Complement activation was evaluated more strictly by the quantitation of the breakdown product of the third complement component (C3). The direct estimation of the serum C3d level and the calcu-lation of the breakdown index which means the alteration rate from β₁ C/A to C3d were carried out in 4 patients with acute glomerulonephritis (AGN), 32 patients with systemic lupus erythematosus (SLE), 14 patients with membranoproliferative glomerulonephritis (MPGN) and 18 patients with chronic prolie ferative glomerulonephritis (CPGN). The C3d level was measured in the polyethylene glycol (PEG) su-pernate by the single radial immunodiffusion assay (SRID). C3d and the breakdown index were sig-nificantly increased in patients with AGN and MPGN, and not increased in patients with CPGN. In the SLE patients C3d was not so increased in spite of low β₁ C/A, however the breakdown index was remarkably high. Follow-up studies revealed that the C3d level did not always indicate complement activation, but the breakdown index had a parallel property with the disease activity.

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The juxtaglomerular cells in the mouse were qualitative and quantitative morphologically studied by electron microscopy. Mice were sialoadenectomized at 60 days of age or gonadectomized at 25 or 60 days of age. For quantitative analysis, the volumic ratios of nucleus, specific granule, Golgi apparatus, rough endoplasmic reticulum and mitochondria to cell were stereologically obtained. In normal mice, the juxtaglomerular cells contained numerous specific granules. Most of the gran-ules contained homogeneous material and some contained small filamentous contents, although there were transitional forms between the two forms of granules. The Golgi apparatus and rough endoplasmic reticulum were usually poorly developed. In sialoadenectomized mice, the juxtaglomerular cells showed significant changes only in males and not in females. In males of which the submandibular glands were removed, the specific granules were decreased in amount 1 week after operation, but increased at 7 weeks. The Golgi apparatus and rough endoplasmic reticulum were well developed 1 and 7 weeks after operation. The granules with crystalline contents were often seen near the Golgi apparatus. In females, no significant changes were seen in the juxtaglomerular cells. In gonadectomized mice, the juxtaglomerular cells showed significant changes only in males, and no significant changes appeared in females. The functional structure of the juxtaglomerular cells was discussed particularly in relation to renin.

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Seventy one patients with primary glomerulonephritis were studied for the presence of circulating immune complexes (CIC) in the sera by iiiI-Clq binding test. The incidence and mean values of CIC were significantly higher in 71 patients than in 50 normal controls. Among 7 groups into which 71 patients were divided based on renal biopsy findings, the incidence and mean values of CIC were higher in acute glomerulonephritis and membranoprolif erative glomerulonephritis Type I and lower in membranous glomerulonephritis. In patients whose renal histological findings were minimal change disease, all patients with positive CIC had nephrotic syndrome as clinical manifestation. In IgA nephropathy the higher incidence of CIC was observed in patients whose renal biopsy findings showed moderate or advanced mesangial changes than in those with minor or mild ones. Serial CIC determinatons demonstrated that initially positive CIC became negative with passage of time in acute glomerulonephritis. In contrast, the detection of CIC was intermittent at relatively low levels in membranous glomerulonephritis but constant at relatively high values in patients with membranoproliferateve glomerulonephritis Type I. These findings might indicate that CIC play an important role in the pathogenesis of various forms of primary glomerulonephritis, depending on their amount and duration of supply to the kidney.

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The role of cell-mediated immunity in glomeruli on the pathogenesis of human glomerulonephritis (GN) was evaluated by the monoclonal antibodies with indirect immunofluorescence (IF). The kidney specimens by open renal biopsies were examined by light microscopy, IF, and electron microscopy. The materials were consisted with 13 cases of lupus nephritis (LN) (4 cases of mesangial LN, 3 of mem-branous LN, 5 of diffuse proliferative LN, and 1 of rapidly progressive LN), 14 cases of primary GN (6 of IgA GN, 2 of minimal change GN, 3 of membranous GN, and 3 of membranoproliferative GN) and 3 cases of normal subjects. Monoclonal antibodies were Ortho's OKT (3, 4, 6, 8) antibodies, Bekton's Leu (1, 2a, 3a) antibodies, Sera-Lab's macrophage (Mφ) and DR antigen antibodies, and Dr. Schlossman's Mφ antibody. The results are as follows: (1) the tissues of the normal subjects were shown to have no specific IF in the glomeruli as well as on tubalar cells and in the interstitium. (2) OKT antibodies showed homogeneous IF in the mesangium and/or on GBM where only when human immunoglobulins were demonstrated by routine IF studies. (3) Leu antibodies disclosed only T, Tγ, and Tμ cells where mononuclear cells were infiltrated in the glomeruli and interstitium. However, regardless of renal histopathologies, the numbers of the T cells found per one glomerulus were less than several. (4) Mφ and DR antigen antibodies revealed more than several Mφ per one glomelulus only in the cases of cell proliferative type GN such as diffuse proliferative GN, rapidly progressive GN, and membranoproliferative GN. In addition, in a case of rapidly progressive LN, Mφ were demonstrated to participate in the formation of crescent only from the side of glomerulus, but not from the side of Bowman's capsule. These findings lead to the conclusion that Mφ, bat not T cells, play important clues in glomeruli on the pathogenesis of proliferative GN.

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In order to evaluate the correlation between the size of CIC and glomerular histology, sera with positive CIC from 6 patients with lupus nephritis were fractionated by sepharose C. L. 6B column chromatography. The fraction thus obtained were divided into three groups and expressed as small (M.W. equivalent or less than IgG), middle (M. W. between IgG and IgM) and large (M. W. between void volume and IgM) size. The CIC activity of each fraction was examined by Raji cell IF assay. The CIC activity in patients with severe diffuse proliferative LN was found mainly in the fraction of middle and large size, whereas the activity in three patients with mesangial proliferative LN was found exclusively in the fraction of small size. As a control study, the size of CIC in patients with non renal SLE (2 cases), SLE+RA (2 cases) and RA (2 cases) were also examined and the CIC activity was only found in the fraction of small size in all cases. It was concluded that CIC size in patients with LN had a definite correlation to the glomerular histology and the determination of CIC size was valuable for the analysis of pathogenesis and prognostic index in patients with LN.

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Little is known, whether the amount of glycosaminoglycans (GAG) excreted in the urine has any bearing on relation to renal function. In order to clarify the relationship between renal function and GAG excretion, daily urinary amount of GAG was measured in 20 healthy subjects, 9 patients with benign prostaic hyperplasia (BPH), in 5 patients with ureteral or renal calculi and in 8 patients with deteriorated renal function due to chronic medicai renal disease. These data were correlated to endogenous creatinine clearance (GFR), magnitude of proteinuria, and renal tubular dysfunction as estimated by serum and urineβ2-microglobulin levels. The amount of urinary GAG was expressed as uronic acid determied by carbazol reaction following the method of Bitter & Muir. The mean values for GFR were 79.9ml/min in healthy subjects, 44.3ml/min in BPH, 39.2ml/min in medical renal disease and 68.0ml/min in urolithiasis. The daily GAG excretion in patients with BPH and urolithiasis was significantly lower than the healthy subjects (p<0.05), whereas in patients with medical renal disease, the level remained as high as that of controls (Table 1). There was no statistically significant correlation between GFR and GAG levels. When the ratios of GAG to GFR were plotted on the ordinate against the serum levels of creatinine, there was a significantly high correlation, which is demonstrated in the regression of y = -1.1 + 1.5 × (r=0.7, p<0.01). This fact indicates that there is a significant increase of GAG excreted in the urine by single nephron with the progression of renal dysfunction. There was no significant difference of the urinary levels of GAG between those who had proteinuria or tubular dysfunction and those who had not. In patients with medical renal disease the distribution of GAG components, which was analysed by two-dimensional electrophoresis, demonstrated a significant decrease in the fractions of chndroitin sulfate and heparan sulfate (p<0.05) and an increase of low sulfatated chondroitin sulfate, which was normally present predominantly in the serum (p<0.01). From these observations, it is concluded that in patients with deteriorated renal function, urinary GAG may be derived directly from the serum, that is excreted in the urine nonselectively by unknown mechanism.

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The relationship between the clinical course and the serial change in urine protein electrophoresis based on molecular size difference was studied in 14 cases of acute glomerulonephritis (AGN). The cases were divided into three groups according to their clinical courses; those with early improvement in whom almost all the clinical symptoms dissappeared within 1 month, those with delayed improvement in whom it took 2 to 3 months before most of the clinical symptoms disappeared, and those with persistent courses in whom various clinical symptoms persisted for over 6 months. In eight of the nine children with early improvement, the urinary protein electrophoretic pattern showed prom-inent high molecular weight (HMW) protein bands besides the albumin band during the initial phase of the illness, but they decreased and disappeared in association with the clinical improvement. In three cases with delayed improvement, HMW protein bands persisted in spite of the fluctuating urine protein excretion during the initial phase. In cases with persistent courses, prominent HMW protein bands persisted for long time. Recovery of the decreased serum complement (C3) level and the improvement in the urinary sediment were slower than that of urine protein excretion and electrophoretic changes. In conclusion, serial urine protein electrophoretic studies seem to reflect the process of improve-ment in most the cases with AGN. Therefore, frequent analysis of urine protein by electrophoresis based on molecular size difference during the initial phase of AGN will contribute to the assessment of the prognosis of AGN.

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Effects of thiazide administrbtion on calcium and phosphate metabolism are investigated in 16 recurrent stone formers associated with hypercalciuria. On the basis of 5 to 30 months with thiazide, the following conclusions are obtained. 1. Stone progression ceases at least 75% of patients who are taking thiazide on a regular basis. 2. In addition to the hypocalciuric action, thiazide reduce urine phosphate and uric acid excretions but elevate oxalate excretion. 3. While serum clacium decreases, serum phosphate and uric acid increase. 4. A good correlation between an increment of serum phosphate and a decrease in 1, 25(OH)2D3, or a decrease in serum clacium and an elevation of serum PTH may provide a clue to the pathophysiology of idiopathic hypercalciuria. Although thiazide is effective in hypercalciuric patients, a watchful observation should be required in those biochemical changes during the long-term use of the agent.

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This study was undertaken to clarify the role of sympathetic beta-adrenergic receptor on renin secretion from juxta-glomerular apparatus in the kidney. Urinary norepinephrine excretion (u-NE) and epinephrine excretion (u-E) were determined in low, normal and high renin essential hypertension (n=93), and next isoproterenol was administrated intravenously, at a dose of 0.02μg/kg/min for 30 min, and blood pressure, pulse rate, plasma renin activity (PRA), plasma cyclic AMP (c-AMP) and plasma aldosterone concentration (PAC) were measured before (0'), during (5', 15', 30') and 30min after (60') the infusion in 6 normal subjects and 19 patients with essential hypertension (EH). u-NE was 16.5±11.8μg/day in low renin EH (LR-EH), 19.7±11.4μg/day in normal renin EH (NR-EH) and 20.2±9.8μg/day in high renin EH (HR-EH), respectively. u-E was 3.6±2.2μg/day in LR-EH, 6.3±5.8μg/day in NR-EH and 8.6±5.0μg/day in HR-EH, respectively. u-E in LR-EH was significantly lower than in NR-EH (p=0.05) and in HR-EH (p=0.01). In normal subjects, pulse rate markedly increased during isoproterenol infusion. PRA and c-AMP did increase, but PAC did not change signifi-cantly with the infusion of isopreterenol. In LR-, NR- and HR-EH pulse rate increased significantly. PRA in LR-EH inconsiderably increased (0': 0.25±0.17ng/ml/h, 5': 0.28±0.23ng/ml/h, 15': 0.31±0.19 ng/ml/h, 30': 0.31±0.14ng/ml/h) during the infusion. PRA in both NR-EH and HR-EH significantly increased during isoproterenol infusion. The increment of c-AMP was observed in LR-EH as well as in NR-EH. PAC did not change significantly during the infusion. These data suggest that the renin secretion after the stimulation of sympathetic nervous system is mediated by renal beta-adrenergic receptor, and that in low renin essential hypertension there may be not only the hypotonicity of sympatho-adrenomedullary system but also the hyporesponsiveness of renin secretion to exogeneous and/or endgeneuos catecholamines.

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The hemodynamic and humoral effects of prazosin were studied in thirteen patients with essential hypertention. Before and after two weeks of continuous administration of prazosin (3-6 mg/day), the following measurements were carried out; blood pressure, heart rate, cardiac index, total peripheral resistance index, plasma renin activity, plasma aldosterone concentration, plasma cathecholamine concentration, serum potassium, and hematocrit. At the same, head-up tilt was performed. Prazosin produced a marked reduction on blood pressure in all cases. Mean blood pressure fell from 126±3 mmHg to 115±3 mmHg. The change of blood pressure was significant (p<0.01). But heart rate and cardiac index remained unchanged. Total peripheral resistance index was significantly reduced (p<0.05). Plasma renin activity and plasma aldosterone concentration decreased significantly (p<0.05). Plasma norepinephrine concentration decreased, but the change was not statistically significant. By head-up tilt, prazosin gave no marked influence on hemodynamic responces. The antihypertensive effect of prazosin was found in patients with essential hypertension, and was not associated with reflex tachycardia or increased renin release. This action was thought to be due to its vasodilating property. These findings may show that prazosin is useful to essential hypertention.

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The case is a 69 year old female, who was admitted because of pretibial edema and massive pro-teinuria (5-8g/day). The criteria of nephrotic syndrome was satisfied. Renal biopsy revealed amyloid kidney. IgA-λ type myeloma was diagnosed by an immunoelectrophoretic analysis and bone marrow picture. Pulselessness in her left arm and defect of the left subclavicular artery from the aorta observed by R-I angiography made us diagnose her as aortitis syndrome. The progression of subclinical hypothyroidism (R-T3 31.6→26.7%, T4 3.6→3.2μg/dl, TSH 10→24μU/ml) and the appearance of sick sinus syndrome (maximum sinus node recovery time: 4565 msec) were ascertained to be due to myeloma related systemic amyloidosis. Disopyramide induced hypoglycemia was seen in her terminal stage.

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