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M Miyamoto

Publications and source records attributed to M Miyamoto.

At least 19 recordsLinked to original sources
PubMed2006

Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder.

Idiopathic REM sleep behavior disorder (RBD) may represent prodromal synucleinopathies. We report markedly reduced cardiac (123)I-metaiodobenzylguanidine uptake, consistent with the loss of sympathetic terminals, in idiopathic RBD. We also demonstrate that this reduction is of the same magnitude as that found in patients with Parkinson disease. The results are consistent with the hypothesis that idiopathic RBD in older patients is a forme fruste of Lewy body disease.

3-Iodobenzylguanidine↗
PubMed2006

Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cancer.

Squamous cell carcinoma antigens SCCA1 and SCCA2 are highly homologous serine proteinase inhibitors which have been widely utilized as serological markers for squamous cell cancers, but it has recently been demonstrated that only SCCA2 is truly specific for certain forms of lung cancer. Using a construct containing the 5'-flanking region of the SCCA2 gene between -460 and +0 bp and the luciferase reporter gene, SCCA2 promoter activity was detected in SCCA2-producing SCC cell lines (LK-2, LC-1), but not in SCCA2-nonproducing lung adenocarcinoma cell lines (A549, ABC-1, and RERF-LC-MS) or normal cells (WI-38, SAEC, and NHEK-Adult). Infection with a recombinant adenovirus vector, Ad-SCCA2-DsRed, resulted in cell-specific expression of the SCCA2 promoter-driven DsRed marker gene only in LK-2 and LC-1 cells. The same strategy was used for SCCA2-driven expression of a proapoptotic gene, (KLAKLAK)2, which can cause mitochondrial disruption by triggering mitochondrial permeabilization and swelling, resulting in the release of cytochrome c and induction of apoptosis. Infection with Ad-SCCA2-KLAKLAK2 specifically reduced the growth of the two human lung SCC cell lines compared to the SCCA2 nonproducing cell lines both in vitro and in vivo, suggesting that the SCCA2 promoter had a tumor-specific effect. These results suggest that transduction of SCCA2 promoter-controlled suicide genes by adenoviral vectors can confer transcriptionally targeted cytotoxicity in SCCA2-producing lung SCC cells, and represents a novel strategy for gene transfer specifically targeted to SCC in the lung.

Adenoviridae↗
PubMed2006

Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma.

The purpose of this study was to clarify the relationship between the number of tumour-infiltrating T lymphocytes and the clinicopathological features and clinical outcome in patients with non-small-cell lung cancer (NSCLC). Tissue specimens from 109 patients who underwent surgical resection for NSCLC were immunohistochemically analysed for CD4 and CD8 expression. Patients were classified into two groups according to whether their tumours exhibited a 'high' or 'low' level of CD8(+) or CD4(+) lymphocyte infiltration. Although the level of infiltration by CD8(+) T cells alone had no prognostic significance, the survival rate for patients with both 'high' CD8(+) and 'high' CD4(+) T-cell infiltration was significantly higher than that for the other groups (log-rank test, P=0.006). Multivariate analysis indicated that concomitant high CD8(+) and high CD4(+) T-cell infiltration was an independent favourable prognostic factor (P=0.0092). In conclusion, the presence of high levels of both CD8(+) T cells and CD4(+) T cells is a significant indicator of a better prognosis for patients with NSCLC, and cooperation between these cell populations may allow a significantly more potent antitumour response than either population alone.

Adult↗
PubMed2006

Immunohistochemical analysis of nuclear survivin expression in esophageal squamous cell carcinoma.

Despite advances in the treatment of esophageal carcinoma, the prognosis for this disease remains poor. Therefore, it is important to obtain a better understanding of the molecular basis of esophageal carcinogenesis. The purpose of this study was to clarify the roles of survivin in esophageal squamous cell carcinoma (ESCC). One hundred 22 ESCC surgical specimens resected from 1989 to 1999 were examined. Survivin expression was assessed by immunohistochemistry. Tumor cells were considered survivin-positive if the immunoreactivity was confined to the nucleus, and a scoring method was applied. Survivin-positive immunostaining was detected in 68 patients (56%). There was a significant association between survivin expression and pN (P = 0.0472). Moreover, the overall survival rate was worse in patients with survivin-positive tumors than in patients with survivin-negative tumors (P = 0.0189). The overexpression of survivin was associated with the overall survival rate and poor prognosis in patients with ESCC. Survivin may be targeted during cancer therapy because of its selective expression in malignant tissue.

Aged↗
PubMed2006

Platelet-rich plasma/osteoblasts complex induces bone formation via osteoblastic differentiation following subcutaneous transplantation.

BACKGROUND AND OBJECTIVE: Platelet-rich plasma (PRP) has been shown to enhance the maturation of bone grafts following local application and to have biological effects on osteoblasts in vitro. However, PRP is not applied by itself clinically as a result of its poor benefits in large bone defects. The present study was undertaken to develop a clinical alternative to autologous bone, by investigating the application of PRP in combination with osteoblastic cells and evaluating its effects after transplantation. MATERIAL AND METHODS: PRP and platelet-poor plasma (PPP) were prepared from blood, obtained from ddY mice, by two centrifugation steps. MC3T3-E1 cells were labeled with fluorescent carbocyanine just before transplantation. The combination of labeled cells and PRP gel was subcutaneously transplanted into the back of severe combined immunodeficient (SCID) mice, and the transplants were evaluated radiographically and immunohistologically after 4 wk. The effects of PRP were assessed by alkaline phosphatase (ALP) staining and von Kossa staining, and the expression of bone-related markers was analyzed by reverse transcription-polymerase chain reaction before transplantation. RESULTS: Before transplantation, PRP enhanced the expression of Osterix and bone sialoprotein mRNAs compared with PPP. Furthermore, PRP elevated ALP activity and induced the formation of mineralized nodules. After transplantation, the combination of labeled cells and PRP gel formed mineralized tissue, and the transplanted cells visualized in the tissue using fluorescence microscopy expressed osteocalcin and type I collagen. CONCLUSION: These results suggest that the application of a PRP/osteoblasts complex has beneficial effects for transplanting engineered cells into bone defects through the promotion of osteoblastic differentiation.

Animals↗
PubMed2005

Hippocalcin-deficient mice display a defect in cAMP response element-binding protein activation associated with impaired spatial and associative memory.

Hippocalcin is a member of the neuronal calcium sensor (NCS) protein family that is highly expressed in hippocampal pyramidal cells and moderately expressed in the neurons of cerebral cortex, cerebellum and striatum. Here we examined the physiological roles of hippocalcin using targeted gene disruption. Hippocalcin-deficient (-/-) mice displayed no obvious structural abnormalities in the brain including hippocampal formation at the light microscopic level. Deletion of hippocalcin did not result in up-regulation of the hippocalcin-related proteins; neural visinin-like Ca(2+)-binding proteins (NVP) 1, 2, and 3. The synaptic excitability of hippocampal CA1 neurons appeared to be normal, as estimated by the shape of field excitatory postsynaptic potentials elicited by single- and paired-pulse stimuli, and by tetanic stimulation. However, N-methyl-d-aspartate stimulation- and depolarization-induced phosphorylation of cAMP-response element-binding protein (CREB) was significantly attenuated in -/- hippocampal neurons, suggesting an impairment in an activity-dependent gene expression cascade. In the Morris water maze test, the performance of -/- mice was comparable to that of wild-type littermates except in the probe test, where -/- mice crossed the previous location of the platform significantly less often than +/+ mice. Hippocalcin-deficient mice were also impaired on a discrimination learning task in which they needed to respond to a lamp illuminated on the left or right side to obtain food reinforcement. No abnormalities were observed in motor activity, anxiety behavior, or fear learning. These results suggest that hippocalcin plays a crucial role in the Ca(2+)-signaling pathway that underlies long-lasting neural plasticity and that leads to spatial and associative memory.

Animals↗
PubMed2005

Epidemiology of blood donors in Japan, positive for hepatitis B virus and hepatitis C virus by nucleic acid amplification testing.

BACKGROUND AND OBJECTIVES: The Japanese Red Cross screens seronegative blood donors by nucleic acid amplification testing (NAT) for hepatitis B, hepatitis C and human immunodeficiency virus-1 markers. NAT-positive donors thus identified seemed to have a different infectious background from serologically positive donors. The purpose of our study was to characterize this background in the hepatitis B virus (HBV) and hepatitis C virus (HCV) NAT-positive donors. MATERIALS AND METHODS: Some 328 HBV DNA-positive and 44 HCV RNA-positive donors were detected by NAT testing of seronegative blood donors. These were characterized regarding age, gender and genotype of HBV and HCV. RESULTS: Those who were HBV NAT-positive were mainly young, in particular teenage girls. In Japan, genotypes C and B have previously been dominant, but recently genotype A has increased, and genotype H was recently detected. In HBV NAT-positive donors, the rate of genotype A was high (12.2%) compared with patients in hospital (1.7-2%). Donors who were HCV NAT-positive were also young, but mostly men in their twenties. The ratio of genotype 1b to 2a or 1b to 2b in HCV NAT-positive donors differed from that of hospitalized patients in Japan. We did not find genotype 1a, which is dominant in the USA. CONCLUSIONS: The high-risk donors detected by NAT were mainly young, with a different distribution of genotypes from that of hospitalized patients, regarding both HBV and HCV. The rare HBV genotype H has been found for the first time in Japan. The findings reflect the present spread of hepatitis viruses B and C.

Adolescent↗
PubMed2005

Cyclin D1, E2F1 expression levels are associated with characteristics and prognosis of esophageal squamous cell carcinoma.

SUMMARY. We performed a multi-institutional analysis of E2F1 and cyclin D1 expression in cases of esophageal squamous cell carcinoma (ESCC). Cyclin D1 and E2F1 are involved in the transition of cell cycle phases and associated with tumor progression. However, no previous studies have concurrently analyzed combined E2F1 and cyclin D1 expression. The purpose of this study was to clarify the relationship of E2F1 and cyclin D1 in ESCC. We studied 122 patients with primary ESCC who underwent surgical tumor resection. Immunohistochemical analyses were performed for E2F1 and cyclin D1. A statistical analysis of immunohistochemistry results, clinicopathological features, and prognosis was performed. E2F1/cyclin D1 (-/-) tumors were present in 31 patients (25.4%) and correlated with reduced tumor progression. In these patients, pT (P=0.0001), pN (P<0.0001), p-Stage (P=0.0019), and survival rates were better than in patients who were positive for either E2F1 or cyclin D1 (P=0.0232). The expression of E2F1 and cyclin D1 is an indicator of tumor progression and prognosis in patients with ESCC. Combined analysis of E2F1 and cyclin D1 expression helps to determine the characteristics and prognosis of ESCC.

Adult↗
PubMed2005

Esophageal pemphigus vulgaris with carcinoma: postoperative steroid therapy based on pemphigus-related antibodies.

A 71-year-old man had been treated as an outpatient for pemphigus vulgaris. Endoscopic examination disclosed an ulcerated lesion in the middle of the esophagus. A biopsy specimen was diagnosed pathologically as squamous cell carcinoma. At surgery, the esophageal mucosa beyond the resection margin appeared edematous and blistered. We carried out anastomosis with sutures rather than staples at the site where the epithelium was least damaged, to minimize likelihood of anastomotic breakdown from poor blood flow. Histopathologic examination of the resected specimen additionally showed blisters and acantholytic cells throughout the esophageal mucosa, so esophageal pemphigus was diagnosed in addition to carcinoma. The patient's general condition deteriorated from worsening of pemphigus. We initiated steroid therapy, making adjustments according to changes in titers of anti-intercellular bridge antibody and antibodies to the cell adhesion molecules (desmoglein 1 and 3). Fever and extensive blistering subsided dramatically, and the patient was discharged in good condition on hospital day 103. When performing esophagectomy in the presence of esophageal pemphigus, the anastomosis must be fashioned cautiously because any mechanical stress can abrade the friable edematous esophageal mucosa. While steroid therapy is known to be effective for pemphigus vulgaris, our findings indicate that in patients with postoperative deterioration of their general condition, marked improvement can be obtained by using antibody titers to guide timing and dose in steroid administration.

Aged↗
PubMed2005

Coronary arterial calcification is associated with albuminuria in type 2 diabetic patient.

AIM: Although microalbuminuria has been suggested as an independent risk factor for ischemic heart disease, the relationship between diabetic nephropathy and macroangiopathy remains unclear. Previously, we reported that coronary artery calcification detected by electron beam computed tomography (EBCT) could indicate the degree of coronary atherosclerosis in type 2 diabetic patients. In this study, we examine the association between coronary arterial calcification and microalbuminuria and aortic calcification and microalbuminuria. METHODS: Two hundred and fifty-six patients, including 177 type 2 diabetic patients (106 patients with normoalbuminuria, 71 with microalbuminuria) and 79 non-diabetic patients were evaluated by assessing the urinary albumin excretion rate and using EBCT to determine a coronary calcification score (CCS) and an aortic calcification score (ACS). RESULTS: No differences were observed regarding age, smoking index or BMI. Diabetic patients exhibited a greater CCS than non-diabetic subjects (non-diabetes 33 +/- 75 vs. diabetes 203 +/- 467, p < 0.05). Diabetic patients with microalbuminuria exhibited the most advanced CCS (253 +/- 491, p < 0.05). In contrast, no difference was observed in ACS among three groups. Multiple regression analysis showed that CCS is significantly associated with urinary albumin excretion rate as well as age, duration of diabetes and serum creatinine (R(2) = 0.31), while ACS is strongly associated with age, smoking, serum creatinine, systolic blood pressure and low-density lipoprotein cholesterol level (R(2) = 0.29). CONCLUSION: Increased urinary albumin excretion is associated with coronary arterial calcification in diabetic patients.

Age Factors↗
PubMed2004

DARPP-32 expression arises after a phase of dysplasia in oesophageal squamous cell carcinoma.

This is the first report to correlate DARPP-32 immunoreactivity (dopamine and cAMP-regulated phosphoprotein, M(r) 32 000) to clinicopathological status in human cancer. DARPP-32 is recognised as a neuronal protein. A recent study demonstrated that DARPP-32, and a truncated isoform t-DARPP, are overexpressed in gastric carcinoma during the process of carcinogenesis. The biological function of DARPP-32, however, is still unclear. The purpose of this study was to clarify the roles of DARPP-32 and t-DARPP in oesophageal squamous cell carcinoma (OSCC). Initially, we investigated DARPP-32 and t-DARPP expression in OSCC cell lines by Reverse transcription-polymerase chain reaction and Western blot. DARPP-32 expression was observed in four out of seven (57.1%) cell lines, but t-DARPP expression was not observed in any cell lines. In oesophageal tissue sample, DARPP-32 expression was observed in four out of seven (57.1%) tumour tissues, while t-DARPP was not observed in any tissues. Subsequently, DARPP expression was assessed by immunohistochemistry, using a polyclonal antibody, in tissue sections from 122 patients with primary OSCC. DARPP immunoreactivity was not observed in any normal oesophageal mucous membranes. On the other hand, positive DARPP immunostaining was detected in 37 patients (30.3%) and correlated inversely with pathologic stage (P=0.0284), pT (P=0.0438), pN (P=0.0303) and tumour size (P=0.012). The overall survival rate was worse in patients with DARPP-negative tumours than in patients with DARPP-positive tumours (P=0.0453). Interestingly, DARPP expression was observed in only one out of 45 cases of dysplasia. These observations suggest that DARPP-32 (rather than t-DARPP) expression arises after a phase of dysplasia in OSCC, and that tumours expressing DARPP-32 progress less rapidly than DARPP-32-negative tumours.

Adult↗
PubMed2004

Fusion of HIV-1 Tat protein transduction domain to poly-lysine as a new DNA delivery tool.

Effective gene therapy depends on the efficient transfer of therapeutic genes to target cells. None of the current technologies, however, satisfy all of the requirements necessary for gene therapy, because the plasma and nuclear membranes of mammalian cells are tight barriers against gene transfer using synthetic delivery systems. The protein transduction domain (PTD) of human immunodeficiency virus type 1 (HIV-1) Tat protein greatly facilitates protein transfer via membrane destabilisation. We synthesised polylysine peptides containing Tat PTD (TAT-pK), or other sequences, and investigated their potential as agents for gene transfer. The synthesised polypeptide TAT-pK retains DNA binding function and mediates delivery of a reporter gene to cultured cells. RGD motif binds with low affinity to alpha integrins which induce cell activation. Two control polypeptides, GGG-pK and RGD-pK, were synthesised and tested, but their gene transfer abilities were weaker than those of TAT-pK. TAT-pK-mediated gene transfer was enhanced in the presence of chloroquine or ammonium chloride, to a greater extent than that of cationic lipid-mediated gene transfer in most cancer cell lines tested. These data suggest that TAT-pK may be a potent candidate delivery vehicle that promotes gene transfer, dependent on the endocytic pathway. We conclude that the TAT-pK/DNA complex is useful as a minimal unit to package therapeutic genes and to transduce them into mammalian cells.

Carcinoma↗
PubMed2004

Over-expression of E2F-1 in esophageal squamous cell carcinoma correlates with tumor progression.

The transcription factor E2F-1, a downstream regulator of the p16-cyclinD-Rb pathway, is required for cell cycle progression. Evidence shows that overexpression of E2F-1 can either promote or inhibit the development of tumors, depending on tissue or experimental conditions. However, the clinical impact of E2F-1 expression on esophageal squamous cell carcinoma (ESCC) remains unknown. To analyze E2F-1 expression in ESCC, we investigated the immunoreactivity of E2F-1 and its correlation with clinicopathological features in 122 patients who underwent surgical resection for ESCC. Positive E2F-1 immunostaining was detected in 73 patients (59.8%). Positive E2F-1 immunostaining correlated positively with pathologic stage (P = 0.0103), p-Grade (P = 0.0014) and pT (P = 0.0192). The overall survival rate was worse in patients with E2F-1-positive tumors than in patients with E2F-1-negative tumors (P = 0.0290). Over-expression of E2F-1 is associated with tumor progression and a worse prognosis after surgery in ESCC.

Adult↗
PubMed2004

Beta-adrenoceptor stimulation and neutrophil accumulation in mouse airways.

This study characterised the effect of beta-adrenoceptor stimulation on endotoxin-induced accumulation of neutrophilic granulocytes in mouse airways, where the cytokines interleukin (IL)-6 and macrophage inflammatory protein (MIP)-2 are involed as mediators. The beta2-adrenoceptor agonist salbutamol (0.025-250 fMol) was administered intranasally in mice 24 h prior to administration of endotoxin (10 microg) intranasally. Bronchoalveolar lavage (BAL) fluid and venous blood, respectively, was harvested (6 or 24 h) after administration of endotoxin. Salbutamol substantially decreased the number of neutrophils in BAL fluid from endotoxin-exposed (6 and 24 h) mice and this effect was dose dependent (24 h). Pretreatment with the beta-adrenoceptor antagonist propranolol attenuated the inhibitory effect of salbutamol on BAL neutrophils (6 and 24 h), an attenuation that was not due to any unspecific effect of propranolol. Salbutamol also substantially decreased IL-6, but not MIP-2 in BAL fluid (6 h). In contrast to BAL fluid, salbutamol caused a moderate increase in blood neutrophils (24 h). In conclusion, as indicated in mouse airways in vivo, beta-adrenoceptor stimulation prior to endotoxin exposure inhibits the induced accumulation of neutrophils at a time point much later than that anticipated from its bronchodilatory effect. Even though the detailed molecular mechanisms behind this sustained "anti-inflammatory" effect remain unknown, it seems likely that this effect is in part due to a decrease in the local concentration of interleukin-6.

Administration, Intranasal↗
PubMed2003

Clinical significance of immune cell infiltration within gallbladder cancer.

To investigate the pathophysiological significance of infiltrating antitumour immune cells, we evaluated the quantity of immune cell intratumoral infiltration in 110 surgically resected gallbladder specimens by immunohistochemistry. We examined 45 cases of gallbladder cancer and 65 cases of benign gallbladder diseases for CD4(+) T cells, CD8(+) T cells, natural killer cells (NKCs), and dendritic cells (DCs). High levels of CD4(+) T cell, CD8(+) T cell, NKC, and DC infiltration were recognised in 51.1% (23 out of 45), 37.8% (17 out of 45), 33.3% (15 out of 45), and 48.9% (22 out of 45) of cancer specimens, respectively. High numbers of infiltrating CD4(+) and CD8(+) T cells correlated with decreasing tumour invasion, and high numbers of infiltrating DCs correlated with decreasing lymph-node tumour metastasis. Furthermore, increased infiltration of CD4(+) and CD8(+) T cells and DCs exhibited a significant correlation with prolonged survival. NKC infiltration, however, did not correlate with any of the clinicopathological factors examined. Additionally, high levels of infiltration were not identified in specimens from benign diseases, consistent with the cancer-specific activity of CD4(+) and CD8(+) T cells and DCs. In this study, we demonstrate that CD4(+) and CD8(+) tumour-infiltrating lymphocyte and DCs, but not NKCs, are important factors in the accurate prognosis of survival after surgical removal of gallbladder adenocarcinoma.

Adenocarcinoma↗
PubMed2003

Overexpression of hypoxia-inducible-factor 1alpha(HIF-1alpha) in oesophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage.

The purpose of this study is to investigate the clinical and histopathologic significance of hypoxia-inducible-factor 1alpha (HIF-1alpha) expression in oesophageal squamous cell carcinoma. One hundred and thirty surgically resected specimens of OSCC were immunohistochemically assessed for HIF-1alpha expression with monoclonal antibody. High HIF-1alpha immunostaining was detected in 40 specimens. The percentage of high HIF-1alpha expression cases increased with tumour stage according to pTNM system. High HIF-1alpha expression correlated with pTNM stage, depth of tumour invasion, lymph node metastasis, distant metastasis, lymphatic invasion and positive surgical margin. The overall survival rate was worse in patients with high HIF-1alpha pattern than in patients with low-expression pattern. Univariate analyses identified high HIF-1alpha positivity, depth of tumour invasion, lymph node metastasis, distant metastasis, lymphatic invasion, and a positive surgical margin as risk factors. Multivariate analyses indicated that depth of tumour invasion, lymph node metastasis and positive surgical margin, but not HIF-1alpha, were independent prognostic factors. Survival in patients with a high HIF-1alpha expression was significantly worse than in those with low expression in patient treated with adjuvant therapy.

Adult↗