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Mitsuhiro Matsuda

Publications and source records attributed to Mitsuhiro Matsuda.

At least 19 recordsLinked to original sources
PubMed2026

Systematic differences in protein stability underlie species-specific developmental tempo.

Human embryonic development proceeds more slowly than in mice. The segmentation clock offers a tractable model for studying species-specific developmental tempo, as its oscillation period in human induced presomitic mesoderm (iPSM) cells is approximately twice that of mouse. While the core clock gene HES7 exhibits slower protein degradation in human cells, it remains unclear whether such cross-species differences in protein stability reflect a general principle. Here, we perform a dynamic stable isotope labeling of amino acids in cell culture (SILAC)-based proteomic analysis of ∼5,000 proteins in human and mouse iPSM, and we uncover a broad trend of slower protein degradation in human cells, regardless of subcellular localization or degradation pathways. Moreover, inhibition of glycolysis in mouse iPSM partially phenocopies the human protein stability profile, and modulation of protein stability alters the tempo of both the segmentation clock and cellular differentiation. Our findings establish protein stability, with systematic differences across species, as a key mediator linking metabolism to developmental tempo.

Animals↗
PubMed2006

Clinical features and outcome of T-lineage acute lymphoblastic leukemia in adults: a low initial white blood cell count, as well as a high count predict decreased survival rates.

Although biological and clinical features differ between B-lineage acute lymphoblastic leukemia (ALL) and T-lineage ALL (T-ALL), there have been few reports that focused on the prognosis for T-ALL in adults, primarily due to its rarity. Here, we studied the long-term outcomes and prognostic factors specific for adult T-ALL by combining patient data from the three prospective trials conducted by the Japan Adult Leukemia Study Group (JALSG). Among 559 patients whose immunophenotypes could be evaluated, 87 (15.6%) were identified as T-ALL. Of them, 66 patients (75.8%) achieved complete remission, and relapse occurred in 41 patients. With a median follow-up for surviving patients of 7.5 years, the probability of overall survival was 35.0% at 5 years. Risk factor analysis revealed that serum albumin levels, initial white blood cell (WBC) counts, and age had independent values for predicting survival. For WBC, not only the high-count group (50 x 10(9)l(-1) or higher), but also the low-count group (less than 3 x 10(9)l(-1)) showed a significantly lower survival rates than the intermediate-count group (p=0.0055 and 0.0037, respectively). Although our findings need confirmation, these results will be helpful in the identification of prognostically distinct subgroups within adult T-ALL.

Adolescent↗
PubMed2006

Possible molecular target therapy with rapamycin in MDS.

The authors previously reported the mRNA expression of Glutathione S-transferases theta (GSTT)-1, wild type (623 bp) and mutant (500 bp) in MDS patients. The deletion of 123 bp creates a sequence that is homologues to mammalian target of rapamycin (mTOR). To analyse the function of mutant GSTT-1 gene, stable transformants for the mutant and wild-type GSTT-1 gene, respectively, were established. In this study, the expression of wild and mutant type GSTT-1 gene of those stable transformants and bone marrow cells from MDS patients by RT-PCR was observed in the presence or absence of rapamycin. In result, exposure of rapamycin led to the disappearance of just the mutant gene band. This phenomenon possibly indicates that rapamycin only attacked the mutant GSTT-1 expressing clone.

Bone Marrow Cells↗
PubMed2005

Clinical features of non-diabetic renal diseases in patients with type 2 diabetes.

Although persistent proteinuria is characteristic of diabetic nephropathy (DN), it is important to differentiate non-diabetic renal diseases (NDRD) in diabetic patients with proteinuria. In order to re-evaluate the indications for renal biopsy in the diabetic patients, we retrospectively analyzed the relationship between clinical features and histological diagnosis in 97 Japanese patients with type 2 diabetes manifesting overt proteinuria. Renal biopsy was performed because they were clinically suspected to have NDRD. Patients were divided into three groups according to the histological diagnosis: (1) the DN group (n=35) had only diabetic lesions, (2) the complicated group (n=16) had histological changes of NDRD superimposed on DN and (3) the non-DN group (n=46) had NDRD without diabetic lesions. We evaluated the specificity and sensitivity of four clinical parameters (duration of diabetes, presence or absence of diabetic retinopathy, microscopic hematuria and granular casts as urinary sediments) for the prediction of NDRD. Short duration of diabetes (<5 years) showed high sensitivity (75%) and specificity (70%). Diabetic retinopathy showed the highest sensitivity (87%) and specificity (93%). The sensitivity and specificity of microscopic hematuria (56 and 58%) and granular casts (68 and 47%) were lower. Our study confirmed that the absence of retinopathy and short duration of diabetes are useful clinical indications for renal biopsy in diabetic patients with overt proteinuria.

Biopsy↗
PubMed2005

Sulfated hyaluronic acid, a potential selectin inhibitor, ameliorates experimentally induced crescentic glomerulonephritis.

BACKGROUND/AIMS: Sulfated polysaccharides are known to interfere with the binding of selectins and their ligands. Recently, we demonstrated that sulfated hyaluronic acid (SHA), a synthetic sulfated polysaccharide, showed preventive and therapeutic effects on experimental mesangial proliferative glomerulonephritis. Here we evaluated the protective potential of SHA on crescentic glomerulonephritis, using nephrotoxic serum (NTS) nephritis in Wistar-Kyoto (WKY) rats. METHODS: Crescentic glomerulonephritis was induced by injection of NTS in WKY rats. Rats subsequently received intraperitoneal administration of SHA (0.5 or 1.5 mg/kg/day) or non-sulfated hyaluronic acid (HA) (1.5 mg/kg/day) for 14 days. The urinary protein excretion was measured, and expression of selectins, intraglomerular leukocytes and crescent formation were examined by immunohistochemistry. In addition, we examined the urinary protein excretion of SHA (1.5 mg/kg/day) administered from day 7 after the induction of crescentic glomerulonephritis. RESULTS: The expression of P-selectin was increased in the glomerulus of crescentic glomerulonephritis. SHA reduced proteinuria, macrophage infiltration, and crescent formation in a dose-dependent manner. Furthermore, administration of SHA (1.5 mg/kg/day) from day 7 also reduced the urinary protein excretion on day 14 compared with that in saline and HA group. CONCLUSION: Our results suggest that SHA inhibits intraglomerular infiltration of macrophages, and prevents progression of experimental crescentic glomerulonephritis. Sulfated polysaccharides might be beneficial for the treatment of crescentic glomerulonephritis.

Adjuvants, Immunologic↗
PubMed2005

Correlation between expression of orotate phosphoribosyl transferase and 5-fluorouracil sensitivity, as measured by apoptosis index in colorectal cancer tissue.

BACKGROUND: 5-Fluorouracil remains a key drug in the treatment of colorectal cancer, and the development of a simple and effective test for selecting patients likely to benefit from postoperative adjuvant chemotherapy is an important objective. AIM OF THE STUDY: This study aimed to clarify the feasibility of measuring apoptotic cell rate (AI%) in tumor after short-term oral 5-fluorouracil administration prior to surgery with the objective of establishing a simpler method to test for sensitivity. METHODS: Forty-five colorectal cancer patients were allocated to two groups, and 21 patients were given oral 5-FU for 3 d prior to surgery. The AI% in surgical specimen, detected by TUNEL staining, was compared in the 5-FU-loaded and control groups. The correlation of AI% with 5-FU metabolic enzyme mRNA levels in tumor was also evaluated. RESULTS: The AI% was significantly higher in the tumor tissue of patients receiving 5-FU than in the control group (p < 0.0005). Although insignificant, thymidylate synthase mRNA level and orotate phosphoribosyl transferase mRNA demonstrated a weak positive correlation with AI%. CONCLUSIONS: The AI% measurement in tumor tissue following a 5-FU oral load for 3 d prior to surgery was feasible. It remains to be elucidated if this measurement as a new 5-FU sensitivity test reflects the prognosis with 5-FU-based postoperative adjuvant chemotherapy.

Administration, Oral↗
PubMed2005

Extramedullary blast crisis derived from 2 different clones in the central nervous system and neck during complete cytogenetic remission of chronic myelogenous leukemia treated with imatinib mesylate.

We describe a patient with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who developed an extramedullary blast crisis in the central nervous system (CNS) and then a subcutaneous tumor of the neck during treatment with imatinib mesylate. Administered 400 mg of imatinib mesylate after the diagnosis of chronic-phase CML, the patient achieved a complete cytogenetic remission 4 months later. However, he developed a mixed myeloid/B-cell blast crisis with additional karyotype abnormalities only in the CNS during a complete cytogenetic remission in the bone marrow. Several doses of intrathecal chemotherapy and whole-brain irradiation were effective in treating the blast crisis in the CNS. After 7 months of complete cytogenetic remission, the patient experienced a subcutaneous tumor in the right neck. A biopsy of the tumor revealed a mixed myeloid/T-cell blast crisis. The cytogenetic analysis showed that the blast crisis clone in the neck tumor was different from that of the CNS. An increased dose of imatinib mesylate was ineffective in treating the neck tumor. Irradiation to the right neck was therefore undertaken. This case suggests that the development of a clone resistant to imatinib mesylate is not always detected in the bone marrow and that multiple Ph-positive clones have the potential to become transformed into a blast crisis.

Adolescent↗
PubMed2004

A perforin/granzyme-positive MDS-derived T cell line, K2-MDS, induces apoptosis in CD34+ cells through the fractalkine-CX3CR1 system.

Fractalkine (CX3CL1) and its receptor CX3CR1 play an important role in natural killer (NK) cell- and cytotoxic T cell-mediated endothelium damage. Here we describe the cytotoxicity of myelodysplastic syndrome (MDS)-derived T cell line, K2-MDS, through the fractalkine-CX3CR1 system. K2-MDS cells induced apoptosis against CD34(+) cells from normal bone marrow (BM) in a direct cell contact manner. K2-MDS cells expressed perforin and granzyme B, but they lacked Fas ligand expression. A specific inhibitor for perforin, concanamycin A, blocked K2-MDS-dependent cytotoxicity. Furthermore, a CX3C-chemokine, fractalkine, was expressed in CD34(+) cells, and its receptor, CX3CR1, was expressed on K2-MDS cells. The neutralizing monoclonal antibody (MoAb) for fractalkine and soluble fractalkine significantly inhibited K2-MDS-dependent cytotoxicity. K2-MDS cells also induced the cytotoxicity against human umbilical cord endothelial cells (HUVECs) expressing fractalkine. These data indicate that K2-MDS may be a perforin-granzyme-positive T cell line that exerts a cytotoxic effect on CD34(+) cells mediated through the fractalkine-CX3CR1 system.

Antigens, CD34↗
PubMed2003

Cerebroside sulfotransferase deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction.

Mononuclear cells infiltrating the interstitium are involved in renal tubulointerstitial injury. The unilateral ureteral obstruction (UUO) is an established experimental model of renal interstitial inflammation. In our previous study, we postulated that L-selectin on monocytes is involved in their infiltration into the interstitium by UUO and that a sulfated glycolipid, sulfatide, is the physiological L-selectin ligand in the kidney. Here we tested the above hypothesis using sulfatide- and L-selectin-deficient mice. Sulfatide-deficient mice were generated by gene targeting of the cerebroside sulfotransferase (Cst) gene. Although the L-selectin-IgG chimera protein specifically bound to sulfatide fraction in acidic lipids from wild-type kidney, it did not show such binding in fractions of Cst(-/-) mice kidney, indicating that sulfatide is the major L-selectin-binding glycolipid in the kidney. The distribution of L-selectin ligand in wild-type mice changed after UUO; sulfatide was relocated from the distal tubules to the peritubular capillaries where monocytes infiltrate, suggesting that sulfatide relocated to the endothelium after UUO interacted with L-selectin on monocytes. In contrast, L-selectin ligand was not detected in Cst(-/-) mice irrespective of UUO treatment. Compared with wild-type mice, Cst(-/-) mice showed a considerable reduction in the number of monocytes/macrophages that infiltrated the interstitium after UUO. The number of monocytes/macrophages was also reduced to a similar extent in L-selectin(-/-) mice. Our results suggest that sulfatide is a major L-selectin-binding molecule in the kidney and that the interaction between L-selectin and sulfatide plays a critical role in monocyte infiltration into the kidney interstitium.

Animals↗
PubMed2003

Collagen XVIII, a basement membrane heparan sulfate proteoglycan, interacts with L-selectin and monocyte chemoattractant protein-1.

Leukocyte infiltration during inflammation is mediated by the sequential actions of adhesion molecules and chemokines. By using a rat ureteral obstruction model, we showed previously that L-selectin plays an important role in leukocyte infiltration into the kidney. Here we report the purification, identification, and characterization of an L-selectin-binding heparan sulfate proteoglycan (HSPG) expressed in the rat kidney. Partial amino acid sequencing and Western blotting analyses showed that the L-selectin-binding HSPG is collagen XVIII, a basement membrane HSPG. The binding of L-selectin to isolated collagen XVIII was specifically inhibited by an anti-L-selectin monoclonal antibody, EDTA, treatment of the collagen XVIII with heparitinase or heparin but not by chemically desulfated heparin. A cell binding assay showed that the L-selectin-collagen XVIII interaction mediates cell adhesion. Interestingly, collagen XVIII also interacted with a chemokine, monocyte chemoattractant protein-1, and presented it to a monocytic cell line, THP-1, which enhanced the alpha(4)beta(1) integrin-mediated binding of the THP-1 cells to vascular cell adhesion molecule-1. Thus, collagen XVIII may provide a link between selectin-mediated cell adhesion and chemokine-induced cellular activation and accelerate the progression of leukocyte infiltration in renal inflammation.

Amino Acid Sequence↗
PubMed2003

Successful treatment of necrotizing fasciitis associated with diabetic nephropathy.

A 50-year-old woman with a 15-year history of type 2 diabetes mellitus was admitted to our hospital due to high fever and a skin lesion with severe pain, swelling and a sensation of heat in the right thigh. Laboratory examination showed elevated C-reactive protein (CRP), thrombocytopenia, nephrotic syndrome and renal dysfunction. Her blood glucose level had been well controlled. Streptococcus agalactiae was detected in both the skin lesion and blood culture, and pathological examination revealed neutrophil infiltration in the fascia and muscle layer. The patient was diagnosed with necrotizing fasciitis, septic shock and disseminated intravascular coagulation. A combination therapy of antibiotics and surgical debridement resulted in the improvement of symptoms as supported by laboratory findings, and the skin lesion also showed improvement. Although group A streptococcus is well known to be implicated in the pathogenesis of necrotizing fasciitis, only S. agalactiae, belonging to group B streptococcus, was isolated from the tissue and blood cultures in this case. Although this organism is not virulent and rarely causes a necrotizing fasciitis, both the superficial fascial layer and underlying muscle were affected in this case. There have been only a few reports of necrotizing fasciitis due to S. agalactiae in patients with diabetes mellitus. Although the blood glucose level was well controlled in our patient, this disease might be caused by other factors, including diminished sense of touch and pain, abnormality of microcirculation and hypogammaglobulinemia due to nephrotic syndrome.

Anti-Bacterial Agents↗
PubMed2003

Pelvic lymphocyst infection associated with maternally inherited diabetes mellitus.

A 45-year-old woman with 20-year history of diabetes mellitus was admitted to our hospital because of high fever and abdominal pain. Radical hysterectomy and bilateral pelvic lymphadenectomy had been performed 4 months before admission for invasive cervical cancer. On admission, elastic hard tumors were palpable in the lower abdomen. Laboratory examination showed positive C-reactive protein (CRP), anemia and renal dysfunction. Computed tomography (CT) revealed several lymphocysts in the pelvis. She was diagnosed with infection of pelvic lymphocysts. Since her mother also had diabetes associated with deafness, we examined mitochondrial DNA in leukocytes and detected an A to G transition at the nucleotide position of 3243 (A3243G mutation). She was diagnosed as maternally inherited diabetes mellitus and deafness (MIDD). Puncture of the cysts followed by administration of antibiotics resulted in marked improvement of symptoms and laboratory findings. This is a rare case of pelvic lymphocyst infection in a patient with a mitochondrial disorder. Although the exact mechanism of infection is not clear, MIDD may represent an unusual risk factor for infection, and further investigation is necessary to assess the influence of mitochondrial dysfunction on the immune system. Pelvic lymphocyst infection should be considered in the differential diagnosis of abdominal pain and fever in patients with MIDD after abdominal surgery.

Abdominal Pain↗
PubMed2003

Mutant type glutathione S-transferase theta 1 gene homologue to mTOR in myelodysplastic syndrome: possible clinical application of rapamycin.

In this study, we observed the expression of the GSTT-1 gene in patients with myelodysplastic syndrome (MDS) at the messenger RNA level. Reverse transcription-polymerase chain reaction (RT-PCR) for GSTT-1 was performed with a pair of primers complementary to the 5' coding section and the 3' coding section of the GSTT-1 cDNA for amplifying the 623-bp band. Among 20 patients with MDS, 8 patients showed the expected 623-bp band on RT-PCR, and 12 patients showed a 500-bp band on RT-PCR, indicating that a 123-bp sequence was deleted as a mutant of the GSTT-1 gene. Furthermore, a BLAST DNA search showed that the deletion of a 123 bp sequence creates a sequence that is 63% homologous to human FKBP-rapamycin associated protein (FRAP); this protein has been termed a mammalian target of rapamycin (mTOR). We respectively transfected the wild type and the mutant type GSTT-1 gene in an expression vector to two cell lines (K562 and HL-60). The stable transformants for the wild type and the mutant type GSTT-1 genes were made by G418 selection. Interestingly, rapamycin could induce significant growth inhibition of the stable transformants for mutant type GSTT-1, which was indicative of apoptosis, but not that of those for wild type GSTT-1. These results suggest that rapamycin could be included in the therapeutic modality for the patients with MDS who have the mTOR sequences in GSTT-1 gene.

Annexin A5↗
PubMed2003

HMG-CoA reductase inhibitor ameliorates diabetic nephropathy by its pleiotropic effects in rats.

BACKGROUND: An inflammatory process may be one of the critical factors that contribute to the development of diabetic nephropathy (DN). We reported previously that intercellular adhesion molecule-1 (ICAM-1) is up-regulated and promotes macrophage infiltration in the glomeruli of diabetic rats. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have recently been emphasized to have anti-inflammatory effects; inhibition of leukocyte adhesion and migration, independent of the cholesterol-lowering effect. The present study was designed to test the hypothesis that statins prevent the development of DN by pleiotropic effects. METHODS: Streptozotocin-induced diabetic rats were treated with cerivastatin (0.5 mg/kg body weight) or vehicle for 4 weeks. We analysed glomerular macrophage infiltration and ICAM-1 expression. We also evaluated major regulators of ICAM-1, activation of nuclear factor-kappa B (NF-kappaB) using electrophoretic mobility shift assay, and oxidative stress. RESULTS: Statin treatment reduced urinary albumin excretion (UAE) (2.96+/-0.18 vs 2.38+/-0.06; log(10) UAE, P<0.05), glomerular size (12 150+/-329 vs 9963+/-307 micro m(2), P<0.05), and lowered blood pressure, compared with untreated diabetic rats. Immunohistochemistry revealed that macrophage infiltration and ICAM-1 expression in glomeruli were increased in diabetic rats and were inhibited by statin treatment. Renal NF-kappaB activity, urinary excretion and renal deposition of 8-OHdG were increased in diabetic rats, and reduced by statin treatment. CONCLUSION: Statin treatment prevented glomerular injury, independent of the cholesterol-lowering effects. Our findings suggest that the beneficial effect might be mediated by pleiotropic effects including an anti-inflammatory action through a reduction of oxidative stress, NF-kappaB activation, ICAM-1 expression and macrophage infiltration in the early phase of DN.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Effect of combination of TS-1 and low-dose cisplatin on sarcoma-180 mouse sarcoma.

TS-1 contains tegaful (FT), 5-chloro-2,4-dihydroxypyridine (CDHP; an inhibitor of 5-fluorouracil (5-FU) degradation) and potassium oxonate (Oxo; an inhibitor of 5-FU assimilation mainly in the digestive tract) in a molar ratio of 1:0.4:1. We evaluated the combination of TS-1 and low-dose cisplatin on mouse sarcoma. Male ddy strain mice at 6 weeks of age were s.c. transplanted with 5 x 106 sarcoma-180 (S-1800) cells and divided into groups of seven animals each: Group A, no treatment; Group B, 5-FU alone by continuous i.p. infusion of 10 mg/kg with a minipump (Alzet); Group C, TS-1 10 mg/kg p.o. alone; Group D, cisplatin 0.2 mg/kg i.p. alone; Group E, B+D; Group F, C+D. Treatment was given for 5 days. Antitumor activity was evaluated on the basis of the tumor weight on day 8, and white blood cell count, red blood cell count, platelet count, BUN, GOT and GPT were determined to detect adverse effects. Tumor weights (g, mean+/-SD) were 0.54+/-0.15 in Group A, 0.52+/-0.17 in Group B, 0.34+/-0.05 in Group C, 0.46+/-0.12 in Group D, 0.34+/-0.07 in Group E and 0.16+/-0.03 in Group F. There were no noticeable adverse effects. The combined TS-1+cisplatin regimen showed considerably enhanced antitumor activities since sarcomas were significantly (p<0.05) decreased as compared with tissue. Mean AUC(0-12) (ng/ml.h) estimated in the groups receiving 5-FU+cisplatin or TS-1 alone was measured to calculate AUC(0-12) by the trapezoidal rule. 5-FU concentrations in blood and tumor from blood concentration data were 435 in Group B, 2651 in Group C, 343 in Group E and 1538 in Group F, while mean AUC(0-12) (ng/g.h) estimated from tumor tissue concentration data were 345 in Group B, 3548 in Group C, 324 in Group E and 2020 in Group F. Cisplatin acted as a modulator of 5-FU, suggesting clinical benefits of the combination of TS-1 and low-dose daily cisplatin.

Animals↗
PubMed2003

Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes.

Diabetic nephropathy is a leading cause of end-stage renal failure. Several mechanisms, including activation of protein kinase C, advanced glycation end products, and overexpression of transforming growth factor (TGF)-beta, are believed to be involved in the pathogenesis of diabetic nephropathy. However, the significance of inflammatory processes in the pathogenesis of diabetic microvascular complications is poorly understood. Accumulation of macrophages and overexpression of leukocyte adhesion molecules and chemokines are prominent in diabetic human kidney tissues. We previously demonstrated that intercellular adhesion molecule (ICAM)-1 mediates macrophage infiltration into the diabetic kidney. In the present study, to investigate the role of ICAM-1 in diabetic nephropathy, we induced diabetes in ICAM-1-deficient (ICAM-1(-/-)) mice and ICAM-1(+/+) mice with streptozotocin and examined the renal pathology over a period of 6 months. The infiltration of macrophages was markedly suppressed in diabetic ICAM-1(-/-) mice compared with that of ICAM-1(+/+) mice. Urinary albumin excretion, glomerular hypertrophy, and mesangial matrix expansion were significantly lower in diabetic ICAM-1(-/-) mice than in diabetic ICAM-1(+/+) mice. Moreover, expressions of TGF-beta and type IV collagen in glomeruli were also suppressed in diabetic ICAM-1(-/-) mice. These results suggest that ICAM-1 is critically involved in the pathogenesis of diabetic nephropathy.

Albuminuria↗