tbuckley/cabot-search huggingface dataset:
Endothelial Nitric Oxide Synthase Limits Left Ventricular Remodeling After Myocardial Infarction in Mice
Authors: Marielle Scherrer-Crosbie, Roman Ullrich, Kenneth D. Bloch, Hiroshi Nakajima, Boris Nasseri, H. Thomas Aretz, Merry L. Lindsey, Anne-Claire Vançon, Paul L. Huang, Richard T. Lee, Warren M. Zapol, Michael H. Picard
Journal: Circulation (2001)

Background To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling after myocardial infarction (MI), the impact of left anterior descending coronary artery ligation on LV size and function was compared in 2- to 4-month-old wild-type (WT) and NOS3-deficient mice (NOS3 −/− ). Methods and Results Two days after MI, both strains of mice had a similar LV size, fractional shortening, and ejection fraction by echocardiography. Twenty-eight days after MI, both strains had dilated LVs with decreased fractional shortening and lower ejection fractions. Although the infarcted fraction of the LV was similar in both strains, LV end-diastolic internal diameter, end-diastolic volume, and mass were greater, but fractional shortening, ejection fraction, and the maximum rate of developed LV pressure (dP/dt max ) were lower in NOS3 −/− than in WT mice. Impairment of diastolic function, as measured by the time constant of isovolumic relaxation (τ) and the maximum rate of LV pressure decay (dP/dt min ), was more marked in NOS3 −/− than in WT mice. Mortality after MI was greater in NOS3 −/− than in WT mice. Long-term administration of hydralazine normalized blood pressure in NOS3 −/− mice, but it did not prevent the LV dilatation, impaired systolic and diastolic function, and increased LV mass that followed MI. In WT mice, capillary density and myocyte width in the nonischemic portion of the LV did not differ before and 28 days after MI, whereas in NOS3 −/− mice, capillary density decreased and myocyte width increased after MI, whether or not hydralazine was administered. Conclusions These results suggest that the presence of NOS3 limits LV dysfunction and remodeling in a murine model of MI by an afterload-independent mechanism, in part by decreasing myocyte hypertrophy in the remote myocardium.
Construction of a D2.B6-Fv-2&lt;sup&gt;r&lt;/sup&gt; Congenic Mouse Strain: Nonlethality of the Homozygous &lt;italic&gt;Fv-2&lt;sup&gt;r&lt;/sup&gt;&lt;/italic&gt; Genotype&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Mark Dizik, Rosemary W. Elliott, Frank Lilly
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Construction of a D2.B6-Fv-2r Congenic Mouse Strain: Nonlethality of the Homozygous Fv-2r Genotype Get access Mark Dizik, Mark Dizik 4Department of. Genetics, Albert Einstein College of Medicine. Yeshiva University, Bronx, N.Y. 10461. Search for other works by this author on: Oxford Academic PubMed Google Scholar Rosemary W. Elliott, Rosemary W. Elliott 5Department of Molecular Biology, Roswell Park Memorial Institute, Buffalo, N.Y. 14263. Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank Lilly Frank Lilly 6 4Department of. Genetics, Albert Einstein College of Medicine. Yeshiva University, Bronx, N.Y. 10461. 6Address reprint requests toDr. Lilly. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 66, Issue 4, April 1981, Pages 755–760, https://doi.org/10.1093/jnci/66.4.755 Published: 01 April 1981 Article history Received: 25 June 1980 Accepted: 14 October 1980 Published: 01 April 1981
Entecavir plus tenofovir combination as rescue therapy in pre-treated chronic hepatitis B patients: An international multicenter cohort study
Authors: Jorg Petersen, Vlad Ratziu, Maria Buti, Harry L.A. Janssen, Ashley Brown, Pietro Lampertico, Jan Schollmeyer, Fabien Zoulim, Heiner Wedemeyer, Martina Sterneck, Thomas Berg, Christoph Sarrazin, Marc Lutgehetmann, Peter Buggisch
Journal: Journal of Hepatology (2011)
Effect of Tamoxifen on Serum Insulinlike Growth Factor I Levels in Stage I Breast Cancer Patients
Authors: M. Pollak, J. Costantino, C. Polychronakos, S.-A. Blauer, H. Guyda, C. Redmond, B. Fisher, R. Margolese
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Effect of Tamoxifen on Serum Insulinlike Growth Factor I Levels in Stage I Breast Cancer Patients Get access Michael Pollak, Michael Pollak * Department of Oncology and Medicine, McGill University and the Jewish General HospitalMontreal, PQ, Canada. Correspondence to: Michael Pollak, M.D., Department of Oncology, Jewish General Hospital, 3755 Chemin de la Cote St. Catherine, Montreal, PQ, Canada H3T 1E2. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph Costantino, Joseph Costantino National Surgical Adjucant Breast and Bowel Project HeadquartersPittsburgh, PA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Constantin Polychronakos, Constantin Polychronakos Polypeptide Hormone Laboratory, McGill UniversityMontreal, PQ, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Sue-Ann Blauer, Sue-Ann Blauer Search for other works by this author on: Oxford Academic PubMed Google Scholar Harvey Guyda, Harvey Guyda Polypeptide Hormone Laboratory, McGill UniversityMontreal, PQ, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Carol Redmond, Carol Redmond National Surgical Adjucant Breast and Bowel Project HeadquartersPittsburgh, PA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Bernard Fisher, Bernard Fisher National Surgical Adjucant Breast and Bowel Project HeadquartersPittsburgh, PA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Margolese Richard Margolese Department of Oncology and Surgery, McGill University and the Jewish General HospitalMontreal, PQ, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 21, 7 November 1990, Pages 1693–1697, https://doi.org/10.1093/jnci/82.21.1693 Published: 07 November 1990 Article history Received: 01 May 1990 Revision received: 03 August 1990 Accepted: 06 August 1990 Published: 07 November 1990
Randomized Trial of Cyclophosphamide, Doxorubicin, and Vincristine Versus Cisplatin and Etoposide Versus Alternation of These Regimens in Small-Cell Lung Cancer
Authors: M. Fukuoka, K. Furuse, N. Saijo, Y. Nishiwaki, H. Ikegami, T. Tamura, M. Shimoyama, K. Suemasu
Journal: JNCI Journal of the National Cancer Institute (1991)

Between April 1985 and May 1988, we conducted a randomized study comparing two standard chemotherapy regimens with the same regimens given on an alternating basis in patients with small-cell lung cancer. The patients were randomly assigned to receive cyclophosphamide at a dose of 800 mg/m2 intravenously (IV) on day 1, doxorubicin at 50 mg/m2 IV on day 1, and vincristine at 1.4 mg/m2 IV on day 1 (CAV); cisplatin at 80 mg/m2 IV on day 1 and etoposide at 100 mg/m2 IV on days 1, 3, and 5 (PE); or CAV alternating with PE (CAV/PE). Each regimen was repeated every 3-4 weeks. Three hundred patients were entered in the study, and 288 of them were eligible for analysis (97 for CAV, 97 for PE, and 94 for CAV/PE). The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%), while the complete response rates were similar (14%, 16%, and 15%, respectively). Nine (23%) of 39 patients who failed to respond to the initial CAV regimen responded to PE when they were crossed over. In contrast, only one (8%) of 13 patients responded to CAV after failing to respond to the PE regimen, suggesting that these two regimens were partially non-cross-resistant. The response duration on CAV/PE was significantly longer than that with CAV (P = .004). The survival time with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (P = .027) or that with PE (9.9 months) (P = .056). In patients with limited disease, the survival in the alternating arm was significantly superior to the survival in the CAV arm (P = .014) or the survival in the PE arm (P = .023). The toxic effects were acceptable in all three chemotherapy regimens. These results favor the alternating chemotherapy over either standard chemotherapy, such as CAV and PE, although the differences are not dramatic.
Seronegative Hashimoto Thyroiditis with Thyroid Autoantibody Production Localized to the Thyroid
Authors: J R Baker, N B Saunders, L Wartofsky, Y C Tseng, K D Burman
Journal: Annals of Internal Medicine (1988)

A patient without serologic evidence of an autoimmune disorder had a thyroidectomy for neck compression caused by her goiter. Histologic examination of the gland revealed pathologic changes compatible with Hashimoto disease, and lymphocytes isolated from her thyroid gland were transformed into lymphoblastoid cells in vitro by Epstein-Barr virus in the presence of cyclosporine. These cells produced antibodies against thyroglobulin, thyroid microsome, thyrocyte membrane, and thyrotropin, whereas lymphoblastoid cells produced from the patient's peripheral blood lymphocytes showed no antithyroid activity. Several human monoclonal antibodies were produced from the intrathyroidal lymphocytes by fusion with the SHM-D33 heteromyeloma, and the resulting cell lines produced antibodies with high-affinity binding specific for thyroid antigens. These studies show that lymphocytes capable of producing antithyroid antibodies can be present in the thyroid glands of patients with Hashimoto disease without evidence of a peripheral immune response, thus indicating that Hashimoto disease can exist as an organ-restricted autoimmune disorder.
Role of mast cells in ion transport abnormalities associated with intestinal anaphylaxis. Correction of the diminished secretory response in genetically mast cell-deficient W/Wv mice by bone marrow transplantation.
Authors: M H Perdue, S Masson, B K Wershil, S J Galli
Journal: Journal of Clinical Investigation (1991)

To investigate the role of mast cells in transport abnormalities during intestinal anaphylaxis, we examined responses to antigen in isolated intestinal preparations from ovalbumin-sensitized genetically mast cell-deficient WBB6F1-W/Wv (W/Wv) mice and congenic normal WBBGF1(-)+/+ (+/+) mice. Changes in ion transport (primarily secretion of chloride ions) were indicated by increases in short-circuit current (Isc). In tissues from +/+ mice, antigen caused increases in Isc which were significantly inhibited by antagonists to histamine (diphenhydramine) and serotonin (ketanserin), by a cyclooxygenase inhibitor (piroxicam) and by a neurotoxin (tetrodotoxin). In preparations from W/Wv mice, antigen-stimulated responses were approximately 30% of that in +/+ mice and were inhibited only by piroxicam. Responses to electrical transmural stimulation of nerves were approximately 50% in W/Wv versus +/+ mice, and were inhibited by antagonists of mast cell mediators in +/+ but not W/Wv mice. Reconstitution of mast cells in W/Wv mice by intravenous injection of +/+ bone marrow cells restored the normal responses to both antigen and nerve stimulation. Our results indicate that mast cell-dependent mechanisms are primarily responsible for the ion secretion associated with intestinal anaphylaxis, but that other cells are also involved. In addition, our data provide evidence for the functional importance of bidirectional communication between nerves and mast cells in the regulation of ion transport in the gastrointestinal tract.
Application of a Time-Varying Covariate Model to the Analysis of CA 19-9 as Serum Biomarker in Patients with Advanced Pancreatic Cancer
Authors: Stefan Boeck, Michael Haas, Rüdiger P. Laubender, Frank Kullmann, Christina Klose, Christiane J. Bruns, Ralf Wilkowski, Petra Stieber, Stefan Holdenrieder, Hannes Buchner, Ulrich Mansmann, Volker Heinemann
Journal: Clinical Cancer Research (2010)

The clinical relevance of CA 19-9 as surrogate biomarker in advanced pancreatic cancer is a matter of debate.This retrospective multicenter study included patients with histologically confirmed advanced pancreatic cancer treated with first-line therapy. Analysis of CA 19-9 was done using the Elecsys assay (Roche Diagnostics). For an analysis of CA 19-9 kinetics, at least three measurements during first-line chemotherapy had to be available. The effect of pretreatment CA 19-9 levels on time-to-progression (TTP) and overall survival (OS) was modeled by Cox proportional hazards regression. The effect of CA 19-9 kinetics was also modeled by Cox proportional hazards regression where CA 19-9 was treated as a time-varying covariate.One hundred and fifteen patients from five German centers were included; 73% of them were treated within prospective clinical trials. Median TTP was 4.4 months and median OS was 9.4 months; univariate analysis indicated that pretreatment CA 19-9 [as continuous variable, log (CA 19-9)] was significantly associated with TTP [hazard ratio (HR), 1.24; P < 0.001] and OS (HR, 1.16; P = 0.002). These associations remained significant within multivariate analysis. For CA 19-9 kinetics during chemotherapy, data from 69 patients (TTP) and 84 patients (OS) were available, respectively; log (CA 19-9) kinetics after start of treatment were found to be a significant predictor for TTP in univariate (HR, 1.48; P < 0.001) and multivariate (HR, 1.45; P < 0.001) analyses, and also for OS (univariate: HR, 1.34; P < 0.001; multivariate: HR, 1.38; P < 0.001).Pretreatment CA 19-9 and CA 19-9 kinetics may serve as a useful serum biomarker in advanced pancreatic cancer.
Hereditary Male Pseudohermaphroditism Associated with an Unstable Form of 5α-Reductase
Authors: Mark Leshin, James E. Griffin, Jean D. Wilson
Journal: Journal of Clinical Investigation (1978)

The properties of 5α-reductase have been compared in genital skin fibroblasts cultured from five patients from three families (Los Angeles, Dallas, and Dominican Republic) in which hereditary male pseudohermaphroditism has been established to result from deficient conversion of testosterone to dihydrotestosterone.
Sucrase-isomaltase deficiency in humans. Different mutations disrupt intracellular transport, processing, and function of an intestinal brush border enzyme.
Authors: H Y Naim, J Roth, E E Sterchi, M Lentze, P Milla, J Schmitz, H P Hauri
Journal: Journal of Clinical Investigation (1988)

Eight cases of congenital sucrase-isomaltase deficiency were studied at the subcellular and protein level with monoclonal antibodies against sucrase-isomaltase. At least three phenotypes were revealed: one in which sucrase-isomaltase protein accumulated intracellularly probably in the endoplasmic reticulum, as a membrane-associated high-mannose precursor, one in which the intracellular transport of the enzyme was apparently blocked in the Golgi apparatus, and one in which catalytically altered enzyme was transported to the cell surface. All patients expressed electrophoretically normal or near normal high-mannose sucrase-isomaltase. The results suggest that different, probably small, mutations in the sucrase-isomaltase gene lead to the synthesis of transport-incompetent or functionally altered enzyme which results in congenital sucrose intolerance.
“False-Positive” Cardiac Catheterization Laboratory Activation Among Patients With Suspected ST-Segment Elevation Myocardial Infarction
Authors: David M. Larson, Katie M. Menssen, Scott W. Sharkey, Sue Duval, Robert S. Schwartz, James Harris, Jeffrey T. Meland, Barbara T. Unger, Timothy D. Henry
Journal: JAMA (2007)

Allowing the emergency department physician to activate the cardiac catheterization laboratory is a key strategy to reduce door-to-balloon times in patients with ST-segment elevation myocardial infarction (STEMI). There are limited data on the frequency of "false-positive" catheterization laboratory activation in patients undergoing percutaneous coronary intervention for suspected STEMI.To determine the prevalence, etiology, and outcomes of false-positive cardiac catheterization laboratory activation in patients with a suspected STEMI.Prospective registry from a regional system that includes transfer of patients with STEMI from 30 community and rural hospitals with pretransfer catheterization laboratory activation for percutaneous coronary intervention at a tertiary cardiovascular center in Minnesota. A total of 1345 patients were enrolled from March 2003 to November 2006.Prevalence of false-positive catheterization laboratory activation in patients with suspected STEMI by 3 criteria: no culprit coronary artery, no significant coronary artery disease, and negative cardiac biomarker results.Of the 1335 patients with suspected STEMI who underwent angiography, 187 (14%; 95% confidence interval [CI], 12.2%-16.0%) had no culprit coronary artery and 127 (9.5%; 95% CI, 8.0%-11.2%) did not have significant coronary artery disease. Cardiac biomarker levels were negative in 11.2% (95% CI, 9.6%-13.0%) of patients. The combination of no culprit artery with negative cardiac biomarker results was present in 9.2% (95% CI, 7.7%-10.9%) of patients. Thirty-day mortality was 2.7% (95% CI, 0.4%-5.0%) without vs 4.6% (95% CI, 3.4%-5.8%) with a culprit coronary artery (P = .33).The frequency of false-positive cardiac catheterization laboratory activation for suspected STEMI is relatively common in community practice, depending on the definition of false-positive. Recent emphasis on rapid door-to-balloon times must also consider the consequences of false-positive catheterization laboratory activation.
Glomerular Function, Structure, and Number in Renal Allografts from Older Deceased Donors
Authors: Jane C. Tan, Biruh Workeneh, Stephan Busque, Kristina Blouch, Geraldine Derby, Bryan D. Myers
Journal: Journal of the American Society of Nephrology (2008)

The 5-yr survival rate of renal allografts is significantly lower for grafts from older deceased donors than from younger deceased donors. For evaluation of the potential contribution of renal senescence in this shortened graft survival, glomerular function and structure were analyzed in allografts from deceased donors older than 55 yr ("aging") or younger than 40 yr ("youthful"). Aging donors had a significantly higher prevalence of sclerotic glomeruli (P < 0.002), and their nonsclerotic glomeruli tended to be larger, had a larger filtration surface area (P = 0.02), and had a higher single-nephron ultrafiltration coefficient (K(f); P = 0.07), suggesting a compensatory response to functional loss of glomeruli. After serum creatinine reached a stable nadir in the transplant recipients, GFR and its hemodynamic determinants were evaluated and the whole allograft K(f) was computed. Compared with the allografts from youthful donors, allografts from aging donors exhibited a 32% lower GFR, which was exclusively attributable to a 45% reduction in allograft K(f) (both P < 0.001). In addition, the number of functioning glomeruli per allograft was profoundly lower in grafts from aging donors than from youthful donors (3.6 +/- 2.1 x 10(5) versus 8.5 +/- 3.4 x 10(5); P < 0.01), and this could not be explained by the relatively modest 17% prevalence of global glomerulosclerosis in the aging group. The marked reduction in overall glomerular number in many aging donors may lead to a "remnant kidney" phenomenon, potentially explaining the shorter mean survival of these allografts.
Clarithromycin Therapy for Mycobacterium avium Complex Bacteremia
Authors: Daniel M. Musher
Journal: Annals of Internal Medicine (1995)

Letters15 July 1995Clarithromycin Therapy for Mycobacterium avium Complex BacteremiaNina Singh and Victor L. YuNina SinghSearch for more papers by this author and Victor L. YuSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-2-199507150-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In the report of the dose-ranging trial of clarithromycin for bacteremic Mycobacterium avium complex disease in patients with human immunodeficiency virus (HIV) infection, Chaisson and colleagues [1] reported that despite significantly faster sterilization of the blood stream and a significantly greater clinical response with the twice-daily 2000-mg dose of clarithromycin than with the twice-daily 500-mg dose, overall survival and median duration of survival were significantly lower in the 2000-mg group. Survival was not associated with severity of illness, level of bacteremia, time from culture positivity to study enrollment, or the CD4 cell count, and the authors did ...References1. Chaisson RE, Benson CA, Dube MP, Heifets LB, Korvick JA, Elkin S, et al. Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. Ann Intern Med. 1994; 22:905-11. Google Scholar2. Zakowski P, Fligiel S, Berlin OG, Johnson L. Disseminated Mycobacterium avium-intracellulare infection in homosexual men dying of acquired immunodeficiency. JAMA. 1982; 248:2980-2. Google Scholar Author, Article, and Disclosure InformationAuthors: Nina Singh; Victor L. Yu PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1995Volume 123, Issue 2Page: 154-155KeywordsBacteremiaBloodCell culturesClinical trial reportingHIVHIV infectionsMycobacterium avium complexRiversSigns and symptoms ePublished: 15 August 2000 Issue Published: 15 July 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Where do we go from here? Clinical drug development in idiopathic pulmonary fibrosis
Authors: Harold R. Collard
Journal: European Respiratory Journal (2015)

Despite the recent success of the nintedanib and pirfenidone programmes [1, 2], idiopathic pulmonary fibrosis (IPF) remains a high-risk disease area for drug development. There are no adequate preclinical models in which to test potential compounds, and no established early clinical development pathway on which to make quick decisions regarding potential efficacy [3]. The historical approach in IPF of moving compounds directly from phase 1 safety and tolerability studies into large phase 2 studies with clinical end-points required major commitments from sponsors and research subjects. Now, with effective therapies reducing the frequency and responsiveness of clinical end-points, sponsors may decide that IPF is too costly a disease to invest in. Efficient IPF drug development is needed to ensure unmet medical need isn't overshadowed by scientific/financial risk <http://ow.ly/K0aEv>
Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock
Authors: Thomas Vogl, Klaus Tenbrock, Stephan Ludwig, Nadja Leukert, Christina Ehrhardt, Marieke A D van Zoelen, Wolfgang Nacken, Dirk Foell, Tom van der Poll, Clemens Sorg, Johannes Roth
Journal: Nature Medicine (2007)