Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

Identification of a novel gene, Mblk-1, that encodes a putative transcription factor expressed preferentially in the large-type Kenyon cells of the honeybee brain.

Mushroom bodies (MBs) are considered to be involved in higher-order sensory processing in the insect brain. To identify the genes involved in the intrinsic function of the honeybee MBs, we searched for genes preferentially expressed therein, using the differential display method. Here we report a novel gene encoding a putative transcription factor (Mblk-1) expressed preferentially in one of two types of intrinsic MB neurones, the large-type Kenyon cells, which makes Mblk-1 a candidate gene involved in the advanced behaviours of honeybees. A putative DNA binding motif of Mblk-1 had significant sequence homology with those encoded by genes from various animal species, suggesting that the functions of these proteins in neural cells are conserved among the animal kingdom.

Concentrated expression of Ca2+/ calmodulin-dependent protein kinase II and protein kinase C in the mushroom bodies of the brain of the honeybee Apis mellifera L.

We have previously used the differential display method to identify a gene that is expressed preferentially in the mushroom bodies of worker honeybees and to show that it encodes a putative inositol 1,4,5-trisphosphate receptor (IP3R) homologue (Kamikouchi et al. [1998] Biochem. Biophys. Res. Commun. 242:181-186). In the present study, we examined whether the expression of some of the genes for proteins involved in the intracellular Ca2+ signal transduction is also concentrated in the mushroom bodies of the honeybee by isolating cDNA fragments that encode the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) homologues of the honeybee. In situ hybridization analysis revealed that the expression of these genes was also concentrated in the mushroom bodies of the honeybee brain: The CaMKII gene was expressed preferentially in the large-type Kenyon cells of the mushroom bodies, whereas that for PKC was expressed in both the large and small types of Kenyon cells. The expression of the genes for IP3R and CaMKII was concentrated in the mushroom bodies of the queen and drone as well as in those of the worker bee. Furthermore, the enzymatic activities of CaMKII and PKC were found to be higher in the mushroom bodies/central bodies than in the optic and antennal lobes of the worker bee brain. These results suggest that the function of the intracellular Ca2+ signal transduction is enhanced in Kenyon cells in comparison to other neuronal cell types in the honeybee brain.

[Effect of liver hydrolysate on hepatic proliferation in regenerating rat liver].

The effect of liver hydrolysate (LH) derived from bovine liver on rat liver regeneration after partial hepatectomy (PH) were investigated. Oral administration of LH increased rat liver weight dose-dependently at 24 h after PH. Hepatic ornithine decarboxylase (ODC) activity and proliferating cell nuclear antigen (PCNA) labeling index were measured in regenerating rat liver as markers of cell proliferation. ODC activities at 4 and 24 h after PH were significantly increased by LH administration. PCNA labeling index at 24 h after PH were also increased by LH administration. These results suggest that LH stimulates liver regeneration in partially hepatectomized rats.

Soldier caste-specific gene expression in the mandibular glands of Hodotermopsis japonica (Isoptera: termopsidae).

Although "polymorphic castes" in social insects are well known as one of the most important phenomena of polyphenism, few studies of caste-specific gene expressions have been performed in social insects. To identify genes specifically expressed in the soldier caste of the Japanese damp-wood termite Hodotermopsis japonica, we employed the differential-display method using oligo(dT) and arbitrary primers, compared mRNA from the heads of mature soldiers and pseudergates (worker caste), and identified a clone (PCR product) 329 bp in length termed SOL1. Northern blot analysis showed that the SOL1 mRNA is about 1.0 kb in length and is expressed specifically in mature soldiers, but not in pseudergates, even in the presoldier induction by juvenile hormone analogue, suggesting that the product is specific for terminally differentiated soldiers. By using the method of 5'- and 3'-rapid amplification of cDNA ends, we isolated the full length of SOL1 cDNA, which contained an ORF with a putative signal peptide at the N terminus. The sequence showed no significant homology with any other known protein sequences. In situ hybridization analysis showed that SOL1 is expressed specifically in the mandibular glands. These results strongly suggest that the SOL1 gene encodes a secretory protein specifically synthesized in the mandibular glands of the soldiers. Histological observations revealed that the gland actually develops during the differentiation into the soldier caste.

Preferential expression of the gene for a putative inositol 1,4,5-trisphosphate receptor homologue in the mushroom bodies of the brain of the worker honeybee Apis mellifera L.

A gene expressed preferentially in the mushroom bodies of the brain of the worker honeybee Apis mellifera L. was identified by the differential display method and its cDNA was isolated. The cDNA fragment of 534 bp (clone A1) contained an open reading frame encoding 177 amino acid residues having 78, 72, 70, 59 and 55% sequence identities with the inositol 1,4,5-trisphosphate (IP3) receptors of Drosophila melanogaster, Xenopus laevis and humans (types 1, 2 and 3), respectively, suggesting that it encodes a putative IP3 receptor homologue of the honeybee. In situ hybridization revealed that the gene encoding clone A1 was expressed preferentially in the mushroom bodies and not in the optic lobes, antennal lobes and central bodies; in the mushroom body, it was expressed strongly in the large type Kenyon cells and weakly in the small type Kenyon cells. Reverse transcription polymerase chain reaction analysis showed that the gene was expressed strongly in the head and weakly in the antennae, legs, thorax, and abdomen. These results suggest that the A1 gene product plays a crucial role in neural transmission in the mushroom bodies of the worker bee brain.

Molecular cloning of cDNA and analysis of expression of the gene for alpha-glucosidase from the hypopharyngeal gland of the honeybee Apis mellifera L.

Previously, we identified and purified an alpha-glucosidase with a molecular mass of 70 kDa from a homogenate of the hypopharyngeal gland of the older worker bee (forager bee) Apis mellifera L. (T. Kubo et al, J. Biochem., 1996, 119, 291-295). Here, we isolated and sequenced a cDNA for the alpha-glucosidase. The cDNA encoded a protein consisting of 650 amino acids, which had high sequence identity with fruit fly and mosquito possible maltase gene products. RT-PCR showed that the gene was expressed specifically in the hypopharyngeal gland of the forager bee.