Kaname Moriwaki

Growth hormone-producing pituitary adenoma with crystal-like amyloid immunohistochemically positive for growth hormone.

Growth hormone (GH)‐producing pituitary adenoma from a 50‐year‐old acromegalic female was studied histochemically, immunohistochemically and electron microscopically. The adenoma was characterized by numerous crystal‐like amyloid bodies of 5 to 40 μm in diameter. In the periphery of the crystal‐like amyloid, bundles of amyloid fibrils were closely associated with deep invaginations of adenoma cells. The adenoma cells had numerous vesicles and vacuoles filled with amyloid fibrils, some of which were continuous with extracellular space. The crystal‐like amyloids, as well as the adenoma cells, were immunohistochemically positive for GH. It might be possible that disorder of hydrolysis of “prohormone,” from which GH is elaborated, is responsible for the amyloid production, and that amyloid discharge is accompanied with immunoreactive GH.

Forskolin potentiates adrenocorticotropin-induced cyclic AMP production and steroidogenesis in isolated rat adrenal cells.

Forskolin, a unique diterpene which directly activates the adenylate cyclase, stimulated production of both cyclic AMP and corticosterone in isolated rat adrenal cells, in vitro. This agent also potentiated the action of adrenocorticotropin and/or cholera toxin on cyclic AMP production and steroidogenesis at lower concentrations. It augmented both an early (cyclic AMP production) and a late (steroidogenesis) action of the hormone in the adrenal gland.

Effect of cholecystokinin receptor antagonists, MK-329 and L-365,260, on cholecystokinin-induced acid secretion and histidine decarboxylase activity in the rat

To elucidate the regulatory mechanism of acid secretion by cholecystokinin (CCK) in vivo, we compared the effects of CCK and gastrin on acid secretion and histidine decarboxylase (HDC) activity. We also examined the effects of MK-329, a specific antagonist for pancreatic-type CCK receptor, and L-365,260, a specific antagonist for gastrin-type CCK receptor, on the action of CCK. Graded doses of CCK or gastrin were intravenously infused into conscious rats with gastric fistula. Gastrin-17 I infusion up to 10 nmol/kg/h resulted in dose-related increases in acid secretion. CCK-8 infusion also caused an increase in acid secretion. However, it reached a peak with 0.3 nmol/kg/h CCK-8 and attenuated with higher concentrations of CCK-8. This attenuating effect of a higher dose of CCK was reversed by MK-329, but not by L-365,260. Both CCK and gastrin were potent in increasing fundic HDC activity, and the effect of CCK on HDC activity was significantly inhibited by L-365,260, but not by MK-329. Taken together, the present study suggests that CCK and gastrin stimulate histamine formation via a gastrin-type CCK receptor, and the attenuating action of CCK with higher concentrations on acid secretion in vivo is mediated by a pancreatic-type CCK receptor.

Familial Renal Hypouricemia with Intact Reabsorption of Uric Acid

Three patients with renal hypouricemia in the same family are described. Serum urate levels in the mother were in the low normal range and were below normal in her 2 sons. In all 3 patients, the ratios of renal urate clearance to creatinine clearance were abnormally elevated. Clear responses to either pyrazinamide or probenecid administration were observed in these ratios. These results suggest that these 3 patients had renal hypouricemia with normal reabsorption of urate as judged by the criteria for differentiating abnormalities in renal urate handling. This corresponds to the previously postulated mechanism as renal urate hypersecretion. Possible limitations to the diagnostic use of probenecid and pyrazinamide are also discussed.

An Enzyme-Linked Immunosorbent Assay (ELISA) For Adenosine 3′, 5′-Cyclic Monophosphate (cAMP) In Human Plasma and Urine Using Monoclonal Antibody

A reliable and sensitive ELISA for cAMP in human plasma and urine is described, using a monoclonal antibody and a 96 well microtiter plate. Succinyl cAMP is conjugated to human serum albumin and adsorbed to the ELISA plate, giving an immobilized antigen approach which simplifies subsequent assay procedures. As low as 1.56 fmol/well of both plasma and urinary cAMP is measurable. Recoveries of added cAMP in plasma and urine were from 99% to 109%. Intra-assay coefficients of variation were less than 6.1% for plasma and 7.0% for urine samples. Inter-assay coefficients of variation for plasma and urine samples were less than 8.9% and 9.5%, respectively. There was a good correlation between the values obtained by ELISA and radioimmunoassay (RIA) (plasma: r = 0.94, n = 66; urine: r = 0.98, n = 64; nephrogenous cAMP: r = 0.96, n = 51).

Forskolin-induced cyclic AMP production and gastric acid secretion in dispersed rabbit parietal cells: Novel evidence for a major role of cyclic AMP in acid release

Forskolin, a unique diterpine which is a direct activator of cyclic AMP-generating systems, stimulated both cyclic AMP and acid production in dispersed rabbit parietal cells. This agent was also capable of augmenting the action of histamine on both cyclic AMP and acid production at a low concentration. These findings provided novel evidence for a major role of cyclic AMP in gastric acid secretion.

Presence of ACTH-Potentiating Factors in Rat Anterior Pituitary Glands

High molecular weight ACTH fractions, obtained through gel filtration of boiled rat anterior pituitary extract, induced a marked increase in corticosterone production from isolated rat adrenal cells in the presence of low concentrations of ACTH-(1-24). This indicates the presence of heat-stable factors augmenting the steroidogenic action of ACTH in the rat anterior pituitary. We also noted that these factors potentiated the activity not only of ACTH-1(1-24) but also of ACTH-(1-8). The ACTH-potentiating factors in rat anterior pituitary extract are possibly present in heterogeneous forms according to their molecular weights (8,000, 10,000 and 15,000), their mobility in ion-exchange chromatography and their content in RIA-ACTH activity. Of these three forms, the former comigrated with biological ACTH activity. The remaining two forms were free of it. Since the effect of potentiating factors on modified ACTH-(1-9), shown to be less susceptible to proteolytic degradation from ACTH-(1-24), was similar to the effect on ACTH-(1-24), it is suggested that potentiation was not due to an inhibition of ACTH proteolysis.

UNALTERED STIMULATION OF PITUITARY ADRENOCORTICOTROPHIN SECRETION BY CORTICOTROPHIN‐RELEASING FACTOR FOLLOWING SODIUM VALPROATE ADMINISTRATION IN A PATIENT WITH NELSON'S SYNDROME

A 53‐year‐old woman with Nelsons syndrome was treated with 600 mg sodium valproate daily. Her plasma ACTH was effectively decreased, whilst the response of plasma ACTH to corticotrophin‐releasing factor (CRF) was unaltered. The result of the CRF test suggested that sodium valproate, at least in the present patient, acted at the hypothalamic level.

Transcatheter arterial chemo-embolization for humoral hypercalcemia of hepatocellular carcinoma

SummaryA 50-year-old male with unresectable hepatocellular carcinoma (HCC) had a hypercalcemic crisis with a serum calcium concentration of 7.8 mEq/ℓ, without any evidence for bone metastases or parathyroid lesions. The hypercalcemia was thought to be due to increased renal reabsorption of calcium and increased bone resorption, which was probably caused by humoral factors derived from the HCC, some being parathyroid hormone-like factors. Since conservative therapy for hypercalcemia was not sufficiently effective and was accompanied by progressive exacerbation of ascites and leg edema, transcatheter arterial chemo-embolization (TACE) was performed. On the following day, serum calcium concentration decreased from 6.3 mEq/ℓ to the normal range, although serum α-fetoprotein levels decreased only slightly. Thereafter hypercalcemia did not develop for about 4 weeks. The results demonstrated that TACE can be effective for humoral hypercalcemia of HCC.

Steroidogenic effect of ent-kaur-16-en-15β-ol (kaurenol) on isolated rat adrenal cells

In an in vitro bioassay system for adrenocorticotropic hormone using isolated rat adrenal cells, kaurenol, a diterpene alcohol, stimulated corticosterone production and augmented the steroidogenic effect of adrenocorticotropin or forskolin, dose-dependently. Kaurenol had no effect on cyclic AMP production by the cells. The diterpene also had no stimulatory effect on the adrenal adenylate cyclase activity in a cell free system. The results suggest that this particular diterpene exerts a steroidogenic effect through a mechanism independent of cyclic AMP generation.