tbuckley/cabot-search huggingface dataset:
The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages.
Authors: M D Miller, M T Warmerdam, I Gaston, W C Greene, M B Feinberg
Journal: The Journal of Experimental Medicine (1994)

Considerable controversy and uncertainty have surrounded the biological function of the Human Immunodeficiency Virus (HIV)-1 nef gene product. Initial studies suggested that this early, nonstructural viral protein functioned as a negative regulatory factor; thus, it was proposed to play a role in establishing or maintaining viral latency. In contrast, studies in Simian Immunodeficiency Virus (SIV)mac-infected rhesus monkeys have suggested that Nef is not a negative factor but rather plays a central role in promoting high-level viral replication and is required for viral pathogenesis in vivo. We sought to define a tissue culture system that would approximate the in vivo setting for virus infection in order to assess the role of HIV-1 Nef in viral replication. We show that infection of mitogen-activated peripheral blood mononuclear cells (PBMC) with Nef+ HIV results in enhanced replication as evidenced by earlier gag p24 expression when compared with infections performed with nef mutant viruses. Moreover, when unstimulated freshly isolated PBMC are infected with Nef+ and Nef- viruses and then subsequently activated with mitogen, the Nef-induced difference in viral replication kinetics is even more pronounced, with the Nef- viruses requiring much more time in culture for appreciable growth. A positive effect of Nef on viral replication was also observed in primary macrophages infected with a recombinant of YU-2, a patient-derived molecular clone with macrophage tropism. These positive effects of Nef on viral replication are dependent on the initial multiplicity of infection (MOI), in that infections of unstimulated PBMC at low MOI are most dependent upon intact nef for subsequent viral growth. We now provide evidence that the Nef+ HIV is more infectious than Nef- HIV from both a tissue culture infectious dose analysis, and a single-cell HIV infection assay. In the latter case, we demonstrate that infection with equivalent doses of HIV based on virion-associated gag p24 yields five- to sixfold more infected cells if Nef+ viral stocks were used. Furthermore, we find that the differential infectivity is not dependent on CD4 down-regulation as Nef+ virus produced from transfected COS cells lacking CD4 is also more infectious. However, normalization of PBMC infections to equivalent infectivity between that of the Nef+ and Nef- viruses continues to reveal delayed viral replication in the absence of Nef, suggesting that secondary viral spread in PBMC is also enhanced in Nef+ infections. We demonstrate this directly by showing a 13-15-fold increase in infectivity of PBMC-derived Nef+ HIC.(ABSTRACT TRUNCATED AT 400 WORDS)
Irisin and FGF21 Are Cold-Induced Endocrine Activators of Brown Fat Function in Humans
Authors: Paul Lee, Joyce D. Linderman, Sheila Smith, Robert J. Brychta, Juan Wang, Christopher Idelson, Rachel M. Perron, Charlotte D. Werner, Giao Q. Phan, Udai S. Kammula, Electron Kebebew, Karel Pacak, Kong Y. Chen, Francesco S. Celi
Journal: Cell Metabolism (2014)
Differences and similarities between arrhythmogenic right ventricular cardiomyopathy and athlete's heart adaptations
Authors: B Bauce, G Frigo, G Benini, P Michieli, C Basso, A F Folino, I Rigato, E Mazzotti, L Daliento, G Thiene, A Nava
Journal: British Journal of Sports Medicine (2008)

Background Regular intensive physical activity is associated with non-pathological changes in cardiac morphology. Differential diagnosis with arrhythmogenic right ventricular cardiomyopathy (ARVC) constitutes a frequent problem, especially in athletes showing ventricular arrhythmias with left bundle branch block morphology. Aim of the study To assess the different clinical and non-invasive instrumental features of the subjects affected by ARVC and by athletes. Methods Three groups of subjects (40 ARVC patients, 40 athletes and 40 controls, mean age 27 (9) years) were examined with family and personal history, physical examination, 12-lead ECG, 24-h ECG, signal-averaged ECG and 2-D and Doppler echocardiography. Results 12-Lead ECG was abnormal in 62% of ARVC patients versus 7.5% of athletes and 2.5% of controls (p&lt;0.0001). Ventricular arrhythmias and late potentials were present in 70% and 55% of ARVC subjects, respectively (vs 5% of athletes and 7.5% of controls, p&lt;0.0001). Left ventricular parietal wall thickness and left ventricular end-diastolic diameters were significantly higher in athletes. Both athletes and ARVC patients presented a right ventricular (RV) enlargement compared with controls. Moreover, RV outflow tract, measured on parasternal long axis and at the level of aortic root, was significantly larger in ARVC patients (33.6 (4.7) mm vs 29.1 (3.4) mm and 35.6 (6.8) mm vs 30.1 (2.9) mm; p&lt;0.0001), and RV fractional shortening and ejection fraction were significantly lower in ARVC patients compared with athletes (40 (7.9)% vs 44 (10)%; p=0.05 and 52.9 (8)% vs 59.9 (4.5)%; p&lt;0.0001). A thickened moderator band was found to be present in similar percentage in ARVC patients and athletes. Conclusions An accurate clinical and instrumental non-invasive evaluation including echocardiography as imaging technique allows to distinguish RV alterations typical of ARVC from those detected in athletes as a consequence of intensive physical activity.
Response Rates, Survival, and Chemotherapy Trials
Authors: R. Pazdur
Journal: JNCI Journal of the National Cancer Institute (2000)

Clinical benefit, a regulatory end point used in traditional drug approval, has generally been characterized by an increase in patient survival, an unambiguous gold standard of efficacy, or by relieving or delaying the onset of disease-related symptoms. The demonstration of improving survival may be obscured by subsequent therapies after disease progression in randomized trials. Relief of tumor-related symptoms has been difficult to document in oncology trials because of traditionally restrictive eligibility criteria that allow only asymptomatic or early symp
Injury rate and injury pattern among elite World Cup snowboarders: a 6-year cohort study
Authors: D H Major, S E Steenstrup, T Bere, R Bahr, L Nordsletten
Journal: British Journal of Sports Medicine (2013)

Background There is limited knowledge on the injury rate and injury pattern in the different disciplines among elite snowboarders. Objective The aim of this study was to describe and compare the injury rate and injury pattern among the different International Ski Federation (Fédération Internationale de Ski, FIS) World Cup (WC) snowboard disciplines. Methods We conducted retrospective interviews with FIS WC snowboard athletes at the end of each season in the period 2007–2012, to register all acute injuries sustained during training or competition during the competitive season requiring attention by medical personnel. To calculate the exposure, we obtained information from result lists from the FIS competition database for all WC competitions for each of the interviewed athletes. Results We registered a total of 574 injuries among 1432 athletes, accounting for an overall injury rate of 40.1 injuries/100 athlete/season. A total of 171 injuries occurred during the FIS WC competitions, corresponding to 6.4 injuries/1000 runs. During competition, injury risk was highest in snowboard cross with 11.9/1000 runs, followed by 6.3 in halfpipe, 3.6 in big air and 2.8 in parallel giant slalom/parallel slalom (PGS/PSL). Snowboard cross also had the highest risk of severe injuries (&gt;28 days absence). No differences in injury risk were detected between male and female snowboarders. The most commonly injured body part was the knee (17.8%), followed by the shoulder/clavicle (13.4%) and head/face (13.2%). The risk of knee injury (the most common injury type) and head injury was significantly higher in snowboard cross and halfpipe compared to PGS/PSL. Conclusions The risk of injuries was higher in snowboard cross than in halfpipe, big air and PGS/PSL. The most commonly injured body part was the knee. Prevention of snowboard injuries among elite snowboarders should focus on knee injuries, severe injuries and snowboard cross athletes.
Murine malignant cells synthesize a 19,000-dalton protein that is physicochemically and antigenically related to the immunosuppressive retroviral protein, P15E.
Authors: G J Cianciolo, M E Lostrom, M Tam, R Snyderman
Journal: The Journal of Experimental Medicine (1983)

Murine tumors contain low molecular weight factors that inhibit macrophage accumulation at inflammatory foci. Certain oncogenic murine leukemia viruses contain similar inhibitory activity and the active component of the retroviruses was shown to be the envelope protein P15E. A number of murine malignant and nonmalignant cell lines, as well as primary tumors, have now been examined to determine whether production of retroviral P15E or a related protein is characteristic of neoplastic cells. Tumor lines examined included the Hep 129 hepatocarcinoma, BP8 fibrosarcoma, RL1 lymphoma, and three variants of the B16 melanoma. Tumor lines were virus negative by electron microscopy. Nonmalignant cells examined included ST0, 3T3/BALB, and 3T3/L1 fibroblasts and unstimulated, as well as mitogen-stimulated murine splenocytes. Cells were pulse-labeled with [35S]methionine, proteins immunoprecipitated with two monoclonal antibodies to P15E and analyzed by SDS-PAGE and gel fluorography. All tumor lines synthesized a approximately 19,000-dalton protein that co-migrated with retroviral P15E on SDS-PAGE. None of the nonmalignant cells synthesized this protein. Two-dimensional gel electrophoresis of the proteins precipitated from two B16 melanoma lines by monoclonal anti-P15E showed them to be physicochemically similar to P15E from Rauscher leukemia virus. A competition ELISA assay for P15E was developed and confirmed the results obtained by metabolic labeling and demonstrated P15E-related antigens in the tumor cell lines and also in the ascites fluid of mice injected with Hep 129 cells. More importantly, P15E antigens were expressed in both a spontaneous mammary adenocarcinoma and in a primary methylcholanthrene-induced fibrosarcoma. Nonmalignant tissues from animals bearing these tumors contained no detectable P15E antigen. Extracts from the primary fibrosarcomas, when injected into the thighs of mice, inhibited the intraperitoneal accumulation of inflammatory macrophages. The inhibitory activity was specifically removed by absorption with monoclonal antibody to P15E. These results suggest that synthesis of the immunosuppressive retroviral protein P15E, or a very similar protein, routinely occurs during the growth of murine neoplastic cells. This P15E-related protein is present in spontaneous murine primary tumors as well as in all murine tumor cell lines tested. The expression of such proteins by transformed cells in vivo could confer a selective advantage for their sustained growth since they would be more likely to escape immune surveillance.
Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors or somatisation?
Authors: L Van Oudenhove, J Vandenberghe, B Geeraerts, R Vos, P Persoons, B Fischler, K Demyttenaere, J Tack
Journal: Gut (2008)

Gastric sensorimotor dysfunction, psychosocial factors and somatisation are all implicated in symptom generation in functional dyspepsia (FD).To determine the relative contribution of each of these factors to overall dyspeptic symptom severity and weight loss in FD.In 201 consecutive tertiary care patients with FD (mean age 40.1 (SD 12.6) years), gastric sensorimotor function was studied using barostat (sensitivity, compliance and accommodation). Psychosocial factors (depression and anxiety disorders, positive and negative affect, perceived stress, alexithymia and history of abuse), somatisation and co-morbid irritable bowel syndrome (IBS) and chronic fatigue symptoms were assessed using self-report questionnaires. Variables were correlated with dyspepsia symptom severity (DSS) and weight loss. Hierarchical multiple linear regression was used to identify determinants of DSS and weight loss.Multiple linear regression identified the following determinants of DSS: gastric sensitivity (beta = 0.77, p = 0.25), depression (beta = 0.12, p = 0.06) and somatisation (beta = 0.48, p<0.0001) (controlling for age and occupation, R(2) = 0.29, p<0.0001). The effect of depression on DSS is partially mediated by somatisation. Gastric sensitivity (beta = 2.87, p = 0.08), history of childhood sexual abuse (beta = 9.37, p = 0.0006), depression (beta = 0.19, p = 0.24) and somatisation (beta = 0.67, p = 0.01) are independent determinants of weight loss (controlling for gender and occupation, R(2) = 0.42, p<0.0001). The effect of depression on weight loss is fully mediated by somatisation.Symptom severity and weight loss in FD are determined by psychosocial factors (depression, abuse history) and somatisation, and only to a lesser extent by gastric sensorimotor function. The importance of psychosocial factors and somatisation compared to gastric sensorimotor function is most pronounced in hypersensitive patients.
Heart rate variability and dispersion of refractoriness increase during recovery from electrical remodeling in the goat
Authors: Y. Biaauw, R.G. Tieleman, J. Brouwer, M.P. van den Berg, P.J. de Kam, J. Haaksma, C.D.J. de Langen, H.J.G.M. Crijns
Journal: Journal of the American College of Cardiology (1998)
Serum KL-6 differentiates neuroendocrine cell hyperplasia of infancy from the inborn errors of surfactant metabolism
Authors: M L Doan, O Elidemir, M K Dishop, H Zhang, E O Smith, P G Black, R R Deterding, D M Roberts, Q A Al-Salmi, L L Fan
Journal: Thorax (2009)

The study was conducted in order to determine if the glycoprotein KL-6 is a useful biomarker in differentiating neuroendocrine cell hyperplasia of infancy (NEHI), a benign form of children's interstitial lung disease, from the more severe inborn errors of surfactant metabolism (IESM), since their clinical presentation can be similar.Serum KL-6 levels were measured in 10 healthy control children, 6 with NEHI and 13 with IESM (4 with surfactant protein C (SP-C) and 9 with ABCA3 mutations). The initial clinical presentation, findings on previous CT scans and interstitial lung disease (ILD) scores at the time of KL-6 testing were compared. Correlations of KL-6 levels with age and with interval from lung biopsy were evaluated.The median (range) KL-6 levels were 265 (1-409), 194 (47-352), 1149 (593-4407) and 3068 (726-9912) U/ml for the control, NEHI, SP-C and ABCA3 groups, respectively. When compared with the control and NEHI groups, median KL-6 levels were significantly higher in the SP-C (p<0.01; p = 0.01, respectively) and ABCA3 groups (p<0.001; p = 0.001, respectively); however, there was no difference between the control and NEHI groups (p = 0.91). An inverse relationship was seen between KL-6 levels and age in the IESM groups, but not in the NEHI or control groups. Children with NEHI had similar presenting clinical features and were equally symptomatic at the time of KL-6 measurement as those with IESM.Children with NEHI have normal KL-6 levels, in contrast to those with IESM, who have elevated serum KL-6 levels; serum KL-6 may be a useful biomarker in distinguishing between these entities when their clinical presentations overlap.
Phenobarbital does not increase early labeling of bilirubin from 4-[14C]-δ-aminolevulinic acid in man and rat
Authors: Hiroaki Okuda, Nicola Tavoloni, Terrence F. Blaschke, Chi-Li Kiang, Mary Jane T. Jones, Jeanne G. Waggoner, Mohinder K. Sardana, Shigeru Sassa, Richard I. Shrager, Paul D. Berk
Journal: Hepatology (1991)

delta-Aminolevulinic acid-4-[14C] and [3H]-bilirubin were administered intravenously to five patients with Gilbert's syndrome and four healthy control subjects on two occasions: before and on days 10 through 14 of a course of phenobarbital (2.5 mg/kg/day). The resulting curves of [3H]-bilirubin and [14C]-bilirubin in plasma were analyzed by computer to determine a number of parameters of physiological interest. As expected, phenobarbital produced a highly significant fall in the plasma concentration of unconjugated bilirubin as a result of a significant increase in hepatic bilirubin clearance in all subjects; plasma bilirubin turnover was unaltered. Surprisingly, the drug produced no change in the incorporation of [14C]-delta-aminolevulinic acid into [14C]-early labeled bilirubin. To explain this unexpected finding, the effects of phenobarbital (75 mg/kg/day for 6 days) on incorporation of [14C]-delta-aminolevulinic acid and 2-[14C]-glycine into [14C]-early labeled bilirubin and on the activity of the enzyme delta-aminolevulinic acid synthase were studied in nonfasted, adult, male Sprague-Dawley rats. At the dose and duration of treatment used, phenobarbital administration increased total hepatic delta-aminolevulinic acid synthase activity and produced a significant increase of 70% in the incorporation of [14C]-glycine into early labeled bilirubin. By contrast, no increase in the incorporation of [14C]-delta-aminolevulinic acid into early labeled bilirubin was observed. These data suggest that delta-aminolevulinic acid is an inappropriate precursor for studies of the rate of heme biosynthesis, presumably because it bypasses delta-aminolevulinic acid synthase, the physiological rate-limiting enzyme in the heme biosynthetic pathway.
‘White out’: a rare cause: Figure 1
Authors: Gurinder Tack, Dhakshinamoorthy Ganeshan, Jonathan Wide, Paul Stockton
Journal: Thorax (2012)

Images in Thorax'White out': a rare cause A patient in their mid-40s presented with a history of worsening dyspnoea.The patient had neurofibromatosis type 1 and had previous spinal surgery for kyphoscoliosis.A chest x-ray showed a right sided 'white out', thought to be a pleural effusion (figure 1A).CT thorax showed a thoracic scoliosis with internal fixation and a large fluid collection within the right hemithorax.A chest drain was scheduled to be inserted.However, further review of the CT images identified an unusual abnormality within the right hemithorax.Several of the thoracic spinal pedicles were absent and there was communication of fluid from a dilated spinal canal to the large fluid collection within the right hemithorax (figure 1B).A thoracic MR image confirmed the appearance was due to a large cerebrospinal fluid collection within the right hemithorax, which directly communicated to the right side of the spinal canal (figure 1C).The appearances were due to a huge intrathoracic meningocoele rather than a pleural effusion.An intrathoracic meningocoele is a rare abnormality due to herniation of spinal meninges through an intervertebral foramen or bony deformity, producing a cerebrospinal fluid filled sac. 1 Despite being rare, it is often associated with neurofibromatosis type 1. 2
Systemic and mucosal antibodies to Klebsiella in patients with ankylosing spondylitis and Crohn's disease.
Authors: S O'Mahony, N Anderson, G Nuki, A Ferguson
Journal: Annals of the Rheumatic Diseases (1992)

Whole gut lavage fluid is a useful source of material for the study of intestinal immunity and inflammation in humans. Systemic and mucosal antibodies to Klebsiella pneumoniae were measured by enzyme linked immunosorbent assay (ELISA) in serum samples and whole gut lavage fluid from 14 patients with ankylosing spondylitis, 14 with Crohn9s disease, and 16 immunologically normal controls. As the concentration of IgG in whole gut lavage fluid reflects disease activity in Crohn9s disease, this approach was used to detect intestinal inflammation in patients with ankylosing spondylitis who also had disease activity and use of non-steroidal anti-inflammatory drugs (NSAIDs) recorded. Small intestinal permeability to cellobiose and mannitol was also studied. In serum samples, levels of IgA antibody to klebsiella were high in patients with Crohn9s disease and in patients with active ankylosing spondylitis, and were significantly correlated with the erythrocyte sedimentation rate in patients with ankylosing spondylitis. Levels of IgG antibody to klebsiella were also high in patients with Crohn9s disease. Studies of whole gut lavage fluid showed similar levels of IgA antibody to klebsiella in the three study groups, but levels of whole gut lavage fluid IgM and IgG antibodies to klebsiella were high in patients with Crohn9s disease. Levels of IgG in whole gut lavage fluid were high in patients with Crohn9s disease but in only one patient with ankylosing spondylitis, though the cellobiose/mannitol permeability ratio was abnormal in eight of 13 patients with ankylosing spondylitis. It is concluded that high levels of serum IgA antibody to klebsiella are not specific to ankylosing spondylitis, and that there is no evidence of an abnormal intestinal IgA antibody response to klebsiella in patients with ankylosing spondylitis.
Circulating immune complexes in patients with lung cancer.
Authors: J Lowe, A Segal-Eiras, P B Iles, R W Baldwin
Journal: Thorax (1981)

Sera from 41 patients with lung cancer and 41 age and sex-matched hospital inpatients with non-malignant disease were tested for the presence of immune complexes using the 125Iodine Clq binding test. All patients were untreated or had recurrences after surgery. An increased Clq binding activity was found in 34% of patients with lung cancer and 24% of patients with non-malignant disease. There was no significant association between increased serum Clq binding activity and histological tumour type or survival but there was an association with the extent of malignant disease. No patient with limited (state 1) disease had raised Clq binding activity but in 42% of patients with extensive disease it was increased. Increased Clq binding activity did not correlate with either an increased total white cell count of ESR. Measurement of Clq binding activity may be of value in serial monitoring of disease progress and response to treatment.
Protein Glycation
Authors: Jean-Luc Wautier, Ann Marie Schmidt
Journal: Circulation Research (2004)

The advanced glycation end products (AGEs) are a heterogeneous class of molecules, including the following main subgroups: bis(lysyl)imidazolium cross-links, hydroimidazolones, 3-deoxyglucosone derivatives, and monolysyl adducts. AGEs are increased in diabetes, renal failure, and aging. Microvascular lesions correlate with the accumulation of AGEs, as demonstrated in diabetic retinopathy or renal glomerulosclerosis. On endothelial cells, ligation of receptor for AGE (RAGE) by AGEs induces the expression of cell adhesion molecules, tissue factor, cytokines such as interleukin-6, and monocyte chemoattractant protein-1. A chief means by which AGEs via RAGE exert their effects is by generation of reactive oxygen species, at least in part via stimulation of NADPH oxidase. Diabetes-associated vascular dysfunction in vivo can be prevented by blockade of RAGE. Thus, agents that limit AGE formation, increase the catabolism of these species, or antagonize their binding to RAGE may provide new targets for vascular protection in diabetes.