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Biomedical subjects

Kazuhiko Koike

Publications and source records attributed to Kazuhiko Koike.

At least 19 recordsLinked to original sources
PubMed2005

Cloning and characterization of a lectin from the octocoral Sinularia lochmodes.

In the present study, the entire amino acid sequence and cDNA structure encoding the d-galactose-binding lectin, SLL-2, isolated from the octocoral Sinularia lochmodes, were determined. SLL-2 regulates the morphology of symbiotic dinoflagellates Symbiodinium spp. through unknown mechanisms. Here, three cDNAs that encode SLL-2 were cloned and characterized. All the SLL-2 cDNAs encoded 142 amino acids with high similarity to each other. The mature subunit of SLL-2 was found to be composed of 94 amino acids and to contain one putative glycosylation site common to all three SLL-2. N-Glycopeptidase F treatment of SLL-2 resulted in a protein band shift from 16.5 to 9.5kDa in SDS-PAGE, confirming that SLL-2s are glycoproteins. Two-dimensional polyacrylamide gel electrophoresis analysis of the deglycosylated SLL-2 indicated a presence of three polypeptides as encoded in SLL-2 cDNAs. The deduced sequences of SLL-2 cDNAs had a similarity to the C-terminal region of discoidin I, the slime mold Dictyostelium discoideum lectin.

Amino Acid Sequence↗
PubMed2005

Development of molecular probes for dinophysis (dinophyceae) plastid: a tool to predict blooming and explore plastid origin.

Dinophysis are species of dinoflagellates that cause diarrhetic shellfish poisoning. We have previously reported that they probably acquire plastids from cryptophytes in the environment, after which they bloom. Thus monitoring the intracellular plastid density in Dinophysis and the source cryptophytes occurring in the field should allow prediction of Dinophysis blooming. In this study the nucleotide sequences of the plastid-encoded small subunit ribosomal RNA gene and rbcL (encoding the large subunit of RuBisCO) from Dinophysis spp. were compared with those of cryptophytes, and genetic probes specific for the Dinophysis plastid were designed. Fluorescent in situ hybridization (FISH) showed that the probes bound specifically to Dinophysis plastids. Also, FISH on collected nanoplankton showed the presence of probe-hybridized eukaryotes, possibly cryptophytes with plastids identical to those of Dinophysis. These probes are useful not only as markers for plastid density and activity of Dinophysis, but also as tools for monitoring cryptophytes that may be sources of Dinophysis plastids.

Animals↗
PubMed2005

Metabolic aspects of hepatitis C viral infection: steatohepatitis resembling but distinct from NASH.

Although the target of hepatitis C virus (HCV) infection is the liver, it has become progressively more evident that HCV can induce diseases in numerous organs. Recently, much attention has been drawn to metabolic disorders in HCV infection. Initially, hepatic steatosis and disturbances in lipid metabolism were found to be characteristic of HCV infection, and, subsequently, a correlation was noted between HCV infection and diabetes. It is now evident that HCV, by itself, can induce insulin resistance by way of disturbing the intracellular signaling pathway of insulin by the function of HCV core protein. Insulin resistance, caused by HCV infection, evolves to type 2 diabetes when superimposed on a high-fat diet and obesity. The fact that HCV infection induces insulin resistance by the virus itself may influence the progression of chronic hepatitis and open up novel therapeutic approaches. When hepatitis C is compared with nonalcoholic steatohepatitis (NASH), there are a number of similarities and several differences. From the metabolic aspect, hepatitis C resembles NASH in numerous features, such as the presence of steatosis, serum dyslipidemia, and oxidative stress in the liver, suggesting that hepatitis C is a steatohepatitis. In contrast, there are noticeable differences between hepatitis C and NASH, in that HCV modulates cellular gene expression and intracellular signal transduction, including the activation of mitogen-activated protein (MAP) kinase and transcription factor activator protein (AP)-1, while such details have not been noted for NASH. This difference may explain the markedly higher incidence of HCC development in chronic hepatitis C compared with that in NASH. HCV infection needs to be viewed not only as a liver disease but also as a metabolic disease, and this viewpoint could open up a novel way to the molecular understanding of the pathogenesis of hepatitis C, as a virus-associated steatohepatitis (VASH).

Animals↗
PubMed2005

Persisting humoral antiviral immunity within the Japanese population after the discontinuation in 1976 of routine smallpox vaccinations.

Concerns have arisen recently about the possible use of smallpox for a bioterrorism attack. Routine smallpox vaccination was discontinued in Japan in 1976; however, it is uncertain exactly how long vaccination-induced immunity lasts. We sought to evaluate the seroprevalence and intensity of anti-smallpox immunity among representatives of the present Japanese population. The subjects included 876 individuals who were born between 1937 and 1982. Vaccinia virus-specific immunoglobulin G (IgG) levels were measured by enzyme-linked immunosorbent assay (ELISA), and 152 of 876 samples were also tested for the presence of neutralizing antibodies. Of the subjects who were born before 1962, between 1962 and 1968, and between 1969 and 1975, 98.6, 98.6, and 66.0%, respectively, still retained the vaccinia virus-specific IgG with ELISA values for optical density at 405 nm (OD(405)) of > or = 0.10. The corresponding figures for retained IgGs with OD405 values of > or = 0.30 were 91.0, 90.3, and 58.2%, respectively. Neutralizing antibodies were also maintained. The sera with OD(405) values of > or = 0.30 showed 89% sensitivity and a 93% positive predictive value for detection of neutralizing antibodies (> or = 4). Thus, approximately 80% of persons born before 1969 and 50% of those born between 1969 and 1975 were also found to have maintained neutralizing antibodies against smallpox. A considerable proportion of the previous vaccinated individuals still retain significant levels of antiviral immunity. This long-lasting immunity may provide some protective benefits in the case of reemergence of smallpox, and the disease may not spread as widely and fatally as generally expected.

Adult↗
PubMed2004

Methylation status of suppressor of cytokine signaling-1 gene in hepatocellular carcinoma.

BACKGROUND: Silencing of the suppressor of cytokine signaling ( SOCS-1) by aberrant methylation at the CpG island in the coding region gene has been reported in hepatocellular carcinoma (HCC). However, principally, it is methylation in the 5'-noncoding region but not that in the coding region which determines the regulation of gene expression. METHODS: Methylation-specific PCR was performed for the analysis of methylation status both in the 5'-noncoding region and the CpG island of SOCS-1 from 22 HCC tissue samples with adjacent non-HCC tissue samples and from two cell lines. RESULTS: Using primers in the CpG island, 9 of 22 HCC samples exhibited aberrant methylation of SOCS-1, while only 1 of 22 adjacent non-HCC samples did so. The unmethylation pattern was detected in 1 of 22 HCC and in 5 of 22 non-HCC samples. Thus, aberrant methylation of SOCS-1 was significantly associated with HCC ( P = 0.0076 by Fisher's exact test). Using primers in the 5'-noncoding region, aberrant methylation was observed in 12 of 22 HCC and in 2 non-HCC samples. The unmethylated pattern was observed in 5 of 22 HCC and in 10 of 22 non-HCC samples ( P = 0.0042). There was no significant correlation between the methylation status of SOCS-1 and clinicopathological findings, such as the presence or absence of cirrhosis or the histological grade of HCC. CONCLUSIONS: Aberrant methylation of the SOCS-1 had a significant correlation with HCC. The rate of aberrant methylation was similar in the 5'-noncoding region and in the CpG island. Aberrant methylation of SOCS-1 may be associated with hepatocarcinogenesis, although further studies are necessary.

Carcinoma, Hepatocellular↗
PubMed2004

Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance.

BACKGROUND & AIMS: Epidemiological studies have suggested a linkage between type 2 diabetes and chronic hepatitis C virus (HCV) infection. However, the presence of additional factors such as obesity, aging, or cirrhosis prevents the establishment of a definite relationship between these 2 conditions. METHODS: A mouse model transgenic for the HCV core gene was used. RESULTS: In the glucose tolerance test, plasma glucose levels were higher at all time points including in the fasting state in the core gene transgenic mice than in control mice, although the difference was not statistically significant. In contrast, the transgenic mice exhibited a marked insulin resistance as revealed by the insulin tolerance test, as well as significantly higher basal serum insulin levels. Feeding with a high-fat diet led to the development of overt diabetes in the transgenic mice but not in control mice. A high level of tumor necrosis factor-alpha, which has been also observed in human chronic hepatitis C patients, was considered to be one of the bases of insulin resistance in the transgenic mice, which acts by disturbing tyrosine phosphorylation of insulin receptor substrate-1. Moreover, administration of an anti-tumor necrosis factor-alpha antibody restored insulin sensitivity. CONCLUSIONS: The ability of insulin to lower the plasma glucose level in the HCV transgenic mice was impaired, as observed in chronic hepatitis C patients. These results provide a direct experimental evidence for the contribution of HCV in the development of insulin resistance in human HCV infection, which finally leads to the development of type 2 diabetes.

Animals↗
PubMed2003

Serum lipid profile of patients with genotype 1b hepatitis C viral infection in Japan.

Hepatitis C virus (HCV) infection is associated with the development of steatosis in the liver. Recently, infection with genotype 3a HCV has been reported to have a closer association with hepatic steatosis than that with genotype 1 or 2 HCV. Moreover, infection with genotype 3a HCV but not with genotype 1 has been shown to be associated with serum hypocholesterolemia or hypobetalipoproteinemia in European countries. We conducted a case control study to characterize the serum lipid profile in patients infected with genotype 1b HCV, which is the most prevalent HCV genotype in Japan. These patients had significantly lower serum cholesterol levels than those infected with HBV or genotype 2a HCV who had similar liver disease progression and body mass index. Further analysis of serum apolipoproteins revealed that not only apolipoprotein B but also apolipoprotein CII and apolipoprotein CIII levels were significantly reduced, while apolipoprotein AI, AII and E levels were similar in patients infected with genotype 1b HCV and those with HBV or genotype 2a HCV. These results indicate that, in Japan, infection with genotype 1b HCV is a cause of lipid metabolism disturbances, which may be associated with the pathogenesis of hepatitis C liver disease.

Journal Article↗
PubMed2003

Hepatitis C virus core protein activates ERK and p38 MAPK in cooperation with ethanol in transgenic mice.

In human chronic hepatitis C, alcohol intake is a synergistic factor for the acceleration of hepatocarcinogenesis. Recently, we showed a significant increase of reactive oxygen species (ROS) in hepatitis C virus (HCV) core-transgenic mice fed ethanol-containing diets. Because previous studies indicated that ROS is closely associated with mitogen-activated protein kinases (MAPK), we examined activities of c-Jun N-terminal kinase, p38 MAPK, and extracellular signal-regulated kinase (ERK) in the liver of core-transgenic and nontransgenic mice with short-term ethanol feeding. Activity of ERK and p38 MAPK was increased in core-transgenic mice compared with nontransgenic mice, whereas neither ERK nor p38 MAPK was activated in core-transgenic mice with normal diets. In addition, activity of cyclic-AMP and serum responsive element, downstream pathways of p38 MAPK and ERK, was also increased. Comparison of gene expression profiles by cDNA microarray and real-time PCR revealed that galectin-1, which is associated with cell transformation, was significantly increased in ethanol-fed core-transgenic mice. On the other hand, glutathione S-transferase (GST), which plays a key role in protecting cells from oxidative stress, was decreased. In conclusion, these results suggest that HCV core protein cooperates with ethanol for the activation of some MAPK pathways, and leads to the modulation of several genes, contributing to the pathogenesis of liver disease of HCV-infected patients with high ethanol consumption.

Activating Transcription Factor 2↗
PubMed2003

Proteasome activator PA28gamma-dependent nuclear retention and degradation of hepatitis C virus core protein.

Hepatitis C virus (HCV) core protein plays an important role in the formation of the viral nucleocapsid and a regulatory protein involved in hepatocarcinogenesis. In this study, we have identified proteasome activator PA28gamma (11S regulator gamma) as an HCV core binding protein by using yeast two-hybrid system. This interaction was demonstrated not only in cell culture but also in the livers of HCV core transgenic mice. These findings are extended to human HCV infection by the observation of this interaction in liver specimens from a patient with chronic HCV infection. Neither the interaction of HCV core protein with other PA28 subtypes nor that of PA28gamma with other Flavivirus core proteins was detected. Deletion of the PA28gamma-binding region from the HCV core protein or knockout of the PA28gamma gene led to the export of the HCV core protein from the nucleus to the cytoplasm. Overexpression of PA28gamma enhanced the proteolysis of the HCV core protein. Thus, the nuclear retention and stability of the HCV core protein is regulated via a PA28gamma-dependent pathway through which HCV pathogenesis may be exerted.

Active Transport, Cell Nucleus↗
PubMed2003

A patient with E. coli-induced pyelonephritis and sepsis who transiently exhibited symptoms associated with primary biliary cirrhosis.

A 28-year-old woman had chief complaints of headache and a 40 degrees C fever. At this time, findings indicative of inflammation including elevated CRP and increased WBC were observed, and E. coli was detected on blood and urine culture. As a result, the patient was diagnosed with pyelonephritis and sepsis. Furthermore, markedly increased hepatobiliary enzymes and elevated anti-mitochondrial antibody were confirmed. The administration of antimicrobial agents resulted in improvement of the pyelonephritis and sepsis and normalization of hepatobiliary enzyme and anti-mitochondrial antibody levels. It has been documented that the incidence of urinary tract infection is high among patients with primary biliary cirrhosis (PBC). The findings obtained from the present patient are of considerable interest in elucidating the mechanism of onset in PBC.

Adult↗
PubMed2003

Acute hepatitis E with elevated creatine phosphokinase.

Acute hepatitis E is caused by infection with hepatitis E virus, which is endemic in developing countries. Recently, the number of cases with acute hepatitis E is increasing in Japan due to increased travel to the endemic areas. This paper reports a case of a Japanese man with acute hepatitis E who had a history of traveling to south China. Serum creatine phosphokinase was elevated on admission without symptoms of muscle damage (isoenzyme MM 100%), and normalized in parallel with resolution of hepatitis, raising the possibility of an association between elevation of creatine phosphokinase and acute hepatitis E. However, we need to investigate further the incidence of elevation of serum creatine phosphokinase in many cases with acute viral hepatitis including hepatitis A, B, and C to determine whether muscle disorder is characteristic of acute hepatitis E.

Creatine Kinase↗
PubMed2002

Alteration of intrahepatic cytokine expression and AP-1 activation in transgenic mice expressing hepatitis C virus core protein.

Hepatitis C virus (HCV) infection often leads to the development of hepatocellular carcinoma (HCC), but its molecular mechanism has not been clearly elucidated. Previously, transgenic mice constitutively expressing HCV core protein have been shown to develop HCC, suggesting a pivotal role of the core protein in hepatocarcinogenesis. Here, we analyzed the expression of cytokines associated with a variety of cellular processes, including cell proliferation, in the mouse model for HCV-associated HCC to define the molecular events prior to oncogenesis. The expression of tumor necrosis factor-alpha and interleukin-1beta was increased at both protein and mRNA levels. In addition, the activities of c-Jun N-terminal kinase and activator protein-1 (AP-1), downstream effectors, were enhanced, while IkappaB kinase or nuclear factor-kappaB activities were not enhanced. Thus, the altered in vivo expression of cytokines with AP-1 activation in consequence to the core protein expression may contribute to hepatocarcinogenesis in persistent HCV infection.

Animals↗
PubMed2002

Hepatocarcinogenesis in hepatitis viral infection: lessons from transgenic mouse studies.

Over the past decade, genetically engineered mouse models have been used for studies of the mechanisms underlying human diseases. One advantage of these models is that the targeted protein executes its function in normal cells in their natural tissue microenvironments. Transgenic mouse models for human viral hepatitis have also been established and have provided new insights into the pathogenesis of hepatitis and hepatocellular carcinoma (HCC). In the search for the mechanism of hepatocarcinogenesis in hepatitis viral infection, two viral proteins, the core protein of hepatitis C virus (HCV) and the HBx protein of hepatitis B virus (HBV), have been shown to possess oncogenic potential through transgenic mouse studies, indicating the direct involvement of the hepatitis viruses in hepatocarcinogenesis. The presence of the hepatitis C virus core or HBx protein, which has an oncogenic potential, may allow some of the steps in multistep hepatocarcinogenesis to be skipped. This may explain the very high frequency of HCC in patients with HCV or HBV infection.

Animals↗