A study was undertaken to evaluate the utility of commercially available peroxidaselabelled antibodies and some processing variables affecting the Immunoelectron microscopic demonstration of immunoglobulins and complement in human glomeruli. Seventeen percutaneous biopsies were used. Findings of Immunoelectron microscopy were compared with those of light microscopic, electronmicroscopic and immunofluorescence examinations by routine methods. Fixation in 2% paraformaldehyde or periodate-lysine-2% paraformaldehyde for 3 hours was good for preservation of both antigenicity and ultrastructure Penetration of antibodies and quality of peroxidase reaction were good in 15-20 μm thick section. Findings of immunoelectron microscopy were well correlated with those of immunofluorescent microscopy, except for some cases concerning IgM, since smaller amount of IgM can be demonstrated with the former.

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Serum immune complex was mesaured by C¹q binding test solid phase assay in 41 potients with chronic glomerulonephritis. Renal tissues were also taken in these patients and examined by light, immunofluorescent and electron microscopic study. Serum levels of I. C., serum complement C₃, complement activity by CH₅₀, and the degree of hematuria or proteinuria were simultaneously examined in these patients. Significantly elevated levels of I. C. in serum were observed much often in those patients who showed prominent hematuria. Those patients with constantly elevated levels of I. C. in serum showed macrohematuria repeatedly. Serum I. C. levels paralleled clinically much often to the occurrence of hematuria than to proteinuria. However, the degree of hematuria did not correlated with the histological changes. The patients with IgG and IgM deposition in their renal glomeruli by immunofluo rescent study showed much frequently the high levels of I. C. in serum. We concluded that hematuria could be the index of activity of glomerulonephritis based on the assumption that the detection of I. C. in serum correspond to the nephritic antigen stimulation.

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To study the significance and the role of serum immhne complex in patients with nephrotic syndrome and in patients with collagen diseases, the serum immune complexes were measured in these patients. Serum immune complex was measured by C₁q binding test solid phase assay in 28 patients with nephrotic syndrome and 13 patients with collagen diseases. Renal tissues were also studied by light, immunofluolescent and electrom microscopy. Serum immune complex was not detected expect one in 12 patients with minimal change type of nephrotic syndrome. In 16 patients with membraneous nephropathy, immune complex was not detected in 14 patients and in only 2 patients immune complex was detected. One of these 2 patients had complication of renal vein thrombosis and a renal cyst. Immune complex was detected significantly with membranoproliferatiue glomerulonephritis. From these we concluded that in minimal change nephrotic syndrome, immune complex did not partipate in its pathogenesis. While in membraneous nephropathy there were two groups, one of which was related to serum positive immune complex and the other group which did not show any significantly elevated serum immune complex. The significance of these different of serum immune complex level in membraneous nephropathy is further to be clarified. In systemic lupus eryhematosis, serum immune coplex level are correlated with ANF titers and inversely correlated with serum complement titers or complement activities and are assumed to play important roles to the pathogenesis and progression of the disease.

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To clarify the point of connection between humoral immunity and cellular immunity in progression of lupus nephritis, serum immune complex were measured by C₁q binding test solid phase assay, and peripheral lymphocyte subpopulations were simultaneously measured by rosette formations. Biopsy renal tissues in these patients also examined by light, immuno fluorescent and electron microscopy. In active stage of SLE, serum immune complex were high in levels, T cell and Tγ cell were supressed and Tμ were relatively elevated. As already known that Tγ had the supresser function and Tμ had the helper function, decreased Tγ and increased Tμ might lead to overproduction of antibody or unusual antibody production. It was also shown that the fluctuation of lymphocyte subpopulations preceded the fluctuation of immune complex. From these results, it would be useful to measure the lymphocyte subpopulations in systemic lupus erythematosis to know the activity and the effect of the therapy.

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Therapeutic effects of dilazep dihydrochloride administrated to the glomerular disease were studied on 16 patients with nephrotic syndrome and 25 patients with chronic glomerulonephritis. All of the patients were received renal biopsy prior to the therapy and given 300mg of dilazep per day (t. i. d) orally for 2 to 24 months. The efficacy of dilazep was judged by paired t-test from the proteinuria, hematuria, endogeneous creatinine clearance (CCr) and additional laboratory findings. Following results were obtained. 1) Global improvement rate of clinical findings was 45.8% at the 6th month of the administration. 2) Significant increase of CCr was observed at 1, 2, 3, 6 and 12 months of the treatment on the whole. In detail, this improvement of CCr was found in chronic glomerulonephritis with mesangial proliferation. 3) As for the urinary findings, improvement rate was both 29% in proteinuria and hematuria and was not significant at the 6th months. 4) The mechanism of the improvement of CCr are supposed to be due to inhibitory effect on platelet aggregation, activating effect on blood fibrinolysis system and increase in renal blood flow. 5) No side effects were observed except for abdominal fullness in a case.

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Membranoproliferative glamerulonephritis (MPGN) has been recognized as one of the most progressive renal disease. In 1973, Japanese government passed the law which required all the elementary and junior-high schools to have an urine test on their school childen. Since then, we have found a great many cases of renal diseases in asymptomatic children. Among them, MPGN with persisting hypocomplementemia is possible to be found by laboratory test, , including complement survey, in the early stage. Although the glomerular lesions of biopsied specimens from asymptomatic hypocomplementemic persistent glomerulonephritis are not necessarily diffuse but in some cases are these focal and/or segmental, we have observed in them the typical morphological changes of MPGN; circumferential mesangial interposition, electron dense deposits at certain area with cellular proliferation. We have the opinion that this finding is representative of an early manifestation of various types of MPGN. Because of the effectiveness of any chemotherapy on 'full-blown' MPGN is badly done and to make 'early detection' of MPGN significant, we have formulated the high-does alternate day corticosteroid administration on them as a positive medical management. Firm conclusions must await evaluation of a much larger series of patients and longer follow up period, as well as serial kidney biopsies.

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Renal biopsies from 40 patients with isolated hematuria were studied with light microscopic and immunofluorescence antibody techniques. And we obtained the conclusions as follows: (1) In 40 patients with isolated hematuria, we found 18 patients with Berger's disease (45%), 3 patients with focal glomerulonephritis (7.5%), in whom the diagnosis of Berger's disease had been ruled out by immunofluorescence, 2 patients with membranous glomerulonephritis (5%), 5 patients with thin basement membrane (or familial benign essential hematuria) (12.5%) and 12 patients with benign essential hematuria (30%). (2) On electron microscopic study, the same type of GBM lesions were found in these different glomerular diseases. The characteristic features of these GBM changes were: (a) focal of diffuse thinning of lamina densa, (b) focal splitting of lamina densa, (c) round granulations of lamina densa and (d) presence of the remnants of cell cytoplasm in GBM. So we suppose that these GBM lesions may explain the histological cause of glomerular bleeding. (3) Additionally, 29 patients were followed up for 0.8 to 10 years from the first clinical manifestation. There was no deterioration of renal function or other clinical data in any instance. However, the outcome of hematuria differed in each glomerular lesions. In Berger's disease, 6 out of 14 patients had no hematuria at the end of follow up. On the contrary, none out of 4 patients with thin basement membrane disease and only one out of 6 patients with benigh essential hematuria had no hematuria at the end of follow up. This fact indicates that the GBM lesions may be reversible in immunologically mediated disease such as Berger's disease, but the lesions may be permanently present in hereditary or non-immunogically mediated diseases such as thin basement membrane or benign essential hematuria.

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Forty-nine patients with lupus nephritis out of the 74 with systemic lupus erythematosus (SLE) followed for an average of 9 years since 1962 were investigated to clarify the longterm outcome and the factors modifying their prognoses. Five year suvival rate of whole SLE patients and those with lupus nephritis were 82 and 84 per cent, and 71 and 66 per cent at 10 years from the onset of clinical manifestations, respectively. Sixteen patients with lupus nephritis and 5 without were dead during the follow-up period. The former included only 2 renal deaths and all 5 deaths in the latter occurred within initial 5 years from an apparent onset. As for outcome of renal function, no relationship with initial glomerular histology was observed, mainly because of possible histologic transformations as observed in 7 of 17 patients. Analyses using a life-table method regarding prognostic indices for lupus nephritis appeared that sex, age at onset and the complication of nephrotic syndrome did not significantly participate in their survival, but hypertension seemed to make them worse. In summary, (i) the lupus nephritis might suggest to appear a life-threatening complication in SLE patients, however, it was rare that a patient died of lupus nephritis itself. (ii) It seemed difficult to make an accurate estimation of long-term outcome in lupus nephritis and SLE from renal histology.

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Actin is shown previously to be present in the glomeruli using Heavy meromyosin coupled with a fluorescent dye, N-(7-Dimethylamino-4-Methylcoumarinyl) Maleimide (DACM), Distribution of actin was evaluated comparing with localization of fibronectin, IgA and IgG by immunofluorescent microscopy on biopsied specimens with various renal diseases. In IgA nephropathy, actin was located in the expanded mesangial area and was thicker than that in minimal change disease. Hemispherical deposit was surrounded with actin. In membranous nephropathy, actin increased on the capillary loops without mesangial changes and was observed enclosing the immune deposits on GBM. Glomerular ultrastructual studies revealeded that the foot process was fused. The same findings were observed in minimal change disease but actin did not increase on the capillary loops. This suggests that thickend actin in membranous nephropathy is not caused by the foot process fusion but the other unknown mechanism, In membranoprolif erative glomerulonephritis, numerous actin was present in the expanded mesangium, whereas on the capillary loops actin did not increase. Though actin in mesangium was increased in width in patients with acute glomerulonephritis, capillary loops appeared to be normal. In lupus nephritis, the distribution patterns of actin were different according to their light microscopic findings. Actin was found surround ing the "wire-loop", but not in it. Increased mesangial actin was also found in Henoch-Schönlein purpura nephritis as same in the IgA nephropathy. Linear actin was detected in periglomerular fibrosis and no actin was detected in glomerular sclerosis. We propose the possibility that increased actin in the mesangium may lead an increase in the mesangial phagocytic function at early stage of the disease, as previously suggested by the study of increasing mesangial actin filament in phalloidin treated rats.

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The purpose of this study is evaluated the characteristics of tolerance and cardiac function in chronic hemodialysis patients (HD patients). Symptom limited treadmill exercise test was carried out in 33 HD patients and the results were compared with them in normal subjects and in ischemic heart disease patients (IHD patients). The following results were obtained that 18.2% of the HD patients indicated positive findings on treadmill exercise test. But 69.7% of the cases had to stop the test by their leg fatigue. In comparison with normal subjects, exercise time, maximum heart rate, maximum VO₂ and maximum pressure-rate products were reduced to the same degree both in HD patients (negative findings on treadmill exercise test) and in IHD patients. Based on these findings, it was recommended to conduct exercise training as part of a cardiac rehabilitation program on HD patients. Generally in considering an exercise training program, a target heart rate is used as an index of the proper exercise loading factor, which is determined by the % HR max method or the Karvonen method. In determining the target heart rate of HD patients, the Karvonen method was proved to be much better than the % HR max method. In HD patients, a strong positive correlation was observed between Ht and r:aximum VO₂ but no significant correlation was observed between the BUN level and either serum Cr level or maximum VO₂. Thus the cause of the marked reduction both in exercise tolerace and in cardiac function in HD patients was considered to be the complication of coronary artery disease, chronic anemia, and early muscular fatigue due to disorder of aerobic metabolism.

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Protein synthetic activities in the liver and muscle of rats with chronic renal failure (CRF) were studied by examining RNA/DNA ratios, polysome profiles and cell-free protein synthetic activities of the isolated polysomes. CRF rats were made by Platt's procedure. The liver and muscle were prepared under the condition of ad-lib feeding or 18-hours starvation. RNA and DNA contents were assayed by Schmidt-Thannhauser's method. Polysome profiles were measured by Steele's mothed. Cell-tree protein and albumin synthetic activities were determined by measuring ³H-leucine incorporation into TCA insoluble protein and immunoprecipitated albumin. In the liver, RNA/DNA ratios, average sizes of free polysomes and cell-free protein synthetic activities were decreased in the CRF rats compared with the controls only in the fed condition. However, in membrane-bound polysome profiles and the ratioe of albumin/ protein synthesis in cell-free system, there was no difference between the CRF rats and the controls. On the contrary, under the fed condition, muscle protein synthetic activities of the CRF rats were nearly equal to the controls, but under the starvation, decreased more remarkkably than those of the controls. These results suggest that the hepatic protein synthetic activity of the CRF rats does not decrease below that of the control rats upon starvation and the abnormality of protein synthesis in the CRF rats might be mainly reflected in muscle.

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In order to clarify the mechanism causing the impaired water excretion in the adrenal insu fficiency, experimentally adrenalectomized New Zealand rabbits were ready for the renal cle glance method, the kidney tissue homogenation method and the isolated tubule microperfusion study. In the adrenalectomized rabbit kidney, there were the remarkable decrease in free water clearance (C_H2O) and C_H2O/C_Osm during acute water load of 3% body weight and decre ase in the corticopapillary osmotic gradient during antidiuresis, and moreover, little responce of these parameters to the administration of f urosemide; suggesting that NaCl transport and free water formation in the ascending limb are extremely suppressed in the adrenalectomized rebbit. This suggestion is favourably supported by the another facts that the transepithelial potential differences (lumen positve) across the isolated medullary thick ascending limb of the adrenalectomized rabbit kidney were remarkably lowered as compared to those of the intact rabbit and restored significantly by the administration of glucocorticoid such as dexamethasone or corticosterone the serosal side. In conclusion, it is suggested that the impaired urinary water excretion in the adrenal insufficiciency is partly due to the impaired free water formation secondary to the intrinsic hypof unction of the ascending limb of Henle.

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