tbuckley/cabot-search huggingface dataset:
Tumour necrosis factor related apoptosis inducing ligand (TRAIL) induces hepatic steatosis in viral hepatitis and after alcohol intake
Authors: B Mundt
Journal: Gut (2005)

Tumour necrosis factor related apoptosis inducing ligand (TRAIL) induces apoptosis in transformed cells and is considered as an agent for cancer therapy. As there is evidence that TRAIL is also essential for apoptosis in animal models of liver injury, we investigated the role of TRAIL in viral hepatitis and after alcohol consumption.Expression of TRAIL was determined by western blot analysis in the liver of patients with chronic hepatitis C virus (HCV) infection as well as in experimental acute adenoviral hepatitis and after alcohol intake in the liver of mice. To investigate the effect of FasL and TRAIL expression, we used low dose adenoviral gene transfer. Apoptosis and steatosis were assessed by TUNEL and fat red staining, and by caspase assays.TRAIL was overexpressed in the liver of patients with HCV associated steatosis while acute adenoviral hepatitis resulted in upregulation of TRAIL-DR5. In contrast with FasL, TRAIL expression was harmless to healthy livers. However, in virally infected livers, TRAIL expression induced apoptosis and steatosis whereas expression of FasL only resulted in apoptosis of hepatocytes without steatosis. After alcohol intake, TRAIL expression led to hepatic steatosis, without apoptosis of hepatocytes, indicating that TRAIL mediated apoptosis and steatosis may be independently modulated after viral infection and alcohol intake. In viral hepatitis and after alcohol intake, Ad-TRAIL mediated steatosis can be inhibited by injection of a neutralising TRAIL antibody.We identified TRAIL as a new mediator of hepatic steatosis in viral hepatitis and after alcohol intake. Consequently, TRAIL mediated hepatotoxicity has to be considered in patients with viral hepatitis and alcoholic liver disease.
Lower Hippocampal Volume in Patients Suffering From Depression: A Meta-Analysis
Authors: Stephanie Campbell, Michael Marriott, Claude Nahmias, Glenda M. MacQueen
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: A number of studies have used magnetic resonance imaging to examine volumetric differences in temporal structures in subjects suffering from major depressive disorder. Studies have reported lower hippocampal and amygdala volume, but results have been inconsistent. The authors were interested, therefore, in examining these studies in the aggregate in order to determine whether hippocampal volume is lower in major depressive disorder. They also examined factors that may contribute to the disparate results in the literature. METHOD: A meta-analysis was conducted of studies that used magnetic resonance imaging to assess the volume of the hippocampus and related structures in patients with major depressive disorder. RESULTS: Patients were seen to have lower hippocampal volume relative to comparison subjects, detectable if the hippocampus was measured as a discrete structure. CONCLUSIONS: Although the effect of major depressive disorder on amygdala volume remains to be conclusively established, inclusion of the amygdala with the hippocampus appears to have decreased the likelihood of detecting volumetric differences in either structure. Slice thickness or other scan parameters did not account for a substantive amount of the variance in results, whereas clinical variables of the populations studied, such as duration of illness or presence of abuse, may account for much of the discrepancy between findings.
Effect of tissue anisotropy on extracellular potential fields in canine myocardium in situ.
Authors: D E Roberts, A M Scher
Journal: Circulation Research (1982)

The extracellular epicardial potential fields produced by simple depolarization waves in the in situ canine left ventricular myocardium were analyzed. A mathematical model that included tissue anisotrophy was developed to explain the observed fields. Values of intracellular (i), extracellular (o), longitudinal (l), and transverse (t) resistivity which gave the best fit between the model and experimental data were (in ohm-cm, mean +/- SD): rol = 852 +/- 232, rot = 1247 +/- 210, ril = 291 +/- 38, rit = 1677 +/- 331. The potential fields around simple stimulated waves on the epicardium can best be explained if the extracellular wavefront voltage is (mean +/- SD) 74 +/- 7 mV for a wave propagating parallel to the local muscle fibers, and 43 +/- 6 mV for a wave propagating perpendicular to these fibers. We conclude that the anisotrophy of the electrical conductivity of cardiac muscle has important effects on he propagation of waves of depolarization and on the potential fields produced by depolarization in the intact heart.
Clinical and laboratory 2‐year outcome of oral immunotherapy in patients with cow's milk allergy
Authors: A. Elizur, M. Y. Appel, M. R. Goldberg, T. Yichie, M. B. Levy, L. Nachshon, Y. Katz
Journal: Allergy (2015)

Abstract Studies examining the long‐term effect of oral immunotherapy in food‐allergic patients are limited. We investigated cow's milk‐allergic patients, &gt;6 months after the completion of oral immunotherapy ( n = 197). Questionnaires, skin prick tests, and basophil activation assays were performed. Of the 195 patients contacted, 180 (92.3%) were consuming milk protein regularly. Half experienced adverse reactions, mostly mild. Thirteen patients (6.7%) required injectable epinephrine. Higher reaction rate after immunotherapy was associated with more anaphylactic episodes before treatment and a lower starting dose ( OR = 2.1, P = 0.035 and OR = 2.3, P = 0.035, respectively). Reaction rate in patients who were 6–15 months, 15–30 months, or &gt;30 months post‐treatment decreased from 0.28/month to 0.21/month to 0.15/month, respectively ( P &lt; 0.01). Milk‐induced % CD 63 and % CD 203c expression was significantly lower in patients &gt;24 months vs in patients &lt;24 months post‐treatment ( P = 0.038 and P = 0.047, respectively). In conclusion, many patients experience mild adverse reactions after completing oral immunotherapy and some require injectable epinephrine. Progressive desensitization, both clinically and in basophil reactivity, occurs over time.
Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial
Authors: Agnès Hartemann, Gilbert Bensimon, Christine A Payan, Sophie Jacqueminet, Olivier Bourron, Nathalie Nicolas, Michèle Fonfrede, Michelle Rosenzwajg, Claude Bernard, David Klatzmann
Journal: The Lancet Diabetes & Endocrinology (2013)
Exhaled Nitric Oxide Decreases during Exercise-induced Bronchoconstriction in Children with Asthma
Authors: AKIHIKO TERADA, TAKAO FUJISAWA, KENJI TOGASHI, TATSUTAKA MIYAZAKI, HAJIME KATSUMATA, JUN ATSUTA, KOUSEI IGUCHI, HITOSHI KAMIYA, HAJIME TOGARI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Nitric oxide (NO) produced in the airways can be either detrimental or protective to the host. To investigate the role of NO in the pathogenesis of exercise-induced bronchoconstriction (EIB), we measured exhaled NO (ENO) after exercise challenge in 39 asthmatic and six normal children. FEV1 and ENO were measured before and at 0, 5, 10, and 15 min after exercise performed on a treadmill for 6 min. EIB was defined as a decrease in FEV1 of more than 15% after the exercise. Normal children (control group) did not have EIB. Twenty-one patients with asthma had EIB (EIB group) whereas the remaining 18 patients did not (non-EIB group). The baseline ENO value was significantly higher in the asthmatic children than in the normal children, and there was a positive correlation between the maximal percent decrease in FEV1 and the baseline ENO value (r = 0.501, p = 0.012). At the end of the exercise, ENO had decreased in all the subjects. In the non-EIB and control groups, ENO rebounded to above the baseline at 5 min after the exercise and thereafter. In contrast, ENO remained at a decreased level in the EIB group. The change in ENO did not correlate with the change in minute ventilation, and β -agonist inhalation at the peak of EIB that accelerated the recovery of FEV1 did not affect the depressed level of ENO, demonstrating that the reduction of ENO is not a simple consequence of increased ventilation nor airway obstruction. Among the EIB group, steroid-treated patients showed sooner recovery in ENO after the exercise than steroid-naive patients. Our study suggests that NO production in response to exercise may be impaired in patients with EIB, and that ENO represents not only airway inflammation but also a protective function of NO in EIB.
Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation: similarity to human PTLD and association with a porcine gammaherpesvirus
Authors: Christene A. Huang, Yasushi Fuchimoto, Zachary L. Gleit, Thomas Ericsson, Adam Griesemer, Rachel Scheier-Dolberg, Elizabeth Melendy, Hiroshi Kitamura, Jay A. Fishman, Judith A. Ferry, Nancy Lee Harris, Clive Patience, David H. Sachs
Journal: Blood (2001)
Pharmacokinetics, Methionine Depletion, and Antigenicity of Recombinant Methioninase in Primates
Authors: Zhijian Yang, Junhua Wang, Takayuki Yoshioka, Baoqiu Li, Quan Lu, Shukuan Li, Xinghua Sun, Yuying Tan, Shigeo Yagi, Eugene P. Frenkel, Robert M. Hoffman
Journal: Clinical Cancer Research (2004)

Abstract Pharmacokinetics, methionine depletion, antigenicity, and toxicity of recombinant methioninase (rMETase), which has shown efficacy in achieving cell kill in a broad range of human tumor models, were examined in macaque monkeys. Dose-ranging studies at 1000, 2000, and 4000 units/kg i.v. identified the 4000 units/kg dose as able to reduce plasma methionine to an undetectable level (less than 0.5 μm) by 30 min, and the level so remained for 8 h. Pharmacokinetic analysis showed that rMETase was eliminated with a T1/2 of 2.49 h. A 2-week i.v. administration of 4000 units/kg every 8 h/day for 2 weeks resulted in a steady-state depletion of plasma methionine to less than 2 μm. The only manifest toxicity was decreased food intake and slight weight loss. Serum albumin and red cell values declined transiently during treatment, which may be related to extensive blood sampling. Re-challenge on day 28 resulted in anaphylactic shock and death in one animal. Subsequent pretreatment with hydrocortisone prevented the anaphylactic reaction, although vomiting was frequently observed. Re-challenge was carried out at days 66, 86, and 116. Anti-rMETase antibodies (at 10−3) were found after the first challenge, and these increased to 10−6 after the fourth challenge and decreased to 10−2 by 2 months post therapy. The main rMETase antibody was IgG, and although it has some in vitro features of being a neutralizing antibody, each challenge dose was effective in depleting plasma methionine levels. Thus, rMETase was able to effectively deplete plasma methionine levels with minimal toxicity in a primate model. These data provide the bases for alteration by polyethyleneglycol conjugation (PEGylation) of the enzyme to increase its duration of effect and reduce its immunogenicity.
The role of<i>BRAF</i>mutations in primary melanoma growth rate and survival
Authors: V.J. Mar, W. Liu, B. Devitt, S.Q. Wong, A. Dobrovic, G.A. McArthur, R. Wolfe, J.W. Kelly
Journal: British Journal of Dermatology (2015)

Background The clinical behaviour and prognosis of primary melanomas harbouring BRAF mutations is not fully understood. Objectives To investigate the effect of mutation status on primary melanoma growth rate and melanoma-specific survival (MSS). Methods A prospective cohort of 196 patients with stage I–III primary cutaneous melanoma were followed for a median of 92 months, pre-dating the institution of BRAF inhibitor therapy. Clinicopathological variables were correlated with mutation status and hazard ratios (HRs) estimated for MSS. Results Of 196 tumours, 77 (39·2%) were BRAF V600E, 10 (5·1%) BRAF V600K and 33 (16·8%) were NRAS mutant. BRAF V600E mutant melanomas were associated with favourable clinical characteristics and tended to be slower growing compared with BRAF V600K, NRAS mutant or BRAF/NRAS wild-type tumours (0·12 mm per month, 0·61 mm per month, 0·36 mm per month and 0·23 mm per month, respectively; P = 0·05). There were 39 melanoma deaths, and BRAF mutant melanomas were associated with poorer MSS in stage I–III disease [HR 2·60, 95% confidence interval (CI) 1·20–5·63; P = 0·02] and stage I–II disease (HR 3·39, 95% CI 1·12–10·22; P = 0·03) after adjusting for other prognostic variables. Considered separately, BRAF V600E mutant melanomas were strongly associated with MSS independently of thickness and nodal status (HR 3·89, 95% CI 1·67–9·09; P < 0·01) but BRAF V600K mutant tumours were not (HR 1·19, 95% CI 0·36–3·92; P = 0·77). Conclusions The presence of a BRAF mutation does not necessarily 'drive' more rapid tumour growth but is associated with poorer MSS in patients with early-stage disease.
C-C chemokine–encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis
Authors: Sawsan Youssef, Gila Maor, Gizi Wildbaum, Nir Grabie, Alumit Gour-Lavie, Nathan Karin
Journal: Journal of Clinical Investigation (2000)

Depending on the method of immunization, a single administration of CFA may result in the development of a local inflammatory process or chronic polyadjuvant-induced arthritis (AA). We administered naked DNA vaccines encoding MIP-1α, MCP-1, MIP-1β, and RANTES to Lewis rats and confirmed that each of these vaccines induced immunological memory to the corresponding gene product. Upon induction of disease, this memory effectively inhibited the development of the autoimmune condition. Self-specific Ab's developed in DNA-vaccinated animals were neutralizing in vitro and could adoptively transfer the beneficial effect of each vaccine. Repeated administration of the constructs encoding MCP-1, MIP-1α, or RANTES inhibited the development and progression of AA, even when each vaccine was administered only after the onset of disease. This suggests a highly effective way by which the immune system could be re-educated to generate protective immunity against its own harmful activities.
Detection of myocardial infarction in vitro based on altered attenuation of ultrasound.
Authors: J W Mimbs, D E Yuhas, J G Miller, A N Weiss, B E Sobel
Journal: Circulation Research (1977)

This study was designed to determine whether attenuation of ultrasound by myocardium is potentially useful in detecting and quantifying infarction. Accordingly, we analyzed 44 regions of myocardium from 11 dogs 4-10 weeks after coronary occlusion. Attenuation of ultrasound in each region was assessed by transmitting a broadband pulse through the tissue in vitro and carefully gating the appropriate pulse into a spectrum analyzer for Fourier analysis (frequency range, 2-9.5 MHZ). An ultrasonic index of attenuation was derived from the slope of the best-fit line relating attenuation and frequency obtained from the Fourier transform. Acquistion of ultrasonic data was improved with the use of a specially designed small diameter receiving transducer. Myocardial creatine kinase content was assayed in each region to provide an independent index of regional injury. Results obtained from ultrasonic and biochemical analyses correlated with a correlation coefficient between the two of 0.80 in 24 regions of myocardium from the six dogs studied 4-5 weeks after infarction, and 0.72 in 20 regions from the five dogs studied 9-11 weeks after infarction. These findings indicate that regional infarction is associated with quantitative changes in ultrasonic attenuation.
The natural history of HCV in a cohort of haemophilic patients infected between 1961 and 1985
Authors: T T Yee
Journal: Gut (2000)

<h3>AIM</h3> This study describes the long term follow up of haemophilic patients infected with hepatitis C virus (HCV) between 1961 and 1985. <h3>METHODS</h3> Clinical and treatment records from 310 patients with inherited coagulation disorders treated with blood product before 1985 were reviewed. Standard survival analysis methods were used to model progression to liver failure and death. <h3>RESULTS</h3> A total of 298/305 (98%) patients tested were anti-HCV positive. Twenty seven (9%) individuals consistently HCV polymerise chain reaction negative were considered to have cleared the virus. By 1 September 1999, 223/310 (72%) were alive, 26 (8%) had died a liver related death, and 61 (20%) had died from other, predominantly human immunodeficiency virus (HIV) related, causes. Kaplan-Meier progression rates to death from any cause and liver related deaths 25 years after exposure to HCV were 47% (95% confidence intervals (CI) 34–60) and 19% (95% CI 10–27), respectively. After 13.3 years from 1985, by which time all patients had seroconverted to HIV, progression rates to death from any cause and liver related deaths were, respectively, 8% (95% CI 4–13) and 3% (95% CI 0.4–6) for those HIV negative, and 57% (95% CI 48–66) and 21% (95% CI 13–31) for those HIV positive (p=0.0001). Using Cox proportional hazard models, the adjusted relative hazard of death for individuals coinfected with HIV compared with those infected with HCV alone was 19.47 (95% CI 9.22–41.10), 0.99 (95% CI 0.39–2.53), 3.47 (95% CI 1.40–8.63), and 9.74 (95% CI 3.91–24.26) for the age groups at infection 10–19 years, 20–29 years, and &gt;30 years, respectively, compared with the age group &lt;10 years. The adjusted relative hazard for genotype 1 compared with other genotypes was 2.7 (95% CI 1.36–5.15) . <h3>CONCLUSIONS</h3> While 25 year follow up of 310 haemophilic patients has shown the potentially lethal combination of HIV and HCV coinfection, HCV singly infected individuals show slow progression of liver disease.
Acute comparative effect of right and left ventricular pacing in patients with permanent atrial fibrillation
Authors: Enrico Puggioni, Michele Brignole, Michael Gammage, Ezio Soldati, Maria Grazia Bongiorni, Emmanuael N. Simantirakis, Panos Vardas, Fredrik Gadler, Lennart Bergfeldt, Corrado Tomasi, Giacomo Musso, Gianni Gasparini, Attilio Del Rosso
Journal: Journal of the American College of Cardiology (2004)
The effects of female sex, viral genotype, and<i>IL28B</i>genotype on spontaneous clearance of acute hepatitis C virus infection
Authors: Jason Grebely, Kimberly Page, Rachel Sacks-Davis, Maarten Schim van der Loeff, Thomas M. Rice, Julie Bruneau, Meghan D. Morris, Behzad Hajarizadeh, Janaki Amin, Andrea L. Cox, Arthur Y. Kim, Barbara H. McGovern, Janke Schinkel, Jacob George, Naglaa H. Shoukry, Georg M. Lauer, Lisa Maher, Andrew R. Lloyd, Margaret Hellard, Gregory J. Dore, Maria Prins
Journal: Hepatology (2013)

Although 20%-40% of persons with acute hepatitis C virus (HCV) infection demonstrate spontaneous clearance, the time course and factors associated with clearance remain poorly understood. We investigated the time to spontaneous clearance and predictors among participants with acute HCV using Cox proportional hazards analyses. Data for this analysis were drawn from an international collaboration of nine prospective cohorts evaluating outcomes after acute HCV infection. Among 632 participants with acute HCV, 35% were female, 82% were Caucasian, 49% had interleukin-28 (IL28)B CC genotype (rs12979860), 96% had injected drugs ever, 47% were infected with HCV genotype 1, and 7% had human immunodeficiency virus (HIV) coinfection. Twenty-eight percent were HCV antibody negative/RNA positive at the time of acute HCV detection (early acute HCV). During follow-up, spontaneous clearance occurred in 173 of 632, and at 1 year after infection, 25% (95% confidence interval [CI]: 21, 29) had cleared virus. Among those with clearance, the median time to clearance was 16.5 weeks (IQR: 10.5, 33.4), with 34%, 67%, and 83% demonstrating clearance at 3, 6, and 12 months. Adjusting for age, factors independently associated with time to spontaneous clearance included female sex (adjusted hazards ratio [AHR]: 2.16; 95% CI: 1.48, 3.18), IL28B CC genotype (versus CT/TT; AHR, 2.26; 95% CI: 1.52, 3.34), and HCV genotype 1 (versus non-genotype 1; AHR: 1.56; 95% CI: 1.06, 2.30). The effect of IL28B genotype and HCV genotype on spontaneous clearance was greater among females, compared to males.
Peptide size selection by the major histocompatibility complex-encoded peptide transporter.
Authors: F Momburg, J Roelse, G J Hämmerling, J J Neefjes
Journal: The Journal of Experimental Medicine (1994)

The major histocompatibility complex (MHC)-encoded heterodimeric TAP1/TAP2 transporter (TAP) translocates cytosolic peptides into the lumen of the endoplasmic reticulum (ER), where peptides of 8 to 11 amino acids long associate with MHC class I molecules. We have studied the selectivity of peptide translocation by TAP in streptolysin O-permeabilized cells using glycosylatable, radioiodinated model peptides to detect import into the ER lumen. TAP-dependent translocation of a radiolabeled nonamer peptide was most efficiently inhibited by unlabeled 9- to 11-mer peptides. Peptides between 7 and 40 amino acids long all could inhibit transport, the longer peptides being least effective. Also, peptides shorter than eight amino acids were inefficiently translocated. The use of directly labeled length variants in translocation assays and TLC analysis of the transported material revealed two pathways for translocation: short peptides (7 to 13 amino acids long) were translocated without prior modification. In contrast, transport of longer peptides was not effective. Instead such peptides were clipped by cytosolic peptidases before efficient transport. Our data suggest that TAP preferentially translocates peptides of appropriate length for class I binding. Furthermore, TAP-translocated peptides were rapidly released from the ER unless they were trapped there by being glycosylated or by binding to MHC class I molecules.
Regression of fundic gland polyps following acquisition of Helicobacter pylori
Authors: N Watanabe
Journal: Gut (2002)

The prevalence of <i>Helicobacter pylori</i> infection is very low in patients with fundic gland polyps (FGPs) of the stomach. We report here two cases with multiple FGPs that regressed following new <i>H pylori</i> acquisition. Patient Nos I and II had multiple FGPs in normal fundic mucosa without inflammatory changes or atrophy. Both were not infected with <i>H pylori</i>. Following acquisition of <i>H pylori</i> infection however, all FGPs in both patients completely disappeared except for one FGP in patient No I. Although the size of the remaining polyp in patient No I was greatly reduced after <i>H pylori</i> acquisition, it became enlarged again after eradication. Interestingly, in the remaining polyp, we found an activating β-catenin gene mutation whereas no such mutations were detected in FGPs of patient No II. Thus <i>H pylori</i> infection may have an inhibitory effect on the development of FGPs.
Mycophenolate mofetil (MMF): Firing at the atherosclerotic plaque from different angles?
Authors: S VANLEUVEN, J KASTELEIN, A ALLISON, M HAYDEN, E STROES
Journal: Cardiovascular Research (2005)

Atherosclerosis is characterized by a persistent, low-grade inflammatory state in which immune cell activation is inseparably linked to plaque formation and destabilization. The T-lymphocyte in particular has emerged as a pivotal player throughout the course of atherogenesis. As a consequence, the concept that immune modulation is a suitable target for cardiovascular prevention is currently an important focus of research.