tbuckley/cabot-search huggingface dataset:
STUDIES ON GONOCOCCUS INFECTION
Authors: John Swanson
Journal: The Journal of Experimental Medicine (1972)

Gonococci have been studied by electron microscopy after freeze-cleavage, freeze-etching and the findings correlated with those obtainable through thin sectioning and negative staining. The outer membrane of the cell wall is composed of round to hexagonal subunits 80 A in diameter. This membrane is also punctuated by 80-A holes visible on the exterior of the organism and extending into the substance or through the outer membrane. Pili coursing over the surface of the organisms appear to maintain a close anatomical relationship with the cell wall. In some instances, the surfaces of the organisms are virtually covered by a layer of pili.
DISCORDANCE BETWEEN TRADITIONAL LIPID PARAMETERS, APOLIPOPROTEINS AND LIPOPROTEIN PARTICLE NUMBER: INSIGHTS FROM THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) CAROTID MRI STUDY
Authors: Salim S. Virani, Diane J. Catellier, Vijay Nambi, Ron C. Hoogeveen, Bruce A. Wasserman, Josef Coresh, Thomas H. Mosley, James D. Otvos, A. Richey Sharrett, Eric Boerwinkle, Christie M. Ballantyne
Journal: Journal of the American College of Cardiology (2010)
Expression of Endomyocardial Nitric Oxide Synthase and Coronary Endothelial Function in Human Cardiac Allografts
Authors: S M Wildhirt, M Weis, C Schulze, N Conrad, S Pehlivanli, G Rieder, G Enders, W von Scheidt, B Reichart
Journal: Circulation (2001)

Inducible nitric oxide synthase (iNOS) is expressed and is functionally active in the presence of transplant arteriosclerosis. However, the early involvement of iNOS in alterations of microvascular endothelial function in the absence of preexisting lesions remains unclear; this information would be of prognostic value. We studied the course of iNOS mRNA expression, transcardiac nitric oxide production, and their potential association with microvascular coronary endothelial dysfunction in human cardiac allografts.A total of 42 patients were studied at 1, 6, and 12 months after heart transplantation. Microvascular coronary flow velocity reserve (CFVR) was tested in an endothelium-dependent (acetylcholine) and -independent manner (adenosine) using a Doppler flow wire. Endomyocardial iNOS expression was determined by reverse transcription polymerase chain reaction. iNOS protein and nitrotyrosine levels were detected by immunohistochemistry. Transcardiac plasma nitrite/nitrate (NOx) levels were measured by the Griess reaction. CFVR was impaired in 26.1% of patients (n=11) at 1 month and in 31% of patients (n=13) at 12 months after heart transplantation. Patients who developed impaired CFVR in the first year showed a significant increase in iNOS gene expression. Patients with impairment of CFVR 1 month after heart transplantation had higher levels of iNOS mRNA than patients with a normal CFVR. Patients with an initial impairment of CFVR who did not improve over time presented with significantly higher iNOS mRNA levels. iNOS protein and nitrotyrosine were expressed in the endomyocardial vessels of patients with impaired CFVR. Transcardiac NOx release was higher in patients with impaired CFVR.In human cardiac allografts, microvascular endothelial dysfunction is associated with an enhanced endomyocardial iNOS mRNA expression and higher transcardiac NOx production and is accompanied by the expression of nitrotyrosine protein, suggesting peroxynitrite plays a role in the disease process. The data from the present study suggest an important role for the iNOS/nitric oxide pathway in the regulation of microvascular function in the absence of preexisting atherosclerotic lesions.
IVS10+12A&gt;G polymorphism in hMSH2 gene associated with prognosis for patients with colorectal cancer
Authors: J.G. Kim, Y.S. Chae, S.K. Sohn, J.H. Moon, B.W. Kang, J.Y. Park, S.W. Jeon, M.-H. Lee, K.-H. Lim, G.S. Choi, S.-H. Jun
Journal: Annals of Oncology (2009)
Recommendations for medical management of hereditary breast and ovarian cancer: The French National Ad Hoc Committee
Authors: F. Eisinger, N. Alby, A. Bremond, J. Dauplat, M. Espié, P. Janiaud, F. Kuttenn, J.-P. Lebrun, J.-P. Lefranc, J. Pierret, H. Sobol, D. Stoppa-Lyonnet, D. Thouvenin, H. Tristant, J. Feingold
Journal: Annals of Oncology (1998)
Quality-of-Life Impairment in Depressive and Anxiety Disorders
Authors: Mark Hyman Rapaport, Cathryn Clary, Rana Fayyad, Jean Endicott
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Previous reports demonstrating quality-of-life impairment in anxiety and affective disorders have relied upon epidemiological samples or relatively small clinical studies. Administration of the same quality-of-life scale, the Quality of Life Enjoyment and Satisfaction Questionnaire, to subjects entering multiple large-scale trials for depression and anxiety disorders allowed us to compare the impact of these disorders on quality of life. METHOD: Baseline Quality of Life Enjoyment and Satisfaction Questionnaire, demographic, and clinical data from 11 treatment trials, including studies of major depressive disorder, chronic/double depression, dysthymic disorder, panic disorder, obsessive-compulsive disorder (OCD), social phobia, premenstrual dysphoric disorder, and posttraumatic stress disorder (PTSD) were analyzed. RESULTS: The proportion of patients with clinically severe impairment (two or more standard deviations below the community norm) in quality of life varied with different diagnoses: major depressive disorder (63%), chronic/double depression (85%), dysthymic disorder (56%), panic disorder (20%), OCD (26%), social phobia (21%), premenstrual dysphoric disorder (31%), and PTSD (59%). Regression analyses conducted for each disorder suggested that illness-specific symptom scales were significantly associated with baseline quality of life but explained only a small to modest proportion of the variance in Quality of Life Enjoyment and Satisfaction Questionnaire scores. CONCLUSIONS: Subjects with affective or anxiety disorders who enter clinical trials have significant quality-of-life impairment, although the degree of dysfunction varies. Diagnostic-specific symptom measures explained only a small proportion of the variance in quality of life, suggesting that an individual’s perception of quality of life is an additional factor that should be part of a complete assessment.
Clinical topics in cystic fibrosis
Authors: Tj David
Journal: Journal of the Royal Society of Medicine (2008)

This supplement arises out of the 21st one-day meeting on cystic fibrosis (CF) organized by the Section of Paediatrics of the Royal Society of Medicine. The proceedings of the first twenty meetings, held between 1985 and 2006, were published as Supplements to the JRSM, and can still be obtained from RSM Press.1–20 This supplement is also available at www.jrsm.rsmjournals.com. This most recent meeting, organized by Dr Ian Balfour-Lynn, was held at the Royal Society of Medicine in London on 20 November 2007. We are grateful to Forest Laboratories Europe for their support.

As in the past, the programme was designed to cover topical practical issues that face those who care for children and adults with CF. The audience comprised a mixture of paediatricians, adult chest physicians, physiotherapists, dietitians, CF specialist nurses, pharmacists and community and primary care medical staff, reflecting the multi-disciplinary approach to the modern management of CF.

Topics covered included newborn screening (Diane Asplin), highlights from the 2007 North American CF Conference (Di Bilton), unusual respiratory organisms (Stuart Elborn), adolescence (Terry Segal), selected CF papers published in 2007 (Ian Balfour-Lynn), a debate about the value of segregation (Steve Conway in favour, Duncan Geddes against) and four presentations by trainees.

It is hoped that all these papers will be of immediate practical interest to all doctors who care for patients with CF. The next RSM CF meeting will be held on 11 November 2008.
Use of magnetic resonance cholangiography in the diagnosis of choledocholithiasis: prospective comparison with a reference imaging method
Authors: S H Zidi, F Prat, O Le Guen, Y Rondeau, L Rocher, J Fritsch, A D Choury, G Pelletier
Journal: Gut (1999)

Background Magnetic resonance cholangiography (MRC) is a new technique for non-invasive imaging of the biliary tract. Aim To assess the results of MRC in patients with suspected bile duct stones as compared with those obtained with reference imaging methods. Patients/Methods 70 patients (34 men and 36 women, mean (SD) age 71 (15.5) years; median 75) with suspected bile duct stones were included (cholangitis, 33; pancreatitis, three; suspected post-cholecystectomy choledocholithiasis, nine; cholestasis, six; stones suspected on ultrasound or computed tomography scan, 19). MR cholangiograms with two dimensional turbo spin echo sequences were acquired. Endoscopic retrograde cholangiography with or without sphincterotomy (n = 63), endosonography (n = 5), or intraoperative cho- langiography (n = 2) were the reference imaging techniques used for the study and were performed within 12 hours of MRC. Radiologists were blinded to the results of endoscopic retrograde cholangiography and previous investigations. Results 49 patients (70%) had bile duct stones on reference imaging (common bile duct, 44, six of which impacted in the papilla; intrahepatic, four; cystic duct stump, one). Stone size ranged from 1 to 20 mm (mean 6.1, median 5.5). Twenty seven patients (55%) had bile duct stones smaller than 6 mm. MRC diagnostic accuracy for bile duct lithiasis was: sensitivity, 57.1%; specificity, 100%; positive predictive value, 100%; negative predictive value, 50%. Conclusions Stones smaller than 6 mm are still often missed by MRC when standard equipment is used. The general introduction of new technical improvements is needed before this method can be considered reliable for the diagnosis of bile duct stones.
Targeted Delivery to Cartilage Is Critical for In Vivo Efficacy of Insulin‐like Growth Factor 1 in a Rat Model of Osteoarthritis
Authors: Francesco S. Loffredo, James R. Pancoast, Lei Cai, Todd Vannelli, Jesse Z. Dong, Richard T. Lee, Parth Patwari
Journal: Arthritis & Rheumatology (2014)

Acute articular injuries lead to an increased risk of progressive joint damage and osteoarthritis (OA), and no therapies are currently available to repair or protect the injured joint tissue. Intraarticular delivery of therapeutic proteins has been limited by their rapid clearance from the joint space and lack of retention within cartilage. The aim of this study was to test whether targeted delivery to cartilage by fusion with a heparin-binding domain would be sufficient to prolong the in vivo function of the insulin-like growth factor 1 (IGF-1).We produced a humanized and optimized recombinant HB-IGF-1 fusion protein. By injecting HB-IGF-1, IGF-1, or saline alone into the knee joints of adult Lewis rats, we tested whether fusion with a heparin-binding domain 1) altered the kinetics of retention in joint tissues, 2) prolonged functional stimulation as measured by radiolabel incorporation, and 3) enhanced efficacy in a rat model of surgically induced OA, using weekly injections.Fusion of heparin-binding domain with IGF-1 prolonged retention in articular and meniscal cartilage from <1 day to 8 days after injection. Unmodified IGF-1 had no functional effect 2 days after injection, whereas HB-IGF-1 stimulated meniscal cartilage at least 4 days after injection. HB-IGF-1, but not IGF-1, significantly slowed cartilage damage in a rat model of OA.Heparin-binding domain fusions can transform rapidly cleared proteins into potential intraarticular therapies by targeting them to cartilage.
Cellular Stress Failure in Ventilator-injured Lungs
Authors: Nicholas E. Vlahakis, Rolf D. Hubmayr
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

The clinical and experimental literature has unequivocally established that mechanical ventilation with large tidal volumes is injurious to the lung. However, uncertainty about the micromechanics of injured lungs and the numerous degrees of freedom in ventilator settings leave many unanswered questions about the biophysical determinants of lung injury. In this review we focus on experimental evidence for lung cells as injury targets and the relevance of these studies for human ventilator-associated lung injury. In vitro, the stress-induced mechanical interactions between matrix and adherent cells are important for cellular remodeling as a means for preventing compromise of cell structure and ultimately cell injury or death. In vivo, these same principles apply. Large tidal volume mechanical ventilation results in physical breaks in alveolar epithelial and endothelial plasma membrane integrity and subsequent triggering of proinflammatory signaling cascades resulting in the cytokine milieu and pathologic and physiologic findings of ventilator-associated lung injury. Importantly, though, alveolar cells possess cellular repair and remodeling mechanisms that in addition to protecting the stressed cell provide potential molecular targets for the prevention and treatment of ventilator-associated lung injury in the future.
Rupture of the ventricular septum from myocardial infarction: Haemodynamic response to surgical treatment
Authors: T. Partington, J. Somerville, T. H. Sellors, L. Resnekov
Journal: Thorax (1969)

A patient aged 59 had a coronary thrombosis complicated by a ruptured ventricular septum. This was successfully repaired surgically about three months after the infarct, and some indications and problems connected with this procedure are discussed.
Effect of a three month course of ciprofloxacin on the late prognosis of reactive arthritis
Authors: T Yli-Kerttula
Journal: Annals of the Rheumatic Diseases (2003)

The value of antibiotics in the treatment of reactive arthritis (ReA) is still controversial.To analyse the long term outcome of patients with ReA, treated with a three month course of ciprofloxacin or placebo.Patients who had had ReA and had participated in a double blind, placebo controlled trial on the effectiveness of ciprofloxacin 4-7 years earlier were invited to a clinical examination. Of the 71 patients who were included in the original study, 53 agreed to visit the clinic for an examination. Twenty six of 53 patients had originally received ciprofloxacin and 27 had belonged to the placebo group. Of these, 20 in the ciprofloxacin and 25 in the placebo group were HLA-B27 positive.11/27 (41%) patients in the original placebo group had now developed chronic rheumatic disease, as compared with only 2/26 (8%) patients originally treated with ciprofloxacin (p=0.006). Two patients who originally had received placebo, none in the ciprofloxacin group had developed ankylosing spondylitis, and three patients in the original placebo group, none in the ciprofloxacin group had recurrent anterior uveitis. The same tendency was seen when several different measures were analysed. Of the patients with chronic spondyloarthropathy, 10 in the placebo and none in the ciprofloxacin group were HLA-B27 positive.Analysis 4-7 years after the initial ReA suggests that a three month course of antibiotics in the acute phase may have a beneficial effect on the long term prognosis.
Disaccharidase activity in the small intestine of gerbils (Meriones unguiculatus) during primary and challenge infections with Giardia lamblia.
Authors: M Belosevic, G M Faubert, J D MacLean
Journal: Gut (1989)

The sequence of changes in the activity of six disaccharidases in the small intestine of gerbils during primary and secondary G lamblia infections was examined. The primary G lamblia infection induced a transient reduction in disaccharidase activity which was related to the highest trophozoite burden in the small intestine. During the primary exposure, a 30% to 85% decrease in the activity of enzymes was observed on days 10 and 20 after infection. Secondary exposure of gerbils to G lamblia caused a sharp decrease in disaccharidase activity as early as 24 h after challenge. The reduction in the enzyme activity was not influenced by the size of the challenge inoculum and occurred even when there were no live trophozoites in the small intestine. Disaccharidase deficiency could also be induced by challenge with the soluble extract of the trophozoites. Multiple challenge administrations of G lamblia trophozoites to gerbils induced a persistent disaccharidase deficiency. The results indicate that disaccharidase deficiency associated with the primary G lamblia infection probably represents a direct effect of the parasite on the brush border of the small intestine. On the other hand, the observed disaccharidase deficiency in the secondary G lamblia infection appears to be induced by the local immune responses of the host.
Nodule size on HRCT scanning may predict infectious agent aetiology in immunocompromised patients with suspected pulmonary infection
Authors: C M O'Driscoll
Journal: Thorax (2003)

Chronic cough is a common problem in childhood.Viral infections are the most prevalent cause, but other rarer disorders should be excluded whenever cough appears unusually severe and/or frequent, and when there is evidence of failure to thrive and growth retardation.The younger the child, the more the need to exclude underlying disease at an early stage.Passive smoking is an important contributor to chronic cough in children.Chronic productive cough with purulent sputum is always reason for concern in children and is not common as a symptom of asthma.More or less specific diagnoses in children include cystic fibrosis, aspirated foreign body, congenital anatomic abnormalities and primary ciliary dyskinesia. . . . . . . . .
Severe Vivax Malaria: Newly Recognised or Rediscovered?
Authors: Stephen J Rogerson, Richard Carter
Journal: PLoS Medicine (2008)

Malignant tertian” and “benign tertian” are terms that have long been used for two of the major diseases we recognise as malaria. The former is generally considered to be synonymous with Plasmodium falciparum and the latter with P. vivax infection. As the names “malignant” and “benign” suggest, the current dogma is that P. falciparum can be severe and life-threatening while P. vivax tends to be mild. However, two studies published in this issue of PLoS Medicine challenge this dogma.
Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis
Authors: G V Papatheodoridis, M Hamilton, P K Mistry, B Davidson, K Rolles, A K Burroughs
Journal: Gut (1998)

Background —The course of inflammatory bowel disease after liver transplantation has been reported as variable with usually no change or improvement, but there may be an increased risk of early colorectal neoplasms. In many centres steroids are often withdrawn early after transplantation and this may affect inflammatory bowel disease activity. Aims —To evaluate the course of inflammatory bowel disease in primary sclerosing cholangitis transplant patients who were treated without long term steroids. Methods —Between 1989 and 1996, there were 30 patients transplanted for primary sclerosing cholangitis who survived more than 12 months. Ulcerative colitis was diagnosed in 18 (60%) patients before transplantation; two had previous colectomy. All patients underwent colonoscopy before and after transplantation and were followed for 38 (12–92) months. All received cyclosporin or tacrolimus with or without azathioprine as maintenance immunosuppression. Results —Ulcerative colitis course after transplantation compared with that up to five years before transplantation was the same in eight (50%) and worse in eight (50%) patients. It remained quiescent in eight and worsened in four of the 12 patients with pretransplant quiescent course, whereas it worsened in all four patients with pretransplant active course (p=0.08). New onset ulcerative colitis developed in three (25%) of the 12 patients without inflammatory bowel disease before transplantation. No colorectal cancer has been diagnosed to date. Conclusions —Preexisting ulcerative colitis often has an aggressive course, while de novo ulcerative colitis may develop in patients transplanted for primary sclerosing cholangitis and treated without long term steroids.
Passage of molecules through the wall of the gastrointestinal tract. II. Application of low-molecular weight polyethyleneglycol and a deterministic mathematical model for determining intestinal permeability in man.
Authors: T Sundqvist, K E Magnusson, R Sjodahl, I Stjernstrom, C Tagesson
Journal: Gut (1980)

The intestinal permeability to low molecular weight polyethyleneglycol (PEG) has been evaluated by means of a simple mathematical model and computer-aided curve-fitting procedures. Macrogolum 400, a mixture of 11 PEGs with molecular weights ranging from 194 to 634 daltons, was taken together with a liquid meal and a six-hour portion of urine collected. The different PEGs were then extracted from the urine, separated from each other by gas-liquid chromatography, and the relative peak area of each individual PEG determined. The distribution of different PEGs in the urine was then compared with the original PEG-distribution in three different ways: (1) by comparing the median values of the molecular weights, (2) by comparing the mean and standard deviation after curve fitting to the normal distribution, and (3) by curve fitting to mathematical filter functions demonstrating molecular exclusion due to size. It thus appeared that molecules were excluded both in the high and in the low molecular weight range, possibly by a combined effect of the intestinal permeability barrier and an escape to other compartments than the urine. However, relatively more of the larger PEGs passed from the intestine to the urine in a patient with Crohn's disease than in an apparently healthy individual.
Tipping the Noxa/Mcl-1 Balance Overcomes ABT-737 Resistance in Chronic Lymphocytic Leukemia
Authors: Jacqueline M. Tromp, Christian R. Geest, Esther C.W. Breij, Judith A. Elias, Jacoline van Laar, Dieuwertje M. Luijks, Arnon P. Kater, Tim Beaumont, Marinus H.J. van Oers, Eric Eldering
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Chronic lymphocytic leukemia (CLL) cells in lymph nodes (LN), from which relapses are postulated to originate, display an antiapoptotic profile in contrast to CLL cells from peripheral blood (PB). The BH3 mimetic ABT-737 antagonizes the antiapoptotic proteins Bcl-XL and Bcl-2 but not Mcl-1 or Bfl-1. Previously, it was shown that CD40-stimulated CLL cells were resistant to ABT-737. We aimed to define which antiapoptotic proteins determine resistance to ABT-737 in CLL and whether combination of known antileukemia drugs and ABT-737 was able to induce apoptosis of CD40-stimulated CLL cells. Experimental Design: To mimic the LN microenvironment, PB lymphocytes of CLL patients were cultured on feeder cells expressing CD40L and treated with ABT-737 with or without various drugs. In addition, we carried out overexpression or knockdown of pro- and antiapoptotic proteins in immortalized primary B cells. Results: Upon CD40 stimulation patient-specific variations in ABT-737 sensitivity correlated with differences in levels of Mcl-1 and its antagonist Noxa. Knockdown of Noxa, as well as Mcl-1 overexpression, corroborated the importance of the Noxa/Mcl-1 ratio in determining the response to ABT-737. Inhibition of NF-κB resulted in increased Noxa levels and enhanced sensitivity to ABT-737. Interestingly, increasing the Noxa/Mcl-1 ratio, by decreasing Mcl-1 (dasatinib and roscovitine) or increasing Noxa levels (fludarabine and bortezomib), resulted in synergy with ABT-737. Conclusions: Thus, the Noxa/Mcl-1 balance determines sensitivity to ABT-737 in CD40-stimulated CLL cells. These data provide a rationale to investigate the combination of drugs which enhance the Noxa/Mcl-1 balance with ABT-737 to eradicate CLL in chemoresistant niches. Clin Cancer Res; 18(2); 487–98. ©2011 AACR.