[Medical-psychiatric units, a concept to be developed].
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
D Marra
Publications and source records attributed to D Marra.
3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing rho GTPase-induced down-regulation of p27(Kip1).
The mechanism by which platelet-derived growth factor (PDGF) regulates vascular smooth muscle cell (SMC) DNA synthesis is unknown, but may involve isoprenoid intermediates of the cholesterol biosynthetic pathway. Inhibition of isoprenoid synthesis with the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, simvastatin (Sim, 1-10 microM), inhibited PDGF-induced SMC DNA synthesis by >95%, retinoblastoma gene product hyperphosphorylation by 90%, and cyclin-dependent kinases (cdk)-2, -4, and -6 activity by 80 +/- 5, 50 +/- 3, and 48 +/- 3%, respectively. This correlated with a 20-fold increase in p27(Kip1) without changes in p16, p21(Waf1), or p53 levels compared with PDGF alone. Since Ras and Rho require isoprenoid modification for membrane localization and are implicated in cell cycle regulation, we investigated the effects of Sim on Ras and Rho. Up-regulation of p27(Kip1) and inhibition of Rho but not Ras membrane translocation by Sim were reversed by geranylgeranylpyrophosphate, but not farnesylpyrophosphate. Indeed, inhibition of Rho by Clostridium botulinum C3 transferase or overexpression of dominant-negative N19RhoA mutant increased p27(Kip1) and inhibited retinoblastoma hyperphosphorylation. In contrast, activation of Rho by Escherichia coli cytotoxic necrotizing factor-1 decreased p27(Kip1) and increased SMC DNA synthesis. These findings indicate that the down-regulation of p27(Kip1) by Rho GTPase mediates PDGF-induced SMC DNA synthesis and suggest a novel direct effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors on the vascular wall.
Aorta↗
Regulation of excision of the conjugative transposon Tn916.
Excision from the donor DNA molecule is the first step in conjugative transposition of Tn916 and is followed by circularization of the transposon and its transfer to a new host. We have demonstrated that, in Gram-positive hosts, the Xis protein, as well as the site-specific recombinase Int, is required for the excision of Tn916. Using assays for closure of the excised covalently closed transposon and for repair of the donor DNA molecule, we found that neither protein alone is rate limiting for excision, but overexpression of Int and Xis together results in increased excision. After excision, the frequency of Tn916 circle formation was found to be the same as the frequency of repair of the donor DNA molecule. This suggests that a single reaction results in the closure of both molecules. We have also identified two transcripts that encode Int, one of which also encodes Xis and one of which does not, suggesting that there are steps in conjugative transposition of Tn916 that require Int without Xis.
Bacillus subtilis↗
Excision of the conjugative transposon Tn916 in Lactococcus lactis.
In Lactococcus lactis excision of Tn916 is limited by the concentration of integrase and is increased by providing more excisionase. However, even with increased excision of Tn916 in L. lactis, no conjugative transfer is detectable. This suggests that L. lactis is deficient in a host factor(s) required for conjugative transposition.
Conjugation, Genetic↗
The frequency of conjugative transposition of Tn916 is not determined by the frequency of excision.
Excision and formation of a covalently closed circular transposon molecule are required for conjugative transposition of Tn916 but are not the only factors that limit the frequency of conjugative transposition from one host to another. We found that in gram-positive bacteria, an increase in the frequency of excision and circularization of Tn916 caused by expression of integrase (Int) and excisionase (Xis) from a xylose-inducible promoter does not lead to an increase in the frequency of conjugative transposition. We also found that the concentration of Int and Xis in the recipient cell does not limit the frequency of conjugative transposition and that increased excision does not result in increased expression of transfer functions required to mobilize a plasmid containing the Tn916 origin of transfer. We conclude that in gram-positive hosts in which the Tn916 functions Int and Xis are overexpressed, the frequency of conjugative transposition is limited by the availability of transfer functions.
Bacillus subtilis↗
Anhedonia and relapse in alcoholism.
The aim of this study was to determine the role of anhedonia among other psychopathological dimensions in the relapse of alcoholics 6 months after withdrawal. Psychometric assessments included: the Social and Physical Anhedonia Scales, the Sensation Seeking Scale, the Pleasure-Displeasure Scale (including Fawcett-Clark's Pleasure Scale), the Depressive Mood Scale, the Thymasthenic Syndrome Rating Scale and the Comprehensive Psychopathological Rating Scale. Forty-four alcoholics participated in the study. The baseline values recorded during the second week of treatment showed that the more anhedonic the alcoholics were, the less they sought sensations. Type 2 alcoholics (Cloninger's classification) scored higher on the Thrill and Adventure Seeking Subscale. Relapsed alcoholics had higher baseline values on the Thrill and Adventure Seeking Subscale. This was in agreement with the step-wise discriminant analysis which showed that this subscale was the main variable that differentiated abstinent alcoholics from those who relapsed. Our results indicate that anhedonia does not predict relapse.
Adult↗
Molecular Probe Data Base (MPDB).
In this paper, the current status of the Molecular Probe Data Base (http://www.biotech.ist.unige.it/interlab/ mpdb.html ) is briefly presented together with a short analysis of its activity during 1997. This has been performed by statistically evaluating the 'logs' of the Internet servers that are used for its distribution with reference to the geographical origin of the requests, the words that were utilized to carry out of the searches and the oligonucleotides that were retrieved. Planned enhancements of this database are also described. They include a revision of its data structure and, even more relevant, of its data management procedures.
Computer Communication Networks↗
Use of the lactococcal nisA promoter to regulate gene expression in gram-positive bacteria: comparison of induction level and promoter strength.
We characterized the regulated activity of the lactococcal nisA promoter in strains of the gram-positive species Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcus faecalis, and Bacillus subtilis. nisA promoter activity was dependent on the proteins NisR and NisK, which constitute a two-component signal transduction system that responds to the extracellular inducer nisin. The nisin sensitivity and inducer concentration required for maximal induction varied among the strains. Significant induction of the nisA promoter (10- to 60-fold induction) was obtained in all of the species studied at a nisin concentration just below the concentration at which growth is inhibited. The efficiency of the nisA promoter was compared to the efficiencies of the Spac, xylA, and lacA promoters in B. subtilis and in S. pyogenes. Because nisA promoter-driven expression is regulated in many gram-positive bacteria, we expect it to be useful for genetic studies, especially studies with pathogenic streptococci in which no other regulated promoters have been described.
Bacillus subtilis↗
Conjugative transposition of Tn916: preferred targets and evidence for conjugative transfer of a single strand and for a double-stranded circular intermediate.
Transposition of conjugative transposons proceeds by excision and formation of a covalently closed circular intermediate that includes at its joint the six flanking bases from its previous host (coupling sequences). To elucidate the role of the coupling sequences in this process and to determine the sequence of targets used by Tn916, we studied its insertion into a plasmid following conjugation. The results differ from those previously observed when Tn916 was introduced by transformation. They suggest that only one specific strand of the transposon molecule is transferred during the conjugation event and that complementary strand synthesis produces a double-stranded transposon circle with no mismatches which serves as the reaction intermediate. Tn916 inserts preferentially at specific sites and the same targets are used when Tn916 comes from donors with different coupling sequences. An analysis of the sequences of preferred targets is presented.
Bacillus subtilis↗
Effect of glutaraldehyde fixation and valve constraint conditions on porcine aortic valve leaflet coaptation.
In an investigation of the influence of glutaraldehyde fixation pressure and subsequent valve constraint on the coaptive characteristics of porcine aortic valves, 14 valves were examined, eight having been fixed at low pressure (congruent to 1 mm Hg) and six at high pressure (80 mm Hg). The coaptive ratios of the left and right coronary leaflets in the low-pressure-fixed valves showed a significant improvement over those of the same leaflets in the high-pressure-fixed valves. Inflation to 80 mm Hg results in a variable "peeling back" of the coaptive margins of the low-pressure-fixed valves but not of the high-pressure-fixed valves. Comparable coaptive ratios are therefore expected during full inflation of the unconstrained valves fixed both at low pressure and at high pressure. Constraining the low-pressure-fixed valves during inflation to simulate the effect of mounting on a rigid stent produced either a reduction or virtual elimination of this "peeling back" motion or in some instances a slight reversal of the effect, thus increasing the width of the coaptive margin. Hence it is expected that the stented low-pressure-fixed valve will manifest better coaptation than the high-pressure-fixed valve. Finally, the experimental findings of this study, combined with the improved mechanical function of the leaflet tissue already known to occur in the low-pressure-treated valves, provide a convincing case for valve fixation to be carried out under lower pressures.
Animals↗
[Case report of an intermittent atrio-ventricular block].
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Cardiac Output↗
[Addictive potential in man: methodological aspects].
Different methods have been developed in clinical abuse liability testing in man. Tolerance, psychic and/or physical dependence must be investigated through clinical studies during drug development of a new substance. Adequate methodology is needed using double-blind, time-blind evaluations, comparisons of different dose levels and duration of treatment for a given drug, abrupt and gradual interruption of treatment, appropriate period of observation after treatment cessation ... The optimal scale to evaluate properly the symptoms occurring after drug discontinuation is still under investigation. These studies will or should permit the differentiation of rebound, withdrawal and recurrence. Methods developed to study reinforcing effects in post-addicts and healthy subjects are self-administration and choice procedures. In addition, the more traditional approach has been through assessing self-reported effects in which standardized questionnaires are used (Addiction Research Center Inventory or A.R.C.I.; Single Dose Questionnaire or S.D.Q.). A third focus of measurement has been discrimination studies performed in individuals with histories of drug abuse as well as healthy subjects. Abuse-liability testing of a new compound needs a multidimensional assessment to optimize the predictivity in defining the relative risk.
Behavior, Addictive↗