Motoko Ojima

Intramedullary spinal cord germinoma producing hcg and precocious puberty in a boy

Extremely high concentrations of human chorionic gonadotropin in the cerebrospinal fluid were found in a 5‐year‐old boy presenting sexual precocity and leg pain. An intramedullary spinal cord tumor was revealed by myelogram and metrizamide computerized tomography, and a biopsy specimen taken at laminectomy. Histologically, the tumor showed germinoma with syncytiotrophoblastic giant cells. The tumor remitted for 5 months after irradiation of 3500 rad and chemotherapy, but recurred in spite of adding 7500 rad and more aggressive chemotherapy. No relapse has been seen for 1 year after amputation of the spinal cord at the T7 level.

Human chorionic gonadotropin and alpha‐fetoprotein in testicular germ cell tumors. An immunohistochemical study in comparison with tissue concentrations

The relation between immunohistochemical demonstration and tissue concentration of humanchorionic gonadotropin (hCG) and alpha‐fetoprotein (AFP) was examined in 17 testicular germ cell tumors. There was a good correlation between their results; e.g., a tumor with high hCG concentration contained numerous hCG positive cells, and vice versa. The immunoperoxidase localization of hCG and AFP was investigated in 57 tumors including above 17. HCG was revealed in syncytiotrophoblastic giant cells of seminoma or embryonal carcinoma as well as syncytial cells of choriocarcinoma, and on rare occasion in mononuclear cells. AFP was localized in tumor cells of yolk sac tumor or embryonal carcinoma and occasionally hyaline globules. No cell was stained concomitantly with hCG and AFP. Pathogenetical significance of cells positively stained was discussed.

An immunohistochemical study of hepatoblastoma producing human chorionic gonadotropin

High tissue concentrations of human chorionic gonadotropin (hCG) and alpha‐fetoprotein (AFP) were revealed by radioimmunoassay in a hepatic tumor which was surgically removed from a two‐year, eight‐month‐old boy manifesting sexual precocity. Histologically the tumor showed an embryonal type hepatoblastoma admixed with multinucleated tumor giant cells. The localization of native hCG and hCG‐beta subunit was immunohistochemically demonstrated in some of the above giant cells, while that of alpha‐fetoprotein was diffusely in the tumor cells of hepatoblastoma of embryonal type. Ultrastructural features of the giant cells were also presented.

Congenital 17α-hydroxylase deficiency: A clinicopathologic study

The histopathologic features of the adrenal glands in three cases of congenital 17α-hydroxylase deficiency are described in relation to clinical and endocrine findings. Diffuse or nodular adrenocortical hyperplasia, particularly in the zonae fasciculata and reticularis, was observed in all cases examined. The hyperplastic adrenal cortices were, composed of cells with morphologic features of hypercorticism and hyperstimulation. Myelolipomatous lesions were detected in two cases. These morphologic findings were consistent with excessive adrenocorticotropic hormone secretion in this disorder. In all the cases examined, the plasma aldosterone concentration was within normal limits, and plasma renin activity was suppressed prior to dexamethasone treatment. Morphologically, however, hyperplasia of the cells with abundant mitochondria and smooth endoplasmic reticulum seemed to involve the zona glomerulosa. Nonencapsulated nests of hypertrophied cortical cells in periadrenal tissue were remarkable in one case. From these morphologic findings, we postulated hyperfunction of the zona glomerulosa as well as involvement of corticosteroids from the zona, glomerulosa in the pathophysiology of this disorder.

Renin and Angiotensin-Converting Enzyme in Human Neuroblastoma Tissue

Abstract: High activity of renin was demonstrated in human neuroblastoma tissue. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 122.8 ng of angiotensin I generated mg of protein −1h −1. It shared some biochemical features with well‐known kidney renin, such as molecular weight, optimum pH, the presence of trypsin‐activatable inactive renin, and glycoprotein nature. Furthermore, angiotensin‐converting enzyme (ACE) activity (2.64 nmol mg of protein−1 min−1) was found in the tissue. This activity was inhibited by captopril, a specific ACE inhibitor, or by omission of chloride ion. These results suggest that true renin in addition to ACE exists in human neuroblastoma tissue.

Ultrastructure of pigment in adrenocortical pigmented adenomas of Cushing's syndrome and in non-functioning pigmented nodules with respect to tissue steroid analyses

Ultrastructural and morphometrical analysis of brown pigment in pigmented (black) and non-pigmented adrenocortical adenomas of Cushings syndrome and non-functioning pigmented adrenocortical nodules was performed in reference to tissue concentrations and in vitro production of steroids by the adenoma tissue. Pigment in pigmented adenomas was of membrane-bound lysosomal nature, while that of pigmented nodules contained membrane-unbound droplets of lipoid character. The morphometrical study showed little difference among individual adenomas. There was no difference between pigmented and non-pigmented adenomas in the amount of production and tissue concentrations of steroids. The steroid concentrations in a pigmented nodule were lower than those in an adenoma of Cushings syndrome, but not significantly. Discussion is focused on the difference of pigment of lysosomal nature and of lipoid peroxidation.

Biochemical evidence for existence of immunoreactive renin in human prolactinoma tissue

High activity of renin was demonstrated in human prolactinoma tissue. This activity was almost completely inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 5.04 ng of angiotensin I generated/mg of protein per h, comparable to that of the pituitary tissue prepared from postmortem human subjects. The biochemical properties of the prolactinoma renin were generally similar to those of well-known kidney enzyme, such as molecular mass (Mr = 46,000), optimum pH (6.0), and glycoprotein nature. However, the isoelectric points (pI) of the prolactinoma renin (pI = 4.90, 5.04, 5.24 and 5.41) differed somewhat from those of plasma and kidney renins reported hitherto. These results indicate that true renin can be produced in human prolactinoma tissue.

Multiple forms of immunoreactive renin in human pituitary tissue

Immunoreactive renin was demonstrated in pituitary tissues of postmortem human subjects with different diseases. The specific immunoreactive renin activity comprised the majority of the tissue renin-like activity (mean, 83%), indicating the absence of nonspecific actions of proteases such as cathepsin D. We used three pituitary specimens with high levels of the specific renin activity for further biochemical characterization of the enzyme. Small differences were found in the molecular mass (45 K, 42 K and 37 K), binding to concanavalin A-Sepharose, and isoelectric points (pI) (4.72, 4.78, 4.86, 5.06, 5.28 and 5.44). These results seem to be interpreted as evidence for the presence of specific renin in the human pituitary with microheterogeneity.

カンレノ酸カリウム (Soldactone) のウシ副腎皮質ステロイド合成酵素系に与える影響

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.

[A case of 21-hydroxylase deficiency and Bartter's syndrome associated with a balanced 6-9 translocation].

A 17-year-old female weighing 37 kg and 140 cm in height was referred to our hospital for evaluation of dwarfism and primary amenorrhea. She was delivered with 3350 g in weight and 50 cm in height after a ten month pregnancy without complications. No abnormal findings were revealed in physical appearance except critomegaly. Episodes of nausea, vomiting and dehydration were rare throughout her childhood, but she had a tendency to salt craving. At the age of 14, her height was 140 cm. On admission, her physical development was markedly retarded for her age, except external genitalia. Diffuse pigmentations on the trunk and extremities were observed. Her blood pressure was normal (112/62 mm Hg). Serum potassium concentration was 2.9 mEq/L. Arterial-blood gas analysis revealed metabolic alkalosis. Both of renin activity (PRA) and aldosterone concentration (PAC) in plasma at rest were markedly elevated to 15.5 ng/ml/h and 107.1 ng/dl, respectively. The plasma concentrations of pregnenolone (1449 ng/dl), progesterone (178 ng/dl), 17-OH-pregnenolone (1613 ng/dl), 17-OH-progesterone (180 ng/dl), dehydroepiandrosterone (3706 ng/dl), androstendione (824.6 ng/dl) and testosterone (900 ng/dl) were high, whereas deoxycorticosterone (15.7 ng/dl), corticosterone (0.65 microgram/dl) and cortisol (6.8 micrograms/dl) were within normal limits. Urinary 17-KS excretion showed high levels between 65.7 and 109.4 mg/day, while urinary 17-OHCS excretion was normal (5.7-7.0 mg/day). Vascular response to angiotensin II (A-II) was attenuated. Distal fractional chloride reabsorption was decreased (CH2O/CH2O+CCl = 0.62, normal: 0.92 +/- 0.04). Moderate hyperplasia of the juxtaglomerular cells was demonstrated in biopsy specimen of the kidney. Cytogenetic studies showed a 46, XX chromosome constitution with translocation of the long arm of chromosome 6 to the short arm of chromosome 9. Her mother as well as younger brother and sister, whose electrolytes and arterial-blood gas analysis showed normal values, had chromosomes with the same translocation. Treatment with dexamethasone (2 mg/day) reduced every adrenal steroids to normal range, but PRA and PAC remained high levels. Furthermore, neither hypokalemic alkalosis nor vasoreactivity to exogenous A-II was improved. Indomethacin (75 mg/day) decreased urinary excretion of prostaglandin E2 from a high level of 738.4 ng/day to 433.4 ng/day and normalized metabolic alkalosis. Vascular response to A-II was moderately improved. However, serum potassium remained low.(ABSTRACT TRUNCATED AT 400 WORDS)