Biosynthesis of various steroids in vitro by isolated adrenal cells in primary aldosteronism, Cushing's syndrome, and adrenogenital syndrome due to adrenocortical adenoma.
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Biomedical subjects
Publications and source records attributed to H Funahashi.
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The preoperative identification of adrenal tumor is essential to correct diagnosis and appropriate treatment. Adrenal venography is one of the most useful adjuncts for this purpose, but catheters of various types introduced in the past are not necessarily well configured to catheterize adrenal veins. The catheter newly designed by us made catheterization of the left adrenal vein much easier even for unskilled hands. Our new catheter has been used in 20 of 55 venographical studies which have been carried out in our service. Determination of cortisol concentrations in adrenal venous blood which was performed in 6 cases failed to give any clue to determine the laterality of the existing adrenal tumor.
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Remarkable changes of parathyroid function immediately after parathyroidectomy were evaluated in primary (PHPT) and secondary (RHPT) hyperparathyroidism. Bone metabolism was also evaluated by new specific markers of bone formation and resorption. A rapid decline into the undetectable range, and a rapid recovery of serum bioactive parathyroid hormone (PTH) concentrations were observed after parathyroidectomy in PHPT. Since the function of the remnant parathyroid glands was not clear, we investigated the transcription of PTH mRNA. Despite the suppression of PTH secretion in the remnant parathyroid glands, no significant difference was found in the amount of PTH mRNA present in an adenoma as compared to a remnant gland when evaluated by cytoplasmic dot hybridization and in situ hybridization. Although measurement of serum PTH concentration by assays of inactive fragment was available for the longterm follow-up of PTH function in RHPT, parathyroid function should be evaluated by biologically active intact PTH immediately after operation. The PTH gradient also was successfully evaluated by the measurement of intact PTH. A discrepancy was observed between bone resorption evaluated by type I collagen cross-linked N-telopeptide as compared to bone formation evaluated by osteocalcin immediately after operation. This discrepancy will improve and bone mineral density will increase in the first 6 months after parathyroidectomy.
As part of an ongoing study of the characteristics of transplanted fresh normal and pathologic parathyroid tissues, we transplanted cryopreserved human parathyroid tissue into nude mice. Hyperplastic glands cryopreserved for various lengths of time (<2 weeks and >1 year) were transplanted into the gluteus muscle of nude mice. Specimens grafted were of two sizes: 10 mg and 30 mg. Serum human parathyroid hormone (hPTH) concentration was estimated by a double-antibody immunoradiometric assay prior to transplantation and 2, 4, and 8 weeks after transplantation. A low-calcium diet was given to some mice to evaluate any effects on the grafts of low serum concentrations of calcium. All mice were killed 4 hours after injection of bromodeoxyuridine (Brd U) for assessment of the cell proliferation in grafted parathyroid tissue. Although hPTH secretion of cryopreserved tissue was only half that of fresh tissue, the cryopreserved tissue released hPTH, as did fresh tissue. hPTH secretion was accelerated by stimulation of a low-calcium diet, and PTH secretion was positively correlated with the volume of transplanted tissue. The number of Brd U-immunoreactive cells was correlated with the serum concentration of hPTH (r = 0.95), which indicates that cell proliferation is closely related to PTH secretion under the condition of successful transplantation. The experimental transplantation of cryopreserved tissue into nude mice, coupled with a concise immunohistochemical study of the grafts conducted prior to their transplantation into humans, can contribute to the evaluation of PTH secretion and cell proliferation.
The effect of synthetic galanin on plasma glucose, insulin and pancreatic glucagon levels in dogs was studied. Infusion of galanin caused a rapid, reversible and dose-dependent reduction in basal insulin level. A maximal increase in blood glucose level accompanying the insulin decrease was observed when galanin was administered at a dose of 4 micrograms/kg per h. Pancreatic glucagon levels showed little change compared with basal secretion. These results indicate that galanin is involved in the regulation of glucose through control of insulin secretion.
Whisky (1 g/kg, 21.5% alcohol) was administered orally to healthy young adult male volunteers, and changes in the plasma concentrations of alcohol, acetaldehyde, gastrin, cholecystokinin (CCK) and serum amylase were measured over time. Values for alcohol and acetaldehyde rapidly reached a peak at 30-45 min after alcohol intake, followed by a gradual decline. The plasma gastrin concentration showed a rapid elevation, while the plasma CCK concentration did not exhibit any significant changes in the early phase after alcohol intake. Elevation of CCK was observed after 75 min, however. These results show that intake of whisky stimulates the secretion of gastrin and is associated with a later increase in CCK.
E-selectin which is expressed on endothelial cells plays an important role in the adhesion of cancer cells to the vascular endothelium, being the ligand for a carbohydrate antigen expressed on cancer cells. In this study, the clinical usefulness of this protein was examined. E-selectin was expressed on the endothelial cells of the small vessels adjacent to the cancer nests in 63 of the 104 (60.6%) primary tumors of breast cancer. The expression of E-selectin in locations adjacent to the cancer nests was more pronounced than that in distant ones. The mean value of serum soluble E-selectin (ng/ml) was 38.3 in benign breast disease, 47.8 in those with no evidence of recurrence, 49.4 in stage I/II primary breast cancer, 75.8 in stage III/IV primary breast cancer, and 93.7 in recurrent breast cancer. The mean value of serum soluble E-selectin was 106.2 ng/ml in patients with distant metastases, and 50.4 ng/ml in those with no evidence of distant metastases. Thus, the concentration of soluble E-selectin was significantly elevated in the sera of patients with distant metastases. These findings suggested that cancer cells induced the expression of E-selectin on endothelial cells and, that serum soluble E-selectin is useful as a tumor marker having a close relationship to metastasis in breast cancer.