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Biomedical subjects

S Sato

Publications and source records attributed to S Sato.

At least 163 records · Page 9Linked to original sources

Transforming growth factor beta1 gene polymorphism in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease and synovial cells, antigen presenting cells, lymphocytes, and their cytokines might be associated with the disease. Transforming growth factor beta1 (TGFbeta1) has been reported to have important roles in unresolved inflammation, immune suppression, fibrosing processes, and angiogenesis. TGFbeta1 is highly expressed in joints in RA and is considered to be a regulator of anti-inflammation in RA. Polymorphisms of TGFbeta1 have been reported to be associated with the production of TGFbeta1 protein, and to increase the risk of acquiring several diseases. It was speculated that these polymorphisms might also be involved in RA, and therefore the TGFbeta1 codon 10 T869C polymorphism in a series of patients and controls was investigated. METHOD: A total of 155 patients with RA and 110 healthy subjects were studied. DNA was extracted from peripheral leucocytes and TGFbeta1 codon 10 T869C polymorphism was determined by polymerase chain reaction restriction fragment polymorphism. RESULTS: A significantly higher proportion of patients with RA with the T allele (CT type or TT type) was found compared with the CC type (p=0.039). CONCLUSION: The T allele, previously reported to be linked with production of TGFbeta1, may be associated with an increased risk of RA.

Adult↗

Health status measured with the CRQ does not predict mortality in COPD.

One purpose of measuring health status is to predict future outcomes. The aim of this study was to investigate the ability of health status derived from the Chronic Respiratory Disease Questionnaire (CRQ) to predict mortality in chronic obstructive pulmonary disease (COPD). One-hundred and forty-three patients with COPD were recruited. Health status, using the CRQ, and pulmonary function were measured at entry. Mortality after 7 yrs was then assessed. Univariate and multivariate Cox proportional hazards analyses were performed to predict those factors related to mortality. Of all the patients, 13 could not be followed up and 40 had died. The survival rate was 69% at 7 yrs. Univariate regression analyses revealed that the dyspnoea and emotional function domains and the total score of the CRQ were weakly but significantly correlated with mortality from all causes. However, multivariate regression analyses revealed that age and forced expiratory volume in one second were the strongest predictors of mortality, and health status was not a significant factor. Although there was a weak but significant relationship between health status and subsequent mortality in chronic obstructive pulmonary disease, it was not significant after an adjustment for age and pulmonary function. Mortality cannot be predicted from Chronic Respiratory Disease Questionnaire scores.

Age Factors↗

A comparative study of Japanese multiple sclerosis patients with and without oligoclonal IgG bands.

The cerebrospinal fluid oligodonal IgG bands (OB) are less frequently observed in Japanese multiple sclerosis (MS) patients compared with Caucasian patients. We studied 40 consecutive Japanese MS patients to investigate the differences in the clinical and magnetic resonance imaging (MRI) features of MS between OB-positive patients and OB-negative ones. Among the 40 patients, 22 (55%) patients were OB-positive by either agarose gel electrophoresis (AGE) or isoelectric focusing (IEF), and 18 (45%) patients were OB-negative by both AGE and IEF. There were differences between the two groups only in the clincal forms of MS, but not in terms of gender, onset age, disease duration, or disease severity. In the OB-negative group, nine (50%) of the patients had the optic-spinal form of MS (OS-MS), but only one patient (4.5%) in the OB-positive group had OS-MS. Although most OB-positive patients showed brain MRI lesions typical of MS, 13 (72%) of the OB-negative patients showed no or few brain MRI lesions and the rest of the OB-negative patients showed atypical MS lesions, such as diffuse white matter lesions or large ring-enhanced lesions. Our results suggest that the majority of OB-negative Japanese MS patents show either no or few brain MRI lesions or atypical brain MRI lesions.

Adult↗

Transforming growth factor-beta gene polymorphism in sarcoidosis and tuberculosis patients.

SETTING: Transforming growth factor-beta (TGF-beta) plays an important role in many diseases, influencing as it does such processes as immune responses, fibrosing processes, and angiogenesis. Recently, polymorphisms have been described for TGF-beta that are associated with the risk of several diseases. In this study, we investigated whether TGF-beta 1 polymorphism has an effect on sarcoidosis and tuberculosis. OBJECTIVE: TGF-beta 1 Codon 10 T869C polymorphism was investigated in 110 healthy control subjects, 104 sarcoidosis patients, and 101 tuberculosis patients. DESIGN: The TGF-beta genotype was determined using polymerase chain reaction restriction fragment length polymorphism. RESULTS: We found no significant differences in TGF-beta genotypes between sarcoidosis patients and healthy controls or tuberculosis patients and controls. The long axis of the tuberculin skin test was larger in the CC type compared with the CT type. However, there was no association between the TGF-beta genotype and the roentgenographic stage, the disappearance of shadows, or organ involvement in sarcoidosis, nor any association between genotype, the extent or type of roentgenographic shadow, or detected volume of tubercle bacilli in tuberculosis. CONCLUSION: From the results, we believe that TGF-beta polymorphisms on the whole do not have a strong influence on disease onset or clinical progression in sarcoidosis and tuberculosis, although this polymorphism might have an effect on the immune response in a tuberculosis host.

Adult↗

Construction of a genetic linkage map of the model legume Lotus japonicus using an intraspecific F2 population.

Among leguminous plants, the model legume Lotus japonicus (Regel) Larsen has many biological and genetic advantages. We have developed a genetic linkage map of L. japonicus based on amplified fragment length polymorphism (AFLP), simple sequence repeat polymorphism (SSRP) and derived cleaved amplified polymorphic sequence (dCAPS). The F2 mapping population used was derived from a cross between two L. japonicus accessions Gifu B-129 and Miyakojima MG-20. These parental accessions showed remarkable cytological differences, particularly with respect to size and morphology of chromosomes 1 and 2. Using fluorescence in situ hybridization (FISH) with BAC clones from Gifu B-129 and TAC (Transformation-competent Artificial Chromosome) clones from Miyakojima MG-20, a reciprocal translocation was found to be responsible for the cytological differences between chromosomes 1 and 2. The borders of the translocations were identified by FISH and by alignment toward the L. filicaulis x L. japonicus Gifu B-129 linkage map. The markers from the main translocated region were located on linkage groups 1 and 2 of the two accessions, Gifu B-129 and Miyakojima MG-20, respectively. The framework of the linkage map was constructed based on codominant markers, and then dominant markers were integrated separately in each linkage group of the parents. The resulting linkage groups correspond to the six pairs of chromosomes of L. japonicus and consist of 287 markers with 487.3 cM length in Gifu B-129 and 277 markers with 481.6 cM length in Miyakojima MG-20. The map and marker information is available through the World Wide Web at http://www.kazusa.or.jp/lotus/.

Chromosome Mapping↗

Structural analysis of a Lotus japonicus genome. I. Sequence features and mapping of fifty-six TAC clones which cover the 5.4 mb regions of the genome.

A total of 56 TAC clones with an average insert size of 100 kb were isolated from a TAC library of the Lotus japonicus genome based on the expressed sequences tags (ESTs), cDNA and gene information, and their nucleotide sequences were determined according to the shot-gun based strategy. The total length of the sequenced regions is 5,473,195 bp. By comparison with the sequences in protein and EST databases and analysis with computer programs for gene modeling, a total of 605 potential protein-encoding genes with known or predicted functions, 69 gene segments, and 172 pseudogenes were identified. The average density of the genes assigned so far is 1 gene/8120 bp. Introns were identified in approximately 78% of the potential genes. There was an average of 3.8 introns per gene and the average length of the introns was 375 bp. DNA markers were generated based on the nucleotide sequences obtained, and each clone was mapped onto the linkage map using the F2 mapping population derived from a cross of L. japonicus Gifu B-129 and Miyakojima MG-20. The sequence data, gene information and mapping information are available through the World Wide Web at http://www.kazusa.or.jp/lotus/.

Base Sequence↗

Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes.

Bacterial lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor (TLR) 4, a member of the TLR family that participates in pathogen recognition. TLRs recruit a cytoplasmic protein, MyD88, upon pathogen recognition, mediating its function for immune responses. Two major pathways for LPS have been suggested in recent studies, which are referred to as MyD88-dependent and -independent pathways. We report in this study the characterization of the MyD88-independent pathway via TLR4. MyD88-deficient cells failed to produce inflammatory cytokines in response to LPS, whereas they responded to LPS by activating IFN-regulatory factor 3 as well as inducing the genes containing IFN-stimulated regulatory elements such as IP-10. In contrast, a lipopeptide that activates TLR2 had no ability to activate IFN-regulatory factor 3. The MyD88-independent pathway was also activated in cells lacking both MyD88 and TNFR-associated factor 6. Thus, TLR4 signaling is composed of at least two distinct pathways, a MyD88-dependent pathway that is critical to the induction of inflammatory cytokines and a MyD88/TNFR-associated factor 6-independent pathway that regulates induction of IP-10.

Adaptor Proteins, Signal Transducing↗

Antinociceptive effect of the novel compound OT-7100 in a diabetic neuropathy model.

We previously reported that OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-alpha]pyrimidine) had antinociceptive potency in various animal models. To further characterize this compound, the present study examined the effects of OT-7100 on mechanical hyperalgesia and motor nerve conduction velocity in streptozotocin-induced diabetic rats. OT-7100 significantly increased the nociceptive threshold in the diabetic rat in a dose-dependent manner. Gabapentin (anticonvulsant agent) and insulin strongly increased the nociceptive threshold but gabapentin increased it above normal levels. An aldose reductase inhibitor slightly increased the nociceptive threshold at a high dose. We also measured glucose levels and motor nerve conduction velocity in OT-7100-treated rats. Insulin decreased glucose levels but OT-7100 had no effect on glucose levels or on motor nerve conduction velocity. These results suggest that OT-7100 alleviates hyperalgesia in a diabetic neuropathy model in a different manner from gabapentin or aldose reductase inhibitor and may be a new treatment for the pain associated with peripheral nerve injury.

Acetates↗

ARR1, a transcription factor for genes immediately responsive to cytokinins.

Cytokinins are a class of phytohormones involved in various physiological events of plants. The Arabidopsis sensor histidine kinase CRE1 was recently reported to be a cytokinin receptor. We used a steroid-inducible system to show that the transcription factor-type response regulator ARR1 directs transcriptional activation of the ARR6 gene, which responds to cytokinins without de novo protein synthesis. This fact, together with characteristics of ARR1-overexpressing plants and arr1 mutant plants, indicates that the phosphorelay to ARR1, probably from CRE1, constitutes an intracellular signal transduction occurring immediately after cytokinin perception.

Adenine↗

A p53 polymorphism associated with increased risk of hepatitis C virus infection.

Incidence of polymorphisms on exon 4 (CGC vs. CCC, p53Arg vs. p53Pro, A2 allele vs. A1 allele at codon 72, respectively) of the p53 gene was compared in 75 cases with hepatitis C virus (HCV) infection and 232 noninfected control subjects in a defined geographical area in Japan. Polymorphism was analyzed by the polymerase chain reaction-single strand conformation polymorphism method using DNA from peripheral blood leukocytes. When all cases and controls were compared, there was no significant correlation between hepatitis C virus (HCV) infection and the p53 polymorphism in question. However, when male cases infected with HCV type 1b, the most common viral genotype, were compared with controls matched by sex and age, significantly higher homozygotes for p53Pro were found in cases compared with controls (P=0.039). Significantly higher allelic frequency of this polymorphism was also observed with cases (P=0.010). We found no significant statistical difference between the p53 polymorphism and other genotypes of HCV (2a, 2b and others). On the basis of our study we believe there exists a significant correlation between male homozygotes for p53Pro with HCV type 1b infection.

Codon↗

Interaction of syntaxin with alpha-fodrin, a major component of the submembranous cytoskeleton.

The soluble N-ethyl maleimide-sensitive factor attachment protein receptor machinery is involved in membrane docking and fusion. In this machinery, the syntaxin family is a central coordinator and participates in multiple protein-protein interactions. In this study we have shown that alpha-fodrin, nonerythroid spectrin, is a new binding partner of the syntaxin family. alpha-Fodrin bound to syntaxin-1a, -3, and -4, all of which are localized on the plasma membrane. Syntaxin-3 interacted with alpha-fodrin in dose-dependent and saturable manners but not with alpha-spectrin, erythroid spectrin. Syntaxin-3 interacted with alpha-fodrin through its C-terminal coiled-coil region. Binding of Munc18 or SNAP-25 to syntaxin-1a inhibited the interaction of alpha-fodrin with syntaxin-1a. Available evidence indicates that alpha-fodrin is implicated in exocytosis, but a precise mode of action of alpha-fodrin in exocytosis remains unclear. Our results suggest that alpha-fodrin regulates exocytosis through the interaction with members of the syntaxin family.

Animals↗

Effect of cernitin pollen-extract on experimental nonbacterial prostatitis in rats.

BACKGROUND: The treatment for chronic nonbacterial prostatitis (NBP) has not been established. Cernitin pollen-extract (CN-009) is reported to have therapeutic effects for NBP. The effects and mechanisms of CN-009 were investigated. METHODS: Ten-month-old rats were used with administration of estradiol after castration, which were similar to human NBP histologically. Since CN-009 consists of T-60 and GBX, these drugs were administered, respectively. The prostate was evaluated histopathologically including glandular damage (epithelial score), stromal ratio and immunohistochemical assays for epithelial function (PAP), stromal evaluation (Vimentin), cell proliferation (PCNA) and apoptosis (deoxyuridine triphosphate biotin nick end-labeling (TUNEL)). RESULTS: Controls revealed severe acinar gland atrophy and stromal proliferation. CN-009 showed diminished these damages. Epithelial score was better (P < 0.01) and PAP positive materials were more abundant in CN-009 and GBX than in Controls. The stromal ratio was lower in CN-009 (P < 0.01) and T-60 (P < 0.05). There was no difference for PCNA positive cells in the epithelium and stroma, and TUNEL positive cells in epithelium. While, the number of TUNEL positive cells in the stroma of CN-009 and T-60 increased (P < 0.01). CONCLUSIONS: These findings suggest that CN-009 protects acinar epithelial cells mainly by GBX and also inhibits stromal proliferation in association with enhanced apoptosis mainly by T-60.

Acid Phosphatase↗

High expression of S-phase kinase-interacting protein 2, human F-box protein, correlates with poor prognosis in oral squamous cell carcinomas.

Reduced expression of p27(Kip1), a cyclin-dependent kinase (Cdk) inhibitor, is frequently found in various cancers, including oral squamous cell carcinoma (OSCC), and is attributable to an enhancement of its degradation. Skp2, an F-box protein necessary for DNA replication, is required for the ubiquitinylation and subsequent degradation of p27(Kip1). In the present study, we examined the expression of Skp2 and its correlation with the expression of p27(Kip1) protein or p27(Kip1) degradation in OSCC. Using immunohistochemistry, we found that high expression of Skp2 was present in 49% of OSCCs and only 20% of epithelial dysplasias. Significantly, high expression of Skp2 was correlated with poor prognosis of OSCC patients. We also found an inverse correlation between the expression of Skp2 and p27 by immunohistochemical analysis. A similar correlation was observed in OSCC cell lines and OSCC tissues by Western blot analysis. Interestingly, OSCC tissues with Skp2 expression had high p27(Kip1) degradation activity. These findings indicate that (a) Skp2 may play an important role for the development of OSCC, (b) Skp2 can be a novel target for OSCC treatment as well as a strong prognostic marker, and (c) the reduction in p27(Kip1) protein may be brought about by enhancement of its degradation mediated by increased levels of Skp2 protein.

Adult↗

Carbonyl reductase as a significant predictor of survival and lymph node metastasis in epithelial ovarian cancer.

We have recently reported a novel function for carbonyl reductase (CR), namely, its ability to modulate the metastatic potential of malignant mouse cells. Because there are currently no data addressing a similar function for CR in human cancers, the aim of this study was to assess a correlation between survival and metastasis, and CR level in epithelial ovarian cancer. Using anti-CR antibody, immunohistochemical staining was performed on 73 epithelial ovarian cancers, 13 borderline malignant tumours, and 25 benign ovarian tumours for a total of 111 specimens. The combined rate for strongly and weakly positive reactions for CR was 32.0% for benign tumours, 38.5% for borderline malignant tumours, and 61.6% for ovarian cancers. The CR-positive rate was 35.7% (weakly positive alone) for ovarian cancers with retroperitoneal lymph node (RLN) metastasis and 67.8% for those without RLN metastasis (P< 0.05). The 5-year survival rate was 62.7% for the patients with CR-negative cancer and 86.1% for those with CR-positive cancer (P< 0.05). The present results indicate that decreased CR expression in epithelial ovarian cancer is associated with RLN metastasis and poor survival.

Adult↗

On the relationship between protein stability and folding kinetics: a comparative study of the N-terminal domains of RNase HI, E. coli and Bacillus stearothermophilus L9.

There is currently a great deal of interest in proteins that fold in a single highly cooperative step. Particular attention has been focused on elucidating the factors that govern folding rates of simple proteins. Recently, the topology of the native state has been proposed to be the most important determinant of their folding rates. Here we report a comparative study of the folding of three topologically equivalent proteins that adapt a particularly simple alpha/beta fold. The folding kinetics of the N-terminal domain of RNase HI and the N-terminal domain of the ribosomal protein L9 from Escherichia coli (eNTL9) were compared to the previously characterized N-terminal domain of L9 from Bacillus stearothermophilus (bNTL9). This 6.2 kDa protein, which is one of simplest examples of the ABCalphaD motif, folds via a two-state mechanism on the millisecond to submillisecond time scale. The RNase HI domain and bNTL9 have very similar tertiary structures but there is little similarity in primary sequence. bNTL9 and eNTL9 share the same biological function and a similar primary sequence but differ significantly in stability. Fluorescence-detected stopped-flow experiments showed that the three proteins fold in a two-state fashion. The folding rates in the absence of denaturant were found to be very different, ranging form 21 s(-1) to 790 s(-1) at 10 degrees C. The diverse folding rates appear to reflect large differences in the stability of the proteins. When compared at an isostability point, the folding rates converged to a similar value and there is a strong linear correlation between the log of the folding rate and stability for this set of proteins. These observations are consistent with the idea that stability can play an important role in dictating relative folding rates among topologically equivalent proteins.

Amino Acid Motifs↗

Cleavage of the C-C linkage between the sugar and the aglycon in C-glycosylphloroacetophenone, and the NMR spectral characteristics of the resulting di-C-glycosyl compound.

The treatment of unprotected mono-C-beta-D-glucopyranosylphloroacetophenone with a cation-exchange resin in anhydrous acetonitrile afforded both a phloroacetophenone and a di-C-beta-D-glucopyranosylphloroacetophenone. Treatment of an unprotected mono-C-(2-deoxy-beta-D-arabino-hexopyranosyl)phloroacetophenone (mono-C-2-deoxy-beta-D-glucopyranosylphloroacetophenone) also afforded both the aglycon and di-C-(2-deoxy-beta-D-arabino-hexopyranosyl)phloroacetophenone. The reaction mixtures were acetylated, and the structures of the isolated products were determined by NMR spectroscopy. This is the first demonstration of the formation of a di-C-glycosyl compound during the chemical cleavage of the C-C linkage between the sugar and the aglycon in an aryl C-glycosyl derivative.

Acetophenones↗