Acquired Immunodeficiency Syndrome: Yamada T

Tokuda H, Sakai F, Yamada H, Johkoh T, Imamura A, Dohi M, Hirakata M, Yamada T, Kamatani N, Kikuchi Y, Sugii S, Takeuchi T, Tateda K, Goto H. · Department of Internal Medicine, Social Health Insurance Central General Hospital, Tokyo. · Intern Med. · Pubmed #18480575 links to  free full text

Abstract: OBJECTIVE: To elucidate the clinical and radiological features of Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA), compared with methotrexate (MTX) pneumonitis in RA and Pneumocystis pneumonia in acquired immunodeficiency syndrome (AIDS). SUBJECTS AND METHODS: Retrospective analysis of 14 PCP cases in RA (RA-PCP), 10 MTX pneumonitis cases in RA (MTX-P) and 11 PCP cases in AIDS (AIDS-PCP) from 9 centers in the Kanto area in the last 6 years. RESULTS: Compared with AIDS-PCP, both RA-PCP and MTX-P developed more rapidly, showing higher serum CRP and lower plasma beta-D-glucan levels, and more severe oxygenation impairment. In most of the RA-PCP cases, a high dose of corticosteroid was administered as adjunctive therapy, resulting in a favorable outcome. The mortality was 14% in RA-PCP, 0% in AIDS-PCP and 0% in MTX-P cases. In RA-PCP patients the CD4 cell count showed only mild suppression, not reaching the predisposing level for PCP in HIV infection, suggesting that there are risk factors for RA-PCP other than immunosuppression. Radiologic analysis revealed some characteristic patterns of each disease. In MTX-P, diffuse homogeneous ground glass opacity (GGO) with sharp demarcation by interlobular septa (type A GGO) was found in 70%, while in AIDS-PCP diffuse, homogeneous or nonhomogeneous GGO without interlobular septal boundaries (type B GGO) was predominant (91%). In RA-PCP, type A GGO was found in 6 cases and type B GGO in 5 cases, showing the complex nature of this disease. CONCLUSION: RA-PCP differed considerably from AIDS-PCP clinically and radiologically. Clinically it occurred without severe immunosuppression, and showed characteristic aspects, with more intense inflammation and less parasite burden. Radiologically it mimicked MTX-P in some cases sharing the conspicuous CT features of MTX-P, rendering the distinction of these two disorders difficult.

Chaudhari A, Fialho AM, Ratner D, Gupta P, Hong CS, Kahali S, Yamada T, Haldar K, Murphy S, Cho W, Chauhan VS, Das Gupta TK, Chakrabarty AM. · Department of Microbiology & Immunology, University of Illinois at Chicago, Chicago, Illinois 60612, USA. · Cell Cycle. · Pubmed #16861897 No free full text.

Abstract: Azurin, a member of a family of copper-containing proteins involved in electron transfer called cupredoxins, demonstrates structural features similar to the variable domains of the immunoglobulin superfamily members. An azurin-like protein called Laz with an additional N-terminal 39 amino acid peptide known as H.8 epitope is present on the surface of gonnococci and meningococci. We demonstrate that azurin, Laz and H.8-azurin can bind to the C-terminal cleavage product MSP1-19 of merozoite surface protein 1 (MSP1) of the malarial parasite Plasmodium falciparum and significantly reduce parasitemia. Azurin and Laz also bound strongly to HIV-1 gp120. Interestingly, azurin could not only bind to gp120 but also to the dendritic cell-specific adhesion receptor DC-SIGN, mimicking the functionality of the intercellular adhesion molecule ICAM-3 with which it also binds avidly. Furthermore, these three proteins significantly suppressed HIV-1 growth in peripheral blood mononuclear cells and such suppression appeared to be occurring at an entry stage in the infection process. The presence of both antimalarial and antiretroviral activity in azurin, H.8-azurin and Laz makes these proteins, or peptides derived from them, potential therapeutic agents in the treatment of malaria, HIV-1 infections or coinfections with both P. falciparum and HIV-1.

Ami Y, Izumi Y, Matsuo K, Someya K, Kanekiyo M, Horibata S, Yoshino N, Sakai K, Shinohara K, Matsumoto S, Yamada T, Yamazaki S, Yamamoto N, Honda M. · Division of Experimental Animal Research, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan. · J Virol. · Pubmed #16188989 links to  free full text

Abstract: Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guérin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-gamma) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-gamma activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.

Sakurai A, Jere A, Yoshida A, Yamada T, Iwamoto A, Adachi A, Fujita M. · Department of Virology, The University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan. · Microbes Infect. · Pubmed #15374001 No free full text.

Abstract: We analyzed the function of human immunodeficiency virus type 1 (HIV-1) vif gene from Japanese long-term nonprogressors (LTNPRs) and progressors (PRs) for acquired immunodeficiency syndrome (AIDS). We constructed a basic HIV-1 infectious clone, which facilitated the incorporation and evaluation of vif from infected individuals. Proviral reporter clones carrying vif from six Japanese LTNPRs and seven PRs were then generated and their in vitro growth kinetics were analyzed. The vif clones, which could confer infectivity on reporter viruses, were considered active, and the ratio of the active clones to the number of clones examined per individual was determined. For the majority of LTNPRs, there was no correlation between presence or absence of functional vif with long-term nonprogression for AIDS. There was one exception in which all the clones examined had inactive vif, suggesting a probable association of inactive vif with the nonprogression. All PRs with high viral load had a high ratio of active vif clones. Our results suggest that the presence of functional vif would influence HIV-1 infectivity and disease progression in infected individuals.

Kitaura H, Ohara N, Kobayashi K, Yamada T. · School of Dentistry, Nagasaki University, Sakamoto 1-7-1, Nagasaki City 852-8588, Japan. · APMIS. · Pubmed #11552951 No free full text.

Abstract: Mycobacterial infection is a common occurrence in patients with acquired immune deficiency syndrome. Incubation of U1, a chronically HIV-1-infected human promonocytic cell line, with Mycobacterium smegmatis, M. avium, M. bovis BCG and M. tuberculosis resulted in enhancement of p24 antigen release in the supernatant, indicating that these mycobacteria could activate HIV replication from this cell line. The amount of p24 in the culture infected with M. smegmatis was higher than in cultures infected with other mycobacteria. The amounts of p24 release in cultures infected with M. avium and M. bovis BCG were intermediate. M. tuberculosis slightly stimulated HIV replication. The amount of TNF-alpha produced by U1 cells was correlated with the amount of p24 antigen release. The IL-1beta and IL-6 levels in the supernatant from cultures infected with all species were the same. The antibody to TNF-alpha inhibited p24 release induced by mycobacterial infections. The anti-IL-1beta and anti-IL-6 antibodies, however, scarcely influenced stimulation of HIV replication by mycobacterial infection. These data suggested that activation of HIV replication by mycobacteria mainly occurred by secondary release of cytokine TNF-alpha.