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Biomedical subjects

Naoaki Hayashi

Publications and source records attributed to Naoaki Hayashi.

At least 19 recordsLinked to original sources
PubMed2004

Development of quantitative neuropsychological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria-multicenter collaborative study in Japanese.

At present, there are no generally accepted diagnostic criteria or methods for subclinical hepatic encephalopathy (SHE) associated with liver cirrhosis. We therefore developed an easily conducted computer-aided quantitative neuropsychiatric function test system for use in routine medical practice. We established normal values in healthy Japanese subjects and determined differences between healthy persons and liver cirrhosis patients without clinical encephalopathy in a multi-center clinical trial. The test system consists of eight tests: number connection tests A and B, a figure position test, a digit symbol test, a block design test, and reaction time tests A, B and C. The test results were affected by age, but not by gender or facility. No learning effect was noted. The results were therefore reported by 5-year quartile ranges and differences were evaluated between 542 healthy subjects and 292 cirrhotic patients. When the cut-off value was set at the 10th/90th percentile of the results in healthy subjects, the results of each of the 8 tests were abnormal in about 25% of cirrhotic patients, and at least 1 of the 8 tests gave values greater than the 10th/90th percentile cut-off value in 58.2% of the 292 liver cirrhosis patients. SHE patients were thought to be included in these 58.2% of patients. The developed test makes it possible to quantitatively assess neuropsychiatric function, and the results obtained can be used as a basis for the diagnosis of SHE.

Journal Article↗
PubMed2004

Histopathologically-diagnosed splenic metastasis in a hepatocellular carcinoma case with adrenal metastasis.

We encountered a patient with hepatocellular carcinoma (HCC), with adrenal gland metastasis, in whom splenic metastasis was diagnosed histopathologically. A 59-year-old man visited our hospital in May 2001 with chief complaints of abdominal distension and pretibial pitting edema. Multiple HCCs associated with HCV-positive liver cirrhosis were detected. Transarterial embolization (TAE) was performed a total of 4 times for HCCs. A left adrenal gland metastatic lesion was detected and it was found to increase in diameter from 3 cm to 6 cm over a four-month period; left adrenalectomy was performed in June 2002. Because of marked splenomegaly and findings of hypersplenism, the spleen was also resected. Although no metastatic lesions were evident on macroscopic examination of the spleen, a small metastatic lesion from moderately differentiated HCC, approximately 0.5 mm in diameter, was detected histopathologically. Splenic metastasis from HCC is rare, usually occurring with metastases involving other organs. Our patient also had adrenal gland metastasis. Therefore, hematogenous metastasis to the congested spleen via the systemic circulation was suspected.

Adrenal Gland Neoplasms↗
PubMed2003

Cell adhesion aside from integrin system can abrogate anoikis in rat liver cells by down-regulation of FasL expression, not by activation of PI-3K/Akt and ERK signaling pathway.

Epithelial cells require contact with extracellular matrix (ECM) to inhibit detachment-induced apoptosis (anoikis). The ERK and PI-3K/Akt signaling pathways have been identified to inhibit anoikis. We present here a different story. An adult rat liver cell line, ARLJ301-3, underwent apoptosis within 4h under suspension conditions even with active forms of Akt and ERK1/2. Once ARLJ301-3 cells are plated on tissue culture plates coated with synthetic polymer, such as poly-(N-p-vinyl benzyl-O-beta-D-galactopyranosyl-D-gluconamide) (PVLA), poly-L-lysine or polystyrene, instead of functional ECM such as fibronectin, they could survive and proliferate without activation of Akt and ERK1/2. The expression of Fas receptor ligand (FasL) is specifically detected in cells under suspension conditions or treated with cytochalasin-D. We present here the first report that FasL expression is up-regulated by the cytoskeletal disruption directed by cytochalasin-D treatment or cell detachment from ECM.

Animals↗
PubMed2003

Molecular analysis of antigenicity and immunogenicity of a vaccine-induced escape mutant of hepatitis B virus.

BACKGROUND: To analyze the mechanisms of mutant escape, we established a murine model of hepatitis B virus (HBV) infection and studied the interaction of the envelope protein of the virion with various kinds of anti-hepatitis B antibody. METHODS: Mutation from glycine to arginine at aa145 was introduced into replication-competent DNA of HBV. The resulting mutant HBV DNA was transfected into cultured hepatoma cells and livers of mice using liposome-mediated gene transfer. Then, interactions between the antigenic envelope protein (in culture or in circulation) and anti-hepatitis B antibody were examined. RESULTS: Mutant envelope protein escaped human hepatitis B immunoglobulin, rabbit polyclonal anti-hepatitis B surface antigen (HBsAg) antibody, and monoclonal anti-a antibody in vitro and in vivo. There was a difference in the degree of inhibition between hepatitis B immunoglobulin and the other two antibody types in vitro. Transfection with an HBV construct containing a mutation in the a-loop resulted in levels of HBsAg in circulation and seroconversion to anti-HBs antibody that were similar to those produced by a wild-type construct. CONCLUSIONS: The degree of escape by the mutant envelope protein differed according to antibody type. Of the three types of antibody used in this study, HBV immunoglobulin was least affected by mutation in the a-loop. There appears to be no correlation between antigenicity and immunogenicity of the escape mutant, and the a-loop mutant may cause hepatitis with the usual serum viral markers.

Animals↗
PubMed2003

Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study.

Primary biliary cirrhosis (PBC) sera contain antibodies which recognize various nuclear envelope proteins of which antibody against gp210 has been proven to be diagnostic for disease. In contrast, the clinical significance of another nuclear envelope antibody, anti-p62 antibody has not been well investigated. In the present study, we have analyzed anti-nuclear envelope antibodies by indirect immunofluorescence and immunoblot using rat liver nuclear envelope proteins and wheat germ agglutinin-bound fraction. Test sera were obtained from 175 patients with PBC and from 120 controls. Anti-gp210, anti-lamina associated polypeptide 2, anti-lamin B receptor, and anti-p62 complex antibodies were detected with a frequency of 26% (46 of 175), 6% (11 of 175), 9% (16 of 175), and 13% (15 of 115), respectively. The confirmation of Scheuer's stage IV was made with a frequency of 27% (4 of 15) in PBC patients with anti-p62 complex antibody, in contrast to only 2% (2 of 100) in PBC patients without anti-p62 complex antibody. This difference was found to be statistically significant. The presence of anti-p62 complex antibody may be related with the progressive or advanced state of PBC.

Animals↗
PubMed2003

Configuration and replication competence of hepatitis B virus DNA in peripheral blood mononuclear cells from chronic hepatitis B patients and patients who have recovered from acute self-limited hepatitis.

Several studies have reported the presence of hepatitis B virus (HBV) DNA in peripheral blood mononuclear cells (PBMCs). However, the mode of existence, infectivity and replication competence of HBV DNA in PBMCs remain unclear. To clarify these questions, we assayed for covalently closed circular DNA (cccDNA) and integrated HBV DNA in PBMCs from ten patients who had recovered from acute self-limited hepatitis B (AHB) and 14 chronic hepatitis B (CHB) patients. HBV DNA was detected in all six CHB patients who were positive for hepatitis B e antigen (eAg), and cccDNA was detected in five. HBV DNA was detected in seven of the eight CHB patients who were negative for eAg, and cccDNA was detected in three. HBV DNA and cccDNA was also detected in five and two of the ten AHB patients, respectively. Integrated HBV was not detected in PBMCs of any patients. HBV DNA presence and replication competence in PBMCs are associated with eAg-positive phenotype. Sequence analysis revealed that the source of HBV DNA differed between PBMCs and serum. Even in patients who have recovered from AHB, replicable HBV may persist in PBMCs.

Journal Article↗
PubMed2003

Genotypic analysis of hepatitis B virus from patients with fulminant hepatitis: comparison with acute self-limited hepatitis.

AIM/BACKGROUND: There is an increasing evidence that certain hepatitis B virus (HBV) strains may contribute to the pathogenesis of fulminant hepatitis B (FHB). Recently, we reported that genotypes of HBV influence the clinical course of acute self-limited hepatitis B (AHB). In this study, we compared clinical features of FHB between different HBV genotypes and compared the prevalence of each genotype between FHB and AHB patients. METHODS: The subjects consisted of seven patients with FHB and 25 patients with AHB. The core promoter and precore region were directly sequenced following polymerase chain reaction, and genotype was determined by restriction fragment length polymorphism analysis of the S gene. RESULTS: Of the seven FHB patients, one had genotype A, one had genotype B, four had genotype C, and one had genotype D. Six of the seven FHB patients were infected by heterosexual contact; one FHB patient who was not infected by heterosexual contact had genotype C. All four FHB patients with genotype C had a short duration clinical course. In one patient with genotype A, the time from onset of hepatitis to hepatic coma was 30 days. These results are similar to those of the patients with AHB, in which clinical course was longer in patients with genotype A than in patients with genotype C. CONCLUSION: Viral genotype can be used to predict the clinical course of both FHB and AHB.

Journal Article↗
PubMed2003

In vitro binding of hepatitis C virus to CD81-positive and -negative human cell lines.

AIM: The aim of the present study is to study the mechanism of entry of hepatitis C virus (HCV) into human cells. We examined the in vitro binding of HCV to various human cell lines with or without CD81 expression. METHODS: We first used three cell lines, two hepatocyte-derived, huH-7 and HepG2, and one colon cancer cell line, Cw2. Among them, HepG2 did not express TAPA-1 (CD81) on their surface but two others did. They were incubated with HCV + serum for 1 h and HCV-RNA in extracted RNA obtained from these cells was examined by using both a quantitative test and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: We found that a significant amount of HCV-RNA was detected in huH-7 and HepG2 but not in Cw2. In addition, the titer of HCV-RNA in serum-incubated CD81-transfected HepG2 was similar to that of the non-transfected titer, and the binding between HCV and huH-7 was not inhibited by anti-CD81. Under the same condition, HCV-RNA tended to be detectable in serum-pulsed hepatocyte-derived cell lines, but not in the others. CONCLUSION: These results suggest that while CD81, as reported, specifically binds to HCV-E2 protein, the entry of HCV into human hepatocytes might be regulated by CD81-unrelated molecule(s).

Antibodies↗
PubMed2003

Influence of TNF gene polymorphism and HLA-DRB1 haplotype in Japanese patients with chronic liver disease caused by HCV.

OBJECTIVE: To clarify the host genomic role in chronic liver disease associated with hepatitis C virus (HCV), we investigated the relationship between the severity of hepatitis and the polymorphisms of the tumor necrosis factor (TNF) gene or the human leukocyte antigen (HLA)-DRB1 haplotypes. METHODS: We analyzed 40 healthy subjects, 50 patients with chronic inactive hepatitis caused by HCV with mean serum ALT concentrations under 40 IU/ml (group A), and 50 patients with chronic active liver disease caused by HCV and mean ALT concentrations over 50 IU/ml (group B). RESULTS: There were no significant differences in the frequencies of TNF promoter gene variants at positions -238 and -308 between the groups. Regarding polymorphisms at the TNF-beta NcoI site, the frequency of B1B1 homozygotes in group A was significantly increased, compared with the healthy subjects and those in group B (controls 7.5%, group A 34%, group B 10%). Regarding the analysis of HLA-DRB1, DRB1*0901 was significantly more frequent in group A than in group B (group A 19%, group B 5%). TNF B1B1 homozygotes were associated with HLA-DRB1*0901 and *1302, and negatively associated with DRB1*0405. Combination analysis revealed that HCV was inactive in the majority of patients who were both DRB1*0901 and B1B1 homozygotes. CONCLUSION: Our data suggest that TNF gene polymorphisms and HLA-DRB1 haplotype may influence the activity of HCV in chronic liver disease.

Female↗
PubMed2003

Chronic hepatitis B with flare due to co-infection of hepatitis delta virus during lamivudine therapy.

In 1997, a 27-year-old homosexual man contracted acute hepatitis B that developed into chronic hepatitis. Because of repeated flares, administration of lamivudine was started in March 2002. Hepatitis B virus (HBV) DNA immediately decreased, but the serum level of alanine aminotransferase gradually increased. Drug-induced hepatitis due to lamivudine was excluded. It was suspected that the progression of liver damage was caused by hepatitis delta virus (HDV), because the patient was positive for both anti-HDV antibody and HDV RNA. Co-infection of HDV should be considered a possibility if liver injury is not improved by lamivudine therapy.

Adult↗
PubMed2002

Angioechographic evaluation of tumor thrombi and the effect of transcatheter arterial embolization in patients with hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial embolization (TAE) is considered to be relatively ineffective in the treatment of portal and/or hepatic vein tumor thrombi associated with hepatocellular carcinoma (HCC). However, we have seen patients with a positively enhanced tumor thrombus on angioechography where necrosis has occurred after TAE. In this study, we compared the angioechographic enhancement of tumor thrombi with the effect of TAE to assess the use of this method in predicting the efficacy of TAE, and in predicting survival. METHODS: Angioechography, using a small amount of CO2 gas injected into the hepatic artery, was performed before TAE in 41 HCC patients with tumor thrombi of the portal vein (PVTT; n = 35) or hepatic vein (HVTT; n = 6). The relationship between the enhancement of the thrombi and the efficacy of TAE was investigated by follow-up ultrasonography. RESULTS: All 13 PVTT that decreased in size had shown positive enhancement (PE) before treatment (P < 0.001), while 6 of the 7 cases (86%) in which the lesions increased in size had shown negative enhancement (NE). The survival of patients with PE was significantly longer than that of patients with NE (P < 0.005). Multivariate analysis identified two clinical variables associated with survival, angioechographic findings of PVTT, and age. There were no correlations between enhancement and HVTT. CONCLUSIONS: Determination of enhancement of PVTT on angioechography was useful in predicting the efficacy of TAE treatment of HCC and the survival time. Angioechography may be valuable in treatment decisions for HCC patients with PVTT, especially as a guide to the effectiveness of TAE.

Aged↗
PubMed2002

Prevalence of herpesviridae and hepatitis virus sequences in the livers of patients with fulminant hepatitis of unknown etiology in Japan.

BACKGROUND: Fulminant non-A, non-B, non-C hepatitis has a high mortality rate, making the identification of its causative agent imperative. Cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, and herpes simplex virus are all members of the herpesviridae family that are associated with fatal hepatic failure. We investigated the involvement of herpesviridae and hepatitis virus in the pathogenesis of fulminant hepatitis. METHODS: The study participants consisted of 11 patients with fulminant hepatitis and 11 with acute hepatitis negative for known hepatitis viral markers and any other liver diseases. Viral DNA was extracted from liver tissues and amplified. In situ hybridization was then performed for 1 patient to detect viral DNA and RNA, and viral protein was localized by monoclonal antibodies. RESULTS: Human herpesvirus-6 was detected in liver tissues from seven patients, (five children and two adults) with fulminant hepatitis and two patients with acute hepatitis. Two patients with fulminant hepatitis also had cytomegalovirus in the liver. Although Epstein-Barr virus and herpes simplex virus were detected in the patients with fulminant hepatitis, they were not specific to these patients. In situ hybridization in one of the patients localized DNA and RNA of human herpesvirus-6 in hepatocyte nuclei, and an envelope antigen of this virus was detected in hepatocyte cytoplasm. CONCLUSIONS: Human herpesvirus-6 was frequently detected in Japanese pediatric patients with fulminant non-A, non-B, non-C hepatitis. Although the significance of human herpesvirus-6 in liver pathogenesis remains unclear, this virus may replicate in hepatocytes in some patients with acute onset hepatitis.

Adult↗
PubMed2002

Small-bowel hemorrhage caused by cytomegalovirus vasculitis following fulminant hepatitis.

We describe life-threatening vasculitis of the small bowel following fulminant hepatitis. A 35-year-old man was admitted to our hospital due to consciousness disturbance and jaundice. He was diagnosed with fulminant hepatitis, and recovered after intensive medical care that included corticosteroid administration and artificial liver support. During reduction of the dosage of steroid, massive gastrointestinal hemorrhage occurred from the upper jejunum, revealed by arteriography. The hemorrhage could not be stopped, so a portion of the ileum, including the bleeding point, was excised. However, the intestinal hemorrhage continued from several small ulcers remaining outside the resected area. Pathological findings revealed an ulcerative region that was diagnosed as cytomegalovirus (CMV) vasculitis. His serum level of CMV (measured by real-time-detection polymerase chain reaction [PCR]) was high. Ganciclovir therapy was started, and manifestations of the CMV infection improved. In addition to CMV, PCR assay for hepatitis A virus (HAV), HBV, HCV, Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6), and herpes simplex virus (HSV) was performed, but no viruses other than CMV were detected. We are the first to report such a case. We conclude that the possibility of CMV enteritis should be considered when patients present with unexplained fever and gastrointestinal hemorrhage following fulminant hepatitis, and we conclude that the early administration of ganciclovir should be considered.

Adult↗
PubMed2002

Different antibody responses against hepatitis B surface antigen among mouse strains transfected with mutant viral DNA.

BACKGROUND: Rapid seroconversion from hepatitis B surface antigen (HBsAg) to anti-HBs antibody is seen in most patients with fulminant hepatitis B. It is unclear whether viral mutation or host immune background is responsible for such enhanced host reaction to hepatitis B virus (HBV). To investigate interaction between virus mutation and host immune background, we established a mouse model of hepatitis B using liposome-mediated gene transfer. METHODS: A mixture of liposomes and full-length viral DNA derived from hepatitis B patients was injected into three strains of purebred mice intrahepatically. After injection, HBsAg and antibody in liver and serum were serially measured. RESULTS: Three days after transfection, viral transcript and antigen were detected in the liver and serum. Ten days after transfection with wild-type DNA, hepatitis B surface antibody was detectable in two of the three strains. Mice that did not produce antibody after transfection with wild-type DNA produced a high amount of serum antibody against surface antigen when transfected with fulminant hepatitis-associated DNA. CONCLUSIONS: The present results are consistent with previous clinical observations of rapid HBsAg seroconversion in patients with fulminant hepatitis B. Further studies are needed to determine which mutations are responsible for differences in immunogenicity between HBV strains.

Animals↗
PubMed2002

Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis.

We describe six patients with non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). From 1990 to 2001, we treated 82 patients with NASH and observed six patients (three men and three women, aged 56-72 years) in this group who were referred with HCC or developed the complication during follow-up. In five of these six patients, NASH was associated with obesity (cases 3, 4 and 5), hyperlipidemia (case 5), or diabetes mellitus (cases 1, 3 and 6). We confirmed the presence of HCC by ultrasonography-guided tumor biopsy or surgery except in case 3 where we diagnosed the tumor by ultrasonography, computed tomography and selective hepatic arteriography. The carcinomas measured 1.5-6.0 cm in diameter and three were well differentiated. When HCC was diagnosed, cirrhosis was present in all instances. Four of the six tumor patients also had esophageal varices but only one patient had a history of variceal bleeding and ascites. Treatment of HCC consisted of surgery (cases 1 and 5), transcatheter arterial embolization or infusion and/or percutaneous ethanol injection (cases 2, 3, 4, and 6). In patients with NASH cirrhosis, the development of treatable HCC is sufficiently common to warrant regular screening for this grave complication.

Aged↗