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Biomedical subjects

Yoshitake Hayashi

Publications and source records attributed to Yoshitake Hayashi.

At least 19 recordsLinked to original sources
PubMed2007

Genotype and variations in core promoter and pre-core regions are related to progression of disease in HBV-infected patients from Northern Vietnam.

Vietnam is one of the countries with a high rate of hepatitis B virus (HBV) infection, but there are only a few reports about relation of HBV genotypes and mutations to clinical course in Northern Vietnam. The characteristics of HBV and its relationship to clinical outcome in patients from Northern Vietnam were analyzed. Serum samples were collected from 183 HBV-infected Vietnamese patients. They were clinically categorized into 4 groups: hepatocellular carcinoma (HCC), liver cirrhosis (LC), chronic hepatitis (CH), and asymptomatic carriers (ASC). HBV serology, alpha-fetoprotein, HBV genotypes, HBV-DNA level and mutations in the core promoter and pre-core regions of HBV-DNA were examined. The majority of sera contained HBV genotype B (67.8%) and C (27.9%). The median age was matched between genotype B and C (38.2 vs. 42.9 years). The rates of HBeAg seroconversion and G1896A for genotype B were significantly higher than those for genotype C (P<0.05). Genotype C had a higher HBV-DNA level than genotype B. C1858 was frequent, especially in genotype C (62.7%). The most prevalent genotype in ASC and CH was genotype B. The presence of the mutation A1762T/G1764A correlated with disease progression. The triple mutation T1753C/A1762T/ G1764A was quite common and was more prevalent in LC and HCC than in CH and ASC. In Northern Vietnamese, HBV genotypes B and C were prevalent. Genotype C and mutations in the core promoter region were associated with progressive, severe liver diseases.

Adolescent↗
PubMed2006

Controlled release of basic fibroblast growth factor from gelatin hydrogel sheet improves structural and physiological properties of vein graft in rat.

OBJECTIVES: Autologous vein grafts are still widely used, but their long-term patency is suboptimal. The objective of the current study was to determine whether wrapping a vein graft in gelatin hydrogel sheet incorporating basic fibroblast growth factor improves their mechanical and physiological properties. METHODS AND RESULTS: Autologous femoral vein was interposed into the abdominal aorta in rats. The rats were divided into 3 groups: nontreated grafts (group A), grafts wrapped in basic fibroblast growth factor-free gelatin hydrogel sheet (group B), and grafts wrapped in basic fibroblast growth factor-impregnated gelatin hydrogel sheet (group C). On day 1, endothelial desquamation was observed in group A, and the media in groups A and B were disrupted, staining positive in the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. In contrast, the media in group C remained intact and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-negative, associated with activation of MAPK. Graft dilation was significantly inhibited in groups B and C compared with group A, with those in group C showing the smallest degree of neointimal proliferation. At 8 weeks grafts in group C developed neointima with homogeneous elastic laminae, presence of rigid neoadventitia that displayed neovascularity, and the highest blood flow velocity. CONCLUSIONS: Wrapping vein grafts in basic fibroblast growth factor-impregnated gelatin hydrogel sheet improved their structural and physiological properties, and might therefore also improve long-term patency.

Anastomosis, Surgical↗
PubMed2006

Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves.

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Carcinoma, Hepatocellular↗
PubMed2006

HLA-DR-negative AML (M1 and M2): FLT3 mutations (ITD and D835) and cell-surface antigen expression.

FLT3 mutations and cell-surface antigen were investigated in 29 DR-negative (DR(-)) M1/M2 AML samples in comparison with 30 DR-positive (DR(+)) M1/M2 AML samples. FLT3-ITD was detected in 59.3% and D835 was detected in 7.4% of the samples. The incidence of FLT3-ITD was higher in the DR(-) group (59.3%) than in the DR(+) group (17.9%; P=0.002). The DR(-) status was associated with the CD34(-) (82.8%), CD7(-) (92.9%) and CD45RO(+) status (76%). Our results indicated that FLT3 mutation is the most common gene alteration found in the DR(-) M1/M2 AML. These results are important for further characterizing this phenotypic AML entity.

Amino Acid Sequence↗
PubMed2006

The LXXLL motif of murine forkhead transcription factor FoxO1 mediates Sirt1-dependent transcriptional activity.

The forkhead transcription factor FoxO1 has been identified as a negative regulator of insulin/IGF-1 signaling. Its function is inhibited by phosphorylation and nuclear exclusion through a PI3K-dependent pathway. However, the structure/function relationship of FoxO1 has not been elucidated completely. In this study, we carried out mutation analysis of the FoxO1 coactivator-interacting LXXLL motif (amino acids 459-463). Expression of a 3A/LXXAA mutant, in which 3 Akt phosphorylation sites (T24, S253, and S316) and 2 leucine residues in the LXXLL motif (L462 and L463) were replaced by alanine, decreased both Igfbp-1 and G6Pase promoter activity and endogenous Igfbp-1 and G6Pase gene expression in simian virus 40-transformed (SV40-transformed) hepatocytes. Importantly, mutagenesis of the LXXLL motif eliminated FoxO1 interaction with the nicotinamide adenine dinucleotide-dependent (NAD-dependent) deacetylase sirtuin 1 (Sirt1), sustained the acetylated state of FoxO1, and made FoxO1 nicotinamide and resveratrol insensitive, supporting a role for this motif in Sirt1 binding. Furthermore, intravenous administration of adenovirus encoding 3A/LXXAA FoxO1 into Lepr db/db mice decreased fasting blood glucose levels and improved glucose tolerance and was accompanied by reduced G6Pase and Igfbp-1 gene expression and increased hepatic glycogen content. In conclusion, the LXXLL motif of FoxO1 may have an important role for its transcriptional activity and Sirt1 binding and should be a target site for regulation of gene expression of FoxO1 target genes and glucose metabolism in vivo.

1-Methyl-3-isobutylxanthine↗
PubMed2006

Case of adult genotype C HBV carrier after acute hepatitis B, losing HBsAg and acquiring HBsAb after IFN and lamivudine treatment.

Here we report the case of a 48-year-old man, carrier of genotype C HBV for longer than 6 months after contracting sexually transmitted acute hepatitis B, who eventually lost HBsAg and acquired HBsAb by IFN/lamivudine therapy. The patient had been negative for HBsAg in 2001, but, during his stay in China from January to July in 2003, he developed acute hepatitis B after having an extra-marital sexual contact there. HBsAg was still positive and a liver biopsy indicated chronic hepatitis when he was admitted to our hospital in December 2003 for detailed examination of liver dysfunction. HBV DNA in his serum, revealed to segregate to genotype C by sequencing on admission, decreased to undetectable levels at the end of a 3-month IFN therapy, and remained undetectable during and after the successive 6-month lamivudine therapy. HBeAg seroconverted to HBeAb during the therapy, and HBsAb appeared after the therapy. To our knowledge, this is the first case of genotype C chronic hepatitis B occurring after acute hepatitis.

Journal Article↗
PubMed2006

His239Arg SNP of HRAD9 is associated with lung adenocarcinoma.

BACKGROUND: It was previously reported that a functional human (h) Rad9 protein accumulated in the nuclei of non-small cell lung carcinoma (NSCLC) cells. Those experiments, however, did not examine whether the hRad9 gene was mutated in those cells. The sequence of the HRAD9 gene in NSCLC cells was investigated. METHODS: The sequence of the HRAD9 was examined in tumor and peripheral normal lung tissues obtained from 50 lung adenocarcinoma patients during surgery. The expression of its mRNA using reverse transcription polymerase chain reaction (RT-PCR) was also examined. RESULTS: No sequence alterations were detected in the HRAD9 gene, which was found to be normally transcribed in surgically resected lung carcinoma cells. However, in eight (16.0%) cases a single nucleotide polymorphism (SNP) was observed at the second position of codon 239 (His/Arg heterozygous variant) of the gene. This frequency was significantly higher than that found in the normal population. CONCLUSIONS: Whereas the capacity to produce a functional hRad9 protein was intact in lung adenocarcinoma cells, a nonsynonymous SNP of HRAD9 was detected that might be associated with the development of lung adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Thioredoxin protects against joint destruction in a murine arthritis model.

Thioredoxin (TRX) is an oxidative stress-inducible biological antioxidant that is highly expressed in the synoviocytes of rheumatoid arthritis (RA) patients. There is much evidence that oxidative stress plays a key role in the inflammation and destruction of RA joints; the functional relationship between TRX and RA remains unknown, however. We therefore investigated the role played by TRX in the inflammatory and joint-damaging processes of RA using a murine model in which arthritis was induced by administering a mixture of anti-type II collagen monoclonal antibodies (mAb) and lipopolysaccharide (LPS). In Wt mice mAb/LPS injection induced neutrophil infiltration, cartilage destruction, and chondrocyte apoptosis within the joints, all of which were dramatically suppressed in TRX transgenic (TRX-Tg) mice. Moreover, the 8-hydoxy-2'-deoxyguanosine (8-OHdG) expression seen in Wt mice after mAb/LPS injection was almost completely inhibited in TRX-Tg mice. The administration of recombinant TRX also suppressed mAb/LPS-induced joint swelling in Wt mice. Taken together, these results suggest that TRX protects against arthritis and is a plausible candidate with which to develop novel therapies for the treatment of RA.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Genome-wide microsatellite analysis of focal nodular hyperplasia: a strong tool for the differential diagnosis of non-neoplastic liver nodule from hepatocellular carcinoma.

Allelic imbalance (AI), which represents certain chromosomal gains or losses, has been described in hepatocellular carcinoma (HCC), but the significance of AI analysis in focal nodular hyperplasia (FNH) has not been fully clarified. We hypothesized, therefore, that comprehensive allelotyping of FNH could be a useful tool for differentiating FNH from HCC. A 27-year-old man was admitted to the hospital because of general fatigue. A computed tomography (CT) scan disclosed a hepatic nodule 8 cm in diameter. No definite diagnosis was made after imaging or by biopsy before surgery. Macroscopically and microscopically, the surgical specimen showed typical features of FNH. Comprehensive microsatellite analysis was carried out with 382 microsatellite markers distributed throughout all chromosomes. To detect AI effectively, the cutoff value of the AI index was set at 0.70. Among the 382 microsatellite markers, 212 loci were informative, but no AI was detected. The absence of gross chromosomal alterations strongly suggested that the large nodule was FNH rather than HCC, in terms of its genetic background. The patient's subsequent clinical course revealed the nodule to be benign. The results suggest that this genome-wide microsatellite analysis is a useful tool for the differential diagnosis of non-neoplastic liver nodules from HCC.

Adult↗
PubMed2006

Placement of self-expanding stents with different diameters in the porcine venous system: an experimental study.

PURPOSE: To study the vascular histologic response after placement of oversized self-expanding stents in the porcine venous system. MATERIALS AND METHODS: Twenty-four oversized stents (range of oversizing, 119.5%-216.0%) were deployed in jugular and iliac veins of six miniature pigs divided into two groups with follow-up times of 1 and 3 months. Necropsy with histologic evaluation of each stent was performed, and the areas of neointimal proliferation were calculated with slices obtained during follow-up from each stent at 5 mm from the proximal and distal edges and at the midpoint. RESULTS: Neointimal proliferation was observed inside the stent lumen. All segments were patent in both groups. However, one jugular stent in the 1-month group and one jugular stent in the 3-month group had migrated at follow-up and were excluded from analysis. There were no significant differences in neointimal growth between the stent edges (proximal and distal) and middle segments of the stents at follow-up in the 1-month group (P = .970) or in the 3-month group (P = .694). Simple linear regression showed strong positive correlation between stent oversizing and neointimal proliferation in the 1-month model (r = 0.791; P < .001) and the 3-month model (r = 0.718; P < .001). There were no significant differences between 1-month and 3-month groups in the degree of neointimal proliferation (P = .072). Also, branched vessels showed no neointimal proliferation at their intersections with the stent-implanted segments. CONCLUSION: Stent oversizing showed a strong positive correlation with neointimal growth in each follow-up model in this study.

Angiography, Digital Subtraction↗
PubMed2006

Histological and cytogenetic characterization of bone marrow in relation to prognosis and diagnosis of myelodysplastic syndromes.

Bone marrow (BM) histology of 102 myelodysplastic syndromes (MDS) patients was analyzed retrospectively. All the cases were reclassified according to the World Health Organization (WHO) classification. Karyotype study was conducted for all except one. Fifteen of the MDS cases were hypoplastic. The cellularity in bone marrow histology is sometimes ineffective in the differential diagnosis of MDS and aplastic anemia (AA). Nonetheless, a marked decrease in the number of megakaryocytes (average, 0.3/mm(2); range, 0-2/mm(2)) even in the hyperplastic foci of the marrow of AA was the most important histological feature differentiating AA from MDS, whereas the number of megakaryocytes increased in most MDS cases (44/mm(2); range, 1-240/mm(2)) and also in hypoplastic MDS (14/mm(2); range, 8-26/mm(2)). Hyperplastic marrow had a significantly high frequency of progress to acute myeloid leukemia (AML) and hypoplastic MDS had a lower rate of progress to AML. Severe myelofibrosis had a significantly poor prognosis. An increase in CD34-positive cells in MDS indicated a high rate of progress to AML. As for the patients with refractory cytopenia with multilineage dysplasia (RCMD; the new category under the WHO classification), the increased number of megakaryocytes was correlated with poor prognosis.

Adult↗
PubMed2005

Ocular adnexal mucosa-associated lymphoid tissue lymphoma treated with radiotherapy.

Forty-two patients with stage IE ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma were retrospectively analyzed. Five-year local control and progression-free survival rates were 100 and 77%, respectively. The most common relapsed site was the contralateral orbit. Thirty Gy of local irradiation seemed to be quite effective and safe.

Adult↗
PubMed2005

Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice.

The protein p27(Kip1) regulates cell cycle progression in mammals by inhibiting the activity of cyclin-dependent kinases (CDKs). Here we show that p27(Kip1) progressively accumulates in the nucleus of pancreatic beta cells in mice that lack either insulin receptor substrate 2 (Irs2(-/-)) or the long form of the leptin receptor (Lepr(-/-) or db/db). Deletion of the gene encoding p27(Kip1) (Cdkn1b) ameliorated hyperglycemia in these animal models of type 2 diabetes mellitus by increasing islet mass and maintaining compensatory hyperinsulinemia, effects that were attributable predominantly to stimulation of pancreatic beta-cell proliferation. Thus, p27(Kip1) contributes to beta-cell failure during the development of type 2 diabetes in Irs2(-/-) and Lepr(-/-) mice and represents a potential new target for the treatment of this condition.

Animals↗
PubMed2005

Accumulation of hRad9 protein in the nuclei of nonsmall cell lung carcinoma cells.

BACKGROUND: DNA damage sensor proteins have received much attention as upstream components of the DNA damage checkpoint signaling pathway that are required for cell cycle control and the induction of apoptosis. Deficiencies in these proteins are directly linked to the accumulation of gene mutations, which can induce cellular transformation and result in malignant disease. METHODS: Using 48 sets of tumor tissue specimens and peripheral normal lung tissue specimens from 48 patients with nonsmall cell lung carcinoma (NSCLC) who underwent surgery, the authors investigated the expression of hRad9 protein, a member of the human DNA damage sensor family, using immunohistochemical and Western blot analyses. RESULTS: Immunohistochemical analysis detected the accumulation of hRad9 in the nuclei of tumor cells in 16 tumor tissue specimens, (33% of tumor tissue specimens examined). Western blot analysis also revealed elevated levels of phosphorylated hRad9 protein in NSCLC cells that was accompanied by the detection of phosphorylated Chk1, a protein kinase that regulates the downstream signaling of the DNA damage checkpoint pathway. Furthermore, strong expression of hRad9 was correlated with an increase in Ki-67 expression index in the tumor cells that were examined. CONCLUSIONS: The findings made in the current study suggest that Rad9 expression may play an important role in cell cycle control in NSCLC cells and may influence NSCLC cell phenotype.

Adult↗
PubMed2005

Serum hepatitis B virus DNA levels differentiating inactive carriers from patients with chronic hepatitis B.

OBJECTIVE: We compared serum hepatitis B virus (HBV)-DNA levels in different states of hepatitis B infection, and investigated whether there is an HBV-DNA value that can be used for differentiating inactive carriers from patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis. METHODS: A retrospective study using sera at a followed endpoint from 64 Japanese patients with chronic HBV infection seen in Kobe University Hospital between 1989 and 2002. Sera of patients were assayed using a polymerase chain reaction-based assay. RESULTS: Genotype C was dominant (95.4%). Patients with chronic hepatitis with an elevation of the serum alanine aminotransferase (ALT) level had significantly higher HBV-DNA levels than patients with persistently normal ALT. For one time observation at a followed endpoint, the mean HBV-DNA level of HBeAg-negative inactive carriers was significantly lower than that of HBeAg-negative chronic hepatitis patients (3.6+/-1.0 versus 4.8+/-1.5 log copies/ml, P<0.005). The use of a cutoff value of 4.5 or 5.0 log copies/ml misclassified 23 and 18% of HBeAg-negative inactive carriers and 50 and 55% of patients with HBeAg-negative chronic hepatitis. If testing were performed on two occasions with approximately a 4-month interval, the cutoff values of 4.5 and 5.0 log copies/ml would misclassify 20 and 10% of HBeAg-negative inactive carriers and 28.6 and 28.6% of patients with HBeAg-negative chronic hepatitis. CONCLUSIONS: The measurement of serum HBV DNA more than twice is useful for assessing chronic hepatitis B surface antigen carriers and confirms that 10 copies/ml may be an appropriate level of HBV for characterizing the inactive carrier state.

Adult↗
PubMed2005

Multiple hypervascular liver nodules in a heavy drinker of alcohol.

A case of hypervascular nodules in the liver, but without hepatitis B or C virus infection in a 38-year-old woman with a history of alcohol abuse is presented. An ultrasound disclosed 1-2-cm hypoechoic tumors in the right and left lobes. Magnetic resonance imaging showed high-intensity tumors at both the T1-weighted and T2-weighted sequences. Incremental dynamic computed tomography and hepatic angiography revealed hypervascular tumors. Ultrasound-guided needle biopsy revealed no evidence of hepatocellular carcinoma, metastatic liver cancer, hemangioendothelioma, inflammatory pseudotumors or pseudolymphoma, but demonstrated stellate-scar fibrosis septa, which contained small unpaired arteries without hyperplasia dividing the nodule. Moreover, marked pericellular fibrosis, neutrophilic infiltration and Mallory bodies were observed in the cytoplasm. There was no evidence of bile duct proliferation. From these findings, the diagnosis of alcohol-induced fibrosis, distinctly different from focal nodular hyperplasia, was tenable. Further studies may provide insights into the pathogenesis of nodule formation and hypervascularity in heavy drinkers of alcohol.

Adult↗
PubMed2005

Prediction of efficacy of interferon treatment of chronic hepatitis C and occurrence of HCC after interferon treatment by a new classification.

One hundred and twenty-one chronic hepatitis C patients were administered interferon (IFN) and divided into two groups: 31 complete responders (CR) with prolonged HCV-RNA negative 1 year after treatment and 90 non-complete responders (non-CR), including partial responders (PR) with transiently negative HCV-RNA and non-responders (NR) with continuously positive HCV-RNA. Liver biopsy specimens were classified into four grades and stages according to the degree of severity and the extent of fibrosis, respectively. No correlation was observed between the rate of IFN efficacy and grading. By staging, however, a difference in the efficacy of IFN was observed between F1 or F2 and F3 (0.05 < p < 0.1 and 0.01 < p < 0.025, respectively). Of the CR, 0% (0/5) were at F0 and 27.9% (24/86) at F1, 42.9% (6/14) at F2, and 6.3% (1/16) at F3. Another group of 118 chronic hepatitis patients (31 CR, 41 PR and 46 NR) followed up for over 2 years after IFN treatment were analyzed. By staging, 7 cases were at F0, 76 at F1, 18 at F2, and 17 at F3. HCC occurred in 1 of the 31 CR cases (representing an annual incidence rate of 1.21%), in 4 of the 41 PR cases (4.08%), and in 4 of the 46 NR cases (3.55%). HCC did not occur in any of the 7 cases at F0 (representing an annual incidence rate of 0%); it occurred in 2 of the 76 cases at F1 (1.01%), in 1 of the 18 cases at F2 (2.28%), and in 6 of the 17 cases at F3 (16.57%). These results suggest that the new classification would be conducive to roughly predicting the efficacy of IFN treatment and the occurrence of HCC after IFN treatment.

Adult↗