bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and correlates of DSM‐IV alcohol abuse and dependence in Australia: findings of the 2007 National Survey of Mental Health and Wellbeing
Authors: Teesson Maree , Hall Wayne , Slade Tim , Mills Katherine , Grove Rachel , Mewton Louise , Baillie Andrew , Haber Paul 
Published: August 2010

ABSTRACTAims  To report nationally representative data on the prevalence and correlates (including psychiatric comorbidity and treatment) of DSM‐IV alcohol abuse and dependence in Australian adults.Design  The 2007 National Survey of Mental Health and Wellbeing (NSMHWB).Setting  Australian nationally representative household survey.Participants  8841 Australian adults (16–85 years).Measurements  Interview schedule that assessed symptoms of the most prevalent DSM‐IV mental disorders in the life‐time and the past 12 months.Findings  Prevalence of life‐time and 12‐month disorders was 18.3% and 2.9% for alcohol abuse and 3.9% and 1.4% for alcohol dependence. Current alcohol abuse and dependence was significantly more common in males and younger adults. There were significant associations between current alcohol use and other drug use disorders (OR 18.2) and between anxiety disorders and alcohol use disorders (OR 2.6). Only 22.4% of those with alcohol use disorders were treated for their alcohol disorder.Conclusions  Alcohol use disorders are highly prevalent, especially among young adult males. Comorbidity between anxiety and other drug use disorders is common and remains a significant challenge for the delivery of effective health‐care services and treatment. The low rate of effective interventions for alcohol problems is a significant public health concern.
Association of ABCB1 polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting
Authors: Choi E. M. , Lee M. G. , Lee S. H. , Choi K. W. , Choi S. H. 
Published: August 2010

SummaryWe investigated whether the 2677G>T/A and 3435C>T polymorphisms of adenosine triphosphate‐binding cassette subfamily B member 1 (ABCB1) affect the efficacy of ondansetron to prevent postoperative nausea and vomiting. One hundred and ninety‐eight patients undergoing general anaesthesia were enrolled. Thirty minutes before the end of surgery, 0.1 mg.kg−1 ondansetron was administered intravenously. The incidence of postoperative nausea and vomiting was compared between genotypes in the 2677G>T/A and 3435C>T polymorphisms of ABCB1. The incidence of postoperative nausea and vomiting was lower in patients with the 2677TT genotype (TT vs Non‐TT = 25.9% vs 53.0%, p = 0.01) and 3435TT genotype (CC + CT vs TT = 52.6% vs 21.7%, p = 0.01) during the first 2 h after surgery. There were no significant differences in the incidence of postoperative nausea and vomiting between the different genotype groupings during period between 2 and 24 h after surgery. In conclusion, ABCB1 genotypes may be a clinical predictor of responsiveness for ondansetron.
Use of the Ambu® aScope™ in 10 patients with predicted difficult intubation
Authors: Pujol E. , López A. M. , Valero R. 
Published: August 2010

SummaryFibreoptic intubation is the gold standard for patients with predicted difficult intubation. The Ambu® aScope™ is a single‐use device for fibreoptic tracheal intubation. We assessed its performance in 10 patients with predicted difficult tracheal intubation. The procedure was easy and successful in nine patients. However, the limited time of use did not permit intubation in one patient who required three attempts with different size tracheal tubes. The limited image resolution that can be expected of a single‐use fibreoptic system and the absence of a suction channel are other potential limitations. On the other hand, being single‐use this device has the advantage of avoiding the risk of infectious disease transmission and is always ready to use.
Repaglinide‐gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism
Authors: Gan Jinping , Chen Weiqi , Shen Hong , Gao Ling , Hong Yang , Tian Yuan , Li Wenying , Zhang Yueping , Tang Yuwei , Zhang Hongjian , Humphreys William Griffith , Rodrigues A. David 
Published: August 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Co‐administration of gemfibrozil significantly increases the exposure of repaglinide.• CYP3A4 and CYP2C8 are important in the metabolism of repaglinide.• OATP1B1 polymorphism is an independent predictor of repaglinide pharmacokinetics.• Gemfibrozil and its O‐glucuronide are CYP2C8 and OATP1B1 inhibitors. WHAT THIS STUDY ADDS • Acyl glucuronidation is a major metabolic pathway of repaglinide in vitro.• Gemfibrozil and its glucuronide inhibit the glucuronidation of repaglinide.• UGT1A1 is a major enzyme responsible for the glucuronidation of repaglinide.AIMTo further explore the mechanism underlying the interaction between repaglinide and gemfibrozil, alone or in combination with itraconazole.METHODSRepaglinide metabolism was assessed in vitro (human liver subcellular fractions, fresh human hepatocytes, and recombinant enzymes) and the resulting incubates were analyzed, by liquid chromatography‐mass spectrometry (LC‐MS) and radioactivity counting, to identify and quantify the different metabolites therein. Chemical inhibitors, in addition to a trapping agent, were also employed to elucidate the importance of each metabolic pathway. Finally, a panel of human liver microsomes (genotyped for UGT1A1*28 allele status) was used to determine the importance of UGT1A1 in the direct glucuronidation of repaglinide.RESULTSThe results of the present study demonstrate that repaglinide can undergo direct glucuronidation, a pathway that can possibly contribute to the interaction with gemfibrozil. For example, [3H]‐repaglinide formed glucuronide and oxidative metabolites (M2 and M4) when incubated with primary human hepatocytes. Gemfibrozil effectively inhibited (∼78%) both glucuronide and M4 formation, but had a minor effect on M2 formation. Concomitantly, the overall turnover of repaglinide was also inhibited (∼80%), and was completely abolished when gemfibrozil was co‐incubated with itraconazole. These observations are in qualitative agreement with the in vivo findings. UGT1A1 plays a significant role in the glucuronidation of repaglinide. In addition, gemfibrozil and its glucuronide inhibit repaglinide glucuronidation and the inhibition by gemfibrozil glucuronide is time‐dependent.CONCLUSIONSInhibition of UGT enzymes, especially UGT1A1, by gemfibrozil and its glucuronide is an additional mechanism to consider when rationalizing the interaction between repaglinide and gemfibrozil.
Experimental autoimmune uveoretinitis (EAU)versusexperimental allergic encephalomyelitis (EAE): a comparison of T cell-mediated mechanisms
Authors: CALDER V L , LIGHTMAN S L 
Published: August 2010

SUMMARYEAU is a model of ocular inflammatory disease. EAU resembles another T cell-mediated autoimmune disease–experimental allergic encephalomyelitis–since both have increased expression of MHC class II molecules in the target tissue, can be adoptively transferred by activated CD4+ T cells and are inhibited by cyclosporin A. The immunological findings will be compared to find out if the same cellular mechanisms are involved in both diseases.
Involvement of dipeptidyl peptidase IV in anin vivoimmune response
Authors: KUBOTA T , FLENTKE G R , BACHOVCHIN W W , STOLLAR B D 
Published: August 2010

SUMMARYDipeptidyl peptidase IV (DP IV) is a serine protease that selectively cleaves X-Pro dipeptides from polypeptides and proteins. Among blood cells, this enzyme occurs preferentially on the surface of CD4+ T cells and the amount of enzyme activity increases with T cell activation. In previous work, two potent and specific peptidyl-boronic acid inhibitors of DP IV. Ala-boroPro and Pro-boroPro, were synthesized and Pro-boroPro was shown to suppress antigen-specific proliferative responses of T cells in vitro. In this study, we tested the in vivo effects of these inhibitors. Subcutaneous injection of Ala-boroPro or Pro-boroPro into BALB/c mice inhibited DP IV activity in serum and spleen cell suspensions. Repeated injections of more than 10 μg of Ala-boroPro or Pro-boroPro at 12 h intervals maintained in vivo DP IV activity at less than 30% of the normal level. Repeated injections of the inhibitors during the primary, secondary or tertiary immune response to bovine serum albumin (BSA) reduced anti-BSA antibody production. Without inhibitor, immunization with BSA was followed by a temporary decrease in serum DP IV activity and then by enhanced serum enzyme activity after several days. These results provide the first direct evidence that DP IV plays an important role in immune response in vivo.
Immunoglobulin heavy chain variable region gene utilization by B cell hybridomas derived from rheumatoid synovial tissue
Authors: BROWN C M S , LONGHURST C , HAYNES G , PLATER-ZYBERK C , MALCOLM A , MAINI R N 
Published: August 2010

SUMMARYRheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects synovial joints. Activated B lymphocytes and plasma cells are present in the synovial tissue and are thought to contribute to the immunopathology of the rheumatoid joint. To investigate rheumatoid synovial B lymphocytes, we have generated B cell hybridomas from synovial tissue of an RA patient. Here we describe the immunoglobulin VH gene repertoire of eight IgM- and 10 IgG-secreting synovial-derived hybridomas. The VH4 gene family is highly represented (38.5% in this panel of hybridomas compared with the frequeney of VH4 gene expression in circulating B lymphocytes reported previously (19-22%) and with the VH4 gene frequency we observed in a panel of hybridomas derived in the same manner from the spleen and tonsil of normal individuals (19%). The increased frequency of VH4 gene expression was not due to the expansion of a single B cell clone in vivo as none of these hybridomas was clonally related. Two synovial-derived hybridomas secreted autoantibodies; one (VH3+) secreted an IgM-rheumatoid factor (RF) and the other (VH4+) secreted IgM with polyreactive binding to cytoskeletal proteins and cardiolipin. The antibodies secreted by the remaining synovial-derived hybridomas were not reactive with the autoantigens tested. The VH gene usage in a proportion (5/17) of synovial-derived hybridomas that expressed CD5 antigen provided preliminary evidence that CD5+ B cells in RA synovium have a similar increase of VH4 gene expression reported for CD5+ B cells from normal individuals and patients with chronic lymphocytic leukaemia.
Activation of IL-6 production by UV irradiation of blood mononuclear cells from patients with systemic lupus erythematosus
Authors: PELTON B K , HYLTON W , DENMAN A M 
Published: August 2010

SUMMARYCultured mononuclear cells from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and normal donors were assayed for their ability to secrete IL-6 both spontaneously and after exposure to UV light. Mononuclear cells from SLE, RA and atopic control patients produced IL-6 spontaneously, while those from normal donors did not. Spontaneous production of IL-6 occurred in the non-adherent cell population. UV light-induced IL-6 production was confined exclusively to the SLE patients and was present only in the macrophage/monocyte fraction. This stimulation was induced by wavelengths in the UVA, UVB but not the UVC portion of the spectrum. These results suggest that cytokine release may be involved in the exacerbations of SLE provoked by photosensitivity.
Serum levels of IL-1, IL-6 and tumour necrosis factors in patients undergoing coronary artery bypass grafts or cholecystectomy
Authors: LAHAT N , ZLOTNICK A Y , SHTILLER R , BAR I , MERIN G 
Published: August 2010

SUMMARYPlasma levels of biologically active IL-1, tumour necrosis factor (TNF) and IL-6 were measured before, during and after coronary artery bypass graftings (CABG) (n= 9) and cholecystectomy (CHO. n= 9), and in normal controls (nine healthy volunteers). Mean pre-operative IL-1 concentration in four of the nine CABG patients was 0.452 ± 0.03 ng/ml, significantly (P &lt; 0.001) higher than that of the other five (0.045 ± 0.009 ng/ml), CHO patients (0.035 ± 0.005 ng/ml) and controls (0.029 ± 0.008 ng/ml). Three of the four patients with high pre-operative IL-1 had functional capacity IV, while the other five had functional capacity IIa or IIb. Slight IL-1 elevation after anaesthesia, followed by reduction after initiation of bypass, elevation on completion of surgery and reduction to basal levels after 7 days was found in patients undergoing CABG. Mean basal TNF levels of CABG and CHO patients did not differ, but were higher than those of controls (2.85 ± 0.5 ng/ml for CABG, 2.05 ± 0.06 ng/ml for CHO, 0.72 ± 007 ng/ml for normals, P &lt; 0.001). A unique kinetics of release during CABG was observed also for TNF. Mean pre-operative IL-6 levels were normal (50 ± 3 ng/ml for CABG. 50 ± 0.5 ng/ml for CHO and 65 ± 10 ng/ml for controls). Gradual elevation to a mean peak of 725 ± 100 ng/ml on completion of CABG was observed as compared with 275 ± 50 ng/ml in CHO (P &lt; 0.01). On the seventh post-operative day mean IL-6 levels returned to normal. Two patients with post-operative low-grade fever (38°C) had high, late eytokine levels. One of these two patients had leucocytosis, sterile discharge from the operative wound and was diagnosed as suffering from the Dressler syndrome. In this study elevated cytokine values and unique kinetics of release into the serum were found in patients undergoing CABG.
IL-4 and transforming growth factor-β suppress human immunoglobulin secretionin vitroby surface IgD− B cells
Authors: NINOMIYA C , SPIEGELBERG H L 
Published: August 2010

SUMMARYThe effect of IL-4 and transforming growth factor-β (TGF-β) on immunogiobulin secretion in vitro by peripheral blood mononuclear cells (PBMC) or purified B cells activated with murine EL4 thymoma cells and phorbol myristate acetate (PMA) was investigated. As previously reported. IL-4 induced IgE and IgG4 secretion by B cells in PBMC preparations and B cells activated with EL4 cells and PMA. However, when B cells, either in PBMC preparations or purified and activated with EL4 cells and PMA, spontaneously secreted large quantities of immunoglobulin, IL-4 suppressed the immunoglobulin secretion of all isotypes. IL-4 also suppressed the IgE secretion by B cells from an atopic dermatitis patient. This suppressive effect was not reversed by adding IL-2 or interferongamma (IFN-γ) to the cultures. We also showed that TGF-β suppressed the immunoglobulin secretion by purified B cells activated by EL4 cells and PMA. To investigate whether IL-4 or TGF-β suppressed immunoglobulin secretion by in vivo‘switched’ and isotype-committed B cells, sIgD-B cells were isolated, activated with EL4 cells and PMA and cultured with IL-4 or TGF-β. Such activated B cells secreted large quantities of IgG1, IgG2, IgG3, IgA1, IgA2 and IgM, and IL-4 and TGF-β suppressed all these isotypes by &gt;80%. The data demonstrated that IL-4 and TGF-β suppress immunoglobulin secretion in vitro by in vivo isotype-committed sIgD-B cells, suggesting that these lymphokines may play a down-regulatory role on differentiated isotype-committed B cells in an isotype-unrestricted manner. The data also showed that IL-4 and TGF-β acted directly on isolated B cells.
A persistent T cell expansion in the peripheral blood of a normal adult male: a new clinical entity?
Authors: GRUNEWALD J , JEDDI-TEHRANI M , DERSIMONIAN H , ANDERSSON R , WIGZELL H 
Published: August 2010

SUMMARYA dramatic and persistent T cell expansion in a healthy adult male was initially identified, using anti-T cell receptor for antigen (TCR)-specific MoAbs. The expanded T cells were found to be expressing TCR containing Vα 12.1 and V β 5.2, and they composed approximately one third of all the CD8+ T cells. The cells were shown to be not only non-activated (HLA-DR−, IL-2R−) but also of ‘virgin’ cell type (CD45RA+/CD45RO−) and they persisted over the observation period of more than one and a half years. Various T and B cell markers, and all other laboratory and physical parameters analysed, were normal. The expanded CD8+ T cells were further characterized by polymerase chain reaction (PCR) amplification, using Vβ- and Cβ-specific primers, followed by hybridization with Jβ-specific probes. Close to 90% of the Vα 12.1+ Vβ 5.2+ T cells were found to utilize the Jβ 2.5 gene segment, thus strongly suggesting the expanded T cells to be monoclonal. The condition may constitute a T cell counterpart to ‘monoclonal gammopathy of undetermined significance’ (MGUS), and by analogy we suggest it should be designated ‘monoclonal T cell expansion of undetermined significance’ (MTUS).
Human MoAbs produced from normal, HIV-1-negative donors and specific for glycoprotein gp 120 of the HIV-1 envelope
Authors: OHLIN M , HINKULA J , BROLIDEN P-A , GRUNOW R , BORREBAECK C A K , WAHREN B 
Published: August 2010

SUMMARYHuman MoAbs of IgM class were developed against three regions of the HIV-1 envelope. Uninfected donor lymphocytes were immunized in vitro with recombinant protein pBI. Four out of five antibodies were directed to different parts of the V3 region, which contains a major neutralizing site. Two out of these antibodies were directed to more than one amino acid sequence, indicating reactivity to discontinuous sites. Two of the human MoAbs inhibited viral spread between cells in tissue culture, interpreted as reactivities to conserved amino acid sequences exposed during viral maturation. No MoAb neutralized virus, which may be explained by the relatively low avidity of the antibodies. One MoAb was directed to a region containing amino acids participating in CD4 binding. This technique appears to allow formation of antibodies with fine specificities other than those obtained in infected hosts.
Bispecific anti-human red blood Rhesus-D antigen × anti FcγRI targeted antibody-dependent cell-mediated cytotoxicity and phagocytosis by mononuclear leucocytes
Authors: DERAMOUDT F-X , GILARD C , LEPINE N , ALONSO J-M , ROMET-LEMONNE J-L 
Published: August 2010

SUMMARYThe Fc receptor mediated antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis induced by bispecific antibody (BsAb) to the high-affinity Fc receptor for IgG (FcγRI) and to human red blood group antigen RhD were studied in vitro, using human mononuclear leucocytes as effector cells. The results were compared with those obtained by using a human monoclonal IgGI anti-RhD used alone and a reference human polyclonal anti-RhD antibody. The effect of non-specific human IgG on FcR-mediated functions by mononuclear leucocytes was checked. The results demonstrate that BsAb presents a high resistance of Fc-mediated function to blockade by non-specific human IgG compared with that of both polyclonal and monoclonal anti-RhD antibodies. These results further encourage possible clinical application of bispecfic antibody in passive immunotherapy.
Decreased polymorphonuclear leucocyte chemotactic response to leukotriene B4 in cystic fibrosis
Authors: LAWRENCE R H , SORRELL T C 
Published: August 2010

SUMMARY
Evidence that leukotriene B4 (LTB4) is a significant inflammatory mediator in chronic pseudomonal respiratory disease was sought in adolescents and young adults with cystic fibrosis. Specific chemotaxis of peripheral blood polymorphonuclear leucocytes (PMN) was used as an indirect measure of remote in vivo exposure to LTB4. PMN from 17 patients showed a significant decrease in chemotaxis to 10−7-10−9m LTB4, but normal responses to 10−8mn-formyl-methionyl-leucyl-phenylalanine and 4 mg/ml casein, when compared with 17 healthy age- and sex-matched controls. This result is consistent with chronic production of LTB4, and specific deactivation of circulating PMN receptors for LTB4 in patients with cystic fibrosis. Pharmacologic inhibition of LTB4 production in vivo may help elucidate its role in the pathogenesis of lung damage in cystic fibrosis.
Characterization of anti-interferon-α antibodies appearing during recombinant interferon-α2a treatment
Authors: RÖNNBLOM L E , TIENSUU JANSONJ E , PERERS A , ÖBERG K E , ALM G V 
Published: August 2010

SUMMARYPatients with malignant midgut carcinoid tumours received recombinant interferon-alpha2a (rIFN-α2a) or rIFN-α2a and chemotherapy (streptozocin and doxorubicin) for 6 months, and then rIFN-α2a alone. Antibodies, mainly of IgG type, binding to rIFN-α2a developed in nine of 22 patients (41%), as determined by immunoassay. In seven patients, antibodies also neutralized the biologic (anti-viral) activity of rIFN-α2a. Anti-IFN-α2a antibodies were equally frequent in both sexes and treatment groups, but were not observed in those patients (n=8) that had previously received other types of IFN. Antibodies appeared after a median of 6 months of rIFN-α2a treatment and had a median duration of 6 months. The anti-IFN-α2a antibody titres declined with time with no obvious relation to change of therapy, also during continued IFN-α2a treatment. High titres of neutralizing antibodies appeared to impair anti-tumoural effects in individual potential responders. Anti-IFN-α2a antibodies further examined in six patients bound to native IFN-α subtypes present in both allogeneic and autologous leucocyte IFN-α. Such autoantibodies neutralized the biologic activity of autologous IFN-α in two patients, and in a third were partially neutralizing.
Protective effects of cyclophosphamide, cyclosporin A and FK506 against antigen-induced lung eosinophilia in guinea-pigs
Authors: NORRIS A A , JACKSON D M , EADY R P 
Published: August 2010

SUMMARYA close association has been recognized between activated T cells and eosinophils in asthma, albeit circumstantial. The present study attempted to investigate this relationship in an animal model of lung eosinophilia using the new generation of T cell-selective immunosuppressants, cyclosporin A and FK506, compared with the myelotoxic immunosuppressive agent cyclophosphamide. Antigen challenge of ovalbumin-sensitized guinea-pigs resulted in a lung eosinophilia which was assessed by bronchoalveolar lavage. All three agents caused a marked suppression of lung eosinophilia at 24 h post-challenge when the compounds were administered at the time of sensitization but not when administered for 3 days before lavage. However, the lung eosinophilia at 72 h post-challenge was reduced significantly by FK506 and by cyclophosphamide, but not by cyclosporin A, when the drugs were administered for 3 days, before lavage. These results strongly suggest the involvement of T cells in antigen-induced late phase (72 h) eosinophilia in guinea-pigs but not at 24 h. The effects of cyclophosphamide were always associated with a reduction in circulating white cell counts, whereas cyclosporin A and FK506 showed no myelotoxic properties. These results suggest the potential therapeutic use of selective, non-cytotoxic immunosuppressive agents in asthma.