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C Girod

Publications and source records attributed to C Girod.

At least 19 recordsLinked to original sources

Mapping of corticotropic cells in the normal human pituitary.

We accomplished the first mapping of corticotropic cells in the whole human adult pituitary. Corticotropic cells were identified by immunocytochemistry (ICC) and quantified by image analysis on 12 pituitaries obtained from people who had died suddenly. An overall view of each pituitary was given by 15-21 sections (mean 18 sections) at 300-micron intervals on six slides. Each section was systematically treated by indirect immunoperoxidase using an anti-ACTH[17-39] polyclonal antiserum. All the measures were done with a x 6.3 objective lens, each field (0. 5 mm2) being considered as the unit area. The mean pituitary density (surface of labeled cells/total surface) of corticotropic cells (9.5 +/- 3.0% per 0. 5 mm2) is significantly higher in men (11.5 +/- 5.1%) than in women (7.0 +/- 1.3%). This difference is due to an inverse relationship between the corticotropic cell density and the weight of the pituitary, which is higher in women than in men. The mean diameter of corticotropic cells is 14.9 micron and their total number per pituitary is approximately 10(7) cells. We confirmed that the spatial distribution of corticotropic cells is nonuniform: they are mainly distributed in the anteromedian part of the anterior lobe. In addition, our results demonstrated that the inferior part of the pituitary contained three times more corticotropic cells than the superior part (mean density 18.0% vs 6.0%) and the anterior part twice as many as the posterior part (mean density 12.3% vs 6.8%). On the horizontal plane, the pituitary was divided into eight zones, in which the mean of area was 2.5-21.0%. The maximal cell density may reach 40-60%. The use of this map should help the pathologist to recognize if there is corticotropic hyperplasia in a small pituitary fragment surgically removed from a patient with Cushing's disease. On the basis of this study, we put forward some criteria for diagnosing corticotropic hyperplasia.

Adrenocorticotropic Hormone

Effects of aluminum on bone surface ion composition.

Aluminum induces net calcium efflux from cultured bone. To determine whether aluminum alters the bone surface ion composition in a manner consistent with predominantly cell-mediated resorption, a combination of cell-mediated resorption and physicochemical dissolution or physicochemical dissolution alone, we utilized an analytic high-resolution scanning ion microprobe with secondary ion mass spectroscopy to determine the effects of aluminum on bone surface ion composition. We cultured neonatal mouse calvariae with or without aluminum (10(-7) M) for 24 h and determined the relative ion concentrations of 23Na, 27Al, 39K, and 40Ca on the bone surface and eroded subsurface. Control calvariae have a surface (depth approximately 6 nm) that is rich in Na and K compared with Ca(Na/Ca) = 24.4 + 1.4, mean + 95% confidence limit of counts per second of detected secondary ions, K+Ca = 13.2 + 0.9). Aluminum is incorporated into the bone and causes a depletion of surface Na and K relative to Ca (Na/Ca = 9.6 + 0.7, K/Ca = 4.9 + 0.4; each p < 0.001 versus control). After erosion (depth approximately 50 nm), control calvariae have more Na and K than Ca (Na/Ca = 16.0 + 0.1, K/Ca = 7.5 + 0.1); aluminum again depleted Na and K relative to Ca (Na/Ca = 4.1 + 0.1 K/Ca = 1.9 + 0.1; each p < 0.001 versus control). Aluminum produced a greater net efflux of Ca (362 +/- 53, mean +/- SE, nmol/bone/24 h) than control (60 +/- 30, p < 0.001). With aluminum, the fall in the ratios of both Na/Ca and K/Ca coupled with net Ca release from bone indicates that aluminium induces a greater efflux of Na and K than Ca from the bone surface and is consistent with an aluminum-induced removal of the bone surface. This alteration in surface ion concentration and calcium efflux is consistent with that observed when calcium is lost from bone through a combination of cell-mediated resorption and physicochemical dissolution.

Aluminum

Inhibitory effects of the dopamine agonists quinagolide (CV 205-502) and bromocriptine on prolactin secretion and growth of SMtTW pituitary tumors in the rat.

The SMtTW tumor, a spontaneous PRL-secreting transplantable tumor, is the only available animal model sensitive to dopamine agonists. This model has been used to compare the long term in vivo effects of CV 205-502 (CV) and bromocriptine (BR) on PRL secretion and tumor growth. These two drugs were given for 2 months to female Wistar-Furth rats bearing either small or large tumors 4 and 6 months after the graft. Untreated grafted rats served as control. In all rats treated with 5 or 10 mg/kg.day BR or 0.3 mg/kg.day CV, a normalization of plasma PRL levels was observed whatever the pretreatment levels (plasma PRL or CV or BR-treated rats, < 15 ng/ml vs. 28253 ng/ml in control rats 8 months after graft). An inhibition of tumor growth was found for both small and large tumors, but the tumors never disappeared completely (mean tumor weights at autopsy, 440 and 660 mg in BR and CV groups vs. 5270 mg in control group 8 months after graft). Experiments performed with increasing doses of BR (0.15-5 mg/kg.day) or CV (0.03-0.6 mg/kg.day) indicated that CV is effective at doses 5-10 times lower than those of BR. A shrinkage under treatment and a regrowth after drug withdrawal were demonstrated for large tumors by in vivo ultrasonographic measurements of tumor size. Histological and ultrastructural effects were similar for the two drugs: decrease in hemorrhage, reduction of the cell size and secretory activity, increase in immunoreactive PRL cellular content, and inhibition of exocytosis. There was no difference in the PRL mRNA content of treated and untreated tumors, as assessed by in situ hybridization. In conclusion, CV and BR exhibit similar inhibitory effects on tumor growth and PRL secretion. These effects are rapidly and fully reversible after drug withdrawal. The present results give a complete account of the actions of the two dopamine agonists under conditions comparable to those used in the treatment of human prolactinomas.

Aminoquinolines

Prenatal and postpartum Pap smears: do we need both?

PURPOSE: The need to perform a Pap smear at the time of entry to prenatal care, as well as at the postpartum check-up, is questionable. A comparison of the rates of recovery of endocervical cells and the incidence of dysplasia on the prenatal and postpartum Pap smears may be helpful in determining an optimal preventive care protocol for patients who are pregnant. METHODS: Demographic and clinical data were collected from the records of 1,377 obstetrical patients at a midwest family practice residency. The yield of endocervical cells and the incidence of dysplasia was determined for both the prenatal and the postpartum Pap smears performed for this group of patients. RESULTS: In women having both exams, endocervical cells were recovered in 44.1% of prenatal Pap smears compared to 82.0% of postpartum smears. The incidence of dysplasia was 2.6% on prenatal Pap smears and 4.8% on postpartum smears. In this study population, 33% of women did not return for their postpartum check-up. CONCLUSIONS: The postpartum Pap smear is of value due to a significant yield of dysplasia. The sensitivity of the prenatal Pap test may be less than desired. Efforts directed toward increased patient compliance regarding the postpartum check-up are needed.

Adolescent

Fetal Niemann-Pick disease type C: ultrastructural and lipid findings in liver and spleen.

We present the first ultrastructural study of liver and spleen from a 20-week fetus with Niemann-Pick disease type C in correlation with lipid studies of these tissues. The lipid storage pattern was characteristic of the disease and although the distribution of the lipid storage was similar to that of affected children, ultrastructural studies emphasized that many inclusions were qualitatively different. These are discussed. Concomitant with this complex lipid storage, ultrastructural evidence of cholestasis was observed and the early hyperplasia of pericanalicular microfilaments leads us to question the presence of a toxic metabolite which might induce cholestasis by acting upon microfilaments.

Fetal Diseases

Farber disease: an ultrastructural study. Report of a case and review of the literature.

A case of Farber disease is reported and the ultrastructural pathology of the disease is reviewed. The present case showed the typical clinical picture of Farber disease. Acid ceramidase deficiency was demonstrated biochemically. Ultrastructural features of one subcutaneous nodule and a skin biopsy are described. Three lysosomal inclusions characterize Farber disease: curvilinear tubular bodies observed mainly in the reticuloendothelial system, "banana bodies" recorded only in the peripheral nervous system and zebra-like bodies which are essentially a neuronal storage. The nature of each is discussed and the skin biopsy is emphasized for its important diagnostic interest.

Biopsy

Variability of hemodynamic values and plasma catecholamine concentrations over a one-hour period in conscious, restrained rats.

Restrained conscious rats have been widely used for physiological and pharmacological hemodynamic studies. In this condition, the variability of the circulation is unclear. Repeated measurements in restrained normal rats showed stable systemic hemodynamics (cardiac output ranging from 130 +/- 14 to 174 +/- 10 mL/min, mean arterial pressure ranging from 109 +/- 9 to 117 +/- 5 mmHg) and splanchnic hemodynamics (splanchnic blood flow ranging from 8.51 +/- 1.89 to 13.01 +/- 1.45 mL min-1 100 g-1 body wt) over a period of 1 hr. Slight but not significant hemodynamic variations, however, occurred in pulmonary blood flow. Similarly, plasma noradrenaline concentrations did not vary over this period (plasma noradrenaline level ranging from 186 +/- 36 to 358 +/- 64 pg/mL). These plasma noradrenaline concentrations were similar to those measured in a group of conscious unrestrained rats 3 hr after recovery from surgery (292 +/- 60 pg/mL). A significant correlation was observed between plasma noradrenaline concentration and heart rate.

Animals

Divergent circulatory effects of betaxolol in conscious and anesthetized normal and portal hypertensive rats.

We aimed to define the circulatory effects of beta 1-blockade in conscious normal and portal hypertensive rats and determine if pentobarbital anesthesia affected these responses. A selective beta 1-antagonist, betaxolol, was given to four groups: conscious and anesthetized sham-operated and portal hypertensive rats. Cardiac output and splanchnic organ blood flows were measured by radioactive microspheres twice in each rat, before and 15 min after betaxolol. Both groups of conscious rats maintained mean arterial pressure despite significant decreases in cardiac output and heart rate, by increasing total peripheral resistance. Anesthetized rats were unable to do this and thus also diminished arterial pressure significantly, with portal hypertensive rats showing greater decreases than sham-operated rats. Portal tributary flow and portal pressure decreased only in the anesthetized rats. Autoregulation of splanchnic blood flow was not uniform between groups or organs: although splenic flow decreased in all four groups, intestinal blood flow decreased only in anesthetized portal hypertensive rats. The greatest decreases in several splanchnic organ blood flows were seen in this latter group. These results indicate that: (i) pentobarbital markedly changes systemic and splanchnic responses to beta 1-blockade; (ii) splanchnic autoregulation is not uniform--the intestinal circulation enjoys more protection than the splenic; and (iii) portal hypertensive rats seem to be more vulnerable to the circulatory effects of beta 1-blockade.

Animals

Somatotropic adenomas without acromegaly.

Seventeen somatotropic adenomas removed from patients without acromegaly were studied. Thirteen of them presented as a prolactinoma with amenorrhea and/or galactorrhea and elevated serum PRL levels. According to basal serum GH levels, the patients were divided into two groups, namely Group I: GH slightly elevated (n = 4) and group II: GH less than or equal to 5 micrograms/l (n = 13). The tumoral GH secretion was proved by immunocytochemistry in all cases and by intratumoral RIA, in vitro study and/or in situ hybridization in five of them. Pathological, clinical and biochemical relationships suggested two anatomoclinical aspects. In group I, the tumors were small, well-differentiated somatotropic adenomas with clinically silent GH hypersecretion. It is probably an early stage of the disease. In group II, the tumors were large with normal GH serum levels. They were poorly differentiated and secreted very low amounts of GH. In nine of them, PRL and/or PRL mRNA expression were also detected. These tumors do not secrete enough GH to increase serum levels and cause acromegaly. The somatotropic adenomas without acromegaly correspond to two anatomoclinical aspects of the disease.

Acromegaly

Spontaneous prolactin transplantable tumor in the Wistar/Furth rat (SMtTW): a new animal model of human prolactinoma.

Two spontaneous prolactinomas, removed from 28-mo-old female Wistar/Furth rats, were grafted by serial passages under the kidney capsule and the skin in 117 females of the same consanguineous strain. The hosts, aged between 2 and 10 mo, were free of estrogen treatment. These transplantable tumors, named SMtTW1 and SMtTW2, were studied until the fifth serial passage. The percentage of success was 100% under the kidney capsule and 20% under the skin. From the radioimmunoassays of prolactin (PRL), growth hormone, and adrenocorticotropic hormone and the immunocytochemical results, the tumors secrete PRL only. The PRL tumoral secretion was detected after 3 to 5 mo of graft; at 8 mo, mean plasma PRL values reached 5150 ng/ml (normal value, 15.2 ng/ml). Plasma growth hormone and adrenocorticotropic hormone values remained normal. Like the primary tumors, the grafted tumors were benign, grew slowly, and were sparsely granulated well-differentiated prolactinomas with exocytosis. They remained identical during the first serial passages. The secretion and the growth of SMtTW2 were inhibited by bromocriptine. In the light of our knowledge of the human prolactinoma, the spontaneous transplantable prolactinoma of the rat may be considered to be an animal model closer to the human pathology than the estrogen-induced "tumors" and the induced transplantable tumors. It is easier to use than the spontaneous prolactinoma of the rat.

Animals

Effects of haemorrhage and volume expansion on portal-systemic collateral vascular resistance in conscious portal hypertensive rats.

1. In order to study the acute effects of blood volume changes on the vascular resistance of portal-systemic collaterals (collateral vascular resistance), a model of total portal vein occlusion with 100% portal-systemic shunts was developed in the rat. In this model, we determined the haemodynamic effects of haemorrhage (1.8 ml/100 g body weight) or intravenous infusion of a volume expander (1.8 ml/100 g body weight). Cardiac output and regional blood flows were measured by the radioactive microsphere method. 2. Haemorrhage significantly reduced arterial pressure from 108 +/- 4 to 92 +/- 4 mmHg (mean +/- SEM), cardiac output from 56 +/- 4 to 24 +/- 2 ml min-1 100 g-1 body weight, portal pressure from 15.1 +/- 1.5 to 10.0 +/- 1.4 mmHg and portal tributary blood flow from 19.9 +/- 2.3 to 8.3 +/- 1.4 ml/min. Consequently, collateral vascular resistance significantly increased from 6.6 +/- 0.9 x 10(3) to 11.1 +/- 2.0 x 10(3) kPa 1(-1) s. 3. Volume expansion reduced arterial pressure from 98 +/- 3 to 90 +/- 3 mmHg, and significantly increased cardiac output from 43 +/- 3 to 55 +/- 3 ml min-1 100 g-1 body weight, portal pressure from 13.9 +/- 0.7 to 16.5 +/- 0.8 mmHg and portal tributary blood flow from 16.4 +/- 1.3 to 28.2 +/- 3.2 ml/min. Consequently, collateral vascular resistance significantly decreased from 7.0 +/- 0.5 x 10(3) to 4.9 +/- 0.4 x 10(3) kPa l-1 s. 4. This study shows that in rats with portal hypertension, portal-systemic collateral vascular resistance is modified by alterations in blood volume.

Animals

Mesenteric venous stenosis reduces hyperammonemia in the portacaval-shunted rat.

Hyperammonemia is a constant finding following portacaval anastomosis (PCA), and has been incriminated in the neurologic deterioration observed following portasystemic shunt in humans. We developed a rat model for mesenteric venous hypertension by modification of a commonly used technique for studying extrahepatic portal hypertension. We then examined serum ammonia levels in rats undergoing sham operation, mesenteric vein stenosis (MVS) alone, PCA alone, and MVS plus PCA. All MVS animals had a significant (p less than 0.05) elevation in mesenteric venous pressures 2-3 weeks after operation. Serum ammonia levels were normal in rats undergoing sham operation and MVS, and were significantly elevated (p less than 0.001) in rats with PCA. However, a significant (p less than 0.01) reduction in serum ammonia levels was realized when PCA and MVS were combined. These data suggest that intestinal ammonia absorption is a function of splanchnic venous pressure. These findings may be relevant to the management of the neuropsychiatric deterioration seen following PCA in man.

Ammonia

Human epithelial thymic tumours: heterogeneity in immunostaining of epithelial cell markers and thymic hormones.

Different hormones (thymulin, thymosin alpha 1, vasopressin), antigenic markers of cortical and subcapsular/medullary thymic areas and tumour associated antigens were studied on paraffin or frozen section and cultures of human epithelial thymic tumours ('thymomas'). Thymulin, thymosin alpha 1 and for the first time vasopressin are found in most tumours. The epithelial cells of five 'thymomas' had markers of both cortical (TE3) and subcapsular/medullary thymic regions (A2B5 and/or TE4 and/or anti-p19). Leu-7, a marker of subcapsular epithelial cells was positive only in two tumours. The histological classification into cortical and medullary tumours does not correspond to our immunofluorescence results. The presence of these markers does not support the theory of different embryologic origin of the cortical and subcapsular/medullary epithelial cells. Transferrin receptors were detected on only some epithelial cells of thymic 'carcinomas'. Adenocarcinoma related antigen and carcino embryonic antigen only stained a few epithelial cells of all the tumours. There is no expected correlation between the presence of epidermal growth factor receptors on cell membranes and the number of proliferative cells stained by the anti-Ki67 antibodies. Immunostainings were heterogeneous according to the epithelial thymic tumours, independent of histological classification and not yet useful for prognosis.

Adult

Scanning ion microprobe assessment of biological sample preparation techniques.

Different preparation techniques for high lateral resolution scanning ion microprobe imaging of biological samples have been investigated. The sharpest histological maps are obtained from chemically fixed and plastic embedded specimens. It is often problematic to correlate ultrastructure and bioaccumulation from analysis of frozen cut and lyophilized sections. The best compromise is to resin-embed frozen samples in order to get a perfectly flat section from tissue where the in vivo ion distribution is maintained. Use of the University of Chicago Ion Microprobe gave us the ability to observe the relative ion translocations induced during sample preparation. As an example, we show the rapid decrease of intracellular K+/Na+ ratio through a fast frozen blood droplet.

Blood Cells

[Normal and tumorous human gonadotropic cells].

Gonadotropic cells are scattered in the anterior and tuberal lobes and make up 10 to 20% of the anterior pituitary cells. Having a morphofunctional plasticity, they secrete FSH and LH, most often simultaneously. These hormones are stored together in the granulations. In addition, under the action of regulating factors, especially GnRH, the cells can secrete one hormone or the other, or even the alpha subunit. Gonadotropic adenomas range third in frequency among operated pituitary adenomas (12% in our series). The diagnosis is based on the presence of at least 5% of immunoreactive cells with specific antibodies to gonadotropic hormones. These adenomas are distributed into 3 major types: FSH-LH adenoma, the most frequent one, FSH adenoma and alpha-subunit adenoma. The LH adenoma and the beta FSH and beta LH adenomas are very rare. Tumoral gonadotropic cells lose their morphofunctional differentiation. They also lose, to an extent varying according to the cases, their control mechanisms as well as their capacity of synthesis and excretion of both subunits. The alpha subunit, the oldest one in ontogeny, remains the most often and longest-secreted substance. There is a continuum from the gonadotropic adenoma with high plasma gonadotropins levels to the non-functioning adenoma.

Adenoma

Discrepancy between portal pressure and systemic hemodynamic changes after incremental doses of propranolol in awake portal hypertensive rats.

The effects of increasing doses of propranolol were studied in awake portal hypertensive rats in order to elucidate the relative effects of the beta-blocker on systemic and splanchnic circulation. Hemodynamic responses to 0.1, 0.2 and 0.4 mg per min infusions of propranolol were compared with placebo in awake rats with portal hypertension due to portal vein stenosis. Heart rate significantly and progressively decreased from 356 +/- 13 to 293 +/- 10 beats per min (mean +/- S.E.). Cardiac output significantly decreased from 54 +/- 3 to 42 +/- 3 ml per min per 100 gm body weight at the highest dose. Significant decrease in portal tributary blood flow from 27 +/- 1 to 18 +/- 1 ml per min, at 0.4 mg per min dose, was due not only to the decrease in cardiac output but also to a significant increase in portal tributary vascular resistance from 269 +/- 17 to 368 +/- 31 dyne per sec per cm5 x 10(3). However, portal pressure showed only an insignificant decrease from 14.9 +/- 1.1 to 14.1 +/- 1.4 mmHg. The reduction in portal pressure being minimal, in spite of a significant decrease in portal tributary blood flow, is explained by an increase in combined hepatic and collateral resistance from 44 +/- 2 to 66 +/- 4 dyne per sec per cm5 x 10(3), p less than 0.05, at 0.4 mg per min dose. We conclude that the systemic and splanchnic effects of propranolol show discrepancy at two levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Mechanisms of a clonidine-induced decrease in portal pressure in normal and cirrhotic conscious rats.

The effects of clonidine on portal pressure and splanchnic blood flow were studied in conscious rats with sinusoidal portal hypertension due to cirrhosis induced by bile duct ligation. In cirrhotic and sham-operated rats, clonidine (20 micrograms per kg body weight, intravenously) significantly reduced portal, pressure from 19.0 +/- 0.6 to 14.5 +/- 1.0 mmHg and from 9.8 +/- 0.9 to 7.3 +/- 0.5 mmHg, respectively. No significant change in systemic hemodynamics was observed. In cirrhotic rats, clonidine reduced portal pressure, probably by producing a significant increase in portal tributary vascular resistance leading to a 25% decrease in portal tributary blood flow (radioactive microsphere method). In sham-operated rats, clonidine reduced portal pressure presumably by decreasing hepatic portal vascular resistance, since no significant change in portal tributary blood flow was observed. In both groups, clonidine administration significantly decreased plasma noradrenaline concentration. Placebo administration produced neither significant hemodynamic nor significant plasma noradrenaline concentration change. These findings indicate that the sympathetic regulation of the splanchnic circulation is impaired in cirrhotic rats.

Animals

Inversely related evolution of growth hormone and prolactin secretions in long-term tissue cultures of human pituitary adenomas from acromegalic patients.

Pituitary tumoral tissue from 20 acromegalic patients was cultured for up to 120 d in a medium containing 5 nM cortisol. In all cultures, growth hormone (GH) release decreased. At the beginning of the culture, prolactin (PRL) was detected in 18 adenomas, varying from 0.5 to 1000 ng per flask per day. Thereafter, in 10 cases PRL secretion increased from 3 to 50 times the basal level, most frequently after a lapse of 9 to 30 d. PRL secretion remained low in three cases, undetectable in one case only. When added at 350 nM, cortisol increased GH secretion up to 20-fold and simultaneously decreased PRL secretion by as much as 10% of the basal level. Withdrawing cortisol reversed the situation. Immunocytochemical studies of the tumor at surgery showed, besides GH immunoreactive (IR) cells, PRL-IR cells (from rare cells to 10% of total cells) in 15 adenomas, correlating with the first days of culture PRL levels. In cultured explants, mitoses were never found. In 5 nM cortisol medium, the number of GH-IR cells decreased and PRL-IR cells increased or appeared. With 350 nM cortisol, the number of GH-IR cells increased, and PRL-IR cells were scarce or absent. Immunoreactivities for GH and PRL were found in different cells. Care was taken to exclude cultures containing normal pituitary tissue, and because no mitoses were found, these results suggest that most somatotropic adenomas can reversibly shift their secretion from GH to PRL in culture. This capacity to secrete PRL, hidden or low in vivo, is revealed by the favorable low cortisol conditions present in vitro.

Acromegaly