[Superantigen-related nephritis(SARN)].
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Biomedical subjects
Publications and source records attributed to A Koyama.
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A case in which the enterotoxins of Staphylococcus aureus may have served as bacterial superantigens is presented. This 71-year-old man developed proteinuria and renal dysfunction after contacting pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), coagulase type II. The infection occurred after surgery for recurrent lung cancer. Staphylococcus enterotoxins B, C, and TSST-1 were detected from the bacillus. Ten days after the onset of pneumonia, proteinuria was noted; urinary protein was as high as 1.8 g/day. The serum creatinine was elevated from 1.0 mg/dl to 3.7 mg/dl. Several immunological reactions were detected; the serum levels of IgG and IgA were increased, and the selective usage of T-cell receptor V beta (TCRV beta) was observed. Serum levels of IL-1 beta, IL-2, IL-6, IL-8, IL-12, and tumor necrosis factor alpha (TNF alpha) were also elevated. Examination of the renal biopsy specimen by light microscopy showed minor to mild mesangial proliferative glomerulonephritis. Immunofluorescence microscopy demonstrated the deposition of IgG, IgA, and C3, mainly along the capillary walls. Electron microscopy revealed electron dense deposits, mainly in the subepithelial areas, and injury to the glomerular basement membrane. When the pneumonia improved following antibiotic therapy, the renal function also improved, and proteinuria decreased. The levels of immunoglobulins and the usage of TCRV beta also decreased. Because staphylococcus enterotoxins act as superantigens, we believe this to be a typical case of superantigen-related glomerulonephritis.
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The present study aimed to determine whether vasoconstriction in active calf occurring during combined exercise diminished or persisted when added low- and high-intensity elbow flexion exercise ceased and single leg exercise continued. Six active women (mean age, 21.2 years) participated in this study. During 10-min plantar flexion exercise at 10% of maximum voluntary contraction (MVC), elbow flexion exercise at 10% MVC was added over the 3rd and 4th min. Calf blood flow did not change significantly upon superimposition and cessation of this elbow flexion exercise. However, when elbow flexion exercise at 50% MVC was added during the 7th and 8th min, calf blood flow above the resting value (2.23 +/- 0.23 mL 100 mL-1 min-1) decreased significantly (P < 0.05) from 6.72 +/- 0.87 (6th min) to 5.14 +/- 1.36 mL 100 mL-1 min-1 after 2 min of combined exercise and was accompanied by a similar change in the non-exercising calf blood flow value. The vascular conductance of the exercising calf decreased significantly (P < 0.01) from 6.48 +/- 1.08 (6th min) to 3.11 +/- 1.27 mL 100 mL-1 min-1 mmHg-1 at the end of the 2nd min of combined plantar flexion exercise with elbow flexion exercise at 50% MVC. After elbow flexion exercise at 50% MVC was discontinued and plantar flexion exercise at 10% MVC alone was performed, the vascular conductance in the exercising calf remained significantly low for the next 2 min. These results indicate that the vasoconstriction induced by adding high-intensity arm exercise is persistent, suggesting a major contribution of metabo-receptor-mediated vasoconstriction rather than central command- and mechano-receptor-mediated vasoconstriction.
We report a case of renovascular hypertension associated with neurofibromatosis complicated by moderate proteinuria. A 16-year-old female was admitted to Kensei General Hospital with a complaint of headache and a blood pressure of 230/120 mm Hg. She was referred to us for further evaluation of the hypertension. On examination, cafe-au-lait spots were seen over her extremities and flank, and a bruit was heard in the right upper abdomen. The urinary protein excretion was 2.1 g/day. The plasma renin activity (PRA) and plasma aldosterone concentration were high, but the levels of catecholamines were normal. The renogram was asymmetric and on venous sampling, the PRA in the right renal vein was 58.3 ng/ml/h and that in the left was 22.1 ng/ml/h. CT scan detected an approximately 10-mm mass in the proximal right renal artery. Arteriography disclosed severe stenosis in the right renal artery and the superior mesenteric artery. Therefore, we concluded that her hypertension resulted from stenosis of the right renal artery due to neurofibromatosis. Accordingly, she underwent an operation to reconstruct that artery. After the operation, her blood pressure and PRA normalized without administration of any anti-hypertensive drug and urinary protein disappeared.
This study investigated the peroxidative state of renal failure by measuring lipid peroxidation. The generation of lipid peroxides by rat hepatic microsomes was compared between experimental renal failure caused by 7/8 nephrectomy and healthy control animals. The concentrations of BUN at the point of sacrifice were 84.2 +/- 18.4 (mean +/- SD) in nephrectomized and 19.8 +/- 4.3 mg/dl in the control group (p < 0.01, n = 5). Microsomal generation of thiobarbituric acid reactive substance was 31.2 +/- 2.8 in the nephrectomized group and 20.9 +/- 4.9 nmol/incubation/min in the control group. There was a significant difference between the groups (p < 0.01, n = 5). In summary, the generation rate of lipid peroxides in the microsomes obtained from the rats with experimental renal failure was significantly higher than the control. This study confirms an increased peroxidative state, and specifies one of the sites of increased lipid peroxide generation in renal failure.
This study aims to raise the possibility of methylguanidine, a peroxidative product of creatinine, as a measure of the peroxidative state. As a known standard, we measured the inhibitory effect of uremic serum on the NADPH-dependent microsomal lipid peroxidation. This is an established method for evaluating the peroxidative state and is compared to the effect of uremic serum on methylguanidine synthesis. The study shows decreased serum antioxidant activity in hemodialysis patients by both methods, though there is no correlation between them. These results support the use of methylguanidine as a peroxidative marker and suggest a difference in the reactive oxygen species involved in the reactions of methylguanidine synthesis and microsomal lipid peroxidation.
Synthesis of guanidinosuccinic acid (GSA), a uremic toxin, has been suggested to relate to the urea concentration and synthetic rate. Among the urea cycle enzymes, inhibition of argininosuccinate (ASA) lyase by urea has been reported. Argininosuccinate which contains a GSA structure is a candidate of a GSA precursor. We found that another uremic toxin, methylguanidine, is formed from creatinine with reactive oxygen species. Therefore, we investigated in vitro whether GSA is formed from ASA with reactive oxygen species. GSA was measured by HPLC by a post-column-labeling method using 9,10-phenathrequinone. When 1 mmol/l ASA was reacted with the hydroxyl radical-generating system for 5 min at pH 7.4, 9 mumol/l GSA was formed. Dimethylsulfoxide, a hydroxyl radical scavenger, markedly inhibited GSA synthesis. The superoxide radical generated by xanthine and xanthine oxidase reaction also formed 1 mumol/l GSA from 1 mumol/l ASA and the GSA formation was inhibited by superoxide dismutase or catalase almost completely. Addition of FeCl2 to the xanthine/xanthine oxidase reaction further increased GSA synthesis. These results indicate that GSA is formed from ASA by reaction with the hydroxyl radical and the superoxide radical.
The synthesis of guanidinosuccinic acid (GSA) increases in uremics, and GSA is implicated as a uremic toxin. The GSA synthesis increases roughly in proportion to the serum urea level that increases in patients with renal failure. Urea is a specific inhibitor of argininosuccinase, the fourth urea cycle enzyme, and might lead to the increase of argininosuccinate (ASA). We found that GSA is formed from ASA by reactive oxygen species in vitro. In this paper, we investigated GSA synthesis from ASA in isolated rat hepatocytes and the effect of reactive oxygen species on this synthesis. When isolated rat hepatocytes were incubated with 5 mmol/l ASA, GSA was formed linearly with time up to 6 h (16 nmol/g wet liver/6 h). GSA was formed depending on the ASA concentration up to 10 mmol/l. Dimethylsulfoxide, a hydroxyl radical scavenger, inhibited GSA synthesis by 65%. GSA was actively formed when the hepatocytes were incubated with 32 mmol/l urea. The GSA formation in the presence of urea was also inhibited by dimethylsulfoxide, although the inhibition was less marked. FeCl2, that increases the hydroxyl radical generation, increased GSA synthesis. These results indicate that GSA is formed from ASA in isolated hepatocytes. The results also suggest that reactive oxygen species are important for GSA synthesis in the cells.
Outline of selected ones among a number of nationwide surveys related to health and welfare services (90 surveys as of 1995) conducted mainly by the Ministry of Health and Welfare periodically in Japan is described. That is, history, purpose, coverage, date, contents, data collection procedure, tabulation and publication were explained in regard to : (1) Population Census, (2) Vital Statistics, (3) Patient Survey, (4) Infectious Disease Surveillance System, (5) Comprehensive Survey of Living Conditions of People on Health and Welfare, (6) Census on Medical Care Institutions, (7) Hospital Report, (8) Survey on Physicians, Dentists and Pharmacists, (9) Statistical Report on Public Health Administration Services, (10) Survey on Social Welfare Institutions, and (11) National Nutrition Survey. On-line data service system of the Ministry of Health and Welfare is also briefly mentioned.
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Between January 1, 1983 and December 31, 1992, 805 patients with asymptomatic proteinuria and/or hematuria were selected in the mass screening of 56,269 adults. We conducted prospective long-term follow-up studies of these patients and evaluated their clinical findings and renal histology. They were divided into three groups according to the first dipstick urinalysis findings: 478 patients with pure hematuria (H), 150 patients with concomitant hematuria and proteinuria (H & P), and 177 patients with proteinuria (P). The mean follow-up period was 5.80 +/- 4.42 years. Of the 478 patients with H, a specific cause of hematuria was found in 46 (9.6%), the remaining 432 (90.4%) patients were diagnosed as having asymptomatic hematuria (ASH). During the follow-up period, in the ASH patients, hematuria disappeared in 44.2%, 43.7% had persistent microhematuria without proteinuria, and 10.6% manifested proteinuria, none of the patients showed renal insufficiency. Of the 150 patients with H & P, 134 were diagnosed as having asymptomatic H & P. During the follow-up period, the hematuria and proteinuria disappeared in 16.4% of these patients, the proteinuria disappeared in 8.2%, and 14.9% of the patients showed renal insufficiency. Of the 177 patients with P, 151 were diagnosed has having asymptomatic P. During the follow-up period, proteinuria disappeared in 23.2%, and 10.6% showed renal insufficiency. Renal biopsy was performed in 151 patients in the study population who had a moderate degree of proteinuria; 68.2% of these patients had IgA nephropathy, 12.6% had non-IgA mesangial proliferative GN, 6.0% had membranous nephropathy, 5.3% had minimal change, and 2.6% had focal and segmental glomerular sclerosis. This study of the mass screening of urinalysis in asymptomatic adults showed that although the patients with pure hematuria did not exhibit renal insufficiency, 10.6% of these patients were proteinuric during the follow-up period. Therefore, careful observation and management are needed in these patients.
We assessed anatomical findings and language defects in 14 right handed patients who had fluent aphasia following left frontal lobe lesion. From the onset of aphasia all of the patients showed fluent speech and excellent repetition but difficulty in word finding and impairment in language comprehension. We administered to all of the patients the Western Aphasia Battery, a 50-item pointing task using line drawings representing single words selected from among common Japanese words for language training for aphasics, and the Token Test. Anatomical analysis was performed using brain CT and/or MRI. The patients were divided into three groups on the basis of the extent of impairment in comprehension of single words: one group showed no impairment, another showed slight impairment and the other showed severe impairment. The lesion site differed among the groups. Each group had a different lesion site. We concluded the following: first, lesions in Brodmann's areas 6 and 9 produce impairment in comprehension of single words, with lesions extending to anterior to Broca's area producing more impairment than those without the extending lesions. Second, lesions in the frontal lobe produce impairment in comprehension of complex sentences.
We report 10 cases of glomerulonephritis following methicillin-resistant Staphylococcus aureus (MRSA) infection. The clinical features of this syndrome were an abrupt or insidious onset of rapidly progressive glomerulonephritis (RPGN) with nephrotic syndrome and occasionally purpura, following MRSA infection. The renal histologic findings showed a variety of types of proliferative glomerulonephritis with varying degrees of crescent formation; immunofluorescence revealed of glomerular deposition of IgA, IgG, and C3. Laboratory findings showed polyclonal increases of serum IgA and IgG, with high levels of circulating immune complexes (ICs). Increased numbers of DR+CD4+, and DR+CD8+T cells were observed in the peripheral circulation, with a high frequency of T cell receptor (TCR) V beta + cells. MRSA produced enterotoxins C and A and toxic shock syndrome toxin (TSST)-1, all of which are known to act as superantigens. From the above observations, we speculate that post-MRSA glomerulonephritis may be induced by superantigens causing production of high levels of cytokines, and polyclonal activation of IgG and IgA. The formation of ICs containing IgA and IgG in the circulation result in development of glomerulonephritis and vasculitis. Accordingly, microbial superantigens may play an important role in the pathogenesis of this unique syndrome of nephritis and vasculitis.