tbuckley/cabot-search huggingface dataset:
Alpha1-antitrypsin deficiency alleles and the Taq-I G--&gt;A allele in cystic fibrosis lung disease
Authors: R Mahadeva, RC Westerbeek, DJ Perry, JU Lovegrove, DB Whitehouse, NR Carroll, RI Ross-Russell, AK Webb, D Bilton, DA Lomas
Journal: European Respiratory Journal (1998)

Cystic fibrosis (CF) is characterized by progressive and ultimately fatal pulmonary disease although there are notable variations in clinical features. This heterogeneity is thought to lie outside the cystic fibrosis transmembrane regulator (CFTR) gene locus and may stem from deficiencies in the antiproteinase screen that protects the lung from proteolytic attack. One hundred and fifty seven patients were recruited from two UK CF centres. The serum concentrations of alpha1-antitrypsin, alpha1-antichymotrypsin and C-reactive protein (CRP) were determined and patients were screened for the common S and Z deficiency alleles of alpha1-antitrypsin and the G--&gt;A mutation in the 3' noncoding region of the alpha1-antitrypsin gene (Taq-I G--&gt;A allele). Alpha1-antitrypsin deficiency phenotypes were detected in 20 (16 MS, 1 S and 3 MZ) out of 147 unrelated tested CF patients and were, surprisingly, associated with significantly better lung function (adjusted mean forced expiratory volume in one second (FEV1) 62.5% of predicted for deficient group and 51.1% pred for normal alleles; p=0.043). The Taq-I G--&gt;A allele was found in 21 out of 150 unrelated patients and had no significant effect on CF lung disease or on levels of alpha1-antitrypsin during the inflammatory response. We show here that, contrary to current thinking, common mutations of alpha1-antitrypsin that are associated with mild to moderate deficiency of the protein predict a subgroup of cystic fibrosis patients with less severe pulmonary disease. Moreover, the Taq-I G--&gt;A allele has no effect on serum levels of alpha1-antitrypsin in the inflammatory response, which suggests that the previously reported association of the Taq-I G--&gt;A allele with chronic obstructive pulmonary disease is not mediated by its effect on the serum level of alpha1-antitrypsin.
Prediction of Survival in Resected Non–Small Cell Lung Cancer Using a Protein Expression–Based Risk Model: Implications for Personalized Chemoprevention and Therapy
Authors: Kathryn A. Gold, Edward S. Kim, Diane D. Liu, Ping Yuan, Carmen Behrens, Luisa M. Solis, Humam Kadara, David C. Rice, Ignacio I. Wistuba, Stephen G. Swisher, Wayne L. Hofstetter, J. Jack Lee, Waun K. Hong
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Patients with resected non–small cell lung cancer (NSCLC) are at risk for recurrence of disease, but we do not have tools to predict which patients are at highest risk. We set out to create a risk model incorporating both clinical data and biomarkers. Experimental Design: We assembled a comprehensive database with archival tissues and clinical follow-up from patients with NSCLC resected between 2002 and 2005. Twenty-one proteins identified from our preclinical studies as related to lung carcinogenesis were investigated, including pathways related to metabolism, DNA repair, inflammation, and growth factors. Expression of proteins was quantified using immunohistochemistry. Immunohistochemistry was chosen because it is widely available and can be performed on formalin-fixed paraffin-embedded specimens. Cox models were fitted to estimate effects of clinical factors and biomarkers on recurrence-free survival (RFS) and overall survival (OS). Results: A total of 370 patients are included in our analysis. With median follow-up of 5.3 years, median OS is 6.4 years. A total of 209 cases with recurrence or death were observed. Multicovariate risk models for RFS and OS were developed including relevant biomarkers, age, and stage. Increased expression of phospho-adenosine monophosphate-activated protein kinase (pAMPK), phospho-mTOR (pmTOR), epithelial cell adhesion molecule (EpCAM), and calcium/calmodulin-dependent serine protein kinase were significant (P &amp;lt; 0.05) predictors for favorable RFS; insulin receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and insulin-like growth factor-1 receptor predicted for unfavorable RFS. Significant (P &amp;lt; 0.05) predictors for favorable OS include pAMPK, pmTOR, and EpCAM; CXCR2 and flap structure–specific endonuclease-1 predicted unfavorable OS. Conclusion: We have developed a comprehensive risk model predictive for recurrence in our large retrospective database, which is one of the largest reported series of resected NSCLC. Clin Cancer Res; 20(7); 1946–54. ©2013 AACR.
CHEMICAL FORM OF CIRCULATING ANTIDIURETIC HORMONE IN RATS
Authors: Niels A. Thorn, Lawrence Silver
Journal: The Journal of Experimental Medicine (1957)

Serum, taken from rats under ether anesthesia after injection of hypertonic saline, contained antidiuretic activity in a concentration equivalent to 1 to 3 millipressor units of pitressin per ml. The active material was retained by a collodion ultrafilter and, on electrophoretic analysis, moved with the beta globulins. Dialysis against 0.2 N acetic acid appeared to dissociate the complex. The antidiuretic factor was found in serum after stimuli known to cause release of pituitary antidiuretic hormone. Inactivation by thioglycolic acid and by proteolytic enzymes paralleled the inactivation of standard pitressin. Control experiments made it unlikely that serotonin, or any other substance released in the clotting of blood, could have contributed to the antidiuretic action. For these reasons it was concluded that the factor studied was native pituitary antidiuretic hormone circulating as a definite protein-peptide complex.
Transcription intermediary factor 1γ is a tumor suppressor in mouse and human chronic myelomonocytic leukemia
Authors: Romain Aucagne, Nathalie Droin, Jérôme Paggetti, Brice Lagrange, Anne Largeot, Arlette Hammann, Amandine Bataille, Laurent Martin, Kai-Ping Yan, Pierre Fenaux, Régine Losson, Eric Solary, Jean-Noël Bastie, Laurent Delva
Journal: Journal of Clinical Investigation (2011)

Transcription intermediary factor 1γ (TIF1γ) was suggested to play a role in erythropoiesis. However, how TIF1γ regulates the development of different blood cell lineages and whether TIF1γ is involved in human hematological malignancies remain to be determined. Here we have shown that TIF1γ was a tumor suppressor in mouse and human chronic myelomonocytic leukemia (CMML). Loss of Tif1g in mouse HSCs favored the expansion of the granulo-monocytic progenitor compartment. Furthermore, Tif1g deletion induced the age-dependent appearance of a cell-autonomous myeloproliferative disorder in mice that recapitulated essential characteristics of human CMML. TIF1γ was almost undetectable in leukemic cells of 35% of CMML patients. This downregulation was related to the hypermethylation of CpG sequences and specific histone modifications in the gene promoter. A demethylating agent restored the normal epigenetic status of the TIF1G promoter in human cells, which correlated with a reestablishment of TIF1γ expression. Together, these results demonstrate that TIF1G is an epigenetically regulated tumor suppressor gene in hematopoietic cells and suggest that changes in TIF1γ expression may be a biomarker of response to demethylating agents in CMML.
Skin Test Reactivity of Asthmatic Patients Associated with Exhaled Breath Condensate IFN-gamma Levels
Authors: D.M. Laber, W.C. Moore, A. MacDowell, J. Krings, R. Smith, A.T. Hastie, S.P. Peters, D. Meyers, E. Bleecker
Journal: Journal of Allergy and Clinical Immunology (2006)
Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency.
Authors: D C Rees, H Kelsey, J D Richards
Journal: BMJ (1993)

We investigated the effects of different neuropeptides on human dendritic cells (DC) maturation. Immature DC, derived from monocytes cultured for 6 days with IL-4 plus GM-CSF, have been exposed to somatostatin, substance P, or vasoactive intestinal peptide (VIP). Among these neuropeptides, only VIP induces the production of bioactive IL-12 and the neoexpression of CD83 on a fraction of the DC population, with an effect significant at 100 and 10 nM, respectively. These effects of VIP are dose-dependent, unaffected by polymixin B, and partly prevented by a VIP receptor antagonist. Although the effects of VIP alone remain modest, it synergizes with TNF-α to induce DC maturation. In the presence of a suboptimal concentration of TNF-α, which has no detectable effect on DC by itself, VIP induces the production of high levels of bioactive IL-12, the neoexpression of CD83 on almost all the DC population (with an effect significant at 10 and 0.1 nM, respectively), and the up-regulation of various adhesion and costimulatory molecule expression. Moreover, DC exposed to VIP plus a suboptimal concentration of TNF-α are as potent as mature DC obtained by treatment with an optimal concentration of TNF-α in stimulating allogenic T cell proliferation. Our data suggest that, in inflammatory sites, VIP may cooperate with proinflammatory mediators, such as TNF-α, to induce DC maturation.
Captopril restores hemodynamic responsiveness to atrial natriuretic peptide in rats with heart failure.
Authors: T E Raya, R W Lee, T Westhoff, S Goldman
Journal: Circulation (1989)

Atrial natriuretic peptide levels are elevated in heart failure. However, the hemodynamic responses to exogenous atrial natriuretic peptide infusion in heart failure are blunted. To determine if captopril can restore hemodynamic responsiveness to atrial natriuretic peptide infusion in rats with heart failure, studies were performed in a rat model of heart failure after coronary artery ligation. Rats with heart failure received either captopril (2 g/l drinking water) or placebo for 4 weeks and then were treated with an infusion of atrial natriuretic peptide (0.3 microgram/kg/min). Captopril treatment alone improved hemodynamics. Left ventricular end-diastolic pressure, mean aortic pressure, and mean circulatory filling pressure decreased from 22 +/- 2 to 14 +/- 1, from 106 +/- 4 to 76 +/- 3, and from 10.5 +/- 0.6 to 8.8 +/- 0.4 mm Hg, respectively. Heart rate, right atrial pressure, and hematocrit were unchanged. Total blood volume decreased from 66.0 +/- 1.0 to 60.0 +/- 1.0 ml/kg; venous compliance increased from 2.1 +/- 0.1 to 2.7 +/- 0.1 ml/kg/mm Hg. Atrial natriuretic peptide alone had minimal hemodynamic effects on rats with heart failure. There was no change in right atrial pressure, mean aortic pressure, left ventricular end-diastolic pressure, mean circulatory filling pressure, and total blood volume. However, atrial natriuretic peptide infusion increased venous compliance from 2.1 +/- 0.1 to 2.4 +/- 0.1 ml/kg/mm Hg. Heart rate and hematocrit increased from 323 +/- 5 to 359 +/- 8 beats/min and from 48 +/- 1% to 51 +/- 1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
A Synthetic Heparanase Inhibitor Reduces Proteinuria in Passive Heymann Nephritis
Authors: Vicki Levidiotis, Craig Freeman, Malcolm Punler, Paul Martinello, Brian Creese, Vito Ferro, Johan van der Vlag, Jo H.M. Berden, Christopher R. Parish, David A. Power
Journal: Journal of the American Society of Nephrology (2004)

The β-D-endoglycosidase heparanase has been proposed to be important in the pathogenesis of proteinuria by acting to selectively degrade the negatively charged side chains of heparan sulfate proteoglycans (HSPG) within the glomerular basement membrane (GBM). A loss of the negatively charged HSPG may result in alteration of the permselective properties of the GBM, loss of glomerular epithelial and endothelial cell anchor points, and liberation of growth factors. This study examined the effect of PI-88, a sulfated oligosaccharide heparanase inhibitor, on renal function, glomerular ultrastructure, and proteinuria. Continuous PI-88 infusion at 25 mg/kg per d did not adversely affect animal behavior, growth, or GFR. Cortical tubular vacuolation, however, was observed by light microscopy, and GBM thickness was significantly reduced in these animals (P < 0.0002). Tissue distribution studies using [35S]-labeled PI-88 revealed high levels of radioactivity in the kidney after a single subcutaneous injection of 25 mg/kg, suggesting protracted accumulation; moreover, active PI-88 was detected in urine. In passive Heymann nephritis, PI-88 delivered as a continuous infusion at 25 mg/kg per d significantly reduced autologous-phase proteinuria, at day 14 (P < 0.009), in the absence of altered sheep antibody deposition, C5b-9 deposition, and circulating rat anti-sheep antibody titers. Glomerular vascular endothelial growth factor and fibroblast growth factor expression was unaffected by PI-88 administration. However, PI-88 administration significantly prevented glomerular HSPG loss as demonstrated by quantitative immunofluorescence studies (P < 0.0001) in the absence of altered agrin distribution. These data therefore confirm the importance of heparanase in the development of proteinuria.
Enterocolitis in Patients With Cancer After Antibody Blockade of Cytotoxic T-Lymphocyte–Associated Antigen 4
Authors: Kimberly E. Beck, Joseph A. Blansfield, Khoi Q. Tran, Andrew L. Feldman, Marybeth S. Hughes, Richard E. Royal, Udai S. Kammula, Suzanne L. Topalian, Richard M. Sherry, David Kleiner, Martha Quezado, Israel Lowy, Michael Yellin, Steven A. Rosenberg, James C. Yang
Journal: Journal of Clinical Oncology (2006)

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms in human CTLA4 are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted in durable cancer regression and immune-mediated toxicities. A report on the diagnosis, pathology, treatment, clinical outcome, and significance of the immune-mediated enterocolitis seen with ipilimumab is presented.We treated 198 patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) with ipilimumab.The overall objective tumor response rate was 14%. We observed several immune mediated toxicities including dermatitis, enterocolitis, hypophysitis, uveitis, hepatitis, and nephritis. Enterocolitis, defined by grade 3/4 clinical presentation and/or biopsy documentation, was the most common major toxicity (21% of patients). It presented with diarrhea, and biopsies showed both neutrophilic and lymphocytic inflammation. Most patients who developed enterocolitis responded to high-dose systemic corticosteroids. There was no evidence that steroid administration affected tumor responses. Five patients developed perforation or required colectomy. Four other patients with steroid-refractory enterocolitis appeared to respond promptly to tumor necrosis factor alpha blockade with infliximab. Objective tumor response rates in patients with enterocolitis were 36% for MM and 35% for RCC, compared with 11% and 2% in patients without enterocolitis, respectively (P = .0065 for MM and P = .0016 for RCC).CTLA4 seems to be a significant component of tolerance to tumor and in protection against immune mediated enterocolitis and these phenomena are significantly associated in cancer patients.
Production of bile duct hyperplasia and gallstones by lithocholic acid.
Authors: R H Palmer, Z Ruban
Journal: Journal of Clinical Investigation (1966)

Lithocholic acid 1 is an important metabolite of cholesterol in man and other animals.Interest in its biological properties stems from its marked toxicity.It is the most potent of the naturally oc- curring steroids that produce intense fever and in- flammation in man (2, 3) and inflammation in a number of other species (3,4).It is also one of the most active steroid hemolysins (5).In addi- tion, its oral administration produces cirrhosis of the liver in rabbits ( 6) and ductular cell hyper- plasia in a variety of species, including rodents (7), reptiles (8), and primates (9).In view of its physiological occurrence, its known toxic proper- ties, and its potential relevance to human disease, we have investigated the effects of feeding large amounts of lithocholic acid to rats.The resulting bile duct hyperplasia and choledocholithiasis are described in this report. MethodsThe acute effects of lithocholic acid and sodium litho- cholate on Sprague-Dawley rats were investigated in *
Herpes simplex virus dispersal by HyfrecatorR electrodes
Authors: G.B. COLVER, J.F. PEUTHERER
Journal: British Journal of Dermatology (1987)

The dispersal of herpes virus by electrodes has been studied. A Birtcher Hyfrecator electrode was used to treat skin biopsy samples to simulate the clinical setting. Discharge of the electrode over a drop of dye demonstrated that droplets can be showered over 5 cm. The virus could survive on a contaminated electrode at room temperature for at least 5 min. Contaminated electrodes were not sterilized by electrical discharge, and virus transfer to skin samples was demonstrated after contact treatment. Virus could not be recovered from probes after treating contaminated skin samples. We conclude that it is essential to sterilize probes between patients to avoid transmission of infection.
Association between muscular strength and mortality in men: prospective cohort study
Authors: J. R Ruiz, X. Sui, F. Lobelo, J. R Morrow, A. W Jackson, M. Sjostrom, S. N Blair
Journal: BMJ (2008)

<b>Objective</b> To examine prospectively the association between muscular strength and mortality from all causes, cardiovascular disease, and cancer in men. <b>Design</b> Prospective cohort study. <b>Setting</b> Aerobics centre longitudinal study. <b>Participants</b> 8762 men aged 20-80. <b>Main outcome measures</b> All cause mortality up to 31 December 2003; muscular strength, quantified by combining one repetition maximal measures for leg and bench presses and further categorised as age specific thirds of the combined strength variable; and cardiorespiratory fitness assessed by a maximal exercise test on a treadmill. <b>Results</b> During an average follow-up of 18.9 years, 503 deaths occurred (145 cardiovascular disease, 199 cancer). Age adjusted death rates per 10 000 person years across incremental thirds of muscular strength were 38.9, 25.9, and 26.6 for all causes; 12.1, 7.6, and 6.6 for cardiovascular disease; and 6.1, 4.9, and 4.2 for cancer (all P&lt;0.01 for linear trend). After adjusting for age, physical activity, smoking, alcohol intake, body mass index, baseline medical conditions, and family history of cardiovascular disease, hazard ratios across incremental thirds of muscular strength for all cause mortality were 1.0 (referent), 0.72 (95% confidence interval 0.58 to 0.90), and 0.77 (0.62 to 0.96); for death from cardiovascular disease were 1.0 (referent), 0.74 (0.50 to 1.10), and 0.71 (0.47 to 1.07); and for death from cancer were 1.0 (referent), 0.72 (0.51 to 1.00), and 0.68 (0.48 to 0.97). The pattern of the association between muscular strength and death from all causes and cancer persisted after further adjustment for cardiorespiratory fitness; however, the association between muscular strength and death from cardiovascular disease was attenuated after further adjustment for cardiorespiratory fitness. <b>Conclusion</b> Muscular strength is inversely and independently associated with death from all causes and cancer in men, even after adjusting for cardiorespiratory fitness and other potential confounders.
Apico-basal Diameters of the Lungs and Mediastinal Shift in Phrenic Nerve Crush and Pneumoperitoneum Therapy: A Study of Eighty Cases
Authors: W. Fox
Journal: Thorax (1950)

The objects of this paper are (a) to report on a study of mediastinal shift and apico-basal diameters of the lungs in a series of 80 patients undergoing phrenic nerve crush and pneumoperitoneum therapy for pulmonary tuberculosis: (b) to discuss the mechanism and therapeutic significance of the mediastinal shift.Although studies of mediastinal shift following phrenic nerve paralysis alone have been reported by Nehil and Alexander (1933) and Hansen and Maly (1934), no previous study of mediastinal shift following phrenic nerve crush and pneumo- peritoneum therapy has been found in a search of the literature. PRESENT STUDYThe series consisted of 80 patients undergoing phrenic nerve crush and pneumo- peritoneum therapy for pulmonary tuberculosis.All were adults, 42 being men and 38 women.There were 40 patients with left, and 40 with right, phrenic nerve crush.The average age of the patients was 27.3 years, the range being 18 to 47 years.Three patients were under 20, 55 in the 20-29, 18 in the 30-39, and four in the 40-49 age-groups.In each case a radiograph before treatment was begun, and a comparable radio- graph when the phrenic nerve crush and pneumoperitoneum therapy was fully established, were selected for the measurement of the reduction of the apico-basal diameter and the mediastinal shift.In selecting the radiographs, particular care was taken to avoid errors of rotation, or of forward and backward tilt of the patient.All the films were postero-anterior radiographs taken in full inspiration with the patient erect, the tube distance from the film being six feet.In investiga- tions of the apico-basal diameters of the lungs, it has always to be assumed that the depth of inspiration is identical at the time of exposure of the two radiographs selected for the measurements.This introduces an unavoidable source of error, but by virtue of the greatly restricted movement of the paralysed hemidiaphragm this error is smaller on the paralysed side than on the unparalysed side. SELECTION OF MATERIALThe comparable radiographs were selected bearing in mind that the shorter the interval between them the greater was the likelihood that any mediastinal shift detected would be due to the therapy rather than to alterations in the disease.
Splice variants of Enigma homolog, differentially expressed during heart development, promote or prevent hypertrophy
Authors: Tomoko Yamazaki, Sébastien Wälchli, Toshitsugu Fujita, Stephan Ryser, Masahiko Hoshijima, Werner Schlegel, Shun'ichi Kuroda, Andrés D. Maturana
Journal: Cardiovascular Research (2010)

Proteins with a PDZ (for PSD-95, DLG, ZO-1) and one to three LIM (for Lin11, Isl-1, Mec-3) domains are scaffolding sarcomeric and cytoskeletal elements that form structured muscle fibres and provide for the link to intracellular signalling by selectively associating protein kinases, ion channels, and transcription factors with the mechanical stress–strain sensors. Enigma homolog (ENH) is a PDZ–LIM protein with four splice variants: ENH1 with an N-terminal PDZ domain and three C-terminal LIM domains and ENH2, ENH3, and ENH4 without LIM domains. We addressed the functional role of ENH alternative splicing. We studied the expression of the four ENH isoforms in the heart during development and in a mouse model of heart hypertrophy. All four isoforms are expressed in the heart but the pattern of expression is clearly different between embryonic, neonatal, and adult stages. ENH1 appears as the embryonic isoform, whereas ENH2, ENH3, and ENH4 are predominant in adult heart. Moreover, alternative splicing of ENH was changed following induction of heart hypertrophy, producing an ENH isoform pattern similar to that of neonatal heart. Next, we tested a possible causal role of ENH1 and ENH4 in the development of cardiac hypertrophy. When overexpressed in rat neonatal cardiomyocytes, ENH1 promoted the expression of hypertrophy markers and increased cell volume, whereas, on the contrary, ENH4 overexpression prevented these changes. Antagonistic splice variants of ENH may play a central role in the adaptive changes of the link between mechanical stress-sensing and signalling occurring during embryonic development and/or heart hypertrophy.