tbuckley/cabot-search huggingface dataset:
Pancreatitis and Pancreatic Cancer: a Population-Based Study
Authors: A. Ekbom, J. K. McLaughlin, B.-M. Karlsson, O. Nyren, G. Gridley, H.-O. Adami, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1994)

Little is known about the etiology of cancer of the exocrine portion of the pancreas, which produces a variety of digestive enzymes. Smoking, certain dietary factors, and diabetes mellitus are considered to be risk factors, although the risk estimates are modest in most instances. A recent cohort study of patients with chronic pancreatitis indicated a ninefold to 16-fold increased risk for pancreatic cancer.Our purpose was to evaluate the relationship between various clinical types of pancreatitis and pancreatic cancer.Data for this study were collected from all inpatient medical institutions in Sweden from 1965 until 1983 by the Swedish National Board of Health and Welfare. Data were recorded on individual hospital admissions and discharges in the Inpatient Register. All patients with records in the Inpatient Register coded for acute, chronic, or unspecified pancreatitis were considered for inclusion in the study. A population-based cohort of 7956 patients with at least one discharge diagnosis of pancreatitis was monitored (up to 19 years of follow-up) for the occurrence of pancreatic cancer by record linkages to the Swedish Cancer Registry and Registry of Causes of Death.A total of 46 pancreatic cancers were diagnosed during follow-up compared with 21 expected (standardized incidence ratio [SIR] of 2.2; 95% confidence interval [CI] 1.6-2.9) for the Uppsala Health Care Region. The excess risk for women and men was similar--most pronounced during the first period of follow-up (2-4 years) after discharge and close to unity after more than 10 years of follow-up. Patients with chronic pancreatitis and patients with more than one discharge diagnosis of either acute or unspecified pancreatitis were at higher risk (SIR = 3.8; 95% CI 1.4-8.2 and SIR = 4.8; 95% CI 1.9-9.9, respectively) compared with those with only one discharge of acute (SIR = 1.6; 95% CI 0.9-2.7) or unspecified (SIR = 2.1; 95% CI 1.2-3.2) pancreatitis.Our finding of a moderate excess of pancreatic cancer among patients with pancreatitis, especially the chronic or recurrent forms, supports some earlier clinical and case-control studies, but it is not consistent with the ninefold to 16-fold risk reported in a recent cohort study. The absence of an increased risk 10 years or more after first discharge for pancreatitis argues against a straight-forward causal relationship. Because of the relatively short interval between diagnosis of pancreatitis and pancreatic cancer, it is possible that some forms of pancreatitis are a precursor to pancreatic cancer or that shared risk factors for both diseases (e.g., cigarette smoking) may also be involved.
Membrane currents and tension in cat ventricular muscle treated with cardiac glycosides.
Authors: T F McDonald, H Nawrath, W Trautwein
Journal: Circulation Research (1975)

The effect of cardiac glycosides on membrane currents and tension in cat ventricular muscle was studied using the single sucrose gap voltage clamp method. Complete tension-voltage and current-voltage relations were obtained in five preparations before and during treatment with dihydro-ouabain (DHO, 1.7 X 10(-5)M). After 1-2 minutes of DHO, the developed tension was 15% greater than control, but there was no change in either the slow inward (calcium) current (Ica) or the level of the outward current flowing at the end of a 300-msec depolarization (Iout). After 6-8 minutes of DHO, there was a 60% increase in developed tension, a noticeable increase in resting tension, a 20% decrease in Ica, and a smaller increase in Iout. It seems possible that the reduction of Ica was due to a reduced driving force. In preparations treated with ouabain (5 X 10(-7)M, 3-5 minutes), developed tension was 45-150% greater than control with no change in Ica or Iout between -45 and + 15 mv. We conclude that the inotropic action of these cardiac glycosides is not mediated by an increase in Ica.
Structure and Molecular Phylogeny of sasA Genes in Cyanobacteria: Insights into Evolution of the Prokaryotic Circadian System
Authors: V. Dvornyk
Journal: Molecular Biology and Evolution (2004)

Cyanobacteria are the simplest organisms known to have a circadian system. In addition to the three well-studied kai genes, kaiA, kaiB, and kaiC, an important element of this system is a two-component sensory transduction histidine kinase sasA. Using publicly available data of complete prokaryotic genomes, we performed structural and phylogenetic analyses of the sasA genes. Results show that this gene has a triple-domain structure, and the domains are under different selective constraints. The sasA gene originated in cyanobacteria probably through the fusion of the ancestral kaiB gene with a double-domain, two-component sensory transduction histidine kinase. The results of the phylogenetic analyses suggest that sasA emerged before the kaiA gene, about 3,000-2,500 MYA, and has evolved in parallel with the evolution of the kaiBC cluster. The observed concordant patterns of the sasA and kaiBC evolution suggest that these genes might compose an ancient KaiBC-SasA-based circadian system, without the kaiA gene, and that such a system still exists in some unicellular cyanobacteria.
Monocyte migration into the subendothelial space of a coculture of adult human aortic endothelial and smooth muscle cells.
Authors: M Navab, G P Hough, L W Stevenson, D C Drinkwater, H Laks, A M Fogelman
Journal: Journal of Clinical Investigation (1988)

Human aortic endothelial cells (EC) and smooth muscle cells (SMC) were isolated and used to form a multilayer of EC-SMC separated by a layer of collagen. SMC and/or collagen layers exerted minimal effects on Na+ transport but impeded the transport of LDL. The presence of an endothelial monolayer markedly reduced the transport of Na+ and LDL. When monocytes were presented to the complete coculture, in the absence of added chemoattractant, one monocyte entered the subendothelial space for every one to three EC present. In contrast, neither collagen nor SMC plus collagen nor EC plus collagen induced comparable monocyte migration. Despite massive migration of monocytes into the coculture, no significant alteration in Na+ transport was observed. LDL transport into the preparation during massive monocyte migration increased modestly, but this was far less than the amount of LDL transported in the absence of an endothelial monolayer. We conclude that (a) the endothelial monolayer was the principal permeability barrier, (b) a substantial migration of monocytes occurred in the absence of added chemoattractant when both EC and SMC were present in the coculture, (c) endothelial barrier function was largely maintained after monocyte migration; and (d) these experiments indicate the need to study all three cell types (monocytes, EC, and SMC) together to understand the complex interactions that occur between these cells.
Compounds Containing Cytosolic Choline in the Basal Ganglia: A Potential Biological Marker of True Drug Response to Fluoxetine
Authors: Shamsah B. Sonawalla, Perry F. Renshaw, Constance M. Moore, Jonathan E. Alpert, Andrew A. Nierenberg, Jerrold F. Rosenbaum, Maurizio Fava
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Studies have identified two types of antidepressant response: true drug response and placebo pattern response. This study examined the relationship between true drug response and choline-creatine ratios in the basal ganglia of depressed patients treated with fluoxetine. METHOD: The authors evaluated drug-free outpatients with major depression before (N=41) and after (N=15) 8 weeks of fluoxetine treatment, 20 mg/day, by using proton magnetic resonance spectroscopy. RESULTS: There was a significant difference in the degree of change from baseline to week 8 in choline-creatine ratios between the true drug response group (N=8) and the placebo pattern response/nonresponse group (N=7); the true drug response patients had a 20% increase in choline-creatine ratios, and the placebo pattern response/nonresponse patients had a 12% decrease in choline-creatine ratios. CONCLUSIONS: These data suggest that true drug response to fluoxetine treatment in depression may be associated with an increase in choline-creatine ratios in the basal ganglia.
An Epidermal Growth Factor Receptor Intron 1 Polymorphism Mediates Response to Epidermal Growth Factor Receptor Inhibitors
Authors: Maria L. Amador, Darin Oppenheimer, Sofia Perea, Anirban Maitra, George Cusati, Christi Iacobuzio-Donahue, Sharyn D. Baker, Raheela Ashfaq, Chris Takimoto, Arlene Forastiere, Manuel Hidalgo
Journal: Cancer Research (2004)

Abstract This study tested the hypothesis that the number of CA single sequence repeat (CA-SSR) in the intron 1 of the epidermal growth factor receptor (egfr) gene, which affects transcription efficiency of the gene, is associated with the response to EGFR inhibitors. To this end, we determined the number of CA dinucleotides in the intron 1 of the egfr gene in a panel of 12 head and neck cancer cell lines that lack egfr gene amplification and measured the expression of EGFR (mRNA and protein), as well as response to EGFR inhibition. Cells with lower number of CA dinucleotides in the CA-SSR had higher expression of the EGFR gene and protein and were more sensitive to the inhibitory effects of erlotinib, a small molecule inhibitor of the EGFR tyrosine-kinase. Phenotypic modification by silencing EGFR mRNA expression in a susceptible cell line induced resistance to the drug. The number of CA dinucleotide was equivalent in genomic and tumor DNA obtained from 30 patients with head and neck cancer. In a clinical study in colorectal cancer, subjects with lower number of CA dinucleotide frequently developed skin toxicity, a feature that is related to the antitumor activity of this class of drugs. These results suggest that polymorphic variations in the intron 1 of the egfr gene is associated with response to EGFR inhibitors and may provide an explanation as to why the development of skin toxicity is associated with a favorable outcome in patients treated with these agents.
An independent association between obstructive sleep apnoea and coronary artery disease
Authors: Y. Peker, H. Kraiczi, J Hedner, S Löth, Å. Johansson, M. Bende
Journal: European Respiratory Journal (1999)

Previous studies of sleep and breathing suggest an independent association between coronary artery disease (CAD) and obstructive sleep apnoea (OSA) in middle-aged males and females. These studies, however, were criticized because they did not properly adjust for all important confounding factors. In order to better control for the impact of these confounders, a case-control study was performed, matching for age, sex and body mass index (BMI), and additionally adjusting for hypertension, hypercholesterolemia, diabetes mellitus and current smoking. A consecutive selection of 62 patients (44 males and 18 females, mean age 69 yrs, range 44-88 yrs) requiring intensive care for angina pectoris or myocardial infarction at the County Hospital of Skaraborg, Skovde, Sweden, as well as 62 age-, sex- and BMI- matched control subjects without history or signs of heart disease underwent an overnight sleep/ventilatory monitoring study. The time interval between discharge from the intensive care unit and the overnight study ranged between 4 and 21 months. OSA, defined as a Respiratory Disturbance Index (RDI) of &gt; or =10 x h(-1), was present in 19 CAD patients but only in eight control subjects (p=0.017). Using a univariate logistic regression analysis, current smoking (odds ratio (OR) 8.1, 95% confidence interval (CI) 2.2-29.0), diabetes mellitus (OR 4.2, 95% CI 1.1-16.1) and OSA (OR 3.0, 95% CI 1.2-7.5), but not hypertension (OR 1.5, 95% CI 0.7-3.2) and hypercholesterolaemia (OR 1.8, 95% CI 0.7-4.1) were significantly correlated with CAD. In a multiple logistic regression model, current smoking (OR 9.8, 95% CI 2.6-36.5), diabetes mellitus (OR 4.2, 95% CI 1.1-17.1) and OSA (OR 3.1, 95% CI 1.2-8.3) all remained independently associated with CAD. In summary, these data suggest a high occurrence of obstructive sleep apnoea in middle-aged and elderly patients with coronary artery disease requiring intensive care, which should be taken into account when considering risk factors for coronary artery disease.
Interleukin-2 Receptor-Directed Therapies: Antibody-or Cytokine-Based Targeting Molecules
Authors: T B Strom, V R Kelley, J R Murphy, J Nichols, T G Woodworth
Journal: Annual Review of Medicine (1993)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Sympathetic Ganglionic Transmission and the Cardiovascular Changes of the Defense Reaction in the Cat
Authors: ARTHUR M. BROWN
Journal: Circulation Research (1969)

The effects of ganglionic blockade on the circulatory components of the defense reaction were studied in 25 anesthetized cats. Hexamethonium alone partially blocked the response; a combination of hexamethonium and atropine was necessary to block it completely. Vasodilation of skeletal muscle was reversed to vasoconstriction during hexamethonium infusion. Direct recording from pre- and postganglionic sympathetic nerves showed persisting ganglionic transmission during hexamethonium infusion that was subsequently blocked by atropine. Unit recordings showed that some ganglion cells were completely blocked by hexamethonium alone. Preganglionic discharge was unaffected. It is suggested that ganglion cells giving rise to cholinergic vasodilator fibers have fewer atropine-sensitive receptor sites than do cells from which adrenergic constrictor fibers arise.
1266 ENHANCED PRODUCTION OF IFN-γ AND AGE ASSOCIATED ALTERATIONS IN CD4+ AND CD8+ PERIPHERAL SUBSETS IN NONALCOHOLIC STEATOHEPATITIS
Authors: M.E. Inzaugarat, N. Ferreyra Solari, C. Lezama, M. Galoppo, R. Abecasis, P. Casavalle, P. Casciato, P. Baz, A. Billordo, A. Cherñavsky
Journal: Journal of Hepatology (2011)
<i>p53 Arg72Pro</i> and <i>MDM2 T309G</i> Polymorphisms, Histology, and Esophageal Cancer Prognosis
Authors: David W. Cescon, Penelope A. Bradbury, Kofi Asomaning, Jessica Hopkins, Rihong Zhai, Wei Zhou, Zhaoxi Wang, Matthew Kulke, Li Su, Clement Ma, Wei Xu, Ariela L. Marshall, Rebecca Suk Heist, John C. Wain, Thomas J. Lynch, David C. Christiani, Geoffrey Liu
Journal: Clinical Cancer Research (2009)

This study aimed to evaluate the prognostic significance of two functional single nucleotide polymorphisms (SNP) in the p53 pathway (p53 Arg72Pro and MDM2 T309G) in patients with esophageal cancer, and to determine the importance of histologic subtype in the SNP-outcome relationships.A cohort of 371 patients with esophageal carcinoma enrolled in Boston, USA from 1999 to 2004 were genotyped for the p53 and MDM2 SNPs. Associations between genotypes and overall survival (OS; the primary outcome) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Cox proportional hazard models, adjusted for age, stage, performance status, and smoking were developed. Interaction analyses were done for histology (adenocarcinoma versus squamous cell carcinoma).At the median follow-up of 33 months, median survival (MS) and PFS were 29.1 and 15.7 months, respectively. p53 Pro/Pro was strongly associated with shorter survival in the entire cohort (MS of 11.8 versus 29.1 months, P < 0.0001; adjusted hazard ratio for death, 2.05; 95% confidence interval, 1.30-3.24; P = 0.002 for Pro/Pro versus Arg/Arg). MDM2 G/G was associated with markedly reduced survival in squamous cell carcinoma (MS of 10.3 versus 49.4 months; adjusted hazard ratio for death, 7.9; 95% confidence interval, 2.4-26.0; P = 0.0007 for G/G versus T/T) but not in adenocarcinoma (SNP-histology interaction P = 0.004).In a large prospective cohort, p53 Arg72Pro Pro/Pro was associated with a 2-fold increased risk of death in all esophageal cancers, whereas MDM2 T309G G/G was associated with a 7-fold increased risk of death in squamous cell carcinoma.
Response Inhibition in Adolescents Diagnosed With Attention Deficit Hyperactivity Disorder During Childhood: An Event-Related fMRI Study
Authors: Kurt P. Schulz, Jin Fan, Cheuk Y. Tang, Jeffrey H. Newcorn, Monte S. Buchsbaum, Angeles M. Cheung, Jeffrey M. Halperin
Journal: American Journal of Psychiatry (2004)

Frontostriatal neural abnormalities have been implicated in the response inhibition impairments that are characteristic of attention deficit hyperactivity disorder (ADHD). However, reports of such abnormalities in adolescents are inconsistent. The present study used behavioral and functional neuroimaging techniques to examine inhibitory control processes in adolescents who had been diagnosed with ADHD during childhood.The authors used functional magnetic resonance imaging (fMRI) during performance of a Go/No-Go task to scan 10 male adolescents who were diagnosed with DSM-III-R ADHD when they were 7 to 11 years old and nine age-, sex-, and IQ-matched comparison subjects with no history of ADHD. Response inhibition was tested by contrasting neural activation during No-Go trials with that during Go trials.The inhibition of a prepotent tendency to respond produced markedly greater activation of the left anterior cingulate gyrus, bilateral frontopolar regions, bilateral ventrolateral prefrontal cortex, and left medial frontal gyrus in the adolescents with childhood ADHD than in the adolescents with no history of ADHD. Activity in the first two regions was inversely related to task performance across the study group.Compared with adolescents who had no history of ADHD, adolescents who were diagnosed with ADHD during childhood exhibited enhanced responses during inhibition in ventrolateral prefrontal cortical areas that subserve response inhibition, as well as in anterior cingulate and frontopolar regions implicated in other executive functions.
Quantitative proteomics on bronchial biopsies from asthma and COPD: Effects of budesonide treatment
Authors: Serena O'Neil, Brigita Sitkauskiene, Agne Babusyte, Algirda Krisiukeniene, Kristina Stravinskaite-Bieksiene, Raimundas Sakalauskas, Carina Sihlbom, Linda Ekerljung, Elisabet Carlsohn, Bo Lundbäck, Jan Lötvall
Journal: European Respiratory Journal (2011)

The global proteome of individual bronchial biopsy material from asthma and COPD patients has not been fully ascertained.  The aim was to determine if mechanisms of disease and responses to treatment can be detected in biopsies from patients with asthma and COPD, using a quantitative proteomics technology.  Endobronchial biopsies, pre and post treatment, were taken from patients with asthma (n=12) and COPD (n=11), as well as non-smoking (n=3) and smoking (n=2) healthy controls. Patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months). Quantitative proteomics technology was used to identify and quantify biopsy proteins. Pathways analysis was conducted to identify global proteome differences.  A total of 1937 proteins were identified from all subjects. Proteome differences in asthma and COPD and changes in response to treatment could be observed. Analysis of the global proteome of COPD revealed that the top protein network contained the function of connective tissue disorder and that metabolic pathways were most relevant. In comparison, the top network in asthma contained dermatological functions, with the pathways being more actin-based. Changes in the proteome could also be observed in response to treatment. The increased relevance of cellular biological processes and decrease of oxidative stress can be seen for both asthma and COPD. Of particular interest, hepatic fibrosis was more associated with the COPD proteome and is altered with budesonide treatment.  These results show that proteome differences can be detected using quantitative proteomics technology on clinically relevant biopsies from individual patients.
Health Care Transition in Patients With Type 1 Diabetes
Authors: Katharine C. Garvey, Howard A. Wolpert, Erinn T. Rhodes, Lori M. Laffel, Ken Kleinman, Margaret G. Beste, Joseph I. Wolfsdorf, Jonathan A. Finkelstein
Journal: Diabetes Care (2012)

OBJECTIVE To examine characteristics of the transition from pediatric to adult care in emerging adults with type 1 diabetes and evaluate associations between transition characteristics and glycemic control. RESEARCH DESIGN AND METHODS We developed and mailed a survey to evaluate the transition process in emerging adults with type 1 diabetes, aged 22 to 30 years, receiving adult diabetes care at a single center. Current A1C data were obtained from the medical record. RESULTS The response rate was 53% (258 of 484 eligible). The mean transition age was 19.5 ± 2.9 years, and 34% reported a gap &amp;gt;6 months in establishing adult care. Common reasons for transition included feeling too old (44%), pediatric provider suggestion (41%), and college (33%). Less than half received an adult provider recommendation and &amp;lt;15% reported having a transition preparation visit or receiving written transition materials. The most recent A1C was 8.1 ± 1.3%. Respondents who felt mostly/completely prepared for transition had lower likelihood of a gap &amp;gt;6 months between pediatric and adult care (adjusted odds ratio 0.47 [95% CI 0.25–0.88]). In multivariate analysis, pretransition A1C (β = 0.49, P &amp;lt; 0.0001), current age (β = −0.07, P = 0.03), and education (β = −0.55, P = 0.01) significantly influenced current posttransition A1C. There was no independent association of transition preparation with posttransition A1C (β = −0.17, P = 0.28). CONCLUSIONS Contemporary transition practices may help prevent gaps between pediatric and adult care but do not appear to promote improvements in A1C. More robust preparation strategies and handoffs between pediatric and adult care should be evaluated.
Early drop in systolic blood pressure and worsening renal function in acute heart failure: renal results of Pre‐RELAX‐AHF
Authors: Adriaan A. Voors, Beth A. Davison, G. Michael Felker, Piotr Ponikowski, Elaine Unemori, Gadi Cotter, John R. Teerlink, Barry H. Greenberg, Gerasimos Filippatos, Sam L. Teichman, Marco Metra
Journal: European Journal of Heart Failure (2011)
Industrial Injuries Insurance
Authors: F. R. Bettley
Journal: BMJ (1964)

Radiological examination is in general reserved for cases in which there is already firm conviction or those with a glaring dis- crepancy between examination and laboratory findings.Aortography, one is surprised to learn, was first suggested for diagnosis 60 years ago, but it is risky and may miss some definite cases.The authors favour pneumoretroperitoneum with three-dimensional tomography.But some tumours are small and at least 14 have been intrathoracic.This is a very stimulating and clearly written book, and it has been well translated.It is difficult to see how it could be improved.It is up to date and authoritative, and must surely become the classic work of reference on these tumours.C. L. COPE.