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Biomedical subjects

M Ojima

Publications and source records attributed to M Ojima.

At least 73 records · Page 4Linked to original sources
PubMed1986

[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↗
PubMed1986

[The effect of metoclopramide and dopamine on mineralocorticoid secretion--in vivo and in vitro studies].

There is considerable information suggesting that dopamine is a physiological regulator of aldosterone secretion. Metoclopramide, a specific dopamine antagonist, elicits a rapid rise in plasma aldosterone independent of the known aldosterone-regulating factors. However, the mechanism and the site of action of metoclopramide, whether adrenal or extra-adrenal, in stimulation of aldosterone production remain to be defined. The present studies were designed to investigate the mechanism of dopaminergic control of corticosteroid secretion and to determine at which step in the aldosterone biosynthetic pathway metoclopramide and dopamine exert their effect. Plasma concentrations of progesterone, 11-deoxycorticosterone (DOC), and cortisol were not altered by a bolus intravenous administration of 10 mg metoclopramide in 8 healthy male volunteers. Metoclopramide increased plasma aldosterone from 6.9 +/- 2.8 (Mean +/- 2SD) ng/100 ml to a maximum level of 18.2 +/- 4.7 ng/100 ml, 18-hydroxycorticosterone (18-OHB) from 12.6 +/- 6.5 ng/100 ml to a maximum of 41.3 +/- 7.3 ng/100 ml and corticosterone from 0.36 +/- 0.09 microgram/100 ml to a maximum of 0.85 +/- 0.22 microgram/100 ml. The aldosterone, 18-OHB and corticosterone responses displayed a parallel time course, with a significant response of each occurring within 5 minutes after metoclopramide administration. These data suggest that metoclopramide may modulate the activities of 18-hydroxylase and 11 beta-hydroxylase. Studies in vitro revealed that metoclopramide (10(-8)-10(-4) M had little effect on basal production of aldosterone, 18-OHB and corticosterone from human adrenal slices. Dopamine (10(-4) M) did not alter the basal secretion of aldosterone, 18-OHB and corticosterone, but suppressed the secretion of these 3 mineralocorticoids by ACTH, which were diminished by addition of 10(-4) M metoclopramide. There was a concentration-dependent inhibitory effect of dopamine on conversion of corticosterone to 18-OHB and DOC to corticosterone in vitro using bovine adrenal mitochondrial fractions. IC50 of dopamine inhibiting 18-hydroxylation and 11 beta-hydroxylation were 7.5 X 10(-7) M and 9.5 X 10(-4) M, respectively. It appears that physiological concentration of dopamine can modulate the activity of 18-hydroxylase enzyme. In summary, it can be concluded that the in vivo and in vitro studies are compatible with a view that dopamine has a physiological role in the regulation of aldosterone by modulating the activity of 18-hydroxylase enzyme.

18-Hydroxycorticosterone↗
PubMed1986

Two adult familial cases of selective hypoaldosteronism due to insufficiency of conversion of corticosterone to aldosterone.

A 57-year-old woman (case 1) and her daughter aged 29 (case 2) with hyperkalemia exhibited subnormal plasma aldosterone (ALD) in the face of elevated plasma renin activity. Their physical findings were normal. Their arterial blood gas analysis showed that metabolic acidosis and renal function of these cases were slightly impaired. Urinary 17-OHCS and 17-KS excretions in these cases were normal. Baseline levels of corticosterone (B) and 18-hydroxycorticosterone (18-OH-B) were clearly elevated. Plasma deoxycorticosterone (DOC), B and 18-OH-B as well as cortisol remarkable increased after ACTH injection, but the increase in plasma ALD was very small. Angiotensin II infusion in case 1 resulted in a clear rise in plasma 18-OH-B but in slight depletion of B, and no increase in ALD. 9-alpha-fludrocortisone acetate treatment was performed in case 1. Serum potassium was normalized and blood pressure elevated from 82/52 to 120/78 mmHg. Arterial blood gas analysis was corrected. We concluded that these two cases with subnormal plasma ALD and hyperreninemia may exist as a congenital and familial abnormality of the final step of aldosterone boisynthesis due to the impairment of the conversion of B to ALD.

Adrenocorticotropic Hormone↗
PubMed1985

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.

Chromatography, Affinity↗
PubMed1985

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.

Child, Preschool↗
PubMed1985

[Biochemical properties of renin in human pituitary tissue].

The biochemical properties of renin, extracted from human pituitary specimens obtained at autopsy, were studied using a specific antirenin antibody raised against human kidney renin. The following results were obtained. The molecular weight of pituitary renin was estimated to be about 37,000 daltons by gel filtration through Sephadex G-100. The optimum pH of pituitary renin was between 6.0 approximately 7.0, while that of a renin-like substance which did not react with the antirenin antibody had an acidic pH of 4.0, with a pH comparable to that of the cathepsin D-like enzyme in the pituitary tissue. The presence of two different isoelectric-point species of pituitary renin was revealed by isoelectric focusing, one with a point of pH 4.47 and the other with that of pH 5.77. The Km value of pituitary renin was 37.9 microM for synthetic human renin substrate. Affinity chromatography of the pituitary renin on a Concanavalin-Sepharose column showed that most (87.4%) of the pituitary renin did not contain glycoprotein residues. Treatment with either trypsin or glandular kallikrein increased the renin activity, indicating the presence of an inactive form of renin in the pituitary tissue. From these findings, it is concluded that specific renin exists in human pituitary tissue. It seems likely that the pituitary renin is of local origin rather than contamination of the circulating enzyme.

Chromatography, Affinity↗
PubMed1985

[The effects of o,p'-DDD on adrenal steroidogenesis and hepatic steroid metabolism].

O,p'-DDD is used for the treatment of adrenocortical carcinoma and Cushing's disease. The inhibitory effect of this drug on the adrenal steroid biosynthesis has been described by many authors, but there are very few reports about the sites of action of this drug on adrenal steroid synthesis. This paper presents in vitro studies on adrenal steroidogenesis and hepatic steroid metabolism. The effects of o,p'-DDD on adrenal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 11 beta-hydroxylase (11 beta-OHlase) and 18-hydroxylase (18-OHlase) were examined in vitro using mitochondrial and microsomal fractions prepared by standard centrifugation procedures from the homogenate of bovine adrenal cortices. The concentrations of o,p'-DDD inducing 50% inhibition of 3 beta-HSD, 11 beta-OHlase and 18-OHlase were 8 X 10(-6) M, 1 X 10(-5) M and 3 X 10(-6) M, respectively. This study clearly demonstrates the marked inhibitory effects of o,p'-DDD on 3 beta-HSD in vitro, which was not described previously. The inhibitory effects of o,p'-DDD on these 3 enzymes were diminished by an addition of 0.05 approximately 0.5 mM of cofactor (NADPH or NAD). The results indicate that o,p'-DDD may reduce NADPH or NAD utilization, resulting in the inhibition of steroidogenesis. The effects of o,p'-DDD on hepatic 5 beta-reductase were examined in vitro using rat liver homogenate. O,p'-DDD inhibits 5 beta-reductase, resulting in the decrease of conversion of cortisol to dihydrocortisol and tetrahydrocortisol at the concentration of 10(-3) M.

18-Hydroxycorticosterone↗
PubMed1985

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 Cushing's 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 Cushing's syndrome, but not significantly. Discussion is focused on the difference of pigment of lysosomal nature and of lipoid peroxidation.

Adenoma↗
PubMed1985

Effects of 6-keto-prostaglandin E1 on ascitic hepatoma-130 in vivo comparison with chemotherapeutic agents.

The inhibitory effect of 6-keto-prostaglandin E1 (pGE1) on the growth and survival of ascitic hepatoma (AH-130) cells in vivo was compared with currently used chemotherapeutic agents. Three days after receiving an intraperitoneal injection of 3 X 10(6) AH-130 tumor cells, Donrhyu rats were injected intravenously or intraperitoneally with one of the following: Thromboxane B2 (TXB2) (0.5 mg/kg), 6-keto-pGE1 (0.5 mg/kg), Mitomycin C (MMC) (1.5 mg/kg), or MMC + 6-keto-pGE1 (1.5 mg/kg + 0.5 mg/kg). The mean survival time, median survival time, and increase of life survival percent (ILS%) during a 60 day period revealed that both 6-keto-pGE1 and 6-keto-pGE1 + MMC significantly inhibited AH-130 tumor cell growth, while TXB2 promoted tumor cell growth. We conclude that 6-keto-pGE1 like anti-tumor agents such as MMC, Diketocoriolin B, Carbazilquinon, Endoxan, and 5-Fluorouracil, can significantly inhibit growth of AH-130 tumor cells in vivo, particularly when administered in combination with the anti-tumor agent MMC.

Alprostadil↗
PubMed1985

Renin and angiotensin-converting enzyme in human neuroblastoma tissue.

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-1 h-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.

Animals↗
PubMed1985

True renin in human pituitary tissue.

Readily detectable levels of renin activity were demonstrated in human pituitary tissues. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. It shared some biochemical features with well-known kidney renin, such as molecular weight, optimum pH, and the presence of trypsin-activatable inactive renin. These results suggest that true renin exists in human pituitary tissue.

Adult↗
PubMed1985

Immunoreactive renin in human brain: distribution and properties.

Readily detectable levels of renin activity were demonstrated in the human brain. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases such as cathepsin D. The pineal gland was found to be the richest source of renin followed by the pituitary, hypothalamus and hippocampus. The substantia nigra, caudate nucleus, putamen and thalamus contained moderately high concentrations of renin. The brain renins from pineal and pituitary glands shared some biochemical features with well-known kidney renin, such as molecular weight (46,000 daltons for pineal renin; 37,000-45,000 daltons for pituitary renin), optimum pH (6.0-7.0), the presence of trypsin activatable inactive renin, and a glycoprotein nature. However, the electrofocusing pattern of renin from pituitary tissue (pI = 4.43, 5.77) differed from that of plasma and kidney enzymes heretofore reported, a discrepancy which could be interpreted as evidence for the endogeneous synthesis of renin in the brain tissue. Furthermore, a high activity of immunoreactive renin was found in human neuroblastoma tissue. The biochemical characteristics of the neuroblastomal renin were generally similar to the known properties of kidney renin in many respects, providing evidence of the presence of the renin-angiotensin system within human neuronal cells.

Brain↗
PubMed1985

Particular cases of Cushing's syndrome--one with adrenocortical carcinoma and the other with double adenomas.

Two particular cases of adrenocortical tumors associated with Cushing's syndrome were documented. In the first case, the steroid pattern suggested a malignancy, and the histology of the excised tumor confirmed it. In the second case, the left adrenal had two distinct tumors; one dark-brown, and the other yellow in color. Recent trends in the diagnosis and treatment of Cushing's syndrome were discussed.

Adenoma↗
PubMed1985

Angioarchitecture of rabbit iris.

We made a scanning electron-microscopic study of the angioarchitecture of the rabbit iris using vascular resin casts, and compared the vascular structure in miosis to that in mydriasis. There were three vascular layers in the iris: the anterior capillary layer, arteriolo-venular layer and posterior capillary layer. The anterior capillary layer was a network which covered the anterior surface of the iris. The posterior capillary layer was a peculiar network composed of many capillary folds, which were arranged radially. The arteriolo-venular layer was sandwiched between the two capillary layers. In this layer, arterioles and venules ran radially toward the pupil. The peripupillary region lacked the posterior capillary layer. In miosis, the vessels of the peripheral iris were straightened radially, while those in the peripupillary region were folded. In mydriasis, the vessels were very tortuous in the peripheral region, while those in the peripupillary region were stretched laterally. The change in the angioarchitecture of the iris was suited to pupillomotoric activity.

Animals↗
PubMed1985

Biochemical identification of renin in human pheochromocytoma.

A high activity of renin was demonstrated in human pheochromocytoma tissue. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific actions of proteases such as cathepsin D. The specific renin shared some biochemical features with well-known kidney renin, such as molecular weight (47,000 daltons), optimum pH (6.0), the presence of trypsin-activatable inactive renin, and glycoprotein nature. However, the isoelectrofocusing pattern of renin from the pheochromocytoma differed from that of kidney and plasma renins hitherto reported, a discrepancy which could be interpreted as evidence for endogenous synthesis of the enzyme. Furthermore, angiotensin converting enzyme activity was found in the tissue. Since pheochromocytoma is considered to be of neural crest origin, these results provide biochemical and immunological evidence for the presence of the renin-angiotensin cycle within human neuronal cells.

Adolescent↗
PubMed1984

Wegener's granulomatosis with destructive ocular manifestations.

A 27-year-old man developed bilateral destructive ocular manifestations of generalized Wegener's granulomatosis. Before the appearance of necrotic granuloma, which replaced almost all the original ocular components, the patient had suffered from severe headache and restricted ocular motility for five years. A general remission was achieved with azathioprine and prednisolone treatment although the patient is blind because of destruction of the globes.

Adult↗
PubMed1984

[The effects of o,p'-DDD on human adrenal steroid synthesis].

In the present study, the effects of o,p'-DDD on plasma levels of pregnenolone, 17 alpha-hydroxypregnenolone, progesterone, 17 alpha-hydroxyprogesterone, 11-deoxycorticosterone, deoxycortisol, corticosterone, cortisol, androstenedione and testosterone were studied in 6 patients with adrenal carcinoma (3 with Cushing's syndrome, 2 with adrenogenital syndrome, one without clinical manifestation) and 6 with Cushing's disease. Plasma levels of these steroids were decreased in all of the patients with adrenal carcinoma. The decrement of progesterone and 17 alpha-hydroxyprogesterone was greater than that of pregnenolone and 17 alpha-hydroxypregnenolone. These results indicate that o,p'-DDD inhibits both cholesterol cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase system. Plasma levels of pregnenolone and 17 alpha-hydroxypregnenolone showed a twofold increase on the 7th day after consecutive administrations of o,p'-DDD in patients with Cushing's disease. Plasma levels of cortisol were decreased to normal one month after continuous o,p'-DDD treatment. Urinary 17-OHCS and 17-KS have been decreased out of proportion to the decrease in plasma cortisol in the first week of o,p'-DDD treatment. Such a disparity suggests that o,p'-DDD might affect the extra-adrenal metabolism of cortisol. However, no evidence was found for the inhibition of hepatic C17-20lyase and glucuronyl transferase. Regression of pulmonary metastases was observed in one case with Cushing's syndrome due to adrenal carcinoma, suggesting that o,p'-DDD causes necrosis of the metastatic adrenal carcinoma. A remission of the disease was obtained in one patient with Cushing's disease after 6 months of continuous o,p'-DDD treatment. The usefulness of o,p'-DDD for the treatment of adrenal carcinoma with metastases and Cushing's disease was confirmed.

17-alpha-Hydroxypregnenolone↗