Biomedical subjects

H Sasano

Publications and source records attributed to H Sasano.

At least 325 records · Page 18Linked to original sources

PubMed1991

Dexamethasone-nonsuppressible cortisol in two cases with aldosterone-producing adenoma.

Forty-one patients with aldosterone-producing adenoma (APA) were subjected to a dexamethasone suppression test (DST) before surgery. Serum cortisol and urinary excretion of 17-hydroxycorticosteroids were suppressed by dexamethasone in 39 patients [DST(+)]. In two patients (cases A and B), they were not suppressed [DST(-)]. Clinical manifestations of the two DST(-) patients were similar to those of DST(+) patients. Hypertension, hypokalemia, high serum aldosterone levels, and suppressed PRA were found in all of the patients. The cut surfaces of the adenomas from all of the patients, including cases A and B, were golden yellow, which is typical of APA. However, atrophies of the adjacent normal tissues were evident exclusively in the two DST(-) patients. After removal of the affected adrenals, the serum cortisol level was suppressed by dexamethasone in one of the DST(-) patients (case B). These findings suggested autonomous cortisol production by APA. To evaluate whether cortisol could be produced from the adenoma tissue, the presence of several steroidogenic enzymes was studied by immunohistochemistry and mRNA analysis in the adenomas and the adjacent nonneoplastic adrenals from the 2 DST(-) and 5 DST(+) patients. Immunohistochemical analysis demonstrated that steroidogenic enzymes were expressed in APA tumor tissues from both DST(-) and DST(+) patients. In both groups, mRNAs coding steroidogenic enzymes were present not only in the nonneoplastic but also in the tumor tissues. Quantitative analysis of the mRNA levels revealed that in the adrenals from DST(+) patients, the mRNAs were more abundant in nonneoplastic tissue than in tumor tissue. However, in those from DST(-) cases, the mRNAs were much more abundant in the tumor tissues than in the nonneoplastic tissues. These results indicate that tumor cells of the two DST(-) patients autonomously synthesized not only aldosterone but also cortisol. The diameters of the tumors from the two DST(-) patients exceeded 3 cm, while those from other DST(+) patients were smaller. In patients with large APA, adrenal insufficiency should be anticipated upon removal of the tumor.

Adenoma↗

PubMed1991

Analysis of point mutations at codon 12 of K-ras in human endometrial carcinoma and cervical adenocarcinoma by dot blot hybridization and polymerase chain reaction.

Samples of human endometrial carcinomas and cervical adenocarcinomas were screened for the presence of single site DNA mutations at codon 12 of the K-ras gene using dot blot hybridization of DNA amplified by the polymerase chain reaction (PCR). Of 21 cases of endometrial carcinoma, point mutations were observed in three cases (14.3%). Mutation from GGT to GTT was seen in one case, and mutation to GAT was observed in two cases. Of seven cases of cervical adenocarcinoma, point mutations were noted in two cases (28.6%). Mutation from GGT to GTT and double mutation to GAT and GCT were in one case each. However, no correlation was found between the presence of point mutation and age, clinical stage, or depth of muscular invasion. With respect to prognosis, of five patients with point mutation, one with cervical carcinoma died, and of 23 patients without mutation, one with endometrial carcinoma died.

Adenocarcinoma↗

PubMed1991

Expression of c-myc, epidermal growth factor receptor and c-erbB-2 in human endometrial carcinoma and cervical adenocarcinoma.

Thirty specimens of human endometrial carcinoma (n = 23) and cervical adenocarcinoma (n = 7) have been analyzed for c-myc, epidermal growth factor receptor (EGFR) and c-erbB-2 by immunohistochemistry. In endometrial carcinomas, expression of c-myc was observed in all cases, EGFR in 21 of 23 cases (91.3%) and c-erbB-2 in 7 of 23 cases (30.4%). In cervical adenocarcinomas, expression of c-myc was seen in 5 of 7 cases (71.6%), EGFR in all cases and c-erbB-2 in 2 of 7 cases (28.6%). c-myc immunoactivity was observed as nuclear or cytoplasmic stain or both, EGFR as membrane and cytoplasmic stain, c-erbB-2 as membrane stain. There was no relationship between expression of these three oncogenes and clinical prognostic factors in the present study.

Adenocarcinoma↗

PubMed1991

Immunohistochemical localization of mineralocorticoid receptor in human gut.

Immunohistochemical localization of mineralocorticoid receptor in the human adult gut was examined by using a polyclonal antibody raised against a mineralocorticoid receptor fusion protein. Immunoreactive staining was observed in columnar cells in the middle of the intestinal glands of the proximal colon, but not in goblet cells. Western blot analysis also revealed the presence of an approximately 100 kDa immunoreactive species consistent with the mineralocorticoid receptor protein in the ascending colon as well as the kidney. These results suggest that aldosterone-sensitive sodium transport and water absorption may be mainly carried out in the proximal colon in human adult gut at non-pathological state.

Aldosterone↗

PubMed1990

An analysis of abnormalities of the retinoblastoma gene in human ovarian and endometrial carcinoma.

The altered expression of the human retinoblastoma (RB) gene has been demonstrated to play an important role in the pathogenesis of RB and other tumors. To determine whether the RB gene might be involved in the pathogenesis of human ovarian and endometrial cancer, DNA from 24 human ovarian tumors, 3 normal ovaries, 3 endometrial carcinomas, and 1 endometrial hyperplasia was examined with an RB complementary DNA probe. Evidence for homozygous deletion of the RB gene was observed in only one specimen. Interestingly, the specimen was an endometrioid tumor of the ovary of low malignant potential (LMP). This patient experienced rapid progression of the tumor and died 8 months after diagnosis. Abnormalities of the RB gene may be involved in the aggressive biologic behavior of certain forms of ovarian carcinoma, particularly those of LMP.

Aged↗

PubMed1990

Serous papillary adenocarcinoma of the endometrium. Analysis of proto-oncogene amplification, flow cytometry, estrogen and progesterone receptors, and immunohistochemistry.

Primary and metastatic tumor tissues of serous papillary adenocarcinoma of the endometrium were examined for the following: (1) amplification of int-2, c-erbB-2 and c-myc proto-oncogenes by Southern blot hybridization; (2) DNA ploidy by flow cytometric study; (3) and expression of specific proteins, such as estrogen and progesterone receptors, keratin, vimentin, and carcinoembryonic antigen (CEA) using immunohistochemical and biochemical techniques. Amplification of c-myc was observed in the specimens from the endometrium (ten-fold) and from omental metastasis (five-fold). Both int-2 and c-erbB-2 amplification were not observed. The tumor showed aneuploidy, with the specimens from the endometrium and omental metastasis exhibiting multiple populations of aneuploid tumor cells. Estrogen and progesterone receptors could not be detected biochemically; however, immunohistochemically, estrogen receptors were observed in tumor cells forming papillary structures but not in the tumor cells of the solid, more poorly differentiated areas. A similar distribution was observed for both low and high molecular weight keratin. The findings of c-myc amplification and aneuploidy in the serous papillary adenocarcinoma of the endometrium are consistent with its aggressive behavior observed clinically and emphasize the importance of distinguishing this lesion from other types of endometrial carcinoma.

Blotting, Southern↗

PubMed1990

Protooncogene amplification and tumor ploidy in human ovarian neoplasms.

DNA from 24 ovarian tumors, including 16 carcinomas, was examined for amplification of the proto-oncogenes c-myc, int-2, and rc-erbB-2. All cases of carcinoma were also examined by flow cytometry for DNA ploidy and cell cycle analysis, and eight cases of carcinoma were examined for estrogen and progesterone receptors. Protooncogene amplification was not detected in the DNA of benign ovarian neoplasms, or of ovarian carcinomas with low malignant potential. Amplification of c-myc was detected in six of 12 cases of invasive carcinoma, int-2 amplification was present in one case, and c-erbB-2 amplification was not detected in any case. Among the seven cases evidencing protooncogene amplification, three cases showed aneuploidy in tumor DNA, while four showed diploidy. Two cases which showed aneuploidy in tumor DNA did not demonstrate any degree of protooncogene amplification. Protooncogene amplification was frequently associated with morphologic nuclear anaplasia and high mitotic count. Six of the seven cases demonstrating c-myc or int-2 were of the serous type or showed some degree of serous differentiation, while none of the four cases of purely mucinous carcinoma had evidence of amplification. While the total number of cases in the study was limited, it would appear from the trend demonstrated by the data that protooncogene amplification (particularly c-myc) may be involved in the pathogenesis of aggressive common epithelial tumors of the ovary.

Adenocarcinoma, Mucinous↗

PubMed1990

Immunohistochemical comparison of new monoclonal antibody 1C5 and carcinoembryonic antigen in the differential diagnosis of adenocarcinoma of the uterine cervix.

The reactivities of new monoclonal antibody 1C5 and anti-carcinoembryonic antigen (CEA) were determined immunohistochemically in 4 adenocarcinomas in situ, 20 invasive adenocarcinomas of various types, and 6 adenosquamous carcinomas of the uterine cervix, as well as in 10 endometrial adenocarcinomas and 10 normal cervices. Among the invasive adenocarcinomas, 90% were positively stained by 1C5 and 55% stained for CEA. Three of four in-situ adenocarcinomas were positively stained by 1C5 and two of four were positively stained by anti-CEA. All adenosquamous carcinomas were stained by 1C5 and four of six stained for CEA. Invasive adenocarcinomas always stained more intensely with 1C5 than did noninvasive lesions in the same specimen. Poorly differentiated adenocarcinomas were stained as strongly with 1C5 as were well-differentiated tumors, but CEA was less effective in identifying poorly differentiated lesions. 1C5 was also more useful than CEA was in distinguishing glandular from squamous neoplastic differentiation, and also appears to be useful in distinguishing endocervical from endometrial differentiation.

Adenocarcinoma↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1989

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↗

PubMed1989

Eosinophilic products lead to myocardial damage.

Eosinophils have been associated with endomyocardial fibrosis. However, their effect on the myocardium and the reactions they elicit have not been emphasized. We describe four patients with extensive myocardial eosinophilic infiltration with and without endomyocardial fibrosis. Patients with a short duration of disease had eosinophilic infiltrates, myocardial eosinophilic abscesses containing granular eosinophilic material, and/or Charcot-Leyden crystals with and without profuse histiocytic and giant cell reaction with granuloma formation. In the early phase, the granular eosinophilic material can be visualized by the Luna stain and/or by electron microscopic examination. In patients with a long duration of symptoms, well-developed granulomas and profuse fibrosis are seen and eosinophilic material may not be visualized. Toxic eosinophil granular protein may be involved in the development of these lesions.

Adult↗

PubMed1989

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↗

PubMed1989

Brenner tumor of the ovary: immunoanalysis of steroidogenic enzymes in 23 cases.

Immunohistochemical analysis of cytochromes P-450 aromatase and P-450 17 alpha-hydroxylase, which catalyze the production of estrogens and androgens, respectively, was performed for 23 cases of ovarian Brenner tumor. Immunoreactivity for P-450 aromatase was observed in the epithelial cells of the tumor distinctly in two cases and faintly in four cases, while immunoreactivity for P-450 17 alpha-hydroxylase was seen in two cases. No immunoreactivity was observed in the stromal cells of the tumors, nor were luteinized cells observed in the cases examined. No correlation was observed between the immunoreactivity of cytochromes P-450 in the epithelial cells of the tumor and endometrial abnormalities. These findings, together with a review of the literature, suggest that the usual Brenner tumor is not associated with specific steroidogenesis. Rare massive Brenner tumors may, however, be capable of androgenic or estrogenic activity.

Aromatase↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗