Acquired Immunodeficiency Syndrome: Murakami T

Komano J, Futahashi Y, Urano E, Miyauchi K, Murakami T, Matsuda Z, Yamamoto N. · Laboratory of Virology and Pathogenesis, AIDS Research Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan. · Jpn J Infect Dis. · Pubmed #15973003 links to  free full text

Abstract: Human immunodeficiency virus type 1 (HIV-1) is a causative agent of acquired immunodeficiency syndrome (AIDS) in humans. In the last decade, the functions of HIV-1-encoded genes have been intensively studied. These studies have contributed to the development of the effective anti-AIDS drugs directing against the HIV-1-encoded enzymes, namely reverse transcriptase and protease. However, even the combination of these drugs is not sufficient enough to stop the progression of AIDS partly due to the emergence of drug-resistant HIV-1 mutants as well as the severe side effects. Understanding the molecular mechanisms by which cellular factors support the efficient replication of HIV-1 should contribute to develop means to control the progression of AIDS. This field is now expanding rapidly. Here we review the host factors involved in the replication of HIV-1 and highlight some findings that have a substantial impact on the retroviral research.

Murakami T, Nakajima M, Nakamura T, Hara A, Uyama E, Mita S, Matsushita S, Uchino M. · Department of Neurology, Kumamoto University School of Medicine. · Intern Med. · Pubmed #11197803 links to  free full text

Abstract: We studied a Japanese patient who developed parkinsonian symptoms over 3 months before the diagnosis of acquired immunodeficiency syndrome. Brain MRI showed multiple lesions with mass effect and ring enhancement in the basal ganglia and subcortical white matter suggesting Toxoplasma infection. Anti-Toxoplasma therapy and highly active antiretroviral therapy for 6 months allowed improvement of parkinsonism, brain MRI findings, and immune system.

Eda Y, Murakami T, Ami Y, Nakasone T, Takizawa M, Someya K, Kaizu M, Izumi Y, Yoshino N, Matsushita S, Higuchi H, Matsui H, Shinohara K, Takeuchi H, Koyanagi Y, Yamamoto N, Honda M. · AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan. · J Virol. · Pubmed #16699037 links to  free full text

Abstract: In an accompanying report (Y. Eda, M. Takizawa, T. Murakami, H. Maeda, K. Kimachi, H. Yonemura, S. Koyanagi, K. Shiosaki, H. Higuchi, K. Makizumi, T. Nakashima, K. Osatomi, S. Tokiyoshi, S. Matsushita, N. Yamamoto, and M. Honda, J. Virol. 80:5552-5562, 2006), we discuss our production of a high-affinity humanized monoclonal antibody, KD-247, by sequential immunization with V3 peptides derived from human immunodeficiency virus type 1 (HIV-1) clade B primary isolates. Epitope mapping revealed that KD-247 recognized the Pro-Gly-Arg V3 tip sequence conserved in HIV-1 clade B isolates. In this study, we further demonstrate that in vitro, KD-247 efficiently neutralizes CXCR4- and CCR5-tropic primary HIV-1 clade B and clade B' with matching neutralization sequence motifs but does not neutralize sequence-mismatched clade B and clade E isolates. Monkeys were provided sterile protection against heterologous simian/human immunodeficiency virus challenge by the passive transfer of a single high dose (45 mg per kg of body weight) of KD-247 and afforded partial protection by lower antibody doses (30 and 15 mg per kg). Protective neutralization endpoint titers in plasma at the time of virus challenge were 1:160 in animals passively transferred with a high dose of the antibody. The antiviral efficacy of the antibody was further confirmed by its suppression of the ex vivo generation of primary HIV-1 quasispecies in peripheral blood mononuclear cell cultures from HIV-infected individuals. Therefore, KD-247 promises to be a valuable tool not only as a passive immunization antibody for the prevention of HIV infection but also as an immunotherapy for the suppression of HIV in phenotype-matched HIV-infected individuals.

Murakami T, Hagiwara T, Yamamoto K, Hattori J, Kasami M, Utsumi M, Kaneda T. · Department of Clinical Research, Nagoya National Hospital (Tokai Area Central Hospital for AIDS Treatment and Research), 4-1-1 Sannomaru, Naka-ku, Nagoya, 460-0001, Aichi, Japan. · J Pathol. · Pubmed #11329152 No free full text.

Abstract: A novel in situ hybridization (ISH) method for detecting human immunodeficiency virus-1 (HIV-1) was developed by applying a peptide nucleic acid (PNA) probe and a catalysed signal amplification (CSA) method. The PNA probe used in the present study possessed 15 base sequences of the HIV-1 protease gene, and the 5' end of the probe was labelled with the fluorescein isothiocyanate (FITC) molecule. The hybridized probe was detected by sequential reactions of the following antibodies and reagents: horseradish peroxidase (HRP)-conjugated anti-FITC antibody, biotinylated tyramide (first amplification), HRP-labelled streptavidin, biotinylated tyramide (second amplification), and streptavidin-conjugated Alexa 488. The signal of Alexa 488 was finally detected by fluorescence microscopy. HIV-1-related dotted signals were clearly obtained in HIV-1 persistently infected cell lines, MOLT4-III(B) and ACH-2, and CD4-positive T lymphocytes from AIDS patients. For light microscopy, HRP-labelled streptavidin was reacted instead of streptavidin-conjugated Alexa 488 at the final treatment, followed by diaminobenzidine as chromogen. This method can detect HIV-1 in either blood smear samples or paraffin-embedded autopsy tissue and is useful as a sensitive non-radioactive method for in situ hybridization.

Murakami T, Suzuki M, Okada S, Suzuki J, Nagaoka T, Sakamoto K, Aoki S, Matsuoka R. · Department of Respiratory Medicine, Showa General Hospital, Tokyo, Japan. · Nihon Kokyuki Gakkai Zasshi. · Pubmed #11061091 No free full text.

Abstract: A 40-year-old man was admitted to our hospital with acute respiratory failure. The patient was given a diagnosis of Pneumocystis carinii pneumonia (PCP) associated with acquired immunodeficiency syndrome (AIDS). After treatment with trimethoprim-sulfamethoxazole and corticosteroid, the respiratory failure was improved and the abnormal shadows disappeared. The serum beta-D-glucan level, significantly elevated (76.0 pg/ml) on admission, returned to the normal range within two weeks. Serum KL-6 (max. 7580 U/ml) and surfactant protein-D (SP-D) (max. 235 ng/ml), which are produced by type II pneumocytes, increased after elevation of the beta-D-glucan level and decreased gradually following successful treatment. These findings suggest that beta-D-glucan may be a serological marker for PCP infection and KL-6 may be a serological marker for lung injury in PCP with AIDS.

Kaneda T, Murakami T, Hagiwara T, Hattori J, Yamamoto K, Sato K, Morishita T, Utsumi M. · No affiliation provided · AIDS. · Pubmed #11399969 No free full text.

This publication has no abstract.