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S Matsuda

Publications and source records attributed to S Matsuda.

At least 55 records · Page 3Linked to original sources
PubMed2001

Cloning and sequencing of a novel human gene which encodes a putative hydroxylase.

Using a conventional two-hybrid technique with MAWD as bait protein, a novel full-length cDNA was isolated and sequenced from a human liver cDNA library. This cDNA consists of 2,575 base pairs and has a predicted open reading frame encoding 255 amino acids. Overall, it is similar to the catalytic enzyme PHZF, catalyzing the hydroxylation of phenazine-1-carboxylic acid to 2-hydroxyphenazine-1-carboxylic acid. Polymerase chain reaction-based mapping with both a monochromosomal hybrid panel and radiation hybrid cell panels placed the gene to human chromosome 10q21.1 near the marker D10S210.

Base Sequence↗
PubMed2001

E-cadherin gene mutations frequently occur in synovial sarcoma as a determinant of histological features.

Synovial sarcoma is a mesenchymal tumor that has an epithelial character and two major histological subtypes, the biphasic type and the monophasic fibrous type. However, the mechanisms involved in its epithelial differentiation are unknown, and furthermore, the determinants for histological subtype in synovial sarcoma remain unclear. In this study, we immunohistochemically examined E-cadherin expression and screened for genetic alterations in the E-cadherin gene from exon 4 to exon 9 in 49 cases of synovial sarcoma. In addition, we also examined the mRNA expressions of E-cadherin and Snail, a direct repressor of E-cadherin gene expression, by reverse transcriptase-polymerase chain reaction in 20 samples of frozen material. Immunohistochemical E-cadherin membranous expression was observed in 12 cases (24.5%), and was predominant in biphasic tumors. Single-strand conformation polymorphism analysis followed by DNA direct sequencing revealed 15 missense E-cadherin mutations in 12 cases (24.5%: monophasic, 11 of 42; biphasic, 1 of 6; poorly, 0 of 1) and 7 silent mutations (14.3%) in 7 cases. Ten of the 12 cases with E-cadherin missense mutations did not show E-cadherin membranous expression. Reverse transcriptase-polymerase chain reaction demonstrated E-cadherin and Snail mRNA expressions in 14 cases (70%) and in all cases, respectively. E-cadherin gene expression was inactivated by missense mutations in three of the eight cases (37.5%) of monophasic fibrous tumors that showed E-cadherin mRNA expressions. The E-cadherin gene was potentially inactivated in a significant number of synovial sarcomas. E-cadherin dysfunction because of its mutation in the central region of the molecule was associated with its decreased immunohistochemical expression and histological fibroblastic and spindle-shaped features of monophasic tumors. Thus, E-cadherin gene mutation may be one of the determinants of histological subtype in synovial sarcoma.

Adolescent↗
PubMed2001

Herpes simplex virus in the vestibular ganglion and the geniculate ganglion-role of loose myelin.

This study presents the first direct evidence for herpes simplex virus type 1 (HSV-1) infection in the neurons of the vestibular ganglion. Although many investigators have reported electron microscopic evidence of HSV-1 infection in sensory ganglia, HSV-1 infection in the vestibular ganglion has not been described. Vestibular ganglion neurons have a unique structure, with a loose myelin sheath instead of the satellite cell sheath that is seen in other ganglia. This loose myelin is slightly different from compact myelin which is known as too tight for HSV-1 to penetrate. The role of loose myelin in terms of HSV-1 infection is completely unknown. Therefore, in an attempt to evaluate the role of loose myelin in HSV-1 infection, we looked for HSV-1 particles, or any effects mediated by HSV-1, in the vestibular ganglion as compared with the geniculate ganglion. At the light microscopic level, some neurons with vacuolar changes were observed, mainly in the distal portion of the vestibular ganglion where the communicating branch from the geniculate ganglion enters. At the electron microscopic level, vacuoles, dilated rough endoplasmic reticulum and Golgi vesicles occupied by virus were observed in both ganglia neurons. In contrast, viral infections in Schwann and satellite cells were observed only in the geniculate ganglion, but not in the vestibular ganglion. These results suggest that loose myelin is an important barrier to HSV-1 infection, and it must play an important role in the prevention of viral spread from infected neurons to other cells.

Animals↗
PubMed2001

The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis.

Chorea-acanthocytosis is a neurodegenerative disorder with peripheral red cell acanthocytosis. Linkage of chorea-acanthocytosis to chromosome 9q21 has been found. We refined the locus region and identified a previously unknown, full-length cDNA encoding a presumably structural protein, which we called chorein. We found a deletion in the coding region of the cDNA leading to a frame shift resulting in the production of a truncated protein in both alleles of patients and in single alleles of obligate carriers.

Chorea↗
PubMed2001

H-ras oncogene mutation in dedifferentiated chondrosarcoma: polymerase chain reaction-restriction fragment length polymorphism analysis.

Dedifferentiated chondrosarcomas, which are known for their poor prognosis, are characterized by conventional chondrosarcoma with high-grade anaplastic components. Activating mutations in ras genes are a common genetic abnormality in human malignancies. The presence of point mutations at codons 12 and 13 of the H-ras gene was studied in 20 formalin-fixed paraffin-embedded chondrosarcomas, comprising 11 cases of conventional chondrosarcoma (six Grade 1 cases and five Grade 2 cases) and nine cases of dedifferentiated chondrosarcoma, using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. H-ras mutations were only seen in two out of the nine cases of dedifferentiated chondrosarcoma (2/9, 22%) and they were not seen in any of the cases of conventional chondrosarcoma (0/11, 0%). Dedifferentiated chondrosarcomas had a worse prognosis than conventional chondrosarcomas (P < .01); among the patients with dedifferentiated chondrosarcomas, those with H-ras mutation (n = 2) tended to have a worse prognosis than those without (n = 7), although the difference was not statistically significant (P = 0.068). Our results would seem to suggest that H-ras mutation may occur during the course of dedifferentiation and may also have some effect on malignant potential.

Adult↗
PubMed2001

A serine/threonine kinase p90rsk1 phosphorylates the anti-proliferative protein Tob.

BACKGROUND: tob is a member of a gene family with anti-proliferative function. Over-expression of Tob in NIH3T3 cells results in the suppression of cell proliferation. The growth suppression is hampered by the presence of activated ErbB2 kinase. The molecular mechanisms by which Tob suppresses cell growth and by which ErbB2 abrogates Tob function remain to be elucidated. RESULTS: We show that Tob is phosphorylated on serines and threonines, but not tyrosines, by a kinase(s) that associates with Tob in the lysates of various cells, including ErbB2-over-expressed cells. We also show that a 95 kDa kinase associates with Tob in vitro. The autophosphorylation activity of this kinase co-chromatographes with Tob-phosphorylating activity, suggesting that the 95 kDa kinase phosphorylates Tob. Among the known kinases with molecular mass around 95 kDa, p90rsk1 associates with Tob in vitro and in vivo, and phosphorylates Tob at least in vitro. Therefore, it is likely that p90rsk1 represents the 95 kDa kinase and is involved in the regulation of Tob function through phosphorylation. CONCLUSION: p90rsk1 associates with and phosphorylates Tob. Because p90rsk1 is activated downstream of receptor tyrosine kinases, we propose that Tob function is at least in part under the control of growth factor-stimulated tyrosine kinases through its phosphorylation by p90rsk1.

3T3 Cells↗
PubMed2001

Secondary malignant giant-cell tumour of bone: molecular abnormalities of p53 and H-ras gene correlated with malignant transformation.

AIMS: We report two cases of secondary malignant giant-cell tumour occurring without irradiation therapy. To elucidate the mechanism of malignant transformation in this tumour, we searched for the molecular abnormalities of p53, MDM2 and the H-ras genes. METHODS AND RESULTS: These cases were retrieved after a review of 103 cases of primary giant-cell tumour of bone, registered in our institute. One case occurred in the distal femur of a 42-year-old female after surgical curettage, while the other arose in the acetabulum of a 25-year-old male after en bloc resection. Microscopically, the malignant tumour in the distal femur was composed of a proliferation of ovoid or fusiform cells arranged in fascicles with high mitotic activities. The malignant transformed tumour in the acetabulum was made up of pleomorphic tumour cells with atypical mitoses. In the tumour of the distal femur, both p53 and H-ras mutations were detected. Abnormal nuclear accumulation of p53 protein and c-myc expression were also revealed by immunohistochemistry. In both cases, the recurrent malignant tumour over-expressed MMP-9 and revealed a higher MIB-1-labelling index compared with the primary conventional giant-cell tumour. CONCLUSIONS: Our results suggest that multiple oncogene or tumour suppressor gene mutations may play an important role during malignant transformation in conventional giant-cell tumours.

Adult↗
PubMed2001

Type 2-biased expression of cytokine genes in lung granulomatous lesions induced by Nippostrongylus brasiliensis infection.

Infections with helminthic parasites occasionally induce pulmonary diseases with possible involvement of immunological mechanisms. In rats infected with the nematode Nippostrongylus brasiliensis, pulmonary granulomatous lesions develop and persist after the larvae have migrated through the lungs. To determine the pathogenesis of this lesion, we examined cytokine gene expression in the lungs using RT-PCR and in situ hybridization. Two weeks after infection, when fully developed lesions appeared, levels of IL-3 and of type2 cytokines IL-4, IL-5, IL-6 and IL-13 gene expression were markedly enhanced in whole lung homogenates. Those of IL-2 and IFN-gamma were also slightly increased 2 weeks postinfection. IL-12 mRNA level did not change after 2 weeks but was slightly increased after 4 weeks. Levels of IL-10 and proinflammatory cytokine TNF gene expression did not show significant changes, although a slight increase was observed in IL-1beta message after 2 weeks. In situ hybridization studies showed that lung granulomatous lesions were composed mainly of lymphoid cells expressing IL-3, IL-4 and IL-13 mRNA, but not IFN-gamma mRNA. IL-5 mRNA-expressing cells were fewer in number than these cells. RMCP II immunohistochemistry revealed that mast cells increased in number in the lung granulomas. From these results, it was concluded that the nematode infection-associated lung granuloma was a type 2 lesion.

Animals↗
PubMed2001

Hyaluronan activates cell motility of v-Src-transformed cells via Ras-mitogen-activated protein kinase and phosphoinositide 3-kinase-Akt in a tumor-specific manner.

We investigated the production of hyaluronan (HA) and its effect on cell motility in cells expressing the v-src mutants. Transformation of 3Y1 by v-src virtually activated HA secretion, whereas G2A v-src, a nonmyristoylated form of v-src defective in cell transformation, had no effect. In cells expressing the temperature-sensitive mutant of v-Src, HA secretion was temperature dependent. In addition, HA as small as 1 nM, on the other side, activated cell motility in a tumor-specific manner. HA treatment strongly activated the motility of v-Src-transformed 3Y1, whereas it showed no effect on 3Y1- and 3Y1-expressing G2A v-src. HA-dependent cell locomotion was strongly blocked by either expression of dominant-negative Ras or treatment with a Ras farnesyltransferase inhibitor. Similarly, both the MEK1 inhibitor and the kinase inhibitor clearly inhibited HA-dependent cell locomotion. In contrast, cells transformed with an active MEK1 did not respond to the HA. Finally, an anti-CD44-neutralizing antibody could block the activation of cell motility by HA as well as the HA-dependent phosphorylation of mitogen-activated protein kinase and Akt. Taken together, these results suggest that simultaneous activation of the Ras-mitogen-activated protein kinase pathway and the phosphoinositide 3-kinase pathway by the HA-CD44 interaction is required for the activation of HA-dependent cell locomotion in v-Src-transformed cells.

Animals↗
PubMed2001

Template directed DNA photoligation via substituted 2'-deoxyuridine.

An efficient and reversible template-directed photoligation of oligodeoxynucleotides (ODNs) using 5-carboxyvinyldeoxyuridine (CVU) was described. We have also demonstrated about photochemical synthesis of circularized DNA and padlocking plasmid DNA via CVU mediated photoreaction.

Base Sequence↗
PubMed2001

Small GTP-binding protein, Rho, both increased and decreased cellular motility, activation of matrix metalloproteinase 2 and invasion of human osteosarcoma cells.

Rho, a member of the small GTP-binding proteins, and one of its downstream effectors ROCK (Rho-associated coiled-coil forming protein kinase) play an important role in the invasion of tumor cells. Lysophosphatidic acid (LPA) activates Rho and ROCK and promotes the organization of stress fibers and focal adhesions. However, the effect of LPA on tumor cell invasion is still controversial. In the present study, human osteosarcoma cells treated with a high concentration of LPA (high LPA) showed considerable formation of stress fibers and focal adhesions compared to the cells treated with a low concentration of LPA (low LPA). C3 (inhibitor of Rho) or Y27632 (an inhibitor of ROCK) inhibited the effects of LPA, indicating that LPA activates the Rho-ROCK pathway in the cells. In addition, Rho activation assay showed that the activation level of Rho can be altered by changing the concentration of LPA. Low LPA stimulated the motility and invasion of the cells, while high LPA reduced both. The disruption of extracellular matrix (ECM) by matrix metalloproteinase 2 (MMP2) is also critical for tumor cell invasion. MMP2 is activated by membranous type-1 MMP (MT1-MMP) and type-2 tissue inhibitor of MMP (TIMP2). High LPA suppressed the activation of MMP2 through down-regulation of MT1-MMP and TIMP2. C3 and Y27632 reversed the suppression of the activation of MMP2 and expression of MT1-MMP and TIMP2, suggesting the involvement of the Rho-ROCK pathway in ECM degradation. Tyrosine phosphorylation of focal adhesion kinase (FAK) was also required for the invasion of tumor cells to occur. Low LPA enhanced the tyrosine phosphorylation of FAK whereas high LPA reduced it. In conclusion, we suggest that Rho has a dual effect on the invasion of osteosarcoma cells by modulating the motility, the ability to degrade ECM and tyrosine phosphorylation of FAK.

Actins↗
PubMed2001

Enhanced formation of azoxymethane-induced colorectal adenocarcinoma in gammadelta T lymphocyte-deficient mice.

T cell receptor (TCR) gammadelta-positive T lymphocytes, which are localized mostly within the intraepithelial space of intestinal epithelium, have been suggested to play a role in maintaining the normal configuration of intestinal epithelium. However, the role of TCRgammadelta-positive T lymphocytes in the formation and progression of colorectal adenocarcinoma that originates from colorectal epithelial cells remains to be elucidated. In this study, TCRalphabeta and TCRgammadelta-positive T lymphocyte-deficient mice (homozygous TCRa and TCRd-gene knockout mice) and the background wild-type mice were administered azoxymethane, and the formation of macroscopic tumors and microscopic aberrant crypt foci in colorectal mucosa were compared among the three types of mice. Well-differentiated adenocarcinoma appeared 5 months after 5 administrations of azoxymethane (10 mg/kg weight) only in a few TCRd -gene knockout mice and the frequency of the carcinoma-bearing mice was increased at 7 and 9 months after the administration. Aberrant crypt foci were also detected in the colorectal mucosa of TCRd -gene knockout mice to a greater extent than in colorectal mucosa of TCRa-gene knockout mice 1 month after the azoxymethane administration. These results suggest that TCRgammadelta-positive T lymphocytes, which are present mainly in the intraepithelial space, play a role in suppression of the formation and progression of colorectal adenocarcinoma in mice.

Adenocarcinoma↗
PubMed2001

Recurrence of myocarditis presenting as pacing and sensing failure after implantation of a permanent pacemaker at first onset.

A 31-year-old woman was admitted to hospital with loss of consciousness and generalized convulsions. Electrocardiography (ECG) showed complete atrioventricular block (AV block) with a pulse rate of 30 beats/min. Endomyocardial biopsy from the right ventricle showed massive necrosis and degeneration of myocardial cells with extensive infiltration of lymphocytes into the interstitial space. These pathological findings suggested fulminant myocarditis. Following glucocorticoid therapy, the patient became asymptomatic, but the AV block did not resolve completely and a bifocal pacemaker was implanted. However, similar symptoms recurred 7 years later. An ECG showed pacing and sensing failure linked to an increase in the pacing threshold and a decrease in the sensing threshold. Endomyocardial biopsy from the right ventricle again showed interstitial infiltration with lymphocytes and eosinophils. After glucocorticoid therapy, she became asymptomatic once more, and the improvement in the pacing and sensing failure, and cardiomegaly, was satisfactory. This patient represents a very rare case of recurrence of acute myocarditis without progression, as much as 7 years after its first occurrence. Glucocorticoid therapy was still effective in treating the recurrent myocarditis presenting with pacing and sensing failure.

Acute Disease↗
PubMed2001

H-ras oncogene mutation in dedifferentiated liposarcoma. Polymerase chain reaction-restriction fragment length polymorphism analysis.

Point mutations of the ras gene family (K-ras, H-ras, and N-ras) are thought to be involved in the development of a variety of human tumors. Dedifferentiated liposarcoma is characterized by the coexistence of well-differentiated (WD) and high-grade anaplastic (HG) components. The presence of point mutations at codons 12 and 13 of the H-ras gene was studied in 34 liposarcomas, comprising 15 well-differentiated liposarcomas and 19 dedifferentiated liposarcomas, and in 8 storiform-pleomorphic type malignant fibrous histiocytomas (MFHs) using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. The 2 components of dedifferentiated liposarcoma were analyzed independently. H-ras mutations were seen only in dedifferentiated liposarcomas (4/19 [21%]), 1 in WD components and 3 in HG components. The mutation was not seen in any of 15 cases of well-differentiated liposarcoma. MFHs showed an H-ras mutation in 1 (12%) of 8 cases. Our results seem to suggest that the H-ras mutation is a relatively uncommon event in dedifferentiated liposarcoma, which may demonstrate an epiphenomenon of dedifferentiation in dedifferentiated liposarcoma.

Adult↗
PubMed2001

p73 is highly expressed in myoepithelial cells and in carcinomas with metaplasia.

p73, a homologue of p53 gene, is expressed in several normal tissues including central nervous system, but data regarding tumors are scant. In this study, we have analyzed the status and expression of the p73 gene in primary breast tumors, as well as 4 normal salivary glands, 2 carcinomas with metaplasia and mixed tumors. We found that periductal myoepithelial cells of all of the mammary gland examined were clearly stained with the specific anti-p73 antibody. Furthermore, we found the expression of p73 in the neoplastic myoepithelial cells in carcinomas with metaplasia and in mixed tumors. The findings in the present study provide valuable information on the characteristics of myoepithelial cells.

Breast↗
PubMed2001

Recombinant human erythropoietin therapy for autologous blood donation in rheumatoid arthritis patients undergoing total hip or knee arthroplasty.

The effect of recombinant human erythropoietin on autologous blood donation was investigated in 73 rheumatoid arthritis patients who underwent hip or knee arthroplasty. Autologous blood donation of 400 mL was successful with recombinant human erythropoietin (12,000 U per week), and no homologous blood was required. The mean period of blood collection was 33.8 days. Mean hemoglobin levels were 9.7 g/dL before treatment, 10.7 g/dL before surgery, and 10.2 g/dL after surgery. This study confirmed recombinant human erythropoietin is effective for enabling preoperative blood donation in rheumatoid arthritis patients.

Aged↗
PubMed2001

Long-term care insurance and integrated care for the aged in Japan.

By the introduction of a public, mandatory program of Long-Term Care Insurance (LTCI) on April 1, 2000, Japan has moved towards a system of social care for the frail and elderly. The program covers care that is both home-based and institutional. Fifty percent of the insurance is financed from the general tax and the other fifty percent from the premiums of the insured. The eligibility process begins with the individual or his/her family applying to the insurer (usually municipal government). A two-step assessment process to determine the limit of benefit follows this. The first step is an on-site assessment using a standardised questionnaire comprising 85 items. These items are analysed by an official computer program in order to determine either the applicant's eligibility or not. If the applicant is eligible it determines which of 6 levels of dependency is applicable. The Japanese LTCI scheme has thus formalised the care management process. A care manager is entrusted with the entire responsibility of planning all care and services for individual clients. The introduction of LTCI is introducing two fundamental structural changes in the Japanese health system; the development of an Integrated Delivery System (IDS) and greater informatisation of the health system.

Journal Article↗