The effect of (-)15-deoxyspergualin (15-dsp), a new immunosuppressant which was originally separated from the culture filtrate of a strain of Bacillus laterosporus, was evaluated in this study. Various doses of 15-dsp were subcutaneously administered to New Zealand black/white F1 hybrid mice (B/WF1) four times a week starting at 14 weeks of age, just prior to the onset of nephropathy. The life span of the treated animals, studied at 0.6 to 6.0 mg/kg body weights, compared with the control mice was significantly prolonged by 15-dsp treatment (percent survival of the treated mice at 50 to 70 weeks of age was significantly higher than that of the control mice, except that of the 0.6 mg group at 60 wks of age, P less than 0.05 by Fisher's exact test). In the 6.0 mg group of mice, complete suppression of spontaneously progressive splenomegaly with decreased total spleen cells was observed at 24 through 36 weeks of age compared with the same-aged control group of mice (P less than 0.01). Absolute numbers of L3T4+ splenocytes determined by flow cytometry, as well as L3T4+/Lyt2+ ratio, were decreased, while in vitro interleukin 2 production by splenocytes induced with staphylococcal enterotoxin A was significantly enhanced. Serum IgG anti-ds DNA antibody levels, measured by radioimmunoassay in the treated mice, were significantly lower at 24 through 36 weeks of age than those in the control mice (P less than 0.01), and the incidence of significant proteinuria (greater than or equal to 100 mg/dl) in the 15-dsp group was lower at both 32 and 36 weeks of age (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A highly sensitive radioimmunoassay to measure atrial natriuretic peptide (ANP) concentration in urine has been established, and its clinical usefulness is presented. ANP in urine was stable at 4 degrees C for several days and was easily measured by our radioimmunoassay. The average ANP excretion in 65 healthy persons was 25.0 +/- 1.4 ng/day (mean +/- SEM) and the fractional excretion of ANP was 0.7 +/- 0.05%. In 14 patients with congestive heart failure, the average ANP excretion was 119.2 +/- 29.4 ng/day, which decreased to 53.3 +/- 11.0 after successful treatment.

The therapeutic effect of 15-deoxyspergualin (DSP) in old New Zealand Black/White F₁ mice (B/W mice) with clinical nephropathy was studied and compared with cyclophosphamide (CY). The mice were treated with 0.05 ml phosphate-buffered saline, subcutaneously, four times/week, with DSP, 6 mg/kg body weight, s.c, four times/week, or with CY, 15 mg/kg, i.p., once a week, starting at the 28th week of age. They were serially semiquantitated for proteinuria, and serum IgG anti-dsDNA antibody was measured by ELISA. Spleen cell surface markers such as L3T4, Lyt 2 and IgG were flow-cytometrically analyzed, and interleukin-2 (IL-2) activity in vitro was measured using CTLL cells. Kidney specimens were studied with light and immunofluorescence microscopy. The mice treated with either CY or DSP survived significantly longer than the control mice. L3T4⁺ cells in the DSP-treated mice at 40 weeks of age were significantly less than those in the 28-week-old control mice (p < 0.05). In contrast, IL-2 generation in the three groups of mice showed no significant variations at 32–40 weeks of age. Serum anti-DNA antibody levels in both of the CY and DSP groups remained low and comparable with that in the 28-week-old mice, and the incidence of significant proteinuria decreased. Likewise, glomerular histology in the treated groups was improved compared with the 28-week-old control mice, and the deposition of IgG and C3 in the treated groups remained unchanged or further decreased. Accordingly, the renal (immuno)histological findings in the DSP group were quite comparable with or even better than those in the CY-treated mice. DSP may have suppressed the abnormal antibody production by modulating the T cell function(s), which is in contrast to the direct action against B cells due to CY.

Regulation of renal excretion of atrial natriuretic peptide (ANP) was studied in kidney disease patients and healthy kidney donors.The measured ANP concentration in the patient's plasma did not correlate with their creatinine clearance (Ccr), while the fractional excretion of ANP (FEANP) significantly correlated with Ccr. FEANP in healthy persons is less than 1%. In the healthy donors of kidneys for transplantation, approximately 80% of the plasma ANP from the renal artery appeared in the renal vein. From these results, this high recovery of ANP in the veins does not appear to be adequately explained by its degradation in the renal arterioles and nephrons. The FEANP from kidney disease patients significantly correlated with FENa, FEK and FEp, but not with FEca and FEMg. The manner of ANP handling in the nephron may possibly differ from that of Ca or Mg.

No abstract

No abstract

No abstract