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Biomedical subjects

G L Rossi

Publications and source records attributed to G L Rossi.

At least 55 records · Page 3Linked to original sources

Equine pituitary adenoma: a functional and morphological study.

Clinico-pathological correlations in horses with pituitary adenomas are poorly understood. This paper describes the functional and morphological features of five cases of equine pituitary adenoma and of a case of multinodular pituitary hyperplasia. New findings reported include immunoreactivity for beta-lipotropin (beta-LPH), beta-melanocyte-stimulating hormone (beta-MSH), gamma 3-MSH, prolactin (PRL), and follicle-stimulating hormone (FSH) in neoplastic cells of the pituitary adenoma; and, in the multinodular hyperplasia, beta-LPH, beta-endorphin (beta-END), alpha-MSH, beta-MSH, gamma 3-MSH and FSH immunoreactivity. It is suggested that the equine pituitary syndrome does not correspond to human Cushing's disease, as generally accepted, but is related to the overproduction of several pro-opiomelanocortin (POMC)-derived peptides by the cells of the tumour or hyperplastic nodules.

Adenoma↗

Megaoesophagus in rats: a clinical, pathological and morphometrical study.

Megaoesophagus was observed in 82 Long-Evans rats aged 3-32 months. Clinically, the hair was coarse, the neck distended, the mouth opened, wetted by saliva and soiled by bedding material, and the respiration characterized by tachypnoea and inspiratory crackles. By radiography, after barium administration, the oesophagus was seen to be dilated and filled with impacted dry food in the precardial region. The size of the dilatation varied depending on the oesophageal region and reached a diameter of 12 mm in the most severe case. Histologically, the muscular layers of the dilated portions showed focal inflammation and single fibre necrosis. Each affected oesophagus had (1) an increased circumference and radius and a reduced number of myenteric ganglion cells in both the thoracic and abdominal portions, and (2) a decreased thickness of the muscular layers in the thoracic portion and at the level of the cardia. A simple geometrical model showed that the reduced ganglion cell number was not due to a change in shape of the dilated oesophagus. Since no sign of infectious disease was found in these animals, and rats of other strains kept at the same time under the same conditions were not affected, a hereditary aetiology is suggested.

Animals↗

Normal circulating triiodothyronine concentrations are maintained despite severe hypothyroidism in growing pigs fed rapeseed presscake meal.

Experiments were designed to study effects of dietary rapeseed presscake meal on the thyroid and on the liver 5'-monodeiodinase activity in growing pigs. Animals were fed rapeseed presscake meal (15% in the ration) of 0-varieties (containing relatively high amounts of glucosinolates and goitrin) or a control diet (soybean meal instead of rapeseed presscake meal) without or with thyroxine added to feed. Food intake and average daily gain were comparable because pigs were pair-fed. Serum thiocyanate concentration was significantly greater in pigs fed rapeseed presscake meal. Pigs fed rapeseed presscake meal developed hypothyroidism. Serum free thyroxine concentrations in rapeseed presscake meal-fed pigs were significantly lower than in controls, normal in thyroxine-supplemented pigs fed rapeseed presscake meal and significantly above normal in thyroxine-supplemented controls. Serum free triiodothyronine concentrations were not significantly influenced by rapeseed presscake meal feeding or thyroxine supplementation. Liver weight and total DNA content in pigs fed rapeseed presscake meal were higher than in controls but were not significantly affected by thyroxine feeding. Hepatic 5'-monodeiodinase activity on a protein basis was lower in pigs fed rapeseed presscake meal and was not normalized by thyroxine supplementation. However, in whole liver, because of greater liver mass, 5'-monodeiodinase activity in pigs fed rapeseed presscake meal was similar to that in controls. The data indicate that serum free triiodothyronine concentrations in pigs fed rapeseed presscake meal could be maintained in the physiological range, probably because of enhanced triiodothyronine secretion and sufficient extrathyroidal thyroxine to triiodothyronine conversion.

Animal Feed↗

[First description of a desmoid tumor in a goat and comparative observations to human fibromatosis. Case report].

The macroscopical, histological, and ultrastructural aspects of the abdominal and extra-abdominal desmoid tumour are reported in a 1 1/2-year old goat (breed: Nera-Verzasca, Tessin mountain goat). Macroscopically, the disease was characterized by glassy, whitish, very hard, plate-forming masses found in the abdominal wall and in the medial aspect of the upper hind limbs. Histologically, the masses consisted of well differentiated fibroblasts which locally infiltrated the surrounding tissues. No capsule formation was found. On electron microscopy, the cells appeared to be active, young, collagen-producing fibroblasts. The pathogenesis of this disease is unknown.

Abdominal Muscles↗

Retinol-binding protein is in the molten globule state at low pH.

Using far- and near-UV circular dichroism, viscosity, tryptophan fluorescence, NMR spectra, binding of a hydrophobic probe, and microcalorimetry, we have shown that the apo form of human retinol-binding protein (RBP) at neutral pH is in a rigid state with properties similar to those of holo-RBP. On the contrary, at acidic pH apo-RBP is in the molten globule state which has been earlier revealed for a number of proteins under mild denaturing conditions. We have also shown that, at equilibrium, the pH-induced retinol release from holo-RBP parallels denaturation of the apoprotein. These findings are consistent with our hypothesis that the transformation of RBP into the molten globule state is involved in the mechanism whereby retinol is delivered to target cells. In particular, a local acidic pH near the membrane surface of target cells might cause the transition of RBP to the molten globule state as well as the release of retinol.

Apoproteins↗

IgE and adenosine 5' triphosphate receptors on immature murine mast cells are functionally linked to signal transduction mechanisms.

Calcium mobilization in response to IgE-receptor cross-linking by antigen was assessed in immature murine mast cells cultured from bone marrow to determine whether the early expression of IgE receptors on such cells may be of functional significance. IgE receptors were expressed by approximately 30% of cells after 1 week in culture and by an increased proportion at 2 and 3 weeks. The ability of a non-IgE-dependent stimulus, adenosine 5' triphosphate (ATP), to increase intracellular calcium in these cells was also tested. Calcium mobilization in large numbers of individual cells was monitored with use of a fluorimetric reagent and flow cytometry. Both antigen and ATP had significant effects on intracellular calcium in cells cultured for as little as 1 week with interleukin-3, when few cells exhibited morphologic or functional characteristics of mast cells. Longer times in culture were associated with an increase in the proportion of cells responding to these stimuli with calcium mobilization, but not with a change in the magnitude of the response. We conclude that the early expression of IgE receptors during mast cell development may be functionally significant, since these receptors appear to be linked to cellular signal transduction mechanisms. The data additionally imply a possible role for ATP in mast cell development.

Adenosine Triphosphate↗

Immunohistochemistry of hepatic IGF-I in calf, pig, and rat.

The liver appears to be the major site of synthesis of somatomedin C or insulin-like growth factor I (IGF-I), yet, the intrahepatic histological localization of this polypeptide is not well known. For this reason we investigated immunohistochemically the liver of calves, pigs, and rats, fixed by perfusion or immersion with Karnovsky solution. In all three animal species the layer of hepatocytes bordering the liver capsule was labeled by anti-IGF-I. In the pig and rats all perivenous hepatocytes were intensively labeled whereas in calves only the periportal hepatocytes contained immunoreactive IGF-I. While preabsorption of the anti-IGF-I antiserum with the antigen abolished the immunoreaction, preabsorption with insulin or IGF-II did not. No labeling occurred when immersion-fixed liver tissue was used.

Animals↗

Reduced number and LH content of marginated secretory granules in pituitary gonadotropes of streptozocin-induced diabetic male rats.

The transport of secretory granules towards the subplasmalemmal (SPL) region of the luteinizing-hormone (LH) gonadotrope is controlled by the LH-releasing-hormone-dependent pathway. The SPL granules contain the most readily releasable LH. To test the effect of diabetes on both the number and LH content of marginated granules, we studied by indirect immunogold-labelling pituitaries from control and streptozocin (STZ)-treated male rats. On electron micrographs we measured the areas of the gonadotrope nucleus and cytoplasm, counted all secretory granules, and counted and measured secretory granules in selected SPL regions. Furthermore, we counted gold particles (IG) on (a) the secretory granules of the SPL regions, (b) the intergranular SPL cytoplasm and (c) the region outside the cell. Finally, in order to evaluate possible diabetes-related changes of the pituicyte cytoskeleton, we measured by densitometry actin, tubulin, vimentin, and desmin in immunocytochemically stained pituitary sections. In diabetic compared with control cells of the studied pituitary region, we observed: (a) cytoplasmic atrophy; (b) the number of secretory granules per unit area increased in the total cytoplasm, and decreased in the SPL cytoplasm (lowered regulated secretion); (c) decreased IG labelling in the SPL granules (reduced amount of hormone transported by each granule towards the cell membrane); (d) decreased IG labelling in the integranular SPL cytoplasm (reduced constitutive secretion), and (e) strongly increased actin and desmin, yet unchanged tubulin and vimentin immunoreactivity. Our data indicate that both regulated and constitutive secretion are possibly reduced in gonadotropes of diabetic male rats. The cytoskeletal alterations may also contribute to the reduced regulated secretion.

Actins↗

Endogenous development of Eimeria intestinalis in rabbits (Oryctolagus cuniculus).

The endogenous life cycle of a pure strain of Eimeria intestinalis was studied by light and electron microscopy in coccidia-free rabbits. Four schizont generations could be observed: the first one, not previously described, was seen between 36 and 144 hr postinoculation (PI), the second one between 64 and 168 hr PI, the third one between 96 and 192 hr PI, and the fourth one between 168 and 240 hr PI. Gamogony apparently started as early as 144 hr PI. Thus, it was possible for oocysts to develop from third generation merozoites, later oocysts developing after the fourth schizont generation. Electron microscopic observation suggested that oocysts were derived mainly from merozoites of the fourth schizont generation. During the first stage of the life cycle, sporozoites were seen in intraepithelial lymphocytes. All asexual generations, except the fourth, were characterized by 2 schizont types: the first, regarded as female, contained mononuclear merozoites and the second, regarded as male, contained polynuclear merozoites.

Animals↗

Crystals of haemoglobin with the T quaternary structure bind oxygen noncooperatively with no Bohr effect.

The relationship between the structure and function of haemoglobin has mainly been studied by comparing its X-ray crystal structures with its function in solutions. To make a direct comparison we have studied the functional properties of haemoglobin in single crystals, an approach that has been an important part of the investigation of several enzyme mechanisms. Here we report on the oxygen binding by single crystals of human haemoglobin grown in solutions of polyethylene glycol. Unlike haemoglobin crystals formed in concentrated salt solution, which crack and become disordered on oxygenation, crystals grown in polyethylene glycol remain intact. X-ray studies have shown that the T (deoxy) quaternary structure of haemoglobin in this crystal at pH 7.0 is maintained at atmospheric oxygen pressure, and that the salt-bridges are not broken. We find striking differences between oxygen binding by haemoglobin in this crystal and by haemoglobin in solution. Not only is oxygenation of the crystal noncooperative, but the oxygen affinity is independent of pH in the range 6.0-8.5, and is much lower than that of the T state in solution. The lack of cooperativity without a change in quaternary structure is predicted by the two-state allosteric model of Monod, Wyman and Changeux. The absence of a Bohr effect without breakage of salt-bridges is predicted by Perutz's stereochemical mechanism. In contrast to the X-ray result that oxygen binds only to the alpha haems, our measurements show that the alpha haems have only a slightly higher affinity than the beta haems.

Allosteric Regulation↗

Morphofunctional study of the effects of fetal exposure to cyproterone acetate on the hypothalamo-pituitary-gonadal axis of adult rats.

Fetal exposure to cyproterone acetate (CPA), while allowing, normal sexual morphogenesis, has previously been shown to lead to functional endocrine abnormalities in adult rats of both sexes. Because of this, we examined morphologically and morphometrically the hypothalamic nuclei involved in sexual dimorphism as well as the pituitary lactotropes of rats exposed in utero from day 15 to 20 of gestation to CPA. Male and female offspring was studied at the age of 70-80 days. In both sexes the brain weight was lower (p less than 0.05) in CPA-treated than in control rats. Morphometrical investigations showed that the surface density (Sv) and the volume density (Vv) of the ventromedial nucleus were higher (p less than 0.05) in CPA-treated male than in control rats. By comparing sexes the Sv and Vv of the ventromedial nucleus were higher (p less than 0.01) in CPA-treated male than in corresponding female rats. Also the nuclear surface of the tyrosine hydroxylase-immunoreactive neurons of the arcuate nucleus was higher (p less than 0.05) in CPA-treated male than in female rats. In lactotropes of the pituitary gland the immunoreactive prolactin (PRL) was densitometrically increased (p less than 0.05) in CPA-treated female compared with control rats. By electron microscopy, PRL granules and autophagocytosis appeared to be more abundant in CPA-treated rats of both sexes. These data show that fetal exposure to CPA results in long-term anatomical and physiological alterations of hypothalamic and preoptic nuclei as well as of the pituitary lactotropes. These permanent changes support the functional endocrine abnormalities observed in adult rats.

Androgen Antagonists↗

A clinico-pathological study of canine Cushing's disease caused by a pituitary carcinoma.

Knowledge of clinico-pathological correlations in canine Cushing's disease is rather poor. Therefore we describe, clinically and pathologically, a case of pituitary tumour-dependent Cushing's disease in an 8-year old female cocker spaniel. Based on our results, the tumour was defined as a non-dexamethasone-suppressive, corticotrophic adenocarcinoma characterized by some new findings such as intracerebral metastases of anti-ACTH-labelled tumour cells and combined alpha-, beta- and gamma 3-MSH immunoreactivity in the tumour.

Adenocarcinoma↗

Sexually dimorphic effects of aging on rat somatotropes and lactotropes.

During the aging process modified functions of hypothalamic factors may cause sexually dimorphic changes in pituitary somatotropes and lactotropes. To test this hypothesis, pituitary tissue from young adult (4 months) and old (20-22 months) male and female rats was labeled immunocytochemically for growth hormone (GH) and prolactin (PRL). The total amount of immunoreactive material as well as the total area and number of immunoreactive structures were evaluated. With increasing age the intracellular GH content was moderately increased in male and decreased in female rats. An age-dependent PRL increase, due both to increased cell number and intracellular hormone content, was present only in female rats. The amount of GH- and PRL-immunoreactive material, distributed into classes of increasing density, differed both between sex and age groups. Our results indicate that the aging process of the somatotrope and lactotrope cell populations in rats appears to be different in the two sexes.

Aging↗

Functional and morphological changes in the hypothalamo-pituitary-gonadal axis of aged female rats.

Age-related functional and morphological alterations in the hypothalamo-pituitary-gonadal axis were investigated in old recurrently pseudopregnant (RPP) female rats, and these alterations were compared with those in young diestrous rats. LHRH in the median eminence (ME) and mediobasal hypothalamus (MBH) as well as plasma FSH, LH, and progesterone were measured by RIA. LHRH in the lateral ME (LME) and pituitary FSH and LH were evaluated by morphometry and densitometrical immunocytochemistry. Furthermore, by light microscopy, we classified and counted the number of ovarian follicles and corpora lutea. LHRH concentrations in the ME and MBH were similar in old and young rats, whereas in old rats, plasma FSH was markedly increased, LH was moderately increased, and plasma progesterone was unchanged. The number and the total area and immunoreactivity of LHRH-labeled axon cross sections in the LME were reduced in old rats. The number of nucleated FSH-labeled cells and total FSH area and immunoreactivity were almost twice in old compared with young animals. The measurements of LH-labeled cells were not different between the two groups. In old rats, the numbers of ovarian follicles and corpora lutea were reduced and that of atretic follicles increased. In conclusion, age-related morphological impairments of LHRH axons associated with an increased number of FSH gonadotropes and higher plasma FSH in our old RPP rats suggest hypothalamic and pituitary disturbances, which may largely contribute to the complex hormonal disarrangement responsible for the decline of reproductive functions in old female rats.

Aging↗

Calcium mobilization in activated mast cells monitored by flow cytometric analysis.

Changes in intracellular calcium levels induced in mast cells by either antigen or ionomycin were monitored using flow cytometry and the calcium binding dye indo-1. Both stimuli increased calcium levels in responsive cells by a similar amount, but not all cells examined were responsive to antigen. Antigen-induced increases in intracellular calcium levels could be completely blocked by the calcium antagonist TMB-8. Flow cytometry appears to be a useful method for monitoring mast cell calcium concentrations, as it provides the capability to study large numbers of individual cells.

Animals↗

The age at onset of diabetes influences functional and structural changes in the pituitary-thyroid axis of streptozocin-diabetic male rats.

Severe structural changes leading to marked alterations in secretory activity are known to occur in the pituitary-thyroid axis 1 month after induction of postpuberal streptozocin (SZ)-diabetes. However, SZ-diabetic rats of different age groups have not been compared, nor has the maturity of the pituitary and thyroid glands at the onset of diabetes been correlated with the type and evolution of functional and structural changes. We thus induced diabetes in 1-month (prepuberal of 3-month (postpuberal) old male rats and compared diabetic with control groups 4 and 8 months after SZ or saline injection. We determined: 1) pituitary and thyroid weights, 2) the basal plasma TSH, T3, and T4 concentrations, and 3) several morphometrical measurements in the pituitary and thyroid glands. After 4 months, 1) the pituitary and thyroid weights were decreased, 2) plasma TSH and T3 were unchanged, plasma T4 was reduced. and 3) the number of thyrotropes, degenerative changes of follicle cells, and colloid area were increased, the follicle cell height as well as the number of fused cold follicles decreased, and the follicle area was unchanged in diabetic compared with control rats. The lesions were more conspicuous in pre- than in postpuberal diabetic animals. After 8 months, plasma TSH, T3, and T4 were decreased in diabetic compared with control rats. Except for the increased colloid area, all other lesions were similar, though more severe in prepuberal diabetic rats after 8 than 4 months. Few changes were found in postpuberal diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Abnormal regulation of the hypothalamo-pituitary-adrenal axis in the genetically obese fa/fa rat.

Adrenalectomy has been shown to reverse most facets of the syndrome of the genetically obese fa/fa rat. However, a detailed analysis of the hypothalamo-pituitary-adrenal (HPA) axis in these animals is lacking. In the present study, morning corticosteronemia was higher in obese rats of both sexes than in lean ones, whereas evening corticosteronemia was higher only in obese male rats. The HPA axis was further investigated using stressful stimuli. Immobilization, ether, and cold stresses resulted in greater corticosterone levels in obese than in lean animals. These abnormalities consisted in upward shifts of the corticosterone response in obese females and absolute increases in that of obese males, indicating that such alterations were more pronounced in obese male than obese female rats. Due to this, the putative origin of the increased corticosterone output of obese rats was studied in males. Greater levels of ACTH were reached in obese than in lean rats when submitted to a cold stress (6 C). Dexamethasone produced a complete suppression of corticosterone output in both lean and obese rats. During the recovery from such suppression, corticosterone levels rose to higher values in obese than in lean rats. This observation together with the greater cold-induced ACTH output in obese rats suggest that the increased activity of the HPA axis of these animals is of central origin. Whatever its precise etiology within the central nervous system, it is proposed that the increased HPA axis activity in obese rats and its resultant hypercorticism play a role in the establishment and maintenance of their syndrome.

Animals↗

Changes in the hypothalamo-pituitary-adrenal axis of genetically obese fa/fa rats: a structural, immunocytochemical, and morphometrical study.

Most metabolic disorders of genetically obese Zucker rats are reversed by adrenalectomy and are restored by corticosterone treatment, thus suggesting that a functional hypercorticosteronemic state is involved in the pathogenesis of the obesity syndrome in fa/fa rats. However, the hormone content and morphology of the hypothalamo-pituitary-adrenal axis of this animal model have to our knowledge not yet been described. We, thus, investigated morphologically and morphometrically the hypothalamic regions involved in CRF synthesis and secretion in male fa/fa rats. To ascertain if the brain is selectively or uniformly affected, we studied the main nuclei of the lateral and mediobasal hypothalamus, i.e. arcuate, lateral hypothalamic, and ventromedial nucleus and the parvicellular portion of the paraventricular nucleus. Moreover, after immunocytochemical labeling, we analyzed densitometrically the CRF-bearing axons of the median eminence and the ACTH-containing cells of the anterior and intermediate lobe of the pituitary gland. Finally, we investigated the adrenal glands by qualitative light microscopy. In fa/fa rats most hypothalamic nuclei were structurally changed. Furthermore, hypothalamic CRF and anterior pituitary ACTH contents as well as adrenal weight were increased, the zona fasciculata of the adrenal cortex was hypertrophic, and the ACTH content of the intermediate lobe was reduced. In conclusion, our results demonstrate that the obesity syndrome in genetically obese fa/fa rats is associated with lesions of the hypothalamo-pituitary-adrenal axis consistent with hyperadrenocorticism due to hyperactivity of the whole adrenal axis. Alterations also occur in the hypothalamic nuclei controlling glycemia, insulinemia, and circadian corticosterone secretion.

Animals↗