tbuckley/cabot-search huggingface dataset:
Clostridium difficile toxin A-induced microvascular dysfunction. Role of histamine.
Authors: I Kurose, C Pothoulakis, J T LaMont, D C Anderson, J C Paulson, M Miyasaka, R Wolf, D N Granger
Journal: Journal of Clinical Investigation (1994)

Clostridium difficile toxin A (Tx-A) mediates secretion and inflammation in experimental enterocolitis. Intravital video microscopy was used to define the mechanisms that underlie the inflammatory reactions elicited by direct exposure of the microvasculature to Tx-A. Leukocyte adherence and emigration, leukocyte-platelet aggregation, and extravasation of FITC-albumin were monitored in rat mesenteric venules exposed to Tx-A. Significant increases in leukocyte adherence and emigration (LAE) and albumin leakage were noted within 15-30 min of Tx-A exposure. These responses were accompanied by mast cell degranulation and the formation of platelet-leukocyte aggregates. The Tx-A-induced increases in LAE and albumin leakage were significantly attenuated by pretreatment with either monoclonal antibodies (mAbs) directed against the leukocyte adhesion glycoproteins, CD11/CD18, intercellular adhesion molecule-1, and P-selectin (but not E-selectin) or with sialyl Lewis x, a counter-receptor for P-selectin. The mast cell stabilizer, lodoxamide, an H1- (but not an H2-) receptor antagonist, and diamine oxidase (histaminase) were also effective in reducing the LAE and albumin leakage elicited by Tx-A. The platelet-leukocyte aggregation response was blunted by an mAb against P-selectin, sialyl Lewis x, and the H1-receptor antagonist. These observations indicate that Tx-A induces a leukocyte-dependent leakage of albumin from postcapillary venules. Mast cell-derived histamine appears to mediate at least part of the leukocyte-endothelial cell adhesion and platelet-leukocyte aggregation by engaging H1-receptors on endothelial cells and platelets to increase the expression of P-selectin. The adhesion glycoproteins CD11/CD18 and intercellular adhesion molecule-1 also contribute to the inflammatory responses elicited by toxin A.
Effect of Histamine H2-Receptor Blockade on Vagally Induced Gastric Secretion in Man
Authors: D. C. Carter, J. A. H. Forrest, M. Werner, R. C. Heading, J. Park, D. J. C. Shearman
Journal: BMJ (1974)

Metiamide, an antagonist of histamine H(2) receptors, was administered intravenously to normal subjects and to patients with a peptic ulcer during vagal stimulation with a constant infusion of insulin. In normal and peptic-ulcer subjects there were reductions of 70% and 71% respectively in gastric-acid output compared with control tests on the same subjects. The decreased acid output resulted from a reduction in both volume of secretion and acid concentration. Metiamide is therefore a potent inhibitor of vagally-induced gastric acid secretion.
An Immunoassay to Measure IgE to Galactose alpha 1,3 Galactose Associated with Red Meat Allergies
Authors: L. Flebbe-Rehwaldt, H. Wells, S. Roberts, P. Walters, M. Ling, C. Brockus, J.F. Halsey, H. James, S. Commins, T. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2011)
The Ethical Problems with Sham Surgery in Clinical Research
Authors: R Macklin
Journal: New England Journal of Medicine (1999)

The recent use of sham surgery in randomized, controlled trials raises three critical questions about research involving human subjects. The first question concerns the tension between the highest standard of research design and the highest standard of ethics.1 When these two standards come into conflict and researchers cannot simultaneously meet both, which should prevail, and how should a balance be struck? The second question points to ongoing uncertainties and disagreements in assessing the risks and benefits of research protocols. When reasonable people — the members of well-established institutional review boards or the sponsors of research — disagree in their risk–benefit . . .
Public satisfaction with emergency care rises
Authors: G. Iacobucci
Journal: BMJ (2013)

The public’s satisfaction with the NHS has changed little in the past 12 months after a record fall in 2011, show the latest results of the British social attitudes survey.

The health policy think tank the King’s Fund said that the results, published this week, show that the record fall in satisfaction recorded in 2011 was not “a blip.”

The annual survey, which tracks the British public’s changing attitudes towards social, economic, political, and moral issues, shows that in 2012 just under two thirds (61%) of respondents were satisfied with the NHS. This is up slightly from the 58% satisfaction rate in 2011 but …
A NEW TEST FOR BILE PIGMENTS IN URINE, BILE AND BLOOD SERUM
Authors: ROBERT KAPSINOW
Journal: JAMA (1924)

While investigating the relation of bile pigments and metabolism in dogs with complete obstructive jaundice, or with biliary exclusion in which the bile was eliminated through the urine by means of a cholecystonephrostomy, we examined the urines as a routine for evidences of intestinal putrefaction as demonstrated by the test for indican. Curiously enough, we rarely found the indican test positive, but instead observed that the urine became deep green in every instance. At first the significance of this was not apparent; but later, on reviewing the phenomenon, we became impressed with the regularity and delicacy of this reaction whenever bile pigment was present. The test for indican employed was the Obermayer test, which was performed by mixing equal parts of Obermayer's reagent with urine. Then from 2 to 3 c.c. of chloroform was added and thoroughly shaken. A positive test was indicated by the chloroform taking the blue color
Hemocompatibility of siRNA loaded dextran nanogels
Authors: Broes Naeye, Hendrik Deschout, Magnus Röding, Mats Rudemo, Joris Delanghe, Katrien Devreese, Jo Demeester, Kevin Braeckmans, Stefaan C. De Smedt, Koen Raemdonck
Journal: Biomaterials (2011)
Inhaled frusemide and exercise-induced bronchoconstriction in children with asthma.
Authors: P Munyard, K F Chung, A Bush
Journal: Thorax (1995)

BACKGROUND--Nebulised frusemide has been shown to be protective against bronchoconstricting stimuli in adult asthmatic subjects and against cold air challenge in children. Animal studies suggest that inhaled frusemide may be more effective in the young. METHODS--A double blind placebo, controlled, crossover study on the effect on exercise of pretreatment with frusemide (20 mg) from a metered dose inhaler via a large volume spacer (Volumatic) was performed in 12 asthmatic children. Exercise testing consisted of eight minutes of running on a treadmill in an environmentally controlled laboratory. RESULTS--Deterioration in lung function was less after frusemide than after the placebo exercise tests. The mean (95% CI) maximum percentage falls in forced expiratory volume in one second (FEV1) were 14.4% (7.7 to 21.0) for placebo and 5.7% (2.3 to 9.0) for frusemide. CONCLUSIONS--Inhaled frusemide via a metered dose inhaler reduces exercise-induced bronchoconstriction in children.
FURTHER OBSERVATIONS ON THE AGGLUTINATION OF BACTERIA IN VIVO
Authors: Carroll G. Bull
Journal: The Journal of Experimental Medicine (1916)

1. Pneumococci, dysentery bacilli of the Shiga type, and Bacillus mucosus capsulatus are agglutinated immediately when injected into the circulation of actively immunized rabbits. 2. Staphylococcus aureus and albus, colon bacilli, meningococci, gonococci, and non-virulent pneumococci agglutinate in the circulation of normal rabbits. 3. Bouillon cultures of Bacillus avisepticus are highly toxic for both rabbits and dogs. The fresh sera of these animals have no bactericidal action upon the bacteria. Dog serum opsonized the bacilli in vitro, and they are agglutinated and opsonized in the circulation and organs of normal dogs. On the other hand, none of this occurs in connection with normal rabbits. A very small quantity of culture produces a fatal septicemia in rabbits, but a subtoxic dose is without effect in dogs. 4. The degree of agglutination and opsonization of bacteria within the animal body is inversely parallel to the infectiousness of the bacteria for the host.
Genome-Wide Analysis of the Heritability of Amyotrophic Lateral Sclerosis
Authors: Margaux F. Keller, Luigi Ferrucci, Andrew B. Singleton, Pentti J. Tienari, Hannu Laaksovirta, Gabriella Restagno, Adriano Chiò, Bryan J. Traynor, Michael A. Nalls
Journal: JAMA Neurology (2014)

Considerable advances have been made in our understanding of the genetics underlying amyotrophic lateral sclerosis (ALS). Nevertheless, for the majority of patients who receive a diagnosis of ALS, the role played by genetics is unclear. Further elucidation of the genetic architecture of this disease will help clarify the role of genetic variation in ALS populations.To estimate the relative importance of genetic factors in a complex disease such as ALS by accurately quantifying heritability using genome-wide data derived from genome-wide association studies.We applied the genome-wide complex trait analysis algorithm to 3 genome-wide association study data sets that were generated from ALS case-control cohorts of European ancestry to estimate the heritability of ALS. Cumulatively, these data sets contained genotype data from 1223 cases and 1591 controls that had been previously generated and are publically available on the National Center for Biotechnology Information database of genotypes and phenotypes website (http://www.ncbi.nlm.nih.gov/gap). The cohorts genotyped as part of these genome-wide association study efforts include the InCHIANTI (aging in the Chianti area) Study, the Piemonte and Valle d'Aosta Register for Amyotrophic Lateral Sclerosis, the National Institute of Neurological Disorders and Stroke Repository, and an ALS specialty clinic in Helsinki, Finland.A linear mixed model was used to account for all known single-nucleotide polymorphisms simultaneously and to quantify the phenotypic variance present in ostensibly outbred individuals. Variance measures were used to estimate heritability.With our meta-analysis, which is based on genome-wide genotyping data, we estimated the overall heritability of ALS to be approximately 21.0% (95% CI, 17.1-24.9) (SE = 2.0%), indicating that additional genetic variation influencing risk of ALS loci remains to be identified. Furthermore, we identified 17 regions of the genome that display significantly high heritability estimates. Eleven of these regions represent novel candidate regions for ALS risk.We found the heritability of ALS to be significantly higher than previously reported. We also identified multiple, novel genomic regions that we hypothesize may contain causative risk variants that influence susceptibility to ALS.
AUTOMATED CONTOUR CORRECTION WITH INSTANTANEOUS REAL-TIME 3D-VOLUME TRANSTHORACIC ECHOCARDIOGRAPHY IMPROVES ACCURACY OF LEFT VENTRICULAR VOLUME MEASUREMENTS IN PATIENTS WITH SYSTOLIC DYSFUNCTION: COMPARISON TO CARDIAC MRI
Authors: Paaladinesh Thavendiranathan, Shizhen Liu, Bogdan Georgescu, Adrien Ntinunu, Anna Calleja, David Verhaert, Helene Houle, Thomas Van Houten, Joel Mancina, Nathalie De Michelis, David Orsinelli, Mary Ellen Orsinelli, Subha Raman, Thomas Ryan, Mani Vannan
Journal: Journal of the American College of Cardiology (2010)
The population bomb has exploded already.
Authors: T Smith
Journal: BMJ (1990)

selected from the hundreds of thousands commissioned by the Farm Security Administration in the United States after the depression.5 Their commentary greatly adds to an under- standing of the photographs, which look, on first sight, to be self explanatory.To check documentary photographs' "inherent tendency to fraudulence" Stoeckle and White suggest shifting the burden of meaning from the producer (the photographer) to the consumer (the audience)."Burden" is the right word: this is hard work.Incorporating the sorts of images found in this issue into histories of medicine has hardly begun.So far all that has been agreed is that medical images are not transparent windows on the past, and defining what they are will be difficult.6In the historical papers published in this issue the hard work of evaluating primary sources has already been done: they are an easy read.Meanwhile, the medical images obstinately remain as primary sources, pending their informed interrogation.For once, looking at the pictures is the more arduous option.
228 Osteopontin induction: possible mechanism behind hepatic neutrophil infiltration during alcoholic steatohepatitis
Authors: U APTE, R MCREE, S RAMAIAH
Journal: Hepatology (2003)

Phosphatase and tensin homolog (PTEN) is a multifunctional phosphatase whose substrate is phosphatidylinositol-3,4,5-triphosphate (PIP3), and it is also a ubiquitously expressed tumor suppressor gene that down-regulates phosphatidylinositol-3-kinases (PI3Ks). Although there are a few reports about PTEN related to hepatocellular carcinoma, the role of PTEN in the liver remains unclear. Therefore, to clarify the role of PTEN in the liver, we generated and analyzed hepatocyte-specific Pten-deficient mice (Pten-deficient mice). The liver of 40-week-old Pten-deficient mice revealed macrovesicular steatosis, ballooning hepatocytes, lobular inflammatory cell infiltration, and perisinusoidal fibrosis that are characteristic of human nonalcoholic steatohepatitis (NASH). By 80 weeks of age, 100% of Pten-deficient livers showed adenomas and 66% had hepatocellular carcinomas. Thus, PTEN is important for the prevention of adipogenic and tumorigenic transformation, and Pten-deficient mice are a novel model for NASH and hepatocellular carcinoma. Our results suggest that the controlled blocking of molecules acting downstream of PI3K might provide significant therapeutic benefit to patients predisposed to NASH and hepatocellular carcinoma.
Studies Highlight Air Pollution Risks
Authors: Mike Mitka
Journal: JAMA (2007)

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 Journals 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
ACUTE INFLAMMATION IN THE RENAL CORTEX AND MEDULLA FOLLOWING THERMAL INJURY
Authors: Heonir Rocha, F. Robert Fekety
Journal: The Journal of Experimental Medicine (1964)

As determined by serial histologic study, the leukocyte component of the acute inflammatory response to thermal injury in the medulla of the kidney of rabbits was markedly delayed and diminished in intensity when compared with the response of the cortex. Similar differences in granulocyte mobilization between cortex and medulla were seen following the inoculation of bacteria. Hydronephrosis produced by ureteral ligation had no discernible effect upon the inflammatory response in either cortex or medulla following thermal burns. The susceptibility of the cortex to E. coli infection was markedly enhanced during leukopenia induced by nitrogen-mustard. These results suggest that deficiencies in granulocyte mobilization play an important role in the increased susceptibility of the renal medulla to bacterial infection.
RADIOACTIVITY IN MAN
Authors: E. V. Hulse
Journal: BMJ (1962)

<h3>Abstract</h3> The phenotypic efficacy of somatic copy number alterations (SCNAs) stems from their incidence per base pair of the genome, which is orders of magnitudes greater than that of point mutations. One mitotic event stands out in its potential to significantly change a cell’s SCNA burden–a chromosome missegregation. We present a general deterministic framework for modeling chromosome missegregations and use it to evaluate the possibility of missegregation-induced population extinction (MIE). The model predicts critical curves that separate viable from non-viable populations as a function of their turnover- and missegregation rates. Missegregation- and turnover rates estimated from a PAN-cancer scRNA-seq dataset of 15,464 cells are then compared to predictions. The majority of tumors across all cancer types had missegregation- and turnover rates that were within viable regions of the parameter space. When a dependency of missegregation rate on karyotype was introduced, karyotypes associated with low missegregation rates acted as a stabilizing refuge, rendering MIE impossible unless turnover rates are exceedingly high. Intra-tumor heterogeneity, including heterogeneity in missegregation rates, increases as tumors progress, rendering MIE unlikely. <h3>Author Summary</h3> When a cell missegregates a chromosome while dividing, the chance is high that its two daughter cells will behave drastically different from each other and from their parental cell. Chromosome missegregations are therefore one of the most powerful forces of phenotypic diversity. We developed a mathematical model of chromosome missegregations that allows for this cell-to-cell diversity to be accounted for. The model serves to help understand how selection acts upon cells with versatile chromosome contents, as a tool for genotype-to-phenotype mapping in various microenvironments. As a first application example we used the model to address whether there exists an upper limit on missegregation rate, beyond which cancer populations collapse. Chromosome missegregations are common. They occur in 1.2-2.3% per mitosis in normal cells [1] and in cancer cells their rate is between one and two orders of magnitudes higher [2]. The model revealed that the upper limit of missegregation rate is a function of the tumor’s turnover rate (i.e. how fast the tumor renews itself). In heterogenous populations however, cells with low missegregation rates protect the population from collapse. Intra-tumor heterogeneity, including heterogeneity in missegregation rates, increases as tumors progress, rendering missegregation-induced extinction unlikely.
Prevalence and Co-Occurrence of Actionable Genomic Alterations in High-Grade Bladder Cancer
Authors: Gopa Iyer, Hikmat Al-Ahmadie, Nikolaus Schultz, Aphrothiti J. Hanrahan, Irina Ostrovnaya, Arjun V. Balar, Philip H. Kim, Oscar Lin, Nils Weinhold, Chris Sander, Emily C. Zabor, Manickam Janakiraman, Ilana R. Garcia-Grossman, Adriana Heguy, Agnes Viale, Bernard H. Bochner, Victor E. Reuter, Dean F. Bajorin, Matthew I. Milowsky, Barry S. Taylor, David B. Solit
Journal: Journal of Clinical Oncology (2013)

Purpose We sought to define the prevalence and co-occurrence of actionable genomic alterations in patients with high-grade bladder cancer to serve as a platform for therapeutic drug discovery. Patients and Methods An integrative analysis of 97 high-grade bladder tumors was conducted to identify actionable drug targets, which are defined as genomic alterations that have been clinically validated in another cancer type (eg, BRAF mutation) or alterations for which a selective inhibitor of the target or pathway is under clinical investigation. DNA copy number alterations (CNAs) were defined by using array comparative genomic hybridization. Mutation profiling was performed by using both mass spectroscopy-based genotyping and Sanger sequencing. Results Sixty-one percent of tumors harbored potentially actionable genomic alterations. A core pathway analysis of the integrated data set revealed a nonoverlapping pattern of mutations in the RTK-RAS-RAF and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways and regulators of G 1 -S cell cycle progression. Unsupervised clustering of CNAs defined two distinct classes of bladder tumors that differed in the degree of their CNA burden. Integration of mutation and copy number analyses revealed that mutations in TP53 and RB1 were significantly more common in tumors with a high CNA burden (P &lt; .001 and P &lt; .003, respectively). Conclusion High-grade bladder cancer possesses substantial genomic heterogeneity. The majority of tumors harbor potentially tractable genomic alterations that may predict for response to target-selective agents. Given the genomic diversity of bladder cancers, optimal development of target-specific agents will require pretreatment genomic characterization.
Localisation and functional significance of ryanodine receptors during β-adrenoceptor stimulation in the guinea-pig sino-atrial node
Authors: Lauren Rigg, Bronagh M Heath, Yi Cui, Derek A Terrar
Journal: Cardiovascular Research (2000)

Objective: Recent evidence shows that calcium released from the sarcoplasmic reticulum (SR) plays an important role in the regulation of heart rate. The aim of this study was to investigate the subcellular distribution of ryanodine receptors in the guinea-pig sino-atrial (SA) node and to determine their functional role in the regulation of pacemaker frequency in response to β-adrenoceptor stimulation. Methods: Monoclonal antibodies raised against the cardiac ryanodine receptor were used with confocal microscopy to investigate ryanodine receptor distribution in single guinea-pig SA node cells. The functional role of ryanodine receptors was investigated in both multicellular SA node/atrial preparations and in single SA node cells. Results: Ryanodine receptor labelling was observed in all SA node cells studied and showed both subsarcolemmal and intracellular staining. In the latter, labelling appeared as transverse bands with a regular periodicity of ∼2 μm. This interval resembled that of the expected sarcomere spacing but did not, however, depend on the presence of transverse tubules. The bands of ryanodine receptors appeared to be located in the region of the Z lines, based on co-distribution studies with antibodies to α-actinin, myomesin and binding sites for phalloidin. Functional studies on single SA node cells showed that application of ryanodine (2 μmol/l) reduced the rate of firing of spontaneous action potentials (measured using the perforated patch clamp technique) and this was associated with changes in action potential characteristics. Ryanodine also significantly decreased the positive chronotropic actions of isoprenaline in both multicellular and single cell preparations. In single cells exposed to 100 nmol/l isoprenaline, ryanodine caused a decrease in the rate of firing and this was associated with a decrease in the amplitude of the measured calcium transients. Conclusions: These findings are the first to show immunocytochemical evidence for the presence and organisation of ryanodine receptor calcium release channels in mammalian SA node cells. This study also provides evidence of a role for ryanodine sensitive sites in the β-adrenergic modulation of heart rate in this species.