Hiroyuki Hosojima

Urinary Excretion of Angiotensin Converting Enzyme in NIDDM Patients With Nephropathy

Twenty-four-hour urinary excretion of angiotensinconverting enzyme (ACE) was investigated in relation to that of albumin and β2-microglobulin (β2M) in 25 noninsulin- dependent diabetes mellitus (NIDDM) patients without nephropathy, 13 NIDDM patients with incipient nephropathy, 18 NIDDM patients with overt nephropathy, and 14 nondiabetic subjects. NIDDM patients without nephropathy and nondiabetic subjects were similar in albumin, β2M, and ACE excretion. NIDDM patients with incipient nephropathy had elevated albumin excretion (P < .01) and similar (β2M and ACE excretion compared with nondiabetic subjects. On the other hand, NIDDM patients with overt nephropathy had elevated albumin, β2M, and ACE excretion compared with nondiabetic subjects (P < .01). In all NIDDM patients studied, a positive correlation was found between ACE excretion and albumin excretion (r = 0.76, P < .001) or β2M excretion (r = 0.52, P < .01). These data suggest that elevated ACE excretion in NIDDM patients with overt nephropathy may be reflective of renal tubular damage.

High-performance liquid chromatographic separation of corticosteroids in plasma of rats. Its application to the determination of the circadian rhythm of 18-hydroxycorticosterone related to aldosterone and corticosterone.

An efficient separation of corticosteroids in plasma of rats was obtained by reversed-phase high-performance liquid chromatography (HPLC). Plasma corticosteroid assays with HPLC separation were used to determine the circadian rhythm of 18-hydroxycorticosterone (18-OHB) and its possible relationship to aldosterone or corticosterone in conscious rats under standard conditions (regular diet; 12-hour light and 12-hour dark cycle). Significant circadian rhythms of plasma corticosterone, 18-OHB and aldosterone were observed with peak values at 20.00 h and nadir values at 08.00 h. The mean ratio of plasma 18-OHB to aldosterone during 24 h was 2.4. The circadian rhythm of 18-OHB was also correlated with that of plasma aldosterone or corticosterone.

Adrenal adenoma with 18-hydroxycorticosterone excess and hypertension: a variant of aldosteronomas

A 46-year-old woman with hypertension, normokalemia, suppressed renin, normal catecholamines, and a left adrenal mass on the CT scan was found to have excessive 18-hydroxycorticosterone (18-OHB) and normal aldosterone levels in plasma, both of which responded poorly to sodium restriction and angiotension II, and supranormally to ACTH. Plasma 18-hydroxydeoxycorticosterone (18-OHDOC) was normal. After adrenalectomy, amelioration from hypertension occurred with a reduction in plasma 18-OHB and aldosterone. The plasma 18-OHDOC remained normal. The adrenal tumor was histologically an adenoma, containing a large amount of 18-OHB and a small amount of aldosterone. Thus, the present adenoma seems to be a variant of aldosteronomas.

Effect of atrial natriuretic factor on aldosterone and its precursor steroid production in adrenal zona glomerulosa cells from spontaneously hypertensive rats.

The effect of alpha-human atrial natriuretic factor (alpha-hANP, 10(-6) M- 10(-8) M) on basal, and maximum angiotensin II (AII, 4.8 X 10(-8) M)-, ACTH (4.3 X 10(-9) M)-, and potassium (8mM)-stimulated levels of corticosterone, 18-hydroxycorticosterone (18-OHB) and aldosterone production were studied in adrenal glomerulosa cells from spontaneously hypertensive rats (SHR) at 14 weeks of age as compared to those in the age-matched Wistar-Kyoto rats (WKY) on a normal sodium diet. Plasma corticosterone, 18-OHB and aldosterone levels and the aldosterone response in vitro to the graded doses of AII were similar in SHR and WKY. Basal, and maximum AII-, ACTH-, and potassium-stimulated levels of corticosterone, 18-OHB and aldosterone also were similar in the cells from SHR and WKY. alpha-hANP similarly inhibited basal and stimulated levels of these corticosteroids in the cells from SHR and WKY. These results indicate that the inhibitory effect of alpha-hANP on aldosteronogenesis is unaltered in SHR at 14 weeks of age on a normal sodium diet.

Direct effects of heparin on basal and stimulated aldosterone production in rat adrenal glomerulosa cells

Direct effects of heparin (0.1-10 IU/ml) on basal and stimulated aldosterone production have been studied using intact rat adrenal glomerulosa cells. Heparin at any dose did not affect basal aldosterone production when added to the incubation medium. Heparin at a 0.01 IU/ml dose had no effect on aldosterone production maximally stimulated by angiotensin II (AII, 4.8 X 10(-8) M), ACTH (4.3 X 10(-9) M) or potassium (8.0 mM). However, heparin at 0.1 and 0.3 IU/ml doses selectively blocked aldosterone production maximally stimulated by AII but not by ACTH or potassium, while the compound at 1 and 10 IU/ml doses inhibited aldosterone production maximally stimulated by these three stimuli. In addition, the inhibitory effect of 0.3 IU/ml heparin occurred as early as 30 min after incubation with heparin. These data suggest that heparin at 0.1 and 0.3 IU/ml doses acts directly on adrenal zona glomerulosa to selectively block the stimulatory action of AII, while the compound at 1 and 10 IU/ml doses inhibits all the stimulatory actions of AII, ACTH and potassium.

Primary Plasmacytoma of the Thyroid

Primary extramedullary plasmacytoma (PEMP) of the thyroid is rare. Only nine patients with PEMP of the thyroid have been reported in Japan to date. We describe an additional autopsy case with PEMP of the thyroid and review of the literature in Japan. A 67-year-old women complaining of swelling of the anterior neck exhibited thin scalp hair, edematous face and a giant, hard, nodular goiter. Laboratory examination showed elevated levels of ESR, collagenous reaction, gammaglobulin, and a M-bow of the IgG-k type in immunoelectrophoresis. No Bence-Jones protein was found in the urine. Thyroid function test revealed a subclinically hypothyroid state, showing a T3 of 1.32 ng/ml, a T4 of 10.0 micrograms/dl, a TSH of 23.4 microU/ml and positive thyroid antibodies. The scintigram and the CT scan of the thyroid showed deviation of the trachea by the thyroid tumor and calcification within homogeneous thyroid gland. She underwent total thyroidectomy because of suspected malignancy. The histological examination of the removed thyroid weighing 117gr revealed a proliferation of plasma cells and lymphocytes and small amounts of atrophied thyroid follicles. The immunohistological examination of the removed thyroid showed the monoclonality to IgG-k chain. Plasma cells were stainable with methylgreenpyronine. Twenty-six months after thyroidectomy, she died due to progressive emaciation, anemia, hypoalbuminemia and ascites. Postmortem examination revealed widespread metastasized plasma cell tumors in the liver, intestine, spleen and mesentery with ischemic changes in heart and kidney. Based on our autopsy case and the nine cases reported in Japan, clinical and histological characteristics of PEMP of the thyroid were discussed.