The pathogenetic mechanism of development of experimental autologous glomerulonephritis of rats induced by immunization with homologous renal antigen, glomerular and tubular component, has been investigated by means of light, immunofluorescent and electron microscopy. 1) In comparison with nephritogenisity, higher grade of renal damage is induced by a tubular antigen than glomerular one. 2) Marked difference in histological and immunological feature of the glomerular lesions is observed by the two kinds of antigen. 3) In the group immunized with tubular antigen, non-prolif erative diffuse membranous glomerulone-phritis is produced. Number of electron opaque deposits are found along the subepithelial aspects of glomerular basement membrane, and r-globulin of the host are present in granular deposits. As a result, glomerular lesin of this group is similar to those of experimental glomerulonephritis induced by circulating non-glomerular antigen-antibody complexes. 4) In comparison with the above-mentioned group, diffuse proliferative or diffuse proliferative and membranous glomerulonephritis is produced in the group immunized with glomerular antigen. From the immunohistological aspect, glomerular lesion is not clearly descriptive. However, linear or linear-granular basement membrane is, in general, indicated. 5) The study of passive transfer of both experimental glomerulonephritis to the normal rat is also carried out. The characteristic find appears to be that r-globulin is observed to localize in glomeruli of recipient rat injected with r-globulin of the immunized rat with glomerular antigen.

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Glucocorticoid treatment for 8 weeks in nephrotoxic nephritis rats produced exudative lesions in renal lomeruli. Such lesions were more prominent than those of animals treated with glucocorticoid or anti-kidney serum alone. It appeared that these exudative lesions had no relation to the presence of glycosuria or hyperglycemia. Glomerulonephritis were observed light microscopically both in animals treated with anti-kidney serum and glucocorticoid, and anti-kidney serum alone, but it was markedly less severe in former group. The concentration of phospholipids, total cholestdrol, and particularly triglycerides in plasma rose up to abnormal high level. It was markedly higher in animals treated with anti-kidney serum and glucocorM ticoid than in those treated with glucocorticoid alone. Although the development mechanism of the exudative lesions are not yet well clarified, it was sug-gested that the exudative lesions in rats may be due to an increased mobilization of plasma lipids and that the acceleration of blood coagulation process may occurs as a secondary phenomen.

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Some influences to immunological reactivity of chronic uremic patients have attracted attension since kidney homotransplantation has become to be used for the treatment of chronic uremia, but it was not defined exactly. The auther attempted to clarify the immunological reactivity of uremic patients by the statistical observations of the responsibility in tuberculin reaction and the appearance rate of blastoid-cell in peripheral leukocyte cultures with phytohaemagglutinin (PHA). The results were obtained as follows ;(1) The responsibility in tuberculin reaction of uremic patients seemed to be lower than that of control subjects.(2) The decrease of tuberculin reaction in uremic patients did not correlated with lymphocytopenia, nor hypo-r-globulinaemia, although it seemed to be slightly correlated with metabolic acidosis.(3) The reactivity of peripheral lymphocytes to PHA in uremic patients was lower than that from control subjects, (4) The decreased reactivity of uremic lymphocytes to PHA was not only restored, but became rather excessive, after the peritoneal dialysis or the haemodialysis.(5) Uremic peripheral lymphocytes improved their reactivity to PHA when they were culturad with normal plasma.(6) Normal peripheral lymphocytes decreased their reactivity to PHA when they were cultured with uremic plasma.(7) The degree of impairement of uremic lymphocytes to PHA seemed to slightly correlated with the level of serum non-protein-nitrogen (NPN) or serum inorganic phospholus, but not with serum-r-globulin concentration, peripheral lymphocyte counts and their reactivity in tuberculin reaction. These results indicated that the cellular immunity was suppressed in uremic patients, and it was -refered to the impairement of reactivity of peripheral lymphocytes. These alternations seemed to be resulted from the suppressive effect of some dialysable substances in uremic plasma. Therefor it was nessessary to consider these results in discussion about lmyphocyte transfer test and Mdonor-recipient lymphocyte mixed culture prepared in tissue typing test for kidney homotransplantation. Further exact characterization of such suppressive materials in uremic plasma might offer a significant suggestion to the fundamental mechanism of uremia.

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In the previous papers of the study it was reported that the estimation of serum antibody response against enterobacterial common antigen is of great value for the diagnosis of chronic pyelonephritis and. that the elevation of common antibody persists longer than that of the antibody against the somatic (O) antigens of infecting organisms. Therefore, attempts were made in this study to determine why the difference between common and. O antibody response occurs. Common and O antigens were separated by ethanol from the supernates of the strains of various species and sero-groups of enteric bacteria according to the technique of Suzuki and others, and were injectedd intravenously to the rabbits solely or in various combinations of the antigens and with various intervals of immunization. The results were as follows: (1) The ethanol-soluble fraction is rich in common antigen and highly immunogenic in the rabbit for the production of common antibody, while the ethanol-insoluble fraction is rich in O antigen and immuno genie for the production of O antibody. (2) The antibody response of rabbits immunized with a single injection of ethanol-soluble or -insoluble fraction from various enteric bacteria showed similar magnitude of titer throughout the observed course. Hence, it is suggested that the difference between common and 0 antibody response in the clinical cases of chronic pyelonephritis is not due to the difference in the antigenicity itself of common and O antigens. (3) Highest and longest elevation of the common antibody response was obtained by repeated injection of ethanol-soluble fraction at ten-day intervals. The antibody response did not differ whether the same: fraction or fractions from various species and sero-groups were used at each injection. (4) Common antibody response was markedly reduced when the soluble and insoluble fractions were given intravenously in the from of mixture, but was not reduced when they were injected simultaneously but separately from different veins. These results suggest that the insoluble fraction has an inhibiting effect on the common antibody response. This inhibition may be a cause of the delayed elevation of common antibody response in the clinical cases of choronic pyelonephritis. (5) From these observations it was assumed that in chronic pyelonephritis, whether it is caused by the recrudescence or reinfection by the enteric Bacteria of the same strain or of different sero-types or species, the common antigen will always act as the indentical stimuli, resulting in the persistent elevation of the common antibody response.

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Whole complement levels (C' H 50) and immune adherence levels (I. A.) in serum were estimated by the method of Mayer and Nishioka respectively. Subjects, mostly in adult age, were 31 patients with nephrotic syndrome and 49 with other renal disorders.(1) Positive correlation was obtained between C' H 50 and I. A. in cases with glomerulonephritis, nephrotic syndrome and lupus nephritis.(2) On Glomerulonephritis Cases (a) In cases with acute glomerulonephritis, C' H 50 returned to normal in 3 weeks from the onset in accordance with the clinical improvement. (b) In case with subacute nephritis, decrease of C' H 50 was observed over 2 months after admissiom, being paralleled with prolonged and stormy course of the disease. (c) In cases with chronic glomerulonephritis which were in latent or terminal stage, C' H 50 was always normal during our observation and remained normal at the time of acute exacerbation and even after tonsillectomy. However it fell markedly after renal transnplantation.(3) On other Renal Diseases (a) In cases with lupus nephritis, changes in C' H 50 were influenced not only by the renal lesion but general pathological activity of SLE. Low level was characteristic in patient of long duration. (b) C' H 50 level was not low in cases with diabetic nephropathy, pyelonephritis and orthostatic proteinuria.(4) On Nephrotic Syndrome (a) Low C' H 50 was observed in nephrotic stage, but not in the stage of remission and terminal stage. (b) Low C' H 50 was observed, mosly in patients whose biopsies showed proliferative glomerulone-phritis or proliferative and membranous glomerulonephritis, and whose duration after the onset was within about a year, but in patients whose biopsies showed membranous glomerulonephritis, low C' H 50 was not observed. (c) The course of C' H 50 was varied and it was characteristic feature. At the time of relapses, C' H 50 levels were decreased or did not change. (b) After the initiation of therapy with steroids and/or 6 MP, cases with low C' H 50 turned to show normal value if the therapy was effective. Whereas among cases with normal C' H 50 before treat-ment, C' H 50 did not change in non-effective as well as effective cases.

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The effect of increased renal vein pressure on the renal hemodynamics was studied in intact-, con-stant-pressure perfused- and constant-flow perfused ki.dneks of rabbits. Pressure-flow and clearance measurements were made in the kidney. Average medullary transit time was also measured with a th.ermodilution technique. Renal vascular resistances were calculated from the data obtained. Renal deep vein pressure was almost equal to intrarenal pressure measured w:th a needle technique. Renal blood flow, calculated from values of CAH, EAH and hematocrit was lower than the directly measured renal venous outflow during a large elevation of renal vein pressure. In the intact kidney preparation, renal venous outflow and Ccr d.d not significantly change until the renal arterio-venous pressure d::fference was decreased to 80 mmHg by a partial constriction of the renal vein. With progressively decreased arterio-venous pressure difference below 80 mmHg, renal venous outflow and Ccr decreased markedly. Both prevenous and venous vascular resistance decreased as renal vein pressure increased. EPAH was not significantly affected by renal vein pressure elevation. Average medullary transit t'me prolonged with a progressive increase of renal vein pressure. Denervation of the renal nerve did not qualitatively modify the above-described changes observed in the innervated intact kidney. Results obtained in the constant-pressure perfused kidney were similar to those in the intact kidney preparation. In the constant-flow perfused kidney, prevenous vascular resistance increased slightly with renal vein pressure elevation. Venous vascular resistance did not significantly change. Ccr and EPATI remained relatively constant through a wide range of renal vein pressure. These findings indicate that alterations in renal vascular resistances following increased renal vein pressure are different depending upon perfusion techniques, and that circulatory changes in intrarenal arterio-venous communications do not participate in changes in renal vascular resistance during renal vein pressure elevation.

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