tbuckley/cabot-search huggingface dataset:
Elevated plasma glucagon-like peptide 1 and 2 concentrations in ileum resected short bowel patients with a preserved colon
Authors: P B Jeppesen
Journal: Gut (2000)

The glucagon-like peptides (GLP) 1 and 2 are secreted postprandially from L cells located mainly in the ileum. Both hormones prolong intestinal transit and GLP-2 is intestinotrophic in rodents. Patients with a jejunostomy have poor adaptation, rapid gastric and intestinal transit, and impaired postprandial GLP-2 secretion. Ileum resected short bowel patients with a preserved colon show evidence of functional adaptation and have normal gastric emptying.To investigate if GLP-1 and GLP-2 contribute to the positive effects of a preserved colon in short bowel patients by measuring circulating levels of GLP-1 and GLP-2 in seven ileum resected short bowel patients with a preserved colon and seven age and sex matched controls.GLP-1 and GLP-2 immunoreactivity was measured by specific radioimmunoassays in plasma collected at fasting and at regular intervals 180 minutes after a test meal.Median (25-75%) fasting GLP-2 values were 72 (69-105) pmol/l versus 23 (19-27) pmol/l (p=0.001) and meal stimulated area under the curve was 21 078 (14 811-26 610) min x pmol/l versus 11 150 (7151-12 801) min x pmol/l (p=0.01) in short bowel patients with a preserved colon compared with control subjects. Fasting GLP-1 values were 10 (6-12) pmol/l versus 5 (3-5) pmol/l (p=0.01) and meal stimulated area under the curve was 3418 (2966-6850) min x pmol/l versus 2478 (1929-3199) min x pmol/l (p=0.04), respectively.Ileum resected short bowel patients with a preserved colon had elevated fasting plasma concentrations of GLP-1 and GLP-2 and significantly larger meal stimulated areas under the curve compared with age and sex matched controls. Elevated GLP-1 and GLP-2 concentrations may contribute to the positive effects of a preserved colon on intestinal motility and functional adaptation in ileum resected short bowel patients.
Osler and the skin
Authors: J.A. Savin
Journal: British Journal of Dermatology (2000)

William Osler was the greatest physician of his time. Specialists reading his textbooks agreed that in their own specialities he was accurate and illuminating. His grasp of dermatology was particularly striking and skin changes are prominent in five of the syndromes named after him and in at least 100 of his papers. This paper describes how his early training in dermatology under Tilbury Fox in London and Hebra in Vienna combined with his unusual personal qualities to enable him to make massive contributions to a wide variety of dermatological topics. These include smallpox, cutaneous tuberculosis, nail growth, leprosy, scleroderma, pigmentation and purpuric eruptions as well as the more obvious hereditary haemorrhagic telangiectasia, angio-neurotic oedema and Osler’s nodes.
Neutrophils in respiratory syncytial virus infection: A target for asthma prevention
Authors: Ruben J. Geerdink, Janesh Pillay, Linde Meyaard, Louis Bont
Journal: Journal of Allergy and Clinical Immunology (2015)

Lower respiratory tract infections by respiratory syncytial virus (RSV) are the foremost cause of infant hospitalization and are implicated in lasting pulmonary impairment and the development of asthma. Neutrophils infiltrate the airways of pediatric patients with RSV-induced bronchiolitis in vast numbers: approximately 80% of infiltrated cells are neutrophils. However, why neutrophils are recruited to the site of viral respiratory tract infection is not clear. In this review we discuss the beneficial and pathologic contributions of neutrophils to the immune response against RSV infection. Neutrophils can limit viral replication and spread, as well as stimulate an effective antiviral adaptive immune response. However, low specificity of neutrophil antimicrobial armaments allows for collateral tissue damage. Neutrophil-induced injury to the airways during the delicate period of infant lung development has lasting adverse consequences for pulmonary architecture and might promote the onset of asthma in susceptible subjects. We suggest that pharmacologic modulation of neutrophils should be explored as a viable future therapy for severe RSV-induced bronchiolitis and thereby prevent the inception of subsequent asthma. The antiviral functions of neutrophils suggest that targeting of neutrophils in patients with RSV-induced bronchiolitis is best performed under the umbrella of antiviral treatment.
Susceptibility and Resistance to Viral Leukemogenesis in the Mouse. II. Response to the Virus Relative to Histocompatibility Factors Carried by the Prospective Host&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Judith R. Tennant
Journal: JNCI Journal of the National Cancer Institute (1965)

Two strains of mice, congenic, with a proved difference at the H-2 locus, manifested a 20 percent difference in susceptibility to viral leukemogenesis when inoculated with the BALB/Tennant-leukemia (B/T-L) virus as sucklings. Crosses were made between females of the BALB/c strain, primary to the virus, and males of each of 8 unrelated “foreign” strains, some of which were resistant and some susceptible to the virus. With one exception (C57BR/cdJ), F1 offspring were 92 to 100 percent susceptible to the virus, regardless of partial or total resistance of the foreign parent; offspring of the (BALB/cJ × C57BR/cd) cross appeared to be totally resistant. F2 subjects of crosses between the BALB/c strain and each of two totally resistant strains (C3HeB/FeJ and C57BR/cdJ) were inoculated as sucklings with virus and serotyped as adults for major H-2 antigens. The first cross yielded 72 percent leukemia induction, the second cross only 39 percent; no correlation was found between the H-2 serotype of the host and its susceptibility or resistance to leukemogenesis by the virus. Backcross individuals of the cross BALB/cJ × C3HeB/FeJ yielded 100 percent leukemia when F1 females were mated to BALB/cJ males, but only 6 percent (within spontaneous incidence bounds) when the males derived from the C3HeB/FeJ strain; again, no correlation was found between H-2 serotype and reactivity of the host to the virus. After one passage through F1, F2, or “foreign” strain mice, virus was returned to the BALB/cJ strain for evidence of alteration of the virus such as might be expected if coating of the virus by protein from the cell membrane had occurred in passage through the intermediate host. No such evidence was found. These results suggest that the H-2 constitution of the host may be a contributing factor to viral leukemogenesis, but is not the predominant factor.
Hepatic mitochondrial glutathione depletion and progression of experimental alcoholic liver disease in rats
Authors: Akeshi Hirano, Neil Kaplowitz, Hidekazu Tsukamoto, Seiichiro Kamimura, Jose C. Fernandez-Checa
Journal: Hepatology (1992)

Long-term ethanol feeding has been shown to selectively reduce hepatic mitochondrial glutathione content by impairing mitochondrial uptake of this thiol. In this study, we assessed the role of this defect in evolution of alcoholic liver disease by examining the mitochondrial glutathione pool and lipid peroxidation during progression of experimental alcoholic liver disease to centrilobular liver necrosis and fibrosis. Male Wistar rats were intragastrically infused with a high-fat diet plus ethanol for 3,6 or 16 wk (the duration that resulted in induction of liver steatosis, necrosis and fibrosis, respectively). During this feeding period, the cytosolic pool of glutathione remained unchanged in the ethanol-fed animals compared with that in pair-fed controls. In contrast, the mitochondrial pool of glutathione selectively and progressively decreased in rats infused with ethanol for 3, 6 or 16 wk, by 39%, 31% and 85%, respectively. Renal mitochondrial glutathione level remained unaffected throughout the experiment. Serum ALT levels increased significantly in the ethanol-fed rats at 6 wk and remained elevated at 16 wk. In the mitochondria with severely depleted glutathione levels at 16 wk, enhanced lipid peroxidation was evidenced by increased malondialdehyde levels. Thus a progressive and selective depletion of mitochondrial glutathione is demonstrated in the liver in this experimental model of alcoholic liver disease and associated with mitochondrial lipid peroxidation and progression of liver damage.
DarkHorse: a method for genome-wide prediction of horizontal gene transfer
Authors: Sheila Podell, Terry Gaasterland
Journal: Genome biology (2007)

Abstract A new approach to rapid, genome-wide identification and ranking of horizontal transfer candidate proteins is presented. The method is quantitative, reproducible, and computationally undemanding. It can be combined with genomic signature and/or phylogenetic tree-building procedures to improve accuracy and efficiency. The method is also useful for retrospective assessments of horizontal transfer prediction reliability, recognizing orthologous sequences that may have been previously overlooked or unavailable. These features are demonstrated in bacterial, archaeal, and eukaryotic examples.
Prognostic Value of Multidetector Computed Tomography Coronary Angiography in Diabetes
Authors: Daniele Andreini, Gianluca Pontone, Saima Mushtaq, Erika Bertella, Edoardo Conte, Andrea Baggiano, Fabrizio Veglia, Piergiuseppe Agostoni, Andrea Annoni, Alberto Formenti, Piero Montorsi, Giovanni Ballerini, Antonio L. Bartorelli, Cesare Fiorentini, Mauro Pepi
Journal: Diabetes Care (2013)

OBJECTIVE To assess the prognostic role of multidetector computed tomography coronary angiography (MDCT-CA) in patients with diabetes with suspected coronary artery disease (CAD). Use of MDCT-CA is increasing in patients with suspected CAD. However, data supporting its prognostic value in patients with diabetes are limited. RESEARCH DESIGN AND METHODS Between January 2006 and September 2007, 429 consecutive diabetic patients were prospectively studied with MDCT-CA for detecting the presence and assessing the extent of CAD (disease extension and coronary plaque scores). Patients were classified according to the presence of normal coronary arteries and nonobstructive (&amp;lt;50%) and obstructive (≥50%) coronary lesions. The composite rates of hard cardiac events (cardiac death, nonfatal myocardial infarction, unstable angina) and all cardiac events (including revascularization) were the end points of the study. RESULTS Twenty-four patients were excluded because MDCT-CA data were not able to be interpreted. Of the remaining 405 patients, clinical follow-up (mean 62 ± 9 months) was obtained in 390 (98%). Multivariate analysis showed that predictors of hard and all events were obstructive CAD, three-vessel CAD, and left main coronary artery (LMCA) disease. Cumulative event-free survival was 100% for hard and all events in patients with normal coronary arteries, 78% for hard events and 56% for all events in patients with nonobstructive CAD, and 60% for hard events and 16% for all events in patients with obstructive CAD. Three-vessel CAD and LMCA disease were associated with a higher rate of hard cardiac events. CONCLUSIONS MDCT-CA provides long-term prognostic information for patients with diabetes with suspected CAD, showing excellent prognosis when there is no evidence of atherosclerosis and allowing risk stratification when CAD is present.
Toward a general theory of infantile attachment: a comparative review of aspects of the social bond
Authors: D. W. Rajecki, Michael E. Lamb, Pauline Obmascher
Journal: Behavioral and Brain Sciences (1978)

Abstract This critical appraisal of contemporary interpretations in the area of infantile attachment begins with an outline of the principal features of the Bowlby-Ainsworth ethological theory, the instrumental/operant learning theory of Gewirtz, and Hoffman's classical conditioning model. Some attention is also given to Cairns's contiguity learning analysis and the Hoffman-Solomon opponentprocess model Discussion of these theories is followed by a review of representative data from infants at four phyletic levels (precocial birds, dogs, monkeys, and human beings), with an emphasis on three aspects of social bonding: (a) the formation and persistence of social ties in the infant under conditions of maltreatment, (b) the role of the attachment object in the adjustment of the infant to the broader environment (the so-called secure base effect), and (c) the infant's reaction to involuntary separation from the attachment object. An attempt is made to judge how well each of the interpretations accounts for all or part of the data, with the conclusion that current theories do not accord completely with documented attachment phenomena. The following criticisms are highlighted: Ethological theory emphasizes that infants' behavior systems have been shaped by the ordinarily expectable environment and depend on that environment for their functioning, yet infants of many species form bonds to objects not typical in any species' environment, or even to sources of maltreatment. Learning theory is faulted for making predictions contradicted by the maltreatment data and for a lack of formal mechanisms to account for the secure base and separation effects. The contiguity analysis is criticized for its inability to account for the emergence of certain response patterns during separation, and the opponent-process model is called into question because of its failure to fit important affective dynamics of social separation (a central focus of this theory). Recommendations for future theories of attachment are offered.
Oesophageal clearance of acid and bile: a combined radionuclide, pH, and Bilitec study
Authors: G H Koek, R Vos, Patrick Flamen, D Sifrim, F Lammert, B Vanbilloen, Jérome Janssens, Jurgen Tack
Journal: Gut (2003)

<b>Background:</b> Studies combining pH and Bilitec monitoring found a high prevalence of both acid and duodeno-gastro-oesophageal reflux in severe reflux disease. Clearance of refluxed material is a major defence mechanism against reflux. Several studies have been devoted to oesophageal acid clearance but oesophageal clearance of refluxed duodenal contents (DC) has rarely been addressed. <b>Aim:</b> To compare oesophageal acid and DC clearance. <b>Methods:</b> Ten healthy volunteers (five women, mean age 23 (1) years) were studied. Firstly, a balloon tip catheter, positioned in the duodenum under fluoroscopy, was used to aspirate DC after stimulation by a high caloric liquid meal (200 ml, 300 kcal). During the second session, pH and Bilitec probes were positioned 5 cm above the lower oesophageal sphincter and a small infusion catheter was introduced into the proximal oesophagus. The subject was placed supine under a gamma camera. One of two different solutions (DC mixed with 0.2 mCi Tc<sup>99m</sup> pertechnetate or citric acid (pH 2) mixed with 0.2 mCi Tc<sup>99m</sup> pertechnetate) was infused into the proximal oesophagus and the subject was instructed to swallow at 20 second intervals. Clearance was assessed using scintigraphy (dynamic acquisition, one frame per second in the anterior view; calculation of time to clear peak counts to background level), pH (time to pH&lt;4) or Bilitec (time absorbance &gt;0.14) monitoring, with or without continuous saliva aspiration. Each condition was studied twice in a randomised design; measurement time was four minutes, interrupted by water flushing, with a two minute rest period. Results are given as mean (SEM) and were compared by Student's <i>t</i> test and Pearson correlation. <b>Results:</b> Scintigraphic evaluation showed a volume clearance time of 29 (3) seconds for acid and 28 (9) seconds for DC (NS). Saliva aspiration had no significant influence on volume clearance of acid or DC (28 (4) and 30 (13) seconds, respectively; NS). pH monitoring showed an acid clearance time of 217 (15) seconds, which was significantly prolonged to 324 (30) seconds during saliva aspiration (p&lt;0.05). Bilitec monitoring showed a DC clearance time of 131 (27) seconds, which was not significantly prolonged by saliva aspiration (176 (36) seconds; p = 0.08). DC clearance was faster than acid clearance, either without or with saliva aspiration (p&lt;0.055 and p&lt;0.05, respectively). <b>Conclusions:</b> Under experimental conditions, liquid acid and DC solutions have comparable volume clearances. Chemical clearance occurs slightly faster for DC than for acid, and saliva plays a major role in the clearance of acid only.
Prognostic Factors Influencing Progression-Free Survival Determined From a Series of Sporadic Desmoid Tumors: A Wait-and-See Policy According to Tumor Presentation
Authors: Sébastien Salas, Armelle Dufresne, Binh Bui, Jean-Yves Blay, Philippe Terrier, Dominique Ranchere-Vince, Sylvie Bonvalot, Eberhard Stoeckle, Louis Guillou, Axel Le Cesne, Odile Oberlin, Véronique Brouste, Jean-Michel Coindre
Journal: Journal of Clinical Oncology (2011)

Desmoid tumors are mesenchymal fibroblastic/myofibroblastic proliferations with locoregional aggressiveness and high ability to recur after initial treatment. We present the results of the largest series of sporadic desmoid tumors ever published to determine the prognostic factors of these rare tumors.Four hundred twenty-six patients with a desmoid tumor at diagnosis were included, and the following parameters were studied: age, sex, delay between first symptoms and diagnosis, tumor size, tumor site, previous history of surgery or trauma in the area of the primary tumor, surgical margins, and context of abdominal wall desmoids in women of child-bearing age during or shortly after pregnancy. We performed univariate and multivariate analysis for progression-free survival (PFS).In univariate analysis, age, tumor size, tumor site, and surgical margins (R2 v R0/R1) had a significant impact on PFS. PFS curves were not significantly different for microscopic assessment of surgical resection quality (R0 v R1). In multivariate analysis, age, tumor size, and tumor site had independent values. Three prognostic groups for PFS were defined on the basis of the number of independent unfavorable prognostic factors (0 or 1, 2, and 3).This study clearly demonstrates that there are different prognostic subgroups of desmoid tumors that could benefit from different therapeutic strategies, including a wait-and-see policy.
Efficacy and Tolerability of Temozolomide in an Alternating Weekly Regimen in Patients With Recurrent Glioma
Authors: Antje Wick, Jörg Felsberg, Joachim P. Steinbach, Ulrich Herrlinger, Michael Platten, Britta Blaschke, Richard Meyermann, Guido Reifenberger, Michael Weller, Wolfgang Wick
Journal: Journal of Clinical Oncology (2007)

Evaluation of toxicity and efficacy of an alternating weekly regimen of temozolomide administered 1 week on and 1 week off in patients with recurrent glioma.Ninety adult patients with recurrent gliomas accrued in one center received chemotherapy with temozolomide at 150 mg/m(2)/d (days 1 through 7 and 15 through 21 every 4 weeks) with individual dose adjustments according to hematologic toxicity.A total of 906 treatment weeks were delivered. Grade 4 hematotoxicity according to the Common Terminology Criteria for Adverse Events (CTCAE; version 3.0) was observed in 24 treatment weeks (2.6%). CTCAE grade 4 lymphopenia eventually developed in 11 patients (12%). There were neither cumulative lymphopenias nor opportunistic infections. The progression-free survival (PFS) rate at 6 months for glioblastoma patients was 43.8%. The median PFS in these patients was 24 weeks (95% CI, 17 to 26 weeks), the median survival time from diagnosis of progression was 38 weeks (95% CI, 30 to 46 weeks), and the 1-year survival rate from progression was 23%. O(6)-methylguanine DNA methyltransferase (MGMT) gene promoter methylation in the tumor tissue was not associated with longer PFS (log-rank P = .37).These data imply that the alternating weekly schedule is feasible, safe, and effective and clearly warrants investigation in randomized studies. Compared with more protracted low-dose temozolomide schedules, the 1-week-on/1-week-off schedule may be less toxic. We provide preliminary evidence that this dose-dense schedule is also active in patients with tumors lacking MGMT gene promoter methylation.
ALCOHOL HYPOGLYCEMIA. I. CARBOHYDRATE METABOLISM OF PATIENTS WITH CLINICAL ALCOHOL HYPOGLYCEMIA AND THE EXPERIMENTAL REPRODUCTION OF THE SYNDROME WITH PURE ETHANOL*
Authors: Norbert Freinkel, David L. Singer, Ronald A. Arky, Sheldon J. Bleicher, John B. Anderson, Cynthia K. Silbert
Journal: Journal of Clinical Investigation (1963)
Vitamin E Combined With Selenium Inhibits Atherosclerosis in Hypercholesterolemic Rabbits Independently of Effects on Plasma Cholesterol Concentrations
Authors: Dawn C. Schwenke, Stephen R. Behr
Journal: Circulation Research (1998)

Abstract —Several antioxidants inhibit atherosclerosis. This study investigated the hypothesis that combining vitamin E, a lipophilic antioxidant, with vitamin C, a hydrophilic antioxidant, and/or selenium, a cofactor of peroxidases that detoxify lipid peroxides, would inhibit atherosclerosis more effectively than vitamin E alone. We also considered whether regional variation in inhibition of atherosclerosis by antioxidants would be associated with regional variation in aortic lipophilic antioxidants. Rabbits were fed an atherogenic diet (control) or an atherogenic diet supplemented with vitamin E, vitamins E and C, vitamin E+selenium, vitamins E and C+selenium, or probucol (positive control). Supplements were as follows: vitamin E, 146 IU/d; vitamin C, 791 mg/d; selenium, 22 μg/d; or probucol, 406 mg/d. Vitamin C did not influence atherosclerosis. After 22 weeks of treatment, rank order of aortic atherosclerosis was control&gt;vitamin E (with or without vitamin C)&gt;vitamin E+selenium (with or without vitamin C)&gt;probucol. Antioxidant treatment reduced aortic cholesterol concentrations 21% to 56%, 29% to 86%, and 19% to 75% for the aortic arch, descending thoracic aorta, and abdominal aorta, respectively ( P &lt;0.025 to P &lt;0.0003 by ANOVA), with slightly greatly reductions for areas of atherosclerotic lesions. Some treatments reduced plasma cholesterol concentrations, but none altered the distribution of cholesterol among lipoproteins. Corrected for differences in plasma cholesterol concentrations, aortic cholesterol concentrations were reduced up to 72% ( P &lt;0.02) by the antioxidant treatments, with equal reductions by vitamin E+selenium and by probucol. Aortic α-tocopherol standardized by aortic cholesterol as a measure of aortic lipids was lower in the abdominal aorta than in the aortic arch of rabbits not given α-tocopherol and increased relatively more in the abdominal aorta than in the aortic arch with α-tocopherol supplementation. The results of this study suggest that vitamin E+selenium inhibited atherosclerosis as effectively as an equally hypocholesterolemic dose of probucol by a mechanism(s) that is in part independent of effects on plasma and lipoprotein cholesterol concentrations. The tendency for greater efficacy of antioxidant treatments in the abdominal aorta than aortic arch may relate to the lower concentrations of α-tocopherol in the abdominal aorta of unsupplemented rabbits.
Transcriptional regulation of protein complexes in yeast
Authors: Nicolas Simonis, Jacques van Helden, George N Cohen, Shoshana J Wodak
Journal: Genome biology (2004)

Multiprotein complexes play an essential role in many cellular processes. But our knowledge of the mechanism of their formation, regulation and lifetimes is very limited. We investigated transcriptional regulation of protein complexes in yeast using two approaches. First, known regulons, manually curated or identified by genome-wide screens, were mapped onto the components of multiprotein complexes. The complexes comprised manually curated ones and those characterized by high-throughput analyses. Second, putative regulatory sequence motifs were identified in the upstream regions of the genes involved in individual complexes and regulons were predicted on the basis of these motifs.