Acquired Immunodeficiency Syndrome: Tanaka Y

Dewan MZ, Terunuma H, Toi M, Tanaka Y, Katano H, Deng X, Abe H, Nakasone T, Mori N, Sata T, Yamamoto N. · Department of Molecular Virology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. · Cancer Sci. · Pubmed #16995875 No free full text.

Abstract: Natural killer (NK) cells are an important component of the innate immune response against microbial infections and tumors. Direct involvement of NK cells in tumor growth and infiltration has not yet been demonstrated clearly. Primary effusion lymphoma (PEL) cells were able to produce tumors and ascites very efficiently with infiltration of cells in various organs of T-, B- and NK-cell knock-out NOD/SCID/gammac(null) (NOG) mice within 3 weeks. In contrast, PEL cells formed small tumors at inoculated sites in T- and B-cell knock-out NOD/SCID mice with NK-cells while completely failing to infiltrate into various organs. Immunosupression of NOD/SCID by treatment with an antimurine TM-beta1 antibody, which transiently abrogates NK cell activity in vivo, resulted in enhanced tumorigenicity and organ infiltration in comparison with non-treated NOD/SCID mice. Activated human NK cells inhibited tumor growth and infiltration in NOG mice. Our results suggest that NK cells play an important role in growth and infiltration of PEL cells, and activated NK cells could be a promising immunotherapeutic tool against tumor or virus-infected cells either alone or in combination with conventional therapy. The rapid and efficient engraftment of PEL cells in NOG mice also suggests that this new animal model could provide a unique opportunity to understand and investigate the mechanism of pathogenesis and malignant cell growth.

Kurbanov F, Kondo M, Tanaka Y, Zalalieva M, Giasova G, Shima T, Jounai N, Yuldasheva N, Ruzibakiev R, Mizokami M, Imai M. · Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. · AIDS Res Hum Retroviruses. · Pubmed #14585203 No free full text.

Abstract: This study investigates the molecular epidemiology of HIV in Uzbekistan--a former Soviet Union (FSU) country located in central Asia. A total of 18,910,370 subjects were involved in an HIV serological examination through a population survey conducted in 1987-2002. Rapid changes in epidemiological dynamics and transmission modes have been observed since 1999: incidence rose from 25 newly HIV-infected subjects per year to more than 100 new cases per month within the first half of 2002, and the rate of intravenous drug use (IVDU)-associated HIV infection increased to 75% per year during the same period. Thirty HIV-1 strains, isolated from specimens obtained in 1999-2000, were directly sequenced in the env region. Phylogenetic analysis revealed a relationship to genotype A in 56.7%, and to 03_CRFAB in 13.3%; both variants have been previously reported in the FSU. The majority (85.7%) of these strains were isolated from IVDUs. The demographic history of the most prevalent HIV strain in Uzbekistan was inferred from reconstructed molecular phylogenies; exponential growth of the viral population size was thus observed to occur after the mid-1990s. In summary, detectable HIV seroprevalence remains low in the general population of Uzbekistan. However, the current study demonstrates a substantially increasing number of new infections, in association with IVDU, and an exponentially growing effective population size of the IVDU-associated HIV strain.

Shimura M, Tanaka Y, Nakamura S, Minemoto Y, Yamashita K, Hatake K, Takaku F, Ishizaka Y. · Department of Intractable Diseases, International Medical Center of Japan, Shinjuku-ku, Tokyo. · FASEB J. · Pubmed #10094923 links to  free full text

Abstract: Vpr, an accessory gene of HIV-1, induces cell cycle abnormality with accumulation at G2/M phase and increased ploidy. Since abnormality of mitotic checkpoint control provides a molecular basis of genomic instability, we studied the effects of Vpr on genetic integrity using a stable clone, named MIT-23, in which Vpr expression is controlled by the tetracycline-responsive promoter. Treatment of MIT-23 cells with doxycycline (DOX) induced Vpr expression with a giant multinuclear cell formation. Increased micronuclei (MIN) formation was also detected in these cells. Abolishment of Vpr expression by DOX removal induced numerous asynchronous cytokinesis in the multinuclear cells with leaving MIN in cytoplasm, suggesting that the transient Vpr expression could cause genetic unbalance. Consistent with this expectation, MIT-23 cells, originally pseudodiploid cells, became aneuploid after repeated expression of Vpr. Experiments using deletion mutants of Vpr revealed that the domain inducing MIN formation as well as multinucleation was located in the carboxy-terminal region of Vpr protein. These results suggest that Vpr induces genomic instability, implicating the possible role in the development of AIDS-related malignancies.