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Shiro Mori

Publications and source records attributed to Shiro Mori.

At least 19 recordsLinked to original sources
PubMed2006

A non-major histocompatibility locus determines tissue specificity in the pathogenic process underlying synovial proliferation in a mouse arthropathy model.

BACKGROUND: The incidence and characteristics of spontaneous ankylosis in the ankle of specific F(1) mice descended from two Fas-deficient strains were reported. Here the coincidence of synovial proliferation and ankylosis in the descendent F(2) mice is reported. AIM: To clarify whether the two distinct manifestations are genetically different. METHODS: An arthropathic group of mice (MCF(2)) were bred by intercrossing MRL/Mp.Fas(lpr)-sap(-)/sap(-) and C3H/He.Fas(lpr) mice. All mice were killed by bleeding under anaesthesia when they were 6 months old. Pathological grades for synovial proliferation were determined by microscopical examination. To obtain a linkage locus, the whole genome of male MCF(2) mice was scanned by using 73 microsatellite markers. RESULTS: Synovial proliferation was equally observed in male and female MCF(2) mice. No correlation was observed between the grades of synovial proliferation and the ankylosis occurring in the MCF(2) mice. A suggestive susceptibility locus was shown in the middle of chromosome 11. This locus was an MRL allele with a recessive inheritance mode. CONCLUSION: The pathogenic mechanisms of synovial proliferation and ankylosis are genetically different. The present locus is overlapped with some loci associated with rheumatoid arthritis and with others associated with experimental arthritides.

Animals↗
PubMed2006

A signal adaptor SLAM-associated protein regulates spontaneous autoimmunity and Fas-dependent lymphoproliferation in MRL-Faslpr lupus mice.

Autoantibody production and lymphadenopathy are common features of systemic autoimmune disease. Targeted or spontaneous mutations in the mouse germline have generated many autoimmune models with these features. Importantly, the models have provided evidence for the gene function in prevention of autoimmunity, suggesting an indispensable role for the gene in normal immune response and homeostasis. We describe here pathological and genetic characterizations of a new mutant strain of mice, the mutation of which spontaneously occurred in the Fas-deficient strain, MRL/Mp.Faslpr (MRL/lpr). MRL/lpr is known to stably exhibit systemic lupus erythematosus-like diseases. However, the mutant mice barely displayed autoimmune phenotypes, though the original defect in Fas expression was unchanged. Linkage analysis using (mutant MRL/lpr x C3H/lpr)F2 mice demonstrated a nucleotide insertion that caused loss of expression of small adaptor protein, signaling lymphocyte activation molecule (SLAM)-associated protein (SAP). SAP is known to be a downstream molecule of SLAM family receptors and to mediate the activation signal for tyrosine kinase Fyn. Recent studies have shown pleiotropic roles of SAP in T, B, and NK cell activations and NKT cell development. The present study will provide evidence for an essential role for SAP in the development of autoimmune diseases, autoantibodies, and lymphadenopathy in MRL/lpr lupus mice.

Amino Acid Sequence↗
PubMed2006

A non-invasive tissue-specific molecular delivery method of cancer gene therapy.

A Japanese word, monozukuri (literally translated "making things") is the philosophy of first having the idea and then the faith in the technical expertise and experience to accomplish the result. We believe that the concept of engineering is monozukuri. Through the process of monozukuri, engineered natural science based on mathematics and physics has been developed. Medicine is the field of study which has been developed for maintaining daily healthy life with diagnosis, treatment, examination, and protection. Biomedical engineering is the interdisciplinary study of engineering and medicine, and should be developed based on monozukuri. In this particular research, we have developed a physical molecular delivery method for cancer gene therapy using nano/microbubbles and ultrasound. First, the behavior of cavitation bubbles and subsequent shock wave phenomena involved in the mechanism of molecular delivery were analyzed, combining theory and computer simulation. In a second step, the methodology was optimized in vitro and in vivo. Finally, the therapeutic potential of the method in pre-clinical models was evaluated using transgenes relevant to cancer gene therapy instead of reporter genes, and whole body, non-invasive imaging using single photon emission computed tomography (SPECT/CT) was used to evaluate the selectivity of gene delivery in vivo.

Animals↗
PubMed2006

Hand preference consistency and eye-hand coordination in young children during a motor task.

Indications of earlier research are that individuals exhibiting a consistent hand preference are better coordinated on selected motor tasks than peers with inconsistent hand preference. The present study examined eye-hand coordination via inter- and intramodal matching behavior by handedness groups for 55 5- and 6-yr.-olds using the Pinboard Test. Analysis indicated the Consistent group scored better, leading to the speculation that children with consistent laterality may possess an advantage in interhemispheric communication, especially when the task requires coordination of both limbs.

Child↗
PubMed2005

Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice.

Potentially, autoimmune diseases develop from a combination of multiple genes with allelic polymorphisms. An MRL/Mp-Fas(lpr) (/) (lpr) (MRL/lpr) strain of mice develops autoimmune diseases, including lupus nephritis, but another lpr strain, C3H/HeJ-Fas(lpr) (/) (lpr) (C3H/lpr) does not. This indicates that MRL polymorphic genes are involved in the development of the diseases. By quantitative trait loci (QTL) analysis using 527 of the (MRL/lpr x C3H/lpr)F(2) mice, we identified a novel locus for susceptibility to lupus nephritis at map position D5Mit115 on chromosome 5, the same alias of the osteopontin (Opn) gene (LOD score =4.0), susceptible in the MRL allele. In functional analyses of the MRL and C3H Opn alleles using synthetic osteopontin (OPN) made with a new method "cell-free system" with wheat germ ribosomes, the MRL-OPN induced higher expression and production of immunoglobulins as well as cytokines including TNF-alpha, IL-1beta and IFN-gamma in splenocytes and/or macrophages than that of the C3H allele. These findings suggest that allelic polymorphism of OPN causes the functional differences in antibody production and macrophage activation between MRL and C3H strains, possibly involved in the development of lupus nephritis.

Alleles↗
PubMed2005

Detection of ABCA7-positive cells in salivary glands from patients with Sjögren's syndrome.

ABCA7 is a member of the subfamily A of adenosine triphosphate-binding cassette (ABC) proteins, and highly homologous to ABCA1, which mediates the release of cellular cholesterol and phospholipid to form high-density lipoprotein. ABCA1 and ABCA7 contain two large extracellular domains, ECD1 and 2, which are thought to be important for their functions. Interestingly, part of ECD1 of ABCA7 is deposited as an autoantigen of Sjögren's syndrome. To determine the relationship between ABCA7 and Sjögren's syndrome, an immunohistochemical study was conducted with salivary gland biopsy samples from patients with Sjögren's syndrome. ECD1 of human ABCA7 (amino acids 45-549) was expressed in Escherichia coli as a protein fused with glutathione-S-transferase and a monoclonal antibody, KM3095, was generated. KM3095-immunoreactive cells were observed in salivary glands from 10 of 18 patients with Sjögren's syndrome. Immunostaining of serial sections with the plasma cell marker NCL-PC indicated that most of the plasma cells infiltrating salivary glands of patients with Sjögren's syndrome were KM3095-immunoreactive. Although the pathological or biological significance is not clear, it will be intriguing to further examine the relationship between ABCA7 and Sjögren's syndrome.

ATP-Binding Cassette Transporters↗
PubMed2003

Genetic basis of tissue specificity of vasculitis in MRL/lpr mice.

OBJECTIVE: To clarify the mode of inheritance of the tissue distribution of vasculitis in MRL/Mp-lpr/lpr (MRL/lpr) lupus-prone mice and to identify the susceptibility loci. METHODS: Vasculitis in individual MRL/lpr, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/lpr x C3H/lpr)F(1), and (MRL/lpr x C3H/lpr)F(2) intercross mice was analyzed by histopathologic grading of main branches of the aorta and of medium-sized arteries in the lower limbs. Genomic DNA samples from F(2) intercross mice were examined by simple sequence-length polymorphism analysis, and the polymorphic microsatellite markers highly associated with vasculitis in each tissue were determined as vasculitis susceptibility loci. RESULTS: A susceptibility locus with significant linkage to vasculitis of main branches of the aorta was mapped on chromosome 4 at D4Mit213 (map position 13.3cM) selectively in males, while vasculitis of medium-sized arteries in the lower limbs was mapped to different chromosomes: at D8Mit31 on chromosome 8 (map position 33.0) selectively in females and at D5Mit36 on chromosome 5 (map position 65.0). All of these were different from the previously defined loci governing susceptibility to vasculitis involving the kidneys. CONCLUSION: Systemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity.

Animals↗
PubMed2003

Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin.

An important clinical problem in the treatment of oral squamous cell carcinoma is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance in vitro (Komatsu et al., Cancer Res 60, 1312-1316,2000). However, the clinical significance of this transporter has not previously been addressed. Our aim of this study was to investigate if ATP7B is expressed in oral squamous cell carcinoma and whether its expression correlates with prognosis and reduced responsiveness to cisplatin treatment. Biopsy tissues were obtained from the tumors of 70 patients with oral SCC, and 51 patients received cisplatin-based preoperative chemotherapy. We performed immunohistochemical analysis of ATP7B using monoclonal antibody against ATP7B in 51 oral SCC and adjacent neoplastic tissues. The significance of ATP7B in the prognosis of patients with oral SCC was also examined in the survival analysis of mortality follow-up data covering the period 1991 through 2000. We retrospectively examined the expression of ATP7B in primary oral SCC carcinoma and its association with chemotherapeutic effect. A variable degree of cytoplasmic staining of tumor cells was observed in 54.9% (28/51 cases) of the analyzed carcinomas. Patients with ATP7B-positive tumors had a significantly inferior response to chemotherapy compared with the patients with ATP7B-negative tumors (P = 0.03). The patients who received cisplatin-based chemotherapy with ATP7B-positive carcinomas had a significantly poorer overall survival than those with ATP7B-negative tumors (P = 0.015). These findings suggest that high levels of ATP7B expression in oral SCC are associated with unfavorable clinical outcome in patients with oral SCCs treated with cisplatin-based chemotherapy. ATP7B expression may be a preoperative indicator for a choice of cisplatin in some patients.

Adenosine Triphosphatases↗
PubMed2003

Expression of copper-transporting P-type adenosine triphosphatase in human esophageal carcinoma.

A major obstacle in the treatment of esophageal carcinoma is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphatase (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the clinical significance of this transporter has not previously been addressed. Our goal was to investigate if ATP7B is expressed in esophageal carcinoma and whether its expression correlates with reduced responsiveness to cisplatin treatment. We retrospectively examined the expression of ATP7B in primary esophageal carcinoma and its association with chemotherapeutic effect. Tissues were surgically removed from 17 esophageal carcinoma patients. Twelve of them received cisplatin-based chemotherapy before surgery. We performed immunohistochemical analysis of ATP7B using a monoclonal antibody against ATP7B in 17 esophageal carcinomas. A variable degree of cytoplasmic staining of tumor cells was observed in 76.5% (13/17 cases) of the analyzed carcinomas. ATP7B expression was not observed in adjacent non-neoplastic tissues. ATP7B positivity was not significant in gender, age, histopathological grading or TNM categories. Patients with ATP7B-positive tumors tended to have an inferior response to chemotherapy compared with the patients with ATP7B-negative tumors. These findings suggest that overexpression of ATP7B in esophageal carcinoma could be associated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Therefore, ATP7B gene expression might be considered as a chemoresistance marker for cisplatin in the patients of esophageal carcinoma and provider of important information on the strategy against esophageal carcinoma.

Adenosine Triphosphatases↗
PubMed2002

Effect of enucleation on the expression of c-Fos protein in the supraoptic nucleus of the Japanese monkey (Macaca fuscata).

The aim of this study was to examine the effects of one eye enucleation on the expression of c-Fos protein in the hypothalamus of the Japanese monkey (Macaca fuscata). Compared with an intact monkey, significantly increased numbers of c-Fos positive neurons were observed in the supraoptic nuclei on both sides at 1 h after eye enucleation. This maximal c-Fos expression then started to decrease at 3 h after eye enucleation. Furthermore, by a dual-labeled immunocytochemical study, the c-Fos immunoreactivity was found mainly in the vasopressinergic but not in the oxytocinergic neurons within the supraoptic nucleus. These results suggest that vasopressinergic but not oxytocinergic neurons within the supraoptic nucleus may have critical roles in the stimulation of this nucleus in response to eye enucleation.

Animals↗
PubMed2002

Uridine phosphorylase is a potential prognostic factor in patients with oral squamous cell carcinoma.

BACKGROUND: Uridine phosphorylase (UPase) catalyzes the reversible phosphorolysis of uridine to uracil. The expression levels and the enzymatic activity of UPase are reported to be higher in human solid tumors than in adjacent normal tissues. However, to the authors' knowledge the clinical significance of UPase expression as determined by immunohistochemical analysis has not been demonstrated in human malignancies. METHODS: The authors prepared the antibody against UPase, examined the staining of UPase in 72 cases of oral squamous cell carcinoma (SCC) with immunohistochemical analysis using the antibody, and analyzed its relation to clinical and pathologic factors. RESULTS: UPase stained mainly within the invasive edges of tumors and macrophages. UPase-positive staining was observed in 56 of the 72 tumors (77.8%). High staining of UPase (defined as > 50% of cells in a tumor biopsy that are positive for UPase) in primary tumors frequently was associated with the presence of metastasis to lymph nodes (P = 0.007 by the Fischer exact test) and with lower overall survival (P = 0.03 by the log-rank test). CONCLUSIONS: The high rate of UPase staining in biopsies from patients with oral SCC may be a prognostic marker for these individuals.

Adult↗
PubMed2002

Arthritis in MRL/lpr mice is under the control of multiple gene loci with an allelic combination derived from the original inbred strains.

OBJECTIVE: To clarify the mode of inheritance and the genome origins of arthritis in a lupus-prone strain of mice, MRL/MpJ, bearing a Fas deletion mutant gene, lpr (MRL/lpr). METHODS: Using non-lupus-prone strains of mice, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/lpr x C3H/lpr)F(1) intercross and MRL/lpr x (MRL/lpr x C3H/lpr)F(1) backcross mice were prepared. Arthritis in individual mice was analyzed by histopathologic grading, and the genomic DNA of the backcross mice was examined by simple sequence-length polymorphism analysis to determine the polymorphic microsatellite markers highly associated with arthritis. RESULTS: Arthritis-susceptibility loci with significant linkage were mapped between D15Mit111 and D15Mit18 (map position 17.8-18.7 cM) on chromosome 15 and between D19Mit112 and D19Mit72 (map position 43.0-55.0) on chromosome 19 (logarithm of odds scores 3.5 and 4.3, respectively). Three other loci, one mapped to each of chromosomes 1, 2, and 7, showed suggestive linkage. Loci homozygous for MRL alleles on chromosomes 1 and 19 enhanced arthritis in both sexes, whereas other loci on chromosomes 2 and 15 selectively affected males. A locus homozygous for MRL alleles on chromosome 7 inhibited arthritis in both sexes. Three of these loci were found to originate from an LG/J strain and 1 from an AKR/J strain. Some combinations of these loci showed an additive effect in a hierarchical manner on the development of arthritis. CONCLUSION: Arthritis in MRL/lpr mice is a complex pathologic manifestation resulting from the cumulative effect of multiple gene loci with an allelic combination derived from the original inbred strains.

Alleles↗
PubMed2002

Copper-transporting P-type adenosine triphosphatase (ATP7B) is expressed in human breast carcinoma.

This is the first report to show that a copper-transporting P-type adenosine triphosphatase, ATP7B, is expressed in certain breast carcinomas, and a priori knowledge of its expression is important for the choice of therapy. We investigated the hypothesis that ATP7B, which was shown to be associated with cisplatin resistance in vitro, is expressed in certain breast carcinomas. To test this hypothesis, ATP7B expression and protein level were examined in 41 breast carcinomas using RT-PCR and immunohistochemistry. ATP7B gene / protein could be detected in 22.0% (9 / 41) of breast carcinomas and ATP7B gene expression was correlated well with the protein expression. In nine ATP7B-positive tumors, adjacent normal breast tissue was similarly analyzed, revealing that ATP7B is upregulated in breast carcinoma. ATP7B gene expression in poorly differentiated carcinoma was significantly higher than that in well- / moderately differentiated carcinoma (P = 0.012). Furthermore, we found no association between the ATP7B gene / protein expression and that of MDR1, MRP1, LRP and BCRP. These findings suggested that ATP7B gene expression might be a chemoresistance marker for cisplatin in patients with poorly differentiated breast carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Effect of metaphorical verbal instruction on modeling of sequential dance skills by young children.

Metaphorical verbal instruction was compared to specific verbal instruction about movement in the modeling of sequential dance skills by young children. Two groups of participants (Younger, mean age 5:3 yr., n = 30: Older, mean age 6:2 yr., n = 30) were randomly assigned to conditions in a 2 (sex) x 2 (age [Younger and Older]) x 3 (verbal instruction [Metaphorical, Movement-relevant, and None]) factorial design. Order scores were calculated for both performance and recognition tests, comprising five acquisition trials and two retention trials after 24 hr., respectively. Analysis of variance indicated that the group given metaphorical instruction performed better than the other two instructions for both younger and older children. The results suggest that metaphorical verbal instruction aids the recognition and performance of sequential dance skills in young children.

Child↗
PubMed2002

Overcoming multidrug drug resistance in P-glycoprotein/MDR1-overexpressing cell lines by ecteinascidin 743.

Ecteinascidin 743 (Et-743) is a novel anticancer agent forming covalent guanine adducts at specific sites in the DNA minor groove. Et-743 has a unique mechanism of action because it kills cancer cells by poisoning transcription-coupled nucleotide excision repair. Recent studies suggested a complex relationship between P-glycoprotein (P-gp)/MDR1 and Et-743. On one hand, Et-743 was reported to down-regulate the MDR1 promoter in vitro. On the other hand, P-gp overexpression was hypothesized to contribute to Et-743 resistance in an ovarian cell line. The present study was performed to further investigate the relationship between P-gp/MDR1 and the activity of Et-743. First, we found no P-gp/MDR1 overexpression (mRNA and protein levels) in two independently generated Et-743-resistant human colon carcinoma cell lines (HCT116/ER5 and SW480/ER0.5). Secondly, we found no cross-resistance to Et-743 in two well-characterized P-gp/MDR1-overexpressing cell lines (KB-8-5 and KB-C-2). Third, Et-743 pretreatment enhanced the cytotoxicity and the cellular accumulation of doxorubicin and vincristine in P-gp/MDR1-overexpressing KB-8-5/KB-C-2 cell lines. Fourth, we observed P-gp/MDR1 down-regulation by Et-743 in KB-C-2 cells. These results indicate that Et-743 does not select for the emergence of a P-gp phenotype in all cell lines made resistant to Et-743 and that P-gp overexpression is not sufficient to confer resistance to Et-743. Furthermore, Et-743 is an effective agent in P-gp-overexpressing cells. Et-743 can potentiate the activity of other chemotherapeutic agents by down-regulating P-gp/MDR1, suggesting that the combination of Et-743 and chemotherapeutic agents that are substrates for P-gp/MDR1 may be valuable in the clinic.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Prolonged expression of c-Fos protein in the lateral habenular nucleus of the Japanese monkey (Macaca fuscata) after eye enucleation.

To elucidate the effect of traumatic stress on the lateral habenular nucleus, we investigated the time course of the expression of c-Fos protein in this nucleus of the Japanese monkey (Macaca fuscata) after enucleation of one eye using c-Fos protein immunocytochemistry. c-Fos protein-like immunoreactive neurons were significantly increased; the increase started 1 h after the enucleation and remained high for 3-9 h in the lateral habenular nucleus on both sides. These results suggest that the prolonged expression of c-Fos protein occurred in the lateral habenular nucleus after traumatic stress through multiple transsynaptic activations.

Animals↗
PubMedDate not supplied

Pin1 is overexpressed in oral squamous cell carcinoma and its levels correlate with cyclin D1 overexpression.

Phosphorylation of serine or threonine residue preceding proline (Ser/Thr-Pro) is a key regulatory mechanism. The conformation of certain phosphorylated Ser/Thr-Pro bonds is regulated specifically by the prolyl isomerase Pin1. Inhibition of Pin1 induces apoptosis and may contribute to neuronal death in Alzheimer's disease. It has been reported that Pin1 is strikingly overexpressed in a subset of human tumors. The differential display screen revealed that Pin1 increases the transcription of several target genes, including cyclin D1 and c-myc genes. Pin1 cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. Pin1 also regulates turnover and subcellular localization of beta-catenin by inhibiting its interaction with adenomatous polyposis coli protein (APC). However, the analysis of Pin1 expression has not been demonstrated in human oral squamous cell carcinoma (OSCC). We examined the expression of Pin1 mRNA and protein in OSCC cell lines, and analyzed Pin1/cyclin D1/beta-catenin expression in OSCC clinical samples by immunohistochemical staining. We report that Pin1 is overexpressed in OSCC and its level correlates with cyclin D1 level. These results indicate that Pin1 is related to oncogenesis of OSCC.

Adult↗