Search PubMed⌕ Search

Biomedical subjects

G Simon

Publications and source records attributed to G Simon.

At least 109 records · Page 6Linked to original sources
PubMed1995

Conservation of cis-acting elements within the tor regulatory region among different Enterobacteriaceae.

The Escherichia coli (Ec) torCAD operon encoding the trimethyl amine N-oxide (TMAO) reductase system is induced by both TMAO and anaerobiosis. The tor regulatory regions from bacteria related to Ec have been amplified by the polymerase chain reaction (PCR) using degenerate oligodeoxyribonucleotide primers based on conserved sequences of the tor products. The amplified regions from Salmonella enteritidis and Sa. typhimurium (St) were the same size as that from Ec and showed 82% identity with it. Interestingly, four boxes of a 10-nucleotide motif (5'-CTGTTCATAT) were found in direct repeat at the same location in the tor regulatory region of the three species. Although the amplified fragment from Shigella sonneï (Ss) was highly homologous to the Ec corresponding segment, the first tor box was missing. In Ec, the St and Ss tor promoters were still regulated by both TMAO and anaerobiosis, but their transcriptional activities were significantly lower than that of the Ec tor promoter. Deletion of the two first boxes of the Ec tor regulatory region inactivated the tor promoter while deletion of the region just upstream from the tor boxes led to a significant decrease in tor expression. Our results strongly suggest that the tor boxes, as well as specific sequences outside the tor boxes, play an important role in the expression of the tor operon.

Base Sequence↗
PubMed1995

Quality and customers: Type 2 change in mental health delivery within health care reform.

The traditional separation of mental health and medical programs is problematic because mental health issues are inseparable from the larger medical system. By contrast, a collaborative primary care model of mental health care, augmented and supported by secondary specialty mental health services, has the potential to optimize quality and cost goals while reinforcing health care reform principles. The flexibility of mental health treatment in this delivery structure provides opportunities to customize services according to patient and purchaser expectations.

Catchment Area, Health↗
PubMed1995

Cost-effectiveness comparisons using "real world" randomized trials: the case of new antidepressant drugs.

While randomized clinical trials remain the "gold standard" for comparisons of treatment efficacy, conventional randomized trials may not reflect the relative effectiveness of treatments under "real world" conditions. Observational data more closely reflect the conditions of actual practice, but are often limited in clinical detail and subject to bias in selection of treatments. The authors use available data on the cost-effectiveness of new antidepressant drugs to illustrate the limitations of these methods. Modifications to the traditional randomized trial may allow more accurate assessment of effectiveness in everyday practice. The authors describe the design of such a "real world" randomized trial comparing newer antidepressants with older alternatives.

Antidepressive Agents↗
PubMed1995

Development of structural vascular changes with subpressor angiotensin II administration in rats.

We investigated whether the slow pressor action of small doses of angiotensin II (ANG II) administered to rats was accompanied by the development of structural vascular changes. Male Sprague-Dawley rats (350 to 400 g) were given ANG II intraperitoneally, 200 ng/kg/min, for 7 to 10 days or 6 weeks, or 100 ng/kg/min for 6 weeks. Sham-treated rats were controls. Lumen and external diameters of arterioles (30 to 60 microns) and small (61 to 120 microns) and intermediate-size (121 to 220 microns) arteries were measured in maximally dilated, pump-perfused (55 to 60 mm Hg), in situ fixed mesenteric and renal vascular beds, and wall-to-lumen ratios were calculated. Systolic blood pressure and vessel dimensions were unchanged in rats receiving ANG II for 7 to 10 days. Systolic blood pressures rose (P < .001) in rats treated with 200 or 100 ng/kg/min ANG II for 6 weeks but were significantly different from those of controls only in rats receiving the higher dose (P < .01). In rats treated with 200 and 100 ng/kg/min ANG II for 6 weeks, wall-to-lumen ratios of mesenteric and renal arteries were increased 23% and 9% (P < .001) and 13% and 6% (P < .01), respectively. With the higher dose of ANG II, the increase of wall-to-lumen ratios of mesenteric arteries was greater than that of renal arteries (P < .005). Initially subpressor doses of ANG II, when applied long enough, may lead to the development of structural vascular changes. There may be significant regional differences in the extent of structural vascular changes induced by ANG II.

Angiotensin II↗
PubMed1995

Pressor and subpressor angiotensin II administration. Two experimental models of hypertension.

Administered dose is an important determinant of the type of hypertension produced by angiotensin II. With chronic administration of pressor doses, there is salt and water retention and expansion of extracellular fluid volume, and the pressure-natriuresis curve is shifted to higher pressures. Important compensatory mechanisms, including resetting of baroreceptors, de novo synthesis of vasodilator prostaglandins, and atrial natriuretic factor release, are triggered by the acute rise of blood pressure. Histologic evidence for vascular injury confounds the interpretation of findings. When angiotensin II is administered in initially subpressor doses, the rise of blood pressure is gradual, there are no detectable changes in salt and water balance, and compensatory mechanisms do not seem to be activated. Autopotentiation of pressor and vasoconstrictor responses by angiotensin II is the characteristic feature of the early stages of hypertension induced by small doses of angiotensin II. Trophic stimulation of vascular tissue, in particular restructuring of extracellular matrix, precedes and may, therefore, be the mechanism responsible for the hemodynamic changes. The pressor and subpressor models of angiotensin II-induced hypertension draw attention to the relative importance of renal and extrarenal mechanisms in the pathogenesis of hypertension. The long-term administration of initially subpressor doses of angiotensin II mimics the development of human hypertension to a greater extent than does the administration of pressor doses.

Angiotensin II↗
PubMed1995

Hypertensive urgency due to cholesterol embolization of kidneys.

Four weeks after left carotid endarterectomy, a 65-year-old man developed severe, acute hypertension due to cholesterol embolization of the kidneys. The diagnosis was established by the demonstration of mobile, protruding atheromata in the descending thoracic aorta and the visualization of distal embolization of a plaque fragment by transesophageal echocardiography.

Acute Disease↗
PubMed1995

Scedosporium apiospermum infection imitating lymphocutaneous sporotrichosis in a patient with myeloblastic-monocytic leukaemia.

A 63-year-old man with a history of myeloblastic-monocytic leukaemia developed partly suppurating cutaneous nodules on the lower left leg. The nodules proceeded to spread in a linear fashion up the limb, following the line of the lymphatic drainage. Mycological examination of a skin biopsy demonstrated Scedoporium apiospermum. This case highlights the potential for Scedosporium species to act as opportunistic infections in immunosuppressed humans.

Dermatomycoses↗
PubMed1995

Binding of the TorR regulator to cis-acting direct repeats activates tor operon expression.

The expression of the Escherichia coli torCAD operon, which encodes the anaerobically expressed trimethylamine N-oxide (TMAO) reductase respiratory system, requires the presence of TMAO in the medium. The response regulator, TorR, has recently been identified as the regulatory protein that controls the expression of the torCAD operon in response to TMAO. The torC regulatory region contains four direct repeats of a decameric consensus motif designated the tor boxes. Alteration by base substitutions of any of the four tor boxes in a plasmid containing a torC'-lacZ fusion dramatically reduces TorR-dependent torC expression. In addition, deletion of the distal tor box (box1) abolishes torC induction whereas the presence of a DNA fragment starting three bases upstream from box1 suffices for normal torC expression. Footprinting and gel-retardation experiments unambiguously demonstrated that TorR binds to the torC regulatory region. Three distinct regions are protected by TorR binding. One of approximately 24 nucleotides covers the first two tor boxes (box1 and box2); the second is located upstream from the -35 promoter sequence and includes the third tor box (box3); the last is found downstream from the -35 sequence and corresponds to the fourth tor box (box4). Binding to the upstream tor boxes (box1 and box2) appears to be stronger than binding to the downstream tor boxes (box3 and box4) since only the upstream region is protected at the lower concentration of TorR used in the footprinting experiments. We propose a model in which multiple binding sites (i.e. the tor boxes) contribute to the formation of a nucleoprotein complex, but only one particular proximal site positions TorR properly so that it interacts with RNA polymerase.

Bacterial Proteins↗
PubMed1995

Health care costs associated with depressive and anxiety disorders in primary care.

OBJECTIVE: The authors examined the overall health care costs associated with depression and anxiety among primary care patients. METHOD: Of 2,110 consecutive primary care patients in a health maintenance organization, 1,962 were screened with the 12-item General Health Questionnaire. A stratified random sample of 615 patients were selected for further diagnostic assessment; 373 of these patients completed the Composite International Diagnostic Interview at baseline and 328 were reassessed 12 months later. Computerized cost records were used to calculate total health care costs for the 6-month period surrounding the baseline assessment and a similar period surrounding the follow-up assessment. Cost accounting data were available for 327 patients at baseline and for 206 patients at both assessments. RESULTS: Primary care patients with DSM-III-R anxiety or depressive disorders at baseline had markedly higher baseline costs ($2,390) than patients with subthreshold disorders ($1,098) and those with no anxiety or depressive disorder ($1,397). Large cost differences persisted after adjustment for medical morbidity. Cost differences reflected higher utilization of general medical services rather than higher mental health treatment costs. Although most patients with baseline anxiety or depressive disorders showed significant improvement, longitudinal analyses did not show any clear relationship between change in psychiatric diagnosis and change in health care cost. CONCLUSIONS: Among primary care patients, anxiety and depressive disorders are associated with markedly higher health care costs even after adjustment for medical comorbidity. In this small sample, improvement in depression over 1 year was not clearly associated with decreases in cost.

Adolescent↗
PubMed1995

In vitro study of THP-doxorubicin retention in human leukemic cells using confocal laser microspectrofluorometry.

Microspectrofluorometry allows the analysis of fluorescent molecules such as anthracyclines in the nucleus of isolated living cells. Using this technique, we confirmed that the amount of doxorubicin or THP-doxorubicin incorporated into the nucleus was related to the resistant or sensitive character of K562 cells. It was then extended to the study of fresh leukemic cells and kinetic studies were performed allowing the calculation of the retention rate (RR) of anthracycline (THP-doxorubicin) into the cell nucleus. A reproducibility study confirmed the accuracy of the method. Blast cells collected in patients with acute myeloid (n = 22) or lymphoid (n = 8) leukemia, at diagnosis (n = 26), or in relapse (n = 4) have been studied. RR varied from 8 to 98% independently of the type of leukemia or the clinical status. RR did not correlate either with P-glycoprotein or with CD34 expression although this latter result should be confirmed on a higher number of subjects. Among 18 patients presenting with AML at diagnosis, 14 have been treated with intensive chemotherapy including anthracyclines; the only one who had resistant disease had the lowest RR value. In conclusion, the results obtained here show that microspectrofluorometry allows the performance of kinetic studies on fresh leukemic cells in order to quantify chemo-resistance phenomena related to drug transport.

Biological Transport↗
PubMed1994

Synaptic disinhibition during maintenance of long-term potentiation in the CA1 hippocampal subfield.

Long-term potentiation (LTP) in the CA1 region of the hippocampus is widely believed to occur through a strengthening of efficacy of excitatory synapses between afferent fibers and pyramidal cells. An alternative mechanism of LTP, reduction of efficacy of synaptic inhibition, was examined in the present report. The present study demonstrates that the maintenance of LTP in the CA1 hippocampal subfield of guinea pigs is accompanied by impairment of type A gamma-aminobutyric acid (GABA) receptor function, particularly at apical dendritic sites of CA1 pyramidal cells. Enhanced excitability of GABAergic interneurons during LTP represents a strengthening of inhibitory efficacy. The net effect of opposite modifications of synaptic inhibition during LTP of CA1 pyramidal cells is an overall impairment of the strength of GABAergic inhibition, and disinhibition could contribute importantly to CA1 pyramidal cell LTP.

Animals↗
PubMed1994

Valproic acid reduces the intracellular level of glutathione and stimulates human immunodeficiency virus.

Modifications of the glutathione (GSH) intracellular level have been implicated in the regulation of human immunodeficiency virus (HIV) transcription and expression. In regard to this hypothesis, we have investigated the effects of valproic acid (VPA) on HIV replication. Indeed, it has been recently reported that VPA inhibits the human red blood cell glutathione reductase. In the supernatant of a CEM-SS T-lymphocytic cell line infected with the LAI strain of HIV-1, we observed an increase, in a dose-dependent fashion, of the reverse transcriptase activity after treatment of cells with VPA. VPA also induced HIV expression in the chronically infected monocytic U1 cell line which constitutively expresses low levels of virus, enhanced the HIV-long terminal repeat (LTR)-directed expression of beta-galactosidase in transiently transfected Jurkat T-cells, and potentiated the PMA effect on the LTR transactivation. GSH assays showed that VPA treatment led to a decrease in the intracellular level of this thiol compound in U937 (U1 parent-cell line) and in Jurkat T-cells. Work to understand the molecular mechanism of VPA-induced HIV transcription and expression are now in progress. VPA seems to be an adequate molecule to study the implications of a GSH decrease in the stimulation of HIV replication. However, a modification of the intracellular balance between reduced and oxidized glutathione, rather than a simple reduction of the intracellular glutathione level, could be of importance in the regulation of HIV replication and we are now testing this hypothesis. Finally, these findings already suggest that VPA, which is an anticonvulsive drug frequently prescribed for the management of various seizure disorders, should not be recommended for treatment of epilepsy or other related illnesses in HIV-positive individuals.

Cell Line↗
PubMed1994

Effects of glutathione precursors on human immunodeficiency virus replication.

Asymptomatic human immunodeficiency virus (HIV)-seropositive individuals have reduced glutathione (GSH) levels. This has led to the suggestion that elevated intracellular thiols levels may inhibit HIV replication and progression of the disease. We confirmed that N-acetyl-L-cysteine (NAC), a cysteine prodrug which maintains intracellular GSH levels during oxidative stress, inhibits in the chronically infected U1 cells, the stimulation of HIV replication induced by phorbol 12-myristate 13-acetate (PMA), interleukin-6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF). However, we found no significant inhibition of PMA-mediated long terminal repeat (LTR)-directed beta-galactosidase expression in transiently transfected Jurkat T-cells. We have compared NAC effects with the effects of other GSH precursors on HIV expression. Treatment of the U1 cell line by L-2-oxo-4-thiazolidine carboxylic acid (OTC), which is converted to cysteine by 5-oxoprolinase, or by homocysteine (HC), a natural cysteine precursor, reduced the PMA-induced HIV expression, but surprisingly, markedly stimulated the expression mediated by IL-6 and GM-CSF. Several experiments to investigate the effect of OTC on LTR transactivation were carried out, but beta-galactosidase activity was never modified in a significant fashion in PMA-induced Jurkat T-cells after OTC treatment. Furthermore, HC stimulated the PMA-mediated HIV-LTR transactivation in Jurkat T-cells. GSH assays showed that treatment of U937 and Jurkat T-cells with NAC and OTC moderately increased the GSH level, while HC led to a significantly higher increase of the thiol level. In conclusion, it appeared that an increase of the GSH intracellular level did not lead solely to an inhibition of HIV replication but could also lead to an activation of viral expression. This seemed the case when HIV replication was stimulated by compounds which act mainly at a post-transcriptional level.

Acetylcysteine↗
PubMed1994

The predictors of persistence of depression in primary care.

164 patients in primary care who were recognized as depressed by their physicians and started on antidepressants were interviewed at 1 and 4 months after initiation of treatment. Ten factors hypothesized to be related to persistence of depressive symptoms were entered into a multivariate analysis to determine predictors of persistence of affective symptoms. Patients with minor depression were significantly older, more likely to be married or cohabitating, more likely to have serious medical illness, and had significantly less comorbid panic disorder, recurrent depression and lower neuroticism scores compared to patients with major depression. Approximately half of the patients in this primary care sample with major depression and one-third of those with minor depression were still distressed at 4 months, although few met criteria for major depression. Severity of depression and high neuroticism scores were the best predictors of persistent depressive symptoms.

Adolescent↗