tbuckley/cabot-search huggingface dataset:
Balancing role of nitric oxide in complement‐mediated activation of platelets from <i>mCd59a</i> and <i>mCd59b</i> double‐knockout mice
Authors: Xuebin Qin, Weiguo Hu, Wenping Song, Price Blair, Gongxiong Wu, Xuemei Hu, Yanli Song, Selena Bauer, Martin Feelisch, Jane A. Leopold, Joseph Loscalzo, Jose A. Halperin
Journal: American Journal of Hematology (2009)

CD59 is a membrane protein inhibitor of the membrane attack complex (MAC) of complement. mCd59 knockout mice reportedly exhibit hemolytic anemia and platelet activation. This phenotype is comparable to the human hemolytic anemia known as paroxysmal nocturnal hemoglobinuria (PNH), in which platelet activation and thrombosis play a critical pathogenic role. It has long been suspected but not formally demonstrated that both complement and nitric oxide (NO) contribute to PNH thrombosis. Using mCd59a and mCd59b double knockout mice (mCd59ab(-/-) mice) in complement sufficient (C3(+/+)) and deficient (C3(-/-)) backgrounds, we document that mCd59ab(-/-) platelets are sensitive to complement-mediated activation and provide evidence for possible in vivo platelet activation in mCd59ab(-/-) mice. Using a combination of L-NAME (a NO-synthase inhibitor) and NOC-18 or SNAP (NO-donors), we further demonstrate that NO regulates complement-mediated activation of platelets. These results indicate that the thrombotic diathesis of PNH patients could be due to a combination of increased complement-mediated platelet activation and reduced NO-bioavailability as a consequence of hemolysis.
Volume and Outcome of Coronary Artery Bypass Graft Surgery-Reply
Authors: Jonathan A. Showstack
Journal: JAMA (1987)

In Reply.—  Wilson et al state that cardiovascular surgery programs should adhere to standard morbidity and mortality criteria rather than case-volume  We agree, as long as criteria are defined a priori (with appropriate recognition of the need to adjust for factors such as a hospital's case mix) and adherence is defined as statistically acceptable evidence that an individual surgery unit has met these criteria. The burden of proof needs to be shifted to hospitals to show that they are providing high-quality services.  Unfortunately, definitive statistical evidence is rarely available for an individual surgery unit. 1 Our data suggest that, given a lack of other evidence, patients might improve their chances of a good outcome if, after consultation with their physician, they choose to have surgery in a high-volume surgery unit.
Abstract 3932: IL13Rα2 regulates cell invasion, and is a therapeutic target for adrenocortical carcinoma
Authors: Meenu Jain, Lisa Zhang, Bharat Joshi, Raj Puri, Mei He, Electron Kebebew
Journal: Cancer Research (2012)

Abstract Adrencortical neoplasms are one of the most common human neopolasms. Furthermore, it is difficult to distinguish localized benign from malignant adrenal tumors. Adrenocortical carcinoma (ACC) is a relatively rare but aggressive malignancy with limited therapeutic options for patients with advanced and metastatic disease. Several genome wide expression studies have shown overexpression of Interleukin-13 Receptor alpha2 (IL13Rα2) in some human malignancies but the function of this gene in cancer cells is poorly understood. We evaluated IL13Rα2 mRNA expression in normal (n=21), and in benign (n=78) and malignant (n=10) adrenocortical tumors. We found 11-fold higher expression in malignant tumors compared to benign (p&amp;lt;0.05) and absent expression in normal adrenocortical tissue. Immunohistochemistry analysis confirmed high protein expression in malignant and benign tumors and absent expression in normal adrenocortical tissues (p&amp;lt;0.05). IL13Rα2 mRNA expression level also had 90% accuracy for distinguishing benign from malignant adrenocortical tumors. We used IL13Rα2 siRNA knockdown to assess its effect on cell proliferation and cell invasion in the NCI H295R cell line, which expressed high levels of IL13Rα2. IL13Rα2 knockdown did not significantly affect cell proliferation but did decrease invasion by 60% as compared to negative control (p&amp;lt;0.05). To determine the significance of IL13Rα2 as a therapeutic target for ACC, we evaluated the sensitivity in two ACC cell lines (NCI-H295R with high IL13Rα2 expression and SW13 with low IL13Rα2 expression) to a highly specific IL-13 targeting immunotoxin (IL-13-PE). We found the IC50 for IL-13-PE was 1.3ng/ml (NCI-H295R) and 1000ng/ml (SW13) in the cell lines. Based on this observation, we then tested the efficacy of IL-13-PE therapy in an ACC xenograft model in athymic nude mice. Mice receiving either intratumoral or intraperitoneal IL-13-PE therapy as compared to control showed a significant reduction in tumor size as well as tumor necrosis (p&amp;lt;0.05), and had prolonged survival (p&amp;lt;0.05). Both routes of IL-13-PE administration were well tolerated with no significant toxicity. Our study indicates that IL13Rα2 is overexpressed in 100% of ACC, is a good diagnostic marker for ACC, regulates ACC cell invasion, and is a novel therapeutic target for the treatment of ACC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3932. doi:1538-7445.AM2012-3932
Multicentric Skeletal Tuberculosis in the Absence of Pulmonary Disease
Authors: Bruce K. Adams, Ekhlaas Ahmed, Zuhair Y. Al-Haider
Journal: Clinical Nuclear Medicine (2004)

A 19-year-old woman presented with a 2-month history of low back pain, night sweats, and weight loss. Examination revealed localized tenderness over the proximal lumbar spine. Her chest was clear and she had no lymphadenopathy. Spinal radiographs were normal and computed tomography (CT) demonstrated a lytic lesion in the spinous process of the L2 vertebra. CT-guided aspiration cytology yielded acid-fast bacilli, and a diagnosis of tuberculous (TB) spondylodiscitis was made. Subsequent investigations showed a raised erythrocyte sedimentation rate, but sputum tests for AFBs were negative and she was human immunodeficiency virus (HIV)-negative. She was treated with antituberculous drugs, including isoniazid (INH), rifampicin, pyrazinamide, and ethambutol for 3 months, and INH and rifampicin for another 9 months, and was then discharged symptom-free. Three years later, she was investigated for infertility. The laparoscopy examination revealed bilateral tubal occlusion presumed to be tuberculous. Her ovaries were normal. She was put on a further course of anti-TB treatment for the next year. She presented on a third occasion 3 months later with a second episode of back pain. A bone scan was done that demonstrated abnormal uptake in the thoracic spine, skull, pelvis, and long bones.
Planning for Epidemics — The Lessons of SARS
Authors: Robert A Weinstein
Journal: New England Journal of Medicine (2004)

In terms of sheer drama, the emergence of the severe acute respiratory syndrome (SARS) rivaled the most exotic Michael Crichton thriller. A novel viral strain spread in “wet markets” from an obscure animal to food handlers; through a rural province in southern China; to Hong Kong, by way of an ill Chinese physician who had traveled to attend a wedding; and in one night at a Hong Kong hotel, from that man to at least 12 other people. These 12 returned to their five home countries and created multiple chains of transmission that, over the course of the next four . . .
Vulnerability of children and the developing brain to neurotoxic hazards.
Authors: B Weiss
Journal: Environmental Health Perspectives (2000)

For much of the history of toxicology, the sensitivity of the developing organism to chemical perturbation attracted limited attention. Several tragic episodes and new insights finally taught us that the course of early brain development incurs unique risks. Although the process is exquisitely controlled, its lability renders it highly susceptible to damage from environmental chemicals. Such disturbances, as recognized by current testing protocols and legislation such as the Food Quality Protection Act, can result in outcomes ranging from death to malformations to functional impairment. The latter are the most difficult to determine. First, they require a variety of measures to assay their extent. Second, adult responses may prove an inadequate guide to the response of the developing brain, which is part of the reason for proposing additional safety factors for children. Third, neuropsychological tests are deployed in complex circumstances in which many factors, including economic status, combine to produce a particular effect such as lowered intelligence quotient score. Fourth, the magnitude of the effect, for most environmental exposure levels, may be relatively small but extremely significant for public health. Fifth, changes in brain function occur throughout life, and some consequences of early damage may not even emerge until advanced age. Such factors need to be addressed in estimating the influence of a particular agent or group of agents on brain development and its functional expression. It is especially important to consider ways of dealing with multiple risks and their combinations in addition to the prevailing practice of estimating risks in isolation.
Role of EP2 and EP4 receptor-selective agonists of prostaglandin E2 in acute and chronic kidney failure
Authors: S. Vukicevic, P. Simic, F. Borovecki, L. Grgurevic, D. Rogic, I. Orlic, W.A. Grasser, D.D. Thompson, V.M. Paralkar
Journal: Kidney International (2006)
Primary Care and Health System Reform
Authors: Allan H. Goroll
Journal: JAMA (2010)

Schering-Plough, Sanofi-Aventis, Isis, Siemens, and Vascular Biogenics; and being listed as a coinventor on patents held by Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease, including the use of high-sensitivity C-reactive protein in the evaluation of patients’ risk of cardiovascular disease. These patents have been licensed to Siemens and AstraZeneca. Neither of the other authors reported financial disclosures.
Perivascular Mast Cells Promote Atherogenesis and Induce Plaque Destabilization in Apolipoprotein E–Deficient Mice
Authors: Ilze Bot, Saskia C.A. de Jager, Alma Zernecke, Ken A. Lindstedt, Theo J.C. van Berkel, Christian Weber, Erik A.L. Biessen
Journal: Circulation (2007)

Background— Mast cells are major effector cells in allergy and host defense responses. Their increased number and state of activation in perivascular tissue during atherosclerosis may point to a role in cardiovascular disorders. In the present study, we investigated the contribution of perivascular mast cells to atherogenesis and plaque stability in apolipoprotein E–deficient mice. Methods and Results— We show here that episodes of systemic mast cell activation during plaque progression in mice leads to robust plaque expansion. Targeted activation of perivascular mast cells in advanced plaques sharply increases the incidence of intraplaque hemorrhage, macrophage apoptosis, vascular leakage, and CXCR2/VLA-4–mediated recruitment of leukocytes to the plaque. Importantly, treatment with the mast cell stabilizer cromolyn does prevent all the adverse phenomena elicited by mast cell activation. Conclusions— This is the first study to demonstrate that mast cells play a crucial role in plaque progression and destabilization in vivo. We propose that mast cell stabilization could be a new therapeutic approach to the prevention of acute coronary syndromes.
Medical students are demoralised by some teachers
Authors: A. D Struthers
Journal: BMJ (2002)

EDITOR—I wish to draw attention to what I think is a serious problem in medical education. Since I became a consultant in 1985, some senior staff have been complaining that medical students nowadays do not know as much as they used to. This complaint has been given greater impetus by the invention of “new” medical curricula, which means that teachers now believe that they have an identifiable reason why today's medical students are not as good as they used to be. …
Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress
Authors: Kazuya Shinozaki, Atsushi Hirayama, Yoshihiko Nishio, Yuichi Yoshida, Tomohito Ohtani, Tomio Okamura, Masahiro Masada, Ryuichi Kikkawa, Kazuhisa Kodama, Atsunori Kashiwagi
Journal: Journal of the American College of Cardiology (2001)
Increased Formation of Distinct F <sub>2</sub> Isoprostanes in Hypercholesterolemia
Authors: Muredach P. Reilly, Domenico Praticò, Norman Delanty, Giovanni DiMinno, Elena Tremoli, Daniel Rader, Shiv Kapoor, Joshua Rokach, John Lawson, Garret A. FitzGerald
Journal: Circulation (1998)

Background —F 2 isoprostanes are stable, free radical–catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. Methods and Results —Specific assays were developed by use of mass spectrometry for the F 2 isoprostanes iPF 2α -III and iPF 2α -VI and arachidonic acid (AA). Urinary excretion of the 2 F 2 isoprostanes was significantly increased in hypercholesterolemic patients, whereas substrate AA in urine did not differ between the groups. iPF 2α -III (pmol/mmol creatinine) was elevated ( P &lt;0.0005) in homozygous familial hypercholesterolemic (HFH) patients (85±5.5; n=38) compared with age- and sex-matched normocholesterolemic control subjects (58±4.2; n=38), as were levels of iPF 2α -VI (281±22 versus 175±13; P &lt;0.0005). Serum cholesterol correlated with urinary iPF 2α -III ( r =0.41; P &lt;0.02) and iPF 2α -VI ( r =0.39; P &lt;0.03) in HFH patients. Urinary excretion of iPF 2α -III (81±10 versus 59±4; P &lt;0.05) and iPF 2α -VI (195±18 versus 149±20; P &lt;0.05) was also increased in moderately hypercholesterolemic subjects (n=24) compared with their controls. Urinary excretion of iPF 2α -III and iPF 2α -VI was correlated ( r =0.57; P &lt;0.0001; n=106). LDL iPF 2α -III levels (ng/mg arachidonate) were elevated ( P &lt;0.01) in HFH patients (0.32±0.08) compared with controls (0.09±0.02). The concentrations of iPF 2 -III in LDL and urine were significantly correlated ( r =0.42; P &lt;0.05) in HFH patients. Conclusions —Asymptomatic patients with moderate and severe hypercholesterolemia have evidence of oxidant stress in vivo.
Domiciliary Family Planning Service in Glasgow
Authors: E. Wilson
Journal: BMJ (1971)

In the first year of the operation of a domiciliary family planning service 50 deprived families accepted contraceptive advice offered in their homes. Associated factors were poverty, unemployment, overcrowding, alcoholism, debt, and disease. The women had previously averaged one pregnancy every 19 months but during the period under review there were only two pregnancies, in contrast to the 37 that would otherwise have been expected. Though the service is expensive in professional time, the overall saving in costs to the community by the prevention of unwanted pregnancies in socially inadequate families fully justifies the scheme.
Environmental effects on the central nervous system.
Authors: G W Paulson
Journal: Environmental Health Perspectives (1977)

The central nervous system (CNS) is designed to respond to the environment and is peculiarly vulnerable to many of the influences found in the environment. Utilizing an anatomical classification (cortex, cerebellum, peripheral nerves) major toxins and stresses are reviewed with selections from recent references. Selective vulnerability of certain areas to particular toxins is apparent at all levels of the CNS, although the amount of damage produced by any noxious agent depends on the age and genetic substrate of the subject. It is apparent that the effects of certain well known and long respected environmental toxins such as lead, mercury, etc., deserve continued surveillance. In addition, the overwhelming impact on the CNS of social damages such as trauma, alcohol, and tobacco cannot be ignored by environmentalists. The effect of the hospital and therapeutic environment has become apparent in view of increased awareness of iatrogenic disorders. The need for particular laboratory tests, for example, examination of CSF and nerve conduction toxicity studies, is suggested. Epidemics such as the recent solvent neuropathies suggest a need for continued animal studies that are chronic, as well as acute evaluations when predicting the potential toxic effects of industrial compounds.
Septicemia from Intravenous Infusions
Authors: Richard J. Duma, John F. Warner, Harry P. Dalton
Journal: New England Journal of Medicine (1971)

HOSPITAL-acquired infections associated with the use of various types of therapeutic equipment are serious problems that occur almost daily in "modern" general hospitals. Some of the most important, as well as most frequent, sources of such infections that need no documentation have been ventilatory and nebulization equipment, urinary-tract drainage tubes and indwelling intravenous catheters. This communication documents still another source, which although not previously recognized, may be very commonplace: intravenous fluids and volume-control sets.BackgroundOn July 5, 1970, a 28-year-old woman with hepatitis died after septicemia due to escherichia. The source was obscure until the intravenous volume-control set was . . .
Adherence to National Cholesterol Education Program Treatment Goals in Postmenopausal Women With Heart Disease
Authors: Helmut G. Schrott
Journal: JAMA (1997)

To determine the proportion of volunteer women with established heart disease who have low-density lipoprotein cholesterol (LDL-C) levels at or below the National Cholesterol Education Program Adult Treatment Panel goals and to determine what factors are associated with levels above goal or not receiving lipid-lowering medication when indicated.Cross-sectional measurement of lipids and lipoproteins, blood pressure, height, weight, and other demographic and cardiovascular risk factors in 2763 postmenopausal women with heart disease.At 18 centers throughout the United States, participants were recruited by means of lists of women with coronary heart disease from coronary units and catheterization laboratories, direct mail to age-eligible women, and advertisements.Mean age of the cohort was 66.7 years (range, 44-79 years) and the distribution by race/ethnicity was 88.7% white, 7.9% African American, 2.0% Hispanic/Latina, 0.8% Asian/Pacific Islander, and 0.7% other.We report cross-sectional analysis of the cohort at baseline.We measured the frequency of achieving 1988 and 1993 Adult Treatment Panel treatment goals, and of being on a regimen of lipid-lowering medication.Although 47% of participants were taking a lipid-lowering medication, 63% did not meet the 1988 treatment goal of LDL-C level less than 3.4 mmol/L (130 mg/dL) and 91% did not meet the 1993 goal of LDL-C level less than 2.6 mmol/L (100 mg/dL). Factors independently associated with achieving the earlier goal were use of lipid-lowering medication, marital status, education, body mass index, exercise, hypertension, diabetes, gallbladder disease, and first diagnosis of coronary heart disease after 1990. Failure to use lipid-lowering medication was associated with age, being African American, marital status, body mass index, lack of exercise, alcohol consumption, current smoking, and first diagnosis of coronary heart disease before 1985.The majority of women enrolled in the trial had LDL-C levels that significantly exceeded the treatment goals set by the 1988 and 1993 Adult Treatment Panel guidelines. Better implementation of these guidelines among women with coronary disease would be highly desirable.
Mechanistic Insights Into Very Slow Conduction in Branching Cardiac Tissue
Authors: Jan P. Kucera, Yoram Rudy
Journal: Circulation Research (2001)

It is known that branching strands of cardiac tissue can form a substrate for very slow conduction. The branches slow conduction by acting as current loads drawing depolarizing current from the main strand (“pull” effect). It has been suggested that, upon depolarization of the branches, they become current sources reinjecting current back into the strand, thus enhancing propagation safety (“push” effect). It was the aim of this study to verify this hypothesis and to assess the contribution of the push effect to propagation velocity and safety. Conduction was investigated in strands of Luo-Rudy dynamic model cells that branch from either a single branch point or from multiple successive branch points. In single-branching strands, blocking the push effect by not allowing current to flow retrogradely from the branches into the strand did not significantly increase the branching-induced local propagation delay. However, in multiple branching strands, blocking the push effect resulted in a significant slowing of overall conduction velocity or even in conduction failure. Furthermore, for certain slow velocities, the safety factor for propagation was higher when slow conduction was caused by branching tissue geometry than by reduced excitability without branching. Therefore, these results confirm the proposed “pull and push” mechanism of slow, but nevertheless robust, conduction in branching structures. Slow conduction based on this mechanism could occur in the atrioventricular node, where multiple branching is structurally present. It could also support reentrant excitation in diseased myocardium where the substrate is structurally complex.
Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets
Authors: Pier Paolo Piccaluga, Claudio Agostinelli, Andrea Califano, Maura Rossi, Katia Basso, Simonetta Zupo, Philip Went, Ulf Klein, Pier Luigi Zinzani, Michele Baccarani, Riccardo Dalla Favera, Stefano A. Pileri
Journal: Journal of Clinical Investigation (2007)

Peripheral T cell lymphoma, unspecified (PTCL/U), the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, and poor prognosis. We demonstrate that PTCL/U shows a gene expression profile clearly distinct from that of normal T cells. Comparison with the profiles of purified T cell subpopulations (CD4+, CD8+, resting [HLA-DR–], and activated [HLA-DR+]) reveals that PTCLs/U are most closely related to activated peripheral T lymphocytes, either CD4+ or CD8+. Interestingly, the global gene expression profile cannot be surrogated by routine CD4/CD8 immunohistochemistry. When compared with normal T cells, PTCLs/U display deregulation of functional programs often involved in tumorigenesis (e.g., apoptosis, proliferation, cell adhesion, and matrix remodeling). Products of deregulated genes can be detected in PTCLs/U by immunohistochemistry with an ectopic, paraphysiologic, or stromal location. PTCLs/U aberrantly express, among others, PDGFRα, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRα and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone deacetylase) were found. These results, which might be extended to other more rare PTCL categories, provide insight into tumor pathogenesis and clinical management of PTCL/U.