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H Sasaki

Publications and source records attributed to H Sasaki.

At least 19 recordsLinked to original sources
PubMed2006

Brain catecholamine alterations and pathological features with aging in Parkinson disease model rat induced by Japanese encephalitis virus.

We analyzed two disease model groups with rats infected by Japanese encephalitis virus (JEV), a 90-day group and a 180-day group after JEV infection. The time measured by the modified pole test showed that motor activities in these two groups were slower than those of age-matched control groups. Striatal dopamine (DA) levels were significantly decreased in all JEV-infected rats. Norepinephrine concentration in brain regions in the 180-day group was significantly decreased in the medulla oblongata and hypothalamus as compared with the control and 90-day group. Tyrosine hydroxylase-positive neurons were significantly decreased in both JEV-infected rat groups. These results suggest that DA decrease and pathological changes in JEV-infected model rats persist for a long time, at least up to 180 days, and this model will be useful for the evaluation of new anti-parkinsonian agents.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Genome-wide profiling of promoter methylation in human.

DNA methylation in the promoter region of a gene is associated with a loss of that gene's expression and plays an important role in gene silencing. The inactivation of tumor-suppressor genes by aberrant methylation in the promoter region is well recognized in carcinogenesis. However, there has been little study in this area when it comes to genome-wide profiling of the promoter methylation. Here, we developed a genome-wide profiling method called Microarray-based Integrated Analysis of Methylation by Isoschizomers to analyse the DNA methylation of promoter regions of 8091 human genes. With this method, resistance to both the methylation-sensitive restriction enzyme HpaII and the methylation-insensitive isoschizomer MspI was compared between samples by using a microarray with promoter regions of the 8091 genes. The reliability of the difference in HpaII resistance was judged using the difference in MspI resistance. We demonstrated the utility of this method by finding epigenetic mutations in cancer. Aberrant hypermethylation is known to inactivate tumour suppressor genes. Using this method, we found that frequency of the aberrant promoter hypermethylation in cancer is higher than previously hypothesized. Aberrant hypomethylation is known to induce activation of oncogenes in cancer. Genome-wide analysis of hypomethylated promoter sequences in cancer demonstrated low CG/GC ratio of these sequences, suggesting that CpG-poor genes are sensitive to demethylation activity in cancer.

Adenocarcinoma↗
PubMed2006

Fish intake and serum levels of organochlorines among Japanese women.

This study evaluates background serum levels of selected organochlorine compounds among Japanese women of reproductive age and investigates whether lifestyle factors, especially dietary factors, may be associated with these levels. A cross-sectional study was performed on 80 Japanese women, aged 26-43 years, who complained of infertility and were confirmed not to have endometriosis. The serum levels of total toxic equivalency (TEQ), 18 polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs), 4 coplanar polychlorinated biphenyls (cPCBs), 36 ortho-substituted polychlorinated biphenyls (PCBs), and 13 chlorinated pesticides or their metabolites were measured and data were collected on the women's age, residence, occupation, body mass index (BMI), smoking and alcohol habit and 6 dietary intakes (fish, meats, rice, vegetables, fruits and dairy products). The serum median level of total TEQ was 25.1 pg TEQ/g lipid, that of PCDDs/PCDFs/cPCBs was 11.5 pmol/g lipid, that of PCBs was 0.46 nmol/g lipid, and that of total pesticides was 1.32 nmol/g lipid. The serum levels of total TEQ, PCDDs/PCDFs/cPCBs, PCBs and pesticides were positively associated with age (P for trend=0.003, 0.01, 0.005 and 0.01, respectively) and frequent fish consumption (P for trend=0.002, 0.003, 0.0003 and 0.006, respectively). Other lifestyle factors were not associated with serum organochlorine levels. The present study suggests that Japanese women who consume fish frequently in their reproductive period tend to accumulate organochlorines in their bodies.

Adult↗
PubMed2006

Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells.

The aim of the study was to examine the effects of a mucolytic drug, carbocisteine, on rhinovirus (RV) infection in the airways. Human tracheal epithelial cells were infected with a major-group RV, RV14. RV14 infection increased virus titres and the cytokine content of supernatants. Carbocisteine reduced supernatant virus titres, the amount of RV14 RNA in cells, cell susceptibility to RV infection and supernatant cytokine concentrations, including interleukin (IL)-6 and IL-8, after RV14 infection. Carbocisteine reduced the expression of mRNA encoding intercellular adhesion molecule (ICAM)-1, the receptor for the major group of RVs. It also reduced the supernatant concentration of a soluble form of ICAM-1, the number and fluorescence intensity of acidic endosomes in the cells before RV infection, and nuclear factor-kappaB activation by RV14. Carbocisteine also reduced the supernatant virus titres of the minor group RV, RV2, although carbocisteine did not reduce the expression of mRNA encoding a low density lipoprotein receptor, the receptor for RV2. These results suggest that carbocisteine inhibits rhinovirus 2 infection by blocking rhinovirus RNA entry into the endosomes, and inhibits rhinovirus 14 infection by the same mechanism as well as by reducing intercellular adhesion molecule-1 levels. Carbocisteine may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.

Aged↗
PubMed2006

Identification of tumor markers and differentiation markers for molecular diagnosis of lung adenocarcinoma.

To identify tumor markers and differentiation markers for lung adenocarcinoma (AdC), we analysed expression profiles of 14,500 genes against three cases of type II alveolar epithelial cells, bronchiolar epithelial cells, and bronchial epithelial cells, respectively, and 10 cases of AdC cells isolated by laser capture microdissection. Hierarchical clustering analysis indicated that AdC cells and noncancerous lung epithelial cells are significantly different in their expression profiles, and that different sets of differentiation markers are expressed among alveolar, bronchiolar and bronchial epithelial cells. Nine genes were identified as being highly expressed in AdC cells, but not expressed in noncancerous lung epithelial cells. Sixteen genes were identified as differentiation markers for lung epithelial cells. Real-time RT-PCR analysis of 45 lung AdC cases further revealed that expression of four tumor markers in AdC cells was significantly higher than that in noncancerous lung cells and that expression of ten differentiation markers was retained in a considerable fraction of lung AdC cases. Five tumor markers and seven differentiation markers were not expressed in peripheral blood cells. Similarities and differences in expression profiles between normal epithelial cells from different lung respiratory compartments and AdC cells demonstrated in this study will be informative for the molecular diagnosis of lung AdC.

Adenocarcinoma↗
PubMed2006

Should we discard the renal allografts from cardiac death donors that have total ischemic time longer than 24 hours?

PURPOSE: The objective of this study was to investigate the outcome of transplantation using kidney grafts donated after cardiac death (DCD) with a total ischemic time (TIT) longer than 24 hours. PATIENTS AND METHODS: We followed 373 kidneys recovered from DCD donors and transplanted at 41 centers. All kidneys were procured from uncontrolled DCD donors. Grafts were classified into two groups according to TIT. We recorded renal function and duration of the survival period for each graft. RESULTS: Fifty-three grafts had a TIT longer than 24 hours (group 1). The other 320 grafts had a TIT less than 24 hours (group 2). The number of never functioning grafts were three in group 1 (5.7%) and 17 in group 2 (5.3%). Delayed graft function (DGF) occurred in 44 group 1 (83.0%) and 254 group 2 kidneys (79.4%) for intervals of 13.5 +/- 12.6 versus 10.9 +/- 12.6 days, respectively. Graft survival rates at 3, 5, and 10 years posttransplant were 84.9%, 73.0%, 64.1% for group 1, and 76.3%, 69.9%, 57.1% for group 2. In a Cox proportional hazards model, TIT longer than 24 hours was not a significant independent risk factor. CONCLUSION: Our results showed that even kidneys with TITs of over 24 hours yielded comparable results despite a higher incidence of DGF.

Death, Sudden, Cardiac↗
PubMed2006

Is pulsatile perfusion necessary for renal transplantation engrafting kidneys from cardiac death donors?

BACKGROUND: There has been a considerable literature describing the use of pulsatile perfusion (PP) to evaluate the efficacy of organs from deceased donors. Since 1979, we recovered 469 kidneys from deceased donors after cardiac death (DCDs), using an in situ regional cooling technique and preservation by simple cold storage. In this study, the posttransplantation outcomes as well as long-term survivals of renal grafts from DCDs were compared with PP data in the recent literature. MATERIALS AND METHODS: We compared our recent data with 176 kidneys recovered between 1993-2002 using an in situ regional cooling technique. Patient and graft survivals were compared with those from the Scientific Registry of Transplant Recipients (SRTR) database. RESULTS: Following transplantation, 4.5% of the grafts never recovered; 10.3% of the grafts showed immediate renal function; 85.2% of the grafts had delayed graft function (DGF) with an average acute tubular necrosis (ATN) period of 13.1 days compared with 54.3% DGF from DCD using PP. Graft survival rates at 1, 3, 5, and 10 years were 90.8%, 86.5%, 77.8%, and 69.0%, respectively, compared with 89% at 1 year and 80% at 3 years reported for DCD by the SRTR in which almost 30% of the grafts underwent PP. CONCLUSIONS: Although PP seemed to have some advantage to decrease the DGF ratio, an in situ regional cooling technique with simple cold storage may provide excellent graft function and long-term graft survival as well as having benefits in cost and transportation.

Adult↗
PubMed2006

Up-regulation of osteopontin, chemokines, adhesion molecule, and heat shock proteins in 1-hour biopsy from cardiac death donor kidneys.

AIMS: Since April 1979, 471 kidneys were retrieved from donors after cardiac death (DCD) using an in situ regional cooling technique, with excellent renal function and good long-term graft survival. However, the precise cascade of events following transplantation of DCD kidneys and the influence of ischemia-reperfusion injury remain unclear. In this study, we performed gene expression profiling using 1-hour biopsy samples from DCD kidneys versus those from living sources. METHODS: All kidney grafts were procured at our center using an in situ regional cooling technique from DCD. Living donor kidneys (LD) were harvested by open nephrectomy. All graft biopsies were performed 1 hour after reperfusion (DCD n = 8, LD n = 9). We analyzed the expression profile of 20,173 genes. RESULTS: One hundred seventy eight genes were up-regulated (>2-fold difference and DCD/LD > 1.5) and 120 down-regulated (<1/2-fold and LD/DCD > 1.5) in DCD kidneys. Expression of osteopontin (22.5 +/- 2.6-fold DCD vs 7.7 +/- 1.7 LD; P < .001), chemokines (CCL4 4.4 +/- 0.7 vs 2.5 +/- 0.3; P < .01), (CCL2 6.0 +/- 1.3 vs 2.8 +/- 0.5), CXCL1 (9.5 +/- 0.4 vs 2.0 +/- 0.2), and CXCL2 (16.7 +/- 5.3 vs 4.8 +/- 1.3; P < .05), adhesion molecule (ICAM-1 4.7 +/- 0.7 vs 2.5 +/- 0.4; P < .05), and heat shock proteins (HSPA1L 6.7 +/- 0.7 vs 1.6 +/- 0.3, HSPA1A 17.7 +/- 2.6 vs 2.4 +/- 0.5, HSPA1B 13.3 +/- 0.2 vs 3.0 +/- 0.7, HSPA5 6.7 +/- 0.8 vs 3.2 +/- 0.3, HSPB1 2.9 +/- 0.2 vs 1.0 +/- 0.1, and HSPH1 19.4 +/- 3.0 vs 5.9 +/- 1.1; P < .001) were up-regulated in the kidneys from DCD. CONCLUSION: This report analyzed global gene expression using 1-hour biopsy samples from DCD kidneys. These results may provide new insight into the identification of novel target genes for the development of therapeutic approaches and for determining graft viability of kidneys from DCD.

Biopsy↗
PubMed2006

Association of susceptibility to the development of pneumonia in the older Japanese population with haem oxygenase-1 gene promoter polymorphism.

BACKGROUND: Oxidative stresses including cigarette smoking are implicated in the pathogenesis of cerebrovascular diseases, which are associated with pneumonia because of frequent aspiration. Haem oxygenase-1 (HO-1) acts in cytoprotection against oxidants, provides anti-inflammatory effects, and inhibits atherogenesis. A (GT)(n) dinucleotide repeat in the human HO-1 promoter modulates HO-1 gene expression and shows length polymorphism, which is grouped into three classes: class S (<27 repeats), class M (> or = 27, <33 repeats), and class L (> or = 33 repeats) alleles. OBJECTIVE: To investigate the correlation between the HO-1 gene polymorphism and development of pneumonia in elderly Japanese. METHODS: The length of the (GT)n repeats was analysed in 200 elderly patients with pneumonia and 200 control subjects. The association of the HO-1 gene polymorphism with risk of pneumonia was estimated by logistic regression. RESULTS: The proportion of allele frequencies in class L, and the proportion of genotypic frequencies in the L-allele carriers (L/L, L/M, and L/S), was significantly higher in patients with pneumonia than in controls (20% v 10% in class L, and 34% v 18% in L-allele carriers). After adjustment for potentially confounding factors, both cerebrovascular disorders and HO-1 gene L-allele carriers were significant and independent risk factors for pneumonia. The adjusted odds ratio for L-allele carriers v non-L-allele carrier was 2.1 (95% confidence interval, 1.2 to 3.6). CONCLUSIONS: The large size of a (GT)n repeat in the HO-1 gene promoter may be associated with susceptibility to pneumonia in the older Japanese population.

Aged↗
PubMed2006

Evolution of the vertebrate DNMT3 gene family: a possible link between existence of DNMT3L and genomic imprinting.

DNA methylation plays an essential role in genomic imprinting observed in eutherian mammals and marsupials. In mouse, one of the two de novo DNA methyltransferases, Dnmt3a, and a related protein, Dnmt3L have been shown to be essential for imprint establishment in the parental germline. To gain insights into the evolution of imprinting mechanisms, we have identified and characterized the DNMT3 family genes in other vertebrate species. We cloned cDNAs for chicken DNMT3A and DNMT3B, whose putative protein products shared 81.5% and 48.6% amino acid sequence identity with their mouse orthologues. Using computer-assisted database searches, we also identified DNMT3A and DNMT3B orthologues in fish (fugu and zebrafish) and marsupials (opossum). We found that, while opossums had an orthologue for DNMT3L, chickens and fish did not have this gene. Thus, unlike the other DNMT3 members, DNMT3L was restricted to the species in which imprinting occurs. The acquisition of DNMT3L by a common ancestor of eutherians and marsupials might have been closely related to the evolution of imprinting.

Amino Acid Sequence↗
PubMed2006

Bisulfite sequencing and dinucleotide content analysis of 15 imprinted mouse differentially methylated regions (DMRs): paternally methylated DMRs contain less CpGs than maternally methylated DMRs.

Imprinted genes in mammals show monoallelic expression dependent on parental origin and are often associated with differentially methylated regions (DMRs). There are two classes of DMR: primary DMRs acquire gamete-specific methylation in either spermatogenesis or oogenesis and maintain the allelic methylation differences throughout development; secondary DMRs establish differential methylation patterns after fertilization. Targeted disruption of some primary DMRs showed that they dictate the allelic expression of nearby imprinted genes and the establishment of the allelic methylation of secondary DMRs. However, how primary DMRs are recognized by the imprinting machinery is unknown. As a step toward elucidating the sequence features of the primary DMRs, we have determined the extents and boundaries of 15 primary mouse DMRs (including 12 maternally methylated and three paternally methylated DMRs) in 12.5-dpc embryos by bisulfite sequencing. We found that the average size of the DMRs was 3.2 kb and that their average G+C content was 54%. Dinucleotide content analysis of the DMR sequences revealed that, although they are generally CpG rich, the paternally methylated DMRs contain less CpGs than the maternally methylated DMRs. Our findings provide a basis for the further characterization of DMRs.

Animals↗
PubMed2006

Tsix-deficient X chromosome does not undergo inactivation in the embryonic lineage in males: implications for Tsix-independent silencing of Xist.

Differential induction of the X-linked non-coding Xist gene is a key event in the process of X inactivation occurring in female mammalian embryos. Xist is negatively regulated in cis by its antisense gene Tsix through modification of the chromatin structure. The maternal Xist allele, which is normally silent in the extraembryonic lineages, is ectopically activated when Tsix is disrupted on the same chromosome, and subsequently the maternal X chromosome undergoes inactivation in the extraembryonic lineages even in males. However, it is still unknown whether the single Tsix-deficient X chromosome (XDeltaTsix) in males is also inactivated in the embryonic lineage. Here, we show that both male and female embryos carrying a maternally derived XDeltaTsix could survive if the extraembryonic tissues were complemented by wild-type tetraploid cells. In addition, Xist on the XDeltaTsix was properly silenced and methylated at CpG sites in adult male somatic cells. These results indicate that the embryonic lethality caused by the maternal XDeltaTsix is solely attributable to the defects in the extraembryonic lineages. XDeltaTsix does not seem to undergo inactivation in the embryonic lineage in males, suggesting the presence of a Tsix-independent silencing mechanism for Xist in the embryonic lineage.

Animals↗
PubMed2006

Treponema denticola in disseminating endodontic infections.

Treponema denticola is a consensus periodontal pathogen that has recently been associated with endodontic pathology. In this study, the effect of mono-infection of the dental pulp with T. denticola and with polymicrobial "red-complex" organisms (RC) (Porphyromonas gingivalis, Tannerella forsythia, and T. denticola) in inducing disseminating infections in wild-type (WT) and severe-combined-immunodeficiency (SCID) mice was analyzed. After 21 days, a high incidence (5/10) of orofacial abscesses was observed in SCID mice mono-infected with T. denticola, whereas abscesses were rare in SCID mice infected with the red-complex organisms or in wild-type mice. Splenomegaly was present in all groups, but only mono-infected SCID mice had weight loss. T. denticola DNA was detected in the spleen, heart, and brain of mono-infected SCID mice and in the spleen from mono-infected wild-type mice, which also had more periapical bone resorption. The results indicate that T. denticola has high pathogenicity, including dissemination to distant organs, further substantiating its potential importance in oral and linked systemic conditions.

Alveolar Bone Loss↗
PubMed2006

HLA-dPB1*0501 is not uniquely associated with opticospinal multiple sclerosis in Japanese patients. Important role of DPB1*0301.

Apart from its unique lesion distribution pattern, the opticospinal form of multiple sclerosis (OSMS) is distinct among Japanese patients who satisfy the diagnostic criteria of MS. OSMS has been suggested to be strongly associated with HLA-DPB1*0501 in Japanese. However, association of DPB1*0301 with non-OSMS and lack of DPB1*0301 in OSMS were also reported. To verify the role of DPB1*0501 and DPB1*0301 in Japanese MS patients we determined the frequencies of these alleles in 26 patients with OSMS, 167 with non-OSMS and 156 normal subjects, who were all residents of Hokkaido, the northernmost island of Japan. All (100%) OSMS were negative for DPB1*0301 while 32 (19%) of the non-OSMS were positive for the allele. In DPB1*0301-negatives, the frequencies of DPB1*0501 in OSMS (85%) and non-OSMS (82%) were similar, but both were higher than in the controls (66%). In DPB1*0301-positives, the frequency of DPB1*0501 was low but similar in non-OSMS (12/32; 38%) and controls (6/14; 43%). Periventricular white matter lesions (PVL) were noted in 31 of 32 (97%) DPB1*0301-positive non-OSMS patients but in only 22 out of 135 (16%) DPB1*0301-negative non-OSMS patients and two out of 26 (8%) OSMS patients. Our findings indicate that DPB1*0501 plays an important role in the development of MS in general, but not in OSMS. The strong association of DPB1*0501 with OSMS may be due to the over-representation of the DPB1*0301 allele among individuals in the non-OSMS group. In addition, DPB1*0301 might be relevant to the development of periventricular lesions in Japanese patients with MS.

Adult↗
PubMed2006

A human case of hypoplastic external iliac artery and its collateral pathways.

During a student dissection course held at the Tokyo Women's Medical University, in a 91-year-old human female cadaver we encountered a very rare case of a hypoplastic right external iliac artery. It continued into the normal femoral artery by anastomoses formed with the enlarged obturator and deep circumflex iliac arteries. While the obturator artery originated from the anterior branch of the internal iliac artery, the deep circumflex iliac artery was supplied by the iliolumbar artery, which in turn formed a common stem to arise from the lateral sacral artery. Whether the hypoplastic external iliac artery arose developmentally or secondarily could not be discerned, but the case nevertheless provides important information regarding the arterial anlage between the pelvis and lower extremity. The case is also clinically significant in that it indicates a possible collateral pathway if the external iliac artery is occluded or ischaemia.

Aged, 80 and over↗
PubMed2005

The clinical and genetic spectrum of spinocerebellar ataxia 14.

Spinocerebellar ataxia 14 (SCA14) is associated with missense mutations in the protein kinase C gamma gene (PRKCG), rather than a nucleotide repeat expansion. In this large-scale study of PRKCG in patients with ataxia, two new missense mutations, an in-frame deletion, and a possible splice site mutation were found and can now be added to the four previously described missense mutations. The genotype/phenotype correlations in these families are described.

Adolescent↗