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Biomedical subjects

K Shiraki

Publications and source records attributed to K Shiraki.

At least 19 recordsLinked to original sources
PubMed2000

Prospective reevaluation of risk factors in mother-to-child transmission of hepatitis C virus: high virus load, vaginal delivery, and negative anti-NS4 antibody.

Of 21,791 pregnant women screened in Tottori Prefecture, Japan, 127 (0.58%) were positive for anti-hepatitis C virus (HCV) antibody and 84 (0.39%) were positive for HCV RNA. Of 84 children followed up for at least 6 months, 7 (8%) were infected. All of them were born to 26 mothers with a high virus load (HVL; >/=2.5x106 RNA copies/mL [27%]), compared with 0 of 58 children born to non-HVL mothers (P<.001). Because all the infected children were vaginally delivered, the infection rate among 16 vaginally delivered children born to the HVL mothers was as high as 44%. The prevalence of anti-NS4 antibody in the mothers with an infectious HVL was significantly lower than that in the mothers with a noninfectious HVL (P=.048). Analysis of our results suggests that maternal HVL, vaginal delivery, and negative anti-NS4 antibody are significant risk factors for the mother-to-child transmission of HCV.

Delivery, Obstetric↗
PubMed2000

Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16(INK4a) and Cdk2/cyclin E complex activation.

Survivin is observed uniquely in tumor cells and developmental cells, which undergo either inappropriate or programmed cell growth. In the current study, we investigated the influence of Survivin on cell cycle. Overexpression of Survivin resulted in accelerated S phase shift, resistance to G1 arrest, and activated Cdk2/Cyclin E complex leading Rb phosphorylation. In addition, nuclear translocation of Survivin followed by an interaction with Cdk4 was detected. Interestingly, Survivin nuclear translocation coincided with S phase shift, and prevention of nuclear transport suppressed Survivin nuclear translocation and S phase shift. Further, we also observed that Survivin competitively interacted with the Cdk4/p16(INK4a) complex in a cell free system and in vivo. These results suggest that Survivin initiates the cell cycle entry as a result of nuclear translocation followed by an interaction with Cdk4.

Amino Acid Sequence↗
PubMed2000

Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase.

Phosphorylation of CPI-17 by Rho-associated kinase (Rho-kinase) and its effect on myosin phosphatase (MP) activity were investigated. CPI-17 was phosphorylated by Rho-kinase to 0.92 mol of P/mol of CPI-17 in vitro. The inhibitory phosphorylation site was Thr(38) (as reported previously) and was identified using a point mutant of CPI-17 and a phosphorylation state-specific antibody. Phosphorylation by Rho-kinase dramatically increased the inhibitory effect of CPI-17 on MP activity. Thus, CPI-17 as a substrate of Rho-kinase could be involved in the Ca(2+) sensitization of smooth muscle contraction as a downstream effector of Rho-kinase.

Animals↗
PubMed2000

Humoral immunoresponse to varicella-zoster virus pernasally coadministered with Escherichia coli enterotoxin in mice.

It is evaluated whether Escherichia coli enterotoxin is useful for induction of immunity to varicella-zoster virus (VZV) as a mucosal adjuvant in mice. When a commercially available live varicella vaccine (Oka strain) and toxin were administered simultaneously via a nasal route three times at 2 or 6 month intervals, an antibody neutralizing VZV was detected in half or all of the mice vaccinated, respectively. The antibody specific to the vaccine strain of VZV reacted to five proteins, molecular weights of which were 110 K, 100 K, 62 K, 54 K and 46 K. These proteins were composed of glycosylated products of all kinds of glycoproteins. These results suggest that although a nasal administration of the vaccine without the adjuvant has little immunogenicity in mice, the simultaneous administration of the live vaccine and the toxin over a long period induces a specific humoral immunity to VZV.

Adjuvants, Immunologic↗
PubMed2000

Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death.

Caspase 3 is an essential death factor for the Fas-mediated cell death, and its inactivation in cells is initiated by an interaction with p21 on mitochondria or with IAP family member ILP. Survivin is also a member of IAP family and is specifically expressed during embryogenesis and in tumor cells and suppresses cell death signaling. In our current study, we demonstrated that Survivin translocation into the nucleus is dependent on Fas stimulation and cell proliferation. Survivin also interacts with the cell cycle regulator Cdk4, leading to Cdk2/Cyclin E activation and Rb phosphorylation. As a result of Survivin/Cdk4 complex formation, p21 is released from its complex with Cdk4 and interacts with mitochondrial procaspase 3 to suppress Fas-mediated cell death. Here, we propose that Survivin supports procaspase 3/p21 complex formation as a result of interaction with Cdk4 resulting in suppression of cell death signaling.

Caspase 3↗
PubMed2000

Inadvertent corneal burn by using indirect wide-field contact lenses and different laser beam delivery systems during experimental fundus photocoagulation.

BACKGROUND AND OBJECTIVE: At fundus photocoagulation by using a wide-field indirect contact lens, the laser radiant exposure may be increased at the anterior segment of the eye. We examined the likelihood of producing inadvertent corneal burn by using parfocal and sharped edge defocus laser delivery systems with various indirect contact lenses. STUDY DESIGN/MATERIALS AND METHODS: The two laser delivery systems were used with four lenses of different viewing angles during fundus photocoagulation in a total 44 eyes of rabbits. RESULTS: By using the lenses, the parfocal system increased corneal radiant exposure more than did the sharped edge defocus system. By using the Widefield PRP 165 lens of the widest viewing angle, there was no difference between the two systems in the corneal burns produced. CONCLUSION: Some indirect contact lenses used in combination with the parfocal system caused inadvertent corneal burns more readily than did the same lenses in combination with the sharped edge defocus system.

Animals↗
PubMed2000

Indocyanine green angiographic features of choroidal rupture and choroidal vascular injury after contusion ocular injury.

PURPOSE: To report features of choroidal rupture and choroidal vascular injury after contusion ocular injury on indocyanine green angiography. METHODS: In a prospective study, nine patients (nine eyes) with choroidal rupture after ocular contusion underwent initial fluorescein angiography and indocyanine green angiography within 19 days after trauma. Eyes that had a distinct abnormality of the retinal pigment epithelium were excluded from this study. Subtraction indocyanine green angiography was also performed. Follow-up fluorescein angiographic and indocyanine green angiographic findings were also studied. RESULTS: Initial ophthalmoscopic examination revealed subretinal hemorrhage in all nine eyes. In five of the nine eyes, choroidal rupture was not seen on initial ophthalmoscopic or fluorescein angiographic examination because it was hidden beneath the subretinal hemorrhage, but it was detected on subsequent examinations. In the remaining four eyes, choroidal rupture was observed by ophthalmoscopy at the time of initial examination, and these eyes exhibited hyperfluorescent streaks on fluorescein angiography in the region of the subretinal hemorrhage. On initial indocyanine green angiography of all nine eyes, observed hypofluorescent streaks became more obvious with time. For each eye, there were more hypofluorescent streaks on indocyanine green angiography than hyperfluorescent streaks on fluorescein angiography. In one eye, the location of indocyanine green leakage nearly coincided with the location of a hyperfluorescent streak on fluorescein angiography. In this case, crescentic streaks of hypofluorescence were seen on the temporal side of the subretinal hemorrhage on indocyanine green angiography, although choroidal rupture was not observed in that region by ophthalmoscopy or fluorescein angiography. In two of the nine eyes, indocyanine green angiography and the subtraction technique demonstrated disturbance of flow into choroidal vessels, especially at the choroidal rupture site. CONCLUSION: After ocular contusion injury, various features of choroidal rupture and choroidal vascular injury were observed on indocyanine green angiography. This technique may contribute to the diagnosis of choroidal rupture and to the understanding of the clinical course after injury.

Accidents, Traffic↗
PubMed2000

Allodynia and hyperalgesia induced by herpes simplex virus type-1 infection in mice.

Human subjects infected with herpes or varicella-zoster viruses complain of pain, such as allodynia, in or near the region with vesicles. However, the mechanisms of the pain are unclear. We show for the first time that infection with herpes simplex virus type-1 (HSV-1) induces allodynia and hyperalgesia in mice. When HSV-1 was inoculated on the hind paw of the mouse, eruption appeared on the back on day 5 post-inoculation, and zosteriform skin lesions were developed on the inoculated side. Allodynia and hyperalgesia became apparent in the hind paw on the inoculated side on day 5 and persisted until at least day 8. HSV-1 DNA was detected in the dorsal root ganglia from days 2 to 8 post-inoculation, with a peak effect on day 5. The application of heat-inactivated HSV-1 induced no allodynia, hyperalgesia and skin lesion. When started from days 0 or 2, repeated treatment with acyclovir, anti-HSV-1 agent, inhibited the appearance of allodynia, hyperalgesia, eruption and the viral proliferation in the dorsal root ganglia. In contrast, when started from days 5 or 6, acyclovir treatment slightly inhibited the development of skin lesions and the viral proliferation, but not allodynia and hyperalgesia. These results suggest that the propagation of HSV-1 in the dorsal root ganglia produces allodynia and hyperalgesia as a result of functional abnormality of the sensory neurons in mice. This may be a useful model for studying the mechanisms of herpetic pain.

Acyclovir↗
PubMed2000

Characterization of acyclovir susceptibility and genetic stability of varicella-zoster viruses isolated during acyclovir therapy.

We have characterized the susceptibility and genetic stability of varicella-zoster viruses (VZV) isolated from skin lesions of three patients with herpes zoster and six patients with varicella treated with conventional short-term acyclovir (ACV) administration. The susceptibilities to ACV of the serial isolates from the patients were examined, and there was no significant difference in the susceptibility to ACV among the isolates before and during the ACV treatment, indicating that conventional short-term ACV treatment did not generate ACV-resistant VZV infections. Polymerase chain reaction (PCR) analyses of these as well as seven thymidine kinase-deficient VZV strains derived from in vitro ACV treatment were carried out to examine their genomic stability. Five regions containing tandem direct reiterations (R1-R5) were amplified by PCR and compared, and the region containing the Pst I-site was also examined. PCR analyses demonstrated that the R1, R5 and the Pst I-sites were stable and useful in epidemiological studies even after ACV treatment. The R2, R3 and R4 sites were far less stable in these experimental conditions. In this paper we discuss the results of the PCR analyses with regard to the dynamics of VZV population in patients with VZV infection treated with conventional short-term ACV administration.

Acyclovir↗
PubMed2000

Long-term gene expression in the anterior horn motor neurons after intramuscular inoculation of a live herpes simplex virus vector.

To clarify the feasibility of the herpes simplex virus (HSV) vector in expressing the foreign gene in the motor neuron, we inoculated a live attenuated HSV expressing beta-galactosidase (beta-gal) activity under a latency-associated transcript promoter in the right gastrocnemius muscle of rats. Expression of beta-gal activity was observed 5 days after inoculation in the bilateral anterior horn cells of the spinal cord that innervates the inoculation muscle. However, the spread of beta-gal activity was not observed in the inoculation muscle. Without significant pathological changes, the spread of beta-gal-expressing neurons was observed in the lumbosacral spinal cord until 14 days after inoculation with staining concentrated in the anterior horn cells. Ninety percent of the anterior horn motor neurons expressed beta-gal activity with expression continuing to at least 182 days after inoculation. Thus beta-gal activity was expressed in the bilateral anterior horn cells at the lumbosacral spinal cord that innervates the inoculated muscle for a long time, possibly a life-long period. This indicates that this recombinant HSV vector system to motor neurons may further improve the understanding and treatment of neurological diseases in motor neurons of the spinal cord.

Animals↗
PubMed2000

Perinatal transmission of hepatitis B virus and its prevention.

In order to prevent liver cirrhosis and hepatocellular carcinoma in later life, it is essential to prevent HBV infection in infants. If the mother is chronically infected with HBV and is also positive for HBeAg, 80-90% of the newborns become chronically infected, whereas if the mother is positive for anti-HBe, only some newborns will develop acute hepatitis or fulminant hepatitis. It is necessary to screen pregnant women for HBsAg and prevent mother-to-infant infection of HBV, treating the infant with hepatitis B hyperimmune globulin at birth, followed by HBV vaccination. In highly endemic areas of HBV, universal HBV vaccination of all newborns is advisable.

Carrier State↗
PubMed2000

Survivin promotes cell proliferation in human hepatocellular carcinoma.

Survivin is a recently described inhibitor of apoptosis. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression and function of survivin in human hepatocellular carcinomas (HCCs). We have shown that 4 HCC cell lines and 7 out of 8 human HCC tissues expressed survivin messenger RNA (mRNA), whereas expression of survivin mRNA was not detected in normal liver and nontumor areas of these tissues using the reverse transcription polymerase chain reaction. Survivin was detected primarily in the nucleus by immunofluorescence staining of HCC cells. In addition, 14 of 20 (70%) HCC tissues showed positive nuclear staining for survivin, whereas nontumor tissues showed little detectable staining by immunohistochemistry. Survivin expression strongly correlated with the proliferation index but not significantly with the apoptosis index in HCC tissues. Therefore, we performed cell cycle analysis after survivin transfection and showed that overexpression of survivin resulted in a decrease in the G(0)/G(1) phase and an increase in the S phase in all 4 HCC cell lines. Furthermore, we have found that survivin interacted with cyclin-dependent kinase 4 (Cdk4) and overexpression of survivin released p21(WAF1/Cip1) (p21) from Cdk4. From these results, we conclude that survivin promotes cell proliferation by interacting with Cdk4 and releasing p21 from Cdk4. This may play an important role in carcinogenesis and progression of human HCCs.

Apoptosis↗
PubMed2000

Chemotherapeutic agents augment TRAIL-induced apoptosis in human hepatocellular carcinoma cell lines.

TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in various transformed cell lines but not in almost-normal tissues. It is regulated by 2 death receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2, and 2 decoy receptors, TRAIL-R3 and TRAIL-R4. We investigated the expression of TRAIL-R- and TRAIL-induced apoptosis in human hepatocellular carcinomas (HCCs). TRAIL-R1, -R2, and -R4 were expressed in 6 HCC cell lines examined, but TRAIL-R3 was expressed in only 2 of the 6 cell lines. In addition, immunohistochemical results revealed a high and prevalent expression of TRAIL-R1 and -R2 in human HCC tissues. Despite the expression of TRAIL-R1 and -R2, all 6 HCC cell lines showed resistance to TRAIL-induced apoptosis with no relation to nuclear factor kappa B (NF-kappaB) levels induced by TRAIL. TRAIL-induced death signal was inhibited with both decreased caspase-8 and caspase-3 activity. However, TRAIL induced significant apoptosis in the presence of a subtoxic level of actinomycin D, indicating that the TRAIL-induced apoptotic pathway is in place in these cell lines. In addition, we found that treatment with conventional chemotherapeutic agents, doxorubicin and camptothecin, dramatically augmented TRAIL-induced cytotoxicity in most of the HCC cell lines. Actinomycin D and camptothecin almost completely suppressed NF-kappaB induction by TRAIL, whereas doxorubicin had little effect. These results indicate that TRAIL, in combination with chemotherapeutic agents, may have therapeutic potential in the treatment of human HCC.

Antibiotics, Antineoplastic↗
PubMed2000

Hepatocyte growth factor promotes cell survival from fas-mediated cell death in hepatocellular carcinoma cells via Akt activation and Fas-death-inducing signaling complex suppression.

The Akt/PI-3 kinase pathway is a system essential for cell survival. In the current study, we showed that hepatocyte growth factor (HGF) activates the Akt/PI-3 kinase pathway to suppress Fas-mediated cell death in human hepatocellular carcinoma (HCC; 3 lines; SK-Hep1, HLE, and Chang Liver cell lines), hepatoblastoma (1 line; HepG2), and embryonic hepatocyte (1 line; WRL). Five tested cell lines showed the resistance to Fas-mediated cell death by the pretreatment of HGF. This HGF-induced cell survival was suppressed by wortmannin (Akt/PI-3 kinase pathway inhibitor), suggesting an involvement of Akt. When cells were pretreated with HGF, Fas-mediated cell death was suppressed, followed by Akt phosphorylation at Ser473. Fas-death-inducing signaling complex (DISC) formation, especially FADD and caspase 8 interaction, was suppressed by HGF and the suppression of the Akt/PI-3 kinase pathway by transient expression of PTEN, resulting in acquisition of Fas-DISC formation and Fas-mediated cell death in HGF-treated cells. We suggest that HGF promotes cell survival in hepatocyte-derived cell lines (HCC, hepatoblastoma, and embryonic hepatocyte) from Fas-mediated cell death via Fas-DISC suppression as a result of Akt activation.

Carcinoma, Hepatocellular↗
PubMed2000

Laparoscopic findings in an adult case of Alagille syndrome.

Laparoscopic findings in a 32-year-old woman presenting with Alagille syndrome are reported. The liver surface showed a segmental whitish discoloration on the surface of both lobes with a transverse sulcus which was not stained enough after an intravenous injection of indocyanine green (ICG). These findings suggested an acquired bile duct injury in addition to a congenital anomaly of the bile duct in this patient.

Adult↗
PubMed2000

Novel immunogenicity of Oka varicella vaccine vector expressing hepatitis B surface antigen.

Recombinant Oka (ROka) varicella vaccine expressing hepatitis B surface antigen (HBsAg) and subunit HBsAg vaccine (SHV) were used as primary and booster HBsAg vaccines in 3 combinations (SHV-SHV, SHV-ROka, and ROka-SHV) in guinea pigs. Immune responses to HBsAg and varicella-zoster virus gE:gI were evaluated. The 3 combinations induced similar levels of the lymphocyte proliferation response to HBsAg. Of the 3 combinations, SHV-SHV induced the strongest antibody response to an "a" loop of HBsAg and to the whole HBsAg. Its ratio of antibody titer to this loop versus HBsAg was significantly higher than that in SHV-ROka, suggesting the supplementary recognition of the conformational epitope of HBsAg in SHV-ROka. SHV-ROka induced delayed-type hypersensitivity (DTH) to the HBsAg and gE:gI produced in infected cells. Thus, ROka induced DTH to HBsAg and enhanced recognition of the conformational epitope. ROka varicella vaccine may serve as a novel vaccine vector to induce a Th1-type immune response.

Animals↗