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Biomedical subjects

F Girard

Publications and source records attributed to F Girard.

At least 145 records · Page 8Linked to original sources

Inhibition of cortisol production in isolated guinea-pig adrenal cells.

Cortisol, added to 1 ml incubation medium containing 3-4 X 10(5) isolated guinea-pig adrenal cells, provoked a decrease in basal and ACTH (250 pg)-stimulated cortisol production, in correlation with the amounts used (50 ng-2,000 ng). A decrease in aldosterone production could be seen when cortisol concentrations reached or exceeded 1,000 ng/ml. There were no variations in either androgens (delta 4-androstenedione, dehydropiandrosterone) or 17-hydroxyprogesterone. Only 11-deoxycortisol was slightly increased. Using increasing concentrations of ACTH (50-250 pg), both in the absence and in the presence of 1,000 ng cortisol, it was noted that the inhibition induced by cortisol was of a competitive type and could be overcome by ACTH. This decrease in cortisol was concomitant with an increase in 11-deoxycortisol. Neither corticosterone nor dexamethasone reduced cortisol production. In addition, it was shown that the conversion of tritiated 11-deoxycortisol to radioactive cortisol increased significantly under the influence of 250 pg ACTH (mean relative variation of 21.7% +/- 7.7 (SEM), n = 6, P less than 0.05); but decreased significantly under the combined effect of 1,000 ng exogenous cortisol and the same dose of ACTH: (mean relative variation of 4.3% +/- 1 (SEM), n = 8, P less than 0.005). There is therefore reason to believe that the concentrations of cortisol at the adrenal level modulate the stimulation induced by ACTH and that this self-adjustment forms part of the control mechanisms involved in corticosteroidogenesis.

Adrenal Glands↗

Simultaneous evaluation of the catecholamine pathway and three opioid peptide-producing systems in human pheochromocytomas.

Tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) activities, dopamine (DA), noradrenaline (NA), adrenaline (A), met 5-enkephalin (Met-Enk), leu5-enkephalin (Leu-Enk), dynorphin (Dyn) and beta-endorphin (beta-end) were measured simultaneously in ten human pheochromocytomas = 1 - TH activity was highly variable, from 22 to 2220 U/g tissue. 2 - DBH activity, in contrast, was rather constant, from 96 to 582 U/g. 3 - Catecholamines (A and NA) concentrations showed only small variations. 4 - The four opioid peptides were detected in all cases and exhibited a wide range of tissue concentrations (Enk much greater than Dyn greater than beta-end). 5 - Met-Enk and Leu-Enk concentrations were highly correlated; no correlation was observed with the other opioid peptides. 6 - A very strong correlation was observed between enkephalins concentrations and both catecholamines concentrations and DBH activities. These results are discussed in term of the significance of the co-localization of these various biologically active substances, principally with regard to the possible regulation of catecholamine synthesis by opioid peptides and conversely.

Adrenal Gland Neoplasms↗

Lung mechanics and breathing pattern during wakefulness and sleep in children with enlarged tonsils.

Thirteen children (mean age, 45 months) with nocturnal symptoms of upper airway obstruction, the result of enlarged tonsils, were tested during wakefulness (W) and sleep (S) induced by chloral hydrate (less than or equal to 50 mg/kg). During W, lung mechanics, blood gas, breathing pattern, and airflows during tidal breathing were in the normal range. During S, total lung resistance increased significantly, and dynamic lung compliance and transcutaneous PO2 decreased significantly. During S, the tidal volume (VT) and the mean inspiratory flow, normalized for body weight (BW), decreased whereas the ratio of the inspiratory time (TI) over the total duration of the respiratory cycle (TTOT) rose, indicating a longer contraction time of the respiratory muscles. The time to reach peak inspiratory flow, measured as a percentage of TI (dTI/TI), increased in seven children, with no change in the ratio of the expiratory flow over the inspiratory flow, both measured at 50% of VT (EF50/IF50). In three other patients dTI/TI decreased with an increase in EF50/IF50. We conclude that in children with enlarged tonsils, S modified lung mechanics, gas exchange, and the inspiratory components of the breathing pattern and airflow.

Airway Obstruction↗

Molecular forms of beta-endorphin in ACTH/LPH hypersecretion syndromes in man.

beta-Endorphin31, beta-endorphin1-27, and their alpha-N-acetyl derivatives were specifically separated by ion exchange chromatography from human beta-endorphin-'like' material obtained from extracts and culture media of corticotropic adenomas and extract of plasma from Nelson's syndrome and ectopic ACTH/LPH syndrome. Studies with pituitary-derived materials have shown that human beta-endorphin1-31 was the major form and human beta-endorphin1-27 a minor form. No other peptide was detected. In plasma from the ectopic ACTH-LPH syndrome human beta-endorphin1-31 was the only detected peptide. In 2 such patients with chronic elevation of human beta-endorphin1-31 the pain sensitivity threshold was normal and naloxone induced no modification, suggesting that circulatory human beta-endorphin has no effect on the central nervous system.

ACTH Syndrome, Ectopic↗

Effects of cyproterone acetate on adrenal steroidogenesis in vitro.

The effects of cyproterone acetate (CA) on steroidogenesis in isolated guinea-pig adrenal cells have been investigated by measuring the production of cortisol, its immediate precursors (11-deoxycortisol and 17-hydroxyprogesterone), and adrenal androgens (delta 4-androstenedione and dehydroepiandrosterone). Used at a dose of 2 micrograms/ml, CA provoked a sharp drop in the production of cortisol, aldosterone and 11-deoxycortisol. By contrast, 17-hydroxyprogesterone, delta 4-androstenedione and dehydroepiandrosterone were increased, which suggests that 21-hydroxylase activity is inhibited. With concentrations above 2 micrograms/ml CA, it would seem to be the 3-beta-ol-dehydrogenase-delta 4,5-isomerase complex that is affected, since dehydroepiandrosterone exhibited a sudden increase, whereas 17-hydroxyprogesterone and delta 4-androstenedione showed a relative decrease. The enzymatic system or systems involved therefore appear to be linked to the concentration of CA used but, whatever the case, the drop in cortisol production is accompanied by a decrease in aldosterone and an increase in adrenal androgen levels.

Adrenal Cortex Hormones↗

The new steroid analog RU 486 inhibits glucocorticoid action in man.

RU 486 [17 beta-hydroxy-11 beta-(4- dimethylaminophenyl )-17 alpha-(prop-1- ynyl )-estra-4,9-dien-3-one] is a new steroid analog which antagonizes glucocorticoid action at the receptor level in animals. To assess its potential antiglucocorticoid activity in man we studied the pituitary-adrenal response to RU 486 in normal men. The compound was administered at 0200 h and plasma cortisol and lipotropins (LPH) were measured hourly for 10 h. After 400 mg RU 486 significant and sustained elevation of both hormones occurred during the 0700-1200 h period: mean (+/- SE) plasma levels after placebo or RU 486 during this interval were, respectively, for cortisol (ng/ml), 63.4 +/- 8.2 and 112.7 +/- 2.9 (P less than 0.02); and for LPH (pg/ml), 34.8 +/- 11.3 and 71.6 +/- 15.4 (P less than 0.01). The 200- and 100-mg doses induced only transient cortisol and LPH increases. Administration of RU 486 (400 mg) at 1400 h induced no increase in plasma cortisol compared to placebo in the corresponding 2000 to 2400 h period. When RU 486 was administered concomitantly with dexamethasone (1 mg) at 2400 h, dose-dependent blockade of the dexamethasone-induced cortisol suppression at 0900 h was found (r = 0.62, P less than 0.01); this blockade was partial after the 100-mg dose, but complete after the 400-mg dose. Plasma LPH and ACTH showed parallel variations. We conclude that RU 486 antagonizes the negative pituitary feedback of both the nocturnal endogenous cortisol rise and exogenously administered dexamethasone. These actions are consistent with an antiglucocorticoid activity of this compound in man.

Adrenocorticotropic Hormone↗

Serum levels of insulin-like growth factor (IGF) and IGF binding protein in constitutionally tall children and adolescents.

Serum insulin-like growth factor (IGF) and IGF binding protein (BP) levels were studied in 89 constitutionally tall children and adolescents (height greater than mean for age + 3 SD in 90% of the subjects). After separation by acidic gel filtration, the samples were assayed for IGF using a protein-binding assay (which measures mainly IGF I-related peptides) and for IGF BP by titration, in both cases using IGF I as tracer. The reference standard was a pool of normal adult serum with an assigned potency of 1 U IGF and 1 U IGF BP/ml. IGF levels increased with age in a manner similar to that in normal subjects, but at higher concentrations (P less than 0.02). The values were 0.77 +/- 0.05 (SE) U/ml in 1- to 5-yr-old children, 0.96 +/- 0.08 U/ml in 5- to 11-yr-old prepubescent children and 1.51 +/- 0.07 U/ml during puberty. BP levels developed in a different way from the above in that the increase with age was slight (0.70 +/- 0.07, 0.67 +/- 0.09, and 0.97 +/- 0.07 U/ml, respectively, for the three periods considered) and the levels were lower than those of normal subjects (P less than 0.005). After fusion of the epiphyses both IGF and BP levels were within the range of normal values. Thirteen girls underwent prolonged treatment (mean, 26 months) with ethinyl estradiol (250-300 micrograms/day). Deceleration in growth was accompanied by a progressive decrease in IGF levels throughout the period of therapy and a rise in BP levels during the first 6 months, after which they stabilized within the range of normal values. Although it is possible that excessive secretion of GH (which was not demonstrated by the usual tests) may be the cause of the elevated IGF levels during growth in these constitutionally tall subjects, it seems likely that the high IGF levels combined with the abnormally low levels of BP were responsible for their excessive growth.

Adolescent↗

Comparison of transcutaneous and alveolar partial pressure of carbon dioxide during carbon dioxide breathing in healthy children.

In 18 healthy children three to 13 years of age, the transcutaneous partial pressure of carbon dioxide (PtcCO2) (Radiometer electrode) and the alveolar partial pressure of carbon dioxide (PACO2) (Beckman analyzer) were measured simultaneously during the breathing of room air and 5 percent carbon dioxide. The PtcCO2 electrode was placed on the anterior thorax and heated to 42 degrees C. The PACO2 was calculated on the 4/5 part of the carbon dioxide expired trace. Minute ventilation (VE) was measured in 11 cases. There was a significant correlation between PtcCO2 (in millimeters of mercury) and PACO2 (in millimeters of mercury) while breathing room air (PtcCO2 = 0.82 PACO2 + 19.7; r = 0.55; p less than 0.02) and while breathing 5 percent carbon dioxide (PtcCO2 = 0.77 PACO2 + 22.5; r = 0.61; p less than 0.01); however, the ratio of PtcCO2 over PACO2 was significantly lower while breathing 5 percent carbon dioxide (p less than 0.01) than while breathing room air. When considering the relationship between the increase in VE (delta VE while breathing 5 percent carbon dioxide and the changes in PACO2 (delta PACO2) or in PtcCO2 (delta PtcCO2), a significant correlation was found only between delta VE and delta PACO2, ie, delta VE = 0.41 delta PACO2 + 0.44 (r = 0.63; p less than 0.01). These results suggest that breathing carbon dioxide modified the factors acting on PtcCO2, possibly by changes in the vasomotor tone of cutaneous blood vessels. These modifications appeared to be variable from subject to subject. Therefore, we conclude that PtcCO2 does not appear to be an accurate quantitative index to assess ventilatory response to carbon dioxide.

Adolescent↗

[Lipotropins (beta- and gamma-LPH). Valid indicators of corticotropic function].

Plasma levels of ACTH and LPH which derive from a common precursor, were determined simultaneously to study the value of LPH as a marker of the corticotropic function, and evaluate its advantage over that of ACTH plasma determination. ACTH and LPH plasma levels were measured: a) in control subjects under basal conditions and after dynamic explorations of the corticotropic axis. Furthermore, in some control subjects plasma LPH levels were measured after a 24 h incubation in blood at room temperature; b) in the venous and arterial blood of the kidney of subjects in whom a nephrectomy of a perfused and functional kidney was to be performed; c) in patients either under hemodialysis for chronic renal failure, or with adrenal insufficiency due to a primary adrenal failure or secondary to a corticotropic deficiency. This study permitted to establish: a) the normal values of basal plasma hormone levels (ACTH less than 10-80 pg/ml, LPH less than 20-200 pg/ml 8-9 a.m.) and to confirm their parallel secretions in physiological conditions; b) the stability of the LPH in blood at room temperature, whereas ACTH is rapidly destroyed in the same conditions; c) the primordial role of the kidney in the LPH catabolism; d) the value of LPH determinations in the diagnosis of primary adrenal insufficiency and corticotropic deficiency. Thus, except for the known situations where ACTH and LPH plasma levels are dissociated, the LPH plasma levels either basal or after dynamic explorations of the corticotropic axis, provide a reliable index of the corticotropic function.

Addison Disease↗

Lung function in children with hypersensitivity pneumonitis.

Pulmonary function tests were performed on 12 children with hypersensitivity pneumonitis (HP) aged from 4-15 years (10 with bird breeder's lung and 2 with farmer's lung). Lung volumes, lung mechanics (lung resistance, dynamic lung compliance (CLdyn], lung transfer factor for CO (TLCO), and blood gases were measured. Eleven children ceased to be exposed to the antigen, and the functional course was studied as a function of time after the cessation of exposure (CE). During the short term (less than 2 months after CE) initial hypoxemia was observed and CLdyn and TLCO were below normal. Two months after CE, blood gases were normal in most of the cases. A persistent hypoxemia appeared to be an unfavorable prognostic factor. CLdyn was normal by the eighth month after CE, while TLCO improved more slowly and remained significantly decreased in one case. In our series the children under 10 years had less functional abnormalities and normalized more rapidly than the older children. The one child without CE, had major functional abnormalities.

Adolescent↗

Influence of inhaled cadmium microparticles on mouse influenza pneumonia.

A study of the effect of inhaled cadmium microparticles (CdO) on the mouse death rate from influenza pneumonia was performed on 936 female specific pathogen-free (SPF) Swiss mice. The test animals received a single short (15 min) exposure to 9 mg Cd/m3 of air (acute exposure), or renewed short exposures to 1 mg/m3 once a day, 5 days a week, for 4 weeks (chronic exposure). The cadmium found in the trachea-bronchus-lung area was about 5 micrograms/g of fresh tissue at the end of acute exposure, and 4 micrograms/g at the end of chronic exposure. The viral challenge was performed 48 hr after acute exposure, or on the 14th day after the beginning of chronic exposure, the mice being reexposed to Cd for an additional 14 days in the latter case. Surprisingly, the infectious death rate of test mice was significantly lower than that of controls, both for acute and chronic exposure to CdO. These results are discussed.

Aluminum Oxide↗

Structure-activity studies on neurobehavioral effects of bombesin (BB) and gastrin releasing peptide (GRP).

In the present study, we evaluated and compared effects of BB, GRP and related C-terminal fragments on body temperature and grooming. Peptides were administered into the left cerebral ventricle of rats. Body temperature and grooming behavior were assessed over a 2 hr period following injections. All peptides significantly decreased body temperature and increased grooming behavior of animals. However, important differences in potency, efficacy and duration of action were found between BB, GRP and their fragments.

Amino Acid Sequence↗

Peptides related to the NH2-terminal end of proopiocortin in man.

Peptides related to the NH2-terminus of proopiocortin in man were studied with three different RIAs directed toward gamma 3MSH, human 16K, and mouse 16K. The culture medium derived from a human corticotropic adenoma (SCH medium), which had previously been used as a human reference standard, generated competitive binding curves parallel to that of purified human 16K in all three RIA systems. Gel exclusion chromatography performed with pituitary-derived materials (adenoma extract and medium, and plasma from patients with Nelson's syndrome) showed that the overall immunoreactive gamma 3MSH eluted as one major peak at the position of human 16K. Its molecular weight estimated under denaturing conditions was 11,000. Gel exclusion chromatography performed with nonpituitary-derived materials (tumor extract and plasma from patient with the ectopic ACTH syndrome) showed that a major peak eluted at the position of human 16K, and a smaller molecular weight peptide eluted in a position intermediary between that of human 16K and synthetic gamma 3MSH. These data show that immunoreactive gamma 3MSH is indeed identical to human 16K in pituitary-derived materials. A different processing of the proopiocortin molecule is likely to occur in nonpituitary tumors and will result in the release of a smaller molecular weight peptide. The exact nature of this peptide is not known. It is speculated that it may serve as a nonpituitary tumor marker.

Adenoma↗

Plasma lipotropin increase in man after growth hormone administration. Comparison between extractive and biosynthetic hormones.

The action of human growth hormone (hGH) on plasma lipotropins (beta-and gamma-LPH) in 15 GH deficient patients was studied by comparing the effects induced by the acute administration of the extracted and biosynthetic molecules. The purified extracted preparation (6 mg/m2 im) induced a dramatic rise in plasma LPH: basal (49 +/- 12 pg/ml (mean +/- SEM); peak 1,658 +/- 262 pg/ml. The same dose of biosynthetic methionyl-hGH (met-hGH) induced no significant change in plasma LPH. Both preparations caused identical plasma GH increases. Six different commercially available extracted hGH preparations (Choay, France; Serono, Italy; France Hypophyse, France; Kabi, Sweden; Nordisk, Denmark; International Standard, Great Britain) all showed definite cross-reactivity in the LPH radioimmunoasay, varying from 0.1 to 1.0%, on a weight basis. No cross reactivity was found with met-hGH (less than 0.0001%). On gel exclusion chromatography, the LPH immunoreactivity of the purified preparations was dissociated from the GH immunoreactivity and eluted at the position of beta-and gamma-LPH. These data show that extracted hGH preparations are all contaminated with LPH and raise the question of the possible consequences of chronically elevated plasma LPH in treated patients. The use of biosynthetic met-hGH should prevent this occurence.

Adolescent↗

Opposite effects of inhaled cadmium microparticles on mouse susceptibility to an airborne bacterial and an airborne viral infection.

An experimental study on 489 mice is reported. The test animals were submitted to a single 15-mn exposure to atmosphere containing about 10 mg of cadmium microparticles (CdO) per m3 of air and the controls to an equivalent amount of aluminium microparticles (Al2o3). At the 48th hour after exposures, the test and control mice were submitted to a bacterial (Pasteurella multocida) or to a viral (Orthomyxovirus influenzae A) challenge, via the respiratory route. The exposure to cadmium significantly increased the death-rate of mice submitted to the bacterial challenge, but it significantly decreased the death-rate following the viral challenge.

Air Pollutants↗

Dexamethasone-suppressible hypercorticosteronism in two 46,XX subjects with ambiguous genitalia and ovarian cysts. Partial defect of 17 alpha-hydroxylase or 17-20-desmolase.

The paradoxical association of female pseudohermaphroditism and androgen deficiency was observed in two 46,XX subjects with high corticosterone plasma levels. Subject 1 has been declared a boy due to clitoris enlargement; she had no vagina and uterus. Subject 2 had ambiguous external genitalia. In both, at age 27 and 17 years, fusion of outer labia, impuberism, ovarian cysts, and histologically normal ovarian tissue were observed. Blood pressure was normal. Basal cortisol levels were normal but unresponsive to ACTH. Progesterone levels were 40 and 62 ng/ml and rose after ACTH (50 and 79 ng/ml). 17-hydroxyprogesterone levels were 25 and 21 ng/ml and did not rise after ACTH. Corticosterone levels were 70 and 92 ng/ml and rose after ACTH (110 and 180 ng/ml). All three steroids were suppressed by dexamethasone. Androgen and estrogen levels were at or below the lower limit for normal women. The sex steroid levels obtained by radioimmunoassay in plasma and a follicular cyst fluid were confirmed by isotope dilution-mass spectrometry. We suggest that the sexual ambiguousness resulted from an excessive production of gestagenic steroids during fetal life, and that the enzyme defect is either a partial 17 alpha-hydroxylase defect combined with a peripheral production of 17-hydroxyprogesterone, or else a partial 17-20-desmolase defect with a secondary 21-hydroxylase defect limited to the cortisol pathway.

Adolescent↗

Control of breathing in children with interstitial lung disease.

Control of breathing at rest was studied in 14 children (4-16 years old) with interstitial lung disease (ILD). Four of them were tested several times. Breathing pattern and the mouth occlusion pressure (P0.1) were measured. Results in ILD children were compared to values in healthy children previously reported. Respiratory frequency and minute ventilation were increased (P less than 0.02). Inspiratory time (TI) was shortened (P less than 0.001), the shortening in TI being significantly related to the increase in lung elastance (EL). The ratio of TI to the total duration of the respiratory cycle (TI/TTOT) was lowered (P less than 0.01). Tidal volume (VT) both in ml and normalized for body weight (BW) was normal. P0.1 was higher than predicted. The increase in P0.1 was significantly related to change in arterial O2 pressure (PaO2) which was reduced in 10 cases. There was a significant relationship between the increase in P0.1 and in EL. The increase in mean inspiratory flow (VTBW/TI) was related to the increase in EL. But VTBW/TI was not increased as much as P0.1. Consequently the effective inspiratory impedance was enhanced. This high effective inspiratory impedance was related to the increased lung elastance.

Adolescent↗