tbuckley/cabot-search huggingface dataset:
Complexity of Inducible Nitric Oxide Synthase
Authors: Betty Y. Poon, Eko Raharjo, Kamala D. Patel, Samantha Tavener, Paul Kubes
Journal: Circulation (2003)

Inducible nitric oxide synthase (iNOS) has been shown to have both beneficial and detrimental effects in sepsis. We focused on a single organ, the heart, and used 2 distinct cell types that express iNOS-the cardiac myocyte and the infiltrating neutrophil-to study the distinct functional effects of iNOS derived from heterogeneous cellular sources.In the first series of experiments, extravascular neutrophils were exposed to isolated single endotoxemic cardiac myocytes. Adhesion of wild-type neutrophils caused a rapid decrease in myocyte shortening and a concomitant increase in neutrophil-derived intracellular oxidative stress within the myocytes that was not observed with neutrophils from iNOS-deficient animals. We previously demonstrated that neutrophil-derived superoxide was essential for myocyte dysfunction; however, superoxide production was not compromised in the iNOS-deficient neutrophils. Because both superoxide and NO were essential for the neutrophil dysfunction, we probed for but could not detect any peroxynitrite assessed by detection of nitrotyrosine. There was a significant increase in length shortening in response to beta-adrenergic stimulation of wild-type myocytes. Surprisingly, myocyte iNOS activity was essential rather than detrimental for the development of beta-adrenergic receptor-mediated increases in shortening in endotoxemic iNOS-deficient myocytes.These results demonstrate that iNOS, when expressed in isolated cardiac myocytes, can regulate the response to beta-adrenergic stimulation during sepsis. However, as the neutrophils migrate in proximity to myocytes, iNOS now becomes essential for the ability of neutrophils to damage myocytes. These findings demonstrate that cellular source strongly modulates the beneficial and detrimental effect of iNOS.
LG-02 * CHALLENGES IN THE MANAGEMENT OF HYPOTHALAMIC JUVENILE PILOCYTIC ASTROCYTOMA
Authors: W. Gump, I. Mutchnick, J. Elster, K. Ayyanar
Journal: Neuro-Oncology (2015)

INTRODUCTION: Juvenile pilocytic astrocytoma is a relatively common pediatric intracranial tumor. In rare cases it arises from the region of the hypothalamus and optic pathways, with extensive anterior skull base involvement. Optimum treatment strategies have not been fully defined. We describe 2 cases in which different approaches were undertaken. METHOD: Patient 1 presented at age 1 year with visual and endocrine disturbance, macrocrania, and diencephalic syndrome. A large enhancing mass involving the anterior skull base and exerting mass effect on the brainstem was seen on MRI. This patient underwent surgery for tissue diagnosis, relief of mass effect on the brainstem, and alleviation of obstructive hydrocephalus. A subtotal resection was achieved. Patient 2 presented at age 5 years with subacute headaches, and recent nystagmus and ataxia. Endocrine evaluation was normal. Brain MRI showed a similar anterior skull base enhancing mass and associated hydrocephalus, although with less mass effect on the brainstem. The patient underwent stereotactic biopsy and ventriculoperitoneal shunt placement. RESULTS: Pathologic diagnosis was juvenile pilocytic astrocytoma in both cases. The postoperative course of patient 1 was complicated by panhypopituitarism and failure of visual acuity to improve. He had disease progression after 2 cycles of monthly carboplatin, and was changed to TPCV chemotherapy per CCG-9952 protocol. There has been some radiographic response over 1 year and he continues on this regimen. Patient 2 has shown good radiographic response to vincristine/carboplatin per CCG-9952, without any shunt complications over 1 year. This patient has remained neurologically normal with intact vision and endocrine axis. CONCLUSIONS: The primary advantage to open surgical debulking may be in the potential for shunt independence in patients with associated hydrocephalus. Neurologic and endocrine function at presentation corresponded with posttreatment status in our patients. Chemotherapy alone can achieve good radiographic results, although long term outcomes are not known.
Is the EMA's window of opportunity as widely open as described?
Authors: B. Toussaint
Journal: BMJ (2014)

Doshi and Groves recommend that readers get the data they might need from the European Medicines Agency (EMA) while they can, in light of potential changes to its policy on access to documents.1 The agency’s transparency requirements are enshrined in the EU directive 200/83/EC, which regulates drug products, and in the European freedom of information regulation (1049/2001).

At Prescrire , an independent drug bulletin, we have conducted …
Prognostic relevance of angiogenesis in stage III NSCLC receiving multimodality treatment
Authors: M. Kreuter, M. Kropff, A. Fischaleck, K. Junker, J. Gerss, A. Heinecke, M. Lindermann, N. Reinmuth, W. E. Berdel, R. M. Mesters, M. Thomas
Journal: European Respiratory Journal (2009)

Compelling evidence indicates that microvessel density (MVD) is a prognostic marker in early nonsmall cell lung cancer (NSCLC). However, its role in lymph node metastases in stage III NSCLC receiving multimodality treatment is unknown. Lymph nodes of 142 patients with stage III NSCLC, treated in a trial of the German Lung Cancer Cooperative group, were evaluated for MVD. Median follow-up was 7.39 yrs. MVD was correlated with demographic and tumour-related variables and survival. MVD (median 33.9) did not correlate with survival. However, in multimodality-treated stage IIIA patients receiving tumour resection with negative margins (R0), those with a high MVD had significantly prolonged overall survival with a median of 4.96 yrs compared with 1.99 yrs for those with low MVD (p = 0.041). Cox regression analysis revealed that MVD was a prognostic factor in R0-resected stage IIIA (hazard ratio 0.417). Furthermore, a significant correlation of MVD to stage was observed, with significantly lower MVD in stage IIIA than IIIB (p = 0.0062), and a significant correlation of MVD to histological subtype was observed, with adenocarcinoma revealing the highest scores (p = 0.0001). Increased angiogenesis within lymph node metastases is a prognostic indicator for better survival in NSCLC patients. Thus, measurement of MVD might be useful in selecting patients for future neoadjuvant treatment decisions.
Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells
Authors: Eberhard Gunsilius, Hans-Christoph Duba, Andreas L Petzer, Christian M Kahler, Kurt Grunewald, Gunther Stockhammer, Christoph Gabl, Stephan Dirnhofer, Johannes Clausen, Gunther Gastl
Journal: The Lancet (2000)
209 Natural history of ascites. Study in 246 cirrhotic patients
Authors: S. Coll, M.A. Alvarez, B. Balleste, S. Montoliu, M. Rivera, M. Miquel, J.A. Galeras, J. Santos, I. Cirera, R.M. Morillas, R. Sola, R. Planas
Journal: Journal of Hepatology (2004)
Many Address Task of Preventing Research Fraud
Authors: Beverly Merz
Journal: JAMA (1988)

ON SEPT 19, Stephen J. Breuning, PhD, entered a plea of guilty in US District Court in Baltimore to two counts of falsifying information to the National Institute of Mental Health (NIMH). The same day the<i>Federal Register</i>published proposed regulations designed to keep situations like Breuning's from happening again. Breuning admitted that he had falsified data in reports to the NIMH while director of the John Merck Program at the University of Pittsburgh's Western Psychiatric Institute. The studies, in which the effects of neuroleptic drugs were compared with those of stimulants in controlling behavior disorders in mentally retarded children, had been conducted earlier at Coldwater Regional Center for Developmental Disabilities in Michigan. According to one of the prosecutors in the case, Assistant US Attorney E. Thomas Roberts, Breuning reported results from 99 patients when data had been taken from only 25. Although the government dropped a charge of obstructing
Women and children suffer most from exposure to coal smoke
Authors: Anne Glusker
Journal: BMJ (2006)

The burning of coal and of biomass fuels such as wood, straw, and cow dung in conditions of poor ventilation increases the risk of lung cancer, a report from the International Agency for Research of Cancer concludes. 

The agency's report, from a meeting in October of 19 scientists from eight countries, says that frying at high temperatures—including stir frying, deep frying, and pan frying—also increases the risk of the disease, regardless of the type of cooking …
An unusual case of donor‐derived myelodysplastic syndrome following double‐unit umbilical cord blood transplantation in acute lymphoblastic leukemia
Authors: Ryan Cotter, Vesna Najfeld, Luis Isola, Gustavo Del Toro, Elizabeth Roman, Bruce Petersen, John Mascarenhas
Journal: American Journal of Hematology (2012)

Umbilical cord-blood transplantation is considered an effective treatment strategy for acute lymphoblastic leukemia (ALL) when a human leukocyte antigen (HLA)-matched donor is unavailable. The use of a second unit helps ensure engraftment in larger adults and those with comorbidities, even though only one unit engrafts in most patients. Herein, we present the clinical and laboratory characteristics of a patient who developed donor-derived myelodysplastic syndrome (ddMDS) after double umbilical cord-blood transplantation (dUCB HSCT). To our knowledge, no cases of ddMDS have been described in a patient with a history of ALL in molecular remission after receiving a dUCB HSCT. Current molecular techniques, including analysis of short tandem repeats (STR) and fluorescence in situ hybridization (FISH) allowed us to firmly establish donor origin.
FDA: No Codeine After Tonsillectomy for Children
Authors: Bridget M. Kuehn
Journal: JAMA (2013)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Impulses in Slowly Conducting Vagal Fibers from Afferent Endings in the Veins, Atria, and Arteries of Dogs and Cats
Authors: HAZEL M. COLERIDGE, JOHN C. G. COLERIDGE, ALBERT DANGEL, CECIL KIDD, JOHN C. LUCK, PETER SLEIGHT
Journal: Circulation Research (1973)

Afferent impulses in 61 fine myelinated or unmyelinated vagal fibers arising from endings in large blood vessels ("vascular endings") were recorded in anesthetized dogs and cats. The endings had a sparse, irregular spontaneous discharge, or they were quiescent. They were stimulated by capsaicin, phenyl diguanide, or veratridine injected into the bloodstream but not by sodium cyanide or hypoxia. Unlike arterial baroreceptors and atrial receptors, which are concentrated in localized areas, vascular endings were widely distributed in the thoracic aorta, the pulmonary artery, the brachiocephalic artery, the splenic artery, the atriovenous junctions, the atrial appendages, the inferior vena cava, and the hepatic vein. Conduction velocity in 28 fibers ranged from 0.8 to 11.0 m/sec (mean 3.1 m/sec), and in 19 of these fibers the velocity was less than 2.5 m/sec (i.e., the fibers were C-fibers). Vascular endings were stimulated by distending the vessels with balloons. Endings in the pulmonary artery and the aorta did not respond to pressures within the physiological range, but they were stimulated by abnormally high pressures (pulmonary artery 60-110 mm Hg, aorta 200-215 mm Hg). The physiological role of the vascular endings is unknown.
Gastric Stasis and Gastric Ulcer after Selective Vagotomy Without a Drainage Procedure
Authors: R. J. Clarke, J. B. McFarland, J. A. Williams
Journal: BMJ (1972)

Two independent trials of selective vagotomy without the addition of a drainage procedure in the treatment of uncomplicated duodenal ulcer have shown that gastric stasis may occur after the operation and that in some cases this may be complicated by gastric ulcer. These findings do not support the contention that selective vagotomy alone allows normal gastric emptying.
Ovarian Failure and Reproductive Outcomes After Childhood Cancer Treatment: Results From the Childhood Cancer Survivor Study
Authors: Daniel M. Green, Charles A. Sklar, John D. Boice, John J. Mulvihill, John A. Whitton, Marilyn Stovall, Yutaka Yasui
Journal: Journal of Clinical Oncology (2009)

These studies were undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on ovarian function and reproductive outcomes. We reviewed the frequency of acute ovarian failure, premature menopause, live birth, stillbirth, spontaneous and therapeutic abortion and birth defects in the participants in the Childhood Cancer Survivor Study (CCSS). Acute ovarian failure (AOF) occurred in 6.3% of eligible survivors. Exposure of the ovaries to high-dose radiation (especially over 10 Gy), alkylating agents and procarbazine, at older ages, were significant risk factors for AOF. Premature nonsurgical menopause (PM) occurred in 8% of participants versus 0.8% of siblings (rate ratio = 13.21; 95% CI, 3.26 to 53.51; P < .001). Risk factors for PM included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score, and a diagnosis of Hodgkin's lymphoma. One thousand two hundred twenty-seven male survivors reported they sired 2,323 pregnancies, and 1,915 female survivors reported 4,029 pregnancies. Offspring of women who received uterine radiation doses of more than 5 Gy were more likely to be small for gestational age (birthweight < 10 percentile for gestational age; 18.2% v 7.8%; odds ratio = 4.0; 95% CI, 1.6 to 9.8; P = .003). There were no differences in the proportion of offspring with simple malformations, cytogenetic syndromes, or single-gene defects. These studies demonstrated that women treated with pelvic irradiation and/or increasing alkylating agent doses were at risk for acute ovarian failure, premature menopause, and small-for-gestational-age offspring. There was no evidence for an increased risk of congenital malformations. Survivors should be generally reassured although some women have to consider their potentially shortened fertile life span in making educational and career choices.
TCT-652 Longitudinal Distribution of Endothelial Shear Stress Along Culprit Lesions and Association with Plaque Characteristics in Patients with Acute Coronary Syndromes: A Three-Dimensional Frequency-Domain Optical Coherence Tomography Study
Authors: Michail I. Papafaklis, Rocco Vergallo, Haibo Jia, Christos Bourantas, Taishi Yonetsu, Lampros Lakkas, Iris McNulty, Anna Kotsia, Hang Lee, Antonios Antoniadis, Bo Yu, Katerina K. Naka, Dimitrios I. Fotiadis, Charles Feldman, Lampros Michalis, Ik-Kyung Jang, Peter Stone
Journal: Journal of the American College of Cardiology (2013)
BNP-Guided Therapy for Heart Failure
Authors: Ileana L. Piña, Christopher O’Connor
Journal: JAMA (2009)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Mechanisms for Evolving Hypervariability: The Case of Conopeptides
Authors: Silvestro G. Conticello, Yoav Gilad, Nili Avidan, Edna Ben-Asher, Zehava Levy, Mike Fainzilber
Journal: Molecular Biology and Evolution (2001)

Hypervariability is a prominent feature of large gene families that mediate interactions between organisms, such as venom-derived toxins or immunoglobulins. In order to study mechanisms for evolution of hypervariability, we examined an EST-generated assemblage of 170 distinct conopeptide sequences from the venoms of five species of marine Conus snails. These sequences were assigned to eight gene families, defined by conserved elements in the signal domain and untranslated regions. Order-of-magnitude differences were observed in the expression levels of individual conopeptides, with five to seven transcripts typically comprising over 50% of the sequenced clones in a given species. The conopeptide precursor alignments revealed four striking features peculiar to the mature peptide domain: (1) an accelerated rate of nucleotide substitution, (2) a bias for transversions over transitions in nucleotide substitutions, (3) a position-specific conservation of cysteine codons within the hypervariable region, and (4) a preponderance of nonsynonymous substitutions over synonymous substitutions. We propose that the first three observations argue for a mutator mechanism targeted to mature domains in conopeptide genes, combining a protective activity specific for cysteine codons and a mutagenic polymerase that exhibits transversion bias, such as DNA polymerase V. The high Dn/Ds ratio is consistent with positive or diversifying selection, and further analyses by intraspecific/interspecific gene tree contingency tests weakly support recent diversifying selection in the evolution of conopeptides. Since only the most highly expressed transcripts segregate in gene trees according to the feeding specificity of the species, diversifying selection might be acting primarily on these sequences. The combination of a targeted mutator mechanism to generate high variability with the subsequent action of diversifying selection on highly expressed variants might explain both the hypervariability of conopeptides and the large number of unique sequences per species.
Novel strategy to identify MHC class II-promiscuous CD4+ peptides from tumor antigens for utilization in vaccination
Authors: Jashodeep Datta, Shuwen Xu, Julia H Terhune, Cinthia Rosemblit, Erik Berk, Elizabeth Fitzpatrick, Brian J Czerniecki
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Although cytotoxic CD8 T lymphocytes (CTL) were historically considered primary effectors of antitumor immunity, solely boosting CTL responses with CD8 vaccines in various tumor types has yielded unpredictable clinical results, possibly because CTLs function suboptimally without
Low Rates of Expression Profile Divergence in Highly Expressed Genes and Tissue-Specific Genes During Mammalian Evolution
Authors: Ben-Yang Liao, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2006)

Evolutionary rates provide important information about the pattern and mechanism of evolution. Although the rate of gene sequence evolution has been well studied, the rate of gene expression evolution is poorly understood. In particular, it is unclear whether the gene expression level and tissue specificity influence the divergence of expression profiles between orthologous genes. Here we address this question using a microarray data set comprising the expression signals of 10,607 pairs of orthologous human and mouse genes from over 60 tissues per species. We show that the level of gene expression and the degree of tissue specificity are generally conserved between the human and mouse orthologs. The rate of gene expression profile change during evolution is negatively correlated with the level of gene expression, measured by either the average or the highest level among all tissues examined. This is analogous to the observation that the rate of gene (or protein) sequence evolution is negatively correlated with the gene expression level. The impacts of the degree of tissue specificity on the evolutionary rate of gene sequence and that of expression profile, however, are opposite. Highly tissue-specific genes tend to evolve rapidly at the gene sequence level but slowly at the expression profile level. Thus, different forces and selective constraints must underlie the evolution of gene sequence and that of gene expression.
Tribunal suspends doctor for acting as expert witness beyond his competence
Authors: C. Dyer
Journal: BMJ (2014)

A psychiatrist has been suspended for three months by the Medical Practitioners Tribunal Service after he was found to have acted beyond his competence in preparing an expert report on a paramedic’s fitness to work.

Richard Pool was instructed by solicitors in October 2011 to provide a report to the Health Professions Council (now the Health and Care Professions Council) on “Ms A,” a paramedic with post-traumatic stress disorder and a personality disorder. His report concluded that she “would be predicted to …