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Biomedical subjects

A Dufour

Publications and source records attributed to A Dufour.

At least 55 records · Page 3Linked to original sources

Prevalence and risk behaviours for HIV infection among inmates of a provincial prison in Quebec City.

OBJECTIVE: To assess HIV prevalence and related risk factors among inmates at the Quebec Detention Centre (QDC). DESIGN: Cross-sectional prevalence study. METHODS: Inmates incarcerated at the QDC in September 1994 were asked to participate in an anonymous survey concerning HIV infection. Volunteers answered a questionnaire and provided a saliva sample during a meeting with an interviewer. RESULTS: The overall participation rate was 95% (618 out of 651). HIV prevalence was 2% (11 out of 499) in men. All HIV-infected men were injecting drug users (IDU) with an HIV prevalence of 9% (11 out of 129) in this group. HIV prevalence was 14% (9/63) among male IDU admitting previous needle-sharing and 3% (two out of 66) among the other IDU (odds ratio, 5.3; P = 0.028). Twelve male inmates admitted injecting drugs during imprisonment, of whom 11 shared needles and three were HIV-positive. HIV prevalence in men reporting sexual intercourse with men prior to incarceration was 10% (five out of 52). Nine of the 119 women were HIV-infected (8%), seven of whom were IDU (prevalence of 16% in female IDU). One of the two non-IDU had sexual contacts with male IDU, and the other with men who had sex with men. Tattooing was not associated with HIV infection in either men or women. CONCLUSIONS: Prisoners constitute a group at high risk of HIV infection mainly because of the high proportion of them who are IDU. Imprisonment offers a good opportunity to provide education and preventive programs to this specific group that might otherwise be difficult to reach.

Female↗

Relative levels and fractionation properties of Bacillus subtilis σ(B) and its regulators during balanced growth and stress.

sigma B is a secondary sigma factor that controls the general stress response in Bacillus subtilis. sigma B-dependent genes are activated when sigma B is released from an inhibitory complex with an anti-sigma B protein (RsbW) and becomes free to associate with RNA polymerase. Two separate pathways, responding either to a drop in intracellular ATP levels or to environmental stress (e.g., heat, ethanol, or salt), cause the release of sigma B from RsbW. rsbR, rsbS, rsbT, and rsbU are four genes now recognized as the upstream half of an operon that includes sigB (sigma B) and its principal regulators. Using reporter gene assays, we find that none of these four genes are essential for stationary-phase (i.e., ATP-dependent) activation of sigma B, but rsbU and one or more of the genes contained within an rsbR,S,T deletion are needed for stress induction of sigma B. In other experiments, Western blot (immunoblot) analyses showed that the levels of RsbR, RsbS, Rsb, and RsbU, unlike those of the sigB operon's four downstream gene products (RsbV, RsbW, RsbX and sigma B), are not elevated during sigma B activation. Gel filtration and immunoprecipitation studies did not reveal the formation of complexes between any of the four upstream sigB operon products and the products of the downstream half of the operon. Much of the detectable RsbR, RsbS, RsbT, and RsbU did, however, fractionate as a large-molecular-mass (approximately 600-kDa) aggregate which was excluded from our gel filtration matrix. The downstream sigB operon products were not present in this excluded material. The unaggregated RsbR, RsbS, and RsbU, which were retarded by the gel matrix, elated from the column earlier than expected from their molecular weights. The RsbR and RsbS fractionation profile was consistent with homodimers (60 and 30 kDa, respectively), while the RsbU appeared larger, suggesting a protein complex of approximately 90 to 100 kDa.

Animals↗

Interactions between noise and signal segments at the decision level are task contingent.

The ways in which unattended line segments influence the discrimination of a single line segment on which attention is focused was studied in two experiments which differed only by the task to be performed. In the first experiment subjects had to determine whether a line segment viewed centrally was oriented to the right or to the left with respect to the vertical, and in the second experiment they had to judge its tilt amplitude (45 deg vs. 55 deg to vertical). It appears that line segments surrounding the target segment did not affect subjects' response times in the same way in the two experiments. Results are interpreted in terms of response competition at the decision level.

Attention↗

The Bacillus subtilis rsbU gene product is necessary for RsbX-dependent regulation of sigma B.

sigma B is a secondary sigma factor of Bacillus subtilis. sigma B-dependent transcription is induced when B. subtilis enters the stationary phase of growth or is exposed to any of a number of different environmental stresses. Three genes (rsbV, rsbW, and rsbX), which are cotranscribed with the sigma B structural gene (sigB), encode regulators of sigma B-dependent gene expression. RsbW and RsbV have been shown to control sigma B activity, functioning as an inhibitory sigma B binding protein and its antagonist, respectively. Using the SPAC promoter (PSPAC) to control the expression of the sigB operon, a ctc::lacZ reporter system to monitor sigma B activity, and monoclonal antibodies to determine the levels of sigB operon products, we have now obtained evidence that RsbX is an indirect regulator of sigma B activity. Genetic data and in vivo measurements argue that RsbX negatively regulates an extension of the RsbV-RsbW pathway that requires the product of an additional regulatory gene (rsbU) which lies immediately upstream of the sigB operon. The results are consistent with RsbU, or a process dependent on RsbU, being able to facilitate the RsbV-dependent release of sigma B from RsbW but normally prevented from doing this by RsbX.

Amino Acid Sequence↗

Separate mechanisms activate sigma B of Bacillus subtilis in response to environmental and metabolic stresses.

sigma B is a secondary sigma factor that controls the general stress response of Bacillus subtilis. sigma B-dependent transcription is induced by the activation of sigma B itself, a process that involves release of sigma B from an inhibitory complex with its primary regulator, RsbW. sigma B becomes available to RNA polymerase when RsbW forms a complex with an additional regulatory protein (RsbV) and, because of this, fails to bind sigma B. Using Western blot (immunoblot) analyses, reporter gene fusion assays, and measurements of nucleotide pool sizes, we provide evidence for two independent processes that promote the binding of RsbW to RsbV. The first occurs during carbon limitation or entry into stationary phase. Activation of sigma B under these circumstances correlates with a drop in the intracellular levels of ATP and may be a direct consequence of ATP levels on RsbW's binding preference. The second activation process relies on the product of a third regulatory gene, rsbU. RsbU is dispensable for sigma B activation during carbon limitation or stationary phase but is needed for activation of sigma B in response to any of a number of different environmental insults (ethanol treatment, salt or acid shock, etc.). RsbU, or a process dependent on it, alters RsbW binding without regard for intracellular levels of ATP. In at least some instances, the effects of multiple inducing stimuli are additive. The data are consistent with RsbW being a regulator at which distinct signals from separate effectors can be integrated to modulate sigma B activity.

Adaptation, Physiological↗

Influence of unattended features on the processing of a single line segment.

This work investigates the interference of unattended line segments (distractors) of different orientations on a single line segment (target) when observer attention is focused on it in order to determine its orientation. It appears that the presence of line segments of different orientations in the visual field strongly influences the observer's decision on the judgement of the target orientation, whereas sensitivity is not affected. Two experiments were carried out to investigate distractor influence as a function of their number (Experiment I) and as a function of their proximity to the target, that is, to the point on which attention is focused (Experiment II). It appeared that distractors close to the target interfered more intensely than distractors at greater distances from the target, even if the latter were far more numerous. The results suggest that the output of the decision system is a function of all the information transmitted by feature detectors which act separately and in parallel.

Adult↗

High-performance liquid chromatographic determination of oxodipine enantiomers, a new 1,4-dihydropyridine, applied to stereoselectivity studies in man and dog.

A specific and reproducible HPLC method using a Chiral-AGP column and UV detection was developed for the evaluation of the pharmacokinetic profile of oxodipine enantiomers in dog and man. Each enantiomer was determined in plasma in the concentration range 1-400 ng/ml using the internal standard calibration method with linear regression analysis. After extraction of oxodipine and the internal standard at alkaline pH with diethyl ether-n-hexane (50:50, v/v), this method permitted the determination of each enantiomer at levels down to 10 ng/ml in dog plasma and 25 ng/ml in human plasma with sufficient accuracy (relative error < 11%, n = 6) and precision (coefficient of variation < 16%, n = 6). The extracted plasma volume was 500 microliters and after evaporation of the organic phase, the dry residue was dissolved in 100 microliters of water-2-propranol; an aliquot of 80 microliters was injected into the HPLC system.

Animals↗

Interactions between a Bacillus subtilis anti-sigma factor (RsbW) and its antagonist (RsbV).

The activity of sigma B, a secondary sigma factor of Bacillus subtilis, is primarily controlled by an anti-sigma factor protein (RsbW) that binds to sigma B and blocks its ability to form an RNA polymerase holoenzyme (E-sigma B). Inhibition of sigma B by RsbW is counteracted by RsbV, a protein that is essential for the activation of sigma B-dependent transcription. When crude B. subtilis extracts were fractionated by gel filtration chromatography or electrophoresis through nondenaturing polyacrylamide gels, a complex composed of RsbW and RsbV that is distinct from the previously observed RsbW-sigma B complex was detected. In analogous experiments, RsbX, an additional regulator of sigma B-dependent transcription that is thought to act independently of RsbV-RsbW, was not found to associate with any of the other sigB operon products. Two forms of RsbV were visualized when crude cell extracts of B. subtilis were subjected to isoelectric focusing (IEF), with the more negatively charged RsbV species absent from extracts prepared from RsbW- strains. In vitro, RsbV became phosphorylated when incubated with ATP and RsbW but not with ATP alone. The phosphorylated RsbV species comigrated during IEF with the RsbW-dependent form of RsbV found in crude cell extracts. These results suggest that the modified RsbV, present in crude cell extracts, is phosphorylated. When gel filtration fractions containing RsbV-RsbW complexes or RsbV alone were subjected to IEF, only the unmodified form of RsbV was found associated with RsbW. The presumed phosphorylated variant of RsbV was present only in fractions that did not contain RsbW. The data support a model whereby RsbV binds directly to RsbW and blocks its ability to form the RsbW-sigma B complex. This activity of RsbV appears to be inhibited by RsbW-dependent phosphorylation.

Adenosine Triphosphate↗

Double-blind trial of dexamethasone versus methylprednisolone in multiple sclerosis acute relapses.

The efficacy of dexamethasone (DX) and methylprednisolone (MP) at high (HD) and low (LD) dose in acute multiple sclerosis (MS) relapses was evaluated by a double-blind trial in 31 patients followed for 1 year. DX and HDMP were similarly efficacious in promoting recovery, while LDMP was ineffective in the short-term outcome and was followed by an early clinical reactivation. The different outcomes seem to be related to different immunomodulating effects, mainly on cerebrospinal fluid (CSF) IgG synthesis and on peripheral blood and CSF CD4+ lymphocyte subsets.

Adult↗

Immunological monitoring and clinical evaluation in cyclophosphamide-treated progressive multiple sclerosis patients.

15 patients with progressive Multiple Sclerosis (MS) were treated by an induction Cyclophosphamide (CFX) schedule followed by bimonthly boosters over one year. Of the 14 patients who completed the trial, only two displayed worsening of neurological status. Cerebrospinal fluid (CSF) total protein, IgG/Alb ratio and IgG index decreased at 6 months and were still low at the end of the treatment. Pretreatment percentages of PB CD8+ and CD4+CD45RA+ lymphocytes were lower in MS patients in comparison with healthy controls. However, no significant shifts occurred in percentage of PB CD4+, CD4+CD45RA+, CD4+CD45RA-, CD8+ lymphocytes of MS patients during immunosuppressive treatment. The lack of changes in the investigated immunological parameters contrasts with the good clinical response and the low rate of serious side effects during this treatment schedule.

Antigens, CD↗

Immunological fluctuations during intrathecal immunotherapy in three patients affected by CNS tumours disseminating via CSF.

The immunological therapy of cancer has been proposed in a number of neoplasms (Borden, Sondel, 1989; Foon, 1989; Rosenberg, 1992) and has recently been adopted in the treatment of Central Nervous System (CNS) tumors in combination with conventional surgical and radiotherapeutical approach. In this context, loco-regional administration of immunomodulating agents (for instance in post-surgical cavity) allows to achieve much higher in situ concentrations than by systemic route. Since these treatments have potential adverse effects, careful assessment of clinical and immunological parameters in phase I trials is needed. CNS tumors disseminating via Cerebrospinal Fluid (CSF) pathways offer a stimulating opportunity for intrathecal immunotherapy. In this context, alpha-IFN and IL2 (alone or in combination with LAK cells) have been employed either loco-regionally or intrathecally (Merchant, Mc Vicar, Merchant & Young, 1992; Schiller, Hank, Storer, Borchert, Moore, Albertini, Bechhofer, Wesley, Brown, Bastin & Sondel, 1993). The rationale for the use of both these substances includes the known anti-tumor action of alpha-IFN (Mahaley, Urso, Whaley, Blue, Williams, Guaspari & Selker, 1985; Nagai, 1988) and the ability of r-IL2 to generate activated cells effective in lysing tumor cell targets (Hayes, Moore, Pierz, Chen, Da Rosso, Nirenberg & Allen, 1993). We treated 3 patients (2 affected by disseminating cerebellar medulloblastoma, 1 by disseminating thalamic glioblastoma) by intrathecal r-IL2 via recervoir. In the first 2 patients, this treatment was preceded by alpha-IFN (also intrathecally). Monitoring of immunological effects of the treatment schedule involved kinetics of CSF and serum TNF-alpha, IL2s and IL2R during the first day of r-IL2 treatment, as well as on day +2 and +4 of both r-IL2 cycles, and assessment of CSF cells, protein and CSF and PB NK cell activity and CD3-CD56+ cells during the course of all treatment cycles. We also assessed clinical and neuroradiological effects of immunotherapy.

Adult↗

High-dose methylprednisolone treatment-induced changes in immunological parameters in progressive MS patients.

The effect of High-Dose Methylprednisolone (HD-MP) treatment on Peripheral Blood (PB) and Cerebrospinal Fluid (CSF) immune parameters was investigated in 9 patients with relapsing-progressive Multiple Sclerosis (MS). Short-time effects included reduction of the percentage of CD3+, CD4+ and CD4+CD45RA+ PB lymphocytes and increase in CD3-CD56+ cells. At the end of the treatment, only increase in PB CD19+ and in CSF CD8+, CD8+CD28+ and decrease of CSF CD4+CD45RA- and serum IL2R levels were observed. No changes in CD11a+CD4+, CD18+CD14+ PB cells were observed after treatment. The results further stress the complex and multifaceted action of HD-MP on immune parameters.

Adult↗

Evidence for a second site of absorption of veralipride in the human small intestine. Use of a new drug delivery telemetric shuttle.

A new telemetric shuttle was used to coadminister veralipride (CAS 66644-81-3) and veralipride-D3 in order to test the assumption that veralipride is absorbed at two sites of the small intestine. Two different pharmacokinetic approaches were used to interpret the obtained data. According to the results, the second site of absorption of veralipride is located at a distance corresponding to 2/3 of the total length of the small intestine.

Animals↗

Presence of T-cell subset abnormalities in newly diagnosed cases of multiple sclerosis and relationship with short-term clinical activity.

Abnormalities of T-cell subsets in patients with multiple sclerosis are well known; in order to assess whether immunological abnormalities are relevant in the pathogenesis of the disease after its clinical onset, peripheral blood lymphocyte subsets (CD3+, CD4+, CD4(+)-CD45RA+, CD4+CD45RA-, CD8+, CD8+CD57+, CD57+, CD25+) were analysed serially in 25 patients at the first clinical episode suggestive of inflammatory demyelinating disease and in an equal number of age- and sex-matched controls. During the follow-up period (12-18 months, mean 14) 6 of 25 patients presented new relapses: in this subgroup of patients, significant changes in CD4+ ratio (% CD4+CD45RA-/%CD4+CD45RA+) were detected in comparison both with healthy controls and with clinically stable patients. Patients clinically stable at follow-up did not display immunological abnormalities, regardless of the presence or absence of cerebrospinal fluid and/or magnetic resonance imaging alterations consistent with multiple sclerosis. These findings suggest a possible prognostic role of early T-cell subset imbalance in multiple sclerosis.

Adolescent↗

Phenotype analysis of unstimulated lymphocytes and anti-CD3-stimulated proliferating T-cells from cerebrospinal fluid and peripheral blood in patients with multiple sclerosis and other neurological diseases.

In 15 patients with multiple sclerosis (MS) and in 11 patients with other neurological diseases (OND), the phenotype of fresh unstimulated CSF and PB mononuclear cells and of "in vitro" expanded T-cells was studied by monoclonal antibody stain and cytofluorimeter analysis. A compartment-specific decrease of CD8+Leu8+ and CD8+Leu8- cells in CSF was detected; moreover, lower levels of CD8+Leu8- cells were seen in MS than in OND patients, both in CSF and in PB. Although the percentages of unstimulated CSF CD4+ cells did not differ between MS and OND, a higher proportion of "in vitro" expanded CD4+ T-cells was obtained from MS patients than from OND. Among MS patients, T-cell growth was very scarce or absent in those sampled during relapses. The results suggest alterations both within the CD4+ "helper" and the CD8+ "suppressor-cytotoxic" populations in the CSF of MS patients, and stress the relevance of functional analysis in conjunction with phenotype studies.

Adult↗

Physical effort-induced changes in immune parameters.

Physical stress induces changes in immune system parameters; these changes depend on effort schedule and are influenced by customary training. The mechanisms whereby they take place are not fully elucidated: sympathetic activation-mediated mobilization of cells of lymphoid organs, including the spleen, has been suggested. We studied exercise-induced changes (20' of cycloergometer test conducted up to 80% of maximal expected heart rate) in white blood cells (WBC), lymphocyte subsets, plasma catecholamine and cortisol levels in three groups of subjects: swimmers, untrained controls and splenectomized individuals. Physical exercise induced increase of WBC and significant changes in the percentage of most investigated lymphocyte subsets (NK, CD3+, CD4+, CD8+ and CD4/CD8 ratio), except for DR+ cells. No changes occurred in the percentage of CD14+ cells. Norepinephrine (NE) levels increased after effort, while epinephrine (E) and cortisol levels were unchanged. Splenectomized patients displayed similar effort-induced changes in investigated parameters as controls and swimmers. The results support the interactions between physical work and immune response and minimize the role of the spleen in this context.

Adult↗