[Localized amyloidosis of the digestive tract].
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Age Factors↗
Biomedical subjects
N Sasano
Publications and source records attributed to N Sasano.
Immunohistochemical study of 3 beta-hydroxysteroid dehydrogenase in sex cord-stromal tumors of the ovary.
3 beta-Hydroxysteroid dehydrogenase (3 beta-HSD), which converts pregnenolone to progesterone, was localized immunohistochemically in 18 thecomas, 23 fibromas, 5 granulosa-cell tumors, 5 sclerosing stromal tumors, and 2 steroid-cell tumors. Immunohistochemical study of estrogen, progesterone, and testosterone was also performed in serial sections of thecomas and fibromas. In thecomas, immunoreactivity of 3 beta-HSD was observed only in luteinized theca cells and thecomatous tumor cells with abundant pale to vacuolated cytoplasm but not in spindled tumor cells and thecomatous tumor cells with small to moderate amounts of pale to vacuolated cytoplasm. Immunoreactivity of steroids was not observed in thecomas except for testosterone immunoreactivity in one case. No immunoreactivity of steroids or the enzyme was present in fibromas. No tumor cells were positive for 3 beta-HSD in any of the cases of granulosa-cell tumor examined. Immunoreactivity of 3 beta-HSD was present in cells in steroid-cell tumors and polygonal tumor cells with prominent cytoplasmic vacuoles in two cases of sclerosing stromal tumor. Thus, 3 beta-HSD can be a good immunohistochemical marker of steroidogenesis in functioning ovarian neoplasms.
3-Hydroxysteroid Dehydrogenases↗
Immunolocalization of 3 beta-hydroxysteroid dehydrogenase in human ovary.
Immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was performed in 55 cases of morphologically normal human ovaries by using a specific polyclonal antibody against purified human placental 3 beta-HSD. In small developing follicles, immunoreactivity was observed only in the theca interna but also became recognizable in the membrana granulosa with development of the follicle. At a late stage of folliculogenesis, the intensity of the 3 beta-HSD activity in the membrana granulosa was nearly equal to that of theca interna in 2 or 3 large follicles examined. One to several layers of theca interna cells just beneath membrana granulosa did not demonstrate any immunoreactivity of 3 beta-HSD or that of cytochrome P-450 17 alpha-hydroxylase. These unstained theca interna cells did not appear to be directly involved in ovarian steroidogenesis and might be designated as 'enzymically inactive theca interna cells.' Marked immunoreactivity was observed in luteinized theca and granulosa cells of the corpus luteum.
3-Hydroxysteroid Dehydrogenases↗
Expression of intermediate filaments in neuroendocrine tumors.
Expression of 160-kilodalton (kd) neurofilament, cytokeratin, and vimentin was immunohistochemically investigated in 45 pheochromocytomas, 12 medullary thyroid carcinomas, and 12 pancreatic islet cell tumors. Four mixed neuroendocrine-neural tumors, two multiple endocrine neoplasia type I tumors, and two multiple endocrine neoplasia type II tumors were included in this study. Neurofilament immunoreactivity was demonstrated in 45 (100%) of the pheochromocytomas, 10 (83%) of the medullary thyroid carcinomas, and 11 (92%) of the islet cell tumors. Cytokeratin and vimentin were detectable in 29% and 24% of the pheochromocytomas, 100% and 25% of the medullary thyroid carcinomas, and 67% and 25% of the islet cell tumors, respectively. Neurofilament was the most frequently detected intermediate filament in the neuroendocrine tumors. Cytokeratin was seen in the intra-adrenal but not the extra-adrenal pheochromocytomas. Coexpression of neurofilament and cytokeratin was common in the neuroendocrine tumors, and occasionally vimentin was also expressed simultaneously. There were no characteristic differences in the expression of intermediate filaments between multiple endocrine neoplasia type I or II tumors and sporadic-type tumors or between metastatic tumors and nonmetastatic tumors.
Adenoma, Islet Cell↗
Nucleolar organizer regions in human adrenocortical disorders.
A silver colloid technique to demonstrate nucleolar organizer region-associated proteins (AgNORs) was performed on sections of 39 human adrenal glands, including normal adrenal cortex, bilateral adrenocortical hyperplasia, adenoma, and carcinoma. In mineralocorticoid and glucocorticoid-producing adrenocortical cells, the mean number of AgNORs per nucleus was lowest in the normal adrenal gland and highest in adenoma, with statistically significant differences. The mean number of AgNORs in bilateral adrenocortical hyperplasia was placed between that of normal adrenal and adenoma. AgNOR numbers in morphologically and clinically verified adrenocortical carcinoma (12 cases) were not different from those in adenoma (17 cases). In adrenal cortex, AgNOR numbers may be correlated with increased steroid hormone production but appear to be of little value in discerning malignancy in adrenocortical neoplasms.
Adenoma↗
Coexpression of cytokeratin, neurofilament and vimentin in carcinoid tumors.
The immunohistochemical expression of intermediate filaments was investigated in 56 carcinoid tumors from 50 cases including 31 rectal and 25 non-rectal sites. Cytokeratin was the most frequently expressed in 55 of the tumours. Only one tumour of the stomach was negative for cytokeratin. Neurofilament (68 kd and 160 kd) was positive in 25 (44.6%) tumours with no preferential pattern of expression in particular tumours. Vimentin was positive in 18 out of the 31 rectal carcinoids (58%), and 3 of the 25 non-rectal carcinoids (12%). There was a significant difference in vimentin immunoreactivity between rectal and non-rectal carcinoids. The coexpression of cytokeratin and neurofilament was 44.6% and that of cytokeratin and vimentin was 37.5%. The coexpression of all three types of intermediate filament was 35.5% in rectal carcinoids, but 8% in non-rectal carcinoids. The present study revealed coexpression of cytokeratin, neurofilament and vimentin in carcinoids and an especially high incidence of vimentin expression in those of rectal origin.
Carcinoid Tumor↗
Immunohistochemical studies of steroidogenic enzymes (aromatase, 17 alpha-hydroxylase and cholesterol side-chain cleavage cytochromes P-450) in sex cord-stromal tumors of the ovary.
Aromatase, 17 alpha-hydroxylase, and cholesterol side-chain cleavage P-450 cytochromes (P-450AROM, P-450(17 alpha,) and P-450SCC, respectively) were immunohistochemically localized in nine granulosa cell tumors, 15 thecomas, ten Sertoli-Leydig cell tumors, two steroid cell tumors, five fibromas, and five sclerosing stromal tumors. In the thecomas, P-450SCC and P-450(17 alpha) were positive in luteinized theca cells and in cells with vacuolated cytoplasm, while P-450AROM was not observed. In the steroid cell tumors, all the P-450 cytochromes were intensely stained. P-450SCC and P-450(17 alpha) were present in cells with vacuolated cytoplasm in two cases of sclerosing stromal tumor. P-450AROM was weakly demonstrated in one of the granulosa cell tumors. P-450(17 alpha,) P-450SCC, and P-450AROM were all faintly stained in the Sertoli-Leydig cell tumors. No P-450 cytochrome immunoreactivity was observed in any fibroma.
Aromatase↗
Immunohistochemical study of cytochrome P-45017 alpha in human adrenocortical disorders.
Cytochrome P-450 specific for steroid 17 alpha-hydroxylation (P-45017 alpha) was immunolocalized in normal and hyperfunctioning adrenal glands of pigs, bovines, and humans, using a specific IgG fraction raised against the enzyme. P-45017 alpha was present in the zona fasciculata (ZF) and zona reticularis (ZR), but not in the zona glomerulosa (ZG), in pig, bovine, and human adrenal glands. In the adrenal glands of patients with Cushing's disease, the positive immunoreactivity to P-45017 alpha was intense in ZF and ZR, particularly in cortical micronodules, corresponding to the sites of active steroidogenesis. Cells of hyperplastic ZG and outer ZF in the adrenal glands of idiopathic hyperaldosteronism were negative for P-45017 alpha. In aldosteronoma, positive immunoreactivity was observed in some tumor cells, which is consistent with cortisol production and its responsiveness to ACTH in aldosteronoma. In the attached adrenal glands of aldosteronoma, the immunoreactive P-45017 alpha was clearly present in the inner ZF and ZR, suggesting persistent androgen production. In Cushing's adenoma, the positive immunoreactivity was intense in tumor cells, and the ZR of the attached adrenal glands was weakly immunoreactive.
Adenoma↗
Immunohistochemical analysis of cytochrome P-450 17 alpha-hydroxylase in pig adrenal cortex, testis and ovary.
Cytochrome P-450 specific for steroid 17 alpha-hydroxylation (P-450(17 alpha] was immunohistochemically observed in pig adrenal cortex, testis and ovary by the biotin-streptavidin method using a specific antibody against P-450(17 alpha) purified from neonatal pig testis. In the adrenal cortex, P-450(17 alpha) was present in the zona fasciculata and reticularis while no immunoreactivity was observed in the zona glomerulosa, confirming the absence of 17-hydroxylated steroid synthesis in the zona glomerulosa. In the testis, P-450(17 alpha) was present exclusively in Leydig cells and immunoreactivity was absent in seminiferous tubules. In the ovary, immunoreactivity was observed only in the theca interna but not in the membrana granulosa of follicles. Among the tissues examined, the relative intensity of immunoreactivity was greatest in the Leydig cells, and progressively less in theca interna cells, outer fasciculata cells and inner fasciculata and reticularis cells.
Adrenal Cortex↗
Immunohistochemical demonstration of cholesterol side-chain cleavage cytochrome P-450 in bovine and human adrenals.
Cytochrome P-450 specific for cholesterol side-chain cleavage (P-450SCC) was purified from the bovine adrenal and a specific antibody was raised in rabbits. The antiserum was applied for immunohistochemical visualization of the P-450SCC in the bovine and human adrenal cortex. The immunoreactivity was intense in the zona fasciculata (ZF) and reticularis (ZR) while weak in the zona glomerulosa (ZG) in the normal adrenals. In adrenocortical hyperplasia, a marked immunoreactivity was observed in the ZG in idiopathic hyperaldosteronism and the inner ZF and reticularis particularly in cells of micronodules in Cushing's disease, corresponding to cells with active steroidogenesis. In aldosteronoma and adenoma with Cushing's syndrome, P-450SCC was generally present in compact cells of adenomas.
Adenoma↗
Immunohistochemical demonstration of adrenodoxin reductase in bovine and human adrenals.
Adrenodoxin reductase (ADR) was purified from bovine adrenocortical mitochondria and specific antibody was raised in rabbits. Immunohistochemical analysis of ADR was performed in the bovine and human adrenals. ADR was present in all of the zones in both bovine and non-pathological human adrenal cortex. In non-pathological human adrenals, the immunoreactivity was particularly prominent in the zona glomerulosa (ZG) and reticularis (ZR). Intensive immunoreactivity was observed in the ZG and some cells of the outer fasciculata and the ZR in the adrenal glands with idiopathic hyperaldosteronism. In adrenal glands with Cushing's disease, immunoreactivity was present in the compact cells of cortical micronodules. In all cases, sites of immunoreactivity correspond to sites of increased steroidogenesis. In aldosteronoma and cortical adenoma with Cushing's syndrome, the immunoreactivity was generally marked in compact cells but not in large cells with clear cytoplasm, ADR was present in the ZG and the ZR, and the ZG in the non-neoplastic adrenal glands attached to aldosteronoma and Cushing's adenoma, respectively. ADR was present in the compact cells in adrenocortical carcinoma clinically manifesting Cushing's syndrome.
Adrenal Gland Diseases↗
What's new in the localization of sex steroids in the human ovary and its tumors?
It is important to understand the distribution of steroidogenesis in steroid producing tissues in order to obtain a better understanding of steroid metabolism. Recent advances in purification and subsequent generation of antibodies against cytochromes P-450 specific for steroid hormone biosynthesis have made it possible to localize the sites of steroidogenesis immunohistochemically. This review provides the localization of sex-steroid hormone biosynthesis in normal and pathological human ovaries including sex-cord stromal tumors, hyperthecosis and Brenner tumor, as determined by the tissue distribution of immunoreactivity of individual enzymes specific for different stages of the biosynthetic process.
Female↗
Demonstration of neuroendocrine cells in ovarian mucinous tumors.
The frequency of argyrophil cells in mucinous cystadenocarcinomas, borderline tumors (MBT) and cystadenomas was 29.8% (14 of 47), 46.7% (7 of 15) and 11.1% (2 of 18), respectively. These were statistically higher than the frequencies in 17 clear cell carcinomas, 43 serous cystadenocarcinomas, and 24 metastatic carcinomas. Immunoreactive cells for serotonin, somatostatin, gastrin, pancreatic polypeptide, growth hormone-releasing hormone, metenkephalin, neuron-specific enolase, and chromogranin-A were detected in almost all these cases with argyrophil cells. However, immunoreactivities for glucagon, vasoactive intestinal polypeptide, and adrenocorticotropic hormone were negative in ovarian mucinous tumors. Immunohistochemical multiplicity of neurohormones was remarkable in 15 MBT (including 5 müllerian and 10 intestinal MBT) and it was not related to the number of argyrophil cells per unit tumor cells. Individual hormones demonstrated here seemed to be present in different cells, but certain cells were immunoreactive for both gastrin and somatostatin by double immunostaining. Based on the high frequency of endocrine cells, borderline tumors seemed to be unique in the spectrum of mucinous ovarian tumors.
Adenocarcinoma↗
Microvascular changes in the stroma of human colorectal carcinomas: ultrastructural histochemical study.
Ultrastructural histochemical studies were performed using Ulex europaeus agglutinin-I lectin (UEA-I) and anti-endothelial monoclonal antibody BMA 120 in order to morphologically characterize the microvasculature of human colorectal carcinomas. In the normal mucosa, UEA-I and BMA 120 were bound to luminal plasma membrane of endothelial cells, usually continuously. Capillaries in the stroma of invasive adenocarcinomas showed remarkable structural changes such as swelling of endothelial cells with well-developed cell organelles and narrowing of the lumen. Reaction products for UEA-I and BMA 120 were both observed along the luminal plasma membrane of endothelial cells, usually discontinuously, partially retaining the features of normal capillaries. Furthermore, we have confirmed an occurrence of solid capillary buds composed of a strand of large endothelial cells with a trace of lumen. They showed almost no reactivity to UEA-I and BMA 120. Conventional electron microscopy revealed that they were present frequently in invasive carcinomas, but infrequently in intramucosal carcinomas and inflammatory lesions. Our results suggest that the stroma of invasive colorectal carcinomas abounds in immature capillaries and their precursors, which may indicate active tumor-induced angiogenesis.
Antibodies, Monoclonal↗
Corticotropin-releasing hormone in the human hypothalamus. Free-floating immunostaining method.
We have clearly demonstrated corticotropin-releasing hormone (CRH) immunoreactive cell bodies and nerve fibers in the human hypothalamus by immunocytochemistry using free-floating sections instead of paraffin-embedded sections. Human hypothalami were obtained at autopsy, fixed and cryostat-sectioned at 40 microns. Free-floating sections were immunostained with antibody to CRH using the Vector ABC system. Most of CRH immunoreactive nerve fibers from the paraventricular nucleus pass under the fornix, while some CRH immunoreactive nerve fibers pass beyond the fornix and some through the fornix. Then the CRH immunoreactive nerve fibers run downward, medially to the supraoptic nucleus and toward the pituitary stalk. This method of immunocytochemistry is a very sensitive and suitable means for immunocytochemical studies of neuropeptides in the human brain.
Aged↗
Calcitonin gene-related peptide in the human hypothalamus.
Calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) in the human hypothalamus was investigated by radioimmunoassay and by immunocytochemistry. CGRP-LI was detected from two hypothalami obtained at autopsy (2.1 and 7.0 ng/g wet tissue) by radioimmunoassay. Reverse phase high performance liquid chromatography revealed that most of the CGRP-LI in the human hypothalamus was eluted in an identical position with synthetic human CGRP. For immunocytochemistry, human hypothalami obtained at autopsy were fixed and cryostat-sectioned at 40 microns. Free floating sections were immunostained with antibody to CGRP. CGRP-immunoreactive cell bodies were found in the supraoptic nucleus, paraventricular nucleus and infundibular nucleus. These findings indicate that CGRP exists in the cell bodies of the supraoptic nucleus, paraventricular nucleus and infundibular nucleus in the human hypothalamus and CGRP may play some roles in the endocrine and other functions of the human hypothalamus.
Aged↗
Immunolocalization of aromatase, 17 alpha-hydroxylase and side-chain-cleavage cytochromes P-450 in the human ovary.
Immunohistochemical localization of cholesterol side-chain-cleavage, 17 alpha-hydroxylase and aromtase cytochromes P-450 was performed in 35 morphologically normal human premenopausal ovaries by using specific antibodies against the enzymes. In well-developed ovarian follicles in the late stages of follicular growth, immunoreactivity of P-450AROM was only seen in granulosa cells while P-450(17 alpha) and P-450SCC activity was confined to theca interna cells, confirming that follicular oestrogen is produced in granulosa cells by the aromatization of androgens derived from the theca interna cells. In the corpus luteum, this functional differentiation is maintained, since immunoreactivity of P-450AROM was exclusively present in luteinized granulosa cells while that of P-450(17 alpha) was present in luteinized theca calls. Immunoreactivity of P-450SCC was present in both types of cells in the corpus luteum.
Animals↗
Steroid 21-hydroxylase and 17 alpha-hydroxylase in microsomal fraction of functioning adrenocortical tumors.
In order to survey the enzymic activities of steroidogenesis in functioning adrenocortical tumors, we investigated the activities of steroid 21-hydroxylase and 17 alpha-hydroxylase in microsomal fractions of 12 surgically resected adrenocortical tumors associated with Cushing's syndrome (5 adenomas and one carcinoma), primary aldosteronism (5 adenomas) and adrenogenital syndrome (AGS) (one carcinoma), and one adrenocortical hyperplasia resulting from Cushing's disease. Seven adrenal cortices from the patients with mammary carcinoma, renal cell carcinoma or pheochromocytoma were used for normal control. In normal controls 21-hydroxylase activities with progesterone as a substrate were 1.61 +/- 0.25 nmole/min/mg protein and those with 17 alpha-hydroxyprogesterone were 5.22 +/- 1.06 nmole/min/mg protein. The activity of 21-hydroxylase was higher in four cases of 5 aldosteronomas than in normal controls. Those activities in Cushing's adenomas were in the range of normal controls in this study. 17 alpha-hydroxylase activities were much variable from case to case even though in normal controls (4.50 +/- 2.40 nmole/min/mg protein), and in most cases of adenomas 17 alpha-hydroxylase activities were in the range of normal controls. Activities of both hydroxylase in carcinomas were lower than in normal controls. The present paper showed the abnormal steroidogenic enzyme activities in aldosteronomas and adrenocortical carcinomas.
Adenoma↗