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Background/Aim: Hepatitis A virus (HAV) infection is still one of the serious health problems worldwide, despite the existence of effective vaccines for HAV. Zinc compounds have antiviral activities against various DNA and RNA viruses. Therefore, we investigated the effects of zinc compounds on the antiviral activity of interferon against HAV. Materials and Methods: The effects of zinc compounds with or without interferon on HAV genotype IIIA HA11-1299 replication were examined in human hepatoma Huh7 cells. Cell viability was examined by the MTS assay. Inflammasome associated gene expression was examined by real-time reverse transcription-polymerase chain reaction. Results: Both zinc sulfate and zinc chloride had an inhibitory effect on HAV replication. Zinc sulfate tended to enhance while zinc chloride significantly enhanced the anti-HAV effect induced by interferon-alpha-2a. Zinc chloride significantly up-regulated mitogen-activated protein kinase 12 (MAPK12) and downregulated 6 related genes [baculoviral IAP repeat containing 3 (BIRC3), interleukin 1 beta (IL1B), proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), prostaglandinendoperoxide synthase 2 (PTGS2), PYD and CARD domain containing (PYCARD), and tumor necrosis factor (TNF)]. Conclusion: Zinc chloride inhibits HAV replication and has additive effects on the anti-HAV activities of interferon. [ABSTRACT FROM AUTHOR]

The reproductive biology of the blue shark (Prionace glauca) in the western North Pacific Ocean was investigated to contribute to future stock assessments because of limitations of recent studies and the lack of information about the reproductive cycle. Reproductive data were obtained from 490 males (precaudal length (PCL), 33.4-252.0 cm) and 432 females (PCL, 33.4-243.3 cm). Size at 50% maturity was estimated to be 160.9 cm for males and 156.6 cm PCL for females. Litter size varied from 15 to 112 (mean 35.5) and was positively correlated with maternal PCL. Parturition, ovulation and mating occurred sequentially from spring to summer. The gestation period was estimated to be 11 months. The ovarian follicles of pregnant females developed synchronously throughout the gestation period along with embryonic growth, indicating that females reproduce annually.Our results showed that the productivity ofNorth Pacific blue sharks is higher than previously thought, based on larger fecundity and a shorter reproductive cycle. These new findings will improve future stock assessments and provide management advice. [ABSTRACT FROM AUTHOR]

Infection with hepatitis A virus (HAV) is a major cause of acute hepatitis globally and it is important to identify the mechanisms of HAV replication. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum (ER) chaperone and serves a role in unfolded protein response pathways. Previous studies have demonstrated that GRP78 functions as an endogenous antiviral factor. In the present study, two loss-of-function studies using GRP78 were completed to elucidate the role of GRP78 in HAV infection. HAV replication was observed to be enhanced by deficient GRP78 although GRP78-deficiency also led to lower expression of ER stress molecules downstream of GRP78. Therefore, GRP78 appears to be a potential novel defensive molecule against HAV in hepatocytes. [ABSTRACT FROM AUTHOR]

Background: The role of irinotecan for elderly patients with LD-SCLC has been unclear, and the timing of TRT combined with chemotherapy has not been fully evaluated.Methods: Patients aged > 70 years with untreated, measurable, LD-SCLC, performance status (PS) 0-2, and adequate organ function were eligible. Treatment consisted of induction with carboplatin on day 1 and irinotecan on days 1 and 8, every 21 days for 4 cycles, and sequential TRT (54Gy in 27 fractions). Carboplatin doses were based on AUC of 4 and 5 (levels 1 and 2, respectively), with a fixed irinotecan dose (50 mg/m2). Primary objective of the phase II study was overall responce rate.Results: Forty-three patients were enrolled and forty-one were finally analyzed (median age: 75 years [range 70-86 years); males 31; PS 0/1/2, n = 22/18/1]. Two patients were excluded because of protocol violation (ascertained to be extensive disease). Twelve patients were accrued at phase I and the number of patients with carboplatin dose-limiting toxicities at levels-1 (n = 6) and -2 (n = 6) were 1(grade 3 hypertension) and 2 (grade 4 thrombocytopenia), respectively. The phase II trial was expanded to 29 additional patients receiving the level 1 carboplatin dose, total of 35 patients. The median number of chemotherapy cycles was 4 (range 1-4), and the median radiation dose was 54Gy (range 36-60). Toxicities were generally mild. There were 4 complete and 27 partial responses (response rate 88.6%). With a median follow-up of 52 months, the median progression-free and overall survival times of phase II were 11.2 and 27.1 months, respectively.Conclusions: Induction chemotherapy of carboplatin plus irinotecan and sequential TRT was well tolerated and effective for elderly patients with LD-SCLC. Additional confirmatory studies are warranted.Trial Registration: Trial registration number: UMIN000007352 Name of registry: UMIN. Date of registration: 1/Dec/2006. Date of enrolment of the first participant to the trial: 6/Feb/2007. Clinical trial registration date: 1/Feb/2006 (prospective). [ABSTRACT FROM AUTHOR]

A previous study revealed that antibodies to hepatitis E virus (HEV) (anti‐HEV) are highly prevalent among healthy individuals and farm pigs in Bali, Indonesia, and suggested that HEV infection may occur via zoonosis among Balinese people. However, there were no reports of acute hepatitis E in Bali. To elucidate whether Balinese HEV strains recovered from infected humans and pigs have significant sequence similarity, serum samples obtained from 57 patients (age, mean ± standard deviation, 31.1 ± 11.9 years) with sporadic acute hepatitis and from one hundred and one 2‐ or 3‐month‐old farm pigs in Bali were tested for anti‐HEV and HEV RNA. Among the 57 patients, 2 (3.5%) had high‐titer IgM/IgA class anti‐HEV antibodies and one of them had detectable HEV RNA (BaliE03‐46). Overall, 58 pigs (57.4%) tested positive for anti‐HEV, while 5 pigs (5.0%) had detectable HEV RNA. Based on the 412‐nucleotide sequence within open reading frame 2, the BaliE03‐46 isolate and the 5 swine HEV isolates recovered from the viremic pigs were phylogenetically classified in genotype 4, but were only 77.3–90.8% identical to the genotype 4 HEV isolates reported thus far in China, India, Japan, Taiwan, and Vietnam. The BaliE03‐46 isolate of human origin shared high identities of 97.3–98.3% with 4 of the 5 Balinese swine isolates, but differed by 16.1% from the remaining swine isolate. These results suggest that indigenous HEV strains of genotype 4 with marked heterogeneity are circulating in Bali, Indonesia, and that pigs are reservoirs of HEV for Balinese people who have a habit of ingesting uncooked pigs. J. Med. Virol. 79: 1138–1146, 2007. © 2007 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]

Although no outbreaks of hepatitis E have been reported in Mongolia, a significant proportion of the general population had antibodies to hepatitis E virus (HEV). To investigate whether pigs are possible reservoirs of HEV in Mongolia, serum samples obtained from 243 2‐ or 3‐month‐old pigs on four swine farms surrounding Ulaanbaatar, the capital city of Mongolia, were tested for the presence of anti‐HEV antibodies and HEV RNA. Overall, 223 pigs (91.8%) tested positive for anti‐HEV, while 89 pigs (36.6%) had detectable HEV RNA. The 89 HEV isolates obtained from the viremic pigs were 78.7–100% identical to each other, and 80.9–85.9% similar to the prototype genotype 3 HEV isolate (US1) in the 412‐nucleotide (nt) sequence within open reading frame 2. They were classified into two novel phylogenetic groups within genotype 3, differing by 16.4–21.3%. The swMN06‐A1288 and swMN06‐C1056 isolates, representing each of the two clusters within genotype 3, had a genomic length of nucleotides (nt) 7,222 nt and 7,223 nt, respectively, excluding the poly(A) tail, and shared only 81.6% over the entire genome. Upon comparison with the 25‐reported genotype 3 HEV isolates over the entire genome, swMN06‐A1288 had identities of merely up to 84.9%, while swMN06‐C1056 of only up to 85.9%. Phylogenetic analysis confirmed the remote relatedness of the Mongolian swine isolates to the genotype 3 HEV isolates reported thus far. These results indicate that farm pigs in Mongolia are frequently infected with presumably indigenous HEV strains of genotype 3 and could be a source of HEV infections in humans in Mongolia. J. Med. Virol. 79: 1128–1137, 2007. © 2007 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]

Mongolia is highly endemic for hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infections among apparently healthy adults. However, the age‐specific prevalence of ongoing HBV, HCV, and HDV infections among children in Mongolia remains unknown. Therefore, samples obtained from a total of 655 apparently healthy children of 0.3–15 years of age (307 boys and 348 girls; age, mean ± standard deviation [SD], 8.4 ± 4.2 years) living in Mongolia, between October 2005 and January 2006, were tested for serological and molecular markers of HBV, HCV, and HDV infections. Although 88.7% of the 655 children studied were immunized against hepatitis B, 64 (9.8%) tested positive for hepatitis B surface antigen (HBsAg) and/or HBV DNA and 13 (2.0%) for HDV RNA. Twenty‐seven children (4.1%) had detectable HCV RNA. Collectively, 82 (12.5%) were viremic for one or more of these viruses, including eight children with dual viremia of HBV/HCV and one child with triple HBV/HCV/HDV viremia. When children without anti‐HBc, anti‐HCV and anti‐HDV IgG (n = 510) served as a control, a history of hospitalization was significantly associated with HBV viremia (P < 0.0001), anti‐HBc positivity (P < 0.0001), and HCV viremia (P = 0.0001). HBsAg mutation was found in 18 (31.6%) of the 57 children with viremia, including those at amino acid position 126, 127, 129, 131, 134, 143 or 144. There were no significant differences in the frequency of HBsAg mutation in relation to age, sex, and hepatitis B vaccination status of the children, suggesting that HBsAg mutation plays a limited role in failure of vaccination in Mongolia. J. Med. Virol. 79: 1064–1074, 2007. © 2007 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in children in Mongolia, the prevalence of HAV and HEV infections was investigated serologically and molecularly among 717 apparently healthy individuals of 0–20 years of age (mean ± standard deviation, 8.6 ± 4.9 years) using serum samples obtained between October 2005 and January 2006. Total antibody against HAV (anti‐HAV [total]) was detected in 494 (68.9%) of the 717 subjects, while IgG antibody against HEV (anti‐HEV IgG) was detected in only five subjects (0.7%) (P < 0.0001). All five subjects who had anti‐HEV IgG, were negative for anti‐HEV IgM and HEV RNA. Anti‐HAV was detectable in 24 (75.0%) of the 32 infants aged 7 days to 6 months, but not in any of the 8 infants aged 7 to <12 months. The prevalence of anti‐HAV was 19.5% (17/87) in the age group of 1–3 years, and it increased to 50.0% (69/138) in the age group of 4–6 years, and further to 81.4% (105/129) in the age group of 7–9 years. Of note, 97.2% of the subjects in the age group of 16–20 years had anti‐HAV. The presence of HAV RNA was tested in all 717 subjects, and three children of 1, 4, or 8 years of age were found to have detectable HAV RNA (subgenotype IA). No subject had a history of hepatitis or jaundice. In conclusion, HEV infection was uncommon, but HAV infection lacking overt clinical features was prevalent among children in Mongolia. J. Med. Virol. 79:18–25, 2007. © 2006 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]

Among six known subgenotypes (IA, IB, IIA, IIB, IIIA, and IIIB) of human hepatitis A virus (HAV), the complete genomic sequence has not been determined for IIIB. In this study, the full‐length genomic sequence of a IIIB HAV isolate (HA‐JNG06‐90F) recovered from a Japanese patient who contracted sporadic hepatitis A in 1990, was determined. The HA‐JNG06‐90F genome, which comprised 7462 nt excluding the poly(A) tail, was related most closely to NOR‐21 of subgenotype IIIA with an identity of 89.1%, and was only 82.6–83.4% similar to human HAV isolates of genotypes I and II over the entire genome. Comparison of full‐length genomic sequences of 20 reported isolates and HA‐JNG06‐90F generated optimal results for separation of different levels: the nucleotide identities were 80.7–86.6% at the genotype level, 89.1–91.9% at the subgenotype level, and 94.6–99.7% at the isolate level. Similar ranges of nucleotide identity were observed when comparing partial nucleotide sequences of the VP1‐2B (481 nt; primer sequences at both ends excluded) and 3C/3D (590 nt) regions, which were amplifiable by PCR with primers designed from well‐conserved areas of the HAV genome. All 66 samples with IgM‐class HAV antibodies tested positive for HAV RNA by both VP1‐2B (481 nt)‐PCR and 3C/3D (590 nt)‐PCR: subgenotype assignment was concordant in all samples tested (IA [n = 61], IB [n = 1], IIIA [n = 2] and IIIB [n = 2]). These results suggest that two broadly reactive PCRs using primers derived from the VP1‐2B and 3C/3D regions, respectively, may be applicable to universal detection and phylogenetic analysis of various HAV strains. J. Med. Virol. 79:8–17, 2007. © 2006 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]

Background. We compared acute hepatitis E (AH-E) and acute hepatitis A (AH-A) to investigate the epidemiology, clinical features, and prognosis of AH-E caused by an indigenous hepatitis E virus (HEV) in Japan. Methods. We enrolled 58 patients diagnosed with AH-A or AH-E (32 men and 26 women; age, 20–72 years) from December 1997 to October 2002. Phylogenetic analysis of the partial 412-nucleotide sequence of open reading frame (ORF) 2 was performed in patients with AH-E. Results. Regarding the geographic distribution of the HEV genotype, genotype III was principally distributed in Honshu Island, and genotype IV in Hokkaido Island (P = 0.0034). The phylogenetic analysis of the ORF2 region revealed that there were significant geographic differences in the distribution of the HEV strains in Japan, with some strains being widespread and some, localized. In comparison with AH-A patients, those with AH-E were older (56.1 ± 10.6 vs 45.9 ± 10.8 years; P = 0.0017). The proportion of males among patients with AH-E was significantly higher (P = 0.0001). Pyrexia was often observed in AH-A, and malaise in AH-E. Laboratory data indicate that AH-E induces a weak immunological reaction, whereas jaundice appears earlier in AH-E than in AH-A. One patient with AH-E died of acute hepatic failure, but none of those with AH-A died during the study period. Conclusions. Our results suggest that there are geographical differences between HEV strains in Japan, and that AH-E is more common in males and older patients than AH-A. Laboratory data indicate a weak immunological reaction and early appearance of jaundice in AH-E. [ABSTRACT FROM AUTHOR]

This paper describes the effect of alkoxy chain length on the physico-chemical properties of 4-nitrophenyl 4-(4-alkoxybenzoyloxyphenyl)benzoates. The homologous series shows a smectic A (SmA) phase commencing from the hexyloxy homologue. While the pentyloxy homologue shows only a nematic (N) phase under microscopic observation, X-ray diffraction shows that the N phase has a cybotactic domain with a layer structure of the SmA phase, where the layer spacings are longer than the calculated molecular lengths by c. Å. The layer spacings for the heptyloxy-nonyloxy homologues are longer than the calculated molecular lengths by 2.2–4.8 Å and are almost independent of temperature. The layer spacings are correlated with the calculated molecular lengths, and based on these results, a new molecular arrangement model for the SmA phase is proposed. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) infection which may become fulminant, especially in elderly people is more common than previously recognized in develop countries. Here we report successful living-donor liver transplantation (LDLT) in a case of acute liver failure due to HEV. A 63-year-old Japanese man with no previous history of liver disease was admitted for severe acute hepatitis. Detection of anti-HEV immunoglobulin A established a diagnosis of this virus-related liver failure. The patient suffered from hepatic encephalopathy 10 days after symptom onset and underwent LDLT. The patient had an uneventful course. The HEV RNA showed spontaneous negative conversion 10 weeks after LDLT. LDLT led to a successful outcome in a patient with acute liver failure due to HEV infection and regular testing for HEV RNA should be performed until HEV RNA is undetectable. [ABSTRACT FROM AUTHOR]