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Biomedical subjects

N Sasano

Publications and source records attributed to N Sasano.

At least 73 records · Page 4Linked to original sources

Demonstration of pituitary tissue with 6 cells immunoreactive to pituitary hormones in a sacrococcygeal teratoma.

A sacrococcygeal teratoma, containing mature-appearing anterior pituitary tissue, was first reported with the result of an immunohistochemical analysis for pituitary hormones. All kinds of adenohypophyseal endocrine cells were demonstrated in the anterior pituitary tissue in this teratoma. This study revealed that the anterior pituitary tissue being contained together with nerve tissues in a sacrococcygeal mature teratoma has the capacity to produce at least six anterior pituitary hormones.

Adrenocorticotropic Hormone↗

Immunoelectron microscopic study of corticotropin-releasing factor in the human hypothalamus and pituitary gland.

Ultrastructural localization of immunoreactive corticotropin-releasing factor (CRF) was visualized for the first time in the human hypothalamus and pituitary gland with specific antibodies against human/rat CRF. In the hypothalamus most of the positive immunoreactivity to CRF was present in granules with a wide range of diameters, 50-250 nm, in the perikarya of parvocellular neurons in the paraventricular nucleus. Among these, neurosecretory type granules, 100-150 nm in diameter, were dominant, and small vesicles, 50-80 nm in diameter, were sparse. Some of surfaces of rough endoplasmic reticulum and polyribosomes were also positive in some of these cells. CRF-positive reactions were also observed in the nerve fibers of the pituitary stalk and the posterior pituitary gland revealing two types of granules: small vesicles, 50-80 nm in diameter, and neurosecretory granules, 100-150 nm in diameter. These results support the theory that the human CRF, which is identical to rat CRF, is synthesized in parvocellular neurons of paraventricular nucleus, transported in nerve fibers, and controls ACTH secretion in the human anterior lobe of pituitary gland via the portal system.

Corticotropin-Releasing Hormone↗

Immunoreactive corticotropin-releasing hormone present in human plasma may be derived from both hypothalamic and extrahypothalamic sources.

Immunoreactive CRH concentrations were determined in human plasma using an immunoaffinity chromatographic extraction procedure and sensitive RIA. Immunoreactive CRH was detectable in the plasma of all normal subjects (mean +/- SD, 6.2 +/- 2.4 pg/mL; n = 15). Basal (0800-1000 h) plasma immunoreactive CRH levels were significantly lower in patients with Cushing's syndrome due to adrenal (2.8 +/- 1.1 pg/mL; n = 4) or pituitary adenomas (2.9 +/- 0.8 pg/mL; n = 5), in patients with hypothalamic hypopituitarism (3.2 +/- 0.9 pg/mL; n = 5), and in glucocorticoid-treated patients (3.9 +/- 1.9 pg/mL, n = 8). Basal plasma CRH levels were also low in patients with acromegaly (2.8 +/- 0.8 pg/mL; n = 14) and insulin-treated diabetic patients whose pituitary-adrenal function was normal (3.6 +/- 1.0 pg/mL; n = 12). In normal subjects plasma CRH levels increased after insulin-induced hypoglycemia; this response was abolished by the prior administration of dexamethasone. In contrast, basal plasma CRH levels were not affected by prior administration of metyrapone or dexamethasone. No evidence for diurnal variation in plasma immunoreactive CRH was found in normal subjects. In addition, in normal subjects oral glucose administration elicited a significant increase in plasma CRH (basal, 7.3 +/- 0.9 pg/mL; peak 30 min after glucose, 16.7 +/- 5.8 pg/mL; n = 5; P less than 0.05) without concomitant changes in ACTH. Gel filtration of extracts of pooled plasma from normal subjects revealed a major component of immunoreactive CRH in the position of synthetic rat CRH. Immunoreactive CRH-sized material had the same retention time as authentic rat CRH in a reverse phase high pressure liquid chromatography system. The content of immunoreactive CRH in human placenta, pancreas, and adrenal gland was much larger than that in hypothalamus. These findings suggest that immunoreactive CRH is present in peripheral plasma; the increase in plasma immunoreactive CRH after insulin-induced hypoglycemia may reflect stimulation of hypothalamic CRH release; the increase in plasma immunoreactive CRH after glucose administration may reflect extrahypothalamic CRH release; and the lack of diurnal variation in plasma immunoreactive CRH together with the lack of suppression of CRH by dexamethasone suggest that basal plasma CRH is of extrahypothalamic origin.

Adolescent↗

Distribution, plasma concentration, and in vivo prolactin-releasing activity of peptide histidine methionine in humans.

The distribution of immunoreactive peptide histidine methionine (PHM) in human tissues and its plasma concentrations were examined using a specific RIA and gel filtration chromatography. The effects of synthetic PHM on anterior pituitary hormone secretion also were studied. Immunoreactive PHM was found in all tissues studied; high concentrations were found in the gastrointestinal tract, lung, and parotid gland. Subsequent but smaller amounts of PHM were found in the hypothalamus, pituitary stalk, olfactory lobe, and cerebral cortex. The distribution of immunoreactive PHM in human tissues was very similar to that of vasoactive intestinal polypeptide (VIP), and PHM and VIP were in equimolar concentrations. Immunoreactive PHM was also detectable in plasma of normal subjects, and similar plasma concentrations were found in patients with prolactinomas. Molecular sieve chromatography of extracts of nonneural tissues and plasma extracts revealed only one peak, eluting in the position of synthetic PHM. Two peaks of immunoreactive PHM were found in brain tissue; one coeluted with synthetic PHM, and the other eluted in the high mol wt region. Bolus injections of synthetic PHM significantly increased plasma PRL levels in a dose-dependent manner. However, PHM did not alter plasma GH, TSH, ACTH, LH, or FSH levels. These results indicate that PHM is distributed widely in human tissues, and posttranslational processing of the VIP-PHM precursor molecule may be different in different tissues. The finding of equimolar distributions of PHM and VIP is consistent with the notion that these two peptides are synthesized from a common precursor. The presence of immunoreactive PHM in human hypothalamic and pituitary stalk tissue and its specific in vivo PRL-releasing activity suggest that PHM may play an important role in the regulation of PRL secretion.

Aged↗

An adrenocortical tumor secreting weak mineralocorticoids.

An adrenocortical carcinoma (15.5 g) secreting excessive amounts of steroids with weak mineralocorticoid activity in a 25-year-old woman was studied with particular reference to its in vivo and in vitro secretions of steroids. Severe hypertension, occasional low serum potassium and suppressed PRA were the major clinical findings, and were improved with removal of the tumor. In the preoperative stage, plasma levels of 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone, corticosterone and 18-hydroxycorticosterone were all increased. However, the plasma level of aldosterone was repeatedly normal. Although plasma levels of pregnenolone, 17-hydroxypregnenolone, progesterone and 17-hydroxyprogesterone were very high, those of other late step steroids, i.e. 11-deoxycortisol, cortisol, dehydroepiandrosterone, androstenedione and testosterone were almost normal. From these findings, a major etiological role of weak mineralocorticoids such as 11-deoxycorticosterone, 18-hydroxycorticosterone and corticosterone in her hypertension was suggested. Pregnenolone and 17-hydroxypregnenolone in tumor tissue were increased, but 11-deoxycorticosterone, corticosterone, aldosterone, cortisol and adrenal androgens such as dehydroepiandrosterone, androstenedione and testosterone were below normal or low normal. In vitro production of 11-deoxycorticosterone, aldosterone or cortisol by the tumor tissue slices was very low and scarcely responded to synthetic ACTH.

17-alpha-Hydroxypregnenolone↗

[A case of prolactinoma in close association with Rathke's cleft cyst].

We report a case of Rathke's cleft cyst in pituitary tumor. A 31-year-old woman admitted to our hospital complained of visual disturbance, headache, amenorrhea and galactorrhea. Serum prolactin level was 3,060 ng/ml. By means of CT scan and MRI, we found suprasellar-extending tumor to have cystic component in the center of the tumor. Transsphenoidal surgery revealed grayish jelly-like content in the cyst. Histologically tumor cells were composed of chromophobic, basophilic and eosinophilic cells. The cyst wall in the pituitary adenoma was composed of ciliated or non-ciliated columnar epithelium intermingled with goblet cells, being similar to Rathke's cleft cyst. Except for the cells of the cyst wall, most of the tumor cells were immunoreactive for prolactin. As for intermediate filament, tumor cells in both solid and cystic portions showed positive immunoreactivity for cytokeratin and GFAP, and not for vimentin and neurofilament. These results suggest that the nature of the intracytoplasmic filament in the pituitary tumor with Rathke's cleft cyst may be not only keratin but also GFAP.

Adenoma↗

[The effects of canrenone K (soldactone) on the adrenocortical steroidogenic enzymes in the bovine adrenal gland].

The effects of canrenone K (Soldactone) on 3 beta-hydroxysteroid dehydrogenase, 11 beta-hydroxylase and 18-hydroxylase activities were determined in vitro using isolated mitochondrial and microsomal fractions of the bovine adrenal glands. There was dose-related inhibition of 3 beta-hydroxysteroid dehydrogenation in the concentration between 10(-8) M and 10(-3) M, and 11 beta-hydroxylation and 18-hydroxylation in the concentration between 10(-7) M and 10(-3) M, respectively. The concentration of 50% inhibition of 3 beta-hydroxysteroid dehydrogenase activity was 8.5 X 10(-7) M and those of 11 beta-hydroxylase and 18-hydroxylase activities were 5 X 10(-5) M and 6 X 10(-6) M, respectively. NADPH added to a mitochondrial fraction or NAD to a microsomal fraction had no effect on the inhibition of conversion in the presence of canrenone K. The results indicate that canrenone K inhibited 3 beta-hydroxysteroid dehydrogenase in the pharmacological dose, 11 beta-hydroxylase and 18-hydroxylase in a higher concentration, and with the exception of NADPH or NAD, it may inhibit the generating system directly.

18-Hydroxycorticosterone↗

Prostate-specific acid phosphatase in carcinoid tumors.

Although prostate-specific acid phosphatase (PASP) has been recognized as a specific marker of tissue of prostatic origin, several investigators have pointed out that some of the carcinoid tumours and islet cell tumours of the pancreas reacted immunohistochemically to PSAP. We investigated 50 cases immunohistochemically comprising 44 carcinoids of the G-I tract, 3 of the bronchus, 1 each of the ovary, kidney and middle ear. PSAP positive cases were, 30 in G-I tract, one each in ovary and kidney. Eighty percent of tumours of hindgut origin were positive. Apart from the immunohistochemical study, the content of PSAP in preoperative serum and tumour tissue was estimated in a case with a rectal carcinoid. Extremely elevated PSAP was confirmed in both the serum and tumour tissue. Neuroendocrine tumours such as pheochromocytoma, medullary thyroid carcinoma, and islet cell carcinoma were investigated as controls. No cells immunoreactive to PSAP were observed in these control cases. Prostate specific antigen was definitely negative in carcinoids. We would emphasize that PSAP may be an excellent marker of carcinoids especially when derived from hindgut.

Acid Phosphatase↗

Second primary cancer following adjuvant chemotherapy, radiotherapy and endocrine therapy for breast cancer: a nationwide survey on 47,005 Japanese patients who underwent mastectomy from 1963-1982.

Out of a total of 47,005 cases of primary breast cancer with curative surgery recorded in Japan in the 20 year period from 1963 to 1982, 764, or 1.6 per cent had a second primary cancer occurring during the same period. The distribution of the second site was gastric cancer in 200 (26.2 per cent), breast cancer in 200 (26.2 per cent), colorectal cancer in 59 (7.7 per cent), cancer of the cervix uteri in 54 (7.1 per cent) and thyroid cancer in 37 (4.8 per cent). The gastric cancer was the Borrmann type 4, and the poorly differentiated scirrhous type. Incidence of the second cancer was enhanced, in the first period before 1971 and by contrast, in the second period after 1971 it was diminished. In the chemotherapy (+) group, the occurrence of the second cancer seemed to be strongly influenced by mitomycin C. In the radiotherapy prescribed group, leukemia was as frequent as esophageal cancer, and in those given endocrine therapy, breast cancer strongly inhibited the current one.

Antineoplastic Agents↗

Hyperplasia of renin-containing cells in a malignant pheochromocytoma: an immunohistochemical and semiquantitative study.

The renin-containing cells in the kidneys of a patient with malignant pheochromocytoma were investigated immunohistochemically. Elevated plasma renin and catecholamine levels were detected during the clinical course. Remarkable hyperplasia of renin-containing cells was observed in the afferent arterioles and interlobular arteries. Semiquantitative assessment was performed to compare this case with cases of renovascular hypertension, with one case of malignant nephrosclerosis, and with six cases without hypertension. The grade of hyperplasia of renin-containing cells in pheochromocytoma was similar to that in renovascular hypertension and was different from that observed in control cases. Histologic examination of the kidneys revealed neither stenosis of the renal arteries nor ischemic changes of glomeruli. Direct stimulation of renin-containing cells by catecholamines is suggested as the cause of the hyperplasia. This is the first morphologic demonstration of hyperplasia of renin-containing cells in pheochromocytoma.

Adult↗

Evidence of hybrid cell of thyroid follicular cell and carcinoid cell in strumal carcinoid.

A strumal carcinoid associated with mature cystic teratoma of the ovary in a 59-year-old was investigated immunohistochemically and electron microscopically. Histologically it was composed largely of trabecular and partly of insular carcinoid and individual thyroid follicles. Intensive argyrophilia was shown in both the cells of carcinoid tumor and follicular structure. Thyroglobulin was strongly positive in the follicular lining epithelium and weakly positive in the carcinoid cells adjacent to the follicular area. Immunoreactive cells for somatostatin and prostatic acid phosphatase were strongly detected in the carcinoid area and gradually blended to the follicular epithelium. Methionine-enkephalin, glicentin, and pancreatic polypeptide were focally detected in the carcinoid area. Whereas calcitonin-positive cells were sparsely observed in the follicular area, carcinoembryonic antigen and serotonin were absolutely negative. Electron microscopic findings revealed abundant neurosecretory granules, microfilaments, and colloid-like droplets in the same cells. We suggest that these hybrid cells are the origin of strumal carcinoid.

Carcinoid Tumor↗

Use of formaldehyde-induced fluorescence for cytological diagnosis of pheochromocytoma.

Eleven cases with pheochromocytoma were cytologically investigated on touch preparations using formaldehyde-induced fluorescence method (FIF) in addition to the usual Papanicolaou's stain (PAP) and May-Grünwald Giemsa stain (MGG). The specific catecholamine fluorescence was successfully observed in the cytoplasm of tumor cells and also in the background. Application of FIF for touch preparation is simple in technique and may greatly contribute for confirmation of the diagnosis of pheochromocytoma. MGG stained the cytoplasm composed of two-tone colors: eosinophilic granular in the perikarya and basophilic granular around nucleus. Electronmicroscopically, they were consistent with catecholamine granules and abundant rough endoplasmic reticulums, respectively. Although, it is fairly difficult to determine whether tumor cells are other malignant tumors or not by using PAP, small N/C ratio might be a useful index for pheochromocytoma. Combination of FIF, MGG, and PAP makes it easy to confirm the diagnosis of pheochromocytoma.

Adrenal Gland Neoplasms↗

The size and number of Langerhans islets correlated with their endocrine function: a morphometry on immunostained serial sections of adult human pancreases.

Surgical and autopsy specimens of normal pancreas from three human adults were submitted to morphometry of Langerhans islets and so-called extra insular islet cells, by measuring the islet radii on serial sections immunostained for either insulin or glucagon. All the islets contained in a test volume were measured including single cells, and the distribution of their radial sizes was studied. It was found that the distribution of islets was strongly skewed and continuous, with the majority of islets having radial values near to the minimum. From the fact that only one peak was found in the distribution curve, it is concluded that in spite of the distinction previously made between islets of Langerhans and so-called extra-islet cells, they are in fact both part of a continuous distribution. Moreover, the Weibull function, assumed as the theoretical distribution, fit well with the empirical histograms, giving support for the contention of continuous distribution with a single peak. Although the small islets account for a majority of the number of islets, they account for only a very small percentage of the islet volume. This is thought to indicate that the bulk of the endocrine functions of the pancreas are carried out by large islets, whereas the so-called extra-islet cells are likely to be their precursors. With regard to the cellular structure of the islets, it was found that the smaller the islet, the smaller the percentage of islets containing A cells, with the vast majority of cells in the smallest islets (often single cells) being B cells.

Adult↗

Corticosteroid binding in human artery.

Mineralo- and glucocorticoid binding in cytosol of surgically obtained human arteries and umbilical arteries were analyzed. Scatchard analysis of glucocorticoid binding in femoral and umbilical arteries revealed the binding parameters of Kd = 4.3, 8.2 X 10(-9) M; Bmax = 42, 90 fmol/mg protein, respectively. Scatchard analysis of mineralocorticoid binding in inferior mesenteric artery showed a curvilinear pattern suggestive of the presence of two binding components, one with a higher affinity and a lower capacity for the ligand (Kd = 3.3 X 10(-10) M, Bmax = 0.8 fmol/mg protein) and the other with lower affinity and higher capacity (Kd = 10 X 10(-7) M, Bmax = 36 fmol/mg protein). Polyacrylamide gel electrophoresis of mineralo- and glucocorticoid binding in the cytosol of popliteal artery also showed the presence of the corticosteroid binding components with limited binding capacity. Sucrose density gradient centrifugation of corticosteroid binding in cytosol of femoral artery revealed the presence of dexamethasone binding molecule sedimenting in the 8-9 S region and deoxycorticosterone binding molecules sedimenting in the 7-8 and 8-9 S regions of the gradinent. Those results revealed the presence of mineralo- and glucocorticoid receptors in human artery and suggest the possible direct actions of corticosteroids upon human artery.

Adult↗

Presence of neurophysins in the human pituitary corticotrophs, Cushing's adenomas, and growth hormone-producing adenomas detected by immunohistochemical study.

Neurophysins have been recognized as the carrier proteins of vasopressin and oxytocin. The distribution of neurophysins is immunohistochemically confirmed in the hypothalamus, median eminence, and posterior lobe of the pituitary gland. The authors detected neurophysins in the human corticotrophs and pituitary adenomas with the use of the immunohistochemical method with antiserum to human neurophysins, which did not cross-react with adrenocorticotropic hormone (ACTH), beta-endorphin, and corticotropin-releasing factor. All of ten pituitary glands obtained by autopsy revealed the presence of neurophysin-positive cells in the anterior, intermediate, and the posterior lobes. The neurophysin-positive cells were similar to the corticotrophs in shape and distribution. Simultaneous staining for ACTH and neurophysins in the serial sections revealed that neurophysin-positive cells were also ACTH-positive. One hundred twenty-four cases of pituitary adenoma operated upon were investigated. All of 7 Cushing's adenomas were composed of neurophysin-positive cells. Six tumors with giantism showed sparsely distributed neurophysin-positive cells. No neurophysin-positive cells were observed in any other cases. This study is the first reported evidence of the presence of neurophysins in the human corticotrophs and pituitary adenomas.

Adenoma↗