Yoichi Ichikawa

Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy

Parathyroid function and calcium metabolism were studied in 44 patients under glucocorticoid therapy (steroid group) and in 25 control subjects. Nephrogenous cAMP and serum immunoreactive parathyroid hormone levels in the steroid group were significantly higher than those in control subjects (p less than 0.001). Nephrogenous cAMP in the steroid group correlated positively with prednisolone dosage (r = 0.424, p less than 0.01), and most patients who showed obvious elevations of nephrogenous cAMP had received over 10 mg/day of prednisolone for at least 2 mo. Fasting urinary calcium in the steroid group [166.1 +/- 78.5 (+/- SD) mg/g creatinine] was about 2 times greater than that in control subjects (74.1 +/- 35.6) (p less than 0.001). Fasting urinary calcium in control subjects correlated negatively with nephrogenous cAMP (r = -0.486, p less than 0.02). In contrast, these values in steroid group showed significant positive correlation (r = 0.631, p less than 0.001), suggesting that increased urinary calcium excretion is an important factor in the development of secondary hyperparathyroidism. Elevated nephrogenous cAMP and serum immunoreactive parathyroid hormone levels decreased after the administration of trichlormethiazide and/or 1 alpha hydroxy-vitamin D3. We conclude that increased urinary calcium excretion plays an important role in the development of secondary hyperparathyroidism in patients under glucocorticoid therapy and that the administration of thiazide and/or vitamin D could improve the secondary hyperparathyroidism caused by glucocorticoid therapy.

Mononuclear cells enhance prostaglandin E2 production of polymorphonuclear leukocytes via tumor necrosis factor α

To clarify the interactions between mononuclear cells and polymorphonuclear leukocytes, and to identify the cytokine(s) that mediate the interaction, the effects of a culture supernatant of LPS-stimulated mononuclear cells on production of arachidonic acid metabolites of polymorphonuclear cells were studied. The culture supernatant of LPS-stimulated mononuclear cells increased production of prostaglandin E2 of polymorphonuclear cells. TNF alpha, but not IL-1, IL-2, IL-6, or IFN gamma, enhanced the prostaglandin E2 production when added in vitro. Additionally, an anti-rTNF alpha monoclonal antibody inhibited the stimulating activity of the culture supernatants. TNF alpha, produced by mononuclear cells, appears to play an important role in the development of inflammation, such as rheumatoid arthritis, by enhancing the arachidonic acid metabolism of the polymorphonuclear cells.

A Case of Unusual SLE Related Syndrome Characterized by Erythema multiforme, Angioneurotic Edema, Marked Hypocomplementemia, and Clq Precipitins of the Low Molecular Weight Type

Our patient and those of Agnello et al. had identical clinical symptoms such as erythema multiforme, arthralgias and angioneurotic edema and both differed from systemic lupus erthematosus in several important points, i.e., in spite of marked hypocomplementemia the nephropathy is not prominent and it needs high-dose steroids to eliminate the clinical and serological abnormalities. In addition to the features reported by Agnello et al. we found increased viral antibody titers in our patients sera.

Metabolism of cortisol-4-C14 in patients with infectious and collagen diseases

Abstract The metabolism of intravenously administered cortisol-4-C14 was studied in patients with infectious and collagen diseases, as to the conversion to cortisone in plasma and to cortols, ∗ cortolones, THF, ATHF and THE in urine. The increase of urinary THF THE and cortols/cortolones ratios was noticed in patients with infectious and collagen diseases and in normal subjects under ACTH stimulation, although the cortisol production rate calculated from the specific activity of urinary THF was not always increased in the patients with infectious and collagen diseases. The ratio of the 20-hydroxy metabolites, cortols and cortolones, to the 20-keto metabolites, THF, ATHF and THE, was significantly increased in patients with liver cirrhosis and with collagen diseases, but not in patients with infectious diseases. After intravenous injection of cortisol-4-C14, the radioactivity appeared rather rapidly in the cortisone fraction of plasma and the ratio of the radioactivity of cortisone to that of cortisol became approximately constant about 60 minutes after the injection. The ratio at the equilibrium was definitely lower in patients with infectious and collagen diseases. These observations indicate that a larger part of cortisol remains as a biologically active form in plasma and may result in the increased urinary 11-OH metabolites in patients with infectious and collagen diseases.

Altered equilibrium between cortisol and cortisone in plasma in thyroid dysfunction and inflammatory diseases

The radioactivities of cortisol and cortisone in plasma were determined following simultaneous injection of 14C-cortisol and 3H-cortisone. The plasma concentrations of 14C-cortisol and 3H-cortisone decreased as a first-order function of time after an initial rapid drop, while there was a prompt appearance of 14C-cortisone and 3H-cortisol in plasma, which also decreased as a first-order function. The biologic half-lives of these four isotopic steroids were essentially identical. The ratio of 14C-cortisone to 14C-cortisol and that of 3H-cortisone to 3H-cortisol in plasma were constant after 60 min following injection and were identical, which suggested that cortisol and cortisone in plasma were at dynamic equilibrium. This ratio was 0.36 ± 0.01 (SE) in normals; it was decreased in patients with hypothyroidism (0.21 ± 0.03) and inflammatory diseases (0.18 ± 0.01) and was variable in hyperthyroid patients (0.42 ± 0.11). The ratio of the metabolic clearance rate of cortisone to that of cortisol was significantly increased in hypothyroid patients and in patients with inflammatory diseases, while urinary 11-ketonic metabolites of cortisol are known to decrease relative to its 11-hydroxy metabolites in these patients. These data and the decreased cortisone-to-cortisol ratio at equilibrium were consistent with the altered equilibrium between cortisol and cortisone, favoring cortisol, in these patients. It was suggested that the altered equilibrium between these steroids may be an important factor in determining the effectiveness of secreted or exogenously administered cortisol and the plasma concentration of cortisone in several disorders.

Progressive renal failure in patients with lupus nephritis

Abstract. Objective. To investigate the mode of progression to renal failure in patients with lupus nephritis in relation to disease activity and responsiveness to corticosteroid therapy.

Fluorometric study of interaction between ACTH fragments and bovine adrenocortical membranes.

Corticotropin1–24 and [Gly1]corticotropin1–18 amide increased the fluorescence of 1-anilinonaphthalene-8-sulfonate which bound to the bovine adrenocortical membranes. The two ACTH fragments interacted with the protein of the membranes and increased the net positive charge of the membranes.