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T Moriyama

Publications and source records attributed to T Moriyama.

At least 73 records · Page 4Linked to original sources
PubMed1999

Regulation of matrix metalloproteinase-2 (MMP-2) by hepatocyte growth factor/scatter factor (HGF/SF) in human glioma cells: HGF/SF enhances MMP-2 expression and activation accompanying up-regulation of membrane type-1 MMP.

Hepatocyte growth factor/scatter factor (HGF/SF) contributes to the malignant progression of human gliomas. We investigated the effect of HGF/SF on matrix metalloproteinase-2 (MMP-2), membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitors of metalloproteinases (TIMPs), expressions of c-Met/HGF receptor-positive human glioblastoma cells. Treatment of U251 human glioblastoma cells with HGF/SF resulted in enhanced secretion of MMP-2 with an increased level of the active form. This was accompanied by enhanced expression (2.5-fold) of mRNA specific for MMP-2. The stimulatory effect of HGF/SF on MMP-2 expression did not occur in the presence of herbimycin A, a protein tyrosine kinase inhibitor. MT1 -MMP, a cell-surface activator of proMMP-2, was also up-regulated by HGF/SF in a dose-dependent manner. By contrast, the level of TIMP- 1 mRNAs was not altered significantly and that of TIMP-2 was reduced mildly by the HGF/SF treatment, suggesting that HGF/SF may eventually modulate a balance between MMP-2 and TIMPs in favor of the proteinase activity in the glioma cell microenvironment. HGF/SF also stimulated MMP-2 expression of other glioblastoma cell lines. Since glioblastomas frequently co-express HGF/SF and its receptor, our results suggest that HGF/SF might contribute to the invasiveness of glioblastoma cells through autocrine induction of MMP-2 expression and activation.

Benzoquinones↗
PubMed1999

Hepatitis C virus structural proteins induce liver cell injury in transgenic mice.

To develop an animal model of hepatitis C virus (HCV) infection, transgenic mice carrying part of the HCV cDNA (C980) encoding HCV-core and envelope proteins under control of the mouse class I major histocompatibility complex gene (H-2K) regulatory region were produced. HCV-C980 RNA and HCV-core protein were present in livers from line H36 as determined by RNase protection assay and immunostaining, respectively. More than 40 animals from line H36 were examined histologically. Most of these H36 mice after 10 months of age developed spontaneous focal infiltration of lymphocytes, hepatocyte necrosis, degeneration, and altered foci with mitotic hepatocytes. These pathological lesions were absent in livers from the age-matched control littermates. Liver cells from these H36 mice were sensitive to damage induced by intravenous administration of an anti-Fas antibody. It is suggested that HCV-C980 proteins by themselves may be one causative agent of liver cell injury in subjects with HCV infection.

Animals↗
PubMed1999

Beta-2-microglobulin and ferritin in cerebrospinal fluid for evaluation of patients with meningitis of different etiologies.

To determine whether or not the beta-2-microglobulin (beta2-m) and/or ferritin levels in cerebrospinal fluid (CSF) can be used as markers for the differential diagnosis of meningitis and determination of the response to treatment, 122 subjects with etiologically well-characterized diagnoses were classified into three groups: bacterial meningitis (n = 5; mean age +/- SD. 1.0+/-1.0 year), viral meningitis (n = 39; 5.9+/-3.8 years), and a non-meningitis group (n = 78; 5.2+/-4.9 years). The levels of beta2-m and ferritin in CSF were determined by means of a latex photometric immunoassay. The statistical significance of the data was analyzed with the Mann Whitney U-test. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of each prediction marker. This study indicated that (1) the levels of beta2-m and ferritin in CSF were related with age in the non-meningitis group: subjects of up to 5 months of age exhibited higher concentrations of these proteins than ones of above 6 months of age (beta2-m, 1.89+/-1.13 vs. 0.84+/-0.65 mg/l. P < 0.01; ferritin, 2.97+/-2.04 vs. 1.81+/-1.34 microg/l, P = 0.09); (2) the beta2-m level was significantly higher in the CSF of patients with viral meningitis than in ones without meningitis (2.41+/-1.23 vs. 0.84+/-0.65 mg/l, P < 0.01): the best cut-off value was 1.2 mg/l (3) the ferritin level was significantly higher in the CSF of patients with bacterial meningitis than in ones with viral meningitis (43.24+/-39.49 vs. 6.81+/-7.41 microg/l, P < (.01): the best cut-off value was 7.5 microg/l; and (4) sequential measurement of the CSF ferritin level was of value for determination of the response to antibiotic treatment for bacterial meningitis. These results only apply to patients of greater than 6 months of age. beta2-m and ferritin in the CSF can be used as an ancillary tool for diagnostic guidance in the acute phase of meningitis and determination of the response to treatment for bacterial meningitis.

Adolescent↗
PubMed1999

Simultaneous up-regulation of urokinase-type plasminogen activator (uPA) and uPA receptor by hepatocyte growth factor/scatter factor in human glioma cells.

Several lines of evidence indicate that hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, may play an important role in progression of human glioma. In this study, effects of HGF/SF on urokinase- type plasminogen activator (uPA)-mediated proteolysis network were examined in c-Met-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of uPA proteins accompanying increased transcription of uPA mRNA in a dose dependent fashion. The levels of uPA receptor (uPAR) mRNAs were also elevated simultaneously upon HGF/SF stimulation, and the cell-surface associated uPA activity was also elevated by the treatment. Since concomitant expression of HGF and its receptor c-Met are frequently observed in malignant gliomas, these results suggest that HGF/SF participates in invasive process of malignant glioma cells not only by its motility-stimulating activity but also through enhanced degradation of the extracellular matrix induced by autocrine activation of uPA proteolysis network.

Central Nervous System Neoplasms↗
PubMed1999

Role of intron 1 in smooth muscle alpha-actin transcriptional regulation in activated mesangial cells in vivo.

BACKGROUND: The activation of glomerular mesangial cells is one of the early, important features of progressive glomerular disease. Smooth muscle alpha-actin (SMalphaA) is an excellent marker of activated mesangial cells. However, the mechanisms of SMalphaA regulation are only available from in vitro investigation. METHODS: We examined in vivo promoter analysis of the SMalphaA gene-utilizing transgenic mice harboring different promoter regions of the SMalphaA gene fused to chloramphenicol acetyl transferase (CAT). CAT activities were tested in primary cultured mesangial cells and in glomerular legions of Habu venom glomerulonephritis. RESULTS: The DNA sequence -891 to +3828, which contains exon 1, intron 1, and the first 14 bp of exon 2 in addition to the 5'-flanking sequence of the SMalphaA gene, induced high levels of transcription in activated mesangial cells in in vivo habu venom glomerulonephritis and in cultured mesangial cells derived from transgenic mice. The DNA region -891 to -124 was a positive element in mesangial cells derived from transgenic mice. Deletions (3316 or 137 bp) in intron 1 reduced transcription to undetectable levels. The 137 bp sequence is highly conserved among several species, containing one CArG box element, which is one of the key motifs for transcriptional activation of contractile-related proteins. In vitro transfection analysis failed to demonstrate these positive effects of intron 1 and region -891 to -124. Conclusions. In vivo promoter analysis of the SMalphaA gene provided new information about the transcriptional regulation of SMalphaA in activated mesangial cells. The DNA region -891 to -124 has a positive effect on SMalphaA transcription in cultured mesangial cells. The intron 1 region (+1088 to +1224) plays a pivotal role in SMalphaA transcription in activated mesangial cells in vivo. Further analysis of this conserved region in intron 1, including the CArG motif, will be of great value in understanding the molecular mechanisms of mesangial activation.

Actins↗
PubMed1999

Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction.

BACKGROUND: Unilateral ureteral obstruction (UUO) is a well-established experimental model of renal injury leading to interstitial fibrosis. The molecular and cellular mechanism(s) of interstitial fibrosis in UUO kidney is beginning to be elucidated. Oxidative stress has been implicated in the pathogenesis of various forms of renal injury; however, little is known about its involvement in the setting of ureteral obstruction. METHODS: To investigate the possible involvement of oxidative stress in the obstructive nephropathy, we studied the occurrence and distribution of Nepsilon-carboxymethyl-lysine (CML) in the kidneys after ureteral obstruction. CML is an integrative biomarker of the cumulative protein damage induced by glycoxidation. Heme oxygenase-1 (HO-1) mRNA and protein expression, which is a sensitive and reliable indicator of oxidative stress, were also examined. RESULTS: CML immunoreactivity was found in the interstitium of UUO kidneys 10 days after the onset ureteral obstruction. HO-1 mRNA was up-regulated as early as 12 hours after ureteral obstruction. HO-1 immunoreactivity was observed in the periglomerular and peritubular interstitium two days after ureteral obstruction. CONCLUSIONS: These results strongly suggested the presence of increased oxidative stress in the interstitium of UUO kidneys. The oxidative stress and the formation of various kind of biological active oxidative products in the interstitium are supposed to play significant roles in UUO kidney.

Animals↗
PubMed1999

Probucol suppresses ICAM-1 expression in rat mesangial cells: possible role of IL-1.

Interleukin-1 (IL-1) participates in the progression of glomerulonephritis by up-regulating intercellular adhesion molecule-1 (ICAM-1) expression in experimental glomerulonephritis. Probucol, an anti-hyperlipidemic agent, ameliorates some types of glomerulonephritis regardless of serum cholesterol levels, and is also reported to inhibit IL-1 release from macrophages in atherosclerotic lesions. However, little is known about the mechanism of this favorable action on glomerular injury. We examined whether or not probucol inhibits ICAM-1 expression by suppression of IL-1 action in cultured rat mesangial cells. In this brief report, we review the actions of probucol on IL-1 secretion and discuss the possible mechanism by which probucol may suppress the glomerular injury.

Animals↗
PubMed1999

Combined effects of fabric air permeability and moisture absorption on clothing microclimate and subjective sensation during intermittent exercise at 27 degrees C.

The present paper aimed at determining the combined effects of two different levels of air permeability and moisture absorption, in terms of clothing microclimate and subjective sensation, in resting and exercising subjects at an ambient temperature of 27 degrees C, a relative humidity of 50% and an air velocity of 0.14 m s-1. Three kinds of clothing ensemble were investigated: (1) polyester clothing with low moisture absorption and low air permeability (A), (2) polyester clothing with low moisture absorption and high air permeability (B), and (3) cotton clothing with high moisture absorption and high air permeability (C). The subjects exercised for 10 min on a cycle ergometer at an intensity of 30% maximal oxygen uptake and then had a 10 min rest. This sequence was repeated four times. The main findings are summarized as follows: (1) The clothing microclimate humidity in the back area was significantly higher in A than in B, and in C than in B. (2) The clothing microclimate temperature in the chest area was significantly higher in B than in A, and in B than in C. (3) The clothing microclimate temperature in the back area was significantly higher in C than in B. (4) The clothing surface temperature was significantly higher in C than in B. (5) Although the positive relationships between the microclimate humidity and forearm sweat rate was significantly confirmed in all three kinds of clothing, the microclimate humidity at chest for the same sweat rate was lower in C than in A and B. (6) Although the positive relationships between subjective sensation and forearm sweat rates were significantly confirmed in all three kinds of clothing, the subjective discomfort seemed to be reduced more effectively in C than in A and B for the same sweat rate. These results were discussed in terms of thermal physiology and combined effects of air permeability and moisture absorbency of the fabrics.

Absorption↗
PubMed1999

Enhanced interstitial expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy.

BACKGROUND: With progressive renal disease, structural derangement increasingly encompasses the tubulointerstitial compartment. Tubulointerstitial injury is a critical determinant of renal functional reserve and prognosis in renal disease. Interstitial cells acquiring characteristic of myofibroblasts are an important contributor to interstitial fibrosis. Caldesmon, a calmodulin or actin binding protein, is a molecular marker of differentiation in smooth muscle cells and has recently been shown by us to be a good marker of mesangial cell activation in IgA nephropathy patients. METHODS. We studied whether the expression of caldesmon in interstitium of the kidney was enhanced in the process of glomerular disease and whether it would be a marker of interstitial activation in specific disease states. We performed immunohistochemical staining with anti-caldesmon antibodies in 38 biopsy specimens from IgA nephropathy patients and analysed them quantitatively with a computer-aided manipulator. Interstitial caldesmon expression were compared with histological changes and clinical parameters. RESULTS: Caldesmon expression was enhanced where interstitial cell infiltration and fibrosis were found. Immunoelectron microscopy revealed that caldesmon staining in the renal interstitium was cytoplasmic, and in the processes of myofibroblast-like cells. Caldesmon expression was more prominent in the intense CD68 infiltrated group than in the low positive cells infiltrated group. Patients showing high intensity of interstitial caldesmon expression had significantly higher urinary protein excretion than those showing low intensity of caldesmon expression. Next, 15 patients were treated with glucocorticoid and heparin for 4-8 weeks and re-biopsies were performed. Caldesmon expression was reduced in concomitant with decreased interstitial cell infiltration. Follow-up of these patients (average 24 months) revealed a significant suppression of urinary protein excretion and significant improvement of creatinine clearance. CONCLUSION: These results suggest that the interstitial caldesmon expression is associated with the progression of IgA nephropathy, and glucocorticoid--heparin therapy may reverse the phenotypic change of interstitial cells during the disease process of glomerulonephritis.

Actins↗
PubMed1999

Purification and characterization of diacylglycerol lipase from human platelets.

Diacylglycerol lipase (DGL) was solubilized from human platelet microsomes with heptyl-beta-D-thioglucoside, and purified to homogeneity on SDS-PAGE using a combination of chromatographic and electrophoretic methods. The molecular mass of the purified DGL was estimated to be 33 kDa. Its apparent pI was pH 6.0, as determined by Immobiline isoelectro-focusing. The enzymatic activity of the partially purified DGL was investigated in the presence of a variety of inhibitors and reagents, as well as its pH and calcium dependence. Thiol reagents such as p-chloromercurubenzoic acid (pCMB), N-ethylmaleimide (NEM), and HgCl2 inhibited the activity, while dithiothreitol (DTT) and reduced glutathione (GSH) enhanced it. In addition, the enzymatic activity was inhibited by two serine blockers, phenylmethylsulfonyl fluoride (PMSF) and diisopropyl fluorophosphate (DFP), and by a histidine modifying reagent, p-bromophenacyl bromide (pBPB). These results suggest that cysteine, serine and histidine residues are required for the enzymatic activity of DGL. DGL was optimally active in the pH range of 7-8 and its activity did not change significantly in the presence of various calcium concentrations, even in the presence of 2 mM EGTA. This indicates that DGL can hydrolyze substrates with a basal cytosolic free Ca2+ level in the physiological pH range. A DGL inhibitor, RHC-80267, inhibited DGL activity in a dose-dependent manner with an IC50 (the concentration required for 50% inhibition) of about 5 microM. Unexpectedly, several phospholipase A2 (PLA2) inhibitors were potent inhibitors of DGL activity (IC50<5 microM), suggesting that the catalytic mechanisms of DGL and PLA2 may be similar. Finally, we show that DGL activity was inhibited by 2-monoacylglycerols (2-MGs), the reaction products of this enzyme. Among the three 2-MGs tested (2-arachidonoyl glycerol, 2-stearoyl glycerol, and 2-oleoyl glycerol), 2-arachidonoyl glycerol was the most potent inhibitor.

Blood Platelets↗
PubMed1999

Effect of a novel immunosuppressant, FK 506, on autoimmune glomerulonephritis in Brown Norway rats.

Mercuric-chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway rats. The effects of a new immunosuppressant FK 506 on this model of glomerulonephritis were studied. Brown Norway rats were treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/ week). Rats developed proteinuria at day 7, which reached a plateau level at day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed a strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Coadministration of FK 506 (1 mg/kg s.c. daily) prevented the appearance of proteinuria at day 14 (621.4 +/- 30.5 vs. 2.2 +/- 2.7 mg/day) and the morphological lesions. These findings suggest that FK 506 could be useful for the therapy of certain types of human glomerulonephritis.

Animals↗
PubMed1999

Effect of FK 506 in the treatment of autoimmune glomerulonephritis in Brown Norway rats.

Mercuric chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway (BN) rats. The effects of a new immunosuppressant, FK 506, on this model of glomerulonephritis were studied. BN rats were treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/week). FK 506 was inoculated subcutaneously daily from day 15 to day 28. Animals were divided into 4 groups: group 1, rats were treated with normal saline alone and sacrificed on day 28; group 2, rats were treated with HgCl2 alone and sacrificed on day 14; group 3, rats were treated with HgCl2 alone and sacrificed on day 28, and group 4, rats were treated with HgCl2 and FK 506 (from day 15 to day 28) and sacrificed on day 28. Rats developed proteinuria by day 7, which reached a plateau level by day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Treatment with FK 506 (1 mg/kg s.c. daily) resulted in a remarkable reduction in proteinuria on day 28 (493.5 +/- 48.3 vs. 24.4 +/- 13.5 mg/day) and an improvement in the morphological lesions. These findings suggest that FK 506 could be useful in the treatment of some human glomerulonephritides.

Animals↗
PubMed1999

Autodegradation of protein disulfide isomerase.

Protein disulfide isomerase (PDI) and its degradation products were found in HepG2, COS-1, and CHO-K1 cells. Whether or not the products were formed through autodegradation of PDI was examined, since PDI contains the CGHC motif, which is the active center of proteolytic activity in ER-60 protease. Commercial bovine PDI was autodegraded to produce a trimmed PDI. In addition, human recombinant PDI also had autodegradation activity. Mutant recombinant PDIs with CGHC motifs of which cysteine residues were replaced with serine or alanine residues were prepared. However, they were not autodegraded, suggesting the cysteine residues of motifs are necessary for autodegradation.

Animals↗
PubMed1999

Renin-angiotensin system component gene polymorphism in Japanese bronchial asthma patients.

The influence of renin-angiotensin system (RAS) component gene polymorphism in the pathogenesis of bronchial asthma was investigated in an association study involving 119 bronchial asthma patients and 208 control subjects. The selected RAS polymorphisms were angiotensinogen (Agt) T235/M235 and angiotensin I-converting enzyme (ACE) insertion/deletion (I/D). The control allelic frequencies of the Agt T235/M235 (0.84/0.16) and ACE I/D (0.63/0.37) in this study were similar to the previous reports in Japanese normal population. The allelic frequencies of the Agt T235/M235 (0.84/0.16) and ACE I/D (0.65/ 0.35) among the asthma patients were not significantly different from those among the control subjects. There was no association between severity of bronchial asthma and the selected RAS component gene polymorphism. From these data, we conclude that in the Japanese population, the RAS component gene polymorphism is not associated with increased risk for bronchial asthma.

Adult↗
PubMed1999

Expression of hepatocyte growth factor/scatter factor and its receptor c-Met in brain tumors: evidence for a role in progression of astrocytic tumors (Review).

Hepatocyte growth factor (HGF) is a multifunctional cytokine which is believed to have important roles in tissue development and regeneration, and tumor progression. It is indistinguishable from scatter factor (SF), a motility factor. HGF/SF is believed to be a mesenchymal cell-derived cytokine acting for epithelial cells bearing its receptor tyrosine kinase, c-Met. Recently, we found that glioblastoma multiforme (GBM), a highly malignant brain tumor of astrocytic origin, concomitantly express HGF/SF and c-Met. This finding indicates a presence of autocrine loop of HGF/SF signaling pathway in GBM. Moreover, GBM cells also co-express HGF activator, a recently identified serine proteinase having efficient HGF/SF activating activity. The expression of HGF/SF and c-Met was low or hardly detectable in low-grade astrocytoma, and c-Met immunoreactivity was correlated with the histological grade of the tumor suggesting that the creation of HGF/SF autocrine loop occurs along with the progression of astrocytic brain tumors. Experimental evidence indicated that HGF/SF exhibits potent migration/invasion-inducing activity for GBM cells bearing c-Met receptor. It is also a significant angiogenesis factor in GBM, and may serve as a cellular growth factor for certain GBM cells. These lines of evidence suggest that HGF/SF signaling pathway may serve as a promising new target of therapeutic intervention of GBM.

Brain Neoplasms↗
PubMed1999

Comparison of magnetic resonance imaging and ultrasonography in the early diagnosis of interstitial pregnancy.

OBJECTIVE: To investigate the usefulness of ultrasonography (USG) and magnetic resonance imaging (MRI) in the early diagnosis of interstitial pregnancy. STUDY DESIGN: Four cases of interstitial pregnancy that showed characteristic ultrasonographic and MRI findings were studied. All cases received cornual resection, and the presence of interstitial pregnancy was confirmed by pathologic examination. RESULTS: Three of four cases had a gestational sac in the uterine cornu or a protruding cornual mass and myometrium between the sac and uterine cavity on both USG and MRI. In the remaining case, preoperative diagnosis was inconclusive because no gestational sac was demonstrated by USG or MRI. Color flow mapping was conducted in three cases and revealed prominent peritrophoblastic blood flow. CONCLUSION: The findings suggest that USG combined with color flow mapping is the first choice in the early diagnosis of interstitial pregnancy. MRI, which is an extremely expensive imaging technology, should be used only if transvaginal USG with color flow mapping is inconclusive in ruling out the diagnosis of interstitial pregnancy.

Adult↗
PubMed1999

A System to Find Genetic Networks Using Weighted Network Model.

We are developing a system which finds a genetic network from data obtained by multiple gene disruptions and overexpressions. We deal with a genetic network as a weighted graph, where each weight represents the strength of activation from a gene to another gene. In this paper, we explain the overview of our system, and our strategy to visualize the weighted network. We also study the computational complexity related to the visualization.

Journal Article↗