Lyophilized Habu snake (Trimeresurus flavoviridis)venom was dissolved in physiologic saline and injected respectively as a single intravenous dose of 0.1 mg, 0.5 mg and 1.0mg per Kg of body weight of rabbits. Open renal biopsy or nephrectomy was performed at intervals from 3 hours to 28 days after injection. The specimens of the renal tissue were observed by light, electron and fluorescent microscopy.
The initial and common glomerular lesion due to Habu snake venom was meangiolysis which was directly caused by various kinds of enzyme of the venom. Capillary cystic lesions due to mesangiolysis were noticed in the focal and segmental glomerular tufts at 3 hours to 28 days after injection of the venom. Normal mesangial cells became degenerative or atrophic in the areas of mesangiolysis.
Focal and segmental hypercellularity and capillary thrombi were not observed in glomeruli of the rabbits injected with 0.1mg venom per Kg of body weight. In the area of capillary cystic lesion, focal and segmental hypercellularity developed between 4 and 5 days, and persisted until 21 days after injection of. 0.5mg venom per Kg of body weight. The proliferating cells in glomeruli were mostly active cells, however macrophages were also demonstrated in a few other hypercellular glomeruli within one week after injection. At two weeks and later, macrophages disappeared from these hypercellular glomeruli, in which only active mesangial cells were persist. Neither immuofluorescent deposits nor electron dense deposits were observed in the hypercellular glomeruli.
In the rabbits injected with 0.5mg venom per Kg of body weight, the frequency of hypercellular glomeruli increased more than that of glomerular capillary thrombi. Rupture of the basement membrane was observed in capillary thrombi where fibrin or fibrin-like substance, erythrocytes, mononuclear cells and neutrophiles infiltrated into Bowman's space. At the level of serum creatinine, more than 2.0mg/dl, the frequency of glomeruli with hyperllularity and thrombi increased. In the rabbits injected with 1.0 mg per Kg of body weight, the frequency of glomerular thrombi increased more than that of hypercellular glomeruli.

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　各種腎疾患を対象に血液および尿中FDPの画分を検討し,下記の成績を得た。1)血液D-dimerは89例中18例(20.2%),尿中D-dimerは59例中22例(37.2%0)に陽性で,これらの例では.血管内および尿路系における二次線溶の存在が推察された。2)血液または尿中D-dimer陽性例は陰性例に比べ,組織障害が強く,臨床的にも腎機能が低下し,血尿の程度が強かった。3)血液または尿中D-dimerの陽性例と陰性例とで,FDP値には差が認められなかったが,尿蛋白量に対する尿中FDPの比は尿中D-dimer陽性例が陰性例に比べて高値を示した。4)尿中D-dimerは,尿中FDPの全画分中の5%以内で,尿中FDPの大半は一次線溶由来のものから成っていた。5)尿中FDPで高分子画分が多くを占めた例では,その多くは糸球体よりの血中フィブリノゲンの漏出に由来するものと思われた。稿を終るにあたり,御懇切な御指導と御校閲を賜った原耕平教授に深甚なる謝意を表するとともに,直接御指導を頂いた堀田覚前助教授,諌早健康保険病院藤田宣士先生,大分医科大学検査部血液室曲泰男先生に深謝いたします。また終始研究に協力していただいた第二内科学教室の腎臓グループの諸先生方に感謝いたします。なお本論文の要旨は第11回日本腎臓学会西部部会,シンポジウム「腎と凝固・線溶」において発表した。

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Several assays have recently been developed for the detection of circulating immune complexes (CC). The PEG-cc test described by G.D. Harkiss is a simple and sensitive assay. We measured CIC by this procedure in the sera obtained from 68 cases, including 37 cases with SLE and 31 cases with primary glomerulonephritis. Then for the purpose of revealing immunoglobulin class and complement in CIC detected by PEG-cc test, we also measured PEG precipitates index (PP index) of IgG, IgA, IgM and C3 in the sera obtained from 24 cases with lupus nephritis by PEG precipitation method using radial immunodiffusion.
The results were as follows:
1. Standard curve for PEC-cc test was prepared using known quantities of aggregated IgG. The lower range of sensitivity was 2μg/ml.
2. The mean CIC value evaluated by PEC-cc test (CIC value) was significantly increased in lupus nephritis (N=25) and membranous nephropathy (N=5) compared to normal (N=20).
3. Between CIC value and C3 concentration in 58 sera obtained from 44 cases, there was significant inverse correlation.
4. The group of active lupus nephritis (N=12) showed significantly higher CIC value than the group of inactive lupus nephritis (n=12).
5. In serial measurements, the patients with lupus nephritis showed high CIC value, high IgG PP index and high C3 PP index in active stage and they returned to be normal in inactive stage. CIC value reversely changed with serum total complement hemolytic activity and C3, whereas it changed in parallel with IgG PP index and C3 PP index.
These results indicate that in lupus nephritis, CIC value, IgG PP index and C3 PP index are useful in evaluation of disease activity and monitoring therapy, and that major portion of CIC detected by PEG-cc test in lupus nephritis may be consisted of IgG binding with C3.

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Heavy meromyosin (HMM) was labelled with a new thiol-directed fluorescent dye, N-(7-dimethylamino-4-methylcoumarinyl) maleimide (DACM) (DACM-HMM). Employing DACM-HMM, we were able to demonstrate the presence of actin in the renal tissue samples from 13 patients with minimal change glomerular lesion. The specificity of this method for actin-myosin complexes was confirmed by blocking test, 5mM ATP treatment and striated staining in skeletal muscle. Actin was demonstrated in the mesangium, glomerular epithelial cells and Bowman's capsule. The glomerular epithelial actin appeared to be present in the foot process. The mesangial actin was likely to be continuous with the smooth muscle actin of the renal arterioles. Contraction of the mesangial actin would be important in the control of intraglomerular blood flow and mesangial phagocytosis.

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Lipid metabolism was examined in daunomycin induced nephrotic rats.
1) Phospholipid, triglyceride, cholesterol, HDL-cholesterol content in serum were increased in daunomycin induced nephrotic rats.
2) Postheparin lipolytic activity was lower in daunomycin induced nephrotic rats than control rats.
3) The daunomycin induced nephrotic rats showed the decreased triglyceride, the increased cholesterol ester content in liver.
4) Phospholipid, triglyceride content in kidney were decreased, but cholesterol ester was increased in daunomycin induced nephrotic rats.
5) Incorporation of ¹⁴C-acetate into cholesterol was studied using liver and kidney slices, and significant increase in liver was observed in daunomycin induced nephrotic rats. There was no difference in renal cholesterogenesis between control and daunomycin induced nephrotic rats.
These results show that the increased cholesterol content in serum and liver is due to increased hepatic cholesterogenesis in daunomycin induced nephrotic rats. The accumulation of cholesterol ester in kidney seems to result from exogenous cholesterol ester in nephrotic rats.

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We studied the suppressive activities in the acute phase serum of children with minimal change nephrotic syndrome upon ³H-thymidine(³H-TdR) incorporation in the phytohemagglutinin-P (PHA-P) stimulated lymphocytes. And, we studied the suppressive mechanisms in association with the suppression of accentuated cellular sterol biosynthesis and cell membrane phospholipid, especially phosphatidylinositol (PI) synthesis, regarding to the lipoprotein classes isolated from ultra-centrifugation separation method.
(1). We separated the serum of acute nephrotics into lipoprotein-deficient serum (LPDS ; d>1. 25), high density lipoprotein (HDL ; 1.063< d <1.21), low density lipoprotein (1.019<d<1.063) intermediate density lipoprotein (1.004< d <1.019) and very low density lipoprotein (d <1.004) and studied each suppressive activities. LPDS and HDL fractions were not accepted to be suppressive.
(2). IDL and VLDL fractions from both nephritics and healthy persons were accepted to be suppressive but, both were not significant respectively and therefore IDL and VLDL fractions were not the main suppressive factors.
(3). Regarding to LDL fraction, LDL from healthy persons were not suppressive but, that of nephrotics were suppressive and we thought it to be the main supcressive factor.
(4). Regarding to the sterol biosynthesis in PHA-P stimulated lymphocytes, LDL fraction from acute nephrotics were significantly suppressive in contrast to that of healthy persons. Therfore, we thought the LDL of acute nephrotics to be different to that of healthy persons regarding to the apoprotein or cholesterol levels.
(5). Also, LDL fraction of acute nephrotics were significantly suppressive in contrast to that of healthy persons regarding to PI synthesis in PHA-P stimulated lymphocytes and this suppression of PI synthesis were thought to be the major factor of the suppression of ³H-TdR incorporation.
We studied the suppressive factor of LDL fraction in the serum of acute nephrotics but, in this experiments we mostly studied the suppressive activities for ³H-TdR incorporation in PHA-P stimulated lymphocytes. Therefore, we will further study the suppressive activities of serum from acute nephrotics for the other mitogen stimulated lymphocytes.

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Outcome of pregnency for both mother and child and remote prognosis of underlying renal disease were studied on 38 pregnancies of 37 patients (25, glomerulonephritis ; 5, toxiemia of pregnancy ; 7, without biopsy) with or without diet control. Patients wer divided into 3 grours. Group I : 11 cases with diet control and renal biopsy performed before pregnency. Group II : 19 cases, renal biopsy done after delivery and no diet cotrol. Group III : 7 cases neither renal biopsy not diet control.
The results obtained were as follows.
1) Duriog course of pregnancy there were more patients who developed either higher blood pressure or increased BUN levels in group II than did in group I.
2) At the end of follow up there were more patients who had lower creatinine clearances in group II when compared to group I.
3) Body weight of newborns was heavier in group I than in group II.
4) Alivebirth rate was higher in group I than gpoup II. All the findings aforementioned were from the patients of group I and group II without towemia of pregnancy and they all were statistically significant.
5) Toxemia of pregnancy resulted in the worst fetal prognosis among our patients studied.
It is concluded that under the careful supervision of life and diet patients with various types of renal diseases may have safe pregnancy and fruitful delivery, whereas patients to whom little medical care was taken before and during pregnancy may result in poorer prognosis when complicated with renal diseases.

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In order to study the left ventricular function in diabetic renal failure, 30 diabetics with nephropathy, 25 patients with end stage renal failure due to chronic glomerulonephritis and 42 normal controls were studied using echocardiography. Ejection fraction was within normal limits in each group. The thickness of the interventricular septal and left ventricular posterior wall and left ventricular mass were significantly increased, and end-diastolic dimension and volume were reduced in diabetic group compared with non-diabetic renal failure group and controls.
The thickness of the interventricular septum and left ventricular posterior wall and the level of blood pressure were gradually increased with fall in reserve of renal function in diabetics. Age, duration of diabetes mellitus and severity of retinopathy were not correlated with the grade of left ventricular wall thicking.
In conculusion, these observations suggest that the left ventricular wall thickning might be based on abnormal myocardial metabolism due to diabetes mellitus and secondary to hypertension.

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Massive and persistent posttransplant proteinuria without graft function deterioration has been observed in a renal allotransplant recipient. Biopsy specimen of renal allograft obtained at the time of 11 months post-transplantation showed major histologic abnormalities in the interstitium and glomeruli. Interstitial fibrosis, tubular degeneration and mild increase in mesangial matrix were present but the glomerular basement membrane was normal on light microscopy. Immunofluorescence microscopy demonstrated linear deposits of IgG and IgA along the GBM, IgM and fibrinogen deposits along the glomerular capillary wall and no C₃ staining. These findings suggested that pathogenesis is associated with chronic rejection rather than recurrent glomerulonephritis.
Urine protein selectivity was determined by the SDS-polyacrylamide gel electrophoresis and % transferrin clearance. Absence in selectivity occurring in this patient suggested severe glomerular and tubular damages resembled to RPGN or MPGN pattern. We discussed about the discrepancies among clinical course, morphologic findings and urine protein nonselectivity.

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It was demonstrated that angiotensin converting enzyme (ACE) was excreted inhuman urine, In order to clarify the biochemical characteristics of ACE in the urine and the pathophysiological significance of ACE of the kidney, this study was performed. ACE from normal human urine was partially purified and ACE activities were measured in urine samples from normal subjects, essential hypertensives and patients with nephrotic syndrome and chronic glomerulonephritis. The results were as follows:1) The assay of ACE activity in human urine was performed using hippuryl-histidylleucine as substrate. The mean activity of theenzyme in normal urine was found0.38±0.1 (SD) units/day (n-18).2) Three different molecular weights of the enzyme (more than 400, 000, 290, 000 and 140, 000) were demonstrated by Sephadex G-200 gel filtration, The enzymic properties of these two enzymes (more than 400, 000 and 290, 000) were identical with those of ACE purified from human kidney with respect to inhibitory effects (EDTA, bradykinin potentiator c, Arg-Pro-Pro and captopril), C1y dependency, pH optimum and Km value.3) It was demonstrated that a high molecular weight form of the enzyme (morethan 400, 000) was mainly excreted in human urine. This form of the enzyme may be originated from brush border of proximal tubules and altered in part to a low molecular weight form (290, 000) by trypsin-like enzymes in human urine.4) The urinary ACE activity in essential hypertensives (WHO stage II) was significantly higher than those in normal subjects and essential hypertensives (WHO stage I). But there was no significant difference between normal subjects and essential hypertensives (WHO stage I). This means that the damage of proximal tubules of the kidney is progressed in essential hypertensives (WHO stageII) with duration of hypertension.5) The urinary ACE activity in patients with nephrotic syndrome was significantly higher than that in normal subjects. This increase in ACE activity was due mainly to increased release of a high molecular weight form of the enzyme. This means that increased urinary ACE excretion under pathological conidtions mainly depends on the damage of proximal tubular cells, 6) It was found a significant correlation between sodium and ACE excretion in normal subjects. Under the pathological conditions such as essential hypertension and renal diseases, however, the significant relationship of sodium and ACE excretion was not observed.

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