Hajime Ueshiba

Cilnidipine, the N- and L-type calcium channel antagonist, reduced on 24-h urinary catecholamines and C-peptide in hypertensive non-insulin-dependent diabetes mellitus

To evaluate the effects of cilnidipine (CNP), L- and N-type calcium channel blocker and nilvadipine (NVP) on 24-h urinary epinephrine (U-EP), norepinephrine (U-NE), dopamine (U-DA) and C-peptide (U-CPR) in patients associated with hypertension and non-insulin-dependent diabetes mellitus (HT-NIDDM), a randomized crossover study was performed with 35 HT-NIDDM patients. The patients were given CNP (10 mg/day) and NVP (8 mg/day), separately, for 4 weeks each. After CNP treatment, U-NE, U-DA and U-CPR levels were significantly reduced compared with pre-treatment levels: 160.4 +/- 12.7 to 111.7 +/- 8.9 microg/day (mean +/- S.E., P < 0.005); 934.8 +/- 163.4 to 590.3 +/- 33.4 microg/day (P < 0.05); 86.7 +/- 9.9 to 57.6 +/- 7.4 microg/day (P < 0.05), respectively. Although no significant differences were observed in U-EP, U-NE, U-DA and U-CPR levels by NVP treatment, U-NE, U-DA and U-CPR levels after CNP treatment were significantly lower than those after NVP treatment: 111.7 +/- 8.9 versus 155.0 +/- 13.7 microg/day (P < 0.02); 590.3 + 33.4 versus 822.2 +/- 104.3 microg/day (P < 0.05); 57.6 +/- 7.4 versus 80.6 +/- 8.1 microg/day (P < 0.05), respectively. In conclusion, it was demonstrated that CNP treatment significantly reduced U-NE, U-DA and U-CPR excretion compared with NVP treatment in HT-NIDDM patients.

Transient hyper-17-OHPnemia unrelated to cross-reactions with residual fetal adrenal cortex products

Objective: To clarify the pathogenesis of transient hyper-17α-hydroxyprogesteronemia, we initiated a laboratory investigation in a pre-term infant with persistently high serum 17α-hydroxyprogesterone (17-OHP) until 2 months of age. Methods: Serum 17-OHP level was measured by high-performance liquid chromatography and radioimmunoassay, and gene analysis of CYP21A2 (21-hydroxylase) was performed. Result: Serum 17-OHP level on the 29th day of life was 25.4 ng/ml, and the urinary steroid profile showed low pregnanetriolone. Gene analysis of 21-hydroxylase disclosed no mutation, and 17-OHP normalized by 3 months of age without specific treatment. Conclusion: Transient elevations in 17-OHP, which do not appear related to cross-reactions with products of a residual fetal adrenal cortex, may occur in the first few months of life.

Establishment and characterization of a novel cell line derived from a human small cell lung carcinoma that secretes parathyroid hormone, parathyroid hormone-related protein, and pro-opiomelanocortin.

There are few case reports describing small cell lung carcinoma (SCLC), which secrete parathyroid hormone (PTH)-related protein (PTHrP) and result in hypercalcemia. We have established a novel cell line, derived from a 37-year-old woman with SCLC, which produced PTH, PTH-rP, and a part of proopiomelanocortin (POMC), and led to hypercalcemia. The cell line, named SS-1, was grown as floating cell clusters in DMEM/F12 medium supplemented with 10% fetal bovine serum and had a population doubling time of 72 h. The modal chromosome number was 47 (88%); marker chromosomes were not observed. The SS-1 cell line secreted not only PTHrP but also PTH, and both were decreased by CaCl2 administration. Decreasing the concentration of Ca++ in the growth medium stimulated the secretion of both PTHrP and PTH. The cell line had calcium sensing receptor (Cas-R). Since PTHrP and PTH secretion from the SS-1 cells was related to Ca++ concentration in the growth medium, the cell line might be useful for the study of PTH-rP and PTH regulation as well as for SCLC analysis. In addition, the cells secreted N terminal POMC, the precursor of adrenocorticotropic hormone, in response to stimulation with corticotropin releasing hormone. In summary, we established a novel cell line, SS-1 from SCLC, which produced PTHrP, PTH and N terminal POMC.

18-Hydroxycortisol and 18-oxocortisol in Cushing's syndrome

In patients with primary aldosteronism due to an aldosterone-producing adenoma and glucocorticoid-suppressible aldosteronism, 18-hydroxycortisol and 18-oxocortisol excretions are elevated. Both steroids are synthesized in the transitional zone between the zona glomerulosa and zona fasciculata. There are no reports concerning production of these steroids in Cushings syndrome due to adrenal adenoma or hyperplasia, as far as we know. We determined the urinary excretion and serum concentration of 18-hydroxycortisol and 18-oxocortisol in eight patients with Cushings syndrome (four due to adrenal adenoma, and four due to adrenal hyperplasia). Two of the four patients with adrenal adenoma had high levels of urinary and serum 18-hydroxycortisol and 18-oxocortisol; on the other hand all the patients with adrenal hyperplasia had normal urinary and serum levels of both steroids. Patients with high concentrations of 18-hydroxycortisol and 18-oxocortisol, however, showed no differences in clinical features, routine laboratory findings and hormonal data compared to patients with normal concentrations of 18-hydroxycortisol and 18-oxocortisol. Our data suggest that some adrenal adenomas causing Cushings syndrome originate from transitional cells.