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Toshihiko Nagasawa

Publications and source records attributed to Toshihiko Nagasawa.

12 recordsLinked to original sources
PubMed2006

DMRT-1 expression during NEC8 human embryonic carcinoma cell differentiation.

To elucidate the relationship between dsx and mab-3 related transcription factor 1 (Dmrt-1) and differentiation, alteration in mRNA levels during differentiation of NEC8 human embryonic carcinoma cells was investigated. After stimulation with 50 nM phorbol 12-myristate 13-acetate (PMA), the cells differentiated into cells with mesenchymal characteristics and upregulated Dmrt-1 mRNA, possibly through the protein kinase C/mitogen-activated protein kinase/activated protein-1 signaling pathway. Conversely, knockdown of Dmrt-1 by small interfering RNA resulted in cell morphology that was different from that after PMA treatment. These results indicated that Dmrt-1 expression was apparently associated with the differentiation of NEC8, and this cell line may be a helpful in vitro tool to clarify the role of Dmrt-1 in the differentiation process.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Concurrent occurrence of allergic granulomatous angiitis and temporal arteritis: a case report and review of the literature.

Allergic granulomatous angiitis (AGA) is a disease entity that was first distinguished from classical polyarteritis nodosa by Churg and Strauss in 1951, and is characterized by the clinical features of allergic rhinitis or bronchial asthma, eosinophilia, and vasculitis. Allergic granulomatous angiitis has been described to mainly involve small vessels. We herein describe a case of Churg-Strauss syndrome which demonstrated the clinical and laboratory findings supporting a diagnosis of AGA and was also associated with the clinical and pathological findings for temporal arteritis, which was characterized by eosinophil infiltration and granuloma formation of the temporal artery (middle-sized vessel).

Journal Article↗
PubMed2004

Alteration of redox state of human serum albumin before and after hemodialysis.

BACKGROUND: Persistent hypoalbuminemia is a predictor of death in long-term maintenance hemodialysis patients, although cardiovascular diseases remain the leading cause of death. A decreased serum antioxidant activity in maintenance hemodialysis patients may contribute to increased oxidative damage, and may be associated with accelerated atherosclerotic changes. METHODS: The aim of this study was to examine the redox state of human serum albumin in maintenance hemodialysis patients by high-performance liquid chromatography (HPLC) using a fluorescence detector. RESULTS: HPLC of human serum albumin on a Shodex-Asahipak ES-502N column at pH 4.85 showed a clear resolution of human mercaptalbumin (HMA) and nonmercaptalbumin (HNA), which are the reduced and oxidized forms of human serum albumin, respectively. The mean +/- SD percentage of the HMA fraction of human serum albumin was significantly lower in maintenance hemodialysis patients than in age-matched normal subjects. The percentage of HMA increased 3-5 h after starting the hemodialysis and then decreased to subnormal levels. CONCLUSION: This suggests that serum albumin may be a major extracellular antioxidant in maintenance hemodialysis patients, and that hemodialysis may rescue serum albumin reduction by inducing intermolecular sulfhydryl-disulfide exchange reaction.

Adult↗
PubMed2004

A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey).

BACKGROUND: A previous double-blind 24-week clinical trial of mizoribine (MZ) vs placebo in steroid-resistant primary nephrotic syndrome (SRPNS) showed that MZ was more effective than placebo in reducing the rate of deterioration of renal function. The present study was conducted to evaluate the efficacy and safety of MZ in patients with SRPNS after 2 years' treatment. METHODS: A multicenter randomized open-label controlled trial in patients with SRPNS was conducted as a 2-year prospective postmarketing study. RESULTS: There was a significant imbalance in the baseline serum albumin level (s-Alb) between the conventional therapy (CT) and MZ onlay therapy groups. Early dropouts were more frequent in the subset of patients in the CT group having a baseline s-Alb < or =3 g/dl. Therefore, the primary analysis (urinary protein level (UP)-improving effect) was performed using a mixed-effects model, with stratification according to the baseline s-Alb value. The analysis revealed that, in the subset of 34 patients with membranous nephropathy (MN) within the stratum of patients with baseline s-Alb < or =3 g/dl (n = 52), the rate of change (slope of change in the UP level/month), in terms of the log (UP+0.2), was -0.0577 in those allocated to the MZ group and -0.0227 in those allocated to the CT group (P = 0.058). In the stratum of patients with a baseline s-Alb >3 g/dl (n = 97), there were no significant differences in the UP between the two treatment groups. Hence, MZ onlay therapy was not considered to be efficacious in this group of patients. No serious adverse reactions to the drug were observed. CONCLUSIONS: The present study yielded significant results, in that it suggested the possibility that long-term MZ therapy may afford further reduction of the UP, in addition to that obtained following CT, in particular, in MN patients in a severe nephrotic state.

Adult↗
PubMed2004

Expression of MMP-9 in mesangial cells and its changes in anti-GBM glomerulonephritis in WKY rats.

BACKGROUND: Matrix metalloproteinase (MMP)-9, a member of the MMP family with specificity towards type IV collagen, is implicated in the turnover of the extracellular matrix in the kidney. To elucidate its physiological and pathophysiological significance, we examined the expression and localization of MMP-9 in the normal kidney and the changes in these features during the course of anti-glomerular basement membrane (GBM) glomerulonephritis induced in WKY rats, along with the changes in these features of tissue inhibitor of metalloproteinase 1 (TIMP-1) and MMP-2. METHODS: The expression of MMP-9, TIMP-1 and MMP-2 mRNA was quantified by ribonuclease protection assay, and the gelatinolytic activities of MMP-9 and MMP-2 were evaluated by gelatin zymography. The localization of MMP-9 was visualized by immunohistochemistry and immunofluorescence microscopy. RESULTS: The ribonuclease protection assay indicated the almost exclusive expression of MMP-9 mRNA in the glomerulus of normal kidneys. Immunohistochemistry and double-label immunofluorescence microscopy showed that MMP-9 was localized in the mesangial cells. During the course of anti-GBM glomerulonephritis, the expression of MMP-9 mRNA in glomeruli increased on day 1, peaked on days 3 to 7, and then decreased on day 14. The change in MMP-9 mRNA expression was accompanied by parallel changes in the gelatinolytic activity of the active form of MMP-9, TIMP-1 mRNA expression, and MMP-9 immunoreactivity in mesangial cells. In contrast, glomerular MMP-2 mRNA expression and its activity increased after the decline of MMP-9. CONCLUSIONS: MMP-9 mRNA was predominantly expressed in the glomerulus in normal rat kidneys and MMP-9 was present in the mesangium. The MMP-9 mRNA expression increased in the glomerulus 3 to 7 days after the induction of anti-GBM glomerulonephritis in WKY rats, in parallel with the development of abnormal glomerular histology and injury, suggesting a role of MMP-9 in proteolysis of the GBM during glomerulonephritis. MMP-2 may participate in the later phase of the nephritis.

Animals↗
PubMed2002

Gene transfection of H25A mutant heme oxygenase-1 protects cells against hydroperoxide-induced cytotoxicity.

Heme oxygenase (HO)-1 is a stress-inducible enzyme protecting cells against oxidative stress, and mechanisms have been considered to depend exclusively on its enzyme activity. This study aimed to examine if the protein lacking catalytic activities could also display such resistance against oxidative stress. Stable transfectants of rat wild type HO-1 cDNA (HO-1-U937) and those of its H25A mutant gene (mHO-1-U937) were established using human monoblastic lymphoma cell U937. HO-1-U937 and mHO-1-U937 used in the study exhibited similar levels of the protein expression, while only the former increased enzyme activities. HO-1- and mHO-1 U937 cells became more and less sensitive to H(2)O(2) than mock transfectants, respectively; such distinct susceptibility between the cells was ascribable to differences in the capacity to scavenge H(2)O(2) through catalase and to execute iron-mediated oxidant propagation. On the other hand, both cell lines exhibited greater resistance to tert-butyl hydroperoxide than mock transfectants. The resistance of HO-1-U937 to hydroperoxides appeared to result from antioxidant properties of bilirubin, an HO-derived product, while that of mHO-1-U937 was ascribable to increased contents of catalase and glutathione. These results provided evidence that gene transfection of the activity-lacking mutant HO-1 protects cells against oxidative stress through multiple mechanisms involving up-regulation of catalase and glutathione contents.

Animals↗
PubMed2002

Useful markers for detecting decreased serum antioxidant activity in hemodialysis patients.

This study evaluates a novel application of a method for measuring serum antioxidant activity, based on the detection of erythrocyte membrane lipid peroxidation in cases of uremia. A human erythrocyte ghost membrane in Tris-HCl was mixed with adenosine 5'-diphosphate and iron chloride (FeCl3; ADP/Fe3+) solution (at a molar ratio of 17:1), and the mixture was incubated under aerobic conditions at 37 degrees C for 2 hours. The concentration of erythrocyte membrane thiobarbituric acid-reactive substances increased proportionally with respect to ADP/Fe3+ concentration, and this increase was inhibited by serum albumin in a dose-dependent manner. In patients undergoing chronic hemodialysis therapy, predialytic sera contained in this reaction mixture were weaker than postdialytic sera in terms of inhibitory effect against erythrocyte membrane lipid peroxidation, whereas serum albumin contents remained at levels equivalent to those of the normal control. A gradual increase in human mercaptalbumin nonmercaptalbumin ratio during hemodialysis treatment might be one of the major factors that leads to the recovery of decreased serum antioxidant activity. We clearly showed that the serum scavenging activity against erythrocyte membrane lipid peroxidation in hemodialysis patients decreases markedly, and this pathological condition is improved by hemodialysis.

Adenosine Monophosphate↗