tbuckley/cabot-search huggingface dataset:
Tularemia and Rhabdomyolysis
Authors: Allen B. Kaiser
Journal: JAMA (1985)

Rhabdomyolysis as a complication of tularemia occurred in four patients in Tennessee over a four-year period. All patients were severely ill and had renal failure. Tularemia was not suspected initially in any of these patients. One patient died of complications of rhabdomyolysis. At autopsy, multiple abscesses were present within skeletal muscle, suggesting that rhabdomyolysis resulted from direct muscle involvement with<i>Francisella tularensis</i>. Tularemia should be considered in the differential diagnosis of patients with an acute febrile illness and rhabdomyolysis. Conversely, in patients with acute tularemia, the possibility of rhabdomyolysis should be entertained early, especially in those with evidence of myoglobinuria and/or impaired renal function. (<i>JAMA</i>1985;253:241-243)
Blood Angiotensinase Activity in Relation to the Breakdown of Angiotensin II Amide and Non-isotopic Phenylthiocarbamyl-Angiotensin II Amide in Hypertensive and Normotensive Patients
Authors: E. C. Osborn, G. Jerums, B. A. Jupp
Journal: Cardiovascular Research (1968)

Investigations have been carried out into the rate of breakdown of valyl5-angiotensin II amide and of phenylthiocarbamyl-valyl5-angiotensin II amide by blood obtained from hypertensive and normotensive subjects. Ability to inactivate the two compounds was found to be similar in the two groups.
Membrane transporters in drug development
Authors: Kathleen M. Giacomini, Shiew-Mei Huang, Donald J. Tweedie, Leslie Z. Benet, Kim L.R. Brouwer, Xiaoyan Chu, Amber Dahlin, Raymond Evers, Volker Fischer, Kathleen M. Hillgren, Keith A. Hoffmaster, Toshihisa Ishikawa, Dietrich Keppler, Richard B. Kim, Caroline A. Lee, Mikko Niemi, Joseph W. Polli, Yuicchi Sugiyama, Peter W. Swaan, Joseph A. Ware, Stephen H. Wright, Sook Wah Yee, Maciej J. Zamek-Gliszczynski, Lei Zhang
Journal: Nature Reviews Drug Discovery (2010)
Ancient large-scale genome duplications: phylogenetic and linkage analyses shed light on chordate genome evolution
Authors: M. J. Pebusque, F. Coulier, D. Birnbaum, P. Pontarotti
Journal: Molecular Biology and Evolution (1998)

Paralogous genes from several families were found in four human chromosome regions (4p16, 5q33-35, 8p12-21, and 10q24-26), suggesting that their common ancestral region underwent several rounds of large-scale duplication. Searches in the EMBL databases, followed by phylogenetic analyses, showed that cognates (orthologs) of human duplicated genes can be found in other vertebrates, including bony fishes. In contrast, within each family, only one gene showing the same high degree of similarity with all the duplicated mammalian genes was found in nonvertebrates (echinoderms, insects, nematodes). This indicates that large-scale duplications occurred after the echinoderms/chordates split and before the bony vertebrate radiation. It has been suggested that two rounds of gene duplication occurred in the vertebrate lineage after the separation of Amphioxus and craniate (vertebrates + Myxini) ancestors. Before these duplications, the genes that have led to the families of paralogous genes in vertebrates must have been physically linked in the craniate ancestor. Linkage of some of these genes can be found in the Drosophila melanogaster and Caenorhabditis elegans genomes, suggesting that they were linked in the triploblast Metazoa ancestor.
A question of medical ethics from Somalia
Authors: Robert T A Scott
Journal: BMJ (2004)

<h3>Abstract</h3> In the mammalian embryo, epiblast cells must exit their naïve state and acquire formative pluripotency. This cell state transition is recapitulated by mouse embryonic stem cells (ESCs), which undergo pluripotency progression in defined conditions <i>in vitro</i>. However, our understanding of the molecular cascades and gene-networks involved in the exit from naïve pluripotency remains fragmented. Here we employed a combination of genetic screens in haploid ESCs, CRISPR/Cas9 gene disruption, large-scale transcriptomics and computational systems-biology to delineate the regulatory circuits governing naïve state exit. Transcriptome profiles for 73 knockout ESC lines predominantly manifest delays on the trajectory from naive to formative epiblast. We find that gene networks operative in ESCs are active during transition from pre- to post-implantation epiblast <i>in utero</i>. We identified 374 naïve-associated genes tightly connected to epiblast state and largely conserved in human ESCs and primate embryos. Integrated analysis of mutant transcriptomes revealed funneling of multiple gene activities into discrete regulatory modules. Finally, we delineate how intersections with signaling pathways direct this pivotal mammalian cell state transition.
Anticonvulsant hypersensitivity syndrome. In vitro assessment of risk.
Authors: N H Shear, S P Spielberg
Journal: Journal of Clinical Investigation (1988)

Arene oxide metabolites of aromatic anticonvulsants (phenytoin, phenobarbital, and carbamazepine) may be involved in the pathogenesis of hypersensitivity reactions. We investigated 53 patients with clinical sensitivity to anticonvulsants by exposing their lymphocytes in vitro to drug metabolites generated by a murine hepatic microsomal system. The diagnosis of a hypersensitivity reaction was corroborated by in vitro rechallenge for each drug (phenytoin, n = 34; phenobarbital, n = 22; carbamazepine, n = 25) when cytotoxicity (% dead cells) exceeded 3 SD above the mean result for controls. Cross-reactivity among the drugs was noted. 7 out of 10 patients who had received all three anticonvulsants had adverse reactions to each. 40 out of 50 patients tested to all three drugs in vitro were positive to each. Adverse reactions were indistinguishable among anti-convulsants. Skin rash (87%), fever (94%), hepatitis (51%), and hematologic abnormalities (51%) were common clinical features of each drug. 62% of reactions involved more than two organs. Cells from patients' parents exhibited in vitro toxicity that was intermediate between values for controls and patients. In vitro testing can help diagnose hypersensitivity to anticonvulsants. Cells from patients may also be used for prospective individualization of therapy to decrease risk of adverse reaction. Cross-reactivity among the major anticonvulsants is common and should be considered before deciding on alternative therapy.
Interleukin 1B proinflammatory genotypes protect against gastro-oesophageal reflux disease through induction of corpus atrophy
Authors: T Ando
Journal: Gut (2005)

The relationship between Helicobacter pylori infection and gastro-oesophageal reflux disease (GORD) is controversial but it is accepted that GORD is associated with increased exposure to gastric acidity. The proinflammatory interleukin (IL)-1B polymorphisms increase the risk of hypochlorhydria and gastric atrophy. We examined the association between proinflammatory cytokine gene polymorphisms, presence of gastric atrophy, and risk of GORD in H pylori positive and negative subjects in Japan.We studied 320 consecutive dyspeptic patients without peptic ulcers or cancers. GORD symptoms were scored using the Carlsson-Dent questionnaire and erosive oesophagitis was assessed endoscopically. H pylori infection was diagnosed by urea breath test, histological examination, and serology. Gastric atrophy was assessed histologically, and polymorphisms in the IL-1B, IL-10, and tumour necrosis factor alpha (TNF-A) genes were genotyped.Two hundred and eight patients were H pylori positive and 112 were negative. One hundred and eight (34%) were found to have erosive oesophagitis by endoscopic criteria (grade A: 78; grade B: 23; grade C: 6; grade D: 1). Erosive oesophagitis and GORD symptoms were significantly more common in H pylori negative compared with H pylori positive subjects (p<0.05). H pylori positive subjects were more likely to have corpus gastric atrophy than H pylori negative subjects (p<0.001). Among H pylori positive patients, those without erosive oesophagitis or GORD symptoms were significantly more likely to have corpus atrophy than subjects with erosive oesophagitis or GORD symptoms (p<0.05). Among H pylori positive patients, subjects homozygous for the proinflammatory allele IL-1B-511T had a significantly lower risk of erosive oesophagitis (odds ratio (OR) 0.06 (95% confidence interval (CI) 0.006-0.51); p=0.01) and GORD symptoms (OR 0.10 (95% CI 0.01-0.85); p=0.04) compared with those homozygous for the -511C allele, while none of the two other proinflammatory cytokine gene polymorphisms had significant correlations with erosive oesophagitis or GORD symptoms.A proinflammatory IL-1B genotype is associated with increased risk of atrophy and decreased risk of GORD in H pylori infected subjects in Japan. These data indicate that in some genetically predisposed subjects, H pylori infection may protect against GORD through induction of gastric atrophy.
Treatment of Alzheimer Disease and Prognosis of Dementia
Authors: Kristine Yaffe
Journal: JAMA (2010)

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
Effects of nitric oxide inhalation on pulmonary serial vascular resistances in ARDS.
Authors: M Rossetti, H Guénard, C Gabinski
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The pulmonary vasculature site of action of nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS) is still unknown. Seven patients were studied during the early stage of ARDS. The bedside pulmonary artery single-occlusion technique, which allows estimation of the pulmonary capillary pressure (Pcap) and segmental pulmonary vascular resistance, was used without NO or with increasing inhaled NO concentrations (15 and 25 parts per million [ppm]). Systemic circulatory parameters remained unaltered during 15 ppm NO inhalation, whereas 25 ppm NO inhalation slightly decreased mean systemic arterial pressure from 76.7 +/- 5.1 (mean +/- SEM) to 69 +/- 5.2 mm Hg (p < 0.01). Mean pulmonary arterial pressure (Ppam) and mean pulmonary capillary pressure (Pcapm) fell during 25 ppm NO inhalation from 27.4 +/- 3.5 to 21 +/- 2.2 mm Hg (p < 0.001) and from 14.8 +/- 1.5 to 10.7 +/- 1.4 mm Hg (p < 0.001) respectively, the total pulmonary resistance decreased by 28% (p < 0.01). The resistance of the capillary-venous compartment fell during 25 ppm NO inhalation from 100 +/- 16 to 47 +/- 16 dyn x s x m(2) x cm(-5) (p < 0.01), whereas the pulmonary arterial resistance was unchanged. In these patients NO inhalation during the early stage of ARDS reduces selectively Ppam and Pcapm by decreasing the pulmonary capillary-venous resistance. This latter effect may reduce the filtration through the capillary bed and hence alveolar edema during ARDS.
Abstract 5536: NAD+ Kinase inhibition synergizes with ROS-inducing chemotherapies.
Authors: Philip M. Tedeschi, John Kerrigan, Debabrata Banerjee, Joseph R. Bertino, Emine E. Abali
Journal: Cancer Research (2013)

Abstract Background: NAD+ kinase (NADK) is at present the only known enzyme that converts NAD+ to NADP+, which is subsequently reduced to NADPH. The demand for NADPH in cancer cells is elevated as reducing equivalents are required for the high levels of nucleotide, protein and fatty acid synthesis found in proliferating cells, as well as for neutralizing high levels of reactive oxygen species (ROS) present in these cells. The aim of this study was to determine whether inhibitors of NADK synergize with chemotherapeutic drugs known to induce ROS. Methods: Using a NADK inhibitor our group previously identified, thionicotinamide adenine dinucleotide phosphate (NADPS), (Mol Pharmacol., in press), we explored combinations of NADPS with various classes of drugs known to induce ROS: tubulin inhibitors (docetaxel, paclitaxel, vinblastine), a nucleoside analog (gemcitabine), topoisomerase I and II inhibitors (irinotecan and doxorubicin, respectively), and a DNA crosslinking agent (cisplatin). Fixed ratios of NADPS and the combination drug based on their EC50 values were tested in a colon cancer cell line (C85) using a MTS assay. The combination index (CI) was determined by the Chou-Talalay method for drug combination based on the median effect analysis. Results: All drugs were found to synergize with NADPS. Knockdown of NADK with siRNA or inhibition of NADK by NADPS in combination with MTX revealed equivalent efficacy. Quantification of intracellular NADPH and ROS levels are currently underway. Conclusions: NADK inhibitors along with drugs that increase ROS- mediated stress may represent an efficacious antitumor combination and should be explored further against in vivo tumor models. Citation Format: Philip M. Tedeschi, John Kerrigan, Debabrata Banerjee, Joseph R. Bertino, Emine E. Abali. NAD+ Kinase inhibition synergizes with ROS-inducing chemotherapies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5536. doi:10.1158/1538-7445.AM2013-5536
Differences, games, and pluralism
Authors: Roger A. McCain
Journal: Behavioral and Brain Sciences (2000)

While concurring that the evidence from individual differences supports a Meliorist view in the rationality debate, this commentary suggests that (1) the evidence does not clearly support a two-systems interpretation against an interpretation in terms of idiosyncratic differences in mental models, and that (2), especially where interactional processing is concerned, evidence from experimental game theory should also be considered.
Inorganic pyrophosphate pool size and turnover rate in arthritic joints.
Authors: M Camerlain, D J McCarty, D C Silcox, A Jung
Journal: Journal of Clinical Investigation (1975)

Recent studies have shown elevated inorganic pyrophosphate (PPi) levels in most knee joint fluid supernates from patients with pseudogout (PG) or osteoarthritis (OA) and more modestly elevated levels in some supernates from patients with gout or rheumatoid arthritis (RA) relative to PPi levels found in the venous blood plasma of normal or arthritic subjects. We measured the intraarticular PPi pool and its rate of turnover to better understand the significance of the joint fluid-plasma PPi gradient. Preliminary studies in rabbits showed that (32-P)PPi passed from joint space to blood and vice versa without detectable hydrolysis. Incubation of natural or synthetic calcium pyrophosphate dihydrate (CPPD) microcrystals with synovial fluid in vitro in the presence of (32P)PPi tracer showed no change in PPi specific activity in the supernate over a 19-h period so that exchange of PPi in solution with that in CPPD microcrystals could be ignored. Clearance rates of (32P)PPi and of (33P)Pi, as determined by serially sampling the catheterized knee joints of volunteers with various types of arthritis over a 3-h period, were nearly identical. The (32P)PPi/(32P)Pi was determined in each sample. A mixture of a large excess of cold PPi did not influence the clearance rate of either nuclide. The quantity of PPi turned over per hous was calculated from the pool size as determined by isotope dilution and the turnover rate. The residual joint fluid nuclide was shown to be (32P)PPi. The PPi pool was generally smaller and the rate of turnover was greater in clinically inflamed joints. The mean plus or minus SEM pool size (mu-moles) and turnover rate (percent/hour) in PG knees was 0.23 plus or minus 0.07 and 117 plus or minus 11.9, hydrolysis rate (%/h) to Pi was 27.7 plus or minus 13.2; in OA knees: 0.45 plus or minus 0.26 and 72 plus or minus 9.2, hydrolysis 6.9 plus or minus 0.9; in gouty knees: 0.8 plus or minus 0.41 and 50 plus or minus 11.6, hydrolysis 9.8 plus or minus 2.8; and in RA knees: 0.14 plus or minus 0.14 and 114 plus or minus 35.8, hydrolysis 236 plus or minus 116. PPi turnover (mumoles/hour) correlated with the degree of OA change present in the joint as graded by radiologic criteria irrespective of the clinical diagnosis. Mean PPi turnover in joints with advanced OA was greater than in those with mild or moderate changes (P smaller than 0.001), but the mild and moderate groups showed no significant difference. We conclude that synovial PPi turnover and elevated PPi fluid concentrations are not specific for PG patients, and that these factors alone cannot be the only determinants of CPPD crystal deposition.
Evaluation of Biomonitoring Data from the CDC National Exposure Report in a Risk Assessment Context: Perspectives across Chemicals
Authors: Lesa L. Aylward, Christopher R. Kirman, Rita Schoeny, Christopher J. Portier, Sean M. Hays
Journal: Environmental Health Perspectives (2012)

Background: Biomonitoring data reported in the National Report on Human Exposure to Environmental Chemicals [NER; Centers for Disease Control and Prevention (2012)] provide information on the presence and concentrations of > 400 chemicals in human blood and urine. Biomonitoring Equivalents (BEs) and other risk assessment–based values now allow interpretation of these biomonitoring data in a public health risk context.Objectives: We compared the measured biomarker concentrations in the NER with BEs and similar risk assessment values to provide an across-chemical risk assessment perspective on the measured levels for approximately 130 analytes in the NER.Methods: We identified available risk assessment–based biomarker screening values, including BEs and Human Biomonitoring-I (HBM-I) values from the German Human Biomonitoring Commission. Geometric mean and 95th percentile population biomarker concentrations from the NER were compared to the available screening values to generate chemical-specific hazard quotients (HQs) or cancer risk estimates.Conclusions: Most analytes in the NER show HQ values of < 1; however, some (including acrylamide, dioxin-like chemicals, benzene, xylene, several metals, di-2(ethylhexyl)phthalate, and some legacy organochlorine pesticides) approach or exceed HQ values of 1 or cancer risks of > 1 × 10–4 at the geometric mean or 95th percentile, suggesting exposure levels may exceed published human health benchmarks. This analysis provides for the first time a means for examining population biomonitoring data for multiple environmental chemicals in the context of the risk assessments for those chemicals. The results of these comparisons can be used to focus more detailed chemical-specific examination of the data and inform priorities for chemical risk management and research.
Exposure to Secondhand Smoke and Biomarkers of Cardiovascular Disease Risk in Never-Smoking Adults
Authors: Andrea Venn, John Britton
Journal: Circulation (2007)

Exposure to secondhand smoke has been associated with a disproportionately high risk of coronary heart disease, thought to be mediated through inflammation, platelet aggregation, and/or endothelial dysfunction. The epidemiological association between objectively measured exposure to secondhand smoke and biomarkers of heart disease risk has not been investigated, however.We have investigated the cross-sectional relation between secondhand smoke exposure, measured objectively as cotinine, and recognized biomarkers of heart disease risk, namely C-reactive protein, homocysteine, fibrinogen, and white blood cell count, in 7599 never-smoking adults from the Third National Health and Nutrition Examination Survey. Compared with subjects with no detectable cotinine, those with detectable but low-level cotinine (range, 0.05 to 0.215 ng/mL) had significantly higher levels of both fibrinogen (adjusted mean difference, 8.9 mg/dL; 95% CI, 0.9 to 17.0; P=0.03) and homocysteine (0.8 micromol/L; 95% CI, 0.4 to 1.1; P<0.001) but not C-reactive protein or white blood cell count. Effect estimates of similar magnitude and significance were seen in subjects in the high category of cotinine exposure (>0.215 ng/mL). The increased levels of fibrinogen and homocysteine seen in relation to secondhand smoke exposure were equivalent to approximately 30% to 45% of those seen for active smoking.Passive smokers appear to have disproportionately increased levels of 2 biomarkers of cardiovascular disease risk, fibrinogen and homocysteine. This finding provides further evidence to suggest that low-level exposure to secondhand smoke has a clinically important effect on susceptibility to cardiovascular disease.
Meta-analyses VII
Authors: P. Sedgwick
Journal: BMJ (2011)

Researchers undertook a meta-analysis of the effects of monitoring blood pressure at home.1 Randomised controlled trials were included if participants had essential hypertension and were attempting to achieve blood pressure targets. Home blood pressure monitoring was achieved with ambulatory monitors, whereas the control intervention was standard blood pressure monitoring in the healthcare system. An extensive search of electronic databases of reports and journal publications identified 13 randomised controlled trials. For these trials, the length of intervention varied between 2 and 36 months.

The meta-analysis reported that home blood pressure monitoring resulted in lower systolic blood pressure than standard monitoring, with an overall mean difference of 4.2 mm Hg (95% confidence interval 1.5 to 6.9). Potential …
Problems and Solutions for Estimating Indel Rates and Length Distributions
Authors: Reed A. Cartwright
Journal: Molecular Biology and Evolution (2008)

Insertions and deletions (indels) are fundamental but understudied components of molecular evolution. Here we present an expectation–maximization algorithm built on a pair hidden Markov model that is able to properly handle indels in neutrally evolving DNA sequences. From a data set of orthologous introns, we estimate relative rates and length distributions of indels among primates and rodents. This technique has the advantage of potentially handling large genomic data sets. We find that a zeta power-law model of indel lengths provides a much better fit than the traditional geometric model and that indel processes are conserved between our taxa. The estimated relative rates are about 12–16 indels per 100 substitutions, and the estimated power-law magnitudes are about 1.6–1.7. More significantly, we find that using the traditional geometric/affine model of indel lengths introduces artifacts into evolutionary analysis, casting doubt on studies of the evolution and diversity of indel formation using traditional models and invalidating measures of species divergence that include indel lengths.
Re: Roman Mayr, Matthias May, Thomas Martini, et al. Comorbidity and Performance Indices as Predictors of Cancer-Independent Mortality But Not of Cancer-Specific Mortality After Radical Cystectomy for Urothelial Carcinoma of the Bladder. Eur Urol 2012;62:662–70
Authors: Michael Froehner, Rainer Koch, Manfred P. Wirth
Journal: European Urology (2012)