Acquired Immunodeficiency Syndrome: Saito N

Shibuya K, Hirata A, Omuta J, Sugamata M, Katori S, Saito N, Murata N, Morita A, Takahashi K, Hasegawa C, Mitsuda A, Hatori T, Nonaka H. · Department of Pathology, Omori Hospital, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo, 143-8541, Japan. · J Infect Chemother. · Pubmed #15990974 No free full text.

Abstract: This review describes the general histopathological features of cryptococcosis in immunocompetent individuals, as well as in patients with acquired immunodeficiency syndrome (AIDS). Details of the histological examination of cryptococcal lesions are described, with the consideration of morphological modifications induced by treatment with highly active antiretroviral therapy (HAART). The essential histological features of cryptococcosis in individuals with impaired T-cell functioning are yeast-cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. Several histological patterns of pulmonary cryptococcal lesions are introduced in this article, some of which could be graded with respect to the degree and type of inflammatory reaction. One pattern was a mild lesion consisting of scattered small foci of intraalveolar cryptococcal proliferation with a histiocytic response. Another pattern involved massive cryptococcal infection, which may have been simply more extensive than that in the mild lesion. Capillary involvement of alveolar septa should be understood as an important common finding in patients with AIDS who had not been treated with HAART. In those patients, the absence of T cells and a decreasing function of antigen-presenting activity in histiocytes were confirmed by immunohistological examination. These findings suggest that the lungs of AIDS patients without HAART offer little resistance to bloodstream dissemination by cryptococci. The unique histological feature demonstrated in patients treated with HAART is characterized by the presence of CD4+ cells, greater response of histiocytes and multinucleated giant-cell formation, and lack of massive capillary involvement.

Nakagawa Y, Yanagita RC, Hamada N, Murakami A, Takahashi H, Saito N, Nagai H, Irie K. · Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. · J Am Chem Soc. · Pubmed #19449873 No free full text.

Abstract: Protein kinase C (PKC) is widely recognized as a therapeutic target in intractable diseases such as cancer, Alzheimer's disease (AD), and acquired immune deficiency syndrome (AIDS). While inhibition of PKC is a general therapeutic strategy for the treatment of cancer, PKC activators are potential therapeutic agents for AD and AIDS. However, concerns have been raised about their therapeutic use since PKC activators such as phorbol esters exhibit potent tumor-promoting activities. Naturally occurring bryostatin 1 (bryo-1), prostratin, and 12-deoxyphorbol 13-phenylacetate (DPP) are fascinating PKC activators without tumor-promoting activities. Bryo-1 is currently in clinical trials for the treatment of cancer and is also effective against AD. Prostratin and DPP are attractive candidates for the adjunctive treatment of human immunodeficiency virus (HIV) infection. However, their limited availability from natural sources and synthetic complexity have hampered further development as therapeutic agents. We report here easy access (22 steps) to a simple analogue (1) of the tumor-promoting aplysiatoxin (ATX) as a novel PKC activator with anticancer and anti-tumor-promoting activities. Anticancer activities of 1 against several human cancer cell lines were comparable to those of bryo-1. Moreover, 1 as well as bryo-1 significantly inhibited the Epstein-Barr virus early antigen (EBV-EA) induction by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA), whereas ATX strongly induced EBV-EA. This inhibitory effect is characteristic of antitumor promoters. Compound 1 as well as bryo-1 displayed significant binding and activation of PKCdelta and induced its translocation to the nuclear membrane in CHO-K1 cells. This study provides a synthetically accessible PKC activator with bryo-1-like activities, which could be another therapeutic lead for cancer, AD, and AIDS.

Fukazawa Y, Miyake A, Ibuki K, Inaba K, Saito N, Motohara M, Horiuchi R, Himeno A, Matsuda K, Matsuyama M, Takahashi H, Hayami M, Igarashi T, Miura T. · Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan. · J Virol. · Pubmed #18400862 links to  free full text

Abstract: To analyze the relationship between acute virus-induced injury and the subsequent disease phenotype, we compared the virus replication and CD4(+) T-cell profiles for monkeys infected with isogenic highly pathogenic (KS661) and moderately pathogenic (#64) simian-human immunodeficiency viruses (SHIVs). Intrarectal infusion of SHIV-KS661 resulted in rapid, systemic, and massive virus replication, while SHIV-#64 replicated more slowly and reached lower titers. Whereas KS661 systemically depleted CD4(+) T cells, #64 caused significant CD4(+) T-cell depletion only in the small intestine. We conclude that SHIV, regardless of pathogenicity, can cause injury to the small intestine and leads to CD4(+) T-cell depletion in infected animals during acute infection.

Miyake A, Ibuki K, Enose Y, Suzuki H, Horiuchi R, Motohara M, Saito N, Nakasone T, Honda M, Watanabe T, Miura T, Hayami M. · Institute for Virus Research, Laboratory of Primate Model, Experimental Research Center for Infectious Disease, Kyoto University, Sakyo-ku, Japan. · J Gen Virol. · Pubmed #16603534 links to  free full text

Abstract: A better understanding of virological events during the early phase of human immunodeficiency virus 1 (HIV-1) infection is important for development of effective antiviral vaccines. In this study, by using quantitative PCR and an infectious plaque assay, virus distribution and replication were examined in various internal organs of rhesus macaques for almost 1 month after intrarectal inoculation of a pathogenic simian immunodeficiency virus/HIV chimeric virus (SHIV-C2/1-KS661c). At 3 days post-inoculation (p.i.), proviral DNA was detected in the rectum, thymus and axillary lymph node. In lymphoid tissues, infectious virus was first detected at 6 days p.i. and a high level of proviral DNA and infectious virus were both detected at 13 days p.i. By 27 days p.i., levels of infectious virus decreased dramatically, although proviral DNA load remained unaltered. In the intestinal tract, levels of infectious virus detected were much lower than in lymphoid tissues, whereas proviral DNA was detected at the same level as in lymphoid tissues throughout the infection. In the thymus and jejunum, CD4CD8 double-positive T cells were depleted earlier than CD4 single-positive cells. These results show that the virus spread quickly to systemic tissues after mucosal transmission. Thereafter, infectious virus was actively produced in the lymphoid tissues, but levels decreased significantly after the peak of viraemia. In contrast, in the intestinal tract, infectious virus was produced at low levels from the beginning of infection. Moreover, virus pathogenesis differed in CD4 single-positive and CD4CD8 double-positive T cells.

Miyake A, Ibuki K, Suzuki H, Horiuchi R, Saito N, Motohara M, Hayami M, Miura T. · Institute for Virus Research, Kyoto University, Kyoto, Japan. · J Med Primatol. · Pubmed #16128924 No free full text.

Abstract: Children infected with human immunodeficiency virus type 1 often have higher viral loads and progress to acquired immunodeficiency syndrome more rapidly than adults. In our previous study of simian-human immunodeficiency virus (SHIV)-infected adult monkeys, immature CD4CD8 double-positive T cells in the thymus and jejunum decreased faster than mature CD4 single-positive T cells. Here, we examined the effect of virus replication on immature T cells from the same SHIV-inoculated newborn monkeys having more immature T cells than adults. The infectious viruses were more abundantly detected in the thymus than in other tissues at both 13 and 26 days post-infection (dpi). However, mature CD4(+) T cells in the thymus declined after 13 dpi and immature CD3(-) CD4 single-positive T cells remained at 26 dpi. These results suggested that many immature CD4(+) T cells in the thymus of newborns support the production of infectious viruses even after the depletion of mature CD4(+) T cells.

Nochi H, Kai R, Saito Y, Nakazawa T, Nanashima T, Maruyama Y, Saito N. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #10590535 No free full text.

This publication has no abstract.