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P Baron

Publications and source records attributed to P Baron.

At least 55 records · Page 3Linked to original sources
PubMed1995

The Beck Depression Inventory: testing and cross-validating a second-order factorial structure for Swedish nonclinical adolescents.

The intent of the present study was to test for the validity and equivalency of a second-order factorial structure of the Beck Depression Inventory for and across three independent samples (n1 = 661; n2 = 239; n3 = 196) of nonclinical Swedish adolescents. The model under study derived from a cross-validated study of Canadian high school adolescents. Model fitting, testing and equating were based on the analysis of covariance structures within the framework of a confirmatory factor analytic model. Of major importance was the tenability of the hypothesized model for Swedish adolescents. Only minor differences where found among samples, which involved correlated errors and one cross-loading (Sample 2). Results are expected to be of substantial interest to both researchers and clinicians whose concerns focus on depression as it bears on this population.

Adolescent↗
PubMed1995

Identifying depressed and suicidal adolescents in a teen health clinic.

PURPOSE: This study examined the 6-month prevalence of depression and suicidal probability among new referrals to an adolescent health clinic. METHODS: All subjects (n = 104) completed the Beck Depression Inventory (BDI) and the Suicide Probability Scale (SPS) prior to being seen by a physician and were categorized according to presenting problem (physical complaints only, psychological complaints only, and physical and psychological complaints combined). RESULTS: Fifty-nine percent of the sample was depressed with 21% falling in the moderate range and 21% falling within the severe range of depression. Almost 23% of the sample demonstrated significant suicidal probability. The BDI and SPS were highly correlated (r = .73, p < .001) and 22% of the sample met criteria for both moderate to severe depression and suicidal probability. A significantly greater proportion of patients presenting with physical and psychological complaints combined (60%) met BDI criteria for depression than was found for the other two groups. Suicidal probability was most prevalent in patients presenting with psychological complaints only (26%) and moderate to severe depression and significant suicidal probability also coexisted to a greater extent within this group (26%). CONCLUSIONS: Results suggest that depression and suicidal probability represent significant mental health problems within the adolescent clinic and the identification of high-risk individuals can be achieved through comprehensive screening practices.

Adolescent↗
PubMed1995

[Not Available].

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Belgium↗
PubMed1995

Inhibition of human immunodeficiency virus type 1 replication by 7-methyl-6,8-bis(methylthio)pyrrolo[1,2-a]pyrazine, an in vivo metabolite of oltipraz.

Oltipraz, an inhibitor of human immunodeficiency virus type 1 replication in vitro (ED50 approximately 10 microM), undergoes extensive metabolism in vivo. Most of the orally administered drug undergoes opening of the dithiolethione ring, reduction, recyclization, and methylation to form 7-methyl-6,8-bis(methylthio)pyrrolo[1,2-a]pyrazine ("metabolite III"). We report here that metabolite III inhibits viral replication in vitro (ED50 approximately 25 microM) in acutely infected H9 and CEM T cell lymphoma cell lines. Although both metabolite III and oltipraz were able to inhibit phorbol-12-myristate-13-acetate-stimulated viral replication in the chronically infected U1 promonocytic leukemia cell line, only metabolite III was able to inhibit phorbol-12-myristate-13-acetate-stimulated viral replication in chronically infected ACH-2 T cell lymphoma cells. The results with ACH-2 cells suggest that oltipraz inhibits an early stage of the viral life cycle, whereas metabolite III affects human immunodeficiency virus type 1 replication at a step distal to viral integration. This is consistent with the finding that oltipraz inhibits reverse transcriptase, whereas metabolite III does not. Although the mean ED50 for metabolite III in acutely infected peripheral blood mononuclear cells was 18 microM, the ED50 was below 5 microM in three of eight independent experiments. Studies of metabolite III in combination with oltipraz in acutely infected peripheral blood mononuclear cells demonstrated significant antiviral synergy. These results raise the possibility that the in vitro potency of oltipraz may underestimate its antiretroviral activity in vivo. Based on these results, the pharmacokinetics of oltipraz and metabolite III will be compared with the pharmacodynamic effects of orally administered oltipraz in a forthcoming phase I/II trial of oltipraz in patients with p24 antigenemia.

Antiviral Agents↗
PubMed1995

[Lymphomas of the colon complicating hemorrhagic rectocolitis].

Colonic lymphoma is a rare complication of ulcerative colitis. We report two cases of B cell colonic lymphoma occurring in two patients who had a left-sided ulcerative colitis for 7 and 24 years respectively. The diagnosis was made during surgery in one case and at colonoscopy in the other. Complete remission was achieved after surgery and chemotherapy with a 8-year and 15-month follow-up respectively.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Expression of P0 protein mRNA along rat sciatic nerve during development.

The temporal and spatial expression of P0 protein mRNA in the spinal nerve roots and in distal (popliteal trifurcation) segments of the developing rat sciatic nerve was examined using in situ hybridization. P0 mRNA was undetectable in the PNS portions at day 16 post-fertilization (E16) but present in the roots as well as in the sciatic nerve by E18. While Schwann cells were labelled by in situ hybridization at E18, it was not until birth (P1) that cells revealed the typical clusters of silver grains in a perinuclear distribution. Hybridization signal rose between P5 and P10, than decreased at P40, with no significant difference of P0 mRNA levels between the different PNS portions at each age studied. These findings demonstrate the lack of proximo-distal gradient in abundance of P0 mRNA during rat PNS development and add further insight in understanding the dynamics of axonal regulation of myelination in the PNS.

Animals↗
PubMed1994

Sulfatides trigger cytokine gene expression and secretion in human monocytes.

We investigated whether sulfatides are able to trigger transmembrane signals and activation of selective cell functions in human monocytes. Sulfatides stimulated an increase in cytosolic free-calcium in monocytes, and this depended on the release of calcium from intracellular stores. Non-sulfated galactocerebrosides had no effect on monocyte cytosolic free calcium. Sulfatides enhanced expression of tumor necrosis factor, interleukin-8, and interleukin-1 beta, but not interleukin-12/natural killer cell stimulating factor mRNAs. Sulfatides also triggered secretion of cytokines into the extracellular medium, although they were much less effective than lipopolysaccharide. Both enhanced expression of cytokine mRNAs and secretion by sulfatides required sulfation of the galactose ring of the glycolipid as non-sulfated galactocerebrosides had no effect. These findings suggest that sulfatides that are released at sites of inflammation can amplify the inflammatory reaction triggering cytokine expression in, and release by, monocytes.

Calcium↗
PubMed1994

Chromosomally encoded cephalosporin-hydrolyzing beta-lactamase of Proteus vulgaris RO104 belongs to Ambler's class A.

Proteus vulgaris RO104 strain produces a chromosomally encoded beta-lactamase that confers resistance to various beta-lactam antibiotics including methoxyimino third-generation cephalosporins. The beta-lactamase hydrolyzes first- and second-generation cephalosporins efficiently and cefotaxime to a lesser extent. Catalytic activity is inhibited by low concentrations of clavulanic acid and sulbactam. By its broad-spectrum substrate profile, beta-lactamase of Proteus vulgaris RO104 belongs to the group 2e defined by Bush. The protein purified to homogeneity by a four-step procedure was characterized by a pI of 8.31 and a specific activity of 1200 U/mg. The beta-lactamase was digested by trypsin, endoproteinase Asp-N and chymotrypsin. Amino-acid sequence determinations of the resulting peptides allowed the alignment of the 271 amino-acid residues of the protein which did not contain any cysteine residue. From amino-acid sequence comparisons, Proteus vulgaris RO104 beta-lactamase was found to share about 68% identity with the chromosomally mediated beta-lactamases of Klebsiella oxytoca D488 and E23004. Therefore, the cephalosporin-hydrolyzing beta-lactamase of Proteus vulgaris RO104 belongs to Ambler's class A.

Amino Acid Sequence↗
PubMed1994

Sulfatides trigger increase of cytosolic free calcium and enhanced expression of tumor necrosis factor-alpha and interleukin-8 mRNA in human neutrophils. Evidence for a role of L-selectin as a signaling molecule.

Sulfatides have been established recently as ligands for L-selectin, and we investigated whether they trigger transmembrane signals through ligation of L-selectin. We found that sulfatides trigger the increase of cytosolic free calcium in neutrophils and that this effect was strictly dependent on sulfation of the galactose ring, as non-sulfated galactocerebrosides were not stimulatory. Chymotrypsin and phorbol 12-myristate 13-acetate treatment of neutrophils caused shedding of L-selectin, but not of class I major histocompatibility complex antigens or beta 2 integrins, and blunted the capability of neutrophils to respond to sulfatides with an increase of cytosolic free calcium. Four different anti-L-selectin antibodies (DREG-200, LAM1/3, LAM1/6, and LAM1/10), but not four control antibodies directed against different surface molecules of neutrophils, also triggered an increase of cytosolic free calcium. The anti-L-selectin antibodies were stimulatory both if used in a soluble form, after cross-linking with anti-mouse F(ab')2 fragments, and immobilized to protein A of Staphylococcus aureus through the Fc fragment. With immobilized antibodies, an increase of cytosolic free calcium was found also by plating neutrophils on antibodies bound to protein A-coated coverslips and monitoring the increase of cytosolic free calcium by fluorescence microscopy. Both sulfatides and anti-L-selectin antibody effects were not inhibited by pertussis toxin, thus indicating that a pertussis toxin-sensitive GTP-binding protein was not involved in signal transduction. Sulfatides also triggered an increase of tumor necrosis factor-alpha and interleukin-8 mRNAs in neutrophils. Also to act as stimuli of cytokine mRNA expression, sulfatides required sulfation of the galactose ring, as non-sulfated galactocerebrosides were not stimulatory, and depended on expression of L-selectin, as shedding of this molecules induced by chymotrypsin blunted their effects. These findings suggest that L-selectin can transduce signals activating selective cell function.

Calcium↗
PubMed1994

Expression of the low-affinity NGF receptor during human muscle development, regeneration, and in tissue culture.

The expression of the low-affinity NGF receptor (LNGFR) during human muscle development, regeneration, and in tissue culture was analyzed using a murine monoclonal antibody to human LNGFR (MAb ME 20.4). Muscle cells from 12-22-week fetuses stained strongly for LNGFR. In adult normal muscle, only intramuscular nerve endings showed immunoreactivity with MAb ME 20.4, but no staining was detected in muscle fibers. In Duchenne muscular dystrophy, immunohistologically demonstrable LNGFR was present in regenerating muscle fibers. In these fibers, LNGFR gene expression was also demonstrated at the transcriptional level using in situ hybridization with riboprobes coding with human LNGFR. Cultures from human fetal and adult muscle were studied by double label indirect immunofluorescence microscopy with MAb ME 20.4 and antisera against human fetal myosin. Most myosin-positive cells, both at the myoblast and myotube stages, displayed surface LNGFR immunostaining. In cells from fetal muscle, LNGFR was detected during the first 2 weeks in vitro, whereas in cells from adult muscle the expression of LNGFR was observed for up to 7 weeks. These findings suggest a potential involvement of LNGFR in human muscle development and regeneration.

Culture Techniques↗
PubMed1994

Gut failure and translocation following burn and sepsis.

Sepsis with multisystem organ failure is a major cause of morbidity and mortality in burns. We studied the anatomic, physiologic, and metabolic changes of gut mucosa as a normal barrier against sepsis and systemic inflammatory response after burn and sepsis in the chronic porcine model. Flow probes were placed on the mesenteric and hepatic arteries and portal vein. Catheters were placed in the pulmonary artery (Swan-Ganz), aorta, superior mesenteric, and hepatic veins. After 5 days, baseline data were collected and studied after a 40%, third degree burn. They were resuscitated with Ringer's lactate solution (Parkland formula). Eighteen hours later, Escherichia coli endotoxin (100 micrograms/kg) was administered. All animals were sacrificed after 30 hr. The data were compared to a group of sham animals. Following thermal injury the cardiovascular status was stable. Endotoxin administration decreased systemic vascular resistance index and mean arterial pressure, but increased cardiac index. Mesenteric blood flow, vascular resistance, and oxygen consumption showed a transient fall after endotoxin infusion with 20, 23, and 40% reduction, respectively. These changes were associated with a rise in plasma levels of conjugated dienes. The intestinal ornithine decarboxylase activity was elevated at the end of the experiment, evidence of gut repair. Gut bacteria translocated into mesenteric lymph nodes, spleen, and burn wounds in 50% of the animals. We concluded that bacterial translocation into mesenteric lymph nodes, spleen, and wound is due to gut mucosal failure after burn trauma and sepsis. These pathophysiologic changes may be the result of mesenteric ischemia and reperfusion injury.

Animals↗
PubMed1994

Developmental expression of P0 mRNA and P0 protein in the sciatic nerve and the spinal nerve roots of the rat.

Expression of myelin P0 protein by myelinating Schwann cells in vivo is dependent on axonal influences. This report describes P0 gene expression during development of rat sciatic nerve and spinal nerve roots using Northern blotting, in situ hybridization and immunohistochemistry. We demonstrate that: (1) the appearance of P0 mRNA and P0 protein in Schwann cells during nerve development in the rat begins prenatally, at day 18 post-fertilization (E18); (2) P0 mRNA and P0 protein have essentially identical developmental profiles, and are expressed in Schwann cells that are many days prior to myelin formation; (3) initial P0 gene expression is greatest in Schwann cells at the periphery of nerve bundles and in Schwann cells in contact with motor axons; (4) the decline in P0 expression with nerve maturation is accompanied by a sharp decline in P0 message levels in most Schwann cells, but a small subpopulation of these cells continue to synthesize very high levels of P0 mRNA. This study provides data on myelin P0 protein gene expression and distribution during PNS development and adds further insights into the axonal influences controlling Schwann cell behaviour during myelination of the rat PNS.

Aging↗
PubMed1994

Virologic, immunologic, and clinical evaluation of human immunodeficiency virus antibody status of symptom-free children born to infected mothers.

STUDY OBJECTIVE: To determine the prevalence of infection by the human immunodeficiency virus (HIV) in a population of symptom-free children who were born to HIV-infected mothers and who subsequently underwent seroreversion from an HIV antibody-positive to an HIV antibody-negative status. DESIGN: Cohort. SETTING: Pediatric HIV program in a community setting. PATIENTS: We used HIV DNA polymerase chain reaction (PCR) and coculture to detect the presence or absence of HIV in peripheral blood mononuclear cells of 134 children aged 6 to 53 months. All children had HIV antibody at birth and underwent a subsequent seroreversion to antibody-negative status. RESULTS: In 134 children with HIV antibody-negative status, 219 of 220 culture results and 242 of 247 HIV-1 DNA PCR assay results were negative. Six positive laboratory results were obtained for six different children, each of whom had negative results on multiple assays. For HIV-infected children, 56 of 62 cultures and 99 of 104 PCR evaluations showed positive results. There was no clinical or laboratory evidence of HIV infection in the group with HIV antibody-negative status. CONCLUSION: We were unable to find evidence of latent HIV type 1 infection in this cohort of symptom-free children who underwent seroreversion to HIV antibody-negative status. The loss of maternal HIV antibody in these children indicates the absence of HIV infection. False-positive PCR and culture results occurred sporadically, indicating that repeated analysis of HIV seropositivity in infants and children is necessary.

Adolescent↗
PubMed1994

Elevation of glutathione levels by phase II enzyme inducers: lack of inhibition of human immunodeficiency virus type 1 replication in chronically infected monocytoid cells.

Supplementation of media with high concentrations of thiols (5-20 mM) inhibits human immunodeficiency virus type 1 (HIV-1) replication in vitro. Compounds that prevent carcinogenesis via induction of phase II enzymes also elevate intracellular GSH levels, thus raising the possibility that chemopreventive enzyme inducers may represent a more pharmacologically feasible method to inhibit viral replication. Previous studies revealed that oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione] was the only GSH inducer tested that could inhibit HIV-1 replication in acutely infected H9 cells. Because thiols are proposed to suppress transcription of the integrated HIV-1 genome by preventing the activation of nuclear factor-kappa B, experiments evaluating inducers of GSH levels in acutely infected H9 cells do not rule out the ability of these compounds to inhibit viral replication in chronically infected cells exposed to cytokines or mitogens. Therefore, we determined the antiviral effects of several inducers in phorbol-12-myristate-13- acetate-stimulated U1 cells, a monocytoid cell line that contains two integrated copies of the HIV-1 genome. Although 1,2-dithiole-3-thione, dimethyl fumarate, and oltipraz can elevate cytosolic thiol levels, only oltipraz inhibited HIV-1 replication. Moreover, decreased nuclear factor-kappa B binding activity could be correlated with increases in cytosolic thiols produced by various treatments (r2 = 0.8) but not with suppression of viral replication (r2 = 0.01). These data suggest that oltipraz-induced increases in GSH are not responsible for the antiviral action of oltipraz and that elevation of intracellular GSH levels by chemopreventive enzyme inducers does not inhibit viral replication.

Antiviral Agents↗
PubMed1993

Production of tumor necrosis factor and other proinflammatory cytokines by human mononuclear phagocytes stimulated with myelin P2 protein.

In this study we examined the effect of myelin P2 protein on some proinflammatory functions exerted by human mononuclear phagocytes. Northern blot analysis demonstrated that P2 protein selectively induced in monocytes and macrophages mRNA accumulation of tumor necrosis factor (TNF), interleukin 1 beta (IL-1 beta), and interleukin 8 (IL-8) in a time-dependent manner. Natural killer stimulating factor (IL-12) mRNA and protein secretion was strongly induced by lipopolysaccharide but not by P2 protein. Supernatants harvested from P2-stimulated monocytes contained significant amounts of TNF, IL-1 beta, and IL-8, whereas those from macrophages contained only TNF and IL-8. The effect of the P2 protein on TNF and IL-8 mRNA accumulation and secretion was not affected by polymyxin B, which, on the other hand, almost completely abolished the effect of lipopolysaccharide. Finally, P2 protein did not directly trigger hydrogen peroxide release but, through the induced release of TNF, potentiated monocyte respiratory burst capability. Since P2 protein is the antigen responsible for the induction of experimental allergic neuritis, these findings identify a potential mechanism involved in the inflammatory reaction and myelin damage during experimental allergic neuritis.

Cytokines↗
PubMed1993

Oltipraz, an inhibitor of human immunodeficiency virus type 1 replication.

Glutathione depletion may play a pivotal role in the pathogenesis of human immunodeficiency virus type-1 (HIV-1) infection. Since certain compounds prevent experimental carcinogenesis by elevating the levels of glutathione and phase II detoxication enzymes, we compared the potencies of several inducers with their ability to inhibit basal levels of HIV-1 replication in H9 cutaneous T-cell lymphoma cells. All monofunctional inducers tested elevated the levels of glutathione and quinone reductase, a marker for phase II enzyme induction. However, only oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione] was effective at inhibiting HIV-1 replication (IC50 = 14.8 +/- 3.1 microM). The antiviral effect of oltipraz was potentiated by 3'-azido-3'-deoxythymidine. Thus, 1,2-dithiole-3-thiones represent a hitherto unrecognized class of anti-HIV-1 agents. Oltipraz behaves kinetically as an irreversible inhibitor of HIV-1 reverse transcriptase in the template-primer binding domain. Oltipraz has been used to treat schistosomiasis in humans and is undergoing clinical evaluation as an anticarcinogen. Thus, oltipraz (and other 1,2-dithiole-3-thiones) may have therapeutic utility in HIV-1-infected individuals, not only because of their antiretroviral activity, but also by preventing the development of HIV-1-associated neoplasms.

Antiviral Agents↗