[Historical remarks on nephrology research in Japan. 2. Clinical research on nephritis and renal biology(discussion)].
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Antibodies, Antineutrophil Cytoplasmic↗
Biomedical subjects
Fumitake Gejyo
Publications and source records attributed to Fumitake Gejyo.
Human glomerulonephritis accompanied by active cellular infiltrates shows effector T cells in urine.
Leukocyturia is associated with postinfectious glomerulonephritis (GN), interstitial nephritis, and renal allograft rejection. In addition, prominent infiltration of T cells and macrophages is commonly observed in the renal tissues of patients with GN, accompanied by cellular crescent formation and/or interstitial cell infiltration. Because these infiltrating T cells were thought to participate in the development of the diseases and to appear in the urinary space while functioning as effector cells in the renal inflammatory lesion, the study focused on the characterization of T cells that appeared in urine. Freshly voided urine cells were analyzed by flow cytometry to determine their phenotype and by reverse transcriptase-PCR to detect cytokine mRNA. In urine from patients with different forms of GN, including IgA nephropathy, Henoch-Schönlein purpura nephritis, and anti-neutrophil cytoplasmic antibody-associated GN, T cells appeared together with macrophages. The urine T cells were mainly CD45RA(-), CD45RO(+), and CD62L (L-selectin)(-), which are the phenotypic features of effector T cells. In agreement with this finding, T cells infiltrating glomeruli, crescents, and tubulointerstitial lesions were also effector type. Moreover, these urine cells expressed mRNA of the T helper lymphocyte 1 cytokines, interleukin-2, and/or interferon-gamma. These findings suggest that the appearance of effector T cells in urine may reflect the cellular immune reaction that occurs in the kidneys of patients with GN accompanied by active cell infiltration.
Adolescent↗
The C677T methylenetetrahydrofolate reductase gene mutation in hemodialysis patients.
Hyperhomocysteinemia, which results from renal impairment, may promote arteriosclerosis and glomerulosclerosis. The combined effect of renal failure and a common mutation (C677T) in the methylenetetrahydrofolate reductase gene that leads to serum homocysteine elevations in dialysis patients was investigated. Genotypes were determined at this locus in 545 dialysis patients and 676 healthy subjects, and serum concentrations of total homocysteine and folate were measured in a subgroup of 464 patients. Multiple regression analysis showed that the TT genotype and low serum folate concentration were independent positive predictors of the serum total homocysteine concentration. The negative slope of a regression line relating homocysteine and folate concentrations was significantly steeper for patients with the TT genotype than for other genotypes. Patients with the TT genotype were significantly younger at the time of the study (54.8 +/- 12.9 versus 59.6 +/- 12.3 yr; P < 0.0001) and at initiation of dialysis (46.6 +/- 16.2 versus 51.2 +/- 15.9 yr; P < 0.02) than those with other genotypes. In patients who were older at the time of the study or at initiation of dialysis, the prevalence of the TT genotype was lower than in control subjects. In the middle quartiles (37.1 to 63.0 yr) for age at the start of dialysis, the prevalence of the TT genotype was lower in patients with a longer duration of dialysis. In this cross-sectional study, genotype and serum total homocysteine concentration were not independent risk factors for vascular disease in dialysis patients. These results indicate that the methylenetetrahydrofolate reductase mutation is a significant independent predictor for serum total homocysteine concentration.
Adult↗
Matrix metalloproteinase-1 activation via plasmin generated on alveolar epithelial cell surfaces.
Plasmin is a potent protease related to tissue repair/remodeling not by fibrinolysis alone but also by activation of cytokines such as transforming growth factor and hepatocyte growth factor and by activation of matrix metalloproteases. We examined whether matrix matalloproteinase-1 was activated via plasminogen activation on surfaces of cultured alveolar epithelial cells (A-549). Cells were cultured overnight with plasminogen, pro-matrix metalloproteinase-1, and type I collagen as a substrate. Sodium dodecil sulfate-polyacrylamide gel electrophoresis was used to detect type I collagen degradation in culture supernatant. Collagen degradation corresponded to cell surface plasmin generation. No such finding was seen in the absence of cells or plasminogen. Alveolar epithelial plasminogen activation is important in matrix metalloproteinase-1 activation and thus presumably in tissue remodeling in pulmonary fibrosing pulmonary diseases such as idiopathic pulmonary fibrosis.
Cells, Cultured↗
The amplification of somatic symptoms in upper respiratory tract infections.
To assess the cultural differences in the role of somatosensory amplification in Japan and North America, we re-examined the role of psychological amplification of objective physical symptoms, as measured by the Somatosensory Amplification Scale (SSAS), in 82 Japanese patients with upper-respiratory tract infections. Anxiety and depression were measured with the Hospital Anxiety and Depression Scale (HADS). We determined the association among continuous variables using the Spearman correlation coefficient. Next, we used multiple regression analysis and selected all symptoms as independent variables. The SSAS was significantly associated with all somatic symptoms. It was also closely related to discomfort, but the SSAS was not significantly correlated with either anxiety or depression. All somatic symptoms were not significantly correlated with the objective physical findings. Multiple regression analyses indicated that amplification by SSAS was a statistically significant predictor of the patient's somatic symptoms and discomfort. The objective findings did not significantly predict the patient's symptoms. Our study provides some empirical evidence regarding psychological amplification of objective physical symptoms, as measured by SSAS, in Japanese patients with upper-respiratory tract infections. Our findings suggest that there is no difference in the role of amplification of bodily sensations between Japanese and North Americans.
Adolescent↗
Pulmonary involvement in mixed connective tissue disease: comparison with other collagen vascular diseases using high resolution CT.
PURPOSE: The purpose of this work was to compare the CT findings of lung involvement in patients with mixed connective tissue disease (MCTD) with those in patients with other CTDs: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and polymyositis and dermatomyositis (PM-DM). METHOD: CT scans of 35 patients with interstitial lung disease and associated MCTD were evaluated retrospectively. The CT assessment included determination of the findings and evaluation of whether the findings in MCTD were different from those in other CTDs. RESULTS: The frequency of ground-glass opacity in MCTD was significantly lower than in CTDs (p < 0.05). The frequency of honeycombing in MCTD was lower than in SSc (p < 0.05) and higher than in PM-DM (p < 0.005). Regarding the predominant CT patterns, the frequency of septal thickening in MCTD was significantly higher than in CTDs (p < 0.05). CONCLUSION: CT findings in MCTD were a combination of those in other CTDs.
Adolescent↗
Efficacy of fluticasone propionate compared with beclomethasone dipropionate in bronchial asthma: improvement in compliance and symptoms by fluticasone.
Recent studies have shown that fluticasone propionate (FP) was more effective than beclomethasone dipropionate (BDP) inhalation even at a dose reduced by twofold or more in the treatment of bronchial asthma. Here, we further compared the effectiveness of FP and BDP, including rates of drug compliance. Forty-two symptomatic patients were treated by BDP (1000 +/- 345; mean +/- SD; microgram/day) for 8 weeks, followed by FP at one-half the respective dose, and peak expiratory flow and forced expiratory volume in 1 second were investigated. In addition, the patients were asked about drug compliance and factors related to compliance (expressed using a visual analogue scale). Significant increases of peak expiratory flow (from 316 +/- 96 L/minute to 345 +/- 86 L/minute) and forced expiratory volume in 1 second (from 1.7 +/- 0.5 L to 1.9 +/- 0.4 L) were found. Furthermore, significantly higher scores were obtained for compliance and various factors related to compliance. These data indicate that FP is more effective than a twofold higher dosage of BDP and that better compliance with the use of FP, probably because of improved various factors associated with FP compliance, contributes to FP efficacy.
Adult↗