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T Yanase

Publications and source records attributed to T Yanase.

At least 145 records · Page 8Linked to original sources
PubMed1989

Deletion of a phenylalanine in the N-terminal region of human cytochrome P-450(17 alpha) results in partial combined 17 alpha-hydroxylase/17,20-lyase deficiency.

Steroid 17 alpha-hydroxylase and 17,20-lyase activities reside within the same polypeptide chain (cytochrome P-450(17 alpha)), and consequently human 17 alpha-hydroxylase deficiencies are characterized by defects in either or both of these activities. Human mutants having these deficiencies represent an excellent source of material for investigation of P-450(17 alpha) structure-function relationships. The CYP17 gene from an individual having partial combined 17 alpha-hydroxylase/17,20-lyase deficiency has been characterized structurally and the homozygous mutation found to be the deletion of the phenylalanine codon (TTC) at either amino acid position 53 or 54 in exon 1. Reconstruction of this mutation into a human P-450(17 alpha) cDNA followed by expression in COS 1 cells led to production of the same amount of immunodetectable P-450(17 alpha) protein as found with expression of the normal human P-450(17 alpha) cDNA. However, 17 alpha-hydroxylase activity of this mutant protein measured in intact cells was less than 37% of that observed upon expression of the wild-type enzyme, whereas 17,20-lyase activity of the mutant was less than 8% of that observed with the normal enzyme. When estimated in intact cells, the Km for 17 alpha-hydroxylation of progesterone was increased by a factor of 2 in the mutant enzyme, whereas the Vmax was reduced by a factor of 3. In order to estimate the kinetic parameters for the 17,20-lyase reaction, microsomes were isolated from transfected COS 1 cells to enrich for this activity. Surprisingly, the specific activity of the mutant 17 alpha-hydroxylase in microsomes was 3-fold less than that observed in intact cells, indicating that the structure of mutant P-450(17 alpha) was dramatically altered upon disruption of COS 1 cells. Apparently the deletion of a single phenylalanine in the N-terminal region of P-450(17 alpha) alters its folding in such a way that both enzymatic activities are dramatically decreased, leading to the partial combined deficiency observed in this individual.

Adrenal Hyperplasia, Congenital↗
PubMed1989

[Cholesterol atheroembolic renal failure after arteriography. Report of a case diagnosed by renal biopsy].

A case of atheroembolic renal failure diagnosed by renal biopsy was presented. A 69-year-old man was referred because of progressive renal failure two months after major angiography for occlusive arterial disease of lower limbs. The physical examination on admission revealed an uncontrollable hypertension. The laboratory findings showed elevated serum creatinine (7.5 mg/dl) and eosinophilia (1022/mm3) with normal urinalysis findings. Renal biopsy disclosed a occlusive lesion of the arcuate artery which contained cholesterol clefts and foam cells, and showed ischemic renal parenchymal changes. These findings were compatible with cholesterol atheroembolic renal disease. In spite of the aggressive medical treatment, renal function had deteriorated progressively and the patient has been on regular hemodialysis. Atheroembolic renal failure after arteriography have been reported recently, but the case diagnosed by renal biopsy has been rare. Since there is no therapeutic way to reverse this type of renal failure, strict selection of patients for the angiographic examination and use of flexible catheter might be mandatory. Subacute course of renal failure after angiography and eosinophilia seem to be the important diagnostic clues for this disorder.

Aged↗
PubMed1988

Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a stop codon in the N-terminal region of 17 alpha-hydroxylase cytochrome P-450.

Steroid 17 alpha-hydroxylase (cytochrome P-450(17)alpha) mediates both 17 alpha-hydroxylase and 17,20-lyase activities. A relatively rare disease, 17 alpha-hydroxylase deficiency is characterized by defects in either or both of these activities. The molecular basis for variability of the defect is not well understood. We have determined the exonic sequence of the mutant P-450(17)alpha gene from one Japanese patient with combined 17 alpha-hydroxylase/17,20-lyase deficiencies. A stop codon (TGA) due to a single point mutation was found at the position of amino acid 17 in exon 1 of the P-450(17)alpha gene. The presence of a stop codon in the N-terminal region of this gene leads to the absence of a functional P-450(17)alpha protein in adrenal cortex and ovary, and consequently hypertension, primary amenorrhea and osteoporosis in this patient.

Adrenal Cortex↗
PubMed1988

A case of glucocorticoid-suppressible hyperaldosteronism with aldosterone producing adenoma.

A 34-yr-old woman with hypertension (142/102 mmHg), hypokalemia, high plasma and urinary aldosterone and low plasma renin activity was studied. A left adrenal tumor and enlarged right adrenal gland were demonstrated by adrenal venography. During administration of dexamethasone (2 mg daily, for 3 weeks), urinary aldosterone excretion decreased abruptly from 22.5 to 9-11 micrograms/day, serum potassium increased and blood pressure fell to 120-130/80-90 mmHg. After left adrenalectomy, all manifestations improved with no medication. The resected adrenal gland revealed clear cell adenoma and micronodular adrenocortical hyperplasia. The patient was considered to be a rare case of glucocorticoid-suppressible hyperaldosteronism with an aldosterone-producing adenoma.

Adenoma↗
PubMed1987

alpha-Neoendorphin-like immunoreactivity in medullary carcinoma of the thyroid.

alpha-Neoendorphin-like immunoreactivities (alpha-NE-IR) were demonstrated in tissues from three patients with medullary carcinoma of the thyroid (MCT). A large amount of alpha-NE-IR was detected in the extracts of primary tumors and metastatic lymphatic tissues by a highly sensitive and specific radioimmunoassay (RIA). Gel filtration analyses showed two different molecular-weight forms of the alpha-NE-IR: One eluted at the void fraction and the other at the position of [125I]-alpha-NE on Sephadex (Pharmacia Fine Chemical, Uppsala, Sweden) G-50 chromatography. Immunohistochemical examination revealed the presence of alpha-NE-IR in the C-cell carcinoma. These data presumably reflect that alpha-NE, the opioid peptide derived from preproenkephalin B, is synthesized in the MCT.

Adolescent↗
PubMed1987

Preproenkephalin A-derived opioid peptides and mRNA of preproenkephalin A in human pheochromocytomas.

Tissue contents of immunoreactive met-enkephalin (Met-Enk), leu-enkephalin (Leu-Enk) and met-enkephalin-Arg-Gly-Leu (Met-Enk-AGL) were determined by specific RIAs in 17 pheochromocytomas and the levels of preproenkephalin A mRNA were compared in some of these tissues by Northern blot hybridization. Remarkably wide distributions in the amounts of immunoreactive Met-Enk, Leu-Enk and Met-Enk-AGL were observed in 17 pheochromocytomas. Medullary pheochromocytomas contained significantly larger amounts of immunoreactive Met-Enk, Leu-Enk and Met-Enk-AGL than did the extramedullary ones. Significant positive correlations of tumor tissue immunoreactivities between Met-Enk and Leu-Enk (r = 0.97, P less than 0.01) and between Met-Enk and Met-Enk-AGL (r = 0.97, P less than 0.01) were observed. No difference in size of mRNA of preproenkephalin A was observed in the pheochromocytomas. Medullary pheochromocytomas contained higher amounts of preproenkephalin A mRA than did the extramedullary ones. The quantities of preproenkephalin A mRNA in nine pheochromocytoma tissues significantly correlated with those of immunoreactive Met-Enk in these tissues (r = 0.94, P less than 0.01). These results indicate that the remarkable difference in tissue immunoreactivities of preproenkephalin A-derived opioid peptides is decided at the transcriptional level but not at the posttranslational level.

Adrenal Gland Neoplasms↗
PubMed1987

Correlation of daily urinary excretion of met-enkephalin-like immunoreactivity and epinephrine in men.

To investigate the source of urinary Met-enkephalin-like immunoreactivity (MELI), 24-h urinary excretion of MELI and catecholamines (CAs) were examined in normal subjects and patients with tuberculous Addison's disease. MELI was present in urine and 24-h urinary excretion of MELI averaged 813.8 +/- 446.9 ng/day in normal subjects (N = 33, Mean +/- SD). 24-h urinary excretion of MELI in normal subjects significantly showed positive correlation with 24-h urinary epinephrine (E) (R = 0.392, P less than 0.05) but no correlation with that of norepinephrine (NE) or dopamine (DA). In two patients with tuberculous Addison's disease, 24-h urinary excretion of MELI and that of E were significantly lower than those of normal subjects. These results indicate that the main source of urinary MELI may be adrenal medulla.

Addison Disease↗
PubMed1987

Studies on adrenorphin in pheochromocytoma.

We studied the secretion and tissue contents of adrenorphin in human pheochromocytomas. In 17 human pheochromocytomas from 11 patients, we found a remarkably wide distribution in immunoreactive adrenorphin levels (3-7771 pg/mg tissue). Adrenomedullary pheochromocytomas contained a significantly larger amount of immunoreactive adrenorphin (2295 +/- 1092 pg/mg, mean +/- SE) than did extramedullary ones (17.8 +/- 8.4 pg/mg). Gel chromatographic studies revealed that immunoreactive adrenorphin consisted largely of material emerging at the position of synthetic adrenorphin in both pheochromocytoma and normal adrenal medulla tissue. Nicotine (10(-5) M) significantly stimulated the secretion of immunoreactive adrenorphin as well as catecholamines from cultured human pheochromocytoma cells. Adrenorphin was a more potent inhibitor of catecholamine secretion evoked by 10(-5) M nicotine than was met-enkephalin in cultured human pheochromocytoma cells. The 50% inhibitory concentrations (IC50) were 1.1 X 10(-6) and 6.5 X 10(-5) M for adrenorphin and met-enkephalin, respectively. The effect of adrenorphin was much the same as that of dynorphin-(1-13) (IC50, 1.0 X 10(-6) M) and BAM-12P (IC50, 4.5 X 10(-6) M). These results indicate the presence and secretion of adrenorphin in human pheochromocytomas. Adrenorphin may play an important role in regulating catecholamine secretion in human pheochromocytoma.

Adolescent↗
PubMed1987

Preproenkephalin B-derived opioid peptides in human phaeochromocytomas.

We demonstrated the presence and the secretion in vivo and in vitro of immunoreactive preproenkephalin B-derived opioid peptides (alpha-neoendorphin, dynorphin and leumorphin) in human phaeochromocytomas. In seventeen human phaeochromocytomas and two human adrenal medullas, the tissue contents of immunoreactive preproenkephalin B-derived opioid peptides (alpha-neoendorphin, dynorphin and leumorphin) and leu-enkephalin were studied by specific RIAs. Compared with a remarkable wide distribution in amounts of immunoreactive leu-enkephalin (1063 +/- 437 pg/mg, mean +/- SE), small amounts of immunoreactive alpha-neoendorphin (22.6 +/- 6.4 pg/mg) and dynorphin (8.5 +/- 1.2 pg/mg) were detected in all seventeen human phaeochromocytomas and the two human adrenal medullas. Leumorphin-like immunoreactivity was detected in only four tumours. Gel chromatographic studies revealed the presence of preproenkephalin B-derived peptides and their high molecular forms. A significant positive correlation between the tumour tissue contents of immunoreactive alpha-neoendorphin and of dynorphin was observed. Nicotine (10(-5), 10(-4) mol/l) significantly stimulated the secretion of immunoreactive alpha-neoendorphin and dynorphin as well as leu-enkephalin and catecholamines from cultured human phaeochromocytoma cells. Administration of 1 mg of glucagon to a patient with medullary phaeochromocytoma induced a rapid increase in the plasma concentration of immunoreactive alpha-neoendorphin with a concomitant increase in plasma catecholamines. These results indicate the presence of preproenkephalin B-derived opioid peptides in human phaeochromocytomas and human adrenal medullas and their secretion in human phaeochromocytomas.

Adolescent↗
PubMed1986

In vivo evidence of regulation by pituitary-adrenal axis of urinary epinephrine excretion in men.

The effect of the pituitary-adrenal axis on epinephrine synthesis in the human adrenal medulla was examined by the estimation of the 24-h urinary epinephrine level after treatment with glucocorticoids in four patients with systemic lupus erythematodes (SLE), one patient with rheumatoid arthritis (RA) and one patient with adrenal pheochromocytoma. 24-h urinary catecholamines (CAs) were measured by HPLC before and after glucocorticoid treatment, dexamethasone or prednisolone was orally given for more than seven days to patients with SLE, RA or isolated ACTH deficiency and five days to a patient with adrenal pheochromocytoma. In patients with isolated ACTH deficiency, the 24-h urinary epinephrine level was significantly lower than the normal range. In patients with SLE or RA, the 24-h urinary epinephrine level was normal and it was significantly suppressed by therapeutic doses of prednisolone 30-40 mg/day. In a patient with adrenal pheochromocytoma, 24-h urinary epinephrine was extremely high and it was significantly increased after dexamethasone 0.5 mg/day. These results suggest that epinephrine synthesis in the human adrenal medulla may be dependent on the pituitary-adrenal axis. But the increase in epinephrine synthesis due to dexamethasone in a patient with pheochromocytoma may reflect the direct effect via the feeding artery to the tumor, as previously shown in an in vitro culture system.

Adrenal Gland Neoplasms↗
PubMed1986

Catecholamines and opioid peptides in human phaeochromocytomas.

The tissue contents of catecholamines (CAs) and methionine-enkephalin-like immunoreactivity (Met-enk) were examined in 8 patients with phaeochromocytomas (Phs). In 6, Ph cells were cultured, and the modes of secretion of CAs and Met-enk were examined. Tissue contents of CAs and Met-enk varied from patient to patient, but larger amounts of Met-enk were found in medullary Phs than extramedullary ones, regardless of the secreting CA type. Three patients with extramedullary Phs had clinically showed a sustained hypertension, whereas five with medullary Phs were normotensive or had occasional paroxysmal hypertension. Nicotine (10(-7) M to 10(-4) M) stimulated simultaneous secretion of CAs and Met-enk from the cultured human Ph cells. Met-enk, however, was not secreted in proportion to either epinephrine (E), norepinephrine (NE) or total CAs (E + NE). Met-enk, FK33-824 (FK) (Met-enkephalin analogue), and dynorphin 1-13 (Dyn) significantly suppressed the secretion of CA evoked by 10(-5) M nicotine. The 50% inhibitory concentrations (IC50) of Met-enk, FK, and Dyn were 5 X 10(-6) M, 9.9 X 10(-5) M, and 9.0 X 10(-8) M, respectively, in one patient and 9.0 X 10(-6) M, 1.5 X 10(-7) M, and 1.4 X 10(-7) M in another. In one patient, 10(-5) M naloxone inhibited the CA secretion evoked by 10(-5) M nicotine and did not reverse the 10(-5) M FK-induced suppression of CA secretion in the presence of 10(-5) M nicotine. These results suggest that human Phs may be heterogeneous with regard to storage and secretion of CAs and opioid peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

[The effects of metoclopramide and dopamine on aldosterone secretion in cultured adrenocortical adenoma cells and adjacent non-adenoma cells from patients with primary aldosteronism].

Several authors have reported that metoclopramide (MCP), a dopaminergic antagonist, stimulates aldosterone secretion and that dopamine (DA) inhibits the MCP-mediated aldosterone secretion in man. However, many controversial results have been reported relating to the direct effect of MCP and DA on the secretion of aldosterone by adrenocortical cells in in vitro experiments. The present studies were designed to determine whether or not MCP and DA exerts its effect directly on the cultured human adrenocortical adenoma cells and adjacent non-adenoma cells obtained from patients with primary aldosteronism. A bolus intravenous injection of 10 mg MCP significantly increased the plasma aldosterone concentration (PAC) from 255 +/- 57 pg/ml (mean +/- SD) to 386 +/- 98 pg/ml after 15 min in patients with primary aldosteronism. But MCP (10(10)-10(-6) M) failed to increase aldosterone secretion from both adenoma cells and non-adenoma cells in culture. DA (10(-9) and 10(-6) M) did not suppress the basal secretion and the enhanced secretion of aldosterone by A II or ACTH in cells of either culture. The analysis by HPLC showed that 57% of dopamine hydrochloride added in the medium was preserved after 60 min incubation. These results suggest that MCP and DA do not act directly on the human adrenal glomerulosa cells in the regulation of aldosterone secretion.

Adenoma↗
PubMed1985

Epinephrine and norepinephrine syntheses are regulated by a glucocorticoid receptor-mediated mechanism in the bovine adrenal medulla.

The bovine adrenal medulla was investigated regarding the presence of glucocorticoid binding protein and the increases in ornithine decarboxylase (ODC) activity and epinephrine and norepinephrine by dexamethasone. Scatchard analysis of specific cytosol [3H] dexamethasone-binding study indicated a single class of high affinity (kd, 35 +/- 5 nM) and limited binding sites (150 +/- 26 fmoles/mg protein). Competition studies of various steroids indicated a high affinity for dexamethasone and hydrocortisone. Sedimentation in sucrose density gradients revealed a 7.3 S binding peak in the cytosol. Dexamethasone caused an increase in ornithine decarboxylase (ODC) activity within 1 to 2 hours after which the norepinephrine and epinephrine contents increased 16 hours after the peak of ODC activity in a dose dependent manner of dexamethasone in bovine adrenal medullary chromaffin cells in primary monolayer culture. These data suggest that the bovine adrenal medulla is a target organ of glucocorticoid hormone and that norepinephrine and epinephrine syntheses are regulated by a glucocorticoid receptor-mediated mechanism.

Adrenal Medulla↗