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C Girod

Publications and source records attributed to C Girod.

At least 37 records · Page 2Linked to original sources

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

Circulatory effects of somatostatin analogue in two conscious rat models of portal hypertension.

A somatostatin analogue, a long-acting octapeptide (SMS 201-995), has been reported to decrease portal pressure, but the mechanism is unclear. To elucidate the effects of this drug on both systemic and splanchnic hemodynamics, it was administered in two conscious rat models of portal hypertension. The dose-response curves showed that the somatostatin analogue significantly decreased portal pressure at a lower dose in rats with cirrhosis than in portal vein-stenosed rats. Calculated ED50 values were significantly different among all groups. Intravenous infusion of 8 micrograms/kg body wt.h of somatostatin analogue significantly decreased cardiac output by approximately 20% in both groups of portal hypertensive rats and increased mean arterial pressure by 7%. Accordingly, systemic vascular resistance markedly increased, indicating vasoconstrictor effects of this drug. The somatostatin analogue also significantly decreased portal tributary blood flow by 18% in portal vein-stenosed rats and 27% in cirrhotic rats. In sham-operated rats, somatostatin analogue had no effect on the systemic or splanchnic circulation. This study shows that somatostatin analogue decreases portal pressure principally by reducing portal tributary blood flow. This reduction may be due to either a direct vasoconstrictive effect or diminution in vasoactive hormone release.

Animals

Model for the study of portal-systemic collateral vascular resistance in the conscious rat.

In order to obtain a model for the study of portal-systemic collateral vascular resistance, total portal vein occlusion was performed in rats 48 hr or 3 wk after partial obstruction. Four groups of conscious restrained rats were studied: a) sham-operated, b) partial portal vein ligated, c) 48 hr-total portal vein occluded, and d) 3 wk-total portal vein occluded. In comparison with the sham group, the three portal vein ligated groups had significantly higher cardiac output, portal tributary blood flow, portal pressure (7.7 +/- 0.4 versus 13.5 +/- 0.5, 13.6 +/- 0.8, and 17.7 +/- 1.1 mmHg, mean +/- SE, respectively) and hepatic arterial blood flow (5.8 +/- 0.6 versus 9.5 +/- 0.7, 8.3 +/- 0.5, and 13.9 +/- 1.9 ml/min, respectively). Cardiac output and portal tributary blood flow did not differ between the portal vein ligated groups, but portal pressure and hepatic arterial blood flow were significantly higher in the 3 wk-total portal vein occlusion group. The 3 wk-total portal vein occlusion group showed 99.1 +/- 0.3% shunting, different from the partial (29.7 +/- 16.9%, p less than 0.01) and 48 hr-total portal vein occlusion (46.5 +/- 14.7%, p less than 0.05) groups. Portography confirmed absence of portal-portal collaterals in the 3 wk-total portal vein occlusion group. It is suggested that rats with 3 wk-total portal vein occlusion are useful for the study of acute modifications of portal-systemic collateral circulation, as shunting is total and consistent in this model.

Animals

The TSH secretion in the human pituitary adenomas.

TSH secretion by a pituitary tumor is very rare (2%) and it is often associated with another hormone: GH or PRL essentially. We present here nine tumors in which the TSH secretion was proved by immunocytochemistry (ICC) and by RIA in the tumor extracts, in the serum and in the culture medium. Four tumors secreted TSH only. Five tumors secreted TSH and GH predominantly. In 3 of them traces of other hormones (PRL and FSH) were also detected. The "pure" TSH adenomas were monomorphous with typical ultrastructural and immunocytochemical features. Plurihormonal TSH adenomas were bimorphous with different cells secreting GH and TSH or monomorphous with one type of cell which secreted TSH or GH or both TSH and GH. In a majority of the cases, the tumoral TSH secretion induced hyperthyroidism but in 2 patients with TSH adenoma there was euthyroidism and in another with TSH-GH adenoma there was no sign of acromegaly and GH serum levels were normal.

Adenoma

Animal models of human pituitary tumors.

Three animal models of pituitary tumors were compared: the spontaneous prolactinoma in Wistar/Furth (W/Fu) rats, an estrogen-induced transplantable tumor in the Fischer rat (MtTF4), and a spontaneous prolactin transplantable tumor in the W/Fu rat (SMtTW1). The spontaneous prolactinoma in W/Fu rats is interesting in that it resembles the human prolactinoma by its morphological characteristics, its benign nature, and its secretion of prolactin alone. It may be useful to study the initial factors of tumorigenesis but it is very expensive and the variability of tumor growth makes it difficult to plan experiments. The MtTF4 tumor is an easy model to study because it is transplantable but this tumor differs from most human pituitary tumors by its induction by estrogen, its malignancy, its undifferentiated aspect and its secretion of ACTH, GH, and prolactin. The SMtTW1 tumor, a new model of transplantable tumor, is close to the human pituitary tumor because the initial tumor is spontaneous, the transplanted tumors are benign and well differentiated. They secrete prolactin only. These transplantable tumors are valuable for studying the factors of growth. Since no single tumor system is a perfect model, researchers have to work on different models each of which is appropriate for investigating specific problems.

Animals

Regional blood flows by the microsphere method: reproducibility in portal hypertensive rats and influence of a portal vein catheter.

To determine the reproducibility of splanchnic blood flow measurements by the microsphere method in rats with portal hypertension and the effects of laparotomy with portal vein cannulation, eight groups of 10 rats were studied. Cardiac output and regional blood flows were measured twice, 10 min apart, in pentobarbital anesthetized or awake, sham-operated or portal vein-ligated rats, with or without portal cannulation. Variability between the two successive measurements was not affected by portal hypertension or portal cannulation, and was not different in the splanchnic territory and in other organs. Laparotomy with portal cannulation had no significant effect in sham-operated rats. In awake portal hypertensive rats, cardiac output (53.9 +/- 3.0 vs 45.8 +/- 2.9 ml.min-1.100 g body wt-1, P less than 0.01) and splanchnic blood flow (12.31 +/- 0.72 vs 9.34 +/- 0.85 ml.min-1.100 g body wt-1, P less than 0.01) were lower in portal vein cannulated rats compared with those of non-cannulated animals. In anesthetized portal hypertensive rats blood flows were unaffected by portal cannulation, but arterial pressure (100.2 +/- 4.3 vs 119.9 +/- 3.4 mm Hg, P less than 0.01) and heart rate (366.5 +/- 10.0 vs 405.5 +/- 7.4 beats.min-1, P less than 0.01) were elevated. Anesthesia also decreased portal pressure (14.8 +/- 0.5 vs 12.0 +/- 0.4 mm Hg, P less than 0.05) in portal hypertensive rats. We conclude that the microsphere method remains reproducible in portal hypertensive rat models. Laparotomy with portal cannulation can alter systemic and splanchnic hemodynamics in portal hypertensive rats; these effects can also be changed during pentobarbital anesthesia. Regional blood flow measurements in portal hypertensive rats should be performed in animals without portal cannulation and preferably in the awake state.

Animals

Immunostaining of a cell type in the islets of Langerhans of the monkey Macaca irus by antibodies against S-100 protein.

S-100 protein-immunoreactive cells were demonstrated by immunocytochemical procedures in the pancreatic islets of Langerhans in the monkey Macaca irus. By use of antibodies against human S-100 protein or bovine S-100 protein, these cells were observed in all islets in the head and tail portions of the pancreas. Immunostained cells were usually located in the center of the islets or sometimes found in a more widely distributed form, but they were never arranged in a regular concentric fashion. The number of immunoreactive cells varied from one islet to another but it was relatively limited making up only 0.75%-6.3% of all insular cells. With the use of the double-immunoenzymatic procedure for demonstration of the four main endocrine cell types (insulin-, glucagon-, somatostatin- and pancreatic polypeptide producing elements), it was possible to establish that S-100 protein-immunoreactive cells represent a distinct cell type. Antibodies against S-100 protein-stained neuroinsular complexes. The present findings speak in favor of a new cell type to be added to the large variety of S-100 protein-immunoreactive cells outside the central nervous system.

Animals

Reduction of intrahepatic vascular space in the pathogenesis of portal hypertension. In vitro and in vivo studies in the rat.

To elucidate a possible role for reduction of intrahepatic vascular space in the pathogenesis of portal hypertension, we studied a partially hepatectomized rat model in vitro and in vivo. The in vitro study used livers from normal, 1/3-hepatectomized, and 2/3-hepatectomized rats, and rats with cirrhosis caused by chronic bile duct ligation, for isolated, perfused flow-pressure plotting. Resistance to perfusion increased such that significant differences were found between all groups except the last two, which showed similar resistances. The in vivo study measured splanchnic blood flow by radioactive microspheres and portal pressure in anesthetized sham-operated and 1/3- and 2/3-hepatectomized rats. Although absolute portal tributary blood flows did not change, portal flow per gram of remnant liver showed significant increases: 1.57 +/- 0.32 ml/min X g liver, 2.52 +/- 0.60 ml/min X g liver, p less than 0.01; 3.48 +/- 1.04 ml/min X g liver, p less than 0.01, respectively. Although intrahepatic resistance increased significantly only in the 2/3-hepatectomized group, portal pressures increased significantly in both groups of hepatectomized rats: normal, 7.5 +/- 1.1 mmHg; 1/3-hepatectomized, 9.4 +/- 1.1 mmHg; and 2/3-hepatectomized, 11.1 +/- 1.2 mmHg. Thus, decreased intrahepatic vascular space caused by resection and hepatocellular hypertrophy leads to portal hypertension, thereby suggesting that this reduction in space may be the pathogenic factor common to a number of different theories of portal hypertension.

Animals

Naloxone does not alter haemodynamics in cirrhosis. Studies in humans and rats.

In order to test the hypothesis that endogenous opioids may mediate some of the circulatory derangements in cirrhosis, we studied the haemodynamic effects of naloxone, an opioid antagonist, in patients and in a rat model of biliary cirrhosis. In 9 patients with alcoholic cirrhosis and 5 control patients without significant liver disease, cardiac output, systemic vascular resistance, mean arterial pressure, heart rate, hepatic venous pressures and O2 content, hepatic and azygos blood flows and serum catecholamines were measured before and 30 min after naloxone 3.2 mg i.v. bolus. No significant changes were observed in either group of patients. Similarly in 16 conscious rats, 8 sham-operated and 8 with cirrhosis due to bile duct ligation, cardiac output, systemic vascular resistance, mean arterial pressure, heart rate, and splanchnic organ blood flows were measured by radioactive microspheres, before and 20 min after naloxone 1 mg/kg i.v. bolus. No significant changes were observed in either group. We failed to detect any evidence that endorphins are involved in tonic haemodynamic control in cirrhosis.

Adult

Immunocytochemical localization of S-100 protein in stellate cells (folliculo-stellate cells) of the adenohypophysis in the monkeys Macaca irus and Cercopithecus aethiops.

With the use of an antibody against bovine S-100 protein, it was possible to reveal a characteristic cell type in the pars distalis and the pars tuberalis of the monkey Macaca irus. In the adenohypophysis of Cercopithecus aethiops, labeled cells were present in the pars distalis, pars tuberalis, and pars intermedia. These cells, so-called folliculo-stellate cells, were found in all pituitaries studied. Surprisingly, an antibody against human S-100 protein did not label the stellate cells of the adenohypophysis. However, in Macaca irus, this antibody gave a strong positive reaction with various other cell types (interstitial cells of the pineal gland, Müller cells of the retina, autonomic ganglionic cells, glial cells of the central nervous system, Schwann cells, Bergmann glia of the cerebellum, fat cells, reticular cells of lymphoid organs). By use of double immunoenzymatic labeling, it was evident that stellate cells are spatially related either to somatotropes, prolactin cells, "corticotropes", or to glycoprotein-containing cells. Thus, a specific relationship to a particular endocrine-cell type could not be observed.

Animals

Comparison of the circulation between fed and fasted normal and portal hypertensive rats.

The radioactive microsphere technique with the reference sample method was used for simultaneous determinations of splanchnic organ blood flow and cardiac output in fed and fasted anesthetized control rats and in rats with portal hypertension due to portal vein stenosis. Portal tributary blood flow was significantly higher in control (27.35 +/- 1.82 versus 14.60 +/- 0.96 ml/min) and in portal hypertensive (25.45 +/- 0.71 versus 20.09 +/- 1.27 ml/min) fed animals than in fasted rats, respectively. This difference was due to an increase in most of the splanchnic organ blood flows expressed in terms of either milliliter per minute or milliliter per minute per gram of tissue. The distribution of the cardiac output to the portal venous territory was also increased in fed animals as compared to fasted rats. In contrast, hepatic arterial blood flow was lower in fed animals than in fasted rats in both groups. Cardiac output was also significantly elevated in fed animals. This study demonstrates that the baseline circulatory state that depends on the digestive condition of these rats must be considered for splanchnic hemodynamic studies.

Animals

Circulatory actions of vasopressin in anaesthetized rats with portal hypertension subjected to haemorrhage.

To assess the influence of vasopressin on splanchnic and renal circulatory changes induced by haemorrhage in portal hypertension, we studied 4 groups of 7 rats with chronic portal vein stenosis. Two groups received saline (C and H) and two groups vasopressin, 0.01 IU/kg/min (VP and VP-H). Ten minutes after starting drug infusion, group H and VP-H animals were allowed to bleed from the superior mesenteric vein. Both haemorrhage and vasopressin alone, decreased portal venous tributary blood flow and pressure but their association was not additive (as reflected by comparable bleeding rate in groups H and VP-H). By contrast, vasopressin increased renal perfusion in bleeding and non-bleeding animals whereas haemorrhage alone decreased renal perfusion. These results indicate that the effects of vasopressin on the splanchnic circulation in bleeding anaesthetized animals differ from the effects observed when blood volume is normal. Therefore, in patients with cirrhosis the effects of vasopressin during bleeding might also differ from those observed in patients in stable condition.

Anesthesia

Alteration in response of the portal tributary vascular bed to the beta-agonist dobutamine in rats with extrahepatic portal hypertension.

The acute effects of 2 doses of the beta-agonist dobutamine on systemic and splanchnic haemodynamics were studied in normal rats and in rats with portal hypertension due to portal vein stenosis. Cardiac output and splanchnic organ blood flow were estimated with the radioactive microsphere method and portal pressure was measured. Low dose (5 micrograms/kg) of dobutamine did not change significantly arterial pressure and portal pressure but, cardiac output was significantly higher after dobutamine than after placebo in both groups of rats. Similar results were observed with 15 micrograms/kg of dobutamine except for a significant decrease in arterial pressure in portal-hypertensive rats. In sham-operated rats, dobutamine significantly increased portal tributary blood flow; this rise was parallel to cardiac output. In contrast, in portal-hypertensive rats, portal tributary blood flow did not change significantly after dobutamine. Accordingly in the former group, portal tributary vascular resistance significantly decreased, whereas in the latter group, no change in this resistance was observed with a low dose and a significant decrease was noted with a high dose. In both groups of rats, hepatic arterial blood flow was not significantly different after dobutamine than after placebo. This study demonstrates that the vasodilatory response of the portal tributary vascular bed to an increase in cardiac output is altered in anaesthetized rats with portal hypertension due to portal vein stenosis.

Animals

Haemodynamic rebound phenomena after abrupt cessation of propranolol therapy in portal hypertensive rats.

The haemodynamic effect of sudden termination of propranolol therapy was studied in sham-operated and portal hypertensive rats. All animals were injected with propranolol (20 mg/kg/day) or saline i.p. for 10 days, then had an isoproterenol infusion test performed 48 h or 72 h after cessation of injections. The dose of isoproterenol required to increase the heart rate by 50 beats/min (CD50), was significantly lower in both sham-operated and portal hypertensive rats at 48 h after propranolol withdrawal. Maximum chronotropic response (Rmax), was significantly higher only in portal hypertensive rats at 48 h after propranolol withdrawal. These results show the existence of a transient beta-adrenergic hypersensitivity state following propranolol withdrawal in normal and portal hypertensive rats.

Animals

Hemodynamic characterization of chronic bile duct-ligated rats: effect of pentobarbital sodium.

Systemic and splanchnic hemodynamics of the chronic bile duct-ligated rat were characterized by radioactive microspheres. Conscious and pentobarbital sodium-anesthetized, bile duct-ligated and sham-operated rats had cardiac output and regional organ blood flows determined. The conscious bile duct-ligated rat compared with the sham-operated showed a hyperdynamic circulation with an increased cardiac output (153.3 +/- 9.8 vs. 112.6 +/- 6.0 ml/min, P less than 0.005) and portal tributary blood flow (21.32 +/- 1.43 vs. 12.79 +/- 1.47 ml/min, P less than 0.005). Pentobarbital sodium anesthesia induced marked hemodynamic changes in both sham-operated and bile duct-ligated rats. The latter group was especially sensitive to its effects; thus, comparison of cardiac output and portal tributary blood flow between anesthetized bile duct-ligated and sham-operated rats showed no significant differences. We conclude that the rat with cirrhosis due to chronic bile duct ligation is an excellent model for hemodynamic investigations but should be studied in the conscious state, since pentobarbital sodium anesthesia eliminates the hyperdynamic circulation.

Anesthesia, General

Ultrastructural observations on folliculo-stellate cells in the pars distalis of the pituitary gland in three rodent species.

Ultrastructural features of folliculo-stellate cells of the anterior lobe of the pituitary gland were described in three rodent species (the mouse, guinea pig, golden hamster). These cells are agranular and form the lining of tiny follicles projecting microvilli. Long cytoplasmic expanding processes are intermingled with granular cells of various morphofunctional types without special relationships to one cell type or another. In the guinea pig, the abundance of intermediate filaments appears as a notable feature in the cytoplasm of the folliculo-stellate cells. The results are compared with those previously published.

Actin Cytoskeleton

The human gonadotropic adenoma: pathologic diagnosis and hormonal correlations in 26 tumors.

Twenty-six out of 400 surgically removed pituitary tumors were identified as gonadotropic adenomas (frequency 6.25%). Morphologic, immunocytochemical, and hormonal characteristics of the gonadotropic adenoma are described. The following morphologic characteristics may suggest the diagnosis: arrangement in cords of cells showing signs of cellular activity, secretory granules, which vary in electron density, form, and size (mean diameter 150 nm) and which are numerous in the extensions near the capillaries, and a rough endoplasmic reticulum arranged in short cisternae. However, owing to the morphofunctional variations from one adenoma to another, we consider that only immunoreactivity with gonadotropin antisera proves the diagnosis. Because the material used to generate the gonadotropin antisera was purified but not pure, for precise characterization of the immunoreactivity, absorption tests with various antigens have to be performed. FSH-LH adenomas (n = 14), FSH adenomas (n = 7), and alpha-subunit adenomas (n = 5) but no LH adenomas were identified in our series. No evident morphologic difference related to the type of immunoreactivity and to the sex was found. Almost all the tumors were large with visual signs caused by suprasellar extension. A recurrence following adenomectomy was noted with a frequency of 12%. The diagnosis of gonadotropic adenoma was considered preoperatively in six out of 26 patients only, on the basis of increased serum gonadotropin levels. Correlations between hormonal levels and pathologic data were established in 17 patients. Seven tumors were associated with high serum gonadotropin levels (FSH and LH: three patients and FSH alone: four patients). In ten cases, the serum gonadotropin levels were normal but serum alpha-subunit assay had not been performed. For the pathologist systematically testing the adenomas with many antisera, gonadotropic adenomas are not as rare as for the clinician. Immunocytochemical studies with gonadotropin antisera and serum gonadotropic determination must be performed in all tumors, especially in those pituitary adenomas that appear nonfunctional.

Adenoma

The human thyrotropic adenoma: pathologic diagnosis in five cases and critical review of the literature.

Five out of 400 surgically removed pituitary tumors (frequency: 1.2%) were identified as thyrotropic adenomas according to the following criteria: identification of tumoral thyrotropic cells by immunocytochemistry and ultrastructural study; elevated serum TSH levels with decrease after surgery; and elevated concentration of TSH in the tumor. Four patients presented with hyperthyroidism and one with euthyroidism. From these five cases and 11 similar observations extracted from a critical review of literature, the morphologic, immunocytochemical, and hormonal characteristics of thyrotropic adenoma are described. Thyrotropic adenomas are more often large tumors but may also be microadenomas. The diagnosis is asserted by immunoreactivity with anti-TSH antisera. The TSH positive tumor cells are numerous. In some tumors, rare cells of other types are also found (PRL, GH, FSH, or ACTH cells). Some morphologic characteristics strongly suggest the diagnosis. The cells are often large with thin processes. They show argyrophil granulations in a slightly basophil cytoplasm and signs of secretory activity. Their secretory granules are round and small without striking variations in size, shape, and electron density. Elevated concentration of TSH in the tumor confirms the diagnosis. The presence of high serum TSH levels and a molar ratio of alpha hTSH to the whole TSH molecule greater than one are other good criteria. Decrease of TSH after surgery may not be observed in invasive tumors. TSH adenoma is most often associated with hyperthyroidism but it can also be associated with hypothyroidism or euthyroidism.

Adenoma