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H Nakayama

Publications and source records attributed to H Nakayama.

At least 19 recordsLinked to original sources
PubMed2006

Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer.

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue will be useful molecular markers for diagnosis and may also be good therapeutic targets. However, little is known about cancer-specific genes, at least in GC. In this study, we searched for GC-specific genes by serial analysis of gene expression (SAGE) data analysis and quantitative reverse transcription (RT)-PCR. Comparing GC SAGE libraries with those of various normal tissues in the SAGEmap database, we identified 54 candidate GC-specific genes. Quantitative RT-PCR analysis of these candidates revealed that APin protein (APIN), taxol resistance-associated gene 3 (TRAG3), cytochrome P450, family 2, subfamily W, polypeptide 1 (CYP2W1), melanoma inhibitory activity (MIA), matrix metalloproteinase-10 (MMP-10), dickkopf homolog 4 (DKK4), GW112, regenerating islet-derived family, member 4 (REGIV), and HORMA domain-containing 1 (HORMAD1) were expressed much more highly in GC than in 14 kinds of normal tissues. Immunohistochemical staining for MIA, MMP-10, and DKK4 was found in 47 (31.1%), 68 (45.0%), and two (1.3%) of 151 GCs, respectively, and staining for both MIA and MMP-10 was correlated with poor prognosis in advanced GC (P=0.0001 and 0.0141, respectively). Moreover, enzyme-linked immunosorbent assay showed high levels of MMP-10 (65/69, 94.2%) in serum samples from patients with GC. Levels of MIA were raised in a small proportion of serum samples from patients with GC (4/69, 5.8%). In Boyden chamber invasion assays, MIA-transfected GC cells were up to three times more invasive than cells transfected with empty vector. Taken together, these results suggest that MMP-10 is a good marker for the detection of GC and that MIA and MMP-10 are prognostic factors for GC. As expression of MIA and MMP-10 is narrowly restricted in cancer, these two molecules may be good therapeutic targets for GC.

Adult↗
PubMed2006

Rifampicin attenuates the MPTP-induced neurotoxicity in mouse brain.

Rifampicin, an antibacterial drug, is highly effective in the treatment of tuberculosis and leprosy. Recently, it has been reported to have neuroprotective effects in in vitro and in vivo models. This study was designed to elucidate its neuroprotective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity (known as an in vivo mouse model of Parkinson's disease). Mice were injected intraperitoneally (i.p.) with MPTP (10 mg/kg) four times at 1-h intervals, and brains were analyzed 3 or 7 days later. Rifampicin at 20 mg/kg (i.p., twice) had protective effects against MPTP-induced neuronal damage (immunohistochemical changes in tyrosine hydroxylase) in both the substantia nigra and striatum. Rifampicin also protected against the MPTP-induced depletions of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. The maximal concentrations of rifampicin between 30 and 240 min after a single rifampicin injection (20 mg/kg, i.p.) were 2.6 microM (at 30 min) in plasma and 0.77 microM (at 60 min) in striatum. Next, the effects of rifampicin on oxidative stress [lipid peroxidation in mouse brain homogenates and free radical-scavenging activity against diphenyl-p-picrylhydrazyl (DPPH)] were evaluated to clarify the underlying mechanism. At 1 microM or more, rifampicin significantly inhibited both lipid peroxidation in the striatum and free radical production. These findings suggest that in mice, rifampicin can reach brain tissues at concentrations sufficient to attenuate MPTP-induced neurodegeneration in the nigrostriatal dopaminergic neuronal pathway, and that an inhibitory effect against oxidative stress may be partly responsible for its observed neuroprotective effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype.

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes whose expression is down-regulated in GC may be tumour suppressor genes. In the present study, genes with decreased expression in GC were screened for by serial analysis of gene expression (SAGE) data analysis and reverse transcription (RT)-polymerase chain reaction (PCR), and CLDN18 (encoding claudin-18) was identified. Quantitative RT-PCR revealed that expression of CLDN18 was down-regulated in 13 (56.5%) of 23 GCs. Immunostaining showed that normal gastric mucosa and Paneth cells of the duodenum expressed claudin-18 on cell membranes. Expression of claudin-18 was reduced in several intestinal metaplasias of the stomach. Of 20 samples of gastric adenoma, 18 (90.0%) showed decreased claudin-18 expression. Down-regulation of claudin-18 was observed in 84 of 146 GCs (57.5%) and correlated with poor survival in 65 advanced GCs (p = 0.0346). In addition, expression of the gastric and intestinal phenotypes of GC was examined by immunostaining for MUC5AC, MUC6, MUC2, and CD10. Of 38 GCs showing only the intestinal phenotype, down-regulation of claudin-18 was observed in 28 (73.7%), whereas in the remaining 108 GC cases, down-regulation of claudin-18 was observed in 56 (51.9%) (p = 0.0224). These results indicate that claudin-18 is a good marker of poor survival in GC. Down-regulation of claudin-18 may be involved in GCs with an intestinal phenotype, and may be an early event in gastric carcinogenesis.

Adenocarcinoma↗
PubMed2006

IL-18 gene polymorphism confers susceptibility to the development of anti-GAD65 antibody in Graves' disease.

AIMS: This study aimed to investigate whether interleukin-18 (IL-18) gene polymorphisms are associated with the development of antibody against the 65-kDa isoform of recombinant human glutamic acid decarboxylase (GAD65Ab) in patients with Graves' disease. METHODS: A total of 398 unrelated Japanese patients with Graves' disease, with and without GAD65Ab, were recruited. Three single nucleotide polymorphisms in the IL-18 gene were examined and the polymorphic allele and the genotype and haplotype frequencies calculated. RESULTS: The frequency of the GG genotype at position -4675 of the IL-18 gene was significantly lower in Graves' disease patients with GAD65Ab than those without (4% vs. 24%, P = 0.0126). The -4675C allele frequency was significantly greater in patients with GAD65Ab than those without (69% vs. 53%, P = 0.0168). The homozygous -4675G/-607A/-137G haplotype was less common in Graves' disease patients with GAD65Ab than those without (4% vs. 23%, P = 0.0144). CONCLUSIONS: These findings in a Japanese population indicate that Graves' disease patients carrying the GG genotype at position -4657 of the promoter of the IL-18 gene or a gene in linkage disequilibrium with the -4675G/-607A/-137G haplotype have a low risk for the development of GAD65Ab in Graves' disease.

Adolescent↗
PubMed2006

Apocrine adenocarcinoma of possible sweat gland origin in a male rabbit.

A five-year-old, male crossbreed rabbit was referred for acute caudal abdominal swelling. On physical examination, the rabbit was slightly depressed and showed an enlarged subcutaneous cyst in the caudal abdomen and an adjacent small, ulcerated solid mass. A drainage tube was placed in the cystic area, and surgical resection of the solid mass was performed. The histopathological diagnosis of the mass was apocrine adenocarcinoma. To the authors' knowledge, this report describes the first case of spontaneous apocrine adenocarcinoma of possible sweat gland origin in a male rabbit.

Adenocarcinoma↗
PubMed2006

Prognosis and morphometrical features of non-bronchioloalveolar cell adenocarcinoma: an assessment of the non-alveolar replacing area and high grade atypical area.

AIM: It has become obvious that the prognosis of bronchioloalveolar cell carcinoma (BAC) in small peripheral adenocarcinoma of the lung is good, but most cases actually treated as pulmonary adenocarcinoma in hospitals tend to be non-bronchioloalveolar cell carcinoma (non-BAC). The prognoses of non-BAC are greatly varied. We studied the relationships between the morphometrical features and the prognoses of non-BAC. METHODS: In total, 69 cases of non-BAC measuring <or=20 mm in diameter across their greatest dimension were evaluated. We considered that the non-alveolar replacing area and the high grade atypical area were related to the prognosis, and therefore defined the ratio of both areas to the total area at the maximum face of the tumours as the non-alveolar replacing area ratio (NAAR) and the high grade atypical area ratio (HAAR), respectively. We thereafter analysed the relationships between both ratios and the prognosis. RESULTS: The NAAR and HAAR were significantly higher in the recurrent cases than in the recurrence free cases. We divided the non-BAC cases at the centre of both ratios into two groups, high and low. The 5 year survival rate of the high NAAR and high HAAR group was 48.3%, while that of the low NAAR and low HAAR group was 72.2%. The groups showing high rates for both ratios had significantly worse prognoses. A multivariate analysis indicated that the HAAR contributes most to the prognosis. CONCLUSIONS: These results suggest that the NAAR and HAAR are closely associated with the prognosis of non-BAC.

Adenocarcinoma↗
PubMed2006

Thymic granulomatous lesions in pigs.

Rare cases of thymic granulomatous lesions were found in pigs. The lesions consisted of epithelioid cells, multinucleated giant cells, and lymphocytes. Such lesions also were observed in the mesenteric lymph nodes, spleen, kidney, and stomach. The cytoplasm of the majority of giant cells and some epithlioid cells was periodic acid-Schiff (PAS) positive. All cells were positive for vimentin, lysozyme, and desmin. Ultrastructurally, the giant cells were rich in organella and attached to adjacent epithelioid cells by membrane interdigitation. The cells included numerous coated vesicles and granules. No etiologic pathogen, including porcine circovirus type 2, was detected in the lesions. This is the rare case of idiopathic thymic granulomatous lesion in pigs.

Animals↗
PubMed2006

Histopathological changes in the brain of mouse fetuses by etoposide-administration.

Etoposide (VP-16), a topoisomerase II inhibitor, is an anti-tumor agent which is also known to show embryotoxicity, and teratogenicity when administered to pregnant rodents. We examined VP-16-induced histopathological changes in the brain of mouse fetuses. Pregnant mice were intraperitoneally injected with VP-16 (4 mg/kg) on day 12 of gestation (GD 12), and fetuses were collected from 1 to 48 hours after treatment (HAT). Mitotic neuroepithelial cells in the telencephalic wall prominently decreased at 2 HAT, and were hardly observed at 4 HAT. The number of pyknotic neuroepithelial cells in the fetal brain began to increase at 4 HAT, and became prominent from 8 to 24 HAT. These pyknotic cells were also positively stained by TUNEL method, which can detect fragmented DNA, and showed ultrastructural characteristics of apoptosis. Additionally, these cells were also positive for cleaved caspase-3, an essential executioner of apoptosis. This indicated that excessive neuroepithelial cell apoptosis was induced in the brain of mouse fetuses following VP-16 treatment on GD 12.

Animals↗
PubMed2006

Cytokeratin-positive subserosal myofibroblasts in gastroduodenal ulcer; another type of myofibroblasts.

To investigate the distribution and origin of alpha-smooth muscle actin (ASMA)-positive stromal cells in the perforation of human gastroduodenal ulcers. Perforative lesions of 24 surgically resected gastroduodenal ulcers were examined immunohistochemically for ASMA, HCD, CD34, CD31, CAM5.2 and HMW-CK, and double staining of ASMA and CAM5.2 was also performed. In addition, to determine the cell source of collagen, in situ hybridization of collagen I mRNA was performed. In the normal gastroduodenal wall, the reticular network of CD34-positive stromal cells was identified in the muscularis mucosa, submucosa, muscular propria, and subserosa. In the subepithelial area, many myofibroblasts were observed, whereas no CD34-positive stromal cells were seen. In areas neighboring ulcerative lesions, no CD34-positive stromal cells were observed, but a significant number of myofibroblasts were present there. In the deep layer of ulceration, numerous fusiform or stellate stromal cells strongly positive for ASMA and CAM5.2 were observed in the subserosal area around the perforation. In the same site, many cells co-expressing ASMA and CAM5.2 were identified by double staining. In contrast, in the surface layer of ulceration, stromal cells expressing only ASMA were observed. The cytokeratin-positive subserosal myofibroblastic cell in human gastroduodenal ulcer is a novel type of myofibroblast.

Actins↗
PubMed2005

Molecular mechanisms of hydroxyurea(HU)-induced apoptosis in the mouse fetal brain.

Hydroxyurea (HU), a potent mammalian teratogen, affects proliferating embryonic cells and inhibits DNA synthesis. The teratogenic potential of HU has been well known in experimental animals for several decades. In this study, we investigated molecular mechanisms of HU-induced apoptosis in the telencephalon of the fetal brain by exposing pregnant mice to HU on day 13 of gestation. The number of TUNEL-positive cells began to increase at 3 h, peaked at 12 h, and rapidly decreased at 24 h. Although changes of p53 mRNA expression were not observed by RT-PCR, a p53-positive reaction was detected immunohistochemically in the nuclei of neuroepithelial cells from 1 h to 6 h, and p53-protein expression was simultaneously identified by Western blot analysis. The expression of p53-target genes was detected at both the mRNA and protein. The mRNA levels of apotosis-related genes (fas, fasL, and bax) and cell cycle-related genes (mdm2 and p21) were significantly elevated, and the degree to and sequence in which these target genes expressed was similar to those for fas, fasL, mdm2 and p21. Flow-cytometric and Western blot analyses of cell cycle-related proteins suggested that neuroepithelial cells are arrested at the S checkpoint from 3 to 6 h and at the G2/M checkpoint at 12 h, respectively. HU-induced apoptosis is considered to be mediated by p53 in the fetal brain.

Animals↗
PubMed2005

Adsorption of gaseous formaldehyde and carboxylic acids by ammonium-ion-exchanged alpha-zirconium phosphate.

Ammonium-ion-exchanged alpha-Zr(HPO(4))(2)H(2)O (alpha-ZrP) was obtained as a single phase with the interlayer distance of 9.4 A by the ion-exchange of proton with ammonium ion. The ammonium ion-exchanged alpha-ZrP could adsorb ill-smelling gases, such as formaldehyde and carboxylic acids (formic acid, acetic acid, propionic acid, and butyric acid). The adsorption amounts of carboxylic acids increased in the order, butyric acid<propionic acid<acetic acid<formic acid, whereas the adsorption amount of formaldehyde was the same as that of butyric acid. It was cleared that the adsorbed formaldehyde was partially decomposed to formic acid and methanol by self oxidation-reduction reaction in the interlayer region as evidenced by solid-state NMR. Thereby the interlayer distance after the adsorption of formaldehyde expanded to 14.4 A. In the case of formic acid, it was cointercalated into the interlayer region, and the interlayer distance expanded to 11.1 A. On the other hand, the interlayer distance of the other carboxylic acid-adsorbed compounds decreased to 7.6 A due to release by the evacuation.

Acetic Acid↗
PubMed2005

Severity of oral mucositis correlates with the response of oral cancer to preoperative radiochemotherapy.

Oral mucositis is a dose-limiting toxic effect of radiotherapy and chemotherapy on oral cancer. The purpose of the present study is to assess the relationship between tumor response and oral mucositis in preoperative radiochemotherapy for oral cancer retrospectively. Fifty-four cases of oral squamous cell carcinoma were treated with concurrent radiochemotherapy prior to surgery. When oral mucositis was evaluated with the WHO scale, severe oral mucositis (Grades 3 and 4) developed in 22 cases (41%). A more than 50% reduction in tumor size was clinically observed in 38 cases (70%). From histopathological analysis of the surgical specimens all tumor cells observed appeared to be non-viable in 16 cases (29%). The cases with Grade 1, Grade 2, Grade 3 and Grade 4 oral mucositis included 33%, 62%, 85% and 89% of clinical good-response cases and 0%, 24%, 31% and 55% of histopathological good-response cases, respectively. This retrospective study suggests that severe oral mucositis promises a good response of oral squamous cell carcinoma to radiochemotherapy.

Aged↗
PubMed2005

The validity of the mangled extremity severity score in the assessment of upper limb injuries.

The Mangled Extremity Severity Score (MESS) may be used to decide whether to perform amputation in patients with injuries involving a limb. A score of 7 points or higher indicates the need for amputation. We have treated three patients with a MESS of 7 points or higher, in two of which the injured limb was salvaged. This scoring system was originally devised to assess injuries to the lower limb. However, a MESS of 7 points as a justification for amputation does not appear appropriate when assessing injuries to the major vessels in the upper limb.

Adult↗