Husbandry and Medical Management of African Hedgehogs

The African hedgehog, Atelerix albiventris, has become a very popular pet in the United States. At one time, this animal was being imported from its native land of Central Africa, but it is now being successfully bred in captivity in the United States. Another species that is also becoming popular is the African pygmy hedgehog, Erinaceinae aethechinus. There are many species and variations of hedgehogs, differing in size, shape, and color. Although hedgehogs have a similar appearance to a porcupine, they are classified with the shrew and the mole in the order Insectivora. Hedgehogs belong to the family Erinacidae, which consists of three genera: Erinaceus (African and Eurasian hedgehogs), Hemiechinus (long-eared desert hedgehogs), and Paraechinus (desert hedgehogs)

A case of generalized lymphatic anomaly causing skull-base leakage and bacterial meningitis

Generalized lymphatic anomaly (GLA) is a multifocal lymphatic malformation that affects the skin, thoracic viscera, and bones. A 7-year-old boy presented with fever and disturbance of consciousness, and bacterial meningitis was diagnosed. Computed tomography and magnetic resonance imaging revealed middle skull-base leakage due to lymphatic malformation. Past history included facial palsy due to cystic tumors in the right petrous bone 4 years before onset of meningitis. At that time, pericardial effusion had been found and GLA had been diagnosed by pericardial biopsy. He achieved complete recovery under intensive care with antibiotics and mechanical ventilation. At the 3-year follow-up, the patient was healthy with no recurrence of meningitis. We should consider GLA among the differential diagnoses for osteolytic diseases in the pediatric population

HIV-1 Derivatives in Rhesus Macaques

A major issue for present HIV-1 research is to establish model systems that reflect or mimic viral replication and pathogenesis actually observed in infected humans. To this end, various strategies using macaques as infection targets have long been pursued. In particular, experimental infections of rhesus macaques by HIV-1 derivatives have been believed to be best suited, if practicable, for studies on interaction of HIV-1 and humans under various circumstances. Recently, through in vitro genetic manipulations and viral cell-adaptations, we have successfully generated a series of HIV-1 derivatives with CXCR4-tropism or CCR5-tropism that grow in macaque cells to various degrees. Of these viruses, those with best replicative potentials can grow comparably with a pathogenic SIVmac in macaque cells by counteracting major restriction factors TRIM5, APOBEC3, and tetherin proteins. In this study, rhesus macaques were challenged with CXCR4-tropic (MN4/LSDQgtu) or CCR5-tropic (gtu + A4CI1) virus. The two viruses were found to productively infect rhesus macaques, being rhesus macaque-tropic HIV-1 (HIV-1rmt). However, plasma viral RNA was reduced to be an undetectable level in infected macaques at 5–6 weeks post-infection and thereafter. While replicated similarly well in rhesus peripheral blood mononuclear cells, MN4/LSDQgtu grew much better than gtu + A4CI1 in the animals. To the best of our knowledge, this is the first report demonstrating that HIV-1 derivatives (variants) grow in rhesus macaques. These viruses certainly constitute firm bases for generating HIV-1rmt clones pathogenic for rhesus monkeys, albeit they grow more poorly than pathogenic SIVmac and SHIV clones reported to date

Double knockdown of α1,6-fucosyltransferase (FUT8) and GDP-mannose 4,6-dehydratase (GMD) in antibody-producing cells: a new strategy for generating fully non-fucosylated therapeutic antibodies with enhanced ADCC

<p>Abstract</p> <p>Background</p> <p>Antibody-dependent cellular cytotoxicity (ADCC) is greatly enhanced by the absence of the core fucose of oligosaccharides attached to the Fc, and is closely related to the clinical efficacy of anticancer activity in humans <it>in vivo</it>. Unfortunately, all licensed therapeutic antibodies and almost all currently-developed therapeutic antibodies are heavily fucosylated and fail to optimize ADCC, which leads to a large dose requirement at a very high cost for the administration of antibody therapy to cancer patients. In this study, we explored the possibility of converting already-established antibody-producing cells to cells that produce antibodies fully lacking core fucosylation in order to facilitate the rapid development of next-generation therapeutic antibodies.</p> <p>Results</p> <p>Firstly, loss-of-function analyses using small interfering RNAs (siRNAs) against the three key genes involved in oligosaccharide fucose modification, i.e. α1,6-fucosyltransferase (<it>FUT8</it>), GDP-mannose 4,6-dehydratase (<it>GMD</it>), and GDP-fucose transporter (<it>GFT</it>), revealed that single-gene knockdown of each target was insufficient to completely defucosylate the products in antibody-producing cells, even though the most effective siRNA (>90% depression of the target mRNA) was employed. Interestingly, beyond our expectations, synergistic effects of <it>FUT8 </it>and <it>GMD </it>siRNAs on the reduction in fucosylation were observed, but not when these were used in combination with <it>GFT </it>siRNA. Secondly, we successfully developed an effective short hairpin siRNA tandem expression vector that facilitated the double knockdown of <it>FUT8 </it>and <it>GMD</it>, and we converted antibody-producing Chinese hamster ovary (CHO) cells to fully non-fucosylated antibody producers within two months, and with high converting frequency. Finally, the stable manufacture of fully non-fucosylated antibodies with enhanced ADCC was confirmed using the converted cells in serum-free fed-batch culture.</p> <p>Conclusion</p> <p>Our results suggest that FUT8 and GMD collaborate synergistically in the process of intracellular oligosaccharide fucosylation. We also demonstrated that double knockdown of <it>FUT8 </it>and <it>GMD </it>in antibody-producing cells could serve as a new strategy for producing next-generation therapeutic antibodies fully lacking core fucosylation and with enhanced ADCC. This approach offers tremendous cost- and time-sparing advantages for the development of next-generation therapeutic antibodies.</p

CXCR4- and CCR5-Tropic HIV-1 Clones Are Both Tractable to Grow in Rhesus Macaques

A major issue for present HIV-1 research is to establish model systems that reflect or mimic viral replication and pathogenesis actually observed in infected humans. To this end, various strategies using macaques as infection targets have long been pursued. In particular, experimental infections of rhesus macaques by HIV-1 derivatives have been believed to be best suited, if practicable, for studies on interaction of HIV-1 and humans under various circumstances. Recently, through in vitro genetic manipulations and viral cell-adaptations, we have successfully generated a series of HIV-1 derivatives with CXCR4-tropism or CCR5-tropism that grow in macaque cells to various degrees. Of these viruses, those with best replicative potentials can grow comparably with a pathogenic SIVmac in macaque cells by counteracting major restriction factors TRIM5, APOBEC3, and tetherin proteins. In this study, rhesus macaques were challenged with CXCR4-tropic (MN4/LSDQgtu) or CCR5-tropic (gtu + A4CI1) virus. The two viruses were found to productively infect rhesus macaques, being rhesus macaque-tropic HIV-1 (HIV-1rmt). However, plasma viral RNA was reduced to be an undetectable level in infected macaques at 5–6 weeks post-infection and thereafter. While replicated similarly well in rhesus peripheral blood mononuclear cells, MN4/LSDQgtu grew much better than gtu + A4CI1 in the animals. To the best of our knowledge, this is the first report demonstrating that HIV-1 derivatives (variants) grow in rhesus macaques. These viruses certainly constitute firm bases for generating HIV-1rmt clones pathogenic for rhesus monkeys, albeit they grow more poorly than pathogenic SIVmac and SHIV clones reported to date

The Effects of Volcanic Disaster on the Prevalence and Severity of Bronchial Asthma

Objectives: To evaluate the impact of volcanic disaster on bronchial asthma, the prevalence and the extent of deterioration of asthma were studied among primary school children aged 6 to 11 years who experienced the volcanic eruption of Mt. Unzen Fugen, Nagasaki, Japan. Methods: Questionnaire data were collected from the parents or guardians of primary school children. Asthma was classified into four categories: diagnosed asthma, current asthma, remitted asthma, and deteriorated asthma, and the prevalence of each category was compared according to sex and grade. We also analyzed the relation between asthma and past illness and family history including experience of volcanic disaster. Results: Multiple logistic regression analysis showed that past illnesses of allergic diseases, such as allergic rhinitis, dermatitis and conjunctivitis were associated with either current asthma or deteriorated asthma. On the effects of volcanic disaster, a change of family member after volcanic disaster was significantly associated with deteriorated asthma (odds ratio=3.20, 95% confidence interval=1.79-5.70). Location of school seemed to somewhat influence the prevalence of deteriorated asthma, which might relate to the distance from the volcanic crater. Conclusion: Our findings suggest that not only gases and ash but also changes in psychosocial conditions by refuge or related anxiety may influence the prevalence of asthma among primary school children

Coexpression of Ang1 and Tie2 in Odontoblasts of Mouse Developing and Mature Teeth?A New Insight into Dentinogenesis

Agiopoieten regulates vascular angiogenesis and stabilization, and is reported to promote bone formation by facilitating angiogenesis. To estimate the role of Ang1 in odontogenesis, we explored the distribution of Ang1 and the receptor, Tie2 in the mouse developing and mature first molar of the mandible. At embryonic day 18, when differentiation of odontoblasts begins, immunosignals for Ang1 were intensely detected in the basement membrane and the distal side, which faced the basement membrane of odontoblasts. In situ hybridization revealed that Ang1 was expressed in odontoblasts and ameloblasts facing the basement membrane. Tie2 was localized in the distal side of odontoblasts. After birth, Ang1 was detected in the predentin, whereas both Ang1 and Tie2 were colocalized in odontoblasts and odontoblast processes. These distributions were retained up to 8 weeks. In contrast to odontoblasts, ameloblasts, cementoblasts and osteoblasts expressed Ang1 but did not express Tie2. Colocalization of Ang1 and Tie2 in odontoblasts and selective expression of Tie2 in odontoblasts among cells responsible for calcified tissue formation suggested the involvement of autocrine signals of Ang1-Tie2 in dentinogenesis

Construction of Childcare Support Program for two-children families: From Cooperation with Higashi-Hiroshima City Childcare Support Centers

The purpose of this study was to construct a childcare support program for the families who have two children to bring up. With the assistance of Higashi-Hiroshima city and childcare support centers, members from early childhood education research facility in Hiroshima University built up the program. In this program, it is demanded that the supporters draft the program while being conscious of four times, specifically approach-time, core-time, free-time and feedback-time. And this program also has four main components including topics, leaflet, picture books and reflection sheets. According to the practice, supporters can not only grow up with mothers and children by making use of their childcare specialty, but also can build a relationship of mutual trust with the participants. Besides, the support of the high quality is maintained by the collaboration of Higashi-Hiroshima city and childcare support centers and Hiroshima University.本研究は平成29年度「広島大学地域連携推進事業」に提案した「地域における虐待防止ペアレントトレーニングの効果検証－親が抱えるリスク要因の低減を目指して－」という研究の一環として，東広島市子ども家庭課の協力で実施したものである