Psychological factors in bipolar disorder.
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Bipolar Disorder↗
Biomedical subjects
P Biswas
Publications and source records attributed to P Biswas.
Sampling methodologies and dosage assessment techniques for submicrometre and ultrafine virus aerosol particles.
AIMS: The aerosolization and collection of submicrometre and ultrafine virus particles were studied with the objective of developing robust and accurate methodologies to study airborne viruses. METHODS AND RESULTS: The collection efficiencies of three sampling devices used to sample airborne biological particles - the All Glass Impinger 30, the SKC BioSampler and a frit bubbler - were evaluated for submicrometre and ultrafine virus particles. Test virus aerosol particles were produced by atomizing suspensions of single-stranded RNA and double-stranded DNA bacteriophages. Size distribution results show that the fraction of viruses present in typical aqueous virus suspensions is extremely low such that the presence of viruses has little effect on the particle size distribution of atomized suspensions. It has been found that none of the tested samplers are adequate in collecting submicrometre and ultrafine virus particles, with collection efficiencies for all samplers below 10% in the 30-100 nm size range. Plaque assays and particle counting measurements showed that all tested samplers have time-varying virus particle collection efficiencies. A method to determine the size distribution function of viable virus containing particles utilizing differential mobility selection was also developed. CONCLUSIONS: A combination of differential mobility analysis and traditional plaque assay techniques can be used to fully characterize airborne viruses. SIGNIFICANCE AND IMPACT OF THE STUDY: The data and methods presented here provide a fundamental basis for future studies of submicrometre and ultrafine airborne virus particles.
Aerosols↗
Natural killer-cell cytotoxicity in HIV-positive and HIV-negative patients with and without severe course of hepatitis B virus infection.
Natural killer (NK) cells represent the first line of defence against viral infections but, in the case of hepatitis B virus (HBV), may also be involved in liver injury. We here compared NK-cell activity of 11 patients with acute HBV infection, either HIV-positive or HIV-negative, with that of 11 healthy subjects. One of the HIV-positive patients, characterized by a severe immunodeficiency, died 3 weeks after hospitalization for HBV-related fulminant hepatitis (FH). He displayed a remarkable NK-cell cytotoxicity against both cell lines and autologous dendritic cells, whereas the NK-cell activity of the remaining patients was significantly reduced as compared with healthy individuals. Our findings suggest that NK-cell-mediated cytotoxicity could contribute to the development of HBV-related acute liver failure in HIV-positive patients with severe immunodeficiency. An immunopathological model of FH in immunocompromised patients was proposed.
AIDS-Related Opportunistic Infections↗
The packaging signal of simian immunodeficiency virus is upstream of the major splice donor at a distance from the RNA cap site similar to that of human immunodeficiency virus types 1 and 2.
Deletion mutation of the RNA 5' leader sequence of simian immunodeficiency virus (SIV) was used to localize the virus packaging signal. Deletion of sequences upstream of the major splice donor (SD) site produced a phenotype most consistent with a packaging defect when analysed by both RNase protection assay and RT-PCR. Sequences downstream of the SD were deleted and produced varying effects but did not affect packaging: a large downstream deletion had little effect on function, whereas a nested deletion produced a profound replication defect characterized by reduced protein production. Secondary structure analysis provided a potential explanation for this. The major packaging signal of SIV appears to be upstream of the SD in a region similar to that of human immunodeficiency virus type 2 (HIV-2) but unlike that of HIV-1; however, the packaging signal of all three viruses are at a similar distance from their respective cap sites. This conserved positioning suggests that it is more important in the virus life cycle than the position of the signal relative to the SD.
5' Untranslated Regions↗
Diffusion with random distribution of static traps.
The survival probability P(c,t) of a random walk of t steps with static traps at concentration c is studied in two and three dimensions by an efficient Monte Carlo method based on a mapping onto a polymer model. On the basis of the theoretical work of Donsker and Varadhan [Commun. Pure Appl. Math. 28, 525 (1975); 32, 721 (1979)] and of Rosenstock [J. Math. Phys. (N.Y.) 11, 487 (1970)] one expects a data collapse for -ln[P(c,t)]/ln(t) plotted vs square root of [lambda t]/ln(t) [with lambda = -ln(1-c)], in two dimensions, and for -t(-1/3)ln[P(c,t)] vs t(2/3)lambda in three dimensions. These predictions are well supported by the Monte Carlo results.
Journal Article↗
The development of iodine based impinger solutions for the efficient capture of Hg0 using direct injection nebulization-inductively coupled plasma mass spectrometry analysis.
Inductively coupled plasma mass spectrometry (ICP/MS) with direct injection nebulization (DIN) was used to evaluate novel impinger solution compositions capable of capturing elemental mercury (Hg0) in EPA Method 5 type sampling. An iodine based impinger solution proved to be very efficient for Hg0 capture and was amenable to direct analysis by DIN-ICP/MS. Hg0 capture efficiency using aqueous iodine (I3-) was comparable to Hg0 capture using acidified potassium permanganate impinger solutions which were analyzed by cold vapor atomic absorption spectrometry (CVAAS), with greater than 98% capture of Hg0 in the first oxidizing impinger. Using DIN-ICP/MS, it was demonstrated for the first time that iodine can be generated just prior to impinger sampling for efficiently oxidizing Hg0 and retaining it in solution as HgI4(2-). Due to the increased interest in Hg speciation from combustion sources and the potential for using DIN-ICP/MS for multiple metals analyses, an impinger sampling train for gaseous Hg speciation and multiple metals analyses using DIN-ICP/MS analyses is presented. The unique feature of such a sampling train is that each impinger solution in the series is amenable to direct analysis by DIN-ICP/MS. A bituminous coal was combusted in a bench scale coal system, and gaseous Hg species (oxidized and elemental) were determined using the proposed impinger train. The DIN-ICP/MS instrumental detection limit was 0.003 ppb, and MDLs ranged from 0.007 to 0.116 microg/L (ppb) in a variety of impinger solutions used for Hg capture.
Air Pollutants↗
The binding subunit of pertussis toxin inhibits HIV replication in human macrophages and virus expression in chronically infected promonocytic U1 cells.
We have recently shown that the binding subunit of pertussis toxin (PTX-B) inhibits the entry and replication of macrophage-tropic (R5) HIV-1 strains in activated primary T lymphocytes. Furthermore, PTX-B suppressed the replication of T cell-tropic (X4) viruses at a postentry level in the same cells. In this study we demonstrate that PTX-B profoundly impairs entry and replication of the HIV-1(ADA) (R5), as well as of HIV pseudotyped with either murine leukemia virus or vesicular stomatitis virus envelopes, in primary monocyte-derived macrophages. In addition, PTX-B strongly inhibited X4 HIV-1 replication in U937 promonocytic cells and virus expression in the U937-derived chronically infected U1 cell line stimulated with cytokines such as TNF-alpha and IL-6. Of interest, TNF-alpha-mediated activation of the cellular transcription factor NF-kappaB was unaffected by PTX-B. Therefore, PTX-B may represent a novel and potent inhibitor of HIV-1 replication to be tested for efficacy in infected individuals. In support of this proposition, a genetically modified mutant of PTX (PT-9K/129G), which is safely administered for prevention of Bordetella pertussis infection, showed an in vitro anti-HIV profile superimposable to that of PTX-B.
Antiviral Agents↗
Tumor necrosis factor-alpha drives HIV-1 replication in U937 cell clones and upregulates CXCR4.
U937 cell clones in which efficient (plus) vs poor (minus) replication of HIV-1 occurs have been described. We evaluated the role of host factors in their differential ability to support HIV-1 replication. Plus clones constitutively produced TNF-alpha and viral replication was inhibited by neutralization of endogenous TNF-alpha. However, HIV-1 replication was strongly upregulated in minus clones by exogenous TNF-alpha, which also further accelerated the kinetics of infection in plus clones. We observed an increased accumulation of proviral DNA within one round of HIV-1 replication following TNF-a treatment of plus cells. This effect was associated with increased surface density of CXCR4 in both plus and minus clones. Our results identify TNF-alpha as one correlate that contributes to the higher ability of U937-plus clones to sustain HIV-1 replication. Furthermore, we suggest that TNF-alpha may affect steps of the viral life cycle that occur earlier than transcription and also enhance HIV-1 replication by increasing the surface density of CXCR4.
Base Sequence↗
Diesel engines: environmental impact and control--a critical review introduction.
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Air Pollution↗
Identification of a new TWIST mutation (7p21) with variable eyelid manifestations supports locus homogeneity of BPES at 3q22.
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Blepharophimosis↗
Troglitazone and liver function abnormalities: lessons from a prescription event monitoring study and spontaneous reporting.
OBJECTIVES: To investigate whether there were any cases of liver function abnormalities possibly associated with troglitazone use in general practice in England. DESIGN: A prescription-event monitoring (PEM) study was undertaken between October 1997 and December 1997. SETTING: Data from prescriptions were obtained electronically for the troglitazone cohort in the immediate postmarketing period. STUDY PARTICIPANTS: Event data were obtained for a total of 1344 patients. RESULTS: Troglitazone was effective in 394 (75%) of the 529 patients for whom an opinion was given. The most frequent reasons for stopping treatment related to drug tolerability were malaise/lassitude (16 reports), abnormal liver function tests (II reports) and nausea/vomiting (9 reports). The major cause of stopping troglitazone was because the drug was withdrawn from the market (1101 reports). 30 patients with liver dysfunction were identified from the cohort. In 9 of these patients there were alternative explanations for the liver dysfunction and hence these patients were not followed up further. 21 patients were followed up, for whom 19 questionnaires were returned. In 5 patients their liver dysfunction was assessed as possibly related to troglitazone, in 6 patients the liver dysfunction was unlikely to be attributed to troglitazone, while in 7 patients it was difficult to assess the causality because of limited information and confounding factors. The remaining patient was not included as this individual did not fit the inclusion criteria of the study. CONCLUSION: Although the cohort is small (the drug was available for only 3 months in the UK), 5 patients with abnormal liver function, considered possibly related to troglitazone were detected in this PEM study. It is possible for PEM to contribute to the elucidation of safety signals in the UK.
Adult↗
Montelukast and improvement of eczema: observations from a prescription event monitoring study in England.
OBJECTIVE: Montelukast is an orally administered cysteinyl receptor antagonist, approved for the treatment of asthma. There is pharmacological plausibility of its effectiveness in the treatment of other immunologically mediated conditions such as eczema and urticaria. The objective of this study was to determine whether there are any beneficial effects of montelukast on eczema and urticaria. METHOD: A non-interventional observational cohort study was conducted between February 1998 and December 1998 using Prescription-Event Monitoring (PEM). During PEM studies, patients are systematically identified from dispensed prescription data and questionnaires are sent to the prescribing general practitioner (GP) asking them to report events occurring during and after treatment. In this study, events reported as eczema or urticaria improved were identified. A simple questionnaire was sent to the GPs for additional information. RESULTS: The cohort comprised 15,612 patients, in which 16 reports of eczema or urticaria improved were identified. Questionnaires were sent to the GPs for additional information. Fifteen of the 16 questionnaires were returned. In 5 cases the GPs thought that there was an improvement of eczema or urticaria with montelukast treatment in patients who had history of longstanding eczema or urticaria. Of the remaining 11 cases there was an alternative explanation for the improvement of eczema or urticaria in 10 cases and one was unassessable. CONCLUSION: PEM is conducted to monitor the safety of medicines, and doctors report events including improvement in pre-existing conditions. Although the number of cases of improvement of eczema or urticaria in this cohort is small, there is a possibility that leukotriene inhibitors may be helpful in the treatment of these diseases. Further studies are needed to provide evidence as to whether montelukast will have a role in the treatment of these conditions.
Acetates↗
Interleukin-6 and glucocorticoids synergistically induce human immunodeficiency virus type-1 expression in chronically infected U1 cells by a long terminal repeat independent post-transcriptional mechanism.
BACKGROUND: Glucocorticoids (GC) such as dexamethasone (Dex) can directly upregulate human immunodeficiency virus type-1 (HIV-1) replication in acutely infected cells and potentiate HIV expression from chronically infected promonocytic U1 cells stimulated with tumor necrosis factor-alpha (TNF-alpha). We have here investigated the potential effect of Dex in U1 cells stimulated with interleukin-6 (IL-6), a cytokine inducing virus expression by acting mostly at a post-transcriptional level on the virus life cycle. MATERIALS AND METHODS: Virus production in culture supernatants was evaluated by reverse transcriptase (RT) activity. GC receptor expression was tested by both binding of [3H]-Dexamethasone 21-mesylate and Northern blotting. Cell-associated HIV protein expression was analyzed by Western blotting, whereas both HIV and monocyte chemoattractant protein-1 (MCP-1) RNA accumulation were evaluated by Northern blotting. HIV transcription was tested by long terminal repeat (LTR) chloramphenicol acetyl transferase (CAT) assay after transient transfection of U1 or U937 cells. Formation of activating protein-1 (AP-1) DNA binding complex in nuclear cell extracts was visualized by electrophoretic mobility shift assay (EMSA), whereas ERK1/2 mitogen-activated protein kinase (MAPK) phosphorylation was studied by Western blotting. RESULTS: IL-6 and Dex synergistically induced HIV expression in U1 cells, and this effect was blocked by RU 486. No substantial HIV RNA accumulation was demonstrated in U1 cells co-stimulated with IL-6 and Dex, whereas IL-6 upregulated the expression of MCP-1 RNA, and this effect was inhibited by Dex. In contrast, Dex potentiated IL-6 induced activation of AP-1 and ERK1/2 MAPK phosphorylation, as revealed by EMSA. HIV-1 LTR driven transcription was observed in U1 cells stimulated with TNF-alpha and this effect was potentiated by Dex. In sharp contrast, no induction of LTR-directed CAT activity was observed in transfected U1 cells (or in their parental uninfected U937 cells) stimulated with IL-6 and Dex either alone or in combination. CONCLUSIONS: High levels of virion production can be induced in latently infected cells by stimulation with IL-6 and Dex in the absence of activation of the HIV LTR or viral transcription in spite of activation of both ERK1/2 MAPK and AP-1. These findings suggest the existence of LTR-independent pathways influenced by cytokine and GC through which HIV can maintain substantial levels of protein expression and virion production.
Autoantigens↗
Engagement of CD30 shapes the secretion of cytokines by human gamma delta T cells.
CD30 is a member of the TNF receptor superfamily, previously shown to be expressed on Hodgkin's lymphoma cells and on normal activated lymphocytes. We here show that CD30 is highly expressed on recently activated human gamma delta T cells. Elevated surface levels of this molecule persisted in long-term cultures of gamma delta cells, without further cell stimulation. CD30 acted as a co-stimulus in gamma delta T cells by potentiating the intracellular Ca(2+) fluxes induced by CD3 cross-linking. The engagement of CD30 enhanced the expression of several cytokines induced upon CD3 stimulation such as IL-4 and IFN-gamma but not IL-10. The CC chemokines RANTES and macrophage inflammatory protein-1beta were constitutively expressed and not affected by stimulation. The inducible expression of the neutrophil chemoattractant IL-8 was enhanced by CD30 co-stimulation, as well as that of the CC chemokines I-309 and MDC, whereas the secretion of the monocyte chemotactic protein-1 was not detected. Triggering of CD30 may therefore modulate the expression of several cytokines released by gamma delta cells; the expression of its physiologic ligand by APC and neutrophils at the site of infection may contribute to determine the outcome of an immune response.
Animals↗
Ex vivo modulation of RANTES and sCD30 by proinflammatory stimuli in HIV-seropositive and -negative individuals.
RANTES and sCD30 were measured in ex vivo culture supernatants of unstimulated or stimulated PBMC in order to investigate their potential role as markers of acute immune activation. Patients in an advanced stage of HIV infection (AIDS A) were compared to AIDS patients who were evaluated for pneumonia at the time of blood withdrawal (AIDS B); HIV(+) individuals with nonprogressive infection (LTNP) and healthy donors (N) served as controls. Constitutive levels of RANTES were significantly elevated in AIDS B patients (P 0.0001), whereas spontaneous release of sCD30 was strongly correlated with the presence of both pneumonia (P 0.002) and HIV infection (P 0.004). LPS was a strong inducer of RANTES in all four categories; however, in AIDS B patients a negative and positive correlation between constitutive and induced levels was observed with LPS (P 0.0004) and IFN-gamma (P 0.006), respectively. We clearly showed that IFN-gamma reached a fourfold superinduction of sCD30 release in both HIV-positive and -negative individuals, whereas IL-6-driven production of both sCD30 and RANTES occurred only in healthy donors. Ex vivo RANTES levels may also be monitored as an index of acute immune activation under conditions of chronic activation of the immune system, whereas sCD30 release may be equally indicative of both acute and chronic processes of T cell activation. Proinflammatory stimuli differentially affected RANTES and sCD30 secretion in ex vivo PBMC cultures, suggesting complex pathways in the in vivo regulation of these two molecules.
Adult↗
The incidence of adverse events and risk factors for upper gastrointestinal disorders associated with meloxicam use amongst 19,087 patients in general practice in England: cohort study.
AIMS: Meloxicam is a novel nonsteroidal anti-inflammatory drug (NSAID) which may be associated with fewer adverse upper gastrointestinal events than other NSAIDs because it preferentially inhibits the inducible enzyme cyclo-oxygenase-2 relative to the constitutive isoform, cyclo-oxygenase-1. The aims of the study were to: determine the rate of adverse events associated with meloxicam in general practice, stratify these rates by selected risk factors, and to identify signals of previously unsuspected adverse events associated with meloxicam. METHODS: As part of the national prescription-event monitoring pharmacovigilance system for newly launched drugs in general practice, all patients prescribed meloxicam in England between December 1996 and March 1997 were identified by the central Prescription Pricing Authority. We sent short questionnaires to all prescribers asking about adverse events experienced within 6 months of the first prescription. RESULTS: There were 19 087 patients in the study. The rate of dyspepsia during the first month of exposure was 28.3 per 1000 patient-months. There were 33 reports of upper gastrointestinal haemorrhage during treatment (rate: 0.4 per 1000 months). A history of gastrointestinal disorder in the previous year was associated with an increased rate of dyspepsia (rate ratio: 3.0; 95% confidence interval: 2.6, 3.4), abdominal pain (2.1; 1.6, 2.6), and peptic ulcer (4.0; 1.4, 13.2). Prior NSAID use was associated with a 20-30% decrease in the rate of dyspepsia and abdominal pain in patients starting meloxicam, while patients prescribed concomitant gastroprotective agents had a two to three-fold increased rate of dyspepsia, abdominal pain and peptic ulceration. Other rare events were thrombocytopenia (n = 2); interstitial nephritis (n = 1) and idiosyncratic liver abnormalities (n = 1). CONCLUSIONS: In the absence of gastro-intestinal risk factors the incidence of gastro-intestinal disturbance was low. Such risk factors should be carefully reviewed prior to prescribing meloxicam.
Anti-Inflammatory Agents, Non-Steroidal↗
The pharmacovigilance of tamsulosin: event data on 12484 patients.
OBJECTIVE: To determine drug effectiveness and adverse effects in a noninterventional observational cohort study of over 10 000 patients treated with tamsulosin in general medical practice. METHODS: Using prescription-event monitoring, data were collected of all prescriptions for tamsulosin issued nationally during June 1996 to January 1998. For each patient entered into the cohort a computerized longitudinal record of exposure was constructed. The outcome data, patient information and an opinion about the effectiveness of the drug were provided by the prescriber, using a standard questionnaire sent 6 months after the initial prescription for tamsulosin. The incidence of each of almost 2000 events listed in the Drug Safety Research Unit computerized dictionary was calculated and scrutinized by medical assessors for possible adverse reactions, and any difference determined between the incidence of each event in the first month and subsequent months of exposure. All deaths were followed up to detect possibly drug-related causes. RESULTS: Event data were obtained on 12484 patients, from the 52.9% of questionnaires returned and that contained valid event data. Tamsulosin was reported to have been effective in 7428 (78.3%) of the 9487 patients in whom the general practitioners expressed an opinion about effectiveness. Suspected adverse drug reactions were reported in only 171 (1.4%) of the cohort. Dizziness, headache, malaise and hypotension were common to the reported adverse reactions, reasons for stopping the drug and events of greatest incidence density. None of the 282 deaths that occurred in this elderly cohort were attributed to the drug. CONCLUSION: This study suggests that tamsulosin has a highly acceptable benefit-to-risk ratio. No untoward features not already mentioned in the prescribing guidance were identified.
Adolescent↗
Characterization of activated carbon fiber filters for pressure drop, submicrometer particulate collection, and mercury capture.
The use of activated carbon fiber (ACF) filters for the capture of particulate matter and elemental Hg is demonstrated. The pressure drop and particle collection efficiency characteristics of the ACF filters were established at two different face velocities and for two different aerosols: spherical NaCl and combustion-generated silica particles. The clean ACF filter specific resistance was 153 kg m-2 sec-1. The experimental specific resistance for cake filtration was 1.6 x 10(6) sec-1 and 2.4 x 10(5) sec-1 for 0.5- and 1.5-micron mass median diameter particles, respectively. The resistance factor R was approximately 2, similar to that for the high-efficiency particulate air filters. There was a discrepancy in the measured particle collection efficiencies and those predicted by theory. The use of the ACF filter for elemental Hg capture was illustrated, and the breakthrough characteristic was established. The capacity of the ACF filter for Hg capture was similar to other powdered activated carbons.
Air Pollution↗