Biomedical subjects

Ichizo Kobayashi

Publications and source records attributed to Ichizo Kobayashi.

22 records · Page 2Linked to original sources

PubMed2003

Identification in methicillin-susceptible Staphylococcus hominis of an active primordial mobile genetic element for the staphylococcal cassette chromosome mec of methicillin-resistant Staphylococcus aureus.

We previously reported that the methicillin resistance gene mecA is carried by a novel type of mobile genetic element, SCCmec (staphylococcal cassette chromosome mec), in the chromosome of methicillin-resistant Staphylococcus aureus (MRSA). These elements are precisely excised from the chromosome and integrated into a specific site on the recipient chromosome by a pair of recombinase proteins encoded by the cassette chromosome recombinase genes ccrA and ccrB. In the present work, we detected homologues of the ccr genes in Staphylococcus hominis type strain GIFU12263 (equivalent to ATCC 27844), which is susceptible to methicillin. Sequence determination revealed that the ccr homologues in S. hominis were type 1 ccr genes (ccrA1 and ccrB1) that were localized on a genetic element structurally very similar to SCCmec except for the absence of the methicillin-resistance gene, mecA. This genetic element had mosaic-like patterns of homology with extant SCCmec elements, and we designated it SCC(12263) and considered it a type I staphylococcal cassette chromosome (SCC). The ccrB1 gene identified in the S. hominis strain is the first type 1 ccrB gene discovered to retain its function through the excision process as judged by two criteria: (i) SCC(12263) was spontaneously excised during cultivation of the strain and (ii) introduction of the S. hominis ccrB1 into an MRSA strain carrying a type I SCCmec whose ccrB1 gene is inactive generated SCCmec excisants at a high frequency. The existence of an SCC without a mec determinant is indicative of a staphylococcal site-specific mobile genetic element that serves as a vehicle of transfer for various genetic markers between staphylococcal species.

Amino Acid Sequence↗

PubMed2003

ONO-4007, a synthetic lipid A analog, induces Th1-type immune response in tumor eradication and restores nitric oxide production by peritoneal macrophages.

We have reported that ONO-4007, a novel synthetic lipid A derivative with low toxic activities, produced large amount of tumor necrosis factor (TNF)-alpha selectively in the tumor tissues and brought about complete cures in about 60% of rats bearing TNF-alpha sensitive KDH-8 cells, which also secreted a large amount of transforming growth factor (TGF)-beta. In our present study, to explore ONO-4007 induced Th1-type immune response, we investigated the mRNA expression of interferon (IFN)-gamma, Interleukin (IL)-1beta, IL-6, IL-10, IL-12 in KDH-8 bearing rats. We next examined the nitric oxide (NO) production. We found that IFN-gamma, IL-1beta, IL-6 and IL-12 mRNA expression of the tumor tissue were higher in the ONO-4007 treated rats than in phosphate buffer saline (PBS) treated rats. Western blotting also revealed that IL-12 protein production was increased. NO production from peritoneal macrophages were suppressed in tumor-bearing rats, but ONO-4007 restored it up to the normal level. These results suggest that ONO-4007 induces and restores Th1-type immune response through cytokine production cascade, followed by initial TNF-alpha production, eventually leading to tumor eradication.

Animals↗

PubMed2002

A reaction-diffusion model for interference in meiotic crossing over.

One crossover point between a pair of homologous chromosomes in meiosis appears to interfere with occurrence of another in the neighborhood. It has been revealed that Drosophila and Neurospora, in spite of their large difference in the frequency of crossover points, show very similar plots of coincidence-a measure of the interference-against the genetic distance of the interval, defined as one-half the average number of crossover points within the interval. We here propose a simple reaction-diffusion model, where a "randomly walking" precursor becomes immobilized and matures into a crossover point. The interference is caused by pair-annihilation of the random walkers due to their collision and by annihilation of a random walker due to its collision with an immobilized point. This model has two parameters-the initial density of the random walkers and the rate of its processing into a crossover point. We show numerically that, as the former increases and/or the latter decreases, plotted curves of the coincidence vs. the genetic distance converge on a unique curve. Thus, our model explains the similarity between Drosophila and Neurospora without parameter values adjusted finely, although it is not a "genetic model" but is a "physical model," specifying explicitly what happens physically.

Crossing Over, Genetic↗

PubMed2002

A DNA methyltransferase can protect the genome from postdisturbance attack by a restriction-modification gene complex.

In prokaryotic genomes, some DNA methyltransferases form a restriction-modification gene complex, but some others are present by themselves. Dcm gene product, one of these orphan methyltransferases found in Escherichia coli and related bacteria, methylates DNA to generate 5'-C(m)CWGG just as some of its eukaryotic homologues do. Vsr mismatch repair function of an adjacent gene prevents C-to-T mutagenesis enhanced by this methylation but promotes other types of mutation and likely has affected genome evolution. The reason for the existence of the dcm-vsr gene pair has been unclear. Earlier we found that several restriction-modification gene complexes behave selfishly in that their loss from a cell leads to cell killing through restriction attack on the genome. There is also increasing evidence for their potential mobility. EcoRII restriction-modification gene complex recognizes the same sequence as Dcm, and its methyltransferase is phylogenetically related to Dcm. In the present work, we found that stabilization of maintenance of a plasmid by linkage of EcoRII gene complex, likely through postsegregational cell killing, is diminished by dcm function. Disturbance of EcoRII restriction-modification gene complex led to extensive chromosome degradation and severe loss of cell viability. This cell killing was partially suppressed by chromosomal dcm and completely abolished by dcm expressed from a plasmid. Dcm, therefore, can play the role of a "molecular vaccine" by defending the genome against parasitism by a restriction-modification gene complex.

Animals↗