tbuckley/cabot-search huggingface dataset:
Fas ligation induces apoptosis of CD40-activated human B lymphocytes.
Authors: P Garrone, E M Neidhardt, E Garcia, L Galibert, C van Kooten, J Banchereau
Journal: The Journal of Experimental Medicine (1995)

Since CD40/CD40 ligand (CD40Lig) interactions are essential in vivo for the generation of germinal center B cells that express Fas (Apo-1/CD95), we explored whether CD40 engagement may modulate Fas expression and function on human B lymphocytes. Resting tonsil B cells, isolated by density gradient centrifugation, express either absent or low levels of Fas. They could be induced to promptly express Fas after ligation of their CD40, however, using either a recombinant human CD40Lig or a cross-linked anti-CD40 mAb. In contrast, engagement of the B cell antigen receptor by immobilized anti-kappa and -lambda antibodies did not turn on Fas expression. Addition of anti-Fas mAb CH11 inhibited the later phases of CD40-induced B cell growth as a result of apoptotic cell death. Furthermore, Fas ligation inhibited proliferation and Ig secretion of CD40-activated B cells in response to recombinant cytokines such as interleukin (IL)-2, IL-4, and IL-10, as well as a cytokine-rich supernatant of phytohemagglutinin-activated T cells, indicating that none of those B cell tropic factors were able to prevent the Fas-induced death. Taken together, the present results show that engagement of CD40 antigen on B cells induces Fas expression and sensitizes them to Fas-mediated apoptosis. The delayed functional response to Fas ligation after CD40 activation may represent a way to limit the size of a specific B cell clone that is generated during T-B cell interactions.
Hypomethylation and expression of BEX2, IGSF4 and TIMP3 indicative of MLL translocations in Acute Myeloid Leukemia
Authors: Sonja Röhrs, Wilhelm G Dirks, Claus Meyer, Rolf Marschalek, Michaela Scherr, Robert Slany, Andrew Wallace, Hans G Drexler, Hilmar Quentmeier
Journal: Molecular Cancer (2009)

Abstract Background Translocations of the Mixed Lineage Leukemia ( MLL ) gene occur in a subset (5%) of acute myeloid leukemias (AML), and in mixed phenotype acute leukemias in infancy - a disease with extremely poor prognosis. Animal model systems show that MLL gain of function mutations may contribute to leukemogenesis. Wild-type (wt) MLL possesses histone methyltransferase activity and functions at the level of chromatin organization by affecting the expression of specific target genes. While numerous MLL fusion proteins exert a diverse array of functions, they ultimately serve to induce transcription of specific genes. Hence, acute lymphoblastic leukemias (ALL) with MLL mutations ( MLL mu) exhibit characteristic gene expression profiles including high-level expression of HOXA cluster genes. Here, we aimed to relate MLL mutational status and tumor suppressor gene (TSG) methylation/expression in acute leukemia cell lines. Results Using MS-MLPA (methylation-specific multiplex ligation-dependent probe amplification assay), methylation of 24 different TSG was analyzed in 28 MLL mu and MLL wt acute leukemia cell lines. On average, 1.8/24 TSG were methylated in MLL mu AML cells, while 6.2/24 TSG were methylated in MLL wt AML cells. Hypomethylation and expression of the TSG BEX2, IGSF4 and TIMP3 turned out to be characteristic of MLL mu AML cell lines. MLL wt AML cell lines displayed hypermethylated TSG promoters resulting in transcriptional silencing. Demethylating agents and inhibitors of histone deacetylases restored expression of BEX2, IGSF4 and TIMP3 , confirming epigenetic silencing of these genes in MLL wt cells. The positive correlation between MLL translocation, TSG hypomethylation and expression suggested that MLL fusion proteins were responsible for dysregulation of TSG expression in MLL mu cells. This concept was supported by our observation that Bex2 mRNA levels in MLL-ENL transgenic mouse cell lines required expression of the MLL fusion gene. Conclusion These results suggest that the conspicuous expression of the TSG BEX2, IGSF4 and TIMP3 in MLL mu AML cell lines is the consequence of altered epigenetic properties of MLL fusion proteins.
Performance of a whole blood interferon gamma assay for detecting latent infection with Mycobacterium tuberculosis in children
Authors: Tom G Connell, Nigel Curtis, Sarath C Ranganathan, Jim P Buttery
Journal: Thorax (2006)

The diagnosis of latent Mycobacterium tuberculosis (MTB) infection with a tuberculin skin test (TST) in children is complicated by the potential influence of prior exposure to Bacille Calmette Geurin (BCG) vaccination or environmental mycobacteria. A whole blood assay has recently been developed to quantitatively measure interferon gamma (IFN-gamma) production by lymphocytes specific to the MTB antigens ESAT-6 and CFP-10, but its use and assessment in children has been limited. A study was undertaken to compare the performance of the whole blood IFN-gamma assay with the TST in diagnosing latent tuberculosis (TB) infection or TB disease in children in routine clinical practice.One hundred and six children with a high risk of latent TB infection or TB disease were enrolled in the study. High risk was defined as contact with TB disease, clinical suspicion of TB disease, or recent arrival from an area of high TB prevalence. The whole blood IFN-gamma assay was undertaken in 101 children.Seventeen (17%) of the 101 assays yielded inconclusive results due to failure of positive or negative control assays. There was poor correlation between the whole blood IFN-gamma assay and the TST (kappa statistic 0.3) with 26 (70%) of the 37 children defined as latent TB infection by TST having a negative whole blood IFN-gamma assay. There were no instances of a positive whole blood IFN-gamma assay with a negative TST. Mitogen (positive) control IFN-gamma responses were significantly correlated with age (Spearman's coefficient = 0.53, p<0.001) and, in children with latent TB infection identified by TST, those with a positive IFN-gamma assay were older (median 12.9 v 6.92 years, respectively, p = 0.007). The whole blood IFN-gamma assay was positive in all nine children with TB disease.There was poor agreement between the whole blood IFN-gamma assay and TST for the diagnosis of latent TB. The whole blood IFN-gamma assay may have lower sensitivity than the TST in diagnosing TB infection in children. A significant proportion of whole blood IFN-gamma assays fail when used as a screening assay in routine practice.
Investigations on the renin-angiotensin system in acute severe asthma
Authors: SG Ramsay, KD Dagg, IC McKay, BJ Lipworth, C McSharry, NC Thomson
Journal: European Respiratory Journal (1997)

The renin-angiotensin system is activated in acute severe asthma. The precise mechanism of activation is at present unknown, but may involve, beta2-agonists, catecholamines or proteases released in airway inflammation. This study aims to identify potential factors involved in the activation of the renin-angiotensin system in acute asthma. Forty asthmatics with severe exacerbations of asthma, assessed by measurement of peak expiratory flow rate (mean (SD) 35 (18)% predicted), oxygen saturation (94 (4)%) and pulse rate (108 (16) beats x min(-1)) were recruited. Nineteen (48%) asthmatics had elevated plasma angiotensin II levels (median (interquartile range) 10.9 (4.3-23.5) pg x mL(-1) (normal range 3-12 pg x mL(-1))) and 10 (25%) had elevated plasma renin concentration (22.0 (10.0-50.0) microU x mL(-1) (normal range 9-50 microU x mL(-1))). Plasma renin and angiotensin II correlated strongly, implying renin-dependent angiotensin II formation. No correlation was found between plasma salbutamol, adrenaline, nor-adrenaline, endothelin-1, histamine, eosinophilic cationic protein, serum angio-tensin-converting enzyme (ACE) activity, total immunoglobulin E (IgE), urea and electrolytes, indicators of the severity of the attack, atopic status, blood pressure and renin or angiotensin II levels. We conclude that although a subpopulation of asthmatics appear to have raised renin and angiotensin II during attacks of acute, severe asthma, the mechanism of activation of the renin-angiotensin system remains unclear.
Unusual Abdominal Tumors
Authors: Azhar Ali Malik, Nauman Moazzam, Anil Potti
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.12.117 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12610200 Unusual Abdominal Tumors CASE 1. SMALL BOWEL CARCINOID PRESENTING AS AN ACUTE ABDOMEN Azhar Ali MalikxAzhar Ali MalikSearch for articles by this author , Nauman MoazzamxNauman MoazzamSearch for articles by this author , Anil PottixAnil PottiSearch for articles by this author Show More Department of Internal Medicine, University of North Dakota, School of Medicine and Health Sciences, Fargo, ND https://doi.org/10.1200/JCO.2003.12.117 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Multicenter Phase II Clinical Study of Iodine-131–Rituximab Radioimmunotherapy in Relapsed or Refractory Indolent Non-Hodgkin’s Lymphoma
Authors: Michael F. Leahy, John F. Seymour, Rodney J. Hicks, J. Harvey Turner
Journal: Journal of Clinical Oncology (2006)

Purpose To evaluate efficacy and safety of iodine-131 ( 131 I) –rituximab chimeric anti-CD20 antibody radioimmunotherapy in patients with relapsed or refractory indolent non-Hodgkin's lymphoma (NHL). Patients and Methods After a standard loading dose of rituximab 375 mg/m 2 , individualized dosimetry was performed by whole-body gamma imaging of a tracer activity of 131 I-rituximab followed by administration of a therapeutic activity of 131 I-rituximab to deliver an estimated whole-body radiation absorbed dose of 0.75 Gy. Results Ninety-one patients were entered onto the trial: 78 patients (86%) had follicular lymphoma, six patients (7%) had mucosa-associated lymphoid tissue/marginal zone lymphoma, and seven patients (8%) had small lymphocytic lymphoma. The objective overall response rate (ORR) was 76%, with 53% attaining a complete response (CR) or CR unconfirmed (CRu). Median duration of response for patients achieving CR/CRu was 20 v 7 months for those with a partial response (P = .0121). Median progression-free survival for the entire cohort was 13 months, with 14% remaining relapse free beyond 4 years. Median follow-up was 23 months, with a 4-year actuarial survival rate of 59% ± 10%. Toxicity was principally hematologic; grade 4 thrombocytopenia occurred in 4% and neutropenia occurred in 16% of patients, with nadirs at 6 to 7 weeks after treatment. Conclusion 131 I-rituximab radioimmunotherapy of relapsed or refractory indolent NHL achieves high ORR and CR rates with minimal toxicity.
Blood Flow in the Aortic Wall
Authors: LEO A. SAPIRSTEIN, MORRIS J. MANDEL
Journal: Circulation Research (1959)

The indicator-fractionation technic for measurement of regional blood flow has been applied to the measurement of blood flow in the aortic wall, using Rb 86 . The aortic-indicator content declines slowly with time during the first minute, which shows that the aorta has a smaller extraction ratio for Rb 86 than the rest of the body. The application of the indicator-fractionation technic when organ content of indicator changes with time is discussed. It is shown that the perfusion rate of rat aorta is at least 1.70 ml./Gm./min. This value is much larger than would be expected from in vitro studies of aortic oxygen utilization.
Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapy
Authors: Kazuaki Chayama, Yoshiyuki Suzuki, Masahiro Kobayashi, Mizuho Kobayashi, Akihito Tsubota, Michie Hashimoto, Yukiko Miyano, Hiromi Koike, Mariko Kobayashi, Isao Koida, Yasuji Arase, Satoshi Saitoh, Naoya Murashima, Kenji Ikeda, Hiromitsu Kumada
Journal: Hepatology (1998)

Treatment of hepatitis B virus (HBV) with lamivudine is effective in suppressing virus replication and results in reduced inflammatory activity. However, the emergence of lamivudine-resistant mutant virus, with amino acid substitution in the YMDD motif of DNA polymerase, has been reported. We report the emergence and takeover of YMDD mutant and re-takeover by wild type during and after long-term lamivudine therapy. YMDD mutants were detected in five patients who showed DNA breakthrough (HBV DNA becoming detectable after a period of DNA negativity), which occurred after 9 to 14 months of lamivudine therapy. Four of five mutants had amino acid sequence YIDD, and the remaining mutant had YVDD. Patients with high HBV-DNA titer and/or hepatitis B e antigen tended to develop breakthrough (P = .038). Using a sensitive and specific polymerase chain reaction (PCR)-based method developed in this study, the emergence of YMDD mutants was detected 1 to 4 months before DNA breakthrough, but not detected in any of the pretreatment sera. The mutants were predominant at breakthrough, but were replaced by wild-type virus 3 to 4 months after cessation of therapy in the two patients who discontinued therapy. One of these patients had a relapse of hepatitis. Mutant continued to replicate in the remaining three patients who continued to receive treatment, and relapse occurred in only one of these patients. Our results suggest that the replication of YMDD mutant viruses is less than wild type and is re-overtaken by wild type after cessation of therapy. Re-administration of lamivudine, possibly combined with other antiviral therapy, might be useful in some patients experiencing hepatitis with lamivudine-resistant variants.
Co-amoxiclav jaundice: clinical and histological features and HLA class II association
Authors: J O'Donohue
Journal: Gut (2000)

<h3>BACKGROUND AND AIMS</h3> Jaundice associated with co-amoxiclav has been increasingly recognised. We aimed to characterise its clinical and histological features and to investigate linkage with human leucocyte antigen class II haplotypes. <h3>METHODS</h3> We identified cases in the west of Scotland in the period 1991–1997 and performed polymerase chain reaction amplification and oligonucleotide probing on whole blood. <h3>RESULTS</h3> Twenty two cases were identified (10 male, mean age 59.1 years). Jaundice occurred a median of 17 days after drug commencement, with a median peak bilirubin level of 225 μmol/l (range 84–598) and median duration of jaundice 69 days (range 29–150). Two patients had primary biliary cirrhosis and two other patients had persistently abnormal liver biochemistry on follow up. One death occurred in a frail elderly woman despite resolving jaundice. The frequency of jaundice was 1 in 78 209 co-amoxiclav prescriptions. Liver biopsy, available in 12 patients, showed perivenular bilirubinostasis, accompanying reactive ceroid laden macrophages, and portal inflammation with focal injury to interlobular bile ducts. Fourteen of 20 patients had DRB1*1501 compared with 27 of 134 controls (p&lt;2.5×10<sup>–6</sup>; odds ratio (OR) 9.25; relative risk (RR) 6.43). Of these, seven patients were homozygous for DRB1*1501(p&lt; 10<sup>–8</sup>; OR 35.54; RR=8.68) compared with two of 134 controls. All patients with DRB1*1501 had the extended haplotype DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602. There were no clinical or histological differences between genotypes. <h3>CONCLUSIONS</h3> Co-amoxiclav associated hepatotoxicity may have a genetic basis and be delayed, severe, and prolonged, although complete recovery is usual.
Primary Prevention of Hypertension&lt;SUBTITLE&gt;Clinical and Public Health Advisory From the National High Blood Pressure Education Program&lt;/SUBTITLE&gt;
Authors: Paul K. Whelton
Journal: JAMA (2002)

The National High Blood Pressure Education Program Coordinating Committee published its first statement on the primary prevention of hypertension in 1993. This article updates the 1993 report, using new and further evidence from the scientific literature. Current recommendations for primary prevention of hypertension involve a population-based approach and an intensive targeted strategy focused on individuals at high risk for hypertension. These 2 strategies are complementary and emphasize 6 approaches with proven efficacy for prevention of hypertension: engage in moderate physical activity; maintain normal body weight; limit alcohol consumption; reduce sodium intake; maintain adequate intake of potassium; and consume a diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat. Applying these approaches to the general population as a component of public health and clinical practice can help prevent blood pressure from increasing and can help decrease elevated blood pressure levels for those with high normal blood pressure or hypertension.
Role of Cell-generated Hydrogen Peroxide in Granulocyte-mediated Killing of Schistosomula of Schistosoma mansoni In Vitro
Authors: James W. Kazura, Mary M. Fanning, Jeffrey L. Blumer, Adel A. F. Mahmoud
Journal: Journal of Clinical Investigation (1981)

Human as well as murine granulocytes have been shown to kill the larval stages of helminth parasites; the mechanism of this cell-mediated cytotoxicity is, however, poorly understood. The present study was designed to assess the role of peroxidative processes in killing of schistosomula of Schistosoma mansoni by human granulocytes in vitro. The rate of H2O2 production by human neutrophils, eosinophils, and basophils was measured upon incubation with schistosomula alone or in the presence of specific antibody or complement. Opsonized parasites (antibody and/or complement) increased the rate of H2O2 production by neutrophils, eosinophils, and basophils by respective percentages of 500, 500, and 371. The rate of H2O2 release was directly related to the number of granulocytes and to the proportion of cells attached to the surface of the schistosomula. Increased hydrogen peroxide release occurred by 10 min of incubation and was demonstrable up to 16 h after addition of leukocytes to schistosomula. The primary source of this oxygen product was found to be the granulocytes adherent to the schistosomula and not those that remained unattached. Hydrogen peroxide production by neutrophils and eosinophils was quantitatively similar (schistosomula coated with antibody plus complement stimulated 5 × 106 neutrophils and eosinophils to release H2O2 at respective rates of 0.35 and 0.40 nmol/min). Granulocyte-mediated parasite killing correlated with rate of H2O2 generation; both processes were inhibited by catalase. To define further the role of oxidative metabolites, neutrophils and eosinophils of two subjects with chronic granulomatous disease were used; marked reduction of granulocyte-mediated parasite mortality was observed.
Making weight: a case study of two elite wrestlers.
Authors: N Maffulli
Journal: British Journal of Sports Medicine (1992)

Two mature elite Sambo wrestlers were studied during a 22-day pre-European Championship period, during which they were to lose weight and maintain their top physical performance characteristics. During this time the athletes underwent intensive training coupled with a hypocaloric diet. Both lost approximately 8% of their initial body weight, while maintaining their pre-weight loss maximum oxygen uptake, anaerobic threshold and maximum isometric strength. These variables therefore increased when expressed relative to the lower body weight. Isometric endurance and short-term sprinting ability, however, were compromised by the weight-loss regimen, decreasing by up to 7% and 13% respectively. Following a well-planned weight-reduction programme coupled with serious training, aerobic power and isometric strength were unaffected and/or improved, but prolonged anaerobic exercise performance was impaired.
Islet Transplantation for Type 1 Diabetes, 2015: What Have We Learned From Alloislet and Autoislet Successes?
Authors: R. Paul Robertson
Journal: Diabetes Care (2015)

The therapeutic potential of pancreatic islet allotransplantation, in which human donor islets are used, as a treatment for type 1 diabetes (T1D) has fascinated diabetes researchers and clinicians for decades. At the same time, the therapeutic potential of total pancreatectomy and islet autotransplantation (TPIAT) (in which one’s own islets are used) as a preventive treatment for diabetes in patients who undergo total pancreatectomy for chronic, painful pancreatitis has received relatively less attention. This is ironic, since the latter has been much more effective than the former in terms of successful glucose management and duration of efficacy. The reasons for this disparity can be partially identified. TPIAT receives very little attention in textbooks of internal medicine and general surgery and surprisingly little print in textbooks of endocrinology and transplantation. T1D is much more predominant than TPIAT as a clinical entity. Provision of insulin or replacement of islets is mandatory and a primary goal in T1D. Provision of pain relief from chronic pancreatitis is the primary goal of total pancreatectomy in TPIAT, whereas treatment of diabetes, and certainly prevention of diabetes, has been more of a secondary consideration. Nonetheless, research developments in both fields have contributed to success in one another. In this Perspective, I will provide a brief history of islet transplantation and contrast and compare the procedures of allo- and autoislet transplantation from three major points of view 1) the procedures of islet procurement, isolation, and transplantation; 2) the role and complications of immunosuppressive drugs; and 3) the posttransplant consequences on β- as well as α-cell function.
Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study
Authors: Jeanne E. Anderson, Kenneth J. Kopecky, Cheryl L. Willman, David Head, Margaret R. O'Donnell, Frederick W. Luthardt, Thomas H. Norwood, I-Ming Chen, Stanley P. Balcerzak, David B. Johnson, Frederick R. Appelbaum
Journal: Blood (2002)
Vascular endothelial growth factor mRNA and protein expression in airway epithelial cell lines<i>in vitro</i>
Authors: S. Koyama, E. Sato, A. Tsukadaira, M. Haniuda, H. Numanami, M. Kurai, S. Nagai, T. Izumi
Journal: European Respiratory Journal (2002)

Vascular endothelial growth factor (VEGF) plays multifunctional roles in vascular permeability, repair and remodelling processes, in addition to the maintenance of vascular structure and function. In the present study, the potential of airway epithelial cell lines, BEAS-2B cells and A549 cells, to release and express VEGF in unstimulated and stimulated conditions was evaluated. The secretion and expression of VEGF were evaluated by enzyme-linked immunosorbant assay and by reverse transcriptase-polymerase chain reaction. The isoforms of released VEGF were determined by high-performance liquid chromatography. BEAS-2B cells and A549 cells released VEGF constitutively. Interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha augmented the release of VEGF in a time- and dose-dependent manner. The released VEGF was 165 amino acid residues in either condition. Pseudomonas aeruginosa lipopolysaccharide (LPS), interferon (IFN)-gamma, smoke extract (SE), neutrophil elastase (NE), and bradykinin stimulated the release of VEGF. Keracinocyte growth factor (KGF), which reduces vascular permeability, also stimulated both cells to release VEGF. VEGF messenger ribonucleic acid (mRNA) was expressed both time- and dose-dependently at 2 h, and declined after 2 h in response to IL-1beta and TNF-alpha. The expression of VEGF mRNA in airway epithelial cells was also augmented by LPS, IFN-gamma, SE, NE, and KGF stimulation. These data suggest that airway epithelial cells may regulate the maintenance of vascular structure and function, as well as vascular permeability, repair and remodelling processes, in a variety of lung conditions by expressing vascular endothelial growth factor.