cyclic nucleotide dependent. The potential clinical role of salicylates as anti-secretory agents in diarrhoeal diseases, particularly in children, requires further investigation.
Oncolytic reovirus enhances rituximab-mediated antibody-dependent cellular cytotoxicity against chronic lymphocytic leukaemia
Authors: C Parrish, G B Scott, G Migneco, K J Scott, L P Steele, E Ilett, E J West, K Hall, P J Selby, D Buchanan, A Varghese, M S Cragg, M Coffey, P Hillmen, A A Melcher, F Errington-Mais
Journal: Leukemia (2015)

The naturally occurring oncolytic virus (OV), reovirus, replicates in cancer cells causing direct cytotoxicity, and can activate innate and adaptive immune responses to facilitate tumour clearance. Reovirus is safe, well tolerated and currently in clinical testing for the treatment of multiple myeloma, in combination with dexamethasone/carfilzomib. Activation of natural killer (NK) cells has been observed after systemic delivery of reovirus to cancer patients; however, the ability of OV to potentiate NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is unexplored. This study elucidates the potential of oncolytic reovirus for the treatment of chronic lymphocytic leukaemia (CLL), both as a direct cytotoxic agent and as an immunomodulator. We demonstrate that reovirus: (i) is directly cytotoxic against CLL, which requires replication-competent virus; (ii) phenotypically and functionally activates patient NK cells via a monocyte-derived interferon-α (IFNα)-dependent mechanism; and (iii) enhances ADCC-mediated killing of CLL in combination with anti-CD20 antibodies. Our data provide strong preclinical evidence to support the use of reovirus in combination with anti-CD20 immunotherapy for the treatment of CLL.
Concepts of Health and Disease: Interdisciplinary Perspectives
Authors: R. Coser
Journal: JAMA (1982)

This anthology is well done. It consists of essays mainly by medical contributors and philosophers focusing on problems of values underlying various assumptions about health and disease. A few contributions by social scientists, among others  economist Victor Fuchs and  sociologist Talcott Parsons, add some analytical specificity to  discussion.  All authors agree that both health and disease are difficult to define although it would be important to do so since, as several point out, one has to know what disease is if one wants to know what is to be treated. However, physicians do not treat only diseases, a fact to which Leon Kass objects. According to him, pregnancy and childbirth, abortion, or plastic surgery for purely cosmetic reasons should not be  concern of physicians. He objects to  definition of  World Health Organization (whose constitution is also reproduced here) that health is the state of
Metabolic Muscle Disease
Authors: Georgirene D. Vladutiu
Journal: Annals of Internal Medicine (1994)

Letters1 August 1994Metabolic Muscle DiseaseGeorgirene D. Vladutiu, PhDGeorgirene D. Vladutiu, PhDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-3-199408010-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with great interest the recent article on metabolic disease in adults by Talente and colleagues [1] and the accompanying editorial by Segal and Roth [2]. Laboratory testing for inborn errors of metabolism has been successfully extended to adults through cooperation between pediatric and adult clinical and laboratory services in academic medical centers.Our laboratory does about 1500 tests annually for metabolic disorders, such as lysosomal storage diseases, aminoacidopathies, and metabolic muscle disease in all age groups. Our core neuromuscular group bridges several departments, including neurology, pediatrics, rehabilitation medicine, and pathology, and every week reviews regionally ...References1. Talente GM, Coleman RA, Alter C, Baker L, Brown BI, Cannon RA, et al. Glycogen storage diseases in adults. Ann Intern Med. 1994; 120:218-26. Google Scholar2. Segal S, Roth KS. Inborn errors of metabolism: a new purview of internal medicine (Editorial). Ann Intern Med. 1994; 120:245-6. Google Scholar3. Taroni F, Verderio E, Dworzak F, Willems PJ, Cavadini P, Di Dontato S. Identification of a common mutation in the carnitine palmitoyltransferase II gene in familial recurrent myoglobinuria patients. Nat Genet. 1993; 4:314-20. Google Scholar4. Wallace DC. Mitochondrial genetics: a paradigm for aging and degenerative diseases? Science. 1992; 256:628-32. Google Scholar5. Vladutiu GD, Hogan K, Saponara I, Tassini L, Conroy J. Carnitine palmitoyl transferase deficiency in malignant hyperthermia. Muscle Nerve. 1993; 16:485-91. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1994Volume 121, Issue 3Page: 234KeywordsAutosomal dominant diseasesAutosomal recessive diseasesLipidsMetabolic disordersMusclesMyalgiaResearch laboratoriesSkeletal musclesTemperatureTransferases Issue Published: 1 August 1994 CopyrightCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...