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Biomedical subjects

P Leblanc

Publications and source records attributed to P Leblanc.

At least 55 records · Page 3Linked to original sources
PubMed1994

Perception of airflow obstruction and associated breathlessness in normal and asthmatic subjects: correlation with anxiety and bronchodilator needs.

BACKGROUND: Perception of bronchoconstriction varies between individuals and its determinants remain to be identified. The perception of airflow obstruction and breathlessness during induced bronchoconstriction was studied, and the effects of anxiety, repetition of the stimulus, and bronchodilator needs on these measurements were examined in normal and asthmatic subjects. METHODS: Fifteen normal (control) and 25 asthmatic subjects had two consecutive methacholine inhalation tests to induce a 20-50% fall in FEV1. Evaluation of the perceived magnitude of airflow obstruction, breathlessness, level of anxiety generated, and bronchodilator needs was obtained before each FEV1 measurement on a modified Borg scale from 0 to 10. RESULTS: Mean (SE) maximal fall in FEV1 in asthmatic and control subjects was of similar magnitude: test 1, 37.6 (1.4)% and 38.7 (3.1)%, and test 2, 36.0 (1.6)% and 27.7 (2.4)% respectively. There was a large interindividual variation in perception of airflow obstruction and breathlessness but, although they were well correlated in asthmatic subjects, they were perceived differently by the control subjects. Perception of airflow obstruction was greater in asthmatic subjects. The level of anxiety and the bronchodilator use were low and did not influence perception. CONCLUSIONS: During induced bronchoconstriction, the overall perception of airflow obstruction and breathlessness were similar among asthmatic subjects but controls showed a higher perception of airflow obstruction for any given level of breathlessness. Asthmatic subjects perceived airflow obstruction and breathlessness to a greater degree than did controls but anxiety and bronchodilator need were not correlated with respiratory sensation. The variability of bronchodilator use for similar degrees of bronchoconstriction suggests that it may be misleading to assess the severity of asthma control using only this indirect measure.

Adult↗
PubMed1994

Perception scoring of induced bronchoconstriction as an index of awareness of asthma symptoms.

Perception of asthma symptoms shows a wide interindividual variability. Poor perception of airflow obstruction may lead to undertreatment of asthma. We reviewed the possibility of using a simple test to detect poor perceivers of bronchoconstriction as part of the investigation of asthmat. We studied 150 consecutive subjects referred for assessment of airway responsiveness. All had a histamine PC20 within the asthmatic range (< 16 mg/ml) and a fall in FEV1 of < 20 percent after saline inhalation. On histamine challenge, before each FEV1 measurement, perception of dyspnea was assessed on a modified Borg scale. A perception score of breathlessness at 20 percent fall in FEV1 (PS20) was obtained by interpolation of the two last points on the perception/fall in FEV1 curve. It was concluded that in a hyperreactive population, PS20 (1) showed a normal distribution pattern; (2) was similar in both genders; and (3) increased with age due to high postcontrol saline inhalation scores. Hypoperceivers or hyperperceivers were similar for age, sex, baseline FEV1, and PC20. The PS20 determination may be a useful additional parameter to obtain during provocation tests to assess perception of symptoms associated with bronchoconstriction. Its correlation with clinical outcome remains, however, to be determined.

Adolescent↗
PubMed1994

"In situ" characterization of GnRH receptors: use of two radioimagers and comparison with quantitative autoradiography.

New radioimagers, the HRRI (high resolution radioimager) and the Phosphorimager (phosphor screen : PS), apt to display more ample linear dose-response scale than radio-sensitive films, were tested in comparison with quantitative autoradiography (QA). GnRH receptor saturation experiments were achieved on tissue sections (rat pituitary, rat brain, human ovary) with a iodinate GnRH agonist (125I-[D-Ala6,Des-Gly10]-LH-RH Ethylamide) for determination of affinity constant (Kd). In rat pituitary, comparable results were obtained with the 3 methods (Kd: 0.4 to 0.6 nM). Discrepancies occurred in the hippocampus and in the granulosa cell layer of the preovulatory follicle, due to low resolutive (PS) or short linear dose-response (films) performances. In the hippocampus GnRH receptor affinity was under-estimated with PS (Kd: 2.3 vs 0.5 and 0.6 nM for QA and HRRI respectively). In the follicular granulosa cell layer it was over-estimated by QA (0.5 vs 50 nM for the HRRI), while PS did not allow resolution of this thin cell layer. In conclusion, the HRRI is a very powerful tool for the quantification of in situ radioligand binding (binding sites study and in situ hybridization) in very discrete areas.

Adult↗
PubMed1994

Management of bullous disease.

Although emphysema is a "medical disease", the removal of large bullae may be beneficial to some patients. Selection for surgery should be based on careful clinical, anatomic, and functional evaluations. Unfortunately, no single preoperative test is considered to be an accurate predictor of improvement. Additionally, the natural history of unresected bullae is poorly understood because some lesions increase rapidly, whereas others remain unchanged for long periods of time.

Emphysema↗
PubMed1993

Preferential distribution of C-terminal fragments of [hydroxyproline9]LHRH in the rat hippocampus and olfactory bulb.

Several molecular forms related to the decapeptide LHRH were characterized and quantified in various brain structures of intact and castrated male and female rats. Distinct moieties were separated by high performance liquid chromatography (HPLC) and radioimmunoassayed against anti-LHRH antibodies of different specificities. The hypothalamus contained the highest concentration of LHRH-like material detected by the antisera. The predominant (89%) molecular form recovered from that structure was LHRH itself; 9% of the material corresponded to [hydroxyproline9]LHRH ([Hyp9]LHRH), an endogenous posttranslational product of the LHRH precursor, and the residual immunoreactivity was accounted for by C-terminal fragments of both decapeptides, as assessed after labelling HPLC columns with appropriate synthetic or endogenous hypothalamic peptides. The proportions were the same in both sexes and were not affected by castration, in spite of a lesser overall LHRH activity in females and in castrates. LHRH and [Hyp9]LHRH were also detected in the olfactory bulb and the hippocampus. In these structures however, most (97%) LHRH-related molecules corresponded to C-fragments derived from [Hyp9]LHRH, whereas only very few fragments derived from the nonhydroxylated decapeptide were found. Sex or castration affected neither total nor relative concentrations of LHRH-derived molecules in the olfactory bulb and the hippocampus. Taken altogether, these observations are suggestive of a different LHRH metabolic regulation in neurons projecting to either the median eminence or extrahypothalamic areas. In the latter case, larger amounts of the LHRH precursor appear processed to [Hyp9]LHRH. Recovery of relatively high concentrations of [Hyp9]LHRH C-fragments in the olfactory bulb and the hippocampus reflects the higher resistance of the Hyp9-Gly10-NH2 than the Pro9-Gly10-NH2 peptide bond to hydrolysis by the postproline cleaving enzyme. In view of reports that intracerebral administration of C-terminal fragments of LHRH are able to trigger sex behavior, our finding that extrahypothalamic structures contain relatively high concentrations of the [Hyp9]LHRH-derived, more stable C-fragments suggests that these catabolites may have a role in the regulation of sex behavior.

Amino Acid Sequence↗
PubMed1993

Perception of acute or progressive resistive loads in normal and asthmatic subjects.

To determine if the rapidity of increase in airway resistance influences its perception, we looked at the perception of acute and progressive expiratory resistive loads in 9 controls (CN) and 9 asthmatics (AS). Each had 4 single-blind tests in a randomized order, during which resistances were increased from 0 to 24 cm H2O/l/s in 1, 3 or 6 steps or decreased in 6 steps. Dyspnea scores were recorded on a modified Borg scale (0-10). FEV1 and lung volumes were measured in all subjects initially and after the last resistance applied during tests C and D. Tidal volume, respiratory rate, the ratio of inspiratory time over total breathing time (Ti/Ttot) and minute ventilation were measured throughout each test. Borg scores were not significantly different from one test to the other. Overall, AS tended to have a higher perception of resistive loads than CN, although it did not reach statistical significance. FEV1 did not change significantly in both groups between the tests and before and after application of resistances. Functional residual capacity was not significantly different between AS and CN or before and after the tests. Residual volume was higher in AS (mean of the 4 tests: 1.6 +/- 0.05 l) compared to CN (1.1 +/- 0.14 l) (p = 0.003) but was unchanged after the applied resistances. Ti/Ttot ratio was similar for AS and CN and decreased significantly from 0 to 24 cm H2O/l/s in both groups (all tests, p < 0.01). Respiratory rate was higher in CN than in AS at all resistances (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗