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S L Asa

Publications and source records attributed to S L Asa.

At least 145 records · Page 8Linked to original sources
PubMed1991

Galanin immunoreactivity in neuroendocrine tumors.

We investigated immunoreactivity for galanin, a 29-amino acid peptide, in formalin-fixed, paraffin-embedded sections of 123 neuroendocrine tumors. Galanin-immunoreactive cells were found in one of 12 hypothalamic gangliocytomas, nine of 18 adrenal pheochromocytomas, nine of 14 pituitary corticotroph adenomas, and one of two thymic endocrine tumors. In pheochromocytomas, galanin-immunoreactive cells were seen either singly or in clusters. In corticotroph adenomas, many tumor cells were positive for galanin, indicating colocalization of corticotropin and galanin in the same tumor cells. No galanin-immunoreactive cells were noted in four extra-adrenal paragangliomas; 10 medullary carcinomas of the thyroid; 35 endocrine tumors arising in the lung, pancreas, and gastrointestinal tract; and 28 pituitary adenomas composed of cells other than corticotrophs. In nontumorous counterparts of these neuroendocrine tumors, galanin immunoreactivity was observed in nerve cells of the hypothalamus, nerve fibers of the duodenum, and adenohypophyseal cells corresponding to corticotrophs. These findings indicate that galanin expression in neuroendocrine tumors is uncommon and restricted to some tumor types.

Endocrine Gland Neoplasms↗
PubMed1991

Reverse hemolytic plaque assay. Electron microscopic observation of plaque-forming single adenoma cells in GH producing adenomas.

In this study, 3 GH-producing adenomas were studied as materials to clarify the usefulness of electron microscopic investigation of plaque-forming single adenoma cells, and ultrastructural morphometric comparisons were made to determine whether some differences exist at the cytoplasmic organelle level between small plaque-forming cells and large plaque-forming cells. In two cases, the relative cytoplasmic volume density of Golgi apparatus and lysosomes were significantly greater and the diameter of seretory granules were significantly smaller in large plaque-forming cells compared to small plaque-forming cells. Moreover, in one of them, not only the diameter but also the cytoplasmic volume density of secretory granules were significantly smaller in large plaque-forming cells. These findings suggest a greater secretory granule synthesis and internal granule destruction, and faster granules secretion at an early stage of formation in large plaque-forming cells compared with small plaque-forming cells. It became apparent through this study that electron microscopic investigation of plaque-forming single cells is practically useful since plasma membrane and cytoplasmic organelles were preserved well after processing for EM in most plaque-forming cells.

Adenoma↗
PubMed1991

Immunoelectron microscopic evidence of mammosomatotrophs in human adult and fetal adenohypophyses, rat adenohypophyses and human and rat pituitary adenomas.

Immunoelectron microscopy, utilizing the double labelling immunogold technique, revealed the presence of mammosomatotrophs in human adult and fetal rat adult adenohypophyses as well as human and rat pituitary adenomas. These cells are characterized by the coexistence of GH and PRL not only in the same cells but also in the same secretory granules.

Adenoma↗
PubMed1990

Parathyroid hormone-like peptide in normal and neoplastic mesothelial cells.

Mesothelioma has not been commonly reported as a cause of hypercalcemia of malignancy. We have studied a patient with malignant mesothelioma and hypercalcemia in association with elevated plasma concentrations of parathyroid hormone-like peptide (PLP). Immunohistochemical analysis of the tumor and seven of eight other mesotheliomas that were not associated with hypercalcemia revealed the presence of PLP cytoplasmic immunopositivity. PLP immunopositivity was also detected in normal and reactive mesothelial cells. The results of these studies suggest that PLP immunoreactivity is common in normal and neoplastic mesothelial cells and raises the possibility that PLP production may play a role in the pathogenesis of hypercalcemia associated with mesothelioma.

Adult↗
PubMed1990

Molecular and cellular analysis of a neoplastic pancreatic A cell tumor.

Endocrine tumors of the pancreas may produce characteristic syndromes attributable to the increased secretion of one or more hormones. These tumors provide valuable opportunities for the analysis of hormone biosynthesis and secretion in the neoplastic human endocrine cell. The authors studied a pancreatic endocrine tumor obtained from a patient with classical glucagonoma syndrome. Characterization of plasma and tumor glucagon-like immunoreactivity (GLI) by high-performance liquid chromatography and radioimmunoassay for GLI showed different chromatographic profiles, with glucagon the major molecular form in the tumor, and glicentin and oxyntomodulin predominating in plasma. Although immunocytochemical staining of the tumor showed only focal weak positivity for glucagon, tumor extracts contained large amounts of immunoreactive GLI peptide. Northern blot analysis of tumor RNA demonstrated that abundant glucagon mRNA transcripts were present, just slightly larger in size than those detected in normal pancreas and intestine. Electron microscopic analysis of the tumor cellular ultrastructure revealed only occasional small electron dense secretory granules. A large number of complex lysosome-like structures of variable size and electron density were detected throughout the cytoplasm and ringing the nucleus of most cells, a feature atypical of endocrine tumors of the pancreas. Primary cultures of dispersed tumor cells were established and, in contrast to previous results, were obtained using normal or neoplastic islet cell models, GLI secretion was found to be stimulated eightfold by incubation with 5 mM dibutyryl cyclic adenosine monophosphate. Phorbol myristate acetate, the calcium ionophore A23187, and sodium butyrate had no effect on GLI secretion in vitro. These observations indicate that neoplastic human A cells may have abnormalities at different points in the biosynthesis and secretion of glucagon.

Adenoma, Islet Cell↗
PubMed1990

Immunoreactive luteinizing hormone in functioning corticotroph adenomas of the pituitary. Immunohistochemical and tissue culture studies of two cases.

Two pituitary adenomas removed from a 37-year-old woman and a 26-year-old woman with typical Cushing's disease were studied by light and electron microscopy, immunohistochemistry and radioimmunoassay of tissue culture media. Both patients had high plasma levels of cortisol and normal levels of luteinizing hormone (LH). Both tumours were monomorphous, composed of densely granulated corticotrophs; the tumour cells contained periodic acid-Schiff positivity, were arranged in a sinusoidal pattern and, ultrastructurally, contained well-developed cytoplasmic organelles. By immunohistochemistry the majority of tumour cells contained immunoreactive adrenocorticotropin (ACTH); approximately 10% of the tumour cell population contained LH immunoreactivity. The LH-positive cells tended to form clusters scattered widely throughout the tumour tissues. LH immunoreactivity was demonstrated in some ACTH-immunoreactive cells on serial sections. Large amounts of immunoreactive ACTH and smaller quantities of LH, follicle stimulating hormone and alpha-subunit were released into the culture media and release of the glycoprotein hormones responded in parallel to corticotropin releasing hormone stimulation or inhibition by cortisol. These findings indicate that LH can be simultaneously produced and released by ACTH-producing tumour cells of otherwise typical functioning corticotroph adenomas. The capacity for LH production may be acquired during neoplastic proliferation. This is the first detailed report of concurrent production of LH by pituitary corticotroph adenomas.

Adenoma↗
PubMed1990

Intermediate filaments in the human pituitary gland: an immunohistochemical study.

Normal pituitaries, pituitaries showing CHC and selected adenomas were assessed for their possible content of intermediate filaments (IF), using immunohistochemical techniques. Normal pituitaries were stained for each of the five known IF (Cytokeratins (CK), glial fibrillary acidic protein (GFAP), desmin, vimentin, and neurofilaments (NF]. Desmin could not be demonstrated, and NF staining was limited to processes in the posterior gland. In serial sections, CK was demonstrated in some corticotrophs, somatotrophs, and lactotrophs. Vimentin was limited to processes in the posterior gland. Folliculo-stellate cells (FSC), demonstrated by staining for S100 protein, exhibited a small subpopulation staining for CK, and another subpopulation staining for GFAP. GFAP was also demonstrated in glial processes in the posterior gland. Cells showing Crooke's hyaline change stained intensely for CK. Null cell adenomas did not stain for CK. Corticotroph adenomas, somatotroph adenomas, with or without fibrous bodies, and lactotroph adenomas contain CK-immunoreactive cells. We conclude that CK is the major IF present in the anterior pituitary gland, within some normal corticotrophs, somatotrophs and lactotrophs, and also in adenomas derived from these cells.

Adenoma↗
PubMed1990

Human pituitary corticotroph adenomas in vitro: morphologic and functional responses to corticotropin-releasing hormone and cortisol.

We examined the direct effects of corticotropin-releasing hormone (CRH) and cortisol on the morphology of cells from 6 functioning human pituitary corticotroph adenomas in culture using both light and electron microscopic morphometry and correlated the structural changes with alterations in adrenocorticotropin (ACTH) release in each case. During incubations lasting 2 or 24 h, ACTH release was increased by CRH and reduced by cortisol. After incubations lasting from 2 to 72 h, light microscopic morphometric analysis showed no significant differences in cell size, nuclear area, cytoplasmic area or nuclear/cytoplasmic ratio between treated and control adenoma cells. Ultrastructural morphometry documented increased cytoplasmic volume density (CVD) of rough endoplasmic reticulum and/or Golgi apparatus and reduced CVD of secretory granules in cells incubated with CRH. There was no consistent change in CVD of endoplasmic reticulum, Golgi apparatus or secretory granules in adenoma cells incubated with cortisol, but in all tumors there were marked filament accumulations indicating a direct effect of cortisol on adenomatous corticotrophs. The changes were similar after 2- and 72-hour exposures. These results indicate that (1) some adenomatous corticotrophs can respond to CRH and cortisol; (2) the morphologic changes observed in cells treated with CRH correlate with increased ACTH release, and (3) accumulation of filaments is the direct effect of cortisol and is associated with reduced ACTH release.

Adenoma↗
PubMed1990

Glucagon and related peptides in fetal rat hypothalamus in vivo and in vitro.

Proglucagon-derived peptides are localized in pancreas, intestine, and the nervous system. We have examined the ontogeny of glucagon and related peptides in developing rat hypothalamus and have developed a fetal rat hypothalamic cell culture model to study the synthesis and secretion of these peptides in cells of neural origin. Fetal rat hypothalamus (19-21 day gestation) was found to contain glucagon-like immunoreactive (GLI) peptides including glucagon. The relative amounts of two of the GLI peptides (glicentin and oxyntomodulin) increased with development such that adult hypothalamus contained a predominance of these peptides over glucagon. The ratio of GLI peptides to glucagon increased from 2.6 +/- 0.5 in fetus to 46 +/- 11 in adult (P less than 0.001). When fetal rat hypothalamic cells (FRHC) were placed into primary culture for 7 days, the presence of neurons, glial cells, and glucagon-containing cells was detected by immunohistochemical staining. Analysis of proglucagon gene expression in FRHC cultures by Northern blotting demonstrated the presence of a single proglucagon messenger RNA (mRNA) transcript identical in size and sequence to that detected in fetal pancreas and intestine. RNase protection analysis of RNA from FRHC cultures, brainstem, and intestine confirmed that the proglucagon mRNA transcripts present in these three tissues were identical. Analysis of FRHC content of GLI peptides and immunoreactive glucagon demonstrated that peptide levels were not significantly different from those of whole fetal rat hypothalamus, and did not vary significantly throughout 2 weeks in culture. FRHC cultures were found to contain substantial amounts of glucagon after 1 week of culture. Release of the GLI peptides on day 7 of culture was increased 3-fold (P less than 0.001) by treatment of FRHC for 1 h with 5 mM (Bu)2cAMP. Rat hypothalamus therefore appears to undergo unique changes in posttranslational processing of proglucagon during development. Primary cultures of FRHC thus provide a promising in vitro model to study the molecular control of proglucagon biosynthesis and GLI peptide secretion in the brain.

Animals↗
PubMed1990

Parathyroid hormone-like peptide in normal and neoplastic human endocrine tissues.

PTH-like peptide (PLP) is produced by tumors commonly associated with hypercalcemia as well as nonneoplastic tissues and several endocrine glands and tumors. To characterize the distribution of PLP in human endocrine tissues and tumors, we localized PLP in formalin-fixed paraffin-embedded material using the avidin-biotin-peroxidase technique with polyclonal antisera. Among peptide hormone-producing tissues, PLP was identified in nontumorous adenohypophysis and pituitary adenomas; medullary thyroid carcinomas; normal, hyperplastic, and adenomatous parathyroids; adrenal medulla and pheochromocytomas; normal pancreatic islets; and endocrine tumors of pancreas, gut, and lung, including small cell carcinomas. In other endocrine tissues PLP was identified in nontumorous thyroid follicular epithelium, colloid nodules, and follicular neoplasms; normal adrenal cortex, adrenocortical adenomas, and carcinomas; nontumorous testicular Leydig cells; normal ovarian granulosa and thecal cells; an ovarian thecoma and a granulosa cell tumor; placental trophoblast; and decidua. These results demonstrate that PLP is localized in many normal and neoplastic endocrine cells, including those not known to influence extracellular calcium homeostasis. The presence of PLP in a variety of endocrine tissues suggests that it may play a local physiological role in the growth or function of endocrine cells.

Adrenal Cortex Neoplasms↗
PubMed1990

Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone.

It has been shown that mice transgenic for human growth hormone-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs and mammosomatotrophs, cells capable of producing both growth hormone and prolactin, by 8 months of age. We now report for the first time that old GRH-transgenic mice, 16 to 24 months of age, develop pituitary mammosomatotroph adenomas. These findings provide conclusive evidence that protracted stimulation of secretory activity can cause proliferation, hyperplasia and adenoma of adenohypophysial cells.

Adenoma↗
PubMed1989

Transforming growth factor-alpha in the mammalian brain. Immunohistochemical detection in neurons and characterization of its mRNA.

In this communication, we demonstrate that adult mammalian brain neurons express transforming growth factor-alpha (TGF-alpha). We used the anti-TGF-alpha monoclonal antibody, MF9, to immunohistochemically localize TGF-alpha in human and rat brain. We found specific immunoreactivity in neurons throughout the brain which was not a result of cross-reactivity of MF9 with the neuropeptide, synenkephalin. Northern blot analysis of bovine and rat brain RNA using human and rat TGF-alpha cDNA probes, respectively, revealed a single 4.8-kilobase pair mRNA with approximately equal abundance in the bovine brainstem, cerebellum, hypothalamus, and cerebral cortex. Fetal rat brain had about 2-fold more TGF-alpha mRNA than did adult rat. The brain TGF-alpha cDNA was cloned from a human neonatal brainstem library. Four identical clones were isolated after screening 10(6) recombinant lambda gt11 phage. The sequence of the 894-base pair cDNA was virtually identical with the cDNA isolated from a human renal cell carcinoma. A single alanine codon was deleted in the brain cDNA at an exon-exon junction. The alanine deletion is within the amino-terminal region of the TGF-alpha precursor that is thought to be removed by proteolytic processing of the precursor to the mature growth factor. These studies indicate that the normal mammalian brain neurons express TGF-alpha.

Animals↗
PubMed1989

Intrasellar gangliocytoma containing gastrin and growth hormone-releasing hormone associated with a growth hormone-secreting pituitary adenoma.

A 74-year-old acromegalic found to have an intrasellar gangliocytocytoma and GH-secreting pituitary adenoma is described. The gangliocytoma contained immunoreactive gastrin and, to a lesser extent, GHRH, and the adenoma immunostained for GH. Gastrin has not been previously reported in hypothalamic gangliocytomas. Since this peptide has been demonstrated in normal hypothalamus and pituitary, and provokes GH release when administered intraventricularly, it may have caused GHRH release from the gangliocytoma by a local paracrine action and led to adenoma formation and acromegaly.

Adenoma↗
PubMed1989

Adenohypophysial changes in mice transgenic for human growth hormone-releasing factor: a histological, immunocytochemical, and electron microscopic investigation.

The effect of protracted GH-releasing factor (GRF) stimulation on adenohypophysial morphology was investigated in six mice transgenic for human GRF (hGRF). All animals had significantly higher plasma levels of GH and GRF and greater body weights than controls. Eight-month-old mice were killed, and the markedly enlarged pituitaries were studied by histology, immunocytochemistry, electron microscopy, and immunogold method, using double labeling at ultrastructural level. In all pituitaries, a massive hyperplasia, chiefly of mammosomatotrophs, was found. These bihormonal cells, containing GH and PRL, were demonstrated by light microscopy and ultrastructural immunocytochemistry. Electron microscopy revealed the presence of cells with characteristics of GH cells in three pituitaries and cells resembling human adenomatous mammosomatotrophs in the other three glands. All of these cells, regardless of their ultrastructural features, contained secretory granules heavily labeled for GH by immunogold technique; PRL labeling varied from cell to cell, with the predominance of a weak immunostaining and was colocalized with GH in secretory granules. These results indicate that chronic exposure to GRF excess leads to mammosomatotroph hyperplasia. It is suggested that GH cells proliferate and transform to mammosomatotrophs in response to GRF stimulation. Focal PRL cell hyperplasia noted in three pituitaries could also be due to a GRF effect. Longer exposure to GRF is needed to clarify whether GRF can cause adenoma.

Animals↗
PubMed1989

Analysis of hormone secretion by clinically nonfunctioning human pituitary adenomas using the reverse hemolytic plaque assay.

The reverse hemolytic plaque assay was used to study hormone release in vitro by seven clinically nonfunctioning human pituitary adenomas associated with no clinical or biochemical evidence of hormone excess. Four of seven tumors were oncocytomas, one a null cell adenoma, and two gonadotroph adenomas based on immunocytochemical and ultrastructural features. In all seven tumors, plaques were formed with antiserum against beta FSH; four produced plaques for beta LH, and five for glycoprotein hormone alpha-subunit. The percentage of plaque-forming cells and the mean size of plaques were smaller than those of clinically functioning adenomas studied for comparison (five GH- and/or PRL-producing adenomas). These results correlated with those of hormone release in tissue culture, immunocytochemistry on paraffin secretions of the tumors, and immunocytochemistry after reverse hemolytic plaque assay. We conclude that clinically nonfunctioning pituitary adenomas release small quantities of hormones, primarily gonadotropins, and that hormone release is attributable to only a small percentage of tumor cells.

Adenoma↗
PubMed1989

The parathyroid hormone-like peptide gene is expressed in the normal and neoplastic human endocrine pancreas.

PTH-like peptide (PLP) is produced by a number of tumors commonly associated with the development of hypercalcemia. Analysis of the expression of the PLP gene has demonstrated that a variety of non-neoplastic endocrine and nonendocrine tissues contain PLP mRNA transcripts. Using a combination of Northern blot analysis, immunohistochemistry, and RIAs, we have demonstrated that the PLP gene is expressed in normal human and rat fetal and adult islets of Langerhans. PLP gene expression was not confined to cells containing a single pancreatic islet hormone, but was found in cells of all four major endocrine subtypes. PLP mRNA transcripts were also detected in RNA prepared from isolated rat islets, and small amounts of PLP immunoreactivity were secreted by cultured rat islets. Fifteen human pancreatic endocrine tumors not associated with hypercalcemia were analyzed and PLP-immunopositive tumor cells were found in 13. These observations demonstrate that the PLP gene is expressed in the normal and neoplastic islets of Langerhans, and suggests a possible role for this peptide in the growth or function of the endocrine pancreas.

Adult↗
PubMed1989

Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization.

Pituitary adenomas, removed surgically from three women with normal or slightly elevated serum growth hormone levels and no evidence of acromegaly, were studied. The tumor cells were shown by electron microscopy to correspond to sparsely granulated somatotrophs but immunocytochemistry showed that they contained no, moderate, or little growth hormone. Two tumors examined in vitro secreted small amounts of growth hormone in the tissue culture medium initially with a spontaneous rise after several days, and responded to growth hormone-releasing hormone stimulation with increased growth hormone release. In situ hybridization demonstrated growth hormone mRNA expression in adenoma cells. Clinically silent somatotroph adenomas represent a hitherto undescribed entity; electron microscopy shows that they consist of somatotrophs, and express growth hormone mRNA but do not secrete growth hormone in amounts needed to raise substantially serum growth hormone levels and cause acromegaly. Further work is required to clarify the mechanisms accounting for the lack of clinical and biochemical evidence of hormone excess associated with these tumors.

Adenoma↗