tbuckley/cabot-search huggingface dataset:
Mechanisms of glycolytic inhibition in ischemic rat hearts.
Authors: M J Rovetto, W F Lamberton, J R Neely
Journal: Circulation Research (1975)

The mechanisms of glycolytic inhibition in ischemic myocardium were investigated in the isolated, perfused rat heart. Glycolysis was inhibited at the level of glyceraldehyde-3-phosphate dehydrogenase. The major factors that accounted for the glycolytic inhibition in the ischemic heart compared with the anoxic heart appeared to be higher tissue levels of lactate and H+ in the ischemic tissue. Increased extracellular pH inhibited glycolysis in anoxic and hypoxic hearts much more readily than it did in aerobic hearts. However, maintenance of both extracellular and intracellular pH caused only a modest acceleration of glycolysis in ischemic hearts. Accumulation of tissue lactate and inhibition of glycolysis were directly proportional to the reduction in coronary bloow flow in both anoxic and ischemic hearts. At intracellular lactate concentrations between 15 and 20 mM, glycolysis was inhibited under both conditions. Addition of either 10, 20, or 40 mM lactate to the perfusate inhibited glycolysis in aerobic, anoxic, and ischemic hearts. The effect of lactate did not appear to be mediated through changes in intracellular pH. It is concluded that accumulation of lactate represents a major factor in the inhibition of glycolysis that develops in ischemic hearts.
QSAR analysis and data extrapolation among mammals in a series of aliphatic alcohols.
Authors: M Tichý, V Trcka, Z Roth, M Krivucová
Journal: Environmental Health Perspectives (1985)

Concepts of QSAR analysis and biological similarity models are combined for use in extrapolation of LD50 values after IP application of a series of aliphatic alcohols (C1-C5) to mouse, hamster, rat, and guinea pig and rabbit. It has been found that although close correlation exists between LD50 values after IP and IV applications for mouse and rat, the QSARs obtained with LD50 after IV application are not suitable for a prediction of LD50 values after IP application for rabbit. Different transformation or distribution processes in mouse, rat, and rabbit after the two types of applications might be the reason. The LD50 values (expressed in mmole/m2 of body surface) seem to be independent of mammalian species used (at least within the mouse, rat, hamster, and probably guinea pig series). This fact makes it possible to predict reasonable values of LD50 after IP application for rabbit. Expression of toxicity in mmole/m2 of body surface may be useful in toxicological studies. The model of quantitative structure-activity-species relationships (QSASR) for the system of alcohols and animals chosen is proposed: log BAij = kj + lj log Xi log BAij = aj + bi log Zj where i denotes an alcohol, j an animal, BA being LD50 (mmole/m2) after IP application, X molecular connectivity 1 chi and Z body surface: body weight ratio. The model is based on the assumption that bi is independent of chemical structure (being zero or close to zero), ai is a function of molecular connectivity 1 chi, kj and lj being independent of animal species. These assumptions resulted from the statistical analysis of QSARs and allometric equations obtained under various conditions.
MDL-28170, a membrane-permeant calpain inhibitor, attenuates stunning and PKCε proteolysis in reperfused ferret hearts
Authors: Ferdinand Urthaler, Paul E Wolkowicz, Stanley B Digerness, Kevin D Harris, Alfred A Walker
Journal: Cardiovascular Research (1997)

This paper tests the hypothesis that calpains are activated in the ischemic (I)/reperfused (R) heart and contribute to myocardial stunning.Isolated ferret hearts were Langendorff perfused isovolumically, and subjected to 20 min of global I followed by 30 min of R in the presence or absence of 0.2 microM MDL-28170, a membrane-permeant calpain inhibitor. Right trabeculae then were isolated from these hearts, skinned chemically, and pCa(2+)-force curves obtained. Samples of left ventricle were extracted subjected to SDS-PAGE, and Western analyzed for PKC epsilon and PKM epsilon.Perfused ferret hearts exhibit a 43% decline in left ventricular developed pressure during R. Pre-treatment of hearts with MDL-28170 prior to I significantly improves function during R. Trabecular myofilaments from normal hearts have a KD for Ca2+ of 6.27 +/- 0.06; I/R decreased the KD to 6.09 +/- 0.04; trabeculae from I/R hearts pre-treated with MDL-28170 have a KD of 6.28 +/- 0.04. Western analysis shows ferret hearts to contain a single approximately equal to 96 kDa species of PKC epsilon. I/R hearts contain the native PKC epsilon and a approximately equal to 25 kDa smaller species of PKC epsilon which corresponds to PKM epsilon, the calpain proteolyzed form of PKC epsilon. Pre-treatment of I/R hearts with MDL-28170 markedly diminishes PKM epsilon in reperfused hearts.Mechanical stunning during R is sensitive to MDL-28170. Depressed mechanical function is reflected in a hyposensitization of trabecular myofilaments to Ca2+. Western analysis shows that PKM epsilon is present in R hearts.
Improving Physician Well-Being
Authors: Sean T. Gregory, Terri Menser
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Sexuality and Intimacy After Definitive Treatment and Subsequent Androgen Deprivation Therapy for Prostate Cancer
Authors: Celestia S. Higano
Journal: Journal of Clinical Oncology (2012)

There are more than 2 million prostate cancer survivors in the United States. Primary therapy with surgery or radiation results in permanent changes in sexual function. More than half of these men are subsequently treated with androgen deprivation therapy (ADT) at some point. The addition of ADT further compromises sexuality, intimacy, and a couple's relationship. This review will highlight the challenges faced by patients and couples and reveal the tremendous need for better education of physicians, patients, and couples as well as for more research in sexuality and intimacy with the goal of improving quality of life for this large population of survivors. Suggestions for clinicians to better help patients and their partners regarding sexuality and intimacy are offered.
Implantable Cardioverter/Defibrillator Therapy in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Thomas Wichter, Matthias Paul, Christian Wollmann, Tayfun Acil, Petra Gerdes, Obaidullah Ashraf, Tonny D.T. Tjan, Rasijd Soeparwata, Michael Block, Martin Borggrefe, Hans H. Scheld, Günter Breithardt, Dirk Böcker
Journal: Circulation (2004)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of ventricular tachycardia (VT) and cardiac arrest in young patients. We hypothesized that treatment with implantable cardioverter/defibrillators (ICDs) is safe and improves the long-term prognosis of ARVC patients at high risk of sudden death.Sixty patients with ARVC (aged 43+/-16 years) were treated with transvenous ICD systems. Despite a higher number of right ventricular sites tested for adequate lead positions (P<0.05), lower R-wave amplitudes (P<0.001) were achieved in ARVC patients compared with other entities. During follow-up of 80+/-43 months (396 patient-years), event-free survival was 49%, 30%, 26%, and 26% for appropriate ICD therapies and 79%, 64%, 59%, and 56% for potentially fatal VT (>240 bpm) after 1, 3, 5, and 7 years, respectively. Multivariate analysis identified extensive right ventricular dysfunction as an independent predictor of appropriate ICD discharge. Fifty-three adverse events occurred in 37 patients during the perioperative (n=10) or follow-up (n=43) period, mainly related to the leads (n=31 in 21 patients). No lead perforation was observed. Freedom from adverse events was 90%, 78%, 56%, and 42% and freedom from lead-related complications was 95%, 85%, 74%, and 63% after 1, 3, 5, and 7 years, respectively.These results strongly suggest an improvement in long-term prognosis by ICD therapy in high-risk patients with ARVC. However, meticulous placement and long-term observation of transvenous lead performance with focus on sensing function are required for the prevention and/or early recognition of disease progression and lead-related morbidity during long-term follow-up of ICD therapy in ARVC.
Video-Assisted Thoracic Surgery Lobectomy: Report of CALGB 39802—A Prospective, Multi-Institution Feasibility Study
Authors: Scott J. Swanson, James E. Herndon, Thomas A. D'Amico, Todd L. Demmy, Robert J. McKenna, Mark R. Green, David J. Sugarbaker
Journal: Journal of Clinical Oncology (2007)

To evaluate the technical feasibility and safety of video-assisted thoracic surgery (VATS) lobectomy for small lung cancers.The Cancer and Leukemia Group B 39802 trial was a prospective, multi-institutional study designed to elucidate the technical feasibility of VATS in early non-small-cell lung cancer (NSCLC) using a standard definition for VATS lobectomy (one 4- to 8-cm access and two 0.5-cm port incisions) that mandated videoscopic guidance and a traditional hilar dissection without rib spreading. Between 1998 and 2001, 128 patients with peripheral lung nodules < or = 3 cm in size with suspected NSCLC were prospectively registered for VATS lobectomy.One hundred twenty-seven patients (66 males and 61 females; median age, 66 years; range, 37 to 86 years), with a performance status of 0 (74%) or 1 (26%), underwent surgery. Patients with lymph nodes more than 1 cm by computed tomography scan underwent mediastinal lymph node sampling to rule out N2 disease. One hundred eleven patients (87%) had stage I lung cancer, and 96 (86.5%) of these 111 patients underwent successful VATS lobectomies. The median procedure length was 130 minutes (range, 47 to 428 minutes), and median chest tube duration was 3 days (range, 1 to 14 days). Fifty-eight (60%) of 97 patients underwent diagnostic biopsy at lobectomy. Within 30 days, three (2.7%) of 111 patient deaths occurred, none of which were directly related to VATS technique; seven (7.4%) of 95 patients had grade 3 or greater complications, with only one case of bleeding.A standardized approach to VATS lobectomy as specifically defined with avoidance of rib spreading is feasible.
Intracellular &lt;italic&gt;p&lt;/italic&gt;H of the Ehrlich Ascites Tumor Cell&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Doris T. Poole, Thomas C. Butler, William J. Waddell
Journal: JNCI Journal of the National Cancer Institute (1964)

A method is described for the measurement of the intracellular pH of ascites tumor cells in vitro. The calculation of intracellular pH was based on the distribution between intracellular and extracellular water of the weak acid, 5,5-dimethyl-2,4-oxazolidinedione-2-C14. Inulin-carboxyl-C14 was used to measure extracellular water. A study was made of the intracellular pH of the Ehrlich ascites tumor cell as it was affected by variation of carbon dioxide tension in a bicarbonate buffer, by variation of pH in bicarbonate buffers at constant carbon dioxide tension, and by variation of pH in phosphate buffers at low carbon dioxide tension.
Interaction of C4-binding protein with cell-bound C4b. A quantitative analysis of binding and the role of C4-binding protein in proteolysis of cell-bound C4b.
Authors: T Fujita, N Tamura
Journal: The Journal of Experimental Medicine (1983)

Purified C4-binding protein (C4-bp) was shown to bind to cell-bound C4b by radioactive tracer techniques. With EAC4 bearing greater than 3,000 C4b-molecules/cell, the number of C4-bp molecules bound was directly proportional to the number of C4b molecule on the cell surface; EAC4 bearing less than 3,000 C4b-molecules/cell bound a very small amount of C4-bp. Scatchard analysis of binding of C4-bp indicated an equilibrium constant of 4.6 X 10(8) L/M and a maximum of 0.43 C4-bp molecules bound per C4b molecule, equivalent to an average of one molecule of C4-bp per two or three molecules of C4b. Fluid-phase C4b inhibited the binding of C4-bp to cell-bound C4b in a dose-dependent manner, whereas native C4 had little effect. C2 inhibited this binding and also released C4-bp from EAC4,C4-bp. However, C2 was 27 times less effective than unlabeled C4-bp on a molar basis and a considerable amount of C4-bp remained bound to C4b on the cell surface even in the presence of a large excess of C2. We also examined the cofactor activity of C4-bp in the cleavage of cell-bound C4b by C3b/C4b inactivator (I). Cleavage of the alpha' chain of C4b on the cell surface by I alone was incomplete and an intermediate cleavage product, alpha-75, was observed. When C4-bp bound to C4b on the cell surface, the alpha' chain of the C4b cleaved into three fragments, alpha 2, alpha 3, and alpha 4. The alpha 3, alpha 4, beta, and gamma peptides (C4c) were released into the fluid phase, and the alpha 2 fragment (C4d) remained linked covalently to the cell membrane via an ester bond. In some situations, therefore, C4-bp enhances the proteolytic activity of I on cell-bound C4b.
Gigantism and Acromegaly Due to Xq26 Microduplications and <i>GPR101</i> Mutation
Authors: Giampaolo Trivellin, Adrian F Daly, Fabio R Faucz, Bo Yuan, Liliya Rostomyan, Darwin O Larco, Marie Helene Schernthaner-Reiter, Eva Szarek, Letícia F Leal, Jean-Hubert Caberg, Emilie Castermans, Chiara Villa, Aggeliki Dimopoulos, Prashant Chittiboina, Paraskevi Xekouki, Nalini Shah, Daniel Metzger, Philippe A Lysy, Emanuele Ferrante, Natalia Strebkova, Nadia Mazerkina, Maria Chiara Zatelli, Maya Lodish, Anelia Horvath, Rodrigo Bertollo de Alexandre, Allison D Manning, Isaac Levy, Margaret F Keil, Maria de la Luz Sierra, Leonor Palmeira, Wouter Coppieters, Michel Georges, Luciana A Naves, Mauricette Jamar, Vincent Bours, T John Wu, Catherine S Choong, Jerome Bertherat, Philippe Chanson, Peter Kamenický, William E Farrell, Anne Barlier, Martha Quezado, Ivana Bjelobaba, Stanko S Stojilkovic, Jurgen Wess, Stefano Costanzi, Pengfei Liu, James R Lupski, Albert Beckers, Constantine A Stratakis
Journal: New England Journal of Medicine (2014)

Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood.We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly.We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein-coupled receptor, was overexpressed in patients' pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone-producing cells.We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).
Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis
Authors: Lawrence Anderson, George J. Schmieder, W. Philip Werschler, Eduardo H. Tschen, Mark R. Ling, Dow B. Stough, Janelle Katsamas
Journal: Journal of the American Academy of Dermatology (2009)
Metabolic Regulation of T Lymphocytes
Authors: Nancie J. MacIver, Ryan D. Michalek, Jeffrey C. Rathmell
Journal: Annual Review of Immunology (2013)

T cell activation leads to dramatic shifts in cell metabolism to protect against pathogens and to orchestrate the action of other immune cells. Quiescent T cells require predominantly ATP-generating processes, whereas proliferating effector T cells require high metabolic flux through growth-promoting pathways. Further, functionally distinct T cell subsets require distinct energetic and biosynthetic pathways to support their specific functional needs. Pathways that control immune cell function and metabolism are intimately linked, and changes in cell metabolism at both the cell and system levels have been shown to enhance or suppress specific T cell functions. As a result of these findings, cell metabolism is now appreciated as a key regulator of T cell function specification and fate. This review discusses the role of cellular metabolism in T cell development, activation, differentiation, and function to highlight the clinical relevance and opportunities for therapeutic interventions that may be used to disrupt immune pathogenesis.
Baclofen therapy for chronic hiccup
Authors: C Guelaud, T Similowski, JL Bizec, J Cabane, WA Whitelaw, JP Derenne
Journal: European Respiratory Journal (1995)

Chronic hiccup is a rare but potentially severe condition, that can be symptomatic of a variety of diseases, or idiopathic. Many therapeutic interventions have been reported, most often as case reports. Among other drugs, baclofen has been suggested as a therapy for chronic hiccup. In a large series of patients, we have evaluated its therapeutic position. In patients with chronic hiccup, defined as hiccup spell or recurring hiccup attacks lasting more than 7 days, investigation of the upper gastro-oesophageal tract (fibroscopy, manometry, and pH monitoring) was systematically performed. Most patients had tried numerous drugs in the past, without success. Baclofen was used as a first treatment in patients without evidence of any gastro-oesophageal disease (n = 17), and was undertaken only after full treatment of such disease (n = 55) had failed to solve the hiccup problem (n = 20). Baclofen has, therefore, been administered to 37 patients with chronic hiccup (average duration 4.6 yrs). Baclofen produced a long-term complete resolution (18 cases) or a considerable decrease (10 cases) of hiccups in 28 of the 37 patients. There was no significant difference between patients with or without gastro-oesophageal disease. We conclude that so-called idiopathic chronic hiccup often results from gastro-oesophageal abnormalities. Also, if controlled studies confirm our encouraging results, baclofen can be a major element in the treatment of chronic hiccup that is idiopathic, or that cannot be helped by treatment of gastro-oesophageal diseases.
Production of nitric oxide (NO) in intrathoracic airways of normal humans.
Authors: I Tsujino, K Miyamoto, M Nishimura, H Shinano, H Makita, S Saito, T Nakano, Y Kawakami
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

To gain insight into the source of exhaled nitric oxide (NO) in normal humans, we examined the effects of respiratory pattern on the concentration of NO in exhaled air while subjects were wearing a noseclip and then under endotracheal intubation, using a specially designed gas sampling system to separate exhaled air into two fractions: the initially exhaled 200 ml (Fraction 1; F1), and the remainder (Fraction 2; F2). We also examined the effect of hypoxic gas inhalation (F(I)O2 = 0.1, 3 min) on the concentration of exhaled NO. The concentration of exhaled NO measured with a chemiluminescence NO analyzer was significantly lower with intubation, by 59.2 +/- 10.6% (mean +/- SD) (F1) and 54.4 +/- 8.0% (F2), than without intubation. The concentration of NO in F1 was consistently higher than that in F2 with or without intubation. With breath holding, the concentration of NO increased markedly only in F1. In contrast, prolongation of the expiratory phase slightly but significantly increased the concentration of NO only in F2. Inhalation of hypoxic gas did not cause any significant change in NO concentration in either fraction. These data indicate that in normal humans wearing a noseclip, about 40 to 45% of NO in exhaled air originates from the lungs, particularly from intrathoracic airways. The concentration of exhaled NO collected from subjects wearing a noseclip is not affected by hypoxic gas inhalation.
SIGNIFICANCE OF BIVALENCE OF ANTIBODY IN VIRAL NEUTRALIZATION
Authors: Robert W. Rosenstein, Alfred Nisonoff, Jonathan W. Uhr
Journal: The Journal of Experimental Medicine (1971)

The role of bivalence of antibody in its capacity to neutralize virus was studied with rabbit antibodies to the bacteriophage, phiX174. Univalent Fab or Fab' fragments of IgG isolated from antiviral antisera obtained early in the immunization schedule had virtually no activity compared to that of the intact IgG. When the antibodies were isolated from antisera of the same rabbits several months later, the univalent fragments and IgG were essentially equal in activity. The results are interpreted on the basis that an IgG molecule, because of its bivalence, has a higher effective combining affinity (avidity) than a univalent fragment. After prolonged immunization, however, the affinity of univalent antibody becomes sufficiently high that it exceeds a threshold value, above which further increase in affinity, through bivalence, is no longer significant. The results could explain the variability in relative effectiveness of univalent antibodies observed in previous studies. These data, and the fact that F(ab')(2) fragments from either "early" or "late" antisera were as effective as IgG, indicate that fragment Fc is not a significant factor in neutralization. No differences in dissociation from the virus of univalent antibody from early and late antisera could be demonstrated by dilution at temperatures up to 47 degrees C. The attachment at sites of neutralization on the virus appears to be functionally almost irreversible in this system.