Biomedical subjects

M Sato

Publications and source records attributed to M Sato.

At least 235 records · Page 13Linked to original sources

PubMed2001

Expression of nucleolar protein p120 predicts poor prognosis in patients with stage I lung adenocarcinoma.

BACKGROUND: P120 is a proliferation-associated nucleolar protein found in most human malignant tumors, but not in resting normal cells. In our previous studies, the expression of p120 was statistically correlated with the proliferation capacity in human lung cancer cells and could be a prognostic marker for resected lung adenocarcinoma. PATIENTS AND METHODS: The expression levels of p120 in tumors were assessed by immunohistochemistry in 59 patients with stage I lung adenocarcinoma who underwent radical resection. Using clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using Cox's proportional hazard model. RESULTS: A mean +/- SD of the labeling index of p120 was 35.3+/-14.4%. No significant correlation was found between the expression levels of p120 and clinicopathological factors. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those having low expression of p120 (P = 0.04). Multivariate analysis revealed that p120 served as an independent and strongest prognostic factor for resected lung adenocarcinoma (P = 0.033). CONCLUSION: This article provides the first evidence that the expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected stage I lung adenocarcinoma.

Adenocarcinoma↗

PubMed2001

Identification of novel single nucleotide substitutions in the NKp30 gene expressed in human natural killer cells.

Cytotoxicity of natural killer (NK) cells is regulated by a balance of signals from two kinds of NK receptors, activating receptors and inhibitory receptors. Natural cytotoxicity receptors (NCR) family, which consists of NKp30, NKp44 and NKp46, is a major human activating NK receptor. NKp30 has been mapped to the HLA class III region near tumor necrosis factor (TNF) family loci. We have analyzed the NKp30 gene of healthy Japanese and found two synonymous substitutions in the coding region, c.111G>A and c.156C>T, and also identified two single-nucleotide polymorphisms (SNPs) in the promotor region, -201G>A and -163G>C. Furthermore, it was confirmed that these polymorphisms of the NKp30 gene show strong linkage disequilibria with each other and with HLA-DRB1 or TNFA polymorphisms. Since susceptibilities to certain diseases were mapped near this region, the NKp30 polymorphisms could be useful genetic markers.

Alleles↗

PubMed2001

Influence of starvation and biofilm formation on acid resistance of Streptococcus mutans.

The aim of this study was to investigate acid resistance induced by starvation or biofilm formation in Streptococcus mutans ATCC 25175. The artificial biofilms were made on cover glasses, starved for 24 h and immersed in 0.1 M lactate buffer at pH 3.8 for 10 min. The biofilms were also exposed to 5% sucrose solution for 20 min to simulate acid shock produced by sucrose metabolism. Confocal laser scanning microscopy with fluorescein isothiocyanate staining measured the resultant minimum pH in biofilms. Live and dead organisms in biofilms were differentiated by confocal laser scanning microscopy with proidium iodide and SYTO9 staining. The same processes were used to treat planktonic organisms. The results showed that starved biofilms or planktonic cells showed significantly more viable bacteria after acid shock induced either by lactic acid or during sucrose consumption than non-starved biofilms or planktonic cells. In addition, biofilms showed greater resistance to acid shock induced by lactic acid than planktonic cells, whereas similar results were obtained where sucrose was used as a carbon source to reduce pH in biofilms and planktonic cells. Thus, it is suggested that starvation protects both biofilm and planktonic S. mutans from acid shock induced either by lactic acid or during sucrose consumption, while biofilm formation seemed to protect bacteria only from acid shock induced by pH 3.8 lactate buffer but not the acid shock of a slightly higher pH produced during sucrose consumption.

Biofilms↗

PubMed2001

Extracellular polysaccharides do not inhibit the reaction between Streptococcus mutans and its specific immunoglobulin G (IgG) or penetration of the IgG through S. mutans biofilm.

The present study investigated whether extracellular polysaccharides inhibit reaction between Streptococcus mutans and its specific immunoglobulin G (IgG) and penetration of the IgG through S. mutans biofilm. The planktonic organisms with or without extracellular polysaccharides were prepared, incubated with rabbit IgG against whole cell of S. mutans and fluorescein isothiocyanate (FITC)-conjugated goat affinity purified antibody to rabbit IgG. Biofilms with or without extracellular polysaccharides were formed on cover glasses and incubated with rabbit IgG against S. mutans and FITC-conjugated goat antibody to rabbit IgG. Then, biofilms were stained with propidium iodide. The amount of specific IgG binding on S. mutans was determined by FITC intensity with a fluorescence microplate reader. The penetration of IgG through biofilms was determined by confocal laser scanning microscopy. The results showed that the fluorescence intensity of FITC in planktonic organisms with extracellular polysaccharides was similar to that in planktonic organisms without extracellular polysaccharides, indicating that extracellular polysaccharides did not inhibit the reaction between S. mutans and its specific IgG. Although biofilms of S. mutans with extracellular polysaccharides were much thicker and denser than those without extracellular polysaccharides, the speed with which IgG penetrated through both of the biofilms did not differ significantly, suggesting that penetration of IgG through S. mutans biofilm was not affected by extracellular polysaccharides.

Animals↗

PubMed2001

Enhancing effects of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogenesis.

The proliferation of mouse submandibular gland carcinoma YT-12 cells was stimulated by endothelial cell growth factor (ECGF)/bovine brain-derived acidic fibroblast growth factor (aFGF) and recombinant human aFGF. To determine whether aFGF was capable of modifying salivary gland carcinogenesis, the effect of brain-derived aFGF was examined in vivo. Mice in Groups 1 and 2 were injected with 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland, and then Group 1 mice received bovine brain-derived aFGF and Group 2 mice received vehicle subcutaneously for 10 weeks. Group 3 and 4 mice received either bovine brain-derived aFGF or vehicle only. Sixteen weeks after the start of the experiment, the incidence of submandibular gland carcinomas in Group 1 was significantly greater than that in Group 2. Immunohistochemical study indicated that ducts in the normal submandibular glands and carcinomas showed positive staining with anti-aFGF antibody. Immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the expression of aFGF in these tissues. FGF receptor (FGFR)-1 and FGFR-4 were detectable in the mouse submandibular glands and carcinomas. These findings suggest that bovine brain-derived aFGF stimulates the proliferation of submandibular gland carcinoma cells and promotes mouse submandibular gland carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

Crystal structure of rat biliverdin reductase.

Biliverdin reductase (BVR) is a soluble cytoplasmic enzyme that catalyzes the conversion of biliverdin to bilirubin using NADH or NADPH as electron donor. Bilirubin is a significant biological antioxidant, but it is also neurotoxic and the cause of kernicterus. In this study, we have determined the crystal structure of rat BVR at 1.4 A resolution. The structure contains two domains: an N-terminal domain characteristic of a dinucleotide binding fold (Rossmann fold) and a C-terminal domain that is predominantly an antiparallel six-stranded beta-sheet. Based on this structure, we propose modes of binding for NAD(P)H and biliverdin, and a possible mechanism for the enzyme.

Amino Acid Sequence↗

PubMed2001

Metaplastic carcinoma of the breast: p53 analysis identified the same point mutation in the three histologic components.

A rare case of metaplastic carcinoma of the breast with both squamous metaplasia and cartilaginous metaplasia was reported. Histologically, the neoplasm revealed complex features, which were consisting of invasive ductal carcinoma, squamous carcinomatous component and chondrosarcomatoid component. Gradual transition of each component was recognized microscopically. p53 mutation analysis disclosed the same point mutation in three histologically different components, but not in the normal epithelium. Based on the morphologic findings, immunohistochemical findings and the p53 mutation analysis, we concluded that these three components in the tumor originated from the same duct progenitor cells.

Base Sequence↗

PubMed2001

HET0016, a potent and selective inhibitor of 20-HETE synthesizing enzyme.

The present study examined the inhibitory effects of N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine (HET0016) on the renal metabolism of arachidonic acid by cytochrome P450 (CYP) enzymes. HET0016 exhibited a high degree of selectivity in inhibiting the formation of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) in rat renal microsomes. The IC(50) value averaged 35+/-4 nM, whereas the IC(50) value for inhibition of the formation of epoxyeicosatrienoic acids by HET0016 averaged 2800+/-300 nM. In human renal microsomes, HET0016 potently inhibited the formation of 20-HETE with an IC(50) value of 8.9+/-2.7 nM. Higher concentrations of HET0016 also inhibited the CYP2C9, CYP2D6 and CYP3A4-catalysed substrates oxidation with IC(50) values of 3300, 83,900 and 71,000 nM. The IC(50) value for HET0016 on cyclo-oxygenase activity was 2300 nM. These results indicate that HET0016 is a potent and selective inhibitor of CYP enzymes responsible for the formation of 20-HETE in man and rat.

Amidines↗

PubMed2001

Systematic screening of type B human natriuretic peptide receptor gene polymorphisms and association with essential hypertension.

C-type natriuretic peptide (CNP) dilates arteries, lowers blood pressure and inhibits proliferation of vascular smooth muscle cells via the type B natriuretic peptide receptor (NPRB). The CNP-NPRB system may play a crucial role in the development of cardiovascular disease. We recently determined the structure of the human NPRB gene. In the present study, our objectives are to identify the polymorphisms of the NPRB gene and investigate the association of this gene with essential hypertension (EH). We used the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to study the NPRB gene polymorphism, and conducted an association study using a novel polymorphic marker. PCR-SSCP analysis of all 22 exons was done in 90 subjects, and abnormally-migrating bands were observed in the analyses of exon 11 and intron 18. Direct sequencing of these DNA fragments revealed the following sequence alterations: a C to T transition at nucleotide (nt) 2077 in exon 11 and a 9-bp insertion/deletion (I/D) in intron 18. PCR-restriction fragment length polymorphism analysis (PCR-RFLP) was developed to detect the C2077T transition. PCR-RFLP analyses of healthy subjects revealed that the C2077T polymorphism had complete linkage to GT repeats in intron 2 reported previously. The I/D polymorphism was identified by polyacrylamide gel electrophoresis, and it was not linked to any known polymorphic alleles of this gene. Therefore, the possible association between the I/D polymorphism and EH was investigated. A total of 123 individuals with EH and 123 age-matched normotensive control subjects were studied. Overall distributions of allele frequencies in the two groups were not significantly different. Although the I/D polymorphism in intron 18 of the NPRB gene was not associated with EH, the results of this study, which identified two novel polymorphisms in the human NPRB gene, will facilitate further genetic analysis of this gene and cardiovascular disease.

Adult↗

PubMed2001

Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive and -negative diffuse large B cell lymphoma.

We analyzed nucleotide sequence and intraclonal diversity of the rearranged immunoglobulin heavy chain gene variable region (VH gene) of CD5+ and CD5- diffuse large B cell lymphoma (DLBCL) to clarify the cell origin of de novo CD5+ DLBCL. Ten cases of CD5+ DLBCL and 29 cases of CD5- DLBCL were analyzed. The frequencies of somatic mutation were 0.7 to 12.9% (average, 6.2%) in CD5+ DLBCL and 2.0 to 25.9% (average, 11.1%) in CD5- DLBCL. The ongoing mutation rate was estimated from the number of further single base-substitutions, expressed as a percentage of the total number of nucleotides in 10 cloned PCR products for each case (%). The averages of the ongoing mutation rate of CD5+ DLBCL (four cases) and CD5 DLBCL (seven cases) were 0.051% and 0.197%, respectively. The rate of CD5+ DLBCL was significantly lower than that of CD5- DLBCL (t-test, P = 0.024). These data may indicate that the cell origin of CD5+ DLBCL is different from that of CD5- DLBCL. CD5 is not an activated antigen in DLBCL, but a specific marker of the B1 subset of the B cells, and de novo CD5+ DLBCL may therefore be derived from this unique subset.

Adult↗

PubMed2001

Sez4 gene encoding an elongation subunit of DNA polymerase zeta is required for normal embryogenesis.

BACKGROUND: Sez4 identified as a seizure-activated gene shows a similarity to the yeast REV3 that encodes a catalytic subunit of the nonessential DNA polymerase zeta which is involved in error-prone translesion synthesis. Although yeast REV3 homologues in mouse and human have recently been identified and characterized, their precise roles remain elusive. RESULTS: Here we investigated the role of mouse pol zeta by targeted inactivation of the Sez4 gene. The homozygous Sez4 mutants died around embryonic day (E) 10.5. This lethal effect was the result of developmental defects and apoptotic cell death within the embryo proper at the gastrulation stage, and it was partially rescued at E12.5 by the expression of a Sez4-transgene. In wild-type embryos, Sez4 transcripts were up-regulated within the embryo proper from E7.5, correlating well with the lethal stage of Sez4-inactivation. CONCLUSION: Our findings indicate that Sez4 is essential for epiblast lineage-specific development and suggests a requirement of mammalian DNA polymerase zeta in the survival of certain subcellular populations which are indispensable to normal embryogenesis.

Animals↗

PubMed2001

Yeast Saccharomyces cerevisiae has two cis-prenyltransferases with different properties and localizations. Implication for their distinct physiological roles in dolichol synthesis.

BACKGROUND: Dolichol is a family of long-chain polyprenols, which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER). We have identified a key enzyme of the dolichol synthesis, cis-prenyltransferase, as Rer2p from Saccharomyces cerevisiae. We have also isolated a multicopy suppressor of an rer2 mutant and named it SRT1. It encodes a protein similar to Rer2p but its function has not been established. RESULTS: The cis-prenyltransferase activity of Srt1p has been proved biochemically in the lysate of yeast cells lacking Rer2p. The polyprenol product of Srt1p is longer in chain length than that of Rer2p and is not sufficiently converted to dolichol and dolichyl phosphate, unlike that of Rer2p. The subcellular localization of these two isozymes has been examined by immunofluorescence microscopy and by the use of GFP fusion proteins. Whereas GFP-Rer2p is localized to the continuous ER and some dots associated with the ER, GFP-Srt1p shows only punctate localization patterns. Immunofluorescence double staining with Erg6p, a marker of lipid particles in yeast, indicates that Srt1p is mainly localized to lipid particles (lipid bodies). RER2 is mainly expressed in the early logarithmic phase, while the expression of SRT1 is induced in the stationary phase. CONCLUSIONS: We have shown that yeast has two active cis-prenyltransferases with different properties. This result implies that the two isozymes have different physiological roles during the life cycle of the yeast.

Dimethylallyltranstransferase↗

PubMed2001

Lung carcinoma with rhabdoid cells: a clinicopathological study and survival analysis of 14 cases.

AIMS: We determined the clinicopathological features of primary lung carcinomas with rhabdoid cells by defining the immunophenotype of rhabdoid cells and analysing survival. METHODS AND RESULTS: Rhabdoid cells are distinctive in having an eccentric nucleus and a large intracytoplasmic inclusion on routinely stained sections. Based on the number of rhabdoid cells, 45 cases of large cell carcinoma were divided into the following three types: lung tumour with a rhabdoid phenotype (LTRP) (n=4), lung carcinoma with a small number of rhabdoid cells (LCSR) (n=10), large cell carcinoma containing no rhabdoid cells (LCNR) (n=31). LTRP is composed of at least 10% rhabdoid cells. In LCSR the percentage of rhabdoid cells is less than 10%. LTRP and LCSR are associated with locally advanced disease. Immunohistochemical stains were positive for epithelial markers in all LTRP and eight LCSR, for neuroendocrine markers in one LTRP and three LCSR. The outcome is worse for patients with LTRP than LCSR or LCNR. LCSR shows a trend close to LCNR. Stage-matched survival analysis, however, revealed no statistically significant difference among the histological subtypes. CONCLUSIONS: Rhabdoid cells are heterogeneous except for epithelial markers and vimentin positivity. Less than 5% of rhabdoid cells has a negligible effect on prognosis.

Adult↗

PubMed2001

Detection of Slackia exigua, Mogibacterium timidum and Eubacterium saphenum from pulpal and periradicular samples using the Polymerase Chain Reaction (PCR) method.

AIM: The purpose of this study was to detect Slackia exigua from root canal samples using a sensitive PCR amplification method. Mogibacterium timidum and Eubacterium saphenum were also included because of their culture-difficult properties. METHODOLOGY: The species-specific PCR primers were prepared according to 16S rDNA sequence analysis data, and confirmed to be effective for PCR amplification as species-specific, respectively. A total of 36 clinical samples were obtained during the first visit of root canal treatment. RESULTS: The sensitivity of detection was a minimum of 10 organisms for S. exigua and five organisms for M. timidum and E. saphenum, respectively. In seven cases of pulpitis, Sexigua was detected in two cases (29%), and M. timidum in two cases (29%), but E. saphenum was not detected. In 17 cases of root canal treatment, S. exigua was detected in seven cases (41%), M. timidum in 12 cases (71%) and E. saphenum in four cases (24%). In 12 cases of root canal retreatment, S. exigua was detected in three cases (25%), M. timidum in three cases (25%) and E. saphenum in two cases (17%). CONCLUSIONS: S. exigua, M. timidum and E. saphenum were present in root canal systems, and may be associated with pulpal and periradicular pathosis.

Actinomycetales Infections↗

PubMed2001

Influence of nocturnal bruxism on the stomatognathic system. Part I: a new device for measuring mandibular movements during sleep.

The purpose of this study was to investigate the influence of bruxism on the stomatognathic system. A new device for measuring nocturnal mandibular movements was developed using a PIN photodiode sensor, integrated with polysomnography including electromyography (EMG), electroencephalography (EEG) and electro oculography (EOG). One bruxing event was defined depending upon EMG activities above 5% maximum voluntary contraction (MVC), and mandibular movement for each event was classified into three patterns (clenching, grinding and mix). Three subjects were selected for this study. Two of these reported a bruxing habit and one subject had some symptoms of temporomandibular dysfunction (TMD). Mandibular movement was analysed for these subjects. Frequency and duration of the bruxism events were 4.5-10.9 and 47.8-174.9 s h(-1) respectively. Clenching type bruxism was most frequently observed for all three subjects and EMG activities during clenching were stronger than grinding.

Adult↗

PubMed2001

Electroconvulsive shock regulates serotonin transporter mRNA expression in rat raphe nucleus.

The antidepressive actions of electroconvulsive shock (ECS) therapy are considered to involve altered neurotransmission of serotonin. In this study, we investigated the effects of acute and chronic ECS on 5-hydroxytryptamine (5-HT) transporter mRNA expression in rat raphe nucleus. We found that serotonin transporter (5-HTT) mRNA expression was decreased in 9 and 24 h after acute ECS and in 3, 9, 24 h and 2 weeks after chronic ECS in rat raphe nucleus. We presume that the adaptive change in 5-HTT mRNA expression is possibly related to the therapeutic efficacy of electroconvulsive therapy (ECT) on medication-resistant depression.

Animals↗

PubMed2001

The effects of flumazenil on sleepiness, task performance and nocturnal sleep after anesthesia with midazolam.

The purpose of the present study was to clarify the changes in psychophysiological functions after anesthesia with midazolam (intravenous (i.v.) benzodiazepine anesthetic) and to examine the ability of flumazenil (benzodiazepine antagonist) to prevent the adverse effects of anesthesia with midazolam. Clinical dose of midazolam (0.1 mg/kg i.v.) was administered to seven healthy volunteers and either flumazenil (0.3 mg i.v.) or saline was injected at the end of the anesthesia. After anesthesia with midazolam, subjective sleepiness and euphoria increased significantly, but these changes were not observed when flumazenil was administered. In addition, sleep latency was prolonged and sleep efficiency decreased significantly after midazolam anesthesia with and without flumazenil. Slow wave sleep decreased significantly only by co-administration of flumazenil.

Adult↗

PubMed2001

Visual event-related potential in mild dementia of the Alzheimer's type.

Visual event-related potentials (ERP) and behavioral measures were recorded during a geometrical-figure discrimination task to examine sensory processing in 10 patients with mild dementia of the Alzheimer's type (DAT) and 10 age-matched controls. No difference existed between the groups in P1, N1, and P2 potentials, which reflects the early stage of sensory processing, as well as in NA potential, which reflects pattern recognition. The patients showed reduced amplitude of P3 potential, retarded reaction time, and increased behavioral errors compared to controls. These findings suggest that the patients with mild DAT were intact in early sensory processing including pattern recognition but were selectively compromised in higher-level processing, including integration of information and memory matching, which may influence behavioral deviation.

Alzheimer Disease↗