tbuckley/cabot-search huggingface dataset:
Abnormalities in proximal small bowel motility in patients with cirrhosis
Authors: Jaime Chesta, Claudia Defilippi, Carlos Defilippi
Journal: Hepatology (1993)

Because altered intestinal motility could be involved in the pathogenesis of small intestine bacterial overgrowth observed in some patients with cirrhosis, we investigated fasting proximal small bowel motility in 16 cirrhotic patients and 8 healthy controls. In addition, the effects of oral tetracycline administration on duodenal motility were investigated in seven cirrhotic patients with evidence of bacterial overgrowth. The mean duration and characteristics of the migrating motor complex were analyzed. Cyclic activity was observed in all healthy controls. It was absent in two cirrhotic patients showing a prolonged phase 2-like pattern. The duration of cycles was significantly longer in the remaining 14 patients with cirrhosis (166 +/- 19 min) compared with controls (81 +/- 14 min; p < 0.02). This difference was caused by a prolonged phase 2 (138 +/- 19 min in patients with cirrhosis vs. 52 +/- 11 min in controls; p < 0.02). Marked changes in the contraction pattern during phase 2 were noted in cirrhotic patients. They were characterized by multiple clusters (frequency, 12 +/- 1/hr; duration, 38 +/- 3 sec) of contractions (frequency, 11 +/- 1 cpm) separated by quiescent periods (duration, 2.4 +/- 0.2 min). This motility profile filled up 58% +/- 8% of the total duration of phase 2, and it was observed in patients with and without bacterial overgrowth. Treatment with tetracycline was followed by only mild modifications, such as a reduction of the fraction of phase 2 occupied by multiple-clustered contractions. In conclusion, an altered proximal small bowel motility has been observed in patients with cirrhosis. These disturbances appear not to be dependent on the presence of bacterial overgrowth.
The gene coding for a major tumor rejection antigen of tumor P815 is identical to the normal gene of syngeneic DBA/2 mice.
Authors: B Van den Eynde, B Lethé, A Van Pel, E De Plaen, T Boon
Journal: The Journal of Experimental Medicine (1991)

We showed previously that mouse mastocytoma P815 expresses several distinct antigens that are recognized by cytolytic T lymphocytes (CTL) of syngeneic DBA/2 mice. Antigens P815A and P815B are usually lost jointly and are targets for immune rejection responses in vivo. We used a cosmid library and a CTL stimulation assay to obtain transfectants expressing tumor rejection antigen P815A. From these transfectants we retrieved gene P1A which transferred the expression of both P815A and B. This gene is unrelated to three previously isolated genes coding for tum-antigens. It encodes a putative protein of 224 amino acids which contains two highly acidic domains showing homology with similar regions of nuclear proteins. The P1A gene expressed by tumor P815 is completely identical to the gene present in normal DBA/2 cells. Expression of the gene was tested by Northern blots. Cells from liver, spleen, and a number of mast cell lines were negative, but mast cell line L138.8A produced a high level of P1A message and was lysed by CTL directed against antigens P815A and B. We conclude that major tumor rejection antigens of P815 are encoded by a gene showing little or no expression in most normal cells of adult mice.
Parenteral Hydration in Patients With Advanced Cancer: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial
Authors: Eduardo Bruera, David Hui, Shalini Dalal, Isabel Torres-Vigil, Joseph Trumble, Joseph Roosth, Susan Krauter, Carol Strickland, Kenneth Unger, J. Lynn Palmer, Julio Allo, Susan Frisbee-Hume, Kenneth Tarleton
Journal: Journal of Clinical Oncology (2012)

The vast majority of patients with cancer at the end of life receive parenteral hydration in hospitals and no hydration in hospice, with limited evidence supporting either practice. In this randomized controlled trial, we determined the effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer.We randomly assigned 129 patients with cancer from six hospices to receive parenteral hydration (normal saline 1 L per day) or placebo (normal saline 100 mL per day) daily over 4 hours. The primary outcome was change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0 = best and 40 = worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Nursing Delirium Screening Scale (NuDESC), Unified Myoclonus Rating Scale (UMRS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Dehydration Assessment Scale, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change by day 4 ± 2 and day 7 ± 2 between groups.The hydration (n = 63) and placebo (n = 66) groups had similar baseline characteristics. We found no significant differences between the two groups for change in the sum of four dehydration symptoms (-3.3 v -2.8, P = .77), ESAS (all nonsignificant), MDAS (1 v 3.5, P = .084), NuDESC (0 v 0, P = .13), and UMRS (0 v 0, P = .54) by day 4. Results for day 7, including FACIT-F, were similar. Overall survival did not differ between the two groups (median, 21 v 15 days, P = .83).Hydration at 1 L per day did not improve symptoms, quality of life, or survival compared with placebo.
CD19+CD5+ B Cells in Primary IgA Nephropathy
Authors: He Yuling, Xiao Ruijing, Ji Xiang, Jiang Yanping, Chen Lang, Li Li, Yang Dingping, Tan Xinti, Liu Jingyi, Tang Zhiqing, Bi Yongyi, Xia Bing, Wu Xinxing, Jin Youxin, David A. Fox, Steven K. Lundy, Ding Guohua, Tan Jinquan
Journal: Journal of the American Society of Nephrology (2008)

The source of IgA and the mechanism for deposition of IgA in the mesangium remain unknown for primary IgA nephropathy. Because CD19+CD5+ B cells are important producers of IgA and contribute to several autoimmune diseases, they may play an important role in IgA nephropathy. In this study, flow cytometry, quantitative PCR, and confocal microscopy were used to assess the frequency, distribution, Ig production, CD phenotypes, cytokine production, and sensitivity to apoptosis of CD19+CD5+ B cells in the peripheral blood, peritoneal fluid, and kidney biopsies of 36 patients with primary IgA nephropathy. All patients with IgA nephropathy were significantly more likely to have CD19+CD5+ B cells in the peripheral blood, peritoneal fluid, and kidney biopsies than were five control subjects and 10 patients with active systemic lupus erythematosus. The 33 patients who had IgA nephropathy and responded to treatment demonstrated a significant decrease in CD19+CD5+ B cells in the peripheral blood, peritoneal fluid, and kidney (all P < 0.01). In the three patients who had IgA nephropathy and did not respond to treatment, the frequency of CD19+CD5+ B cells did not change. CD19+CD5+ B cells isolated from patients with untreated IgA nephropathy expressed higher levels of IgA, produced more IFN-γ, and were more resistant to CD95L-induced apoptosis than cells isolated from control subjects and patients with lupus; these properties reversed with effective treatment of IgA nephropathy. In conclusion, these results strongly suggest that CD19+CD5+ B cells play a prominent role in the pathogenesis of primary IgA nephropathy.
MicroRNA-196 represses Bach1 protein and hepatitis C virus gene expression in human hepatoma cells expressing hepatitis C viral proteins
Authors: Weihong Hou, Qing Tian, Jianyu Zheng, Herbert L. Bonkovsky
Journal: Hepatology (2009)

Hepatitis C virus (HCV) directly induces oxidative stress and liver injury. Bach1, a basic leucine zipper mammalian transcriptional repressor, negatively regulates heme oxygenase 1 (HMOX1), a key cytoprotective enzyme that has antioxidant and anti-inflammatory activities. microRNAs (miRNAs) are small noncoding RNAs (≈22 nt) that are important regulators of gene expression. Whether and how miRNAs regulate Bach1 or HCV are largely unknown. The aims of this study were to determine whether miR-196 regulates Bach1, HMOX1, and/or HCV gene expression. HCV replicon cell lines (Con1 and 9–13) of the Con1 isolate and J6/JFH1-based HCV cell culture system were used in this study. The effects of miR-196 mimic on Bach1, HMOX1, and HCV RNA, and protein levels were measured by way of quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. The Dual Glo Luciferase Assay System was used to determine reporter activities. miR-196 mimic significantly down-regulated Bach1 and up-regulated HMOX1 gene expression and inhibited HCV expression. Dual luciferase reporter assays demonstrated that transfection of miR-196 mimic resulted in a significant decrease in Bach1 3′-untranslated region (UTR)–dependent luciferase activity but not in mutant Bach1 3′-UTR–dependent luciferase activity. Moreover, there was no detectable effect of mutant miR-196 on Bach1 3′-UTR–dependent luciferase activity. Conclusion: miR-196 directly acts on the 3′-UTR of Bach1 messenger RNA and translationally represses the expression of this protein, and up-regulates HMOX1. miR-196 also inhibits HCV expression in HCV replicon cell lines (genotype 1b) and in J6/JFH1 (genotype 2a) HCV cell culture system. Thus, miR-196 plays a role in both HMOX1/Bach1 expression and the regulation of HCV expression in human hepatocytes. Overexpression of miR-196 holds promise as a potential novel strategy to prevent or ameliorate hepatitis C infection, and to protect against liver injury in chronic HCV infection. (Hepatology 2010.)
Computer Model of Cardiac Potential Distribution in an Infinite Medium and on the Human Torso during Ventricular Activation
Authors: PAUL D'ALCHÉ, PIERRE DUCIMETIERE, JACQUES LACOMBE
Journal: Circulation Research (1974)

The cardiac electrical field produced by the depolarization of the ventricles of a human heart was simulated with a computer, and the results were presented as isopotential maps. Computations were first done with the heart theoretically immersed in an infinite homogeneous medium and then with it located inside a homogeneous human torso. The principal feature of the model was that only the cardiac regions actually engaged in the depolarization generated an electrical current. Owing to their thinness, these regions could be reduced to the surfaces separating active and inactive cardiac zones at a definite instant. The surfaces used were the isochronal surfaces published by Durrer et al. for the pattern of ventricular excitation in a human heart. The assumption was made that the current flowed perpendicularly and with the same strength at each point on the surfaces. The isopotential maps were drawn on a cylindrical surface surrounding the heart and on the torso. The simulated maps were described in connection with the cardiac activation and compared with experimental maps.
Missense Mutations Located in Structural p53 DNA-Binding Motifs Are Associated With Extremely Poor Survival in Chronic Lymphocytic Leukemia
Authors: Martin Trbusek, Jana Smardova, Jitka Malcikova, Ludmila Sebejova, Petr Dobes, Miluse Svitakova, Vladimira Vranova, Marek Mraz, Hana Skuhrova Francova, Michael Doubek, Yvona Brychtova, Petr Kuglik, Sarka Pospisilova, Jiri Mayer
Journal: Journal of Clinical Oncology (2011)

Purpose There is a distinct connection between TP53 defects and poor prognosis in chronic lymphocytic leukemia (CLL). It remains unclear whether patients harboring TP53 mutations represent a homogenous prognostic group. Patients and Methods We evaluated the survival of patients with CLL and p53 defects identified at our institution by p53 yeast functional assay and complementary interphase fluorescence in situ hybridization analysis detecting del(17p) from 2003 to 2010. Results A defect of the TP53 gene was identified in 100 of 550 patients. p53 mutations were strongly associated with the deletion of 17p and the unmutated IgVH locus (both P &lt; .001). Survival assessed from the time of abnormality detection was significantly reduced in patients with both missense (P &lt; .001) and nonmissense p53 mutations (P = .004). In addition, patients harboring missense mutation located in p53 DNA-binding motifs (DBMs), structurally well-defined parts of the DNA-binding domain, manifested a clearly shorter median survival (12 months) compared with patients having missense mutations outside DBMs (41 months; P = .002) or nonmissense alterations (36 months; P = .005). The difference in survival was similar in the analysis limited to patients harboring mutation accompanied by del(17p) and was also confirmed in a subgroup harboring TP53 defect at diagnosis. The patients with p53 DBMs mutation (at diagnosis) also manifested a short median time to first therapy (TTFT; 1 month). Conclusion The substantially worse survival and the short TTFT suggest a strong mutated p53 gain-of-function phenotype in patients with CLL with DBMs mutations. The impact of p53 DBMs mutations on prognosis and response to therapy should be analyzed in investigative clinical trials.
Genetics and Cell Biology of Building Specific Synaptic Connectivity
Authors: Kang Shen, Peter Scheiffele
Journal: Annual Review of Neuroscience (2010)

The assembly of specific synaptic connections during development of the nervous system represents a remarkable example of cellular recognition and differentiation. Neurons employ several different cellular signaling strategies to solve this puzzle, which successively limit unwanted interactions and reduce the number of direct recognition events that are required to result in a specific connectivity pattern. Specificity mechanisms include the action of contact-mediated and long-range signals that support or inhibit synapse formation, which can take place directly between synaptic partners or with transient partners and transient cell populations. The molecular signals that drive the synaptic differentiation process at individual synapses in the central nervous system are similarly diverse and act through multiple, parallel differentiation pathways. This molecular complexity balances the need for central circuits to be assembled with high accuracy during development while retaining plasticity for local and dynamic regulation.
Tumor Necrosis Factor-α Promotes In Vitro Calcification of Vascular Cells via the cAMP Pathway
Authors: Yin Tintut, Jignesh Patel, Farhad Parhami, Linda L. Demer
Journal: Circulation (2000)

Background —Vascular calcification is an ectopic calcification that commonly occurs in atherosclerosis. Because tumor necrosis factor-α (TNF-α), a pleiotropic cytokine found in atherosclerotic lesions, is also a regulator of bone formation, we investigated the role of TNF-α in in vitro vascular calcification. Methods and Results —A cloned subpopulation of bovine aortic smooth muscle cells previously shown capable of osteoblastic differentiation was treated with TNF-α, and osteoblastic differentiation and mineralization were assessed. Treatment of vascular cells with TNF-α for 3 days induced an osteoblast-like morphology. It also enhanced both activity and mRNA expression of alkaline phosphatase, an early marker of osteoblastic differentiation. Continuous treatment with TNF-α for 10 days enhanced matrix mineralization as measured by radiolabeled calcium incorporation in the matrix. Pretreatment of cells with a protein kinase A–specific inhibitor, KT5720, attenuated cell morphology, the alkaline phosphatase activity, and mineralization induced by TNF-α. Consistent with this, the intracellular cAMP level was elevated after TNF-α treatment. Electrophoretic mobility shift assay demonstrated that TNF-α enhanced DNA binding of osteoblast specific factor (Osf2), AP1, and CREB, transcription factors that are important for osteoblastic differentiation. Conclusions —These results suggest that TNF-α enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular cells through the cAMP pathway.
Iron-cofactored Superoxide Dismutase Inhibits Host Responses to<i>Mycobacterium tuberculosis</i>
Authors: KATHRYN M. EDWARDS, MICHAEL H. CYNAMON, RAMA K. R. VOLADRI, CYNTHIA C. HAGER, MICHELLE S. DeSTEFANO, KYI T. THAM, DAVID L. LAKEY, MARKIAN R. BOCHAN, DOUGLAS S. KERNODLE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Superoxide dismutase (SOD) is a ubiquitous metalloenzyme in aerobic organisms that catalyzes the conversion of superoxide anion to hydrogen peroxide. Mycobacterium tuberculosis is unusual in that it secretes large quantities of iron-cofactored SOD. To determine the role of SOD in pathogenesis, we constructed mutants of M. tuberculosis H37Rv with reduced SOD production. Compared with controls, SOD-diminished isolates were more susceptible to killing by hydrogen peroxide. The isolates were markedly attenuated, exhibiting nearly 100,000-fold fewer bacilli than virulent control strains in the lungs and spleens of C57BL/6 mice 4 wk after intravenous inoculation. In the lung, SOD-attenuated M. tuberculosis induced robust interstitial mononuclear cell infiltration within 24 h and many cells were apoptotic by TUNEL staining, whereas virulent H37Rv exhibited minimal early inflammatory response and only rare interstitial mononuclear cell apoptosis. During prolonged infections, C57BL/6 mice tolerated SOD-attenuated M. tuberculosis better than BCG, exhibiting 68% greater weight gain, quicker eradication of bacilli from the spleen, and less alveolar lung infiltration. These results establish the importance of SOD in the pathogenesis of tuberculosis. Its effect appears to be mediated in part by inhibiting innate host immune responses, including early mononuclear cell infiltration of infected tissues and apoptosis.
1-Antitrypsin deficiency and lung disease: risk modification by occupational and environmental inhalants
Authors: O. Senn, E. W. Russi, M. Imboden, N. M. Probst-Hensch
Journal: European Respiratory Journal (2005)

Chronic obstructive pulmonary disease (COPD) is a prevalent and preventable disease associated with high morbidity and mortality. Severe and intermediate alpha1-antitrypsin (AAT) deficiency (serum levels <11 and 11-20 micromol.L(-1), respectively) increase the risk of COPD in active smokers. However, little is known about the interaction of severe and intermediate AAT deficiency with modifiable COPD risk factors other than active smoking. In this study, a MEDLINE search was carried out for studies investigating the combined effect of environmental inhalants (occupation and passive smoking) and AAT deficiency in the lung. A total of 18 studies using established methods for the assessment of AAT deficiency were included in this review. Occupational exposures and passive smoking affected lung function decline or prevalence of respiratory symptoms in four out of five studies investigating subjects with severe AAT deficiency, and in eight out of 13 studies with a focus on intermediate AAT deficiency. While study designs mostly prohibited formal assessment of effect modification, an interaction between intermediate AAT deficiency and passive smoking was identified in two studies with children. Additional study limitations included small sample size, poor adjustment for confounding and misclassification of environmental exposure as well as AAT activity. In conclusion, population-based epidemiological studies with associated biobanks are needed to identify gene-environment interactions and population subgroups susceptible to alpha1-antitrypsin deficiency.
Impact of initial antibiotic choice on mortality from pneumococcal pneumonia
Authors: J. Aspa, O. Rajas, F. Rodriguez de Castro, M. C. Huertas, L. Borderías, F. J. Cabello, J. Tábara, S. Hernández-Flix, A. Martinez-Sanchis, A. Torres
Journal: European Respiratory Journal (2006)

To determine the impact of initial antimicrobial choice on 30-day mortality rate in patients with community-acquired pneumonia due to Streptococcus pneumoniae (CAP-SP), a prospective, observational study was conducted in 35 Spanish hospitals. A total of 638 patients with CAP-SP were identified. Antimicrobials were chosen by the attending physician. Patients were grouped into the following categories: β-lactam monotherapy (n = 251), macrolide monotherapy (n = 37), β-lactam plus macrolide (n = 198), levofloxacin alone/combination (n = 48), and other combinations (n = 104). The reference category was β-lactam+macrolide. The 30-day survival probability was 84.9%. Using multivariate survival analysis, factors related to mortality in the entire population were: bilateral disease, suspected aspiration, shock, HIV infection, renal failure and pneumonia severity index (PSI) score Class IV versus I–III and categories V versus I–III. The association of β-lactams+macrolides was not better than the use of β-lactams alone. The current authors analysed the different groups of patients with significant mortality/morbidity: intensive care unit, PSI Class &gt;III, renal failure, chronic lung disease and bacteraemia. Only in patients with PSI Class &gt;III, who had undergone initial antimicrobial choice classified as other combinations, were associated with higher mortality. In conclusion, the current authors have not demonstrated an independent association between initial antimicrobial regimen and 30-day mortality in community-acquired pneumococcal pneumonia patients, except for those with a higher pneumonia severity index score.
GW25-e0873 Lipid-lowering therapy and lipid goal attainment in patients with metabolic syndrome in China: subgroup analysis of the Dyslipidemia International Study-China (DYSIS-China)
Authors: Wang Fan, Hu Dayi, Zhao Shuiping, Wang Yongjun, Mu Yiming, Yu Bilian, Yan Xiaowei, Li Zhanquan, Wei Yidong, Baishali M. Ambegaonakr, Min Yin, Ping Ye
Journal: Journal of the American College of Cardiology (2014)
Sustained improvement in photodamaged skin with reduced tretinoin emollient cream treatment regimen: Effect of once-weekly and three-times-weekly applications
Authors: Elise A. Olsen, H.Irving Katz, Norman Levine, Thomas P. Nigra, Peter E. Pochi, Ronald C. Savin, Jerome Shupack, Gerald D. Weinstein, Laura Lufrano, Hann-Chang Jou
Journal: Journal of the American Academy of Dermatology (1997)
The Pathology of Rigors: Illustrated by a Case of Hemiplegia, from Dislocation of the Atlas, Preceded and Accompanied by Constant Shivering and Sense of Coldness
Authors: J. B. Yeo
Journal: BMJ (1868)

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