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S Picard

Publications and source records attributed to S Picard.

At least 73 records · Page 4Linked to original sources

Effects of C-type natriuretic peptide on rat astrocytes: regional differences and characterization of receptors.

We have compared the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) on the accumulation of cyclic GMP (cGMP) in secondary cultures of rat astrocytes. The order of potency of these peptides was CNP > ANP > BNP, which would be compatible with a predominance of guanylate cyclase B (GC-B)- versus guanylate cyclase A (GC-A)-type receptors in these cells. Accordingly, we found by northern blot analysis that the mRNA transcripts of GC-B were much more abundant in astrocytes than the transcripts of GC-A. In addition, astrocytes from diencephalon accumulated two times more cGMP in response to CNP than astrocytes from cortex. Binding experiments with 125I-labeled ANP or [Tyro]-CNP established that these ligands recognized only clearance-type receptors on astrocytes. However, the number of binding sites was approximately 100 times higher in astrocytes from cortex than in astrocytes from diencephalon and thus was inversely correlated to the amplitude of the cGMP response in the same cells. We found no further evidence for differences in the levels of GC-B receptors in astrocytes from the two regions because (a) the abundance of GC-B mRNA was similar and (b) there was no difference in particulate guanylate cyclase activity in astrocytes from each region. In addition, occupancy of clearance receptors with C-ANP4-23 did not affect the accumulation of cGMP in response to CNP; this makes it unlikely that the differences in cGMP responsiveness can be accounted for by binding and sequestration of CNP to the clearance receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL.

Atherosclerotic lesions contain relatively large quantities of IgG. We have previously shown that both human and rabbit sera contain autoantibodies against epitopes of oxidized (Ox) low-density lipoprotein (LDL) and that LDL isolated from atherosclerotic lesions contains small amounts of tightly bound IgG. However, it is not known whether IgG isolated from atherosclerotic lesions recognizes epitopes present in native LDL or Ox-LDL. IgG was isolated from Watanabe heritable hyperlipidemic (WHHL) rabbit atherosclerotic lesions by sequential salt extractions, purified by fast protein liquid chromatography on protein G, and used in a solid-phase radioimmunoassay. IgG and immune complexes were also isolated from the saline extracts of human lesions by adsorption onto latex beads coated with anti-human IgG antibodies or protein A. IgG isolated from rabbit lesions showed significant titers against malondialdehyde (MDA)-modified LDL and LDL oxidized by copper ions for 4 and 18 hours but not against native LDL. On Western blots, lesion IgG stained MDA-LDL and fragments of Ox-LDL. Western blots of immune complexes isolated from human lesions revealed the presence in the isolated complexes of both apoprotein B and apoprotein B fragments, which reacted with antibodies to MDA-lysine. Furthermore, rabbit lesion IgG immunostained epitopes of Ox-LDL present in human atherosclerotic lesions. Immunostains obtained with rabbit lesion IgG were similar to those obtained with a monoclonal antibody specific for MDA-lysine. The results show that human and rabbit atherosclerotic lesions contain IgG that recognizes epitopes characteristic of Ox-LDL. These data suggest that immunologic processes may be an important component of the atherogenic process.

Adult↗

Development of a therapist activity rating scale: preliminary findings.

A 61-item scale was constructed of relatively explicit descriptions of behavior in which a psychotherapist might engage. The scale is largely noninferential, is basically atheoretical but applicable to psychodynamically oriented therapy, may be completed by either the therapist or an independent rater with minimal training, and may be used to rate entire therapy sessions or specific segments of sessions. The scale shows high interrater reliability and discriminant validity.

Humans↗

Aminoguanidine inhibits oxidative modification of low density lipoprotein protein and the subsequent increase in uptake by macrophage scavenger receptors.

Aminoguanidine decreases the formation of advanced glycosylation end products that occurs during chronic hyperglycemia. Presumably this occurs because early glycosylation products preferentially bind to aminoguanidine rather than to lysine groups of adjacent proteins. Because oxidative modification of low density lipoprotein (LDL) also involves derivatization of lysine residues of apolipoprotein (apo) B by reactive aldehydes formed during the decomposition of oxidized fatty acids, we postulated that aminoguanidine might also inhibit the oxidatively induced modification of LDL protein. To test this hypothesis we oxidized LDL by incubation with Cu2+ or with endothelial cells in the absence or presence of aminoguanidine. Aminoguanidine prevented apo B lysine modification, as measured by fluorescence spectroscopy, and inhibited in a dose-dependent manner the oxidatively induced increase in subsequent macrophage uptake. At concentrations that inhibited apo B modification (5-10 mM), aminoguanidine increased the lag time in diene conjugation but did not affect the plateau value reached. These data indicate that aminoguanidine inhibits oxidative modification of LDL protein in large part by binding reactive aldehydes formed during lipid peroxidation and preventing their subsequent conjugation to apo B. Thus, aminoguanidine (and related compounds) may be of dual benefit in inhibiting atherosclerosis, both by inhibiting formation of advanced glycosylation end products and by inhibiting the modification of LDL apo B that makes it a ligand for scavenger receptors.

Animals↗

[Association of atherosclerosis and nephropathy in diabetes mellitus. Role of lipid anomalies].

Atherosclerosis is the main cause of mortality in diabetic patients, and the incidence of coronary heart disease is increased in the presence of microalbuminuria. The mechanisms of this association are not known and could involve genetic factors (predisposition to hypertension), renal disease and dyslipidemia. An increase in plasma triglyceride and apoprotein B levels, a decrease in plasma HDL cholesterol, qualitative abnormalities of VLDL and HDL are related to cardiovascular risk in diabetic patients. All these factors are worsened by nephropathy. Lipoproteins abnormalities could be involved in the progression of renal injury. In microalbuminuric patients, it seems important to reduce glomerular hyperfiltration and to normalize glycemia and blood pressure in order to prevent impairment of renal injury and dyslipidemia induced by nephropathy. Early treatment of lipoprotein abnormalities could decrease the incidence of cardiovascular complications.

Albuminuria↗

Effect of physiological concentrations of insulin and glucagon on the relationship between nonesterified fatty acids availability and ketone body production in humans.

To determine the effect of insulin and glucagon on the transformation of nonesterified fatty acids (NEFA) into ketone bodies (KB), we measured simultaneously in normal subjects NEFA and KB kinetics at different NEFA levels in the presence of basal (control test) or increasing insulin concentrations with glucagopenia (somatostatin + insulin infusion, insulin test) and without glucagopenia (somatostatin + insulin + glucagon infusion, glucagon test). NEFA levels were controlled during these tests by an intravenous (IV) infusion of a triglyceride emulsion. During the control test, a moderate increase of NEFA (464 +/- 30 to 715 +/- 56 mumol/L) increased the percentage of NEFA converted into KB (13.3% +/- 1.4% to 26.4% +/- 2.1%, P less than .05), and there was a linear relationship between this percentage and NEFA levels (r = .788, P less than .01). During the insulin and glucagon tests, the progressive increase in NEFA induced by the triglyceride emulsion infusion was associated, despite the increase of insulinemia, with an increase in KB production rate (P less than .05) and in the proportion of NEFA used for ketogenesis in the presence (8.1% +/- 1.2% to 14.2% +/- 6.3%, P less than .05) and absence (15.7% +/- 2.8% to 25.2% +/- 3.99%, P less than 0.05) of glucagopenia. In both tests, this percentage was always linearly related with NEFA levels (P less than .05) and the slopes of these relationships were comparable to that observed in the control test. However, the fraction of NEFA used for ketogenesis was always higher (P less than .05) during glucagon substitution than in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Altered expression of inhibitory guanine nucleotide regulatory proteins (Gi alpha) in spontaneously hypertensive rats.

We have recently shown that the stimulatory effects of guanine nucleotides and some agonists on adenylate cyclase activity were diminished in aorta and heart sarcolemma (SL) of spontaneously hypertensive rats (SHR). In the present studies we have examined the activity of GTP-binding proteins (G-proteins) at ADP-ribosylation level, by using pertussis toxin (PT) and cholera toxin (CT) at protein level, by using specific antibodies against Gi (inhibitory) and at mRNA level, by using cDNA probes encoding G-proteins. The labeling of Gi by PT was significantly increased in the aorta and heart SL from SHR as compared to their Wistar-Kyoto control rats (WKY). However, no change in the labeling of Gs (stimulatory) by CT was observed in SHR. Furthermore, immunoblotting experiments using AS/7 antibody which reacts with both Gi alpha-1 and showed an increased immunoprecipitation of Gi alpha-2 in heart SL from SHR. In addition, when the expression of G-proteins was probed at the mRNA levels by Northern blot analysis using cDNA probes, the mRNA levels of Gi2 alpha and Gi3 alpha were significantly enhanced in aorta and heart from SHR. However, the mRNA levels of Gs alpha were not altered in SHR. These results indicate that the gene of Gi and not of Gs is overexpressed in heart and aorta from SHR.

Adenylate Cyclase Toxin↗

Interrelations between ego functions and personality traits: their relation to psychotherapy outcome.

Ninety consecutive admissions to a large outpatient clinic of a municipal hospital completed two self-report questionnaires: the Self-Evaluation Questionnaire (SEQ) which consists of four 10-item scales that assessed four areas of ego functioning; and the 89-item Personality Profile Index (PPI) that provided measures of eight dimensions of personality traits and also a measure of conflict. Results indicated that the four measures of ego functioning had good internal consistency, and three of the four ego functions had a highly similar pattern of relations to the personality trait dimensions and to the conflict measure. It thus appears that each set of constructs amplifies and sheds light on the other. Two of the ego function measures were significant predictors of psychotherapy outcome. They correlated highly with one another and also with a third measure of ego functioning. This fact, together with the similarity of their correlations with the personality traits, suggests that these ego functions represent different aspects of an underlying construct that could be called Ego Strength. Therefore, combining the three ego functions into a 30-item Ego Strength measure could provide an even more sensitive predictor of therapy outcome and a useful new instrument for psychotherapy research.

Adult↗

Sex differences in personality traits and coping styles of hospitalized alcoholics.

Forty inpatients on an alcohol detoxication unit of a large municipal hospital were administered a battery of tests consisting of a Coping Styles scale, a Personality Profile scale, a Depression scale and the Brief MAST. A demographically comparable comparison group of 40 outpatients attending the medical screening clinic at the same hospital also completed the battery. The two groups did not differ in terms of age, education or the ratio of men to women. There were significant differences in coping styles and personality characteristics between alcoholics and nonalcoholics and, to a large extent, between men and women within the alcoholic group. Practically no significant differences were found between the men in the two groups, but female alcoholics differed greatly from nonalcoholic women in terms of coping styles, personality variables and also in terms of conflict. These findings indicate that the differences between alcoholic and nonalcoholics in the sample were due largely to patterns uniquely characterizing the female alcoholic group. Results are discussed in terms of cultural expectations.

Adaptation, Psychological↗

Interactions of glucagon and free fatty acids with insulin in control of glucose metabolism.

To study the interactions of physiological glucagon and free fatty acids (FFA) concentrations with insulin in the control of glucose metabolism, we determined in normal subjects the response of endogenous glucose production (EGP) and glucose utilization (Rd) to a progressive and moderate increase of insulinemia in the presence of glucagon and FFA levels either decreased (somatostatin [SRIF] and insulin infusion, C test) or maintained to normal postabsorptive values isolated (SRIF + insulin + glucagon infusion, G test; SRIF + insulin + Intralipid infusion, IL test) or in association (SRIF + insulin + glucagon + Intralipid infusion, IL + G test). Compared with the C test, maintenance of glucagon level had only small and inconsistent effects on glucose Rd, but induced a shift to the right of the dose-response curve to insulin of EGP (apparent ED50: C test, 10.9 mU.L-1; G test, 15.2 mU.L-1). Intralipid infusion resulted, whether glucagon was substituted or not, in a near total suppression of the insulin-induced increase of glucose Rd (Rd at the end of the tests: C test, 6.13 +/- 0.85 mg.kg-1.min-1; G test, 7.29 +/- 0.87 mg.kg-1.min-1; IL test, 3.30 +/- 0.65 mg.kg-1.min-1; IL + G test, 3.57 +/- 0.42 mg.kg-1.min-1). In the absence of glucagon, substitution Intralipid infusion also antagonized the action of insulin on EGP. However, this effect was no longer apparent when glucagon was replaced (dose-response curve to insulin of EGP during the G and the IL + G test were comparable).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Is there a relation between the seriousness of suicidal intent and the lethality of the suicide attempt?

The relation between the strength of an individual's intent to commit suicide and the nature and seriousness (lethality) of any suicide attempt has been a controversial one. Some studies suggest a positive correlation, while others report no connection. The present investigation included 60 patients, who were studied shortly after they had been admitted to a medical service after a suicide attempt. Measures of depression, impulsivity, suicidal intent, seriousness of the attempt, and efforts to prevent intervention were obtained. Results reveal that both depression and impulsivity correlate positively with the strength of the intent to commit suicide, but there appears to be almost no correlation in this population between measures of intent and seriousness of the attempt.

Adolescent↗

Desensitization of the stimulatory A2 adenosine receptor-adenylate cyclase system in vascular smooth muscle cells from rat aorta.

We have previously shown that adenylate cyclase present in rat aorta vascular smooth muscle cells can be stimulated by adenosine, its analogs and other agonists. In the present studies, we have examined the effect of preexposure of aorta vascular smooth muscle cells to N-ethylcarboxamide adenosine (NECA) on adenylate cyclase activity stimulated by NECA and other agonists. The vascular smooth muscle cells, when exposed to NECA, resulted in a concentration- and time-dependent loss of NECA-stimulated adenylate cyclase activity. NECA stimulated adenylate cyclase activity by about 120% in control cells, which was decreased to 20% in cells pretreated with 50 microM NECA for 30 min at 37 degrees C. However, GTP-, isoproterenol-, and forskolin-sensitive adenylate cyclase activities were not affected by such treatment, suggesting that NECA treatment of the cells resulted in homologous desensitization. Similarly, the exposure of the cells to isoproterenol resulted in the desensitization of isoproterenol-stimulated adenylate cyclase activity without affecting the NECA-stimulated adenylate cyclase activity. Furthermore, when NECA-treated cells were washed free of agonist, the desensitized state was reversed and the cells regained about 75% responsiveness to NECA stimulation of adenylate cyclase.

Adenosine↗

Ethics in the practice of psychotherapy: a survey.

One hundred and one psychotherapists responded to a survey designed to obtain data concerning beliefs about various ethical issues encountered in psychotherapy. Opinions about ethical standards in many areas were quite varied for the entire sample. Differences also emerged when therapists were compared in terms of orientation and years of experience.

Confidentiality↗

19-Hydroxyprostaglandin B2 as an internal standard for on-line extraction-high-performance liquid chromatography analysis of lipoxygenase products.

Variable recovery of polar compounds is a potential pitfall in the on-line extraction-reversed-phase HPLC analysis of lipoxygenase products. Therefore, the addition of a polar internal standard to biological samples, which permits the assessment of the recovery of the polar components in individual samples, appears to be essential. 19-Hydroxyprostaglandin (PG) B2 was found to be a suitable compound for this application. It was easily prepared from deproteinized human semen by base-catalyzed dehydration of 19-hydroxy-PGE2, and purified in a single step by reversed-phase HPLC. Similarly to PGB2, already used as internal in HPLC, 19-hydroxy-PGB2 has excellent chemical stability and carries a strong uv chromophore that enables detection at 280 nm. Most importantly, it is eluted just prior to the polar arachidonic acid metabolites 20-hydroxy- and 20-carboxy-leukotriene B4, 12-oxo-dodecatrienoic acid and the lipoxines A and B. The measurement of the ratio of PGB2 and 19-hydroxy-PGB2 used in combination as internal standards in HPLC analysis of lipoxygenase products, provides a simple and reliable way to assess sample to sample recovery of the polar components when using on-line extraction procedures.

Calcimycin↗

Longitudinal evolution of individuals having appealed their committal to the C.A.S.

The longitudinal evolution of 66 patients admitted between 1976 and 1986 at the Centre Hospitalier Robert-Giffard, and who have appealed their case before the Commission des Affaires Sociales (C.A.S.) was studied. After a review of the literature, the authors compare the evolution of the patients whose appeal was accepted and who left the hospital against medical advice to those individuals whose appeal was rejected. The authors wanted to see if the first group of patients had a less favourable short-term and medium term evolution. From a study of the files and of the case notes prepared by the physicians for the C.A.S. hearings, the authors draw a profile of the typical individual of this group and they study the influence of 16 factors of dangerousness on the Commission's decisions. The results show that the short and medium term evolution of the patients who have appealed their case before the Commission does not differ significantly in the area of dangerousness, whether their appeal was accepted or rejected. However, the length of stay of those patients who had to remain in hospital was significantly longer and that may be the reason why the period of time between their discharge and their re-hospitalization was afterwards much longer. In light of these results, the authors comment on the importance given by the Commission to the legalistic rather than therapeutic aspects of cases.

Adult↗

Comparison of 5- and 15-lipoxygenase activities in blood and alveolar leukocyte preparations from normal subjects and patients with eosinophilia.

The arachidonic acid lipoxygenase metabolites of polymorphonuclear leukocyte (PMNL) preparations obtained from 31 subjects with eosinophilia (eosinophil content of PMNL preparations: 27.0%, 4-73, median with range) and 29 normal donors (4.5%, 0-15) were analyzed by reversed phase high performance liquid chromatography. More leukotriene (LT) C4 and 15-hydroxyeicosatetraenoic acid (HETE) (p less than 0.001) and less LTB4 (p less than 0.005) were found in eosinophil-rich preparations in comparison to controls on incubations with ionophore and arachidonic acid. In incubations with arachidonic acid alone, only small amounts of 5-lipoxygenase metabolites were produced by both groups, but the PMNL preparations from patients with eosinophilia showed higher capacity to release LTC4 and 15-HETE (p less than 0.005). In the eosinophil-rich preparations, the percentage of eosinophils correlated positively with the production of LTC4 and negatively with LTB4 (p less than 0.05, incubations with ionophore +/- arachidonic acid), and positively with 15-HETE (p less than 0.01, incubations with arachidonic acid +/- ionophore). Moreover the eosinophil-rich preparations produced more LTC4 per eosinophil in incubations with arachidonic acid alone (p less than 0.001) than normal PMNL preparations. The predominant release of LTC4 and 15-HETE by eosinophils was further confirmed by the analysis of bronchoalveolar lavage cells. Lavage cells containing eosinophils released LTC4 and 15-HETE while normal bronchoalveolar lavages, which were poor in eosinophils, did not produce detectable amount of LTC4 and 15-HETE. These results show that eosinophils release preferentially LTC4 and 15-HETE in contrast to LTB4 for the neutrophils.

Adolescent↗

Decreased leukotriene B4 synthesis in smokers' alveolar macrophages in vitro.

Recent studies have shown that alveolar macrophages (AM) are able to release leukotrienes (LTs). Since cigarette smoking inhibits the cyclooxygenase pathway of arachidonic acid metabolism in the AM, we evaluated the LT production by AM from smokers and nonsmokers. AM were obtained from 35 volunteers, 16 nonsmokers, and 19 smokers. The cells were incubated under various conditions including stimulation with 30 microM arachidonic acid, 2 microM ionophore A23187, or both. Each experiment was performed in parallel using cells from a smoker and a nonsmoker. Lipoxygenase products were analyzed by reverse-phase high performance liquid chromatography. After stimulation, nonsmokers' AM produced LTB4 and 5-hydroxy-eicosatetraenoic acid (5-HETE). In incubations of AM with arachidonic acid and ionophore, the amounts of products formed were: LTB4, 317 +/- 56 pmol/10(6) cells and 5-HETE, 1,079 +/- 254, mean +/- SEM. No metabolites were generated under control conditions (no stimulation). In all incubations performed, the peptido-LTs (LTC4, LTD4, and LTE4) were undetectable. In comparison with AM from nonsmokers, those from smokers showed a 80-90% reduction of 5-HETE and LTB4 synthesis (P less than 0.05 to P less than 0.001 according to stimulatory conditions). This defective lipoxygenase metabolite production in AM from smokers was observed over a wide range of stimuli concentrations and incubation times; AM from smokers also had lower levels of intracellular (esterified) 5-HETE than nonsmokers' AM. We also studied blood polymorphonuclear leukocytes (PMNL) and no difference in the synthesis of 5-lipoxygenase products in these cells was noticed between smokers and nonsmokers. These data show that cigarette smoking causes a profound inhibition of the 5-lipoxygenase pathway in AM but not in blood PMNL.

Adult↗