Search PubMed⌕ Search

Biomedical subjects

S L Asa

Publications and source records attributed to S L Asa.

At least 163 records · Page 9Linked to original sources
PubMed1989

Spontaneous pituitary gonadotroph nodules in aging male Lobund-Wistar rats.

Spontaneous pituitary changes with aging were studied in 130 male Lobund-Wistar rats by light and electron microscopy and immunohistochemistry. These 69 healthy rats (6, 18, and 30 months) and 61 moribund rats (17-50 months) had been maintained in four different groups with the following environmental conditions: conventional full fed, convention food restricted, germ free-full fed, and germ free-food restricted. Gonadotroph nodules were the most frequent proliferative lesions (27 rats). It was difficult to determine whether these nodules were hyperplastic or neoplastic. They were found in aging rats (26 months or older) and their development was delayed by food restriction and germ-free status parallel to prolongation of life-span. No significant difference in incidence of gonadotroph nodules was demonstrated among the four groups. Six lactotroph adenomas, a thyrotroph nodule, and a mixed thyrotroph and lactotroph nodule were also noted in aging rats (30 months or older). In extranodular adenohypophyses, variable numbers of hyperactive gonadotrophs histologically similar to those in gonadotroph nodules were observed in almost all rats including 6-month rats, suggesting that gonadotrophs were continuously hyperactive during their lifetime from an early stage. The mechanism accounting for the development of gonadotroph nodules remain to be established. It can be concluded that food restriction and germ-free status may have a retarding effect but no preventative role in the development of gonadotroph nodules, which are the most common age-associated pituitary lesions of male Lobund-Wistar rats.

Aging↗
PubMed1989

Adenohypophysial changes in conventional, germ free and food-restricted aging Lobund-Wistar rats. A histologic, immunocytochemical and electron microscopic study.

The pituitaries of aging male Lobund-Wistar rats were investigated by histology, immunocytochemistry and electron microscopy. In contrast to previous studies undertaken on aging rats of various strains, no lactotroph hyperplasia was found in the adenohypophysis of the present study. Lactotroph adenomas producing PRL were infrequent, whereas gonadotroph adenomas containing FSH and LH were common. The frequency of gonadotroph adenomas was decreased in germ free as well as food-restricted rats and in those in which the germ free state was associated with reduced food intake.

Adenoma↗
PubMed1988

Reversible sellar enlargement due to growth hormone-releasing hormone production by pancreatic endocrine tumors in a acromegalic patient with multiple endocrine neoplasia type I syndrome.

A 28-year-old woman presented with hypoglycemia and acromegaly associated with pituitary sellar enlargement. Preoperative plasma levels of insulin and growth hormone (GH) were markedly elevated and there was mild hyperprolactinemia. Laboratory tests suggested hyperparathyroidism. Partial pancreatectomy was performed and two tumors were found. Morphologic examination revealed two well-differentiated pancreatic endocrine neoplasms with distinct histologic, immunohistochemical, and ultrastructural features. Immunoreactivity for insulin was present in the larger tumor; the smaller tumor contained glucagon, gastrin, somatostatin, and pancreatic polypeptide. Both neoplasms demonstrated growth hormone-releasing hormone (GRH) immunopositivity and released GRH in vitro. Subsequent studies confirmed abnormally elevated preoperative plasma levels of GRH. Postoperatively, blood glucose, insulin, GRH, and GH normalized and there was regression of acromegalic features with significant reduction in sellar size. The clinicopathologic findings indicate that, in patients with multiple endocrine neoplasia type I (MEN-I), GRH production by pancreatic tumors can stimulate hypophysial somatotrophs resulting in GH excess and acromegaly due to a reversible pituitary lesion, most likely somatotroph hyperplasia.

Acromegaly↗
PubMed1988

Oncocytomas and null cell adenomas of the human pituitary: morphometric and in vitro functional comparison.

In this study, light microscopic and ultrastructural morphometric features of oncocytomas and null cell adenomas were compared and the morphometric data were correlated with in vitro endocrine activity. All tumours were unassociated with clinical or biochemical evidence of hormone excess and were diagnosed as oncocytomas or null cell adenomas, using histology, immunohistochemistry and electron microscopy. In oncocytomas, when compared with null cell adenomas, light microscopic morphometry revealed that total cell areas were significantly larger and nuclear cytoplasmic ratios were smaller due to an increase in cytoplasmic areas. Ultrastructural morphometry disclosed an abundance of mitochondria in oncocytomas. Absolute volumes of cytoplasmic organelles per cell were not reduced in oncocytomas compared with those of null cell adenomas. These results indicate that accumulating mitochondria do not replace other cytoplasmic organelles, and furthermore that the functional potential of oncocytomas is not lost. In vitro study demonstrated the production of pituitary hormones, primarily gonadotropins in oncocytomas and null cell adenomas. It can be concluded that oncocytomas, which represent the final stage of oncocytic transformation, have a close relationship with null cell adenomas based on morphometric comparison as well as in vitro studies.

Adenoma↗
PubMed1988

Primary thyroid thymoma: a distinct clinicopathologic entity.

A 51-year-old man presented with a paratracheal tumor. He had undergone resection of a thyroid tumor 15 years previously; at that time, the histologic diagnosis had been anaplastic carcinoma. When the tumor recurred, the presumptive clinical diagnosis was medullary thyroid carcinoma. Histologic examination revealed a poorly differentiated epithelial tumor with immunoreactivity for keratins, carcinoembryonic antigen, and, focally, S-100 protein. The tumor was negative for calcitonin and thyroglobulin. There were scattered lymphocytes and plasma cells. Ultrastructural examination showed elongated epithelial cells with prominent desmosomes and bundles of cytoplasmic tonofilaments but no secretory granules; amyloid was not present ultrastructurally or histochemically. The characteristic ultrastructural and immunocytochemical features and the clinical behavior of this tumor verify the existence of primary thyroid thymoma. This new primary thyroid neoplasm is of clinical importance, considering the more benign behavior of primary thyroid thymoma than of other tumors in the differential diagnosis of this lesion.

Adult↗
PubMed1988

In vitro studies of human pituitary adenomas.

The application of morphologic and tissue culture techniques to the study of human pituitary adenomas allows further investigation of structure-function correlations. Using these methods, we have documented morphometric differences between densely and sparsely granulated somatotroph adenomas but the release of growth hormone in vitro and responses to adenohypophysial hormones/drugs do not correlate with tumor type. The morphologic and functional alterations in somatotroph adenomas exposed to SMS 201-995 appear to be reversible in vitro. Incubation of lactotroph adenomas with bromocriptine for 3 days directly reduces tumor cell size, cytoplasmic volume and cytoplasmic volume densities of endoplasmic reticulum and Golgi regions; these changes are similar to the effects of longterm bromocriptine therapy in vivo. Tissue culture studies of gonadotroph adenomas of men confirm that gonadotropin-releasing hormone (GnRH) stimulates gonadotropin release by tumor cells and yields morphologic evidence of increased hormone synthesis whereas these tumors have variable sensitivity to gonadal steroids; structural changes in tumor cells correlate with hormone release after stimulation, suggesting that morphologic parameters may reflect the hormonal milieu of these adenomas. Null cell adenomas and oncocytomas release small quantities of glycoprotein hormones, predominantly gonadotropins in vitro and there are no functional differences between these 2 tumor types; gonadotropin release responds to GnRH stimulation and, paradoxically, to other adenohypophysiotropic hormones, but such stimulation does not result in secretion of other adenohypophysial hormones by these tumors.

Adenoma↗
PubMed1988

Human fetal adenohypophysis. Electron microscopic and ultrastructural immunocytochemical analysis.

The pituitary glands were removed from 63 human fetuses from 5 weeks of gestation to term and studied by electron microscopy and ultrastructural immunocytochemistry to document the development of cell differentiation and hormone production in the adenohypophysis. At 5 weeks of gestation, Rathke's cleft was lined by columnar epithelium with abundant cytoplasmic glycogen and occasional secretory granules. By 6 weeks of gestation, cells resembling corticotrophs were identified; in 8-week-old fetuses, type I microfilaments were found in those cells. Well-differentiated somatotrophs were seen in adenohypophyses of 8- to 9-week-old fetuses. Although secretory granules were numerous, the Golgi complex was inconspicuous in early fetal glands. After 10 weeks of gestation, there was a change with morphologic evidence of active hormone secretion; large Golgi regions and sparsely granulated cells were found. Some somatotrophs at this stage contained aggregates of type II microfilaments which resembled the fibrous bodies of sparsely granulated somatotroph adenomas. Densely granulated mammosomatotrophs containing growth hormone and prolactin were identified at 12 weeks of gestation. Cells with characteristics of the glycoprotein hormone cell line were seen in pituitaries at 12 weeks of gestation; thyrotrophs and gonadotrophs were identified after 15 weeks. Typical lactotrophs were not recognized before 23 weeks, but were numerous in pituitaries of fetuses older than 35 weeks. This study documents for the first time the existence of a bihormonal mammosomatotroph in the human fetal pituitary and confirms that somatotrophs and lactotrophs, the two acidophil cell types, are embryologically related.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1988

Effect of bromocriptine on secretion and morphology of human prolactin cell adenomas in vitro.

The direct effect of short-term bromocriptine administration on human prolactin cell adenomas in vitro was studied by light and electron microscopy and correlated with the effect on hormone release. The light microscopic and, for the first time, ultrastructural characteristics of adenomatous prolactin cells in control and treated cultures were analyzed morphometrically and the changes induced by bromocriptine were quantified. Following 72 h treatment which lowered levels of prolactin release, there was a marked reduction in cell size, cytoplasmic volume and cytoplasmic volume densities of endoplasmic reticulum and Golgi apparatus. In contrast, the percentage of cytoplasm occupied by lysosomes increased. There was no consistent change in number and diameter of secretory granules. These findings indicate that prolactin cell involution is a direct effect of bromocriptine and suggest that reduction in endoplasmic reticulum and Golgi complex is largely responsible for the decreased cell size. Lysosomal degradation of cytoplasmic components may play a role in this process.

Adult↗
PubMed1988

Growth hormone-releasing hormone-producing tumors: clinical, biochemical, and morphological manifestations.

This paper has reviewed current knowledge of clinical, biochemical, and morphological manifestations of extracranial GRH-producing tumors. Excessive GRH release stimulates pituitary somatotrophs causing elevation of blood GH levels and acromegaly. In some patients with GRH-containing tumor, blood GH concentrations are normal and no acromegaly develops. GRH-producing tumors associated with acromegaly are rare. Based on a critical analysis of the literature, 30 tumors are accepted as definitive. They possess unique features: occurrence in young age, female preponderance, foregut derivation, benign biological behavior, small secretory granules, and frequent association with MEN type I syndrome. The pancreas and lung are common primary sites. GRH-containing tumors unassociated with acromegaly include those of gut and thymus, small cell carcinoma of lung, and medullary carcinoma of thyroid. Several tumors are plurihormonal. In contrast to somatotroph adenoma seen in patients with classical acromegaly, the hypophysial lesion represents somatotroph hyperplasia in acromegalic patients with GRH-producing tumor. This finding indicates that GRH not only increases somatotroph secretory activity but causes somatotroph proliferation. Studies of GRH-producing tumors are of fundamental importance in obtaining a deeper insight into endocrine activity of pituitary somatotrophs and the pathogenesis of GH-secreting pituitary adenomas associated with acromegaly; the importance of GRH in the etiology of acromegaly is still unresolved. The relationship between GRH-secreting tumors and MEN type I syndrome is controversial; further studies are required to elucidate whether they represent two distinct entities or whether GRH-producing tumors accompanied by acromegaly are only forme fruste manifestations of MEN type I syndrome.

Acromegaly↗
PubMed1988

Structure-function correlations of human pituitary gonadotroph adenomas in vitro.

Two pituitary gonadotroph adenomas were studied in vitro to characterize structure-function correlations. Both tumors were from men, aged 63 and 69 years, who had elevated blood levels of follicle-stimulating hormone (FSH) and normal blood luteinizing hormone (LH) and testosterone values. The surgically resected adenomas contained diffuse immunohistochemical positivity for beta-FSH, beta-LH, and alpha-subunit of glycoprotein hormones; by electron microscopy they were composed of well-differentiated gonadotrophs. In vitro, both tumors released FSH, LH, and alpha-subunit. Morphometric studies were performed on surgically resected and cultured adenoma cells. Compared with the surgical specimens, the cultured cells had decreased cytoplasmic volume densities of endoplasmic reticulum and Golgi apparatus and slightly increased cytoplasmic volume densities of secretory granules. Incubation with gonadotropin-releasing hormone (GnRH) for 2 and 24 hours increased FSH, LH, and alpha-subunit release by both tumors; morphometry after 2 consecutive days of exposure confirmed significant increases in cytoplasmic volume densities of endoplasmic reticulum and Golgi regions and marked decreases in that of secretory granules. There was no significant change in cell size, nuclear/cytoplasmic ratio, or secretory granule diameter. The two tumors differed in their response to gonadal steroids. Estradiol, testosterone, and progesterone stimulated release of FSH, LH, and alpha-subunit by one tumor and the morphologic changes paralleled the biochemical response; addition of testosterone suppressed the secretory and morphologic response to GnRH. The other tumor showed no significant response to estradiol or testosterone and addition of these steroids did not alter the response to GnRH. The results are consistent with the interpretation that GnRH stimulates not only release but also synthesis of gonadotropins by gonadotroph adenomas of men. The data also indicate variable sensitivity of these tumors to gonadal steroids with paradoxical stimulation alone and inhibition of response to GnRH. The structural changes correlate with the hormone release response in vitro.

Adenoma↗
PubMed1987

Vasoactive intestinal peptide-containing nerves in Peyer's patches.

Vasoactive intestinal peptide (VIP) is a neuropeptide that is well represented in the gut tract. Previous work has demonstrated that murine T lymphocytes have high-affinity specific receptors for VIP and has implicated their interaction with VIP in the control of T-cell migration into Peyer's patches in vivo. It was postulated that this effect was mediated by interactions in the vicinity of the specialized endothelium of the postcapillary venules of Peyer's patches. We report the localization of VIP-like immunoreactivity in mouse Peyer's patches. Immunohistochemical staining was performed with heterologous antiserum against VIP using the avidin-biotin-peroxidase complex technique. VIP positivity was present near vessels of various sizes and in close proximity to small caliber vessels lined with specialized polygonal endothelial cells. These findings provide an anatomical basis for the concept that VIP may be available as a local neurophysiological signal during the migration of lymphocytes from the blood into Peyer's patches.

Animals↗
PubMed1987

Immunohistologic localization of corticotrophin-releasing hormone in human tumors.

The authors investigated formalin-fixed, paraffin-embedded human tissues for the presence of corticotrophin-releasing hormone (CRH) using the avidin-biotin-peroxidase technic. Immunopositivity was demonstrated in nontumorous hypothalami, 1 of 8 hypothalamic gangliocytomas, 3 of 9 bronchial endocrine tumors, 1 of 30 small cell lung carcinomas, 1 of 8 ileal endocrine neoplasms, 2 of 20 pancreatic endocrine tumors, 2 of 10 medullary thyroid carcinomas, and 1 of 3 small cell prostate carcinomas. Of the tumors containing immunoreactivity, most were associated with Cushing's syndrome; the ileal and thyroid tumors were not. Adrenocorticotrophic hormone was immunohistochemically localized in two bronchial and one pancreatic tumor, which contained CRH-like immunoreactivity. No CRH was detected in nontumorous extrahypothalamic tissues from which the CRH-containing tumors derived, two mediastinal endocrine carcinomas, six endocrine tumors of the stomach/duodenum/appendix, eight pheochromocytomas, one Merkel cell tumor, and 32 squamous and adenocarcinomas of the lung/gut. CRH-like immunoreactivity may be found in tumors composed of peptide-hormone-producing endocrine cells; hypersecretion of CRH by those neoplasms may be significant in the development of Cushing's syndrome.

Adolescent↗
PubMed1987

Lipid degeneration in pheochromocytomas mimicking adrenal cortical tumors.

A case of bilateral adrenal pheochromocytomas with unusual morphologic features is reported in a 27-year-old man with a family history of von Hippel-Lindau disease. In both glands, the medulla was replaced by neoplasms with two distinct gross and microscopic appearances. There was typical pheochromocytoma in areas of dusky red tissue. The yellow nodules noted on gross examination were microscopically composed of large cells with vacuolated cytoplasm. Fat stains confirmed the presence of lipid in these areas. Immunohistochemistry revealed positivity for neuron-specific enolase and chromogranin in the cytoplasm of pheochromocytes, as well as in the perinuclear cytoplasm and processes of cells scattered in the yellow nodules. Ultrastructural examination of the yellow lesions showed characteristics of pheochromocytoma and an extensive accumulation of lipid. Although gross and light-microscopic examination of the yellow tissue suggested adrenal cortical nodules, immunohistochemistry and electon microscopy elucidated lipid degeneration within pheochromocytoma, a finding not previously described.

Adrenal Cortex Neoplasms↗
PubMed1987

Effect of SMS 201-995, a long-acting somatostatin analogue, on the secretion and morphology of a pituitary growth hormone cell adenoma.

The present study reports the effects of SMS 201-995, a long-acting somatostatin analogue, on blood GH levels, glucose tolerance and tumour morphology in a 36-year-old, previously untreated acromegalic woman. Treatment (50 micrograms s.c., 8-hourly) resulted in marked suppression of GH concentration and an improvement in glucose tolerance. After 10 d of treatment, the tumour was removed by transsphenoidal surgery and studied by histology, immunohistochemistry, transmission electron microscopy and morphometry. Histologically, the tumour was an acidophilic adenoma which contained immunoreactive GH in many adenoma cells. By electron microscopy, the tumour was composed of densely granulated somatotrophs containing numerous large secretory granules and many lysosomes showing crinophagy. No cell necrosis or vascular impairment were evident. Using morphometry, the tumour was compared with 10 densely granulated somatotroph adenomas, removed from acromegalic patients not treated with somatostatin. The nuclear and cytoplasmic areas of the adenoma subjected to SMS 201-995 treatment were smaller, and the lysosomes occupied more of the cytoplasmic volume than those of controls. The nuclear/cytoplasmic ratio, cytoplasmic volume densities of endoplasmic reticulum, Golgi apparatus, mitochondria, secretory granules and secretory granule diameters were within the range of control adenomas. In vitro, treated adenoma cells secreted GH and retained responsiveness to both GRH stimulation and somatostatin suppression. The morphologic findings after SMS 201-995 treatment, are consistent with suppression of GH release. There is no evidence that somatostatin has any direct cytotoxic or vasotoxic effects. It appears that SMS 201-995 represents a potent and promising drug in the medical treatment of acromegaly, however, more work is needed to elucidate the mechanism of somatostatin suppression and to provide evidence for adenoma shrinkage.

Acromegaly↗
PubMed1987

Alpha-transforming growth factor in the bovine anterior pituitary gland: secretion by dispersed cells and immunohistochemical localization.

A growth factor secreted by bovine calf anterior pituitary cells in culture was purified, and its N-terminal amino acid sequence was determined. This sequence shows near-identity with human and rat alpha-transforming growth factor (alpha TGF). With the use of an anti-alpha TGF monoclonal antibody generated against a C-terminal rat alpha TGF synthetic peptide, alpha TGF-like material was localized by immunohistochemical techniques in the cytoplasm of normal bovine adenohypophysial cells. The antibody staining was immunospecific because it could be completely inhibited by saturating concentrations of the synthetic peptide to which it was raised. There was no immunoreactivity in cells of the intermediate and posterior lobes. Some of the cells containing alpha TGF immunoreactivity also contained PRL; alpha TGF immunoreactivity was not demonstrated in cells containing ACTH, TSH, FSH, and LH. This is the first report documenting the secretion of alpha TGF by nonneoplastic adult cells and the presence of alpha TGF immunoreactivity in the corresponding normal adult tissue.

Animals↗
PubMed1987

Ovarian transforming growth factor-alpha gene expression: immunohistochemical localization to the theca-interstitial cells.

Rat ovaries were examined for the presence of transforming growth factor-alpha (TGF-alpha). Immature diethylstilbestrol-primed rats were treated for 3 days prior to sacrifice with or without FSH. Their ovaries were either fixed in formaldehyde for immunohistochemistry or the RNA was extracted for northern blot analysis. Hybridization with a rat TGF-alpha cDNA probe revealed a 4.5 kilobase mRNA whose abundance was markedly stimulated in the rats treated with FSH. Immunohistochemical staining, using a sequence specific monoclonal antibody to TGF-alpha, MF9, detected immunoreactive TGF-alpha only in the interstitial and theca cells. FSH treatment resulted in no appreciable change in the immunostaining. These results suggest that TGF-alpha is synthesized in the ovary, perhaps in the theca-interstitial compartment.

Animals↗
PubMed1987

Pancreatic endocrine tumour producing growth hormone-releasing hormone associated with multiple endocrine neoplasia type I syndrome.

We report the first documentation of GHRH production by a tumour associated with proven multiple endocrine neoplasia (MEN). A 30-year-old woman had hypoglycaemia, hyperparathyroidism, and pituitary adenoma with hyperprolactinaemia. Serum growth hormone elevation was attributed to hypoglycaemia but plasma GHRH was elevated. Subtotal pancreatectomy revealed multiple endocrine tumours and nesidioblastosis. Immunohistochemistry demonstrated insulin, glucagon, and somatostatin in several tumours. GHRH was localized in the largest one and was released from that tumour in vitro. Post-operative plasma GH returned to normal. Excess secretion of humoural factors by one tumour may stimulate growth of other tumours in MEN syndromes. The prevalence of GHRH in MEN-I tumours remains to be established.

Adult↗