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Biomedical subjects

P Leblanc

Publications and source records attributed to P Leblanc.

At least 19 recordsLinked to original sources
PubMed1992

A Ca2+ calmodulin dependent kinase rather than protein kinase C is involved in up-regulation of the LHRH receptor.

Stimulation of protein kinase C (PKC) by phorbol ester (PMA) was reported previously to increase total binding of the peptide in whole rat pituitary cells. The effect could be obtained in cells from intact, not from spayed animals, suggesting a different level of spontaneous phosphorylation in both conditions. In the present work, endogenous PKC was desensitized in pituitary cells sampled from intact or 3 weeks castrated male rats and maintained in primary culture. Desensitization was induced by overnight incubation with 1 microM PMA. The maximum number of plasma membrane LHRH receptors (Bmax) present on cells from in intact animals was higher (+ 98 +/- 9%) when binding was performed at 0.5 degrees C instead of 21 degrees C as already observed in non PKC-desensitized cells. PMA (100 nM) was ineffective to increase Bmax, suggesting effectiveness of enzyme desensitization. In contrast, ionomycin 1 microM increased Bmax (53 +/- 10%). This increment was inhibited by W7, a calmodulin inhibitor, with an IC50 = 1 +/- 0.35 10(-6) M. No temperature dependency of the Bmax was observed in cells from castrated rats as already shown in the absence of PKC desensitization. Under these conditions, a Bmax decrease of 34 +/- 6% and 36.5 +/- 7.5% respectively was observed in the presence of H7, a PKC inhibitor, or of W7 (IC50 = 1 +/- 0.5 10(-5) M and IC50 = 0.8 +/- 0.2 10(-6) M). We conclude that a Ca2+ calmodulin dependent protein kinase rather than PKC itself is responsible for unmasking LHRH receptors.

Animals↗
PubMed1992

A second endogenous molecular form of mammalian hypothalamic luteinizing hormone-releasing hormone (LHRH), (hydroxyproline9)LHRH, releases luteinizing hormone and follicle-stimulating hormone in vitro and in vivo.

In vitro and in vivo release of pituitary hormones were studied in the presence of (hydroxyproline9)LHRH ((Hyp)LHRH), a newly characterized endogenous molecular form of LHRH. Results were compared to those obtained with LHRH itself. (Hyp)LHRH, as LHRH, stimulated both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in a homothetic manner. The hydroxylated compound was, however, 24 times (in vitro) and 5 times (in vivo) less potent than LHRH. The lower activity of (Hyp)LHRH than of LHRH in the in vitro assay correlated well with a 28-fold lesser potency in a binding test using pituitary membrane preparations. The higher relative potency and the prolonged effect of (Hyp)LHRH in the in vivo test were related to a lesser susceptibility of the hydroxylated form to proteolytic degradation. Effects of LHRH and of (Hyp)LHRH were not additive, both peptides were equally able to desensitize gonadotrophs to a subsequent challenge by the other. Taken together, these observations suggest that both forms of LHRH act at the same receptor site. The lesser affinity of the hydroxylated compound is compensated to a certain extent by its higher resistance to enzymatic degradation. It is concluded that in spite of its lesser potency, (Hyp)LHRH may participate in the regulation of gonadotropins.

Animals↗
PubMed1992

Exercise capacity and ventilatory, circulatory, and symptom limitation in patients with chronic airflow limitation.

Dyspnea, leg effort (Borg 0 to 10 scale), ventilation, and heart rate (VEmax/VEcap; HRmax/HRcap expressed as a percentage of capacity) were measured at maximal exercise (cycle ergometer) in 97 patients with chronic airflow limitation (CAL) (FEV, 46.6 +/- 14.23% of predicted) and compared with 320 matched control subjects. Patients with CAL achieved a maximum power output of 86 +/- 39.5 W (60 +/- 23.2% of predicted) compared with 140 +/- 37.5 W (98 +/- 14.5% of predicted) in controls (p less than 0.0001), VEmax/VEcap was 72 +/- 19.3% compared with 53 +/- 18.6% (p less than 0.0001), and HRmax/HRcap was 76 +/- 13.5% compared with 82 +/- 13% (p less than 0.001). These findings were expected. The median intensity of dyspnea was 6 (severe to very severe) and leg effort was 7 (very severe) in both groups, and these findings were unexpected. The patients with CAL were handicapped by an increase in both dyspnea and peripheral muscular effort relative to the actual power output. The rating of dyspnea exceeded leg effort in 25 (26%) of CAL versus 69 (22%) control subjects: the rating of leg effort exceeded dyspnea in 42 (43%) CAL and 117 (36%) control subjects; both were rated equally in 30 (31%) CAL and 134 (42%) control subjects, respectively (NS). VEmax/VEcap and HRmax/HRcap were not significantly different in those limited by dyspnea, leg fatigue, or a combination of both. All values are expressed +/- SD.

Cardiac Output↗
PubMed1992

[New data on a second endogenous molecular form of mammalian hypothalamic LHRH, (hydroxyproline 9) LHRH].

An endogenous hydroxylated form of LHRH, (Hyp) LHRH, is able to displace LHRH bound to pituitary membrane preparations. In parallel, it stimulates release of both LH and FSH from pituitary cells in primary culture. The potency ratio of (Hyp)LHRH is approximately 1:20 and 1:5 with respect to the native decapeptide when peptidasic degradation is or is not inhibited. This correlates with a greater resistance of (Hyp) LHRH towards enzymatic degradation; in contrast to LHRH, the C-terminal (residues 6 to 10) end of (Hyp) LHRH is not degraded and generates C-terminal fragments which account for 64% of the LHRH immunoreactivity in extrahypothalamic areas as the hippocampus. Besides its weak gonadotropin releasing activity and its action or its localization in peripheral organs (placenta, gonads), a major role of the hydroxylated decapeptide may thus be to serve as a precursor of smaller active fragments on targets other than pituitary receptors.

Animals↗
PubMed1991

Junctional region sequences of T-cell receptor beta-chain genes expressed by pathogenic anti-DNA autoantibody-inducing helper T cells from lupus mice: possible selection by cationic autoantigens.

We rescued from the spleens of 10 (SWR x NZB)F1 (SNF1) mice with lupus nephritis the T cells that were activated in vivo and cloned 268 T-cell lines and hybridomas. Only 12% of these T-cell clones had the functional ability to preferentially augment the production of pathogenic anti-DNA autoantibodies. Among these, 16 helper T-cell (Th-cell) clones that were mostly CD4+ and had the strongest autoantibody-inducing ability were analyzed for T-cell receptor (TCR) beta-chain gene usage. Seven of the 16 Th-cell clones expressed beta-chain variable region (V beta) V beta 8 (8.2 or 8.3) genes and three expressed V beta 4, whereas two clones each used a V beta 1 or V beta 2 or V beta 14 gene, suggesting some restriction in TCR gene usage. Although heterogeneous, the V-D-J junctional region sequences of TCR beta-chain genes used by these Th-cell clones invariably encoded one or more negatively charged residues (aspartic or glutamic acid) that had been generated in most cases by unspecified nucleotide (N) additions. Representative pathogenic autoantibody-inducing Th-cell clones could rapidly induce the development of lupus nephritis when injected into young prenephritic SNF1 mice. The pathogenic autoantibody-inducing Th cells expressing the anionic residues in their TCR beta-chain junctions (complementarity-determining region CDR3) were probably selected by some cationic autoantigenic peptide presented by the anti-DNA B cells they preferentially helped. These results offer a clue regarding the nature of the primary autoantigen that may drive the pathogenic autoimmune response in lupus.

Amino Acid Sequence↗
PubMed1991

Bronchoalveolar mast cells in normal farmers and subjects with farmer's lung. Diagnostic, prognostic, and physiologic significance.

To evaluate the specificity and significance of increased lavage mast cells in farmer's lung, we examined the lavage cell differentials of 89 farmers and 19 normal nonfarming control subjects. The farmers were divided into four groups: acute farmer's lung (n = 17), farmers with one or more prior episodes of farmer's lung who remained in daily contact with hay (n = 26) or quit farming (n = 14), and normal farmers (n = 36). A total of 14 of the subjects with prior episodes of farmer's lung and still farming and 15 normal farmers were evaluated twice at a 2-yr interval. The lavage mast cell numbers were significantly higher in acute farmer's lung (7.5 +/- 7.3 x 10(3)/ml, mean +/- SD) and ex-farmer's lung who were still farming (1.2 +/- 1.3 x 10(3)/ml) than in normal farmers (0.1 +/- 0.1 x 10(3)/ml) (p less than 0.01). A total of 8 of 14 exfarmer's lung patients who had quit farming and 18 of 36 normal farmers had an increased number of mast cells in lavage, but mast cell count never exceeded 0.5% of total recovered cells. In the acute farmer's lung and ex-farmer's lung-still farming groups, the mast cell count correlated with the lymphocyte count: r = 0.83 and r = 0.69 (p less than 0.001), respectively. In the two groups evaluated twice, mast cell numbers at the first study did not correlate with changes seen at the second study in chest roentgenogram and pulmonary functions. We conclude that an increase in lavage mast cells occurs commonly as a part of the immune response against thermophilic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

GnRH receptors in rat brain, pituitary and testis; modulation following surgical and gonadotropin-releasing hormone agonist-induced castration.

The regulation of rat gonadotropin-releasing hormone (GnRH) receptors in male rat pituitary, hippocampus and testis was studied, in vivo, under steady-state conditions during treatment with D-Trp6 GnRH (triptorelin, slow-release form, at 300 micrograms/kg/month). GnRH receptors were characterized on tissue sections by quantitative autoradiography using 125I-GnRHa as a tracer. Castrating doses of triptorelin strongly down-regulated pituitary GnRH receptors (50% of reduction after 8 h, 80% on days 1-30); in contrast, only a transient decrease (20% at 8 h) was observed in the hippocampus with a rapid return to control levels. Triptorelin induced a marked (2-fold) increase in GnRH receptors in testicular interstitial tissue during 5 days with a return to control value by day 20. Administration of a GnRH antagonist (BIM 21009, 1 mg/kg/24 h) induced a rapid reduction of pituitary and testicular receptors to undetectable levels at 24 h, while hippocampal receptors were strongly reduced only. This indicates that GnRH receptors with similar pharmacology are differently controlled in various tissues and that brain receptors are likely to be also regulated by GnRH agonists and antagonists.

Animals↗
PubMed1988

Inspiratory muscles during exercise: a problem of supply and demand.

The capacity of inspiratory muscles to generate esophageal pressure at several lung volumes from functional residual capacity (FRC) to total lung capacity (TLC) and several flow rates from zero to maximal flow was measured in five normal subjects. Static capacity was 126 +/- 14.6 cmH2O at FRC, remained unchanged between 30 and 55% TLC, and decreased to 40 +/- 6.8 cmH2O at TLC. Dynamic capacity declined by a further 5.0 +/- 0.35% from the static pressure at any given lung volume for every liter per second increase in inspiratory flow. The subjects underwent progressive incremental exercise to maximum power and achieved 1,800 +/- 45 kpm/min and maximum O2 uptake of 3,518 +/- 222 ml/min. During exercise peak esophageal pressure increased from 9.4 +/- 1.81 to 38.2 +/- 5.70 cmH2O and end-inspiratory esophageal pressure increased from 7.8 +/- 0.52 to 22.5 +/- 2.03 cmH2O from rest to maximum exercise. Because the estimated capacity available to meet these demands is critically dependent on end-inspiratory lung volume, the changes in lung volume during exercise were measured in three of the subjects using He dilution. End-expiratory volume was 52.3 +/- 2.42% TLC at rest and 38.5 +/- 0.79% TLC at maximum exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Characterization and distribution of receptors for gonadotropin-releasing hormone in the rat hippocampus.

Distribution and properties of receptors for gonadotropin-releasing hormone (GnRH) were analyzed in the brain of adult male rats. Binding of the iodinated GnRH agonist Des-Gly10-(D-Ala6)-GnRH ethylamide was studied in hippocampus and anterior pituitary using three convergent approaches: quantitative autoradiography on frozen tissue, binding to fresh slices, and binding to crude membrane preparations. In all cases, binding was specific, saturable, and time, pH, and temperature dependent. Quantitative autoradiography revealed that the density of binding sites was high in the stratum oriens and stratum radiatum of the CA1-CA4 regions of Ammon's horn. The pyramidal cell layer was faintly labelled. Binding was almost undetectable in the dentate gyrus. The highest density of sites (Bmax = 11.6 +/- 1.0 fmol/mg protein) was observed in the stratum radiatum of the CA3 region. Under the same conditions the value obtained for pituitary tissues was 20.7 +/- 2.8 fmol/mg protein. Analysis of saturation curves indicated only one class of high-affinity sites for the hippocampus (CA3; Kd = 0.28 +/- 0.03 nM) and for the pituitary (Kd = 0.29 +/- 0.08 nM). Both native GnRH and GnRH antagonist were potent competitors of binding. Fresh slices and membrane preparations from whole hippocampus confirmed these autoradiographic data and yielded affinity constants of 0.28 +/- 0.01 and 0.52 +/- 0.08 nM, respectively. In addition, a very high binding density was present in the amygdaloid complex, while binding was barely detectable in the hypothalamus. These results demonstrate that high densities of specific GnRH receptors are present in areas concerned with the regulation of behavioral functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

[Dysgerminoma of the ovary. Current diagnosis and therapy].

From a review of the literature, the authors present some new facts on the diagnosis of ovarian dysgerminoma, as well as a therapeutic protocol for the treatment of extended forms, as well as the conservative treatment of localized forms in women wishing to become pregnant.

Dysgerminoma↗
PubMed1987

Variations of phospholipid methyltransferase(s) activity in the rat pituitary: estrous cycle and sex differences.

We previously demonstrated a specific stimulatory action of estrogens on phosphatidylethanolamine methylation in rat pituitary membranes. To investigate the physiological relevancy of this effect, the activity of methylating enzyme(s) was evaluated during the rat estrous cycle, a period in which both endogenous ovarian steroid levels and the sensitivity of pituitary membrane receptors fluctuate. Anterior pituitary membranes (P2) were prepared from adult female rats at different stages of the estrous cycle and assayed for phospholipid methylation in the presence of S-adenosyl-[methyl-3H]methionine as a donor of 3H-methyl groups. Methylated phospholipids were separated by TLC. Formation of phosphatidyl-mono- and dimethylethanolamine and that of phosphatidylcholine increased significantly in the morning, reaching maximal values on the afternoon of proestrus; they decreased thereafter during estrus, metestrus, and diestrus. Plasma estradiol concentrations increased in late diestrus and then varied similarly with the fluctuations of phospholipid methyltransferase activity throughout the cycle. In parallel, plasma levels of LH and PRL were significantly elevated during the afternoon of proestrus, but remained low throughout the rest of the cycle. Under the same experimental conditions, phospholipid methylation in membranes prepared from mediobasal-hypothalamic structures was not affected. These data demonstrate that under physiological conditions the increased pituitary methyltransferase activity is associated with the progressive increment of plasma estradiol levels occurring shortly before proestrus and precedes the release of LH and PRL. Ovariectomy significantly decreased methyltransferase activity; however, 17 beta-estradiol treatment of ovariectomized rats for 5 days restored the enzyme activity, which was further augmented after progesterone administration. Attempting to investigate variations of pituitary methyltransferase activity in male rats, we demonstrated that the intact males showed weaker activity than that of females; orchidectomy diminished the phospholipid methylation, but adrenalectomy had no effect.

Adrenalectomy↗
PubMed1987

[Low transverse laparotomy with rectus abdominus section in gynecology and obstetrics. Apropos of 1,000 cases].

The authors report 1,000 cases (357 cesarean sections, 230 hysterectomies for benign lesions, 157 conservative utero-adnexal procedures, 128 tubal plasties, 58 prolapse or incontinence procedures, 70 cancers) ,of laparotomies performed according to the technique described by Mouchel in 1980, i.e. strictly supra-pubic and transverse, from skin to peritoneum, including section of the rectus abdominis. This incision enables to perform in ideal technical conditions, with a minimal complication rate (3 hematomas, 2 incisional hernias for 1,000), and satisfactory esthetic results, almost all of the gynecological and obstetrical surgical procedures (90% of two among the authors' practice). The only contra-indications are, except for cases of previous median laparotomy, ovarian tumors. Neither the high risk of infection, nor obesity, extended hysterectomy, nor fetal distress, represent contra-indications, which is a definite advantage over the Pfannenstiel incision. As compared with the median incision which at some time offered similar results, the esthetics and mainly the strength of the abdominal wall are markedly superior.

Abdominal Muscles↗
PubMed1987

[Demonstration and topographical distribution of LHRH receptors in the central nervous system in the normal and castrated male rat].

The topographical distribution of [125I]-LHRH binding sites was studied on brain sections of adult male rat by quantitative autoradiography. High density of sites was observed in the hippocampus, amygdala and entorhinal cortex (4-7 fmol of LHRH bound/mg protein). Lower density of sites was observed in the septum and frontal cortex. The receptor density was not significantly modified at day 5 following castration. Under the same conditions the pituitary receptors were significantly increased. The presence of specific LHRH binding sites in the limbic system may explain the behavioural effect observed following intracerebroventricular injection of LHRH. However, their functions under physiological conditions remain to be elucidated.

Animals↗
PubMed1986

Relationships between radiographic change, pulmonary function, and bronchoalveolar lavage fluid lymphocytes in farmer's lung disease.

Ninety four dairy farmers were investigated by chest radiography, pulmonary function tests, and bronchoalveolar lavage. They were divided into five groups--1: 11 subjects with acute farmer's lung; 2: 25 subjects with previously diagnosed farmer's lung who had stayed on their farm; 3: 15 farmers with previously diagnosed farmer's lung who had left the farm; 4: 23 precipitin positive symptomless farmers; 5: 20 precipitin negative symptomless farmers. The study evaluated the relationships between radiographic changes measured with a scoring system derived from the International Labour Office (ILO) classification, the results of pulmonary function tests, and bronchoalveolar lavage fluid. Thirty eight subjects had radiographic evidence of interstitial pulmonary infiltrates. Group 1 had the highest percentage of lymphocytes recovered by bronchoalveolar lavage (mean 66.3 (SD 19.2]. For all subjects carbon monoxide transfer factor (TLCO) and total lung capacity were negatively correlated with radiographic changes (r = -0.45 and -0.30; p less than 0.001 and less than 0.01 respectively). TLCO was also negatively correlated with radiographic change in group 2 (r = -0.59, p less than 0.005). The percentage of lavage lymphocytes was correlated with radiographic changes for all subjects (r = 0.36, p less than 0.001), but this correlation was not seen within groups. This study shows good correlation between radiographic abnormalities, pulmonary function changes and the cellular composition of bronchoalveolar lavage fluid.

Adolescent↗
PubMed1986

Breathlessness and exercise in patients with cardiorespiratory disease.

Previous studies have led to the revival of the hypothesis that breathlessness is the perception of respiratory muscle effort and is present when the tension developed by muscles increases, when the muscles are weak, or when both conditions are present simultaneously. Using a category scale, the intensity of breathlessness was measured in 20 subjects (2 normal subjects and 18 patients) undergoing an incremental exercise test (50 to 100 kpm/min) to maximal capacity. The patients were selected to provide a heterogeneous group of pulmonary diseases, obesity, muscular weakness, and cardiac disease, with a wide variability in exercise capacity (250 to 1,900 kpm/min) and severity of dyspnea. Maximal inspiratory pressure (MIP), pleural pressure (Ppl), the extent of shortening of the inspiratory muscles as indicated by the tidal volume expressed as a percent of vital capacity (VT/VC), the rate of shortening as indicated by flow rate, the frequency of contraction as indicated by breathing frequency (fb), and the duty cycle (TI/Ttot) were measured throughout exercise to assess their relative contribution to the intensity of breathlessness. Using multifactorial analysis, the perception of breathlessness was significantly (p less than 0.01) related to the Ppl, inspiratory flow rate (VI), VT/VC, TI/Ttot, and fb. A multiple linear regression equation that included all these variables explained 69% of the variance, with no single factor being identified as uniquely predominant: Breathlessness = 3.0 (Ppl/MIP) + 1.2 (VI) + 4.5 (VT/VC) + 0.13 (fb) + 5.6 TI/Ttot) - 6.2 (R = 0.83). The intensity of effort required to produce a given pressure increases when the muscle is weak, when the velocity of contraction increases, or when the muscle shortens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Estradiol activates methylating enzyme(s) involved in the conversion of phosphatidylethanolamine to phosphatidylcholine in rat pituitary membranes.

17 beta-Estradiol (E2) affects the sensitivity of pituitary cells to several neurohormones as LHRH, TRH, or dopamine, presumably by modulating receptor coupling mechanisms. We attempted to pinpoint the membrane processes underlying this modulation and studied the effect of E2 on pituitary membrane phospholipid methylation. Anterior pituitary membranes prepared from ovariectomized (ovx) or ovx plus E2-treated rats were assayed for phospholipid methylation. Methylated phospholipids were separated by TLC. Incorporation of [3H]methyl groups into phospholipids increased with membrane concentration and incubation time with S-adenosyl-L-methyl [3H]methionine; it was not Mg2+ dependent and was inhibited in a dose-dependent manner by S-adenosyl-L-homocysteine, methyltransferase inhibitor. pH was found to be critical. Formation of phosphatidyl-monoethanolamine, phosphatidyl-dimethylethanolamine, and phosphatidylcholine was markedly stimulated by treatment with E2. The effect increased progressively when animals were killed 15 h to 5 days after E2 implantation. The response involved a shift in the maximum velocity (Vmax) although there was no change in the available substrate for the methylating enzyme. This change in Vmax probably reflects changes in the amount of the methylating enzyme itself. Administration of 17 alpha-estradiol, an inactive stereoisomer of E2 was ineffective, pointing to a stereospecific interaction. After differential centrifugation of pituitary membranes, the highest specific methyltransferase activity was found in light mitochondrial (L) and microsomal (P) fractions and the lowest in nuclei (N) and the heavy mitochondrial (M) fractions. After sucrose density gradient centrifugation, methylated phospholipids were preferentially recovered from fractions corresponding to the endoplasmic reticulum and/or secretory granules. E2 treatment for 5 days did not modify the subcellular distribution of methyltransferase activity but stimulated it in all fractions; in contrast, it did not modify the activity of the other enzymes measured as fraction markers. Under the same experimental conditions, phospholipid methylation in membranes prepared from cortex, and anterior and mediobasal hypothalamic structures was not affected by the steroid, with the exception of a slight increment of [3H]methyl incorporation into mediobasal hypothalamic membrane phospholipids after 5 days of E2 treatment. These results indicate that E2-induced changes in pituitary responsiveness might be concomitant with selective effects of the steroid on specific membrane enzymatic activities involved in coupling mechanisms.

Animals↗