Expansion of Lung Vα14 NKT Cells by Administration of α-Galactosylceramide-pulsed Dendritic Cells

NKT cells, a novel murine lymphoid lineage bearing an invariant T cell receptor encoded by Vα14 and Jα281 gene segments, recognize a specific ligand glycolipid, α-galactosylceramide (α-GalCer) in a CDld-dependent manner. Recent research has revealed that activated Vα14 NKT cells have dramatic antitumor effects against a wide variety of tumor cell lines in vivo and in vitro. Here, we demonstrate strong in vivo antitumor effects brought about by treatment with α-GalCer-pulsed dendritic cells in comparison with in vitro -activated Vα14 NKT cells. Furthermore, we show a significant expansion of endogenous Vα14 NKT cells in the lung following the administration of α-GalCer-pulsed dendritic cells. The feasibility of immunotherapy with α-GalCer-pulsed dendritic cells is discussed.     

The Effect of Human Gammaglobulin Derivatives on Human Lymphoblastoid Cell Lines Persistently Infected with Herpes Simplex Virus

Human lymphoblastoid cells (NC-37) were infected with two strains of herpes simplex virus type 1 (HSV-1). Persistent infections with two strains (a freshly isolated strain, Seike strain, and Miyama strain) of HSV-1 were established in NC-37 cells. In NC-37 cells infected with HSV-1 (Seike), the growth of cells was inhibited, 6–72% of viable cells were positive for HSV-antigen by fluorescent antibody technique, and the percentage of HSV-antigen positive cells seemed to be inversely related to that of viable cells. Growth of cells and infectious viruses was seen for more than 396 days without external support. NC-37 cells infected with HSV-1 were subcultured with fresh medium containing human gammaglobulin derivatives. The percentage of HSV-antigen positive cells decreased and no infectious viruses were detected in the treated cells and cultured fluids after more than 16 days. It is thought that HSV continues to associate with T-lymphocytes stimulated in vivo for a long period of time after the appearance of circulating antibody, at least for two weeks, and lymphocytes persistently infect with HSV have a relation to the patho-genesis of herpesvirus encephalitis in oider children and adults similar to the pathogenesis of SSPE. (Acta Paediatr Jpn 23(2): 201–207 1981)     

Ability of fourteen chemical agents used in dental practice to induce chromosome aberrations in Syrian hamster embryo cells

To assess the genotoxicity of 14 chemical agents used in dental practice, the ability of these agents to induce chromosome aberrations was examined using Syrian hamster embryo (SHE) cells. Statistically significant increases in the frequencies of chromosome aberrations were induced in SHE cells treated with 7 of 10 chemical agents used as endodontic medicaments, that is, carbol camphor, m-cresol, eugenol, guaiacol, zinc oxide, hydrogen peroxide, and formaldehyde. The other 3 chemical agents, that is, thymol, glutaraldehyde, and iodoform, did not increase the levels of chromosome aberrations. Of the 4 chemical agents that are used as an antiseptic on the oral mucosa, chromosome aberrations were induced by iodine, but not by the other 3 antiseptics, benzalkonium chloride, benzethonium chloride, and chlorhexidine. Among the 6 chemical agents exhibiting a negative response in the assay, only thymol induced chromosome aberrations in the presence of exogenous metabolic activation. Our results indicate that chemical agents having a positive response in the present study are potentially genotoxic to mammalian cells and need to be studied further in detail.     

Distribution of OL-protocadherin in axon fibers in the developing chick nervous system

OL-protocadherin (OL-pc) is a homophilic cell adhesion molecule that belongs to the cadherin gene superfamily. We cloned and characterized the chicken homologue of OL-pc and examined its expression pattern in chick embryos mainly from embryonic day (E) 3.5 to E6.5. The structure of chick OL-pc was found to be essentially the same as that of mammalian OL-pc's except for some small deletions and insertions in the amino acid sequence. OL-pc protein was detected prominently along developing axonal fibers in the brain and also in the peripheral nervous system. In addition, it was detected in some mesenchymal cells and in the embryonic ectoderm of the mandible and limb bud. In the spinal cord, OL-pc was specifically expressed in motor neurons, and the protein was distributed along motor nerves. Motor nerves merged gradually with sensory nerves showing negative/faint OL-pc expression, but their fibers remained separated as small bundles in the nerves. Interestingly, OL-pc-positive motor nerves such as those to the sternocoracoideus became segregated from OL-pc-faint/weak motor nerves at the plexus region. Moreover, OL-pc was distributed along the path of the branchial nerves. These results suggest that OL-pc might play some roles in axon navigation such as in axon elongation, selective fasciculation, and pathfinding in the early stage of neural development.     

Diversity of the muscarinic and nicotinic responses of subfornical organ neurons in rat slice preparations

Recently we found that subfornical organ (SFO) neurons were activated through nicotinic receptors as well as muscarinc. In this study, the preferential responses of single SFO neurons to both muscarine and nicotine were examined by using rat slice preparations, and current and voltage clamp recordings. When the amplitudes of the depolarizations and inward currents by muscarine and nicotine in single SFO neurons were compared, some neurons showed a higher sensitivity to muscarine than to nicotine while others showed vice versa. These data indicate that acetylcholine activates SFO neurons preferentially through either muscarinic or nicotinic receptors and suggest a diversity of cholinergic responses in the SFO.     

Unambiguous identification of <Emphasis Type="Italic">JC polyomavirus</Emphasis> strains transmitted from parents to children

Summary. JC polyomavirus (JCV), the etiological agent of progressive multifocal leukoencephalopathy, is ubiquitous in humans, infecting children asymptomatically, then persisting in renal tissue. It has been proposed that JCV is transmitted mainly from parents to children through long-term cohabitation. The objective of this study was to further elucidate the mode of JCV transmission. In 5 families, we selected parent/child pairs between whom JCV was probably transmitted (judged on the basis of the identity of a 610-bp JCV DNA sequence between the parent and child). We established 5 to 9 complete JCV DNA clones from the urine of each parent or child. The complete sequences of these clones were determined and compared in each family. Nucleotide substitutions were detected in 4 parents and 1 child, and sequence rearrangements (deletions or duplications) were found in 2 parents and 2 children. Phylogenetic comparison of the detected sequences indicated that the diversity of JCV DNA sequences was generated in each family (i.e. not caused by multiple infection). We found that in 4 of the 5 families, a sequence detected in the parent was completely identical to one in the child. These findings provided further support for the proposed mode of JCV transmission, i.e. parent-to-child transmission during cohabitation.     

Detection of identical JC virus DNA sequences in both human kidneys

Summary. We studied JC virus (JCV) DNA sequence diversity among kidneys derived from cadavers with various causes of death. The 610-bp JCV DNA sequences we evaluated were identical not only among specimens derived from the same kidney but also among those derived from both kidneys of the same cadaver. Because the left and right kidneys are anatomically independent, our findings suggest that the viremia that has been proposed to occur after primary infection distributes the same JCV strain to both kidneys.