Biomedical subjects

Yoshihisa Watanabe

Publications and source records attributed to Yoshihisa Watanabe.

At least 19 recordsLinked to original sources

PubMed2006

Glucose transporter type 1 expression are associated with poor prognosis in patients with salivary gland tumors.

The objective of this study was to investigate the expression of Glucose transporter type 1 (GLUT1) and its relation to clinicopathologic parameters in patients with salivary gland tumors. Tissue samples were 49 cases of malignant tumors, 38 cases of benign tumors, mainly pleomorphic adenoma and 10 cases of normal salivary glands. Immunohistochemically, GLUT1 Labeling Index of malignant tumor was significantly higher than benign tumor. In RT-PCR assay, GLUT1 mRNA level in malignant tumor were higher than that of normal tissue. In malignant tumors, expression of GLUT1 correlated significantly with tumor size (p=0.002) and distant metastasis (p=0.007). Cumulative survival rate of high expression group was significantly lower than that of low (p<0.001). In multivariable analysis, overall survival significantly correlated with lymph node metastasis (p=0.042) and GLUT1 expression (p=0.022). These results suggest that GLUT1 expression may provide useful prognostic information in patients with salivary gland carcinoma.

Biomarkers, Tumor↗

PubMed2006

Inverted ductal papilloma of minor salivary gland: case report with immunohistochemical study and literature review.

Inverted ductal papilloma (IDP) is a type of ductal papilloma arising in ducts of minor salivary glands. Very few cases, and no cases in Japan, have been reported. Reported herein is a case of IDP with a review of the literature. The patient was a 49-year-old man presenting with a lump in the right buccal mucosa of the premolar area of the mandible. The tumor was excised en bloc after a biopsy diagnosis of IDP. On the surface of the covering epithelium, an opening was seen to be filled with mucinous material. On cut surface the opening led to the tumor cavity. The major portion of the tumor parenchyma was made up of papillary proliferation of basaloid squamous cells. Some crypts, microcysts, and mucous cells were seen. There were no findings suggestive of a malignant tumor. The patient's postoperative course was uneventful and there has been no recurrence after 1 year's follow up. Immunohistochemical analysis of the present case supports the hypothesis that IDP originates from squamous metaplasia and proliferation of minor salivary gland duct cells.

Biomarkers, Tumor↗

PubMed2005

Hepatocyte growth factor expression correlates with cyclooxygenase-2 pathway in human salivary gland tumors.

It has been reported that cyclooxygenase-2 (COX-2) plays roles in cell proliferation, tumor invasion and inhibition of apoptosis. We reported COX-2 expression in salivary adenoma and its involvement in inhibition of apoptosis. COX-2 is known to induce a number of cytokines and growth factors. On the other hand, hepatocyte growth factor (HGF) plays roles such as cell migration, proliferation, angiogenesis and inhibition of apoptosis. Recently it has been reported that HGF also plays a role in tumor differentiation in salivary gland tumors. So, we investigated that whether COX-2 expression affected HGF expression clinicopathologically, and discussed the roles of COX-2 pathway in salivary gland tumors. Tissues samples were pleomorphic adenomas (n = 40) obtained surgically. COX-2 expression and HGF expression were examined immunohistochemically. Immunostaining intensities of COX-2 and HGF were classified as +3 to 0. Spearman's rank correlation was used to examine correlation of COX-2 and HGF expression. Furthermore, a salivary gland tumor cell line, HSG, was cultured after administration of either 0, 10, 100 units of COX-2 and quantification of HGF mRNA was analyzed by Real Time PCR using the Light Cycler System. In pleomorphic adenoma, COX-2 and HGF were mainly expressed in luminal tumor cells, and the sites of expression of the two were almost the same. Immunostaining intensity of COX-2 expression was significantly correlated with intensity of HGF expression (p = 0.003, r = 0.457). Moreover, the content of HGF mRNA expression increased when COX-2 was administered to salivary gland tumor cell line HSG. It is suggested that COX-2 expression may induce HGF expression in salivary gland tumors.

Adenoma, Pleomorphic↗

PubMed2005

Surgery for gastric cancer combined with cardiac and aortic surgery.

HYPOTHESIS: Therapeutic strategies for patients who require procedures for both cardiac or aortic diseases and gastric cancer are controversial. Prognostic factors for them should be clearly identified. DESIGN: Retrospective review of 14 patients who underwent surgical intervention for both gastric cancer and cardiac or aortic diseases between January 1, 2000, and June 30, 2004. SETTING: Tertiary referral university hospital. PATIENTS: Cardiac and aortic diseases included coronary artery disease in 5 patients, thoracic aortic aneurysms in 3 patients, and abdominal aortic aneurysms in 6 patients. Coronary artery bypass graftings were performed with an off-pump procedure, and aneurysms were replaced with prosthetic grafts in all of the cases. The surgical stages of gastric cancers were stage I in 8 patients, stage II in 2 patients, stage III in 3 patients, and stage IV in 1 patient. According to our original therapeutic strategies, 4 patients underwent simultaneous procedures and 10 received staged procedures. MAIN OUTCOME MEASURE: Overall survival rates. RESULTS: There was 1 hospital death caused by multiple organ failure. No prosthetic graft infection was noted. Thirteen patients were discharged, and 3 died of cancer recurrence during an average follow-up period of 26.3 months. The cumulative survival rate was 76.6% at 1 year and 68.1% at 3 years. One-year survival rates were 90.0% in stages I and II gastric cancer and 50.0% in stages III and IV gastric cancer. CONCLUSION: Prognosis of patients who underwent surgical intervention for both gastric cancer and cardiac or aortic diseases was mainly limited by the clinical stage of gastric cancer.

Aged↗

PubMed2005

Expression and localization of chromogranin A gene and protein in human submandibular gland.

Human saliva chromogranin A (CgA) is clinically promising as a psychological stress marker. However, expression of CgA is poorly understood in humans, although salivary gland localization of CgA in other mammals, such as rodents and horses, has been demonstrated. In the present study, we investigated the expression and localization of CgA in the human submandibular gland (HSG) using various methods. CgA was consistently localized in serous and ductal cells in HSG, as detected by immunohistochemistry and in situhybridization. Reactivity was stronger in serous cells than in ductal cells. In addition, strong immunoreactivity for CgA was observed in the saliva matrix of ductal cavities. Western blotting gave one significant immunoreactive band of 68 kDa in the adrenal gland, HSG and saliva. Finally, CgA was detected in secretory granules of serous and ductal cells by immunoelectron microscopy. In conclusion, CgA in humans is produced by HSG and secreted into saliva.

Adrenal Glands↗

PubMed2005

Paenibacillus macerans possesses two types of 16S rDNA copies in a genome with a length difference of twelve base pairs.

Two Paenibacillus macerans strains, JCM 2500T and MCRI 12, exhibited two types of 16S rDNA copies in their genomes, accompanied by a length difference of 12 bp at positions 203 to 214 (Escherichia coli numbering). The long-type sequences were newly identified for P. macerans 16S rDNA, and the copy numbers were different between the two strains. Both types of 16S rRNA were expressed in each strain, and it was predicted that the polymorphism at this position is located in helix H10, based on a comparison with the E. coli 16S rRNA secondary structure model.

Bacillus↗

PubMed2005

Metabolic syndrome from the view point of public health: with special reference to nonalcoholic fatty liver disease.

Changes in human behavior and lifestyle over the last century have resulted in a dramatic increase in the incidence of obesity, type 2 diabetes, and the metabolic syndrome. Differences in the reported overall prevalence of the metabolic syndrome, which is generally in the range of 10-30% depend on the diagnostic criteria and subjects of the study. Recently, Japanese criteria for diagnosis of the metabolic syndrome were defined. With these criteria, presence of visceral obesity is essential for the diagnosis and is simply determined by measurement of waist circumference. Reflecting a dramatic increase in the incidence of obesity and type 2 diabetes, the incidence of the metabolic syndrome is increasing in Japan as well as in Western countries, regardless of the criteria applied. Recently, the number of workers with elevated liver enzymes, in whom virus hepatitis, alcoholic liver disease, drug induced hepatitis, autoimmune hepatitis, and iron overload were ruled out as causal agents, has also be found to be increasing at workplace health checkups. Most of such workers have components of the metabolic syndrome and the presence of steatosis in the liver, this pathologic condition now being termed nonalcoholic fatty liver disease (NAFLD). In this review, we describe the relationship between NAFLD and the metabolic syndrome.

Adult↗

PubMed2004

Molecular cloning and tissue-specific expression analysis of mouse spinesin, a type II transmembrane serine protease 5.

We have previously reported novel serine proteases isolated from cDNA libraries of the human and mouse central nervous system (CNS) by PCR using degenerate oligodeoxyribonucleotide primers designed on the basis of the serine protease motifs, AAHC and DSGGP. Here we report a newly isolated serine protease from the mouse CNS. This protease is homologous (77.9% identical) to human spinesin type II transmembrane serine protease 5. Mouse spinesin (m-spinesin) is also composed of (from the N-terminus) a short cytoplasmic domain, a transmembrane domain, a stem region containing a scavenger-receptor-like domain, and a serine protease domain, as is h-spinesin. We also isolated type 1, type 2, and type 3 variant cDNAs of m-spinesin. Full-length spinesin (type 4) and type 3 contain all the domains, whereas type 1 and type 2 variants lack the cytoplasmic, transmembrane, and scavenger-receptor-like domains. Subcellular localization of the variant forms was analyzed using enhanced green fluorescent protein (EGFP) fusion proteins. EGFP-type 4 fusion protein was predominantly localized to the ER, Golgi apparatus, and plasma membrane, whereas EGFP-type 1 was localized to the cytoplasm, reflecting differential classification of m-spinesin variants into transmembrane and cytoplasmic types. We analyzed the distribution of m-spinesin variants in mouse tissues, using RT-PCR with variant-specific primer sets. Interestingly, transmembrane-type spinesin, types 3 and 4, was specifically expressed in the spinal cord, whereas cytoplasmic type, type 1, was expressed in multiple tissues, including the cerebrum and cerebellum. Therefore, m-spinesin variants may have distinct biological functions arising from organ-specific variant expression.

Amino Acid Sequence↗

PubMed2004

Amplicons on human chromosome 11q are located in the early/late-switch regions of replication timing.

Amplicons are frequently found in human tumor genomes, but the mechanism of their generation is still poorly understood. We previously measured the replication timing of the genes along the entire length of human chromosomes 11q and 21q and found that many "disease-related" genes are located in timing-transition regions. In this study, further scrutiny of the updated replication-timing map of human chromosome 11q revealed that both amplicons on human chromosomal bands 11q13 and 11q22 are located in the early/late-switch regions of replication timing in two human cell lines (THP-1 and Jurkat). Moreover, examination of synteny in the human and mouse genomes revealed that synteny breakage in both genomes occurred primarily at the early/late-switch regions of replication timing that we had identified. In conclusion, we found that the early/late-switch regions of replication timing coincided with "unstable" regions of the genome.

Animals↗

PubMed2004

Hepatocyte growth factor and c-Met immunoreactivity are associated with metastasis in high grade salivary gland carcinoma.

Interactions between hepatocyte growth factor (HGF) and its receptor, c-Met, have been associated with invasion, metastasis and carcinogenesis in in vitro experiments. We investigated the relationship between HGF/c-Met immunoreactivity and the clinical features of 33 patients with high grade salivary gland carcinomas. c-Met and stromal HGF (expression of HGF in fibroblasts adjacent to tumor nests) were found to significantly correlate with regional lymph node and distant metastasis (p<0.05), but not with HGF expression, in tumor cells. Stromal HGF was also found to correlate with tumor size (p<0.05). In addition, a significant correlation between c-Met and stromal HGF expression (p<0.0001) was observed. Overall survival in patients with c-Met and stromal HGF immunoreactivity was significantly worse than in patients without c-Met and stromal HGF immunoreactivity (p=0.0002). The present findings suggest that HGF may bind to c-Met in a paracrine fashion, thereby enabling metastasis of high grade salivary gland carcinomas. Thus, HGF/c-Met immunoreactivity might be associated with a poor prognosis in patients with high grade salivary gland carcinomas.

Adenocarcinoma, Mucinous↗

PubMed2003

A unifying model for functional difference and redundancy of presenilin-1 and -2 in cell apoptosis and differentiation.

Mutations in genes encoding the highly homologous proteins presenilin-1 and -2 (PS1 and PS2) are linked to the early onset of Alzheimer's disease (AD). Here, we report that polyclonal antibodies against Xenopus PSbeta (PS2), but not PSalpha (PS1), suppress the in vitro apoptotic activation of Xenopus egg extracts. To clarify the relationship between structural and functional differences in presenilins, we searched for presenilin homologues in various living sources, and found that presenilins were divided into three distinct groups, named alpha-, beta- and gamma-types, based on the size of the large hydrophilic loop (HL) regions as follows: HLalpha/HLbeta/HLgamma=4:3:6. No such size conservations were found in the N-terminal (NT) hydrophilic regions. Phylogenetic studies revealed that the presenilin genes were duplicated independently in different lineages of phyla/divisions, suggesting that there were functional requirements for and constraints on the generation and conservation of these HL sizes. On the basis of these findings, we propose a model postulating that both PS1 and PS2 can be differentiative or apoptotic when they are proteolytically processed within the HL regions or not, respectively, and PS1 may be more sensitive than PS2 to auto-proteolytic cleavage due to the larger size of the HL region of the former. Furthermore, the model assumes that C-terminal fragments (CTF) stabilized by phosphorylation may inhibit both the activities due to the dominant-negative effect. The model explains not only the functional redundancy but also apparently conflicting observations reported so far for PS1 and PS2.

Animals↗

PubMed2003

Differential expression of presenilin-alpha and -beta (PSalpha and PSbeta) in Xenopus laevis: embryonic phosphorylation of PSalpha.

Mutations in genes encoding the highly homologous proteins, presenilin-1 and -2 (PS1 and PS2), are linked to the development of early-onset Alzheimer's disease. On the other hand, presenilins are known to play a critical role(s) in cell fate decisions during embryonic development in Caenorhabditis elegans. The messenger RNAs (mRNAs) of amphibian presenilin homologues PSalpha and PSbeta are most abundantly synthesized in the brain and the ovary, but are differentially degraded upon oocyte maturation and at the midblastula transition (MBT), respectively. In this study, we examined the spatiotemporal distribution of PSalpha and PSbeta proteins and their post-translational modification. The results were essentially consistent with the mRNA data and revealed moreover that PSalpha was present exclusively as processed molecules in the early embryos, while PSbeta was present mainly as unprocessed molecules (90%). Furthermore, the C-terminal fragment (CTF) of PSalpha was phosphorylated upon oocyte maturation and dephosphorylated at MBT, while no phosphorylation of the PSbeta CTF was detectable. Human PS1 CTF exogenously injected was also phosphorylated in Xenopus oocytes induced to mature in vitro by progesterone treatment. Two phosphorylation loci were mapped at Thr(320) and Ser(334) in the hydrophilic loop region of PSalpha. Our results suggest that PS1 and PS2 may play different roles under physiological conditions despite their high structural similarity.

Amino Acid Sequence↗

PubMed2003

DNA typing from cigarette butts.

We performed DNA typing for D1S80, HLADQA1, TH01 and PM using the butts of 100 cigarettes that were smoked by ten different individuals (ten cigarettes per individual). The results obtained from DNA typing for D1S80 agreed with the results obtained using bloodstains in 76 cigarette butt samples. Sixteen samples produced false results, showing the loss of the longer allelic hetero-band. When examined using agarose gel electrophoresis, high-molecular weight DNA was not observed in these samples. The same results were also observed for buccal swab samples and saliva stains obtained from the same individuals. In the remaining eight cigarette butt samples, PCR products were not detected. The results obtained from DNA typing for TH01, HLADQA1 and PM agreed with the results obtained using bloodstains in 90 samples. In the remaining ten samples of a specific kind of cigarette (Marlboro), the PCR products were not detected. The extracts from the ends of the Marlboro cigarettes were stained yellow. When the DNA extracted from Marlboro cigarette butts was treated with Microcon-100 (amicon) or SizeSep 400 Span Columns (Amersham Pharmacia Biotech), PCR products could be detected. When PCR amplification was performed after adding extracts from the ends of unsmoked Marlboro cigarettes to DNA extracted from bloodstains, PCR products could not be detected. The present data indicate that the degradation of high-molecular weight DNA and the inhibition of PCR by dyes of the cigarette end should be kept in mind when performing DNA typing using cigarette ends.

Adult↗

PubMed2003

Quality and quantity of DNA in cadavers' serum.

We investigated the quality and quantity of DNA in sera obtained from 16 cadavers who were left at room temperature or placed in a refrigerator for cadavers within 3 days of their death. The causes of death were as follows: asphyxia, 4; hemorrhage, 4; fire, 3; cold, 1; subdural bleeding, 1; sepsis, 1; cerebral contusion, 1; and pulmonary thromboembolism, 1. When examined using agarose gel electrophoresis, the samples from the victims who died from sepsis and pulmonary thromboembolism exhibited smear patterns, while the other samples exhibited ladder patterns. The size of each band was an integer multiple of approximately 180 bp, considered to be characteristic of apoptosis. The DNA concentration in the cadavers' sera ranged from 3.0 to 258.9 ng/ml. DNA types (D1S80, HLADQA1, TH01, and PM) were determined for all the samples except for the sample from the victim who died from sepsis. The detected types were the same as those obtained from paired bloodstain samples, except for in the asphyxia victim. D1S80 typing of the serum sample from the asphyxia victim showed the loss of the longer allelic hetero-band. These results suggest that the quantity of DNA in serum from cadavers is sufficient for DNA typing, but that the degradation of DNA may proceed quickly, depending on the temperature of the area in which the cadaver is left as well as the pathological conditions that the victim had experienced.

Adolescent↗

PubMed2003

Association of hepatocyte growth factor expression with salivary gland tumor differentiation.

To clarify the significance of hepatocyte growth factor (HGF) expression in salivary gland tumors, HGF distribution in tissue sections and HGF concentrations in saliva and serum were examined. Sixty salivary gland adenomas, 61 salivary gland carcinomas and three autopsy fetuses were studied. Hepatocyte growth factor expression was observed in the duct-type luminal cells by immunohistochemical staining and in situ hybridization. However, HGF failed to be expressed in acinar cells and myoepithelium of normal salivary gland tissue. Hepatocyte growth factor tended to be expressed more intensely in benign salivary gland tumors than in malignant salivary gland tumors (P < 0.0001). In highly malignant tumors, the expression was limited in some cases. Salivary and serological HGF concentrations of 18 patients, comprised of 12 benign cases and six malignant cases, were analyzed before and after operation by an ELISA system. The concentrations were distinctly elevated after operation, in both saliva and serum, compared to before operation (P < 0.0005). However, there were no significant relationships between HGF concentration and histology, age, gender, size or location. Our findings suggest that HGF may play an important role in the development of salivary ducts of normal salivary tissues and differentiation of ductal structures of their neoplasms, while HGF kinetics in saliva and serum would be less likely to reflect the neoplastic character, benign or malignant.

Adenoma↗

PubMed2003

Recurrent multiple superficial mucocele on the palate: Histopathology and laser vaporization.

A 55-year-old Japanese woman presented with recurrent multiple vesicles on the soft palate. Some vesicles ruptured spontaneously but soon recurred, and the patient felt mild pain and discomfort. Histopathologically, intraepithelial mucocele with mucus retention in the salivary ducts was observed. The lesion was successfully treated with Nd: YAG Contact Laser. There has been no recurrence for 3 years.

Female↗

PubMed2002

Chromosome-wide assessment of replication timing for human chromosomes 11q and 21q: disease-related genes in timing-switch regions.

The completion of the human genome sequence will greatly accelerate development of a new branch of bioscience and provide fundamental knowledge to biomedical research. We used the sequence information to measure replication timing of the entire lengths of human chromosomes 11q and 21q. Megabase-sized zones that replicate early or late in S phase (thus early/late transition) were defined at the sequence level. Early zones were more GC-rich and gene-rich than were late zones, and early/late transitions occurred primarily at positions identical to or near GC% transitions. We also found the single nucleotide polymorphism (SNP) frequency was high in the late-replicating and replication-transition regions. In the early/late transition regions, concentrated occurrence of cancer-related genes that include CCND1 encoding cyclin D1 (BCL1), FGF4 (KFGF), TIAM1 and FLI1, was observed. The transition regions contained other disease-related genes including APP associated with familial Alzheimer's disease (AD1), SOD1 associated with familial amyotrophic lateral sclerosis (ALS1) and PTS associated with phenylketonuria. These findings are discussed with respect to the prediction that increased DNA damage occurs in replication-transition regions. We propose that genome-wide assessment of replication timing serves as an efficient strategy for identifying disease-related genes.

Alzheimer Disease↗

PubMed2002

Loss-of-function of a rice brassinosteroid biosynthetic enzyme, C-6 oxidase, prevents the organized arrangement and polar elongation of cells in the leaves and stem.

Molecular genetic and physiological studies on brassinosteroid (BR)-related mutants of dicot plants have revealed that BRs play important roles in normal plant growth and development. However, little is known about the function of BR in monocots (grasses), except for the phenotypic analysis of a rice mutant partially insensitive to BR signaling. To investigate the function of BR in monocots, we identified and characterized BR-deficient mutants of rice, BR-deficient dwarf1 (brd1). The brd1 mutants showed a range of abnormalities in organ development and growth, the most striking of which were defects in the elongation of the stem and leaves. Light microscopic observations revealed that this abnormality was primarily owing to a failure in the organization and polar elongation of the leaf and stem cells. The accumulation profile of BR compounds in the brd1 mutants suggested that these plants may be deficient in the activity of BR C-6 oxidase. Therefore, we cloned a rice gene, OsDWARF, which has a high sequence similarity to the tomato C-6 oxidase gene, DWARF. Introduction of the wild-type OsDWARF gene into brd1 rescued the abnormal phenotype of the mutants. The OsDWARF gene was expressed at a low level in all of the examined tissues, with preferential expression in the leaf sheath, and the expression was negatively regulated by brassinolide treatment. On the basis of these findings, we discuss the biological function of BRs in rice plants.

Alleles↗