tbuckley/cabot-search huggingface dataset:
Co-stimulatory molecule CD80 expression may correlate with anti-HCV treatment outcome
Authors: A. Sacchi, C. Agrati, G. D'Offizi, C. Vlassi, F. Martini
Journal: Gut (2010)

It was estimated that up to 70% of hepatitis C virus (HCV)-infected subjects became chronically infected, and these patients have an increased risk of developing cirrhosis and hepatocellular carcinoma.1 The standard treatment for HCV-infected patients is pegylated interferon α (IFNα) in combination with ribavirin; however, data on the correlation between treatment outcome and the activation state of components of the immune system are missing. A very interesting paper by Mengshol et al was published in Gut regarding the effect of anti-HCV treatment on the activation state of circulating dendritic cells (DCs).2 The authors showed that levels of CXCR3 and CXCR4 on plasmacytoid DC (pDCs) were higher at baseline compared with controls, and decreased with treatment. Pretreatment levels of the co-stimulatory marker CD40 and the maturation marker CD83 were higher in pDCs of patients chronically infected with HCV compared with healthy controls; moreover, levels of both markers dropped significantly with treatment in the sustained virological responder (SVR) group only. Finally, baseline pDCs chemotaxis to CXCL12 …
P31 Routine analysis of pleural aspirates for AFB in patients with pleural effusion of unknown cause is of limited use
Authors: P. K. Agarwal, M. Ali, J. Keane, S. Barrett, S. O. Ansari
Journal: Thorax (2011)

The investigation of pleural effusion of unknown cause may include analysis of pleural aspirate for presence of acid-fast bacilli (AFB) by smear and culture. We reviewed data on all pleural aspirates sent for AFB analysis over 11 years (January 2000 to December 2010) to identify the diagnostic yield of pleural aspirate AFB smear and culture in our hospital where there is a low incidence of tuberculosis (TB). Data were crosschecked with the TB notification list obtained from the Consultant in Communicable Disease Control (CCDC) to ensure identification of all tuberculous effusions. A list of all AFB positive specimens (including smears, cultures and histology) was also obtained from the pathology laboratory. The medical records of patients with AFB positive aspirates were reviewed. We also reviewed the medical records of patients with AFB negative pleural effusion who were diagnosed to have TB by other means. In total, 960 pleural aspirate samples were sent for AFB analysis. None of these were smear positive and only 13 (1.4%) were found to be positive on cultures. The ethnic breakdown of this figure was one, five, and seven cases for Asian, Caucasian, and Afro-Caribbean patients, respectively. Five of these patients were known or found to be HIV positive, all of whom were Afro-Caribbean. Eight of the 13 patients with positive pleural aspirate cultures underwent pleural biopsy (three by thoracoscopy), all of which confirmed a diagnosis of TB. One patient with positive cultures of pleural aspirate also had TB confirmed on culture of bronchial washings. A further ten patients (1%) whose pleural aspirates were AFB negative on smear and culture were diagnosed with tuberculosis by other means. The yield of AFB analysis on pleural aspirate is very low. Its role in commencing treatment in those who ultimately are diagnosed to have tuberculosis is limited. Risk factors for tuberculosis need to be considered before sending aspirate for AFB analysis. Where risk of TB is considered to be significant, pleural fluid aspiration should be combined with simultaneous pleural biopsy, as the latter may provide crucial diagnostic information at an earlier stage.
Using biomarkers to predict the presence of FAS mutations in patients with features of the autoimmune lymphoproliferative syndrome
Authors: Iusta Caminha, Thomas A. Fleisher, Ronald L. Hornung, Janet K. Dale, Julie E. Niemela, Susan Price, Joie Davis, Katie Perkins, Kennichi C. Dowdell, Margaret R. Brown, V. Koneti Rao, João Bosco Oliveira
Journal: Journal of Allergy and Clinical Immunology (2010)
Role of Pulse Pressure on Cardiovascular Risk in Chronic Kidney Disease Patients
Authors: Gema Fernandez-Fresnedo, Emilio Rodrigo, Angel Luis Martin de Francisco, Saturnino Sanz de Castro, Olga Castañeda, Manuel Arias
Journal: Journal of the American Society of Nephrology (2006)

Epidemiologic studies have emphasized the close relationship between high BP and cardiovascular disease (CVD). Recently published prospective studies have focus on systolic and pulse pressure (PP). Systolic BP seems to be a more important factor than diastolic BP on cardiovascular and all-cause mortality in older patients. PP reflects stiffness of the large arteries and increases with age. Increasingly, PP is recognized as an independent predictor of myocardial infarction, congestive heart failure, and cardiovascular death, even in hypertensive patients who undergo successful antihypertensive drug therapy, especially in older individuals. Chronic kidney disease (CKD) is a major public health problem. The progression of kidney disease and its associated cardiovascular complications are the major causes of morbidity and mortality. This holds true for all stages of kidney disease, including ESRD that requires renal replacement therapy. Most of the traditional CVD risk factors are highly prevalent in CKD, and several nontraditional factors also are associated with atherosclerosis in CKD. The burden of hypertension is present at all stages of CKD. Several studies have shown that PP is a reliable prognostic factor for mortality and CVD in patients who have CKD and are on hemodialysis and in renal transplant patients. The purpose of this review is to show the importance of PP on cardiovascular risk in patients with CKD, including kidney transplant recipients.
Estimated population prevalence of obstructive sleep apnoea in a community of German third graders
Authors: D. Finn, P. McNally
Journal: European Respiratory Journal (2011)

To the Editors:

We read with interest the article by Urschitz et al. 1 which estimated the population prevalence of obstructive sleep apnoea (OSA) in an urban community of German third graders. This article highlights the fact that OSA is one of the most common chronic respiratory …
Outcomes with the paclitaxel-eluting stent in patients with acute coronary syndromes
Authors: Jeffrey W. Moses, Roxana Mehran, Eugenia Nikolsky, John M. Lasala, Woodrow Corey, Glenn Albin, Cary Hirsch, Martin B. Leon, Mary E. Russell, Stephen G. Ellis, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2005)
Phenotypes and phosphatidylinositol glycan-class A gene abnormalities during cell differentiation and maturation from precursor cells to mature granulocytes in patients with paroxysmal nocturnal hemoglobinuria
Authors: Tatsuyuki Kai, Tsutomu Shichishima, Hideyoshi Noji, Tetsuo Yamamoto, Masatoshi Okamoto, Kazuhiko Ikeda, Yukio Maruyama
Journal: Blood (2002)
Interleukin 1 production during accessory cell-dependent mitogenesis of T lymphocytes.
Authors: N Bhardwaj, L L Lau, S M Friedman, M K Crow, R M Steinman
Journal: The Journal of Experimental Medicine (1989)

We have studied the control and significance of IL-1 production in human leukocyte cultures during accessory cell-dependent, T lymphocyte mitogenesis using sensitive bioassays and immunolabeling techniques. In primary antigen-dependent systems like the MLR, IL-1 production was not detected in accessory cells (monocytes, dendritic cells) or T cells, suggesting that it is not an early product in these responses. However, monocytes could be induced to make IL-1 after interacting with sensitized antigen-specific T cells. Both alloreactive T cell clones or freshly prepared lymphoblasts induced IL-1 provided the monocytes carried the HLA-DR antigens to which the T cells were initially sensitized. Even in these circumstances, dendritic cells and B cells failed to make IL-1. The mechanism whereby activated T cells induce IL-1 in monocytes was explored. Supernatants from cocultures of monocytes and T cells or several recombinant cytokines induced little or no IL-1. A more potent antigen independent pathway of IL-1 induction was identified. IL-1 could be induced in third-party HLA-DR nonspecific monocytes in cocultures of alloreactive T cell clones or blasts and HLA-DR-specific dendritic cells. The induction was factor independent since dendritic cells and T blasts placed in a chamber separate from third-party monocytes by a semipermeable membrane did not induce monocyte IL-1. These results suggest that a cell contact mechanism rather than an IL-1-inducing factor leads to IL-1 production. The role of IL-1 in T cell proliferation was tested with a polyclonal anti-IL-1 antibody. The antibody failed to block the proliferation of primary T cells, or alloreactive T cell clones and blasts stimulated with HLA-specific monocytes or dendritic cells, even though IL-1 in the medium was neutralized.
Quality of Life in Long-Term Survivors of Adult-Onset Cancers
Authors: Carolyn Cook Gotay, Miles Y. Muraoka
Journal: JNCI Journal of the National Cancer Institute (1998)

The long-term survival of cancer patients has risen dramatically during the last few decades, yet little is known about the quality of life experienced by these survivors. This paper reviews research on the quality of life in long-term cancer survivors to identify quality-of-life concerns in this population, to provide a critical evaluation of the literature, and to suggest areas for future research. Searches of computerized literature databases were conducted to identify all studies of quality of life in cancer survivors that were published in English language journals during the period from January 1, 1980, through February 12, 1998, and that were based on responses from individuals who have survived 5 or more years after the diagnosis of adult-onset cancers. Thirty-four papers were identified. Most studies utilized self-report questionnaires to measure quality of life. Although methodologies and cancer patient populations varied greatly, most studies showed that many survivors continue to experience negative effects of cancer and/or treatment on their daily lives well beyond the completion of therapy. Sexual functioning and/or satisfaction and psychological functioning were found to be concerns for many survivors. Several reports documented positive coping strategies and enhanced quality of life in long-term cancer survivors, supporting the need to measure positive aspects of quality of life as well as problems in this population. Study designs that more accurately measure quality of life among survivors of cancer by adjusting for the effects of aging and long-term therapy and the impact of second cancers should be utilized. Additional data are needed to understand the needs of long-term survivors, especially of those in groups underrepresented in published quality-of-life studies, and to determine what kinds of support survivors want.
GD3, a prominent ganglioside of human melanoma. Detection and characterisation by mouse monoclonal antibody.
Authors: C S Pukel, K O Lloyd, L R Travassos, W G Dippold, H F Oettgen, L J Old
Journal: The Journal of Experimental Medicine (1982)

Mouse monoclonal antibody AbR24 has a high degree of specificity for human melanoma cells when tested on viable cultured cells using the protein A mixed hemagglutinin serological assay. The antigen detected by this antibody has been isolated from melanoma cells and shown to be GD3 ganglioside by compositional and partial structural analysis and by comparison with authentic GD3 in thin layer chromatography (TLC). AbR24 reacts with authentic GD3, but not with any other ganglioside tested. Using TLC and reactivity with AbR24, a wide range of cells and tissues was examined for the presence of GD3. A new serological assay, termed glycolipid-mediated immune adherence, was devised for assaying the reactivity of AbR24 with gangliosides. Melanomas (cultured cells or tumor tissue) were shown to have GD3 and GM3 as major gangliosides. Other cells and tissues examined also contained GD3, but usually only in low amounts. Melanomas (and MOLT-4, a T cell line) were characterized by a simplified ganglioside profile with GD3 and GM3 as major components. The apparent discrepancy between the ubiquitous presence of GD3 and the serological specificity of AbR24 for melanoma cells can be explained in terms of localization and concentration of GD3 in different cells.
The additional effect of orthotic devices on exercise therapy for patients with patellofemoral pain syndrome: a systematic review
Authors: Nynke M Swart, Robbart van Linschoten, Sita M A Bierma-Zeinstra, Marienke van Middelkoop
Journal: British Journal of Sports Medicine (2011)

The aim of the study is to determine “the additional effect of... function” for patellofemoral pain syndrom (PFPS). The additional effect of orthotic devices over exercise therapy on pain and function. A systematic literature search was conducted in MEDLINE, CINAHL, EMBASE, Cochrane and PEDro. Randomised controlled trials and controlled clinical trials of patients diagnosed with PFPS evaluating a clinically relevant outcome were included. Treatment had to include exercise therapy combined with orthotics, compared with an identical exercise programme with or without sham orthotics. Data were summarised using a best evidence synthesis. Eight trials fulfilled the inclusion criteria, of which three had a low risk of bias. There is moderate evidence for no additive effectiveness of knee braces to exercise therapy on pain (effect sizes (ES) varied from −0.14 to 0.04) and conflicting evidence on function (ES −0.33). There is moderate evidence for no difference between knee braces and exercise therapy versus placebo knee braces and exercise therapy on pain and function (ES −0.1–0.10). More studies of high methodological quality are needed to draw definitive conclusions.
Counterselection against Dμ Is Mediated through Immunoglobulin (Ig)α-Igβ
Authors: Shiaoching Gong, Mercedes Sanchez, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (1996)

The pre-B cell receptor is a key checkpoint regulator in developing B cells. Early events that are controlled by the pre-B cell receptor include positive selection for cells express membrane immunoglobulin heavy chains and negative selection against cells expressing truncated immunoglobulins that lack a complete variable region (Dμ). Positive selection is known to be mediated by membrane immunoglobulin heavy chains through Igα-Igβ, whereas the mechanism for counterselection against Dμ has not been determined. We have examined the role of the Igα-Igβ signal transducers in counterselection against Dμ using mice that lack Igβ. We found that Dμ expression is not selected against in developing B cells in Igβ mutant mice. Thus, the molecular mechanism for counterselection against Dμ in pre-B cells resembles positive selection in that it requires interaction between mDμ and Igα-Igβ.
Vorinostat in solid and hematologic malignancies
Authors: David Siegel, Mohamad Hussein, Chandra Belani, Francisco Robert, Evanthia Galanis, Victoria M Richon, José Garcia-Vargas, Cesar Sanz-Rodriguez, Syed Rizvi
Journal: Journal of Hematology & Oncology (2009)

Vorinostat (Zolinza®), a histone deacetylase inhibitor, was approved by the US Food and Drug Administration in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. This review summarizes evidence on the use of vorinostat in solid and hematologic malignancies and collated tolerability data from the vorinostat clinical trial program. Pooled vorinostat clinical trial data from 498 patients with solid or hematologic malignancies show that vorinostat was well tolerated as monotherapy or combination therapy. The most commonly reported drug-related adverse events (AEs) associated with monotherapy (n = 341) were fatigue (61.9%), nausea (55.7%), diarrhea (49.3%), anorexia (48.1%), and vomiting (32.8%), and Grade 3/4 drug-related AEs included fatigue (12.0%), thrombocytopenia (10.6%), dehydration (7.3%), and decreased platelet count (5.3%). The most common drug-related AEs observed with vorinostat in combination therapy (n = 157, most of whom received vorinostat 400 mg qd for 14 days) were nausea (48.4%), diarrhea (40.8%), fatigue (34.4%), vomiting (31.2%), and anorexia (20.4%), with the majority of AEs being Grade 2 or less. In Phase I trials, combinations with vorinostat were generally well tolerated and preliminary evidence of anticancer activity as monotherapy or in combination with other systemic therapies has been observed across a range of malignancies. Ongoing and planned studies will further evaluate the potential of vorinostat in combination therapy, including combinations with radiation, in patients with diverse malignancy types, including non-small-cell lung cancer, glioblastoma multiforme, multiple myeloma, and myelodysplastic syndrome.
Comparison between five reference equations for the 6 minute walk test in healthy brazilian men
Authors: Luciana Chiavegato, Alexandher Negreiros, Monica Moraes, Rosane Bernardes, Rosimeire Padula
Journal: European Respiratory Journal (2013)

The 6-minute walk test (6MWT) is widely used in clinical practices to assess functional capacity and exercise resistance. Most reference equations for 6MWT in healthy subjects were established based on American and European populations, with only a few proposed for the Brazilian population. Objectives: To compare the distance walked in 6 minutes by healthy males with the predicted distance values obtained from five reference equations, evaluate the difference between them and which would be most reliable for use in the Brazilian population. Methods: We evaluated 104 individuals (mean age 34.12 ± 8.88 years), the level of physical activity, respiratory symptoms, handgrip strength and 6MWD. T Test was performed in order to compare the distance walked with the predicted distances obtained in the five reference equations. Results: The average distance walked by the participants in the 6MWT (6MWD) was 663.43 ± 93.01 meters. The predicted values that were closest to those obtained by Enright & Sherrill, Am J Respir Crit Care Med. 1998;158(5):1384-7 (640.66 ± 100.70 meters) and Iwama et al. Brazilian Journal of Medical and Biological Research 2009: 42: 1080-85 (621.27 ± 15.65 meters), which was proposed for the Brazilian population. Conclusions: We conclude that the Enright & Sherrill and Iwama et al equations can be used in order to estimate a predicted distance walked in 6 minutes in healthy Brazilian men.
Gain of function of cardiac ryanodine receptor in a rat model of type 1 diabetes
Authors: Chengju Tian, Chun Hong Shao, Caronda J. Moore, Shelby Kutty, Timothy Walseth, Cyrus DeSouza, Keshore R. Bidasee
Journal: Cardiovascular Research (2011)

Ventricular myocytes isolated from hearts of streptozotocin (STZ)-diabetic rats exhibit increased spontaneous Ca2+ release. Studies attribute this defect to an enhancement in activity of type 2 ryanodine receptor (RyR2). To date, underlying reasons for RyR2 dysregulation remain undefined. This study assesses whether the responsiveness of RyR2 following stimulation by intrinsic ligands is being altered during experimental type 1 diabetes (T1D). M-mode echocardiography established a cardiomyopathy in 8 weeks STZ-diabetic rats. Confocal microscopy confirmed an increase in the spontaneous Ca2+ release in isolated ventricular myocytes. Western blots revealed no significant change in steady-state levels of the RyR2 protein. When purified to homogeneity and incorporated into planar lipid bilayers, RyR2 from STZ-diabetic rats (dRyR2) exhibited reduced current amplitude at ±35 mV. dRyR2 was also more responsive to intrinsic cytoplasmic activators Ca2+, adenosine triphosphate, and cyclic adenosine diphosphate ribose and less responsive to the cytoplasmic deactivator Mg2+. Threshold for the activation of RyR2 by trans (luminal) Ca2+ was also reduced. These changes were independent of phosphorylation at Ser2808 and Ser2814. Two weeks of insulin treatment starting after 6 weeks of diabetes blunted the phenotype change, indicating that the gain of function is specific to the diabetes and not the result of STZ interacting directly with RyR2. These data show, for the first time, that RyR2 is acquiring a gain-of-function phenotype independent of its phosphorylation status during T1D and provides new insights for the enhanced spontaneous Ca2+ release in myocytes from T1D rats.
Beta-Adrenergic Receptors and Isoproterenol-stimulated Potassium Transport in Erythrocytes from Normal and Hypothyroid Turkeys
Authors: Haruyasu Furukawa, John N. Loeb, John P. Bilezikian
Journal: Journal of Clinical Investigation (1980)

We have previously reported that in hypothyroid turkeys the number of beta-adrenergic receptors in intact erythrocytes is reduced by ∼50% without any changes in the affinity of the receptor for the agonist, isoproterenol. In view of the physiological action of the catecholamines to stimulate bidirectional ion fluxes in these cells, we have now examined the possibility that the decrease in beta receptor number might be associated with concomitant changes in catecholamine-dependent potassium ion transport. Hypothyroid turkey erythrocytes display decreased sensitivity to isoproterenol-stimulated potassium influx. Half-maximal stimulation of potassium influx occurs at 9.2±1.7 nM in hypothyroid cells as opposed to only 3.8±0.4 nM in normal cells (P < 0.005). A maximal stimulatory concentration of isoproterenol (100 nM) leads to the same increment in ion flux in erythrocytes from hypothyroid and normal turkeys. Analysis of the quantitative relationship between isoproterenol concentration, receptor occupancy, and associated effects upon potassium influx shows that at low levels of isoproterenol, where occupancy is linear with agonist concentration, occupation of a given number of beta receptors leads to a stimulation of potassium transport that is identical in erythrocytes from normal and hypothyroid turkeys. Thus, decreased sensitivity to catecholamine-stimulated potassium transport in hypothyroidism can be attributed to the decrease in receptor number and the resulting two- to threefold higher isoproterenol concentration required for occupancy of the same number of beta receptors. Once a single receptor is occupied, however, the more distal components of the sequence of events mediating the physiological response to beta-adrenergic agonists in the hypothyroid cell function as they do under normal circumstances. It would appear, therefore, that the decrease in sensitivity to isoproterenol-dependent ion flux in the hypothyroid turkey erythrocyte can be accounted for solely by the decrease in receptor number. These changes are shown to occur in the absence of any modifications in the number of Na+-K+ ATPase effector units per cell.