A comparative study between the disease activity of minimal change nephrotic syndrome (MCNS) and immunodynamics indicated by change of serum immunoglobulin (Ig) levels, and T and B lymphocyte subsets were conducted, trying to compare with those of focal glomerular sclerosis (FGS). For the analyses, monoclonal antibodies termed as OKT 3, OKT 4, and OKT 8 were used for identification of T 3 (peripheral T lymphocytes), T 4 (helper/inducer) and T 8 (suppressor/cytotoxic), respectively. B lymphocytes were classified into four subsets, i. e. Bγ, Bα, Bμ or Bε according to their own intrinsic surface Igs, which were identified using monospecif is antibodies for human γ, α, or ε heavy chain, respectively. In an active phase of MCNS, T 3 tended to decrease, while in a remitting phase induced by prednisolone therapy, T 3, T 4 were decreased and T 8 was increased significantly with a consequent reduction of T 4/T 8 ratio. However, they returned to normal range in a completely remitted phase with no necessity of therapy. As for B lymphocyte subsets and serum Igs, IgE, IgM Bγ, Bμ and Bε were increased significantly in an active phase in spite of marked reduction of serum IgG. In a remitting phase, they tended to normalize and were normalized in a remitted phase except for serum IgE and IgM, which remained at a higher level. Concerning FGS, there was no essential difference in response patterns of B lymphocytes and serum Igs from those of MCNS, while T 3 and T 4 in an active phase of FGS tended to decrease but were normalized in a remitting phase. These results suggest that acceleration of IgE and IgM producing systems and dysfunction of IgG synthetic system, which may be caused dysregulation of T lymphocyte function, were characteristics of immuneresponse in MCNS and FGS.

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For the preparation of brush border membrane from renal proximal tubules in rats, the brush border membrane vesicles (BBMV) isolated by Ca²⁺ precipitation procedure have been further purified by the application of molecular sieving with porous glass-beads column chromatography. The BBMV have the spherical shape and the diameter of about 95 nm in isotonic solution. The specific activities of alkaline phosphatase and leucine aminopeptidase for brush border enzymes were increased to 18 and 17 times respectively compared with the original homogenate. The uptake of D-glucose by the purified BBMV reached 8.53±0.32 nmole/mg protein in the presence of NaSCN gradient. SDS-polyacrylamide gel electrophoresis showed approximately thirty major bands of protein subunits by staining with coomassie brilliant blue. These experimets showed that the renal BBMV with homogenous size and remarkably high specific activities of marker enzymes could be obtained by the glass-beads column chromatographic fractionation from the mixture of huge particles of different size.

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Various types of immune complexes (IC) were prepared with rabbit a-DNP-1251 and DNP 27-BSA. These ICs were equivalent precipitated IC, 50 folds antigen excess soluble IC (AgE), antiody only (Ab), solubilized IC, serum treated AgE IC (S-AgE) and serum treated Ab (S-Ab). We studied the behavior of these ICs after injection intravenously into normal rats and complement-depleted rats. The sedimentation pattern of AgE had a single 11S peak, while S-AgE had major 19S peak and minor 7S peak. The size of solubilized IC was recovered in a broad peak larger than 19S. The clearance kinetics were in the oder precipitated IC > solubilized IC > AgE IC=S-AgE IC > Ab=S-Ab. There were no difference in normal rats and complement depleted rats. Then we studied the tissue localizations at 120 minutes after injection. Ab and S-Ab showed low uptakes in all tissues. AgE IC and S-AgE IC primarily localized in the liver. Precipitated IC and solubilized IC also mainly localized in the liver, though rela-tively high uptakes were recognized in the lung. The oilers were as follows, precipitated IC + complement depleted rats > precipitated IC + narmal rats > solubilized IC + complement depleted rats > solubilized IC + normal rats. These findings suggested that precipitated IC was trapped in the lung capillary plexsus but in normal rats solubilization occured and the IC was released from the lung. We concluded that solubilized IC was cleared more quickly than soulble IC and solubilization really occured in vivo.

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We studied the levels of serum and urinary sialic acids in children with idiopathic nephrotic syndrome (INS). Serum sialic acid levels were increased on onsets and became normalized on remissions. Urinary bound sialic acid levels were also increased. relapses, and But, they did not become normalized for some time after remission, suggesting delayed or incomplete recovery of increased permeability of glomerular basement membrane to negative-charged sialic acids. Sephadex G-200 gel-chromatography ro serum sialic acids showed 3 peaks in large mederate and low-molecular fractions. Comparing these data with other serum or urinary components, we suggest that some glycoproteins containing sialic acid residues may play important roles in initiation and progression of INS.

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To elucidane adaptation mechanism to dietary phosphorus, the changes in phosphorus (P), calcium (Ca), magnesium (Mg) contents and alkaline phosphatase (Al-Pase) activities in urine, plasma, soft tissue and bone were evaluated in rats, fed diets containing 0.1% phosphorus (LP), 0.5 % phosphorus (NP) and 1.5 % phosphorus (HP). Urinary P contents in LP rats were almost undetectable and in HP rats were significantly increased within the 1st day of experiment. A significant increment in urinary Ca and Mg excretion occurred the 1st day in LP rats. Plasma P concentrations fell significantly in LP rats and did not change in HP rats. plasma Mg concentrations in LP and HP rats were decreased during the 10th day of experiment. P, Ca and Mg contents in renal medulla were elevated in rats fed HP diet and bone Mg contents were decreased in HP and LP rats. The total activities of Al-Pase increased in plasma and tissue in LP rats and decreased in HP rats during the experimental period. The following results were obtained; A) Renal adaptation to dietary phosphorus occurred within the 1st day of experiment and phosphate excretion of urine in HP rats caused tubular calcification. B) Plasma and bone Mg contents were maintained by optimal content of dietary phosphorus. C) There was an inverse correlation between Al-Pase and dietary phosphorus but Al-Pase seemed to have no direct relation to the adaptation mechanism.

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For the purpose of investigating the cause of uremic dyslipoproteinemia which was observed in patients with chronic renal failure on regular hemodialysis treatment, profiles of serum lipoprotein were studied in hemodialysis patients at Shimane Prefectural Central Hospital (HD-Izumo ; n=34) using serum lipoprotein polyacrylamide-gel disc-electrophoresis, and the results were compared with the data obtained in 1976 on the hemodialysis patients in Ube (HD-Ube ; n=18) which had been reported previously. Serum triglycerides levels in both groups were elevated, that is 144.7±8.7 (mean±SE) mg/dl in the HD-Izumo and 203.1±33.3 mg/dl in the HD-Ube, though serum total cholesterol levels were normal. Broad midband pattern (BMP) on serum lipoprotein electrophoretogram was observed in 74% of the HD-Izumo, which was almost comparable to 8900 of the HD-Ube. Most of the BMP in the HD-Izumo was, however, atypical and lesser change than in the HD-Ube. BMP-a which was most typical and specific type of BMP was in lower frequency (12%) of the HD-Izumo than in those (50%) of the HD-Ube. In other words, uremic dyslipoproteinemia was of lesser degree in the HD-Izumo than in the HD-Ube. Then, aiming to explore contributing factors of the uremic dyslipoproteinemia, method of hemodialysis treatment and dietary components of the patients were analyzed in both groups. There was a marked difference in the concentration of glucose contained in the dialysate, that is, 200 mg/dl in the HD-Izumo and 408.3 mg/dl in the HD-Ube. Morever the diet in the HD-Izumo consisted of lower calories (40 kcal/kg⋅BW) and lesser carbohydrates (5.2g/kg⋅BW : 52%) than in the HD-Ube (45-50 kcal/kg⋅BW, and 6.0-7.0 g/kg⋅BW:55.2%). The results in this study suggested that a state of high carbohydrates intake trans-ferring from dialysate and taking as diet was, at least, one of the most contributing and aggravating factor of the uremic dyslipoproteinemia which was observed in hemodialysis patients.

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The effects of sodium lactate dialysate on acetate intolerance was studied 850 times in 15 patients on maintenance hemodyalysis. Most of the intradialystic clinical distress (fatigue, itch, anorexia, and/or abdominal distress, and headache) was improved by utilization of sodium lactate dialysate, and there were no significant side effects. In 4 out of the 5 patients the incidence of intradialystic hypotension decreased when lactate dialysate was utilized, and sodium chloride bolus infusion required to treat hypotension during dialysis was also decresed. The improvements of acid base status by lactate hemodialysis were less effective than bicarbonate hemodialysis. However, there were no significant differences in post dialysis blood chemistries and acid base status after treatment with either acetate dialysate or lactate dialysate. These findings suggst that acetate influx itself may play an important role in etiology of so called acetate intolerance but acid base status may not. The lactate hemodialysis is easily used with standard hemodialysis system, and it needs no special system using bicarbonate hemodialysis.

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To study the effects of Ca-antagonistic drug, nifedipine, on receptor operated systemic and renal vascular reactivities to angiotensin II (A II), norepinephrine (NE), vasopressin (VP), bradykinin (BK) and prostaglandin E₂ (PGE₂), Japanese white rabbits weighing 3.2 to 3.9 kg (n=38) were used. Anesthesia was introduced by urethan (450 mg/kg) and a-chlorarose (45 mg/kg). Catheters were placed into the abdominal aorta (PE 60) through the femoral artery and into the vena cava inferior through the femorall vein (PE 50). For blood flow measurement, the lelt renal artery was exposed through a flank incision. A 27 gauge needle was inserted into the left renal artery for the infusion of vasoactive substances. Renal blood flow was measured by an electromagnetic flow meter. Systemic and renal vascular reactivities to All, NE, VP, BK and PGE₂ were studied before and after the administration of nifedipine (50 μg/kg) intravenously. The intrarenal infusion of nifedipine (0.5, 1.0, and 2.5 μg/kg/min) produced a dose dependent increse in renal blood flow. pressor responses to vasopression (10, 20, and 50 mU /kg/min) and angiotensin II at low dose (10 ng/kg/min) was significantly diminished after the administration of nifedipine (50 μg/kg), whereas it had no effect at high doses of AII (20, 50 and 100 ng/kg/min) and norepinephrine (0.25, 0.5, 1.0 and 2.5 μg/kg/min). The decrease of renal blood flow induced by the intrarenal infusion of angiotensin II (2.5, 5.0 and 10 ng/kg/min) was attenuated significantly after the administration of nifedipine. The decrease of renal blood flow induced by the intrarenal infusion of vasopressin (10, 20 and 50 mU/kg/min) was also attenuated by nifedipine. However, the renel vasoconstrictor reaction to norepinephpine (25, 50 and 100ng/kg/ min) did not change significantly after the administration of nifedipine. The increased renal blood flow induced by the intrarenal infusion of bradykinin (2.5, 5.0 and 10ng/kg/ min) and prostaglandin E₂ (20, 50 and 100 ng/kg/min) was not affected by nifedipine. These results suggest that receptor operated vasoconstrictor reaction to All and VP is mediated through the same Ca⁺⁺ mobilization mechanism but that of NE is not. It is confirmed that the renal vasodilator effect of BK and PGE₂ is not modulated bynifedipine in anesthetized rabbits.

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Following the recent advancement in renal surgery, conservative operations tend to be often performed. And, ischemic renal surgery may be required in some of these cases. It is presumable that diseased kidneys are more vulnerable to ischemia than normal kidneys. Even the short ischemic time, generally considered harmless for normal kidneys, may be harmful for diseased kidneys. The experimental studies in female mongrel dogs were performed concerning the effects of ischema on the obstructed kidneys. Effects of 60 minutes warm ischemia on the normal kidneys were minimum. Mean Ccr of the experimental side four weeks later was 70.8% of control pre-ischemic value. Unilateral ureteral ligation for one week resulted in slight renal damage. Mean Ccr four weeks after release of obstruction was 79.9% of control. 60 minutes renal artery clamp were performed on the kidneys with ureteral ligation for one week, which resulted in severe renal damage and poor functional recovery after release of obstruction. Mean Ccr at four weeks after release was 12.4% of control. Moreover, V/GFR, FENa and FECa⁺⁺ of the experimental side after release were extremely high in this group. Histological examination revealed severe tubular damage with marked interstitial fibrosis. In another group, renal ischemia for 60 minutes with simple surface cooling were performed on the kidney with ureteral ligation for one week. Functional recovery were considerably after release of obstruction. Mean Ccr of the experimental side four weeks later was 63.6% of control value. Although, high V f GFR, FENa and FECa⁺⁺ were also shown in this group. The results indicate that, although the obstructed kidneys are more vulnerable to ischemia, even the short ischemic time, renal cooling seems to be valuable. Surgical intervention on such diseased kidneys will need care to prevent significant hemodynamic alterations.

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One hundred and twenty-three patients with primary and secondary renal diseases entered the protocol of a trial of intravenous urokinase therapy given at a dose of either 60, 000 or 120, 000 IU once daily for 14 days. The diagnosis of renal diseases was based on the clinical features and histological examination of renal biopsy. Of the patients studied, 46 had primary chronic glomerulonephritis (GN), 64 primary nephrotic syndrome, 5 lupus nephritis, 4 anaphylactoid purpura GN 3 rapidly progressive GN, and 1 renal lesion associated with periarteritis nodosa. Comparisons were made of laboratory tests before and after the therapy. A significant increase in urine volume was observed in the patients, especially those whose urine volumes were initially less than 1, 000 ml/day. The increase in creatinine clearance (Ccr) was significant in those with pretreatment Ccr level below 80 ml/min, and the decreasein urine protein was significant in those with pretreatment urine protein level over 5 g/day. Significant increases in total serum protein (T. P.) and serum albumin (Alb.) were noted in the whole group. When data were analized according to histological findings, T.P. and Alb. significantly increased in patients with proliferative GN with focal crescents. Urine volume, T.P. and Alb. increased and urine protein decreased in patients with membranous nephropathy, and T. P. significantly increased in patients with membranoproliferative GN. Significant decreases in plasma fibrinogen and increases in serum and urine FDP were observed in the patients with urokinase administration. An effect of urokinase therapy is likely to result from the activation of fibrinolytic activity in the circulating blood and the kidney or an improvement in renal blood flow. No appreciable adverse effects developed. Thus the present study indicates that intravenous administration of urokinase 60, 000 or 120, 000 IU/day can be an effective therapeutic alternative for chronic GN and the nephrotic syndrome.

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Peritoneal dialysis (PD) with less influence on the cardiac function is generally performed rather than hemodialysis (HD) under the apprehension of reduced cardiac function in cases of chronic renal failure (CRF) complicated with heart disease. However, PD has such problems as lower efficiency of dialysis and higher risk of infection, etc. than HD. In the present study the final diagnosis was established by the examinations including echocardiogram, carotis tracing, radiocardiological examination, Swan-Ganz catheterization and aortography in a case of CRF complicated with aortic insufficiency. In this case an internal shunt was made and HD was carried out after the cardiac function was confirmed not to be reduced using cardiac index, pulmonary capillary wedge pressure, left ventricular stoke work index, left ventricular ejection fraction, ejection time f Preejection period and otheres as indexes. Any of these indexes showed no evidence for aggravation 5 and 10 months after starting HD. It was considered from the results that HD could be carried out safely and effectively, under close surveillance of the cardiac function by the above-mentioned method even in a case of CRF complicated with heart disease.

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A 40-year-old man was admitted to our hospital because of pretibial edema. Physical examination showed generalized edema and rashes on the trunk and the perineum. The pharynx was slightly reddened and the tonsils were enlarged. The relevant laboratory findings were summarized as belows. Urinalysis showed 4+ test for protein with one or two red blood cells, five or six white blood cells, two or three hyaline casts and four or six epithelial cells per highpower field and with one granulated cast per two or three high-power fields. The total serum protein was 3.3 g per 100m1. No Β-haemolytic streptococci were present in the throat culture. Serum antistreptolysin o titer was under 20 dils. Serum complements were not decreased. The ANA test was negative. Serologic tests for syphilis were strongly positive. Renal biopsy showed mild mesangial cell proliferation in the glomeruli and round cell infiltrations of the interstitial tissues on light microscopy. A few small adhesions of the capillary loops to the parietal layers of Bowmann's capsules were also seen. Immunofluorescent study demonstrated a coarse granular deposits of IgG and faint granular deposits of C₃ in the capillary loops. The histological diagnosis was membranous glomerulonephritis. The dermatologist diagnosed the rashes on the trunk and the perineum as the secondary syphilitic rash. The final diagnosis was the nephrotic syndrome due to syphilis. He was treated with penicillin. Proteinuria was rapidly decreased. The titers of serum TPHA and STS were also markedly reduced. The nephrotic syndrome disappeared completely. So far as we know, there has been few reports in Japan on the nephrotic syndrome due to syphilis.

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