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Biomedical subjects

C Baron

Publications and source records attributed to C Baron.

At least 91 records · Page 5Linked to original sources
PubMed1992

Absence of correlation between graft-versus-host associated immunosuppression and cytotoxic T cell activity in response to major histocompatibility antigens.

Studies in mice suggest that the T cell subset involved in graft-versus-host-reaction (GvHR) across the major histocompatibility complex (MHC) depends on the class of MHC antigens recognized by the donor cells. However, the correlation between phenotype and function is not absolute. Using a functional approach, we investigated in a parent --> F1 hybrid model differing at the whole MHC, whether graft-versus-host (GvH) associated immunosuppression was correlated with donor cytotoxic T cell activity. The immunodeficiency was tested by the ability of the F1 mice to generate a cytotoxic T cell response against trinitrophenyl-modified syngeic cells (TNF-self) or an alloantigen. F1 specific parental cytotoxic T cells, generated in vitro, induced less immunosuppression than naive parental cells. Specific in vivo priming increased the cytotoxicity of parental spleen cells, but decreased their capacity to induce GvH-associated immunosuppression. In contrast, nonspecific priming resulted in the usual immunodeficiency. In conclusion, there was no correlation between GvH-associated immunosuppression and cytotoxic T cell activity of the parental cells.

Animals↗
PubMed1992

The family of the asthmatic child.

The authors report clinical study of 34 asthmatic children between the ages of ten and 15, followed at a specialized outpatient clinic of a large pediatric hospital in Montreal. Evaluation of the children and their families involved the use of clinical scores with inter-rater agreement. The study found strong associations between certain personality traits and an excessive use of medication, and between personality traits and family structure. Regardless of the severity of their asthma, children with high levels of anxiety and dependence were more likely to live with highly cohesive families and to use greater quantities of cortisone than children with better adapted personality structures. Pathological family settings are known to cause more emotional and behaviour problems in children. We suggest there is a reciprocal influence, and we consider the effects on the family of an early childhood disease that is persistent, worrisome, unpredictable, and necessitates repeated hospitalization. Prospective studies of the high-risk subgroups identified in this study could facilitate early intervention for asthmatic children and their families.

Adolescent↗
PubMed1992

Variations of lipid profile in animals caused by adenosine analogs: N6 (amido-3-propyl) adenosine hydrochloride and (carboxamido-3-propylamino)-6-(triproprionyl) 2',3',5'beta (D-ribosyl)-9-purine.

N6-substituted adenosine analogues are powerful inhibitors of lipolysis in the adipose tissues of animals and humans, because of their agonist effect on A1 purine receptors. Using a model of hypertriglyceridemia provoked by intravenous injection of Triton WR 1339, we observed that Agr 529 [N6(amido-3-propyl)adenosine hydrochloride] at 2 mg.kg-1 intravenous in rabbits, and intraperitoneally and orally in rats led to a return of the levels of circulating triglycerides to normal values. In addition, Agr 529 and its prodrug, Agr 540 [(carboxamido-3-propylamino)-6-(triproprionyl)2', 3',5'beta(D-ribosyl)-9-purine] administered to rats at 3 and 30 mg.kg-1, respectively, returned plasma triglyceride concentrations to normal levels. Intravenous administration of Agr 529 to normal rats led to decreased concentrations of plasma fatty acids, phospholipids, triglycerides and total cholesterol as a function of dose. The decrease began at 0.1 mg.kg-1 and was highly significant at 3 mg.kg-1. In the same conditions, the intraperitoneal administration of Agr 529 caused a dose-dependent hypolipemia. There was no apparent effect on cholesterol and on the triglycerides of high density lipoproteins. A kinetic study showed that the antilipemic effect of Agr 529 intravenously injected at 3 mg.kg-1 began 30 minutes after the injection with a maximum effect at 2 hours. The effect persisted up to 8 hours after injection. The present results show that the administration of Agr 529 and Agr 540 to normal animals causes hypolipemia (decrease in fatty acids, phospholipids, triglycerides and cholesterol) and restores induced hypertriglyceridemia. These effects may be attributed to an interaction of the molecules with A1 purinergic receptors of adipose tissue.

Adenosine↗
PubMed1991

Nitrate-inducible formate dehydrogenase in Escherichia coli K-12. II. Evidence that a mRNA stem-loop structure is essential for decoding opal (UGA) as selenocysteine.

fdnG, encoding the selenopeptide of Escherichia coli formate dehydrogenase-N, contains an in-frame opal (UGA) codon at amino acid position 196 that directs selenocysteine incorporation. We have identified sequences that contribute to the mRNA context required for decoding this UGA as selenocysteine. We identified a potential stem-loop structure immediately downstream of UGA196 that is comparable in size and structure to a stem-loop predicted to form in fdhF, which encodes the selenopeptide of E. coli formate dehydrogenase-H. Mutational analysis of the fdnG stem-loop structure suggests that it is critical for decoding UGA196 as selenocysteine. Our data indicate that both stability and specific nucleotide sequences of the stem-loop likely contribute to the appropriate mRNA context for selenocysteine incorporation into the fdnG gene product.

Base Composition↗
PubMed1991

The length of the aminoacyl-acceptor stem of the selenocysteine-specific tRNA(Sec) of Escherichia coli is the determinant for binding to elongation factors SELB or Tu.

Mutations in selC, which reduce the 8-base pair aminoacyl-acceptor helix to the canonical 7-base pair length (tRNA(Sec)(delAc] or which replace the extra arm of tRNA(Sec) by that of a serine acceptor tRNA species (tRNA(Sec)(ExS), block the function in selenoprotein synthesis in vivo (Baron, C., Heider, J., and Böck, A. (1990) Nucleic Acids Res. 18, 6761-6766). tRNA(Sec), tRNA(Sec)(delAc), and tRNA(Sec)(ExS) were purified and analyzed for their interaction with purified seryl-tRNA synthetase, selenocysteine synthase and translation factors SELB and EF-Tu. It was found that seryl-tRNA synthetase displays 10-fold impaired Km and Kcat values for tRNA(Sec) in comparison to tRNA(Ser), decreasing the overall charging efficiency (Kcat/Km) of tRNA(Sec) to 1% of that characteristic for tRNA(Ser). tRNA(Sec)(ExS) was a less efficient substrate for the enzyme (Kcat/Km 0.2% of the tRNA(Ser) value) whereas the tRNA(Ser)(delAc) variant was charged with an approximately 2-3-fold improved rate compared to wild-type tRNA(Sec). Both mutant tRNA variants, when charged with L-serine, were able to interact with selenocysteine synthase to give rise to selenocysteyl-tRNA with tRNA(Sec)(ExS) being as efficient as wild-type tRNA(Sec). Seryl-tRNA(Sec)(delAc), on the other hand, was selenylated very slowly. Reduction of the length of the aminoacyl-acceptor stem to 7 base pairs prevented the interaction with translation factor SELB but allowed binding to EF-Tu, irrespective of whether tRNA(Sec)(delAc) was charged with serine or selenocysteine. The aminoacyl-acceptor helix of tRNA(Sec), therefore, is a major determinant directing binding to SELB and precluding interaction with EF-Tu.

Bacterial Proteins↗
PubMed1991

Selenoprotein synthesis: an expansion of the genetic code.

A number of enzymes employ the unusual amino acid selenocysteine as part of their active site because of its high chemical reactivity. Selenocysteine is incorporated into these proteins co-translationally: biosynthesis occurs on a specific tRNA and insertion into a growing polypeptide is directed by a UGA codon in the mRNA. In E. coli, this requires a specific translation factor. Selenocysteine thus represents a unique expansion of the genetic code.

Animals↗
PubMed1990

Mutagenesis of selC, the gene for the selenocysteine-inserting tRNA-species in E. coli: effects on in vivo function.

The selenocysteine-inserting tRNA (tRNA(Sec)) of E. coli differs in a number of structural features from all other elongator tRNA species. To analyse the functional implications of the deviations from the consensus, these positions have been reverted to the canonical configuration. The following results were obtained: (i) inversion of the purine/pyrimidine pair at position 11/24 and change of the purine at position 8 into the universally conserved U had no functional consequence whereas replacements of U9 by G9 and of U14 by A14 decreased the efficiency of selenocysteine insertion as measured by translation of the fdhF message; (ii) deleting one basepair in the aminoacyl acceptor stem, thus creating the canonical 7 bp configuration, inactivated tRNA(Sec); (iii) replacement of the extra arm by that of a serine-inserting tRNA abolished the activity whereas reduction by 1 base or the insertion of three bases partially reduced function; (iv) change of the anticodon to that of a serine inserter abolished the capacity to decode UGA140 whereas the alteration to a cysteine codon permitted 30% read-through. However, the variant with the serine-specific anticodon efficiently inserted selenocysteine into a gene product when the UGA140 of the fdhF mRNA was replaced by a serine codon (UCA). Significantly, none of these changes resulted in the non-specific incorporation of selenocysteine into protein, indicating that the mRNA context also plays a major role in directing insertion. Taken together, the results demonstrate that the 8-basepair acceptor stem and the long extra arm are crucial determinants of tRNA(Sec) which enable decoding of UGA140 in the fdhF message.

Anticodon↗
PubMed1990

Study of the thymocyte cell cycle by bivariate analysis of incorporated bromodeoxyuridine and DNA content.

The in vivo cell cycle of normal murine thymocytes was studied by bivariate analysis of bromodeoxyuridine and total DNA content in the 24 h following a single injection of the thymidine analogue. Bromodeoxyuridine incorporation was strictly limited to cells in S phase and 98% of S phase cells were labeled, demonstrating high efficiency and specificity. Cell-cycle parameters were determined by measuring the DNA content of bromodeoxyuridine-labeled cells, related to their distribution in the different phases. The changes of this distribution as a function of time reflected the progression of the cells along the cell cycle. The duration of total cycle, S phase, and both G2/M and G1 was 10 h, 6.5 h and 1.5 h, respectively. All thymocytes labeled in S phase entered G2/M, divided and returned to the G0/G1. Seventy percent of them remained in the resting state, and the other 30% re-entered a second S phase. Cell-cycle parameters of isolated CD4-CD8- cells were also determined. No evidence of cell loss during S or G2/M phase was found, suggesting that intrathymic cell death is not directly linked to the proliferative phases of differentiation.

Animals↗
PubMed1990

Accumulation of bromodeoxyuridine-labeled cells in central and peripheral lymphoid organs: minimal estimates of production and turnover rates of mature lymphocytes.

Daily lymphocyte production in both central and peripheral lymphoid organs was evaluated by associating in vivo incorporation of bromodeoxyuridine (BrdUrd) with cell surface labeling and multi-parameter flow analysis. At least 10% of mature T and B lymphocytes are generated every 24 h. The kinetic behavior of these cell populations differs, however, in that mature B cells are generated predominantly in the precursor compartments of the bone marrow, while most mature T cell generation occurs at the periphery. Therefore, peripheral expansion is the major mechanism of mature T cell production in the adult mouse. By following the accumulation of BrdUrd-labeled cells in peripheral lymphoid organs we found that the progeny of the daily lymphocyte production was sufficient to renew 30%-40% of all peripheral T and B cells every 48 h, demonstrating a high turnover rate of mature lymphocytes. We also examined the conditions of BrdUrd labeling of cycling cells in vivo. We found that while greater than 90% of bone marrow and thymus cells in S phase were labeled with a single injection of BrdUrd, in peripheral lymphoid compartments 70% of T and B cells in S failed to incorporate BrdUrd. Particular schedules of BrdUrd administration were required to overcome the low labeling efficiency of mature cells in vivo. Prolonged BrdUrd administration, however, had toxic effects on resident cells. The low labeling efficiency of BrdUrd incorporation by mature cells, as well as its potential toxicity during prolonged administration, may explain controversial results obtained by the different strategies used to study lymphocyte population dynamics.

Animals↗
PubMed1990

A multicenter, double-blind, placebo-controlled trial of the efficacy of prazosin in the treatment of dysuria associated with benign prostatic hypertrophy.

An 8-center, double-blind, placebo-controlled trial of 39 patients with benign prostatic hypertrophy was conducted to assess the effects of prazosin HCl treatment on functional urologic variables after a treatment period of 4 weeks. The randomized groups were comparable for demographic variables and symptoms, except for the mean residual urinary volume, which was significantly higher in the prazosin HCl group. Prazosin HCl elicited statistically significant improvements in the mean prostatic urethral pressure and prostate area (Mann-Whitney U test: p = 0.001 for both variables as compared with the placebo group). Functional bladder capacity also improved significantly in the group receiving the test drug (Mann-Whitney U test: p = 0.05, as compared with the placebo group). Clinical improvements were also observed in the mean maximum urinary flow, decreased nocturia frequency, and residual urinary volume. Patient preference significantly favored the prazosin HCl treatment (Mann-Whitney U test: p = 0.001). Seven patients on prazosin HCl and 5 receiving placebo reported one or more side effects during the trial phase; these were mild to moderate and disappeared or were tolerated. No statistically significant effects on blood pressure or heart rate were observed.

Double-Blind Method↗
PubMed1990

Changes in plasma catecholamine levels after the intraperitoneal and intracerebroventricular administration of adenosine analogues and of clonidine in conscious rats.

When an adenosine analogue, N6-(amido-3-propyl) adenosine hydrochloride (Agr 529) is administered systemically, it causes a substantial release of epinephrine (E) by the adrenal medulla with no change in plasma norepinephrine (NE) levels. Low doses of N6-R-phenylisopropyl adenosine (L-PIA), an agonist of adenosine A1 receptors, has no significant effect on plasma epinephrine levels, which are increased by high doses of the analogue. Low doses of 5'-N-ethylcarboxamido-adenosine (NECA), an agonist of adenosine A2 receptors, however, lead to increases. The intracerebroventricular (icv) administration of Agr 529 leads to a significant decrease in plasma NE without affecting E levels. This action is synergistic with that of clonidine icv. The mechanism of central action of this effect is discussed. It can be admitted that the inhibitory effect of adenosine analogues icv occurs via an inhibition of the posterolateral hypothalamus and the locus coeruleus, although we cannot rule out an action on more rostral-situated brain regions. The authors suggest that the central effect of Agr 529 results primarily from the inhibition of central acetylcholine release caused by adenosine analogues and review experimental arguments enabling this hypothesis to be supported. On the other hand, the considerable release of plasma epinephrine seen when adenosine analogues are administered systemically can be attributed to their stimulation of ACTH secretion by the pituitary and the increase in glucocorticoids in the adrenal medulla, as a result of the existence of the cortico-medullary portal system. These glucocorticoids stimulate phenylethanolamine-N-methyltransferase, which transforms norepinephrine to epinephrine.

Adenosine↗
PubMed1988

Phosphoinositide metabolism and metabolism-contraction coupling in rabbit aorta.

We tested a hypothesis that metabolism-contraction coupling in vascular smooth muscle is controlled by the rate of delivery of energy to ATP-dependent reactions in the inositol phospholipid transduction system that generate second messengers exerting control on smooth muscle force. Rabbit aorta was contracted by norepinephrine (NOR) under conditions of normoxia and hypoxia (bath PO2 less than 40 mmHg), and changes in inositol phospholipid pool sizes and metabolic flux rates (JF) were determined. JF was determined by labeling free cytosolic myo-inositol by incubation of unstimulated muscle with myo-[3H]inositol and then measuring rates of incorporation of this isotope into inositol phospholipids and inositol phosphates when the muscle was activated by NOR. JF measured during maintenance of NOR-induced force was markedly inhibited during hypoxia to 40-50% of that determined during normoxia; rates of increases in inositol phosphate radioactivities were similarly depressed during NOR activation under hypoxia. The hypoxia-induced decrease in JF was associated with four- to fivefold increase in phosphatidylinositol 4-phosphate (PIP) total pool size, suggesting PIP kinase was inhibited and rate limiting. Total pool sizes of phosphatidylinositol, phosphatidylinositol bisphosphate, and phosphatidic acid were unchanged from values seen during activation under normoxia. These data suggest that activation of inositol phospholipid metabolism, which generates inositol 1,4,5-trisphosphate (IP3) and diacylglycerol, is blunted under conditions where aerobic energy production is inhibited. Data are consistent with "rate-limiting" effects of decreased ATP delivery, or decreased phosphate potential, on PIP kinase and reactions that control resynthesis of phosphatidylinositol.

Animals↗
PubMed1986

Psychomaintenance of childhood asthma: a study of 34 children.

Following the study on psychomaintenance of asthma by Kinsman, Dirks, and Jones (1977), we adapted the Battery for Asthma Illness Behavior (BAIB) to children. Thirty-four children aged 9.3 to 15.4 years were tested with this modified BAIB. They were scored simultaneously on a semistructured psychological interview. Three groups emerged out of these data: low-, medium-, and high-panic-fear personalities. Patients were also rated with regard to their pulmonary function and clinical status, including medication prescribed. The high-panic-fear personality was significantly associated with a higher intensity of prescribed medication, in particular corticosteroids. These results were independent of spirometric pulmonary measurements. We conclude that doctors may overreact to the exaggerated distress of high-panic-fear patients. Psychotherapy could be of help for this group.

Adolescent↗
PubMed1984

AMP and IMP binding to glycogen phosphorylase b. A calorimetric and equilibrium dialysis study.

Reaction microcalorimetry and equilibrium dialysis have been used to study the binding of AMP and IMP to glycogen phosphorylase b (EC 2.4.1.1) at 25 degrees C and pH 6.9. The combination of both techniques has enabled us to obtain some of the thermodynamic parameters for these binding processes. Four binding sites were found to be present in the dimeric active enzyme for both AMP and IMP. The binding to two high-affinity sites, which, in our opinion, correspond to the activator sites, seems to be cooperative. The two low-affinity sites, which would then correspond to the inhibitor sites, appear to be independent when the nucleotides bind to the enzyme. The negative delta G0 of binding/site at 25 degrees C is the result in all cases of a balance between negative enthalpy and entropy changes. The large differences in delta H and delta S0 for the binding of AMP to the activator sites (-27 and -70 kJ mol-1; -22 and -150 J X K-1 mol-1) suggest the existence of rather extensive conformational changes taking place in phosphorylase b on binding with the allosteric activator. Whereas the affinity of AMP for the activator sites is about 1 order of magnitude higher than that of IMP, the affinity of both nucleotides, including their delta H and delta S0 values, seems to be the same for the inhibitor sites.

Adenosine Monophosphate↗