Experimental animal model of human nephrotic syndrome with minimal change group and focal glomerular sclerosis was produced in rats with puromycin aminonucleo-side (AMN), and the renal hemodynamics was investigated. Renal cortical blood flow (CBF) was evaluated with radioisotope-labeled microsphere in rats at 6 days after injection of AMN and compared to those of control rats. In nephrotic rats, serum albumin was significantly diminished and urine protein excretion was increased. Renal water content in outer cortex, inner cortex and medulla increased. Actual increase and redistribution of CBF became significant after calculating with tissue dry weight. Despite of the reduction of renal function, CBF was increased and distributed more to deep cortex. Considering the decrease in glomerular capillary plasma flow rate in AMN rats by micropuncture method reported by Bohrer (1977), these changes suggest that lymphatic drainage of the juxtaglomerular area and/or periglomerular area may increase in AMN rats (Fig. 3). The author suggests the increased lymphatic drainage in AMN rats might be to dysfunction of mesangial transport, which in turn would help to the formation of glomerular sclerosis.

抄録全体を表示

Hematoxylin bodies are considered to be the only pathognomonic feature of systemic lupus erythematosus. In this paper, the ultrastructure of hematoxylin bodies is described in a patient with active lupus glomerulonephritis. For identification of hematoxylin bodies, electron micrographs at low magnification were compared with H & E-stained, Eponembedded sections from the same block. One electron micrograph at low magnification displayed a whole glomerulus. The bodies were then studied under higher magnification. Hematoxylin bodies were usually in and around the mesangial cells or in the monocytes in mesangial areas. The bodies appeared to contain elements of cellular origin, that is aggregates of clumped chromatin, degenerated granules, vesicles and vacuoles. Sometimes they also contained electron-dense substances of the same density as electron-dense deposits in the mesangial and subendothelial areas.

抄録全体を表示

Ninety-four of 994 renal biopsy specimens observed under both light and immunofluorescence microscopes revealed predominant or sole immunoglobulin M (IgM) deposition in glomeruli. These were minimal change nephrotic syndrome (MCNS) in 22, focal glomerular sclerosis (FGS) in 11, mesangial proliferative glomerulonephritis in 21, membranoproliferative glomerulonephritis in 8 and other diseases, but none was not able to be diagnosed using already established definitions of renal diseases. As for MCNS and FGS, IgM deposition was observed in 27 out of 56 (47%) patients with MCNS mainly in mesangial areas and in 11 out of 15 (73%) patients with FGS mainly in mesangial areas in four and mainly in the capillary walls in the other seven patients. Electron microscopic examination per-formed on eight patients with MCNS and IgM deposition disclosed dense mesangial deposits in three patients. Simultaneous deposition of C3c with IgM was found in 18 out of 27 (67%) patients with MCNS and in 7 out of 11 (64%) patients with FGS. However, no statistical difference were present between those with glomerular IgM deposition and those without in MCNS and FGS, concerning resposiveness to steroid treatment, incidence of relapse and outcome of renal function. Six patients with MCNS and IgM deposition had repeat biopsy, which revealed no progression to FGS. From this study it become evident that predominant or sole IgM deposition can be seen in various glomerular diseases and IgM deposition in MCNS or FGS did not predict a poor response or outcome. Thus, we conclude that IgM deposition in glomeruli has no relation to specific glomerular lesions or clinical courses.

抄録全体を表示

We have developed a solid phase direct radioimmunoassay (RIA) for urinary throm-boxane B₂. We raised anti-TXB₂ rabbit antiserum, using TXB₂ conjugated to throglobulin as the immunogen. The antiserum which was diluted 1.5×10⁵ times was used in a solution phase RIA system. ID₅₀ and minimum detectable dose (ID₁₀) were 9 and 1.5 pg/tube, respectively. Dissociation constant (Kd) was 4.1×10^-11 M. The crossreactivities were 0.1% with PGF_2α, 0.06% with PGD₂ and less than 0.01% with other PGs. The antiserum was coupled to polyacrylamide beads to obtain the solid phase antiserum. In the solid phase RIA system, ID₅₀ and ID₁₀ were 11 and 2 pg/tube, respectively. Kd was 2.9×10^-10M. Recovery rates of authentic TXB2 added to a urine sample ranged from 97 to 125% at concentrations of 2 to 125 pg/tube in the direct assay system. The blank value was less than 1 pg/tube. Coefficients of variation for intra and interassay variation were 6.1 and 7.2%, respectively. The values measured by the solid phase direct RIA significantly correlated with those by the solution phase RIA, which required extraction of TXB₂ from urine samples. Utilizing the solid phase direct RIA, urinary excretion rates of TXB₂ were measured in 32 patients with biopsy-proven chronic primary glomerulonephritis. The excretion rates ranged from 73 to 568 pg/min. There was not a definite relationship between the urinary excretion rates of TXB₂ and the histological types of the glomerulonephritis. The direct assay system for urinary TXB₂ that we have developed is simple, time-saving and highly sensitive. Thus, the assay system seems to be useful for clinical applications.

抄録全体を表示

Five patients showing proliferative, exudative lesions, lobulations and subendothelial immune deposits but no marked double contour in glomeruli were studied. They were three males and two females. Ages at onset ranged from 8 months to 61 years. The onsets were abrupt in three patients presenting edema and insidious (chance proteinuria) in the other two patients. The latter two and one of the former initially showed nephrotic syndrome. Histological examinations using light, electron and immunofluorescence microscopes revealed polymorphonuclear cell infiltration and subendothelial immune deposits in glomeruli in all patients but moderate lobulation in only two and mild to moderate double contour in three patients. Their clinical courses were divergent. In one patient with moderate double contour and persistent hypocomplementemia, nephrotic syndrome has continued throughout the follow-up period of 50 months and the glomerular filtration rate reduced to 78 ml/min. The other four patients with mild or absent double contour and non-persistent hypocomplementemia eventually achieved incomplete remission type II and type I in two and disappearance of urinary protein in the other two patients. Renal function was kept at normal levels except for one patients who experienced a relapse and consequent slowly progressive azotemia after 10 year-clinical remission. These results suggest that there are a group of patients with an intermediate form of glomerulonephritis between acute glomerulonephritis and membranoproliferative glomerulonephritis, characterized by proliferative, exudative glomerular changes and subendothelial immune deposits, and that the prognosis could be predictable by the duration of hypocomplementemia and the grade of double contour of glomerular capillary walls.

抄録全体を表示

A 42 year.old woman was admitted to Nagasaki University Hospital with complaint of general edema on Jan, 1970. She had been treated for general edema at a nearby hospital since March 1968. On admission, she was diagnosed as nephrotic syndrome, but her renal function was within normal. After the treatment of steroid and cyclophosphamide, she became the condition of complete remission in Dec. 1971. In July 1980 (8 years and 7 months after complete remission and 6 years and 5 months after termination of steroid therapy), she was readmitted to our hospital with general edema. No predisposing factor was found. At the second admission, she was diagnosed as nephrotic syndrome again, and her renal function was slightly decreased. The lightmicroscopic (LM) findings of renal biopsy specimens at the first admission (Jan. 1970) showed thickening of the glomerular basement membrane (GBM) without cell proliferation. (Electronmicroscopic (EM) findings showed thickening of basementmembrane associated with electron dense deposits and some already lucent deposits in subepithelial areas and completely fused foot processes of epithelial cells.) On the other hand, during the period of complete remission (April 1967), LM findings changed to show almost normal GBM and also EM findings changed to show few small subepithelial electron dense deposits and smooth, but not thickened, glomerular basement membrane. Regeneration of foot processes of epithelial cells was observed. At the time of relapse (OCT. 1980), LM findings showed slight thickening of GBM again and EM findings showed subepithelial electron dense deposits and foot processes of epithelial cells were fused. To sum up, this is a case of membranous glomerulonephritis that showed relapse not only clinically but histologi-cally after a long term of remission.

抄録全体を表示

A 47 year-old man with an acute nephritic syndrome who showed very similar histov pathological findings as dense deposits disease is presented. He was admitted in our hospital on because of edema, hypertension and congestive heart failure. He was treated with diureticus and prazosin Hcl. Edema and congestive heart failure were improved rapidly but hypertension was persisted. Proteinuria and hypocomplementemia were recovered after one month and three months, respectively. This clinical course was compatible with that of the acute glomerulonephritis. First renal biopsy obtained about one month after the onset showed the increase of mesangial cells and matrixes, and of endothelial cells. Marked infiltration of polymorphonuclear leukocytes and narrowing of the capillary lumens were also observed. The glomerular basement membranes showed the segmental "double contour". Electron microscopic studies showed numerous humps on the epithelial side of the glomerular basement membranes, striking changes of circumferential mesangial cell interpositions and electron dense deposits in the lamina densa which were similar to dense deposit disease. Immunofluorescent studies showed the granular depositions of IgG, C₃ and fibrinogen in the mesangium and in the capillary walls. The second biopsy obtained nine months after the onset showed the disappearance of polymorphonuclear leukocytes, the improvement of the mesangial and endothelial changes, and the reopened capillary lumens. Electron microscopic studies showed the disappearance of humps and the decrease of the amount of dense deposits in the lamina densa. Immunofluorescent studies only showed the depositions of fibration.

抄録全体を表示

Ten patients with primary mesangial proliferative glomerulonephritis (Mes PGN) with mild, irregular but distinct thickening of glomerular capillary walls observed by the light microscopy were studied. Silver staining revealed mesangial interposition and spike formation as well as apparent but not severe mesangial proliferation in all patients, but none of them showed lobular formation of glomerular tufts. Mesangial interposition were estimated as circumferential and diffuse similar to membranoproliferative glomerulonephritis (MPGN) type III in two patients, but in the other eight the interposition was only partial, so that the diagnosis of MPGN was considered to be improper for them. Electron microscopic examination, performed in seven patients, revealed mild to moderate deposition of subepithelial, subendothelial and mesangial dense deposits in almost equal severity. However, the immunofluorescence study for immunoglobulins (Ig) and C3 were rather predominant in the capillary wall than in the mesangial area and predominance was found in IgG in seven and in C3 in three patients. Their initial symptoms were acute nephritic syndrome (1), edema (1) and chance proteinuria (8). Their initial urinary protein was rather prominent compared to individual mesangial proliferation. Nephrotic syndrome appeareed in three patients in their clinical course but did not last longer than 6 months. None of them showed persistent hypocomplementemia. During the follow-up period, which ranged from 14 to 121, with a mean of 56 months, only one had fallen into chronic renal failure requiring regular hemodialysis after a 22 year clinical course and seven patients have kept normal renal function of glomerular filtration rate greater than 80 ml/min. Mild to moderate proteinuria has persisted in eight patients but eventually none remained in nephrotic state and proteinuria disappeared in two patients. These results strongly suggest that there exists an intermediate type of glomerulone phritis between MesPGN and MPGN from both clinical and pathological points of view.

抄録全体を表示

Wistar strain rats were given three series of aminonucleoside puromycin (AN) and after 120 days the glomerular lesions of the rats were examined by a light microscope, and also electron-microscopically. The animals were divided into 3 groups : Group 1 was given AN only, group 2 was given 0.25% AgNO₃ and AN, and group 3 (control) was given AgNO₃ only. There was no essencial morphological difference between group 1 and 2, but silver grains on the GBM in group 2 served as a good marker to observe the definite glomerular change in severely involved parts of the glomeruli. As slight changes, detachment of podocytes, denudation of the GBM and adhesion to the Bowman's capsule were observed, even in the small parts of glomeruli which showed no sclerosis. In the glomeruli which showed more widespread adhesion, segmental sclerosis was also seen in these lesions. In more severely injured glomeruli, two or three glomerular capillaries were hardened into a mass and exposed the GBM, and were surrounded by fiocculent material which adhered to the Bowman's capsule . In these lesions, wrinkling or collapse of the GBM was not always seen, and there were foam cells and electron dense material in the capillarv lumen. These findings suggest that the process starting from the damage of podocytes, denudation of the GBM, the adhesion between the capillary and the Bowman's capsule and ending with segmental or global sclerosis is the main process, and that the collapse of the GBM and the increase of mesangal matrix occur incidentally in this experimental model.

抄録全体を表示

To analyze the characteristic of rat renal adrenergic receptor, a radioreceptor assay for catecholamine, using ³H-dihydroergocryptine (³H-DHE), a potent alpha-adrenergic antagonist, and ³H-dihydroalprenolol (³H-DHA), a potent beta-adrenergic antagonist, was performed. Binding of both ³H-DHE and ³H-DHA were rapid and specific. And the pH optimal for binding was 7.5, with substantial decrease at more acid and alkaline pH. The order of potencies for several sympathomimetic drugs in competing for the binding of ³H-DHE to renal microsomal fraction was clonidine>norepinephrine≥epinephrine ≥alprenolol>dopamine >isoproterenol. And the order of potencies for these drugs in competing for the binding of ³H-DHA to the microsomal fraction was isoproterenol>alprenolol>epinephrine>dopamine >>clonidine. The maximal number of binding sites of alpha- and betareceptor was 363 fmol/mg·protein and 72 fmol/mg protein, respectively. The equibrium constant of alpha-and beta receptor was 1.16×10¹²/M and 1.10×10¹²/M, respectively. These results suggest that thee rat renal microsomal fraction contains both alpha- and beta-receptor, and that the order of affinity of the sympathomimetic drugs for renal adrenergic receptor was almost in agreement with their alpha or beta adrenergic potencies.

抄録全体を表示

To investigate the mechanism of hypertriglyceridemia in uremic state, we have determined apoliporotein (apo) C-II and apo E in both serum and lipoproteins in sex or age matched 15 normal controls and in 15 patients on maintenance hemodialysis. Consequently, the following results were summarised. 1) Hypertriglyceridemia was found in the uremic patients while their serum total cholesterol levels remained within normal range. 2) There was a significant positive relationship between serum apo C-II and apo E levels in both normal controls and patients on maintenance hemodialysis. 3) Serum apo C-II levels did not show the significant change between two groups, while serum apo E levels tended to be be low in the patient group. 4) In only uremics, serum triglyceride levels showed a significant positive correlation to serum apo C-II and apo E levels. 5) In the percent distribution of apo C-II in lipoproteins, the patient group had a significant increase in high density lipoproteins and a significant decrease in very low density lipoproteins when compared to those of the control group. Similar alteration in terms of apo E distribution in lipoproteins was observed between two groups accompanied by the additional significant changes such as an increase in low density lipoproteins and a decrease in intermediate density lipoproteins in the natient grnup

抄録全体を表示

Granulomatous glomerulonephritis is a peculiar lesion most characteristically observed in patients with Wegener's granulomatosis. The fully developed lesion was made up of epithelioid cells, giant cells and variable numbers of other inflammatory cells radially arranged around the ramants of a glomerulus. We performed a clinicopathologic study on the kidneys in 24 autopsy cases with Wegener's granulomatosis, and elucidated the incidence and the pathogenesis of granulomatous glomerulonephritis. A pathologic review of the kidneys revealed a significant degree (more than five per cent of all glomeruli) of this granulomatous type of glomerular lesion in eight cases. These cases took a rapid declining course of the disease consistent with the classic description of Wegener's granulomatosis, and six died in uremia. Morphologic examination indicated that existence of a severe glomerular lesion is a necessary condition in the development of granulomatous glomerulonephritis, because granulomatous glomerular lesion was typically seen in company with the widely distributed glomerular lesion represented by thrombotic and necrotic occlusion of capillary tufts and crescent formation. In addition, necrotizing vasculitis in the kidneys was invariably noted in cases with granulomatous glomerulonephritis, especially in small branches of renal arteries and vasa recta. With serial section study of the most typical two cases, it was highly conceivable that granulomatous inflammation originated in hilar arteriolitis extended along the pericapsular space, and developed into diffusely circumferential periglomerular inflammation. In conclusion, the results obtained indicate that two factors seem to act in dispensable parts simultaneously, inside and outside of the glomerulus, in the pathogenesis of granulomatous glomerulonephritis ; the first, thrombotic and necrotic lesion of capillary tuft and, the second, pericapsulitis originated in hilar arteriolitis.

抄録全体を表示

Four illustrative cases are presented of their different degrees or seventies of renoparenchymal or renal pedicle injuries. An immediate excretory urogram and urinalysis have been performed for each patient to identify urinary tract injury. These simple studies resulted in the early diagnosis of renal pedicle injury as well as renal lacerations. The salvage of functioning renal tissue and conservative management of the clinically stable patient often provide a good result. Unnecessary harvest of surgical complications or loss of working renal tissue should be evaded. However, immediate surgery was indispensable in a patient with renal pedicle injury and another patient with major renal laceration such as a shattered kidney. Reparative procedures involved a drainage at perirenal injured region and a diverculectomy of renal calices due to renal injury. A case of pedicle injury and a patient with shatted kidney resulted in respective nephrectomy. All of these 4 patients survived with no serious complications on follow-up. Some advantages, disadvantages or limitations of surgical treatment in renal trauma are discussed in this report.

抄録全体を表示