After administration of Habu snake venom (0.5 mg/Kg of body wt), carbon black suspension, 150 mg/Kg of body wt, was injected into rabbits. Open renal biopsy and/or nephrectomy were performed at intervals from 4 hours to 14 days after the injection of carbon black suspension. The specimens were studied by light and electron microscopy. The results were as follows. Many aggregated carbon particles within the glomerular capillary lumina were found in the widened subendothelial space of capillary loops, endothelial fenestrae close to the portion of glomerular tufts and adjacent mesangial matrix in normal and hypercellular areas at 4 hours after carbon loading. By this time, many carbon particles were phagocytosed by normal and degenerative mesangial cells, which were found in the areas showing normal cellularity, and were enclosed in the vacuoles with a single limiting membrane. At 24 hours and later after carbon loading the relative concentration of carbon particles in the mesangium of normal cellularity was reduced in the experimental animals as well as in the control ones. Increase of carbon particles within :mononuclear cells in the glomerular lesions showing focal and segmental hypercellularity, however, were demonstrated from 24 hours to one week after carbon loading. The cells in hypercellular glomerular lesions were active mesangial cells, which contained either a few or many carbon particles, up to one week after the administration of Habu snake venom. In addition, macrophages with many carbon particles were frequently observed in these hypercellular areas. However, two weeks and later after the adminis-tration of the venom, the hypercellular glomerular lesions consisted only of active mesangial cells with many carbon particles. Many carbon particles within the peritubular capillary lumina were observed in the widened endothelial cellular spaces as well as in the adjacent interstitium. Thereafter these carbon particles were phagocytosed by fibroblasts and macrophages in the interstitium. Carbon particles were also demonstrated in the lacis cells and smooth muscle cells of juxtaglomerular apparatus at 24 hours and later after carbon loading.

抄録全体を表示

The patient was a 37-years-old housewife with no history of nephritis. In September 1979, ten days after the onset of tonsillitis, edema of the eyelids and fingers, together with oliguria, appeared. At the time of admission to our hospital, the patient showed marked depression of serum complement (CH50), urinary protein 3.0 g/day, T. P. 5.4, a large number of erythrocytes in the urine, and ASO, ASK, anti NADase were WNL. In the initial renal biopsy, performed 27 days after the initial onset of the disease, histological findings were that of typical acute glomerulonephritis, and in the fluorescent microscopy, deposition of C3 in granular form along GBM was observed, with IgG and IgA demons-trating granular and weakly interrupted linear deposition. Approximately two years later, in December 1981, the patient was re-admitted to the hospital with the complaint of fatigue and aggravated proteinuria/hematuria. In the second renal biopsy which was performed 27 months after the onset of the disease, the findings consisted of mild mesangial prolife-rative GN. By fluorescent microscopy, IgG, IgA and C3 were stained in a mesangial pat-tern, with IgA becoming dominant in the staining, thus the patient was diagnosed as having IgA nephropathy. In this case, it was evident that acute non-poststreptococcal glomerulonephritis turned chronic in the form of IgA nephopathy. This is a valuable clinical case, as we have been able to confirm the course of the disease by the kidney biopsy over a time interval.

抄録全体を表示

In order to study the role of renal glomerular tissue thromboplastin (TTP) on intra-glomerular coagulation in Masugi Nephritis and liquoid-induced DIC, the relation between TTP activity of isolated glomeruli and histological intraglomerular coagulation was exa-mined in rats. TTP activity of isolated glomeruli was assayed by modified Astrup's method. The following results were obtained. (1)The method of TTP activity assay with isolated glomeruli was proved to be useful for quantitative analysis for TTP activity of renal glomeruli. (2)Renal glomeruli had high TTP activity as in lung and brain, and TTP activity of renal cortex was moderate whereas that of medulla was the lowest. These findings may explain the hypercoagulability in glomeruli. (3)The release of TTP from isolated glomeruli increased in Masugi Nephritis and liquoid-induced DIC. This increase of TTP release was papalleled to the development of histological intraglomerular coagulation in both cases. (4)In liquoid-induced DIC, the increase of glomerular TTP activity was reduced by premedication of rats with cycloheximide. (5)In Masugi Nephritis and liquoid-induced DIC, the TTP release from isolated glo-meruli in vitro shows energy-dependency : temperature-sensitive and metabolic inhibitors (2-deoxyglucose, 2, 4-dinitrophenol) -sensitive. (6)In both Masugi Nephritis and liquoid-induced DIC, administration of cortisol and ouabain at therapeutic doses depressed the increase of TTP release from isolated glomeruli. Especially, ouabain depressed TTP release markedly and gave histological improvement of intraglomerular coagulation. These observations may give an account for the potential of ouabain in clinical practice in DIC.

抄録全体を表示

In order to evaluate the effect of RES blockers on the clearing function of mesangium, suspension of colloidal carbon was injected intravenously to female ICR mice, which were divided into three groups according to the previously administered RES blockers. The group I received carbon injections alone, while group II and III, prior to carbon injections, were treated with injections of carrageenan and dextran sulfate respectively. Following carbon injections, the disappearance rate of carbon from the circulation, as well as chro-nological changes in intraglomerular localizations of carbon particles, was estimated in all three groups. Despite a significant delay in disappearance of intravascular carbon in both groups treated with the RES blockers (group II and III), the mesangial depositions of carbon particles in these groups were reduced in comparison with those in control animals (group I). Observations by electron microscopy revealed a marked increase of carbon-phagocytizing mononuclear cells in glomeruli two days after carbon injections, particularly in animals treated with dextran sulfate (group III). Such mononuclear cells were also found in peripheral blood samples, but with much less frequency than those in glomeruli. Therefore, it seems likely that peak amount of intraglomerular carbon particles, obtained two days following the injections in animals of group III, may reflect mobilized mononuclear phagocytes, rather than carbon-phagocytizing mesangial cells per se. The above findings indicate that RES blockers may have suppressed the mesangial uptake of carbon particles and that infiltrating mononuclear cells in glomeruli may contribute to salvaging of foreign substances. It is also suggested that dextran sulfate may have activated such a salvaging function of mononuclear cells.

抄録全体を表示

Three cases of idiopathic MN, 2 of MPGN and 3 of LN were demonstrated IgG de-posits along glomerular capillary walls in granular pattern and were dissociated after incubation with human γ-globulin. Furthermore, the dissociation of IgG in glomeruli was observed following incubation with plasmin-treated, PEG-treated, sulfonated kuman γ-globulin and Fc fragment, but not with pepsin-treated human γ-globulin, indicating that Fc fragment may play an important role for the dissociation. These results suggest that immune complexes in the glomeruli consist of the patient's own denatured IgG and IgG-RF. On the basis of these findings, all of the patients were treated with large intravenous dose of plasmin-treated γ-globulin (5g/day, 610 times). In all patients the urine protein and/or hematuria rematuria remarkedly decreased or disappeared within 7 days to 40 days. During 60 to 90 days of observation all patients with these renal diseases could be main-tained in improved status from nephrotic syndrome. No untoward effects of γ-globulin therapy were observed. Thus, administration of high-dose intravenous γ-globulin is useful treatment for MN, LN and MPGN.

抄録全体を表示

In order to find whether the electrophoretic patternes of urine proteins had any rela-tion to clinical and histopathological classifications of various renal diseases, sodium dodecyl sulfate polyacrylamide 4-30% gradient gel electrophoresis (SDS-PAGE) was carried out using SDS and 2-mercaptoethanol on the urine of 6 healthy subjects and 100 patients. Urine proteins were classified into five zones according to their molecular weight (MW). They were high MW (HMW), middle MW (MMW), moderately low MW (MLMW), low MW (LMW) and very low MW (VLMW). A nearly equal distribution from HMW to LMW was found in normal subjects and in minimal change of chronic glomerulonephritis. Predominant MMW was found in minimal change nephrotic patients. Though the histological findings revealed minimal change, the appearance of LMW and VLMW as well as MMW suggested the possibility of focal glomerulosclerosis. A wide range of excretion from HMW to VLMW, especially high density of VLMW was found in chronic renal failure and crescentic glomerulonephritis with normal serum creatinine level. Characteristic patterns were also found in renal tubular acidosis and multiple myeloma. It was found that the SDS-PAGE patterns of urine proteins had a good correlation with clinical and histopathological classifications in some renal diseases.

抄録全体を表示

To investigate the possible mechanism of abnormal VLDL-IDL retension in uremia, we have determined serum levels of VLDL and IDL, and postheparin lipolytic activity (PHLA), lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) activity, in seven normal controls and in eight patients on maintenance hemodialysis. Consequently, the results were as follows. 1) Patient group had a significant increase in VLDL (p<0.02) and IDL (p<0.01) levels, and a significant decrease in VLDL/IDL ratio (p<0.01) when compared to the respective parameters of control group. 2) With respect to the percent chemical composition of VLDL and TUL, patient group had a significant increase in protein, total cholesterol (p<0.02, respectively) and a significant decrease in triglycerides (p<0.02) as compared with those of control group, while no significant changes in IDL chemical composition between two groups were observed. 3) PHLA showed a significant lower level (p<0.01) in patients than in controls. The decrease was due to a specific reduction of H-TGL activity in the patient group. These results suggest that an increase in the VLDL and IDL, particularly IDL, of patients on maintenance hemodialysis may be due to a selective deficiency of H-TGL activity.

抄録全体を表示

The patients aged 32-71 years on long-term hemodialysis were investigated to evaluate the effect of a polyunsaturated fat enriched diet on serum very low density lipoprotein (VLDL) levels, and its chemical and apoprotein compositions as well as postheparin lipoly-tic activity, lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) activity. The base line diet (diet I) comprised 13% protein, 58% carbohydrate, 29% fat and 250-350 mg cholesterol and its polyunsaturated/saturated (p/s) ratio was 0.7. Diet II and diet III were identical to diet I, except that their p/s ratio were 1.5 and 2.5, respectively. Eeah diet was given to the patients for a month, respectively. Consequently, serum triglyceride and VLDL levels were significantly lowered, and serum total cholesterol and high density lipoprotein-cholesterol tended to be lowered as the p/s ratio increased, while there was no significant change in the activity of LPL and H-TGL or in the apoprotein composition of VLDL. These yfindings suggest that the polyunsaturated fat enriched diet may decelerate VLDL synthesis in the liver of patients on maintenance hemodialysis.

抄録全体を表示

The present study was designed to determine the sex difference in the renin-aldos-terone system. Basal plasma renin activity (PRA) and plasma aldosterone cocentration (PAC) were slightly higher for the males than those for the females in the elderly sub-jects as well as in the younger subjects, and the ratio of PAC response to PRA response by furosemide injection, however, was larger for the females than for the males in the both age group. Female subjects who were administrated testosterone or anabolic steroid showed slightly high PRA and low PAC, although not statistically significant. Cryoactivation of PRA were larger in the females than in the males. While PRA was not correlated with PAC, cryoactivated renin activity (CAR) was significantly (P<0.05) cor-related with PAC in the males. These results strongly suggest sex difference in the renin-aldosterone system, and raise the possibility that male hormone as well as female hormone may be related to the sex difference. It must be considered that renin value determined as PRA at present does not correlate with CAR and PAC, or does not reflect endogenous renin action, in cetain cases.

抄録全体を表示

A 19 year old student presented with syncope and convulsion developed a few hours after he took marathon running under hot weather. He also complained of generalized muscle aching. On examination, he was dehydrated and hypotensive. Serum GOT, GPT and LDH were markedly elevated. Myoglobin in urine was 41 ng/ml. He developed acute renal failure and hemodialysis was performed. Renal biopsy done on 57th day showed intact glomerulus. It was considered that aggresive exercise performed under hot environment led to acute rhabdomyolysis and subsequent acute renal failure in the present case.

抄録全体を表示

A peculiar case of Rendu-Osler's disease associated with a giant hematoma in the mesocolon and renovascular hypertension caused by idiopathic renal artery thrombosis is reported. A 38-year-old woman was admitted for further examination of long lasting hypertension. At the night admitted, she suddenly developed a severe abdominal pain and mass formation in the right hypochondrium. Abdominal hematoma was suspected because of decrease in hemoglobin concentration. Rendu-Osler's disease was diagnosed because of her facial spotty telangiectasia, recur-rent epistaxis and family history of hemorrhagic diathesis. Renovascular hypertension was suspected by high plasma renin activity and blood pressure reduction by angiotensin II antagonist and confirmed by renal arteriogram. Hematoma in the mesocolon was removed surgically and hypertension was cured by renal autotransplantation. Renal arterial thrombosis was confirmed at the operation. Laboratory tests of blood coagulation shows prolonged secondary bleeding time and decreased platelet adhesiveness. Rumpel-Leede was positive. Her nephew also had abnormalities in coagulation. Causes of renalartery throm-bosis are unknown.

抄録全体を表示

Prokallikrein in the kidney was partially purified with immunoaffinity and DEAE Sephadex A-50 column chromatographies and its biochemical properties were studied in comparison to three active glandular kallikreins purified from kidney, serum and urine of the rat. The properties of the enzymes obtained by trypsin and α-chymotrypsin activation of prokallikrein were identical with those of active glandular kallikreins from kidney, serum and urine of the rat. Apparent molecular weights of prokallikrein, trypsin-activated kal-likrein, α-chymotrypsin-activated kallikrein, active renal kallikrein and glandular kallikrein in rat serum were 38, 000 and that of active urinary kallikrein was 37, 000. Prokallikrein fraction was activated by trypsin and α-chymotrypsin. But, it was not activated by acidification, kaolin-activated rat serum, plasmin, thrombin, urokinase, rat urinary esterase A, carboxypeptidase B, cathepsin D, elastase, papain and pepsin treatment. Renal kallikrein, purified in the presence of soybean trypsin inhibitor (SBTI), contained 85% prokallikrein, but the enzymatic fraction, purified in the absence of SBTI, contained 23% prokallikrein. Prokallikrein contents of urinary kallikrein and glanddular kallikrein in rat serum were 16% and 20% respectively. These results suggests that prokallikrein is produced in the kidney, exists in the membrane fraction and is activated easily by trypsin-like or chymotrypsin-like enzymes. Prokallikrein activator exists in the kidney tissue, and not in the serum. Since rat serum contained active glandular kallikrein, a part of which may come from kidney, renal kallikrein may play an important role not only to control renal circulation, but also to control the systemic blood pressure.

抄録全体を表示