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H Moriyama

Publications and source records attributed to H Moriyama.

At least 19 recordsLinked to original sources
PubMed2006

A new model of insulin-deficient diabetes: male NOD mice with a single copy of Ins1 and no Ins2.

AIMS/HYPOTHESIS: We describe a novel model of insulin-deficient diabetes with a single copy of the gene encoding insulin 1 (Ins1) and no gene encoding insulin 2 (Ins2). MATERIALS AND METHODS: We constructed five lines of mice: mice with two copies of Ins1 (NOD( Ins1+/+,Ins2-/-)), mice with a single copy of Ins1 (NOD( Ins1+/-,Ins2-/-)), mice with two copies of Ins2 (NOD( Ins1-/-,Ins2+/+)), mice with a single copy of Ins2 (NOD( Ins1-/-,Ins2+/-)) and NOD( Ins1+/-,Ins2-/-) mice with a transgene encoding B16:Ala proinsulin. RESULTS: By 10 weeks of age, all male NOD( Ins1+/-,Ins2-/-) mice were diabetic, whereas all female NOD( Ins1+/-,Ins2-/-) were not diabetic (p < 0.0001). In contrast, neither male nor female NOD( Ins1-/-,Ins2+/-) with a single copy of Ins2 (rather than single copy of Ins1) developed early diabetes and no mice with two copies of either gene developed early diabetes. Islets of the diabetic male NOD( Ins1+/-,Ins2-/-) at this early age had no lymphocyte infiltration. Instead there was heterogeneous (between islet cells) weak staining for insulin. Although only male NOD( Ins1+/-,Ins2-/-) mice developed diabetes, both male and female NOD( Ins1+/-,Ins2-/-) mice had markedly decreased insulin content. In NOD( Ins1+/+,Ins2-/-), there was also a significant decrease in insulin content, whereas NOD( Ins1-/-,Ins2+/+) mice, and even NOD( Ins1-/-,Ins2+/-) mice, were normal. Male NOD( Ins1+/-,Ins2-/-) mice were completely rescued from diabetes by introduction of a transgene encoding proinsulin. On i.p. insulin tolerance testing, male mice had insulin resistance compared with female mice. CONCLUSIONS/INTERPRETATION: These results suggest that Ins1 is a 'defective gene' relative to Ins2, and that the mouse lines created provide a novel model of sex-dimorphic insulin-deficient diabetes.

Animals↗
PubMed2006

Comparison of muscular and articular factors in the progression of contractures after spinal cord injury in rats.

STUDY DESIGN: Experimental, controlled trial. OBJECTIVES: To identify the relationship between the muscular and articular factors in the progression of contractures after spinal cord injury (SCI). SETTING: Hiroshima University, Hiroshima, Japan. METHODS: In total, 48 female Wistar rats were used. The 24 experimental rats that underwent a spinal cord transection and the other 24 control rats that underwent a sham-operation were assessed at 2, 4, 8, 12, 16, or 24 weeks postsurgery. Knee joint motion was measured for flexion and extension. Myotomy of the transarticular muscles was then performed and range of motion was measured again. The degree of contractures was assessed by goniometry measuring the femorotibial angle before and after the myotomies. RESULTS: The spinal cord-injured rats demonstrated flaccid paralysis during the first few days postsurgery and thereafter spastic paralysis. Intra- and inter-rater reliabilities for all measurements were >0.814. Knee flexion contractures developed in the all experimental rats, and progressed for the first 12 weeks and plateaued thereafter. Both the muscular (48+/-5%) and articular (52+/-5%) factors contributed almost equally to the overall progression of the contracture. CONCLUSION: The present findings may shed light on the underlying pathophysiology of contractures and should help guide research towards finding the elucidation of contracture development after SCI.

Animals↗
PubMed2006

Retroperitoneoscopic radical nephrectomy in obese patients: outcomes and considerations.

OBJECTIVE: To determine whether obesity is associated with surgical outcome in Japanese patients undergoing retroperitoneoscopic radical nephrectomy (RRN). PATIENTS AND METHODS: Between November 1999 and March 2005, we performed 98 RRN procedures for patients with renal cell carcinoma. Patients with a body mass index (BMI) of 25.0 or more were defined as obese (group A, n=33) and those with a BMI of <25.0 were defined as non-obese (group B, n=65), in accordance with the criteria of the Japan Society for the Study of Obesity. Patient background, degree of surgical invasiveness, and period of convalescence were compared between groups A and B. RESULTS: No statistically significant differences were observed between the groups in terms of age, gender, tumor laterality, tumor size, and time until resumption of oral intake and ambulation. However group A had a significantly longer insufflation time (172.1 vs. 137.4 min), greater blood loss (195.3 vs. 48.4 ml) and higher renal specimen weight (440.0 vs. 306.0 g) than group B. CONCLUSION: Obesity is not a factor that affects patient eligibility for RRN, but is a risk factor for longer insufflation time and greater blood loss.

Carcinoma, Renal Cell↗
PubMed2006

Primary extramedullary plasmacytoma of the small intestine. A case report and review of the literature.

A case of primary extramedullary plasmacytoma of the small intestine in a 73-year-old Japanese woman was reported. The patient underwent local resection of the tumor, and showed no signs of local recurrence or dissemination of the disease after 28 months follow-up. The tumor cells had relatively large nuclei with distinct nucleoli and wide and slightly basophilic cytoplasm with a high N/C ratio which showed the morphology of atypical plasma cells. Immunohistochemical examination revealed that the tumor cells contained IgG gamma-type immunoglobulin in their cytoplasm but they did not contain IgA, IgM, IgD, and kappa-light chains. The tumor cells were also positive for CD79a and CD138 and negative for LCA, CD20 and CD45RO. These findings clearly indicated this case to be plasmacytoma.

Aged↗
PubMed2005

The wide distribution of endornaviruses, large double-stranded RNA replicons with plasmid-like properties.

The International Committee on Taxonomy of Viruses (ICTV) recently accepted Endornavirus as a new genus of plant dsRNA virus. We have determined the partial nucleotide sequences of the RNA-dependent RNA polymerase regions from the large dsRNAs (about 14 kbp) isolated from barley (Hordeum vulgare), kidney bean (Phaseolus vulgaris), melon (Cucumis melo), bottle gourd (Lagenaria siceraria), Malabar spinach (Basella alba), seagrass (Zostera marina), and the fungus Helicobasidium mompa. Phylogenetic analyses of these seven dsRNAs indicate that these dsRNAs are new members of the genus Endornavirus that are widely distributed over the plant and fungal kingdoms.

Basidiomycota↗
PubMed2004

T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes.

AIMS/HYPOTHESIS: Fulminant Type 1 diabetes is a novel subtype of Type 1 diabetes that involves the abrupt onset of insulin-deficient hyperglycaemia. This subtype appears to be non-autoimmune because of the absence of diabetes-related autoantibodies in the serum, and of insulitis in pancreatic biopsy specimens. The pathogenesis of the disease is still unknown. In this study, we investigated whether T cell autoimmune responses are involved in fulminant Type 1 diabetes. METHODS: Cellular immune responses to beta cell autoantigens were studied by enzyme-linked immunospot (ELISPOT) assay in 13 fulminant Type 1 diabetic patients and 49 autoantibody-positive autoimmune Type 1 diabetic patients. Results were compared with those of 18 Type 2 diabetic patients, six secondary diabetic patients (diabetes due to chronic pancreatitis) and 35 healthy controls. RESULTS: Nine of 13 (69.2%) GAD-reactive Th1 cells, and three of 12 (25%) insulin-B9-23-reactive Th1 cells were identified in fulminant Type 1 diabetic patients by ELISPOT, as in autoantibody-positive Type 1 diabetic patients. Four fulminant Type 1 diabetic patients possessed the highly diabetes-resistant allele DR2, three of whom had GAD-reactive Th1 cells in the periphery. CONCLUSIONS/INTERPRETATION: Peripheral immune reaction was observed in 69.2% of fulminant Type 1 diabetic patients, indicating that autoreactive T cells might contribute, at least in part, to the development of fulminant Type 1 diabetes.

Adolescent↗
PubMed2004

Differential immune response to B:9-23 insulin 1 and insulin 2 peptides in animal models of type 1 diabetes.

Mice have two insulin genes that differ in the insulin sequence by two amino acids, including the B9 position. Given prior studies of the B:9-23 insulin peptide in NOD mice, a fundamental question is whether the immune response to the B:9-23 peptide of the two insulins is identical. We investigate responses to the immunization with B:9-23 insulin 1 and 2 peptides in NOD and RIP-B7.1 Balb/c mice. NOD and F1 (Balb/c x C57/Bl6) B7.1 transgenic mice were given either B:9-23 insulin 1, B:9-23 insulin 2 or tetanus toxoid (TT) control peptide. Insulin autoantibodies (IAA), and anti-B:9-23 antibodies (IgG1 and IgG2c) were measured. Subcutaneous injection of the insulin 2 but not the insulin 1 peptide significantly protected NOD mice from diabetes. Conceptually similar, insulin 1 peptide immunization accelerated diabetes in the B7.1 mice compared with insulin 2 peptide. Insulin 1 and 2 peptides induced similar levels of IAA in the NOD mice except at week 26, where insulin 2 induced higher levels of IAA. Anti-IgG1 B:9-23 peptide antibodies were higher in the insulin 2 immunized group of NOD mice, while IgG2c anti-B:9-23 peptide antibodies were higher in the insulin 1 group. Adoptive transfer of splenocytes from insulin 1 immunized mice to NOD.scid mice demonstrated accelerated diabetogenicity. The protection afforded by insulin 2 peptide but not insulin 1 peptide in the NOD mouse is reflected by its predominant Th2 humoral response. This may relate to the protection conferred by the insulin 1 knockout when bred onto NOD mice in contrast to acceleration of disease with an insulin 2 knockout.

Animals↗
PubMed2004

Two-step three-field lymph node dissection is beneficial for thoracic esophageal carcinoma.

Aggressive surgery including extensive lymph node dissection is considered necessary to improve the long-term survival of patients with esophageal carcinoma. While three-field lymph node dissection is widely performed for patients with thoracic esophageal carcinoma, cervical lymph node metastasis is uncommon. In order to reduce surgical stress, we have developed a two-step three-field lymph node dissection procedure for thoracic esophageal carcinoma. In the first-step operation, total thoracic esophagectomy through a right thoracotomy is performed. Mediastinal and abdominal lymph node dissection is performed synchronously. When recurrent nerve lymph node metastasis is pathologically positive, cervical lymph node dissection is performed about 3 weeks after the first operation (second step). Of 343 patients with carcinoma of the esophagus surgically treated in our department between 1990 and 2001, 146 underwent the operation described above. Three-field dissection was performed in 68 patients (group A), while two-field dissection was performed in 78 patients (group B). In the 68 group A patients, cervical lymph node metastasis was positive in 15 patients (22%). There was no marked difference in the onset of major complications between the two groups. The 5-year survival rate was 58% for group A and 61% for group B, not a statistically significant difference. In 78 of the 146 patients, it was possible to avoid cervical lymph node dissection without negatively affecting therapeutic outcomes. Two-step three-field lymph node dissection can reduce surgical stress of patients with good clinical outcome.

Aged↗
PubMed2003

Critical roles of CD30/CD30L interactions in murine autoimmune diabetes.

CD30/CD30L is a member of tumour necrosis factor (TNF) receptor/TNF superfamily and has been implicated in immune-regulation. A genetic study has also suggested a possible implication of CD30 in spontaneous autoimmune diabetes in NOD mice. In this study, we investigated the involvement of CD30/CD30L in the development of diabetes in NOD mice. Flow cytometric analysis showed that CD30 and CD30L were highly expressed on CD4+ or CD8+ T cells in the spleen and pancreatic lymph node of younger NOD mice. In addition, islet-specific CD4+ or CD8+ T cell lines expressed CD30 and CD30L. Administration of a neutralizing anti-CD30L monoclonal antibody (mAb) from 2 to 10 week of age completely suppressed the development of spontaneous diabetes in NOD mice. In addition, the treatment with anti-CD30L mAb also inhibited the development of diabetes induced by adoptive transfer of spleen cells from diabetic NOD mice or islet-specific CD4+ or CD8+ T cell lines into NOD-SCID mice. Furthermore, anti-CD30L mAb inhibited T cell proliferation in response to islet antigens. These results suggested that CD30/CD30L interaction plays important roles in both induction and effector phases of autoimmune diabetes in NOD mice.

Adoptive Transfer↗
PubMed2003

Resection surgery with neoadjuvant chemoradiotherapy improves outcomes of patients with T4 esophageal carcinoma.

The prognosis of patients with T4 esophageal carcinoma is poor, and thus an effective treatment needs to be established. The present study assessed the effect of chemoradiotherapy (CRT), postoperative morbidity and mortality, and survival time in 41 patients with T4 esophageal carcinoma. Of these, 24 received CRT followed by surgery (group A) and the remaining 17 were treated with CRT alone (group B). Postoperative complications in group A were compared with 251 patients (group C) who underwent surgery without CRT during the same period. Postoperative complications were more frequent in group A than group C (29.2% vs 8.4%, P < 0.05). The overall median survival of group A was statistically longer than that of group B (13.8 months and 3.3 months respectively, P < 0.001). Complete histologic response (grade 3) was documented in 4 group A patients (16.7%). The overall median survival of grade 3 patients was statistically longer than the rest of group A (38.9 months vs 8.8 months, P < 0.05). The data confirm that chemoradiotherapy creates tumor regression in some patients and allows resection surgery in T4 esophageal carcinoma. Moreover, surgery with CRT confers a survival advantage in T4 esophageal carcinoma.

Aged↗
PubMed2003

High level concentration of pyrimidine nucleoside phosphorylase in esophageal squamous cell carcinoma but no correlation with clinicopathological parameters.

Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine to 5'-fluorouracil, which exerts an anticancer effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). Recently, PyNPase has been shown to be identical to a potent angiogenic factor, platelet-derived endothelial cell growth factor. We analyzed the concentration of PyNPase and DPD in 33 patients with esophageal squamous cell carcinoma in fresh-frozen samples by enzyme-linked immunosorbent assay. In addition, we evaluated the clinical significance and prognostic value of PyNPase expression in esophageal carcinoma. The PyNPase concentration of tumor tissue was statistically higher than that of normal tissue of the esophagus (248 +/- 146 U/mg protein vs 73 +/- 63 U/mg protein, P = 0.0001), whereas DPD showed no difference (90 +/- 62 U/mg protein vs 88 +/- 62 U/mg protein, P = 0.825). The ratio of PyNPase to DPD of tumor tissue was statistically higher than that of normal tissue of the esophagus (3.3 vs 0.95, P = 0.0001). There were no significant differences between the group with high tumor to normal tissue ratios of PyNPase concentration and the low-ratio group in terms of the tumor length, depth, lymph node metastasis, lymph vessel invasion, vascular invasion, stage and survival. In conclusion, 5'-deoxy-5-fluorouridine may be effective on esophageal carcinoma and PyNPase concentration in esophageal carcinoma may not be a useful prognostic marker for patients with esophageal squamous cell carcinoma.

Adult↗
PubMed2002

Nuclear BAG-1 expression reflects malignant potential in colorectal carcinomas.

BAG-1 is a recently identified Bcl-2-interacting anti-apoptotic protein. The aim of our study was to investigate the immunohistochemical staining pattern of BAG-1 protein in patients with colorectal cancer and examine associations of BAG-1 expression with various clinicopathological factors and patient survival. Tumour samples were collected from 86 patients diagnosed with colorectal cancer. There was significant variation in the immunohistochemical staining patterns for BAG-1, including absent staining and staining of either the cytoplasm, nucleus or both. Twenty-one colorectal carcinomas (24.4%) exhibited a nuclear staining pattern whilst 56 (65.1%) exhibited cytoplasmic staining. The percentage of cases exhibiting nuclear BAG-1 positivity was significantly higher in distant metastasis-positive cases (55.6%) than in distant metastasis-negative cases (20.8%; P=0.036). Overall survival was significantly shorter for patients with tumours exhibiting BAG-1 positive nuclei than those with absent nuclear BAG-1-staining (P=0.011). In addition, the multivariate cox proportional hazard models indicated that nuclear BAG-1 expression was the only independent prognostic variable for mortality (P=0.013). These studies demonstrate that nuclear BAG-1 expression is a useful predictive factor for distant metastasis and a poor prognosis in patients with colorectal cancer.

Carrier Proteins↗
PubMed2002

Interferon-gamma production changes in parallel with bacterial lipopolysaccharide induced bone resorption in mice: an immunohistometrical study.

It has been reported that bacterial lipopolysaccharide (LPS) induces alveolar bone resorption and that the host immune system, especially activated T cells, plays a crucial role in osteoclastogenesis. On the other hand, interferon-gamma (IFN-g), which is produced by activated T cells, suppresses bone resorption both in vitro and in vivo. Thus, the question arises as to whether or not IFN-g production increases with increasing bone resorption. We previously demonstrated that repeated injections of Escherichia coli LPS into mouse gingiva causes osteoclast formation in alveolar bone. In the present study we observed changes in the IFN-g production of infiltrating cells in concurrence with bone resorption. Mice were repeatedly injected with 5 mg LPS 26 times every 48 hours. After the 16th injection, when the alveolar bone resorption reached a plateau, the concentration of LPS was altered (25 mg LPS or PBS alone). The level of bone resorption became significantly elevated, and the number of IFN-g- and interleukin-1 beta (IL-1b)-bearing cells also increased significantly in relation to bone resorption within the 25 mg LPS-injected group. On the other hand, few tartrate-resistant acid phosphatase positive cells, or IFN-g- and IL-1b-bearing cells, were seen in the PBS-injected group. These results suggest that alteration in IFN-g-bearing cells might play a role in counterbalancing LPS-induced bone resorption resulting from osteoclast activating cytokines such as IL-1b.

Animals↗
PubMed2002

Allelic imbalance and microsatellite instability in plasma DNA released from polyclonal pancreatic adenocarcinoma.

Evidence of circulating soluble DNA in blood-stream of cancer patients has emerged. Because the plasma DNA is largely derived from cancer cells, genetic analysis of plasma DNA is important to understand the molecular events occurred in cancer patient. Seven microsatellite markers in the soluble plasma DNA from patients with pancreatic adenocarcinoma and other pancreato-biliary malignant tumors were examined for microsatellite instability (MSI) and allelic imbalance (AI). A variety of genetic alterations including MSI and AI were detected in the plasma DNA. Some alterations were detected before recurrence of the tumor was verified. Analysis of five primary pancreatic adenocarcinomas by microdissection revealed that the heterogeneous nature of pancreatic tumors is associated with both MSI and AI in the same tumor. The presence of altered plasma DNA including MSI and/or AI from the same pancreatic cancer patient may be important evidence for the presence of these alterations in heterogeneous primary tumors. Analysis of plasma DNA could become one of the diagnostic or therapeutic measures for this type of pancreatic adenocarcinoma.

Aged↗
PubMed2002

E2F-4 mutation in hereditary non-polyposis colorectal cancer.

Defects in the DNA mismatch repair function are known to cause microsatellite instability (MSI) in hereditary non-polyposis colorectal cancer (HNPCC) as well as in a subset of sporadic colorectal cancer (CRC). We previously reported that the E2F-4 gene, which encodes an important transcription factor in cell cycle control, had frequent tumor-specific mutations at a coding region of trinucleotide microsatellite (CAG)n in a subset of human sporadic CRC with high-frequency MSI (MSI-H). In this study, we assessed mutations of E2F-4 in HNPCC as well as other target genes of defective DNA mismatch repair function. Eighteen colorectal cancer (CRC) patients from 13 kindreds meeting the Amsterdam criteria for HNPCC were analyzed and compared to sporadic CRC patients with MSI-H. We detected mutations of E2F-4 at the same repeat sequence in HNPCC. The frequency of the E2F-4 mutation in HNPCC was comparable with that in sporadic CRC with MSI-H. E2F-4 was considered to be one of the important target genes responsible for the carcinogenesis of HNPCC.

Base Pair Mismatch↗
PubMed2001

Drug design, synthesis, and evaluation of a non-sugar-based selectin antagonist.

We have designed a series of simple rigid compounds (2) having a phenyl ring attached to three essential groups necessary for selectin binding, i.e., a fucose unit, a carboxylic acid, and the hydrophobic part. In this series of compound 2, 2a exhibited strong inhibitory activity in in vitro P-selectin mediated cell adhesion assay. The novel type of compound 2a would be a potential lead compound for selectin antagonist.

Benzoates↗
PubMed2001

Thermostabilization of a chimeric enzyme by residue substitutions: four amino acid residues in loop regions are responsible for the thermostability of Thermus thermophilus isopropylmalate dehydrogenase.

A chimeric 3-isopropylmalate dehydrogenase, named 2T2M6T, made of parts from an extreme thermophile, Thermus thermophilus, and a mesophile, Bacillus subtilis, was found to be considerably more labile than the T. thermophilus wild-type isopropylmalate dehydrogenase. In order to identify the molecular basis of the thermal stability of the T. thermophilus isopropylmalate dehydrogenase, 11 amino acid residues in the mesophilic portion of the chimera were substituted by the corresponding residues of the T. thermophilus enzyme, and the effects of the side chain substitutions were analyzed by comparing the reaction rate of irreversible heat denaturation and catalytic parameters of the mutant chimeras with those of the original chimera, 2T2M6T. Four single-site mutants were successfully stabilized without any loss of the catalytic function. All these four sites are located in loop regions of the enzyme. Our results strongly suggest the importance of these loop structures to the extreme stability of the T. thermophilus isopropylmalate dehydrogenase.

3-Isopropylmalate Dehydrogenase↗