tbuckley/cabot-search huggingface dataset:
Isoniazid-associated Hepatitis and Antiretroviral Drugs during Tuberculosis Prophylaxis in HIV-infected Adults in Botswana
Authors: Zegabriel Tedla, Samba Nyirenda, Crandall Peeler, Tefera Agizew, Thabisa Sibanda, Oaitse Motsamai, Andrew Vernon, Charles D. Wells, Taraz Samandari
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Little is known about the incidence of isoniazid-associated hepatitis in HIV-infected Africans who receive both isoniazid preventive therapy (IPT) and antiretroviral therapy (ART).To assess the rate of and risk factors for isoniazid (INH)-associated hepatitis in persons living with HIV (PLWH) during IPT.PLWH recruited for a clinical trial received 6 months of open-label, daily, self-administered INH at public health clinics. At screening PLWH were excluded if they had any cough, weight loss, night sweats, or other illness. Alcohol abuse was defined as meeting any CAGE criterion. INH-associated hepatitis (INH-hepatitis) was defined as having either alanine or aspartate aminotransferase greater than 5.0 times the upper limit of normal regardless of symptoms when INH was not excluded as the cause.Of 1,995 PLWH enrolled between 2004 and 2006, 1,762 adhered to at least 4 months of IPT and were analyzed. Nineteen (1.1%) developed hepatitis probably or possibly associated with INH including one death at month 6; 14 of 19 (74%) occurred in months 1-3. Antiretroviral therapy (ART) was received by 480 participants but was not statistically associated with INH-hepatitis (relative risk [RR], 1.56; 95% confidence intervals [CI], 0.62-3.9); those receiving nevirapine had a higher rate (2.0%) than those receiving efavirenz (0.9%; P = 0.34). Although alcohol use did not reach significance (RR, 1.42; 95% CI, 0.57-3.51), meeting at least one CAGE criterion approached statistical significance (RR, 2.37; 95% CI, 0.96-5.84). Neither age greater than 35 years nor the presence of hepatitis B virus core antibody was associated with INH-hepatitis.The observed rates of INH-hepatitis were similar to published data. Six months of IPT, which is recommended by the World Health Organization, was relatively safe in this, the largest cohort of African PLWH. Clinical trial registered with www.clinicaltrials.gov (NCT 00164281).
Discrimination of polycythemias and thrombocytoses by novel, simple, accurate clonality assays and comparison with PRV-1 expression and BFU-E response to erythropoietin
Authors: Enli Liu, Jaroslav Jelinek, Yves D. Pastore, Yongli Guan, Jaroslav F. Prchal, Josef T. Prchal
Journal: Blood (2003)
Functional Evaluation of Lipid-Lowering Therapy by Pravastatin in the Regression Growth Evaluation Statin Study (REGRESS)
Authors: Wim R. M. Aengevaeren, Gerard J. H. Uijen, J. Wouter Jukema, Albert V. G. Bruschke, Tjeerd van der Werf
Journal: Circulation (1997)

Background Lipid-lowering therapy during 2 years in the Regression Growth Evaluation Statin Study (REGRESS) was associated with less progression of coronary atherosclerosis in the pravastatin group compared with the placebo group. The effect of lipid-lowering therapy on the functional state of the coronary circulation is less well known. The purpose of this study was to evaluate this effect. Methods and Results In a substudy of REGRESS, 69 patients were randomized to pravastatin or placebo. Thirty-seven of these patients were allocated to the medical management stratum. Quantitative coronary angiography, regional myocardial perfusion, exercise testing, and classification of angina pectoris were assessed at baseline and after 2 years of therapy. Regional myocardial perfusion was assessed by digital subtraction angiography after intracoronary papaverine with videodensitometric calculation of the hyperemic mean transit time (HMTT) of contrast. In the medical management stratum, regional myocardial perfusion was assessed in 31 regions in the pravastatin group and 25 regions in the placebo group. The change in HMTT in the pravastatin group was −0.18 seconds (−5%) and in the placebo group +0.52 seconds (+18%), a difference of 0.70 seconds ( P =.004). The mean difference in change in classification of angina pectoris (scale, 1 to 4) between pravastatin and placebo was 0.7 ( P =.03) in favor of the pravastatin-treated patients. The change in HMTT was correlated with the change in exercise time ( r =−.65, P =.002). Conclusions In patients with symptomatic coronary artery disease, treatment with the HMG-coenzyme A reductase inhibitor pravastatin during 2 years resulted in a preserved regional myocardial perfusion, whereas patients on placebo deteriorated. The classification of angina pectoris improved only in patients receiving pravastatin. In lipid-lowering therapy, the evaluation of myocardial perfusion by assessment of the HMTT reveals a combined measure of functional and structural changes in the coronary circulation.
Information Processing Deficits in Acutely Psychotic Schizophrenia Patients Medicated and Unmedicated at the Time of Admission
Authors: William Perry, David Feifel, Arpi Minassian, Indira Bhattacharjie, David L. Braff
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: In patients with schizophrenia, information processing deficits, such as those reported in studies that measured prepulse inhibition of the human startle response and habituation of startle magnitude, may be improved with atypical antipsychotic treatment. However, it remains unclear whether antipsychotic medication is directly responsible for the improvement or whether differences in prepulse inhibition reflect other factors, such as acuity status. The present study investigated the effects of antipsychotics on prepulse inhibition and startle habituation in acutely hospitalized patients with schizophrenia. METHOD: Forty-one acutely psychotic schizophrenia patients (21 who were unmedicated at the time of admission and 20 who had been receiving antipsychotic treatment) were tested within 72 hours of hospital admission. Thirteen healthy subjects were also studied for comparative purposes. Primary dependent measures were startle responsivity, reactivity, prepulse inhibition, and startle habituation. RESULTS: Schizophrenia patients, whether medicated or unmedicated at admission, showed prepulse inhibition deficits compared with healthy subjects and did not statistically differ from each other in startle magnitude, prepulse inhibition, or habituation. There was a higher number of startle "nonresponders" among those who had been receiving medication versus those unmedicated at the time of admission. CONCLUSIONS: The present findings suggest that antipsychotic effects on prepulse inhibition may not be evident at a time when schizophrenia patients are acutely symptomatic. These results suggest that the neurobiological substrate underlying prepulse inhibition deficits may be dysregulated during acute psychotic states while the patients are in early phases of medication treatment.
Chromosomal Breakpoints Affecting Immunoglobulin Loci Are Recurrent in Hodgkin and Reed-Sternberg Cells of Classical Hodgkin Lymphoma
Authors: José I. Martín-Subero, Wolfram Klapper, Anna Sotnikova, Evelyne Callet-Bauchu, Lana Harder, Christian Bastard, Roland Schmitz, Susanne Grohmann, Jorge Höppner, Jennifer Riemke, Thomas F.E. Barth, Françoise Berger, Heinz-Wolfram Bernd, Alexander Claviez, Stefan Gesk, Georgiy A. Frank, Irina B. Kaplanskaya, Peter Möller, Reza M. Parwaresch, Thomas Rüdiger, Harald Stein, Ralf Küppers, Martin L. Hansmann, Reiner Siebert
Journal: Cancer Research (2006)

Abstract Chromosomal breakpoints affecting immunoglobulin (IG) loci are recurrent in many subtypes of B-cell lymphomas. However, despite the predominant B-cell origin of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL), the presence of chromosomal translocations in IG loci has not yet been systematically explored. Therefore, we have investigated a series of cHL for chromosomal breakpoints in the IGH (n = 230), IGL (n = 139), and IGK (n = 138) loci by interphase cytogenetics. Breakpoints in the IGH, IGL, or IGK locus were observed in the HRS cells of 26 of 149 (17%), 2 of 70, and 1 of 77 evaluable cHLs, respectively. The IG partners could be identified in eight cHLs and involved chromosomal bands 2p16 (REL), 3q27 (BCL6, two cases), 8q24.1 (MYC), 14q24.3, 16p13.1, 17q12, and 19q13.2 (BCL3/RELB). In 65 of 85 (76%) cHLs evaluable for an IGH triple-color probe, the HRS cells showed evidence for a (partial) deletion of the IGH constant region, suggesting the presence of class switch recombination (CSR). Furthermore, analyses with this probe in cases with IGH breakpoints indicated that at least part of them seem to be derived from CSR defects. Our results show that chromosomal breakpoints affecting the IG loci are recurrent in cHL. (Cancer Res 2006; 66(21): 10332-8)
Multiple Signaling States of G-Protein-Coupled Receptors
Authors: Dianne M. Perez, Sadashiva S. Karnik
Journal: Pharmacological Reviews (2005)

Studies have been amassed in the past several years indicating that an agonist can conform a receptor into an activation state that is dependent upon an intrinsic property of the agonist usually based upon its chemical composition. Theoretically, each different agonist could impart its own unique activation state. Evidence for multiple signaling states for the G-protein-coupled receptors will be reviewed and is derived from many different pharmacological behaviors: efficacy, kinetics, protean agonism, differential desensitization and internalization, inverse agonism, and fusion chimeras. A recent extension of the ternary complex model is suggested by evidence that the different processes that govern deactivation, such as desensitization and internalization, is also regulated by conformers specific to the agonist. Rhodopsin may serve as a primer for the study of multiple activation states. Therapeutic implications that utilize multiple signaling states hold vast promise in the rationale design of drugs.
Peptide-induced stabilization and intracellular localization of empty HLA class I complexes.
Authors: E J Baas, H M van Santen, M J Kleijmeer, H J Geuze, P J Peters, H L Ploegh
Journal: The Journal of Experimental Medicine (1992)

The human cell line T2 has been reported to be class I assembly deficient, and accordingly expresses reduced amounts of HLA-A2 and no HLA-B5 at the cell surface. By immunoblotting we observe the steady-state class I heavy chain levels of T2 to be near normal when compared with the identical class I alleles of the wild-type cell line T1. In pulse chase experiments, formation of heavy chain beta 2-microglobulin complexes is observed for both HLA-A2 and HLA-B5. Culture at reduced temperatures (26 or 20 degrees C) does not increase the amount of class I molecules transported, unlike what has been reported for the class I assembly-deficient mouse mutant cell line RMA-S. The HLA-B5 and the HLA-A2 complexes formed by T2 are thermolabile in cell lysates, albeit to different degrees. The thermolability of HLA-B5 can be overcome by addition of HLA-B5-presentable peptides, obtained by trifluoroacetic acid extraction from an HLA-B5-positive cell line, underlining the necessity of peptide for class I stability and indicating that T2-derived class I complexes are devoid of peptide. Cytoplast fusion of T2 cells with RMA-S cells shows the defect in class I assembly of RMA-S to be similar to that of T2. Localization of class I molecules observed by immuno-electron microscopy reveals the accumulation in the T2 cell line of both HLA-B5 and HLA-A2 in the endoplasmic reticulum (ER). Class I molecules are present in all the cisternae of the Golgi complex of T2, but the ratio of HLA-A and -B locus products in the Golgi area differs significantly from that at the cell surface. We conclude that the requirement for peptide in transport of class I molecules manifests itself at a stage beyond the ER, most likely the Golgi area.
Interaction between FEZ1 and DISC1 in Regulation of Neuronal Development and Risk for Schizophrenia
Authors: Eunchai Kang, Katherine E. Burdick, Ju Young Kim, Xin Duan, Junjie U. Guo, Kurt A. Sailor, Dhong-Eun Jung, Sundar Ganesan, Sungkyung Choi, Dennis Pradhan, Bai Lu, Dimitrios Avramopoulos, Kimberly Christian, Anil K. Malhotra, Hongjun Song, Guo-li Ming
Journal: Neuron (2011)
Neutrophil chemotaxis in ankylosing spondylitis, Reiter's disease, and polymyalgia rheumatica.
Authors: A G Mowat
Journal: Annals of the Rheumatic Diseases (1978)

Neutrophil chemotaxis was found to be normal in 14 patients with ankylosing spondylitis, in 10 patients with Reiter's disease, and in 8 patients with polymyalgia rheumatica.
Systemic microRNAs: novel biomarkers for colorectal and other cancers?
Authors: H. M. Heneghan, N. Miller, M. J. Kerin
Journal: Gut (2010)

We read with interest the recent article by Ng et al which concludes that plasma microRNAs (miRNAs) hold potential as non-invasive screening tools for colorectal cancer (CRC).1 Investigation of miRNAs in the circulation has recently gained momentum, upon recognising their potential as novel tumour markers.2 In our institution we have recently identified that circulating miR-195 and let-7a are significantly elevated in blood from patients with breast cancer (n=83) compared with controls (n=44). Similar to Ng and colleagues, we observed a postoperative decrease in systemic miRNA levels, and a significant correlation between systemic and tumour miRNA levels, and stage of disease.3 Whilst we agree with Ng et al that plasma miRNAs may be useful CRC biomarkers, we have several comments in relation to their article.

First, the use of plasma above serum or whole blood is questionable. There is as yet …
Alk Translocation in Sarcomatoid Carcinoma of Head and Neck and Treatment Effect of Crizotinib: a Case Series
Authors: Sungmin Kim, Myung-Ju Ahn, Jong-Mu Sun, Keunchil Park, Moon Jin Kim, Yunla Choi, Young Hye Go, Chung-Hwan Baek, Young-Ik Son
Journal: Annals of Oncology (2014)
Biosynthesis of lipoxygenase and cyclo-oxygenase products from [14C]-arachidonic acid by human colonic mucosa.
Authors: N K Boughton-Smith, C J Hawkey, B J Whittle
Journal: Gut (1983)

The human colon synthetises several prostanoids which may have a role in inflammatory bowel diseases. As lipoxygenase products of arachidonate metabolism have been implicated in inflammatory processes, we have now investigated the formation of both lipoxygenase and cyclo-oxygenase metabolites from [14C]-arachidonic acid [(14C]-AA) by human colonic tissue. Homogenates of human colonic mucosa were incubated with [14C]-AA and after extraction into diethyl ether, separated by thin layer chromatography using two solvent systems that allowed resolution of cyclo-oxygenase and lipoxygenase products. The predominant cyclo-oxygenase products, as identified by their chromatographic mobility, were PGE2 greater than PGF2 alpha greater than PGD2 greater than TXB2 greater than 6-keto-PGF1 alpha. The formation of these products was inhibited both by indomethacin (1-10 microM) and the dual pathway inhibitor, BW755C (1-30 microM). The predominant lipoxygenase products formed, which had the chromatographic mobility of 11-, 12-, 15-HETE (which ran together) were inhibited by BW755C (19 microM) but not by indomethacin (3 microM). Further resolution of this TLC band, performed using normal phase HPLC, indicated that both 12-HETE and 15-HETE were major lipoxygenase products formed by human colonic homogenate. The present findings indicate that human colonic tissue can convert [14C]-AA into lipoxygenase as well as cyclo-oxygenase products and support the suggestion that lipoxygenase products may have a role in inflammatory bowel disease.
Relationship between inflammatory cells and structural changes in the lungs of asymptomatic and never smokers: a biopsy study
Authors: K Amin, A Ekberg-Jansson, Claes-Göran Löfdahl, P Venge
Journal: Thorax (2003)

<b>Background:</b> A study was undertaken to investigate the relationship between inflammatory cells and structural changes in the mucosa of the airways in an epidemiological sample of a group of asymptomatic smokers (smokers who had never sought medical attention for respiratory problems) and in non-smoking subjects. <b>Methods:</b> Bronchial biopsy specimens were taken from 29 smokers and 16 never smokers and stained with monoclonal antibodies HNL, EPO, AA1, CD68 in order to identify neutrophils, eosinophils, mast cells, and macrophages, respectively. The biopsy specimens were also stained with monoclonal antibodies to the cytokines interleukin (IL)-1β and IL-8. Structural changes were identified by staining the biopsy specimens with antibodies to tenascin and laminin and by evaluating the condition of the epithelial layer. <b>Results:</b> The numbers of all inflammatory cells and of cytokine staining cells were significantly increased in smokers. The thickness of the tenascin and laminin layers was increased in the smoking group and the integrity of the epithelial layer was significantly reduced. In smokers the epithelial integrity was negatively correlated with the number of eosinophils and macrophages. The thickness of the tenascin and laminin layers was positively correlated with AA1 and EPO positive cells only. <b>Conclusion:</b> High numbers of inflammatory cells are present in the bronchial mucosa of asymptomatic smokers which have a clear relationship with the impaired epithelial integrity. The increased thickness of the laminin and tenascin layers in these subjects was strongly related to the presence of eosinophils and mast cells, suggesting a role for these cells in tissue remodelling of the airways of smokers.
partial reversal and the functions of lateralisation
Authors: richard john andrew
Journal: Behavioral and Brain Sciences (2005)

the use of lateralised cues by predators and fellows may not strongly affect lateralisation. conservatism of development is a possible source of consistency across vertebrates. individuals with partial reversal, affecting only one ability, or with varying degree of control of response by one hemisphere do exist. their incidence may depend on varying selection of behavioural phenotypes such as risk taking.
P102 Post-Hospitalisation Outpatient Pulmonary Rehabilitation: A Translational Gap?
Authors: SE Jones, SA Green, AL Clark, MJ Dickson, A-M Nolan, C Moloney, SSC Kon, J Godden, C Howe, BM Haselden, S Fleming, WD-C Man
Journal: Thorax (2012)

<h3>Background</h3> Recent trials and meta-analyses of early post-hospitalisation pulmonary rehabilitation (PR) in COPD have demonstrated improvements in exercise capacity, health-related quality of life and a reduction in hospital readmissions (Man <i>et al.</i>, 2004; Seymour <i>et al.</i> 2010; Puhan <i>et al.</i> 2011). However anecdotal observation and evidence from recent trials suggest poor uptake of outpatient PR. The aim of the study was to map patient journeys to identify gaps or deficiencies in the referral pathway. <h3>Methods</h3> All 224 patients discharged from Hillingdon Hospital following an acute exacerbation of COPD between November 2011 and May 2012 were included in the analysis. Referrals for post-exacerbation PR from Hillingdon Hospital were monitored during the same time period. A collaborative of 18 stakeholders from seven organisations across primary, secondary and community care services was convened and performed local process mapping. Structured telephone interviews were held with a convenience sample of 36 COPD patients who declined post-hospitalisation PR. <h3>Results</h3> Despite excellent compliance with a COPD discharge bundle (95%), only 63 (28%) of the 224 discharges from Hillingdon Hospital were referred to the local PR provider. All referrals were offered initial assessment for PR within 2 weeks of discharge but 18 failed to attend on at least 2 occasions. A further 9 patients failed to start PR despite attending initial assessment. In total, only 36 (16%) patients out of all hospital discharges over a 6-month period started outpatient PR. The main reasons for patients declining outpatient PR were accessibility issues (40%), commitment to PR “too time-consuming” (20%) or “too unwell” (13%). <h3>Conclusion</h3> Despite a strong evidence base, there is poor uptake of post-hospitalisation early PR. The majority of missed opportunities occur at the initial referral stage, although there is a significant drop-out even in those referred. Ongoing experience based design work will explore staff and patient attitudes that may influence referral and uptake rates.
Role of Docetaxel in the Treatment of Newly Diagnosed Advanced Ovarian Cancer
Authors: P. A. Vasey
Journal: Journal of Clinical Oncology (2003)

Docetaxel is currently licensed for use in a variety of malignancies, including breast cancer and lung cancer, and is the preferred taxane in breast cancer treatment. In ovarian cancer, the taxane of choice has historically been paclitaxel; however, there is now substantial evidence that docetaxel also may be the preferred taxane in this disease. Docetaxel has many preclinical advantages over paclitaxel and has been shown to be effective in both platinum- and paclitaxel-resistant disease. Phase I and II studies have shown docetaxel plus carboplatin to be feasible, and the combination is associated with a tolerable adverse-effect profile. The Scottish Randomized Trial in Ovarian Cancer (SCOTROC) trial randomly assigned 1,077 patients with International Federation of Gynecology and Obstetrics stage Ic to IV disease to six cycles of docetaxel plus carboplatin (DC) or paclitaxel plus carboplatin (PC) as primary chemotherapy. Progression-free survival is not statistically different, and to date, no differences are apparent in overall survival. Toxicity differences were evident. There was more myelosuppression with DC but no additional mortality. More neuropathy was present with PC, with more patients stopping paclitaxel because of this toxicity during chemotherapy. Quality-of-life analyses highlighted important differences, all favoring the DC treatment arm. Additional SCOTROC studies using docetaxel are ongoing. These data indicate that docetaxel and carboplatin represent a reasonable first-line option for patients with newly diagnosed epithelial ovarian cancer.
Experience with a tuberculosis antigen test in Rhodesia.
Authors: J B Cookson, J G Cruickshank, B P Ellis
Journal: Thorax (1977)

Experience with a new serological method for the diagnosis of tuberculosis is reported in a predominantly black population. We have found that in only 69% of 167 patients was there agreement between serology and the presence or absence of tuberculosis. Both false positive and false negative results were common. Of 47 healthy controls, 80% were positive. These results are less satisfactory than previous studies but differences in the reading of the results seems an unlikely explanation. Differences in the populations studied may be an important factor.
Pregnancy in patients with Wegener's granulomatosis: report of five cases in three women
Authors: C. Auzary
Journal: Annals of the Rheumatic Diseases (2000)

Five cases of pregnancy occurring in three women with previously diagnosed Wegener9s granulomatosis are described. The disease was diffuse in one case and localised in the other. Initial treatment consisted of a combination of corticosteroids and intravenous cyclophosphamide in two women, and methotrexate in one. Four pregnancies ended in live births despite pre-eclampsia in two cases. One therapeutic abortion was induced because of encephalocele. Comparable reported cases were reviewed to examine the implications of immunosuppressive treatment on the fetus. A relapse occurred during pregnancy in 40% of the cases, but in 25% if only pregnancies beginning during inactive disease were taken into account. No other indicator for maternal and fetal outcome was obvious. Pregnancy should be planned after complete disappearance of disease activity. In the case of a relapse a combination of immunosuppressive drugs and corticosteroids should be chosen rather than corticosteroids alone because the outcome of pregnancy is poor in cases of undertreatment. Prematurity remains common.