Biomedical subjects

R Shimano

Publications and source records attributed to R Shimano.

At least 19 recordsLinked to original sources

PubMed2005

Study of orthoexciton-to-paraexciton conversion in Cu(2)O by excitonic Lyman spectroscopy.

Using time-resolved 1s-2p excitonic Lyman spectroscopy, we study the orthoexciton-to-paraexciton transfer, following the creation of a high density population of ultracold 1s orthoexcitons by resonant two-photon excitation with femtosecond pulses. An observed fast exciton-density dependent conversion rate is attributed to spin exchange between pairs of orthoexcitons. Implication of these results on the feasibility of Bose-Einstein condensation of paraexcitons in Cu(2)O is discussed.

Journal Article↗

PubMed2002

Efficient two-photon light amplification by a coherent biexciton wave.

A reversible coupling between photon pair states and a long-lived, highly coherent biexciton wave in CuCl allows efficient phase-sensitive two-photon amplification or attenuation of ultrashort light pulses. We demonstrate a gain of 350 cm(-1) for a pump intensity of 1 MW/cm(2), nearly 2 orders of magnitude higher than that achievable with conventional parametric crystal amplifiers. We develop a theoretical model that describes this new type of parametric converter where the light pump is replaced by a coherent biexciton wave and show that it is well suited for the generation of entangled photons and the squeezing of an optical beam with ultrafast time gating.

Journal Article↗

PubMed2001

Electron-hole droplet formation in direct-gap semiconductors observed by mid-infrared pump-probe spectroscopy.

Mid-infrared pump-probe measurements with subpicosecond time resolution reveal the existence of a metastable condensed phase of the electron-hole ensemble in a direct-gap semiconductor CuCl. High-density electrons and holes are directly created in a low-temperature state by the resonant femtosecond excitation of excitons above the Mott transition density. Strong metallic reflection with a plasma frequency Planck's over 2pi(omega)p approximately 0.5 eV builds up within 0.3 ps. Within a few picoseconds, the mid-infrared reflection spectrum is transformed from metalliclike into colloidlike. The observed resonance feature at Planck's over 2pi(omega)p/sqrt[3] allows us to obtain the carrier density in the metastable electron-hole droplets of 2x10(20) cm(-3).

Journal Article↗

PubMed1999

Cell-dependent replication potentials of HIV-1 gag mutants.

An infectious molecular clone of human immunodeficiency virus type 1 (HIV-1), designated pNLaiKH, which is tropic for both lymphocytic and monocytic cells, was constructed. To study the early function of HIV-1 Gag proteins in two types of cells, the mutations known to give host cell-dependent early defects were introduced into pNLaiKH, and the replication potentials and defective replication sites in the cells of the resultant mutants were monitored. All mutants grew in some lymphocytic cells, but not at all in monocytic cells. A nucleocapsid mutant was found to be defective at an early replication phase in all the cell lines to various extent, as expected. In contrast, a matrix mutant and a capsid mutant displayed a replication defect in a producer-cell-dependent manner. These results demonstrated that complex interactions of cell factors and Gag proteins are involved in an early process of HIV-1 replication.

Cell Line↗

PubMed1999

Inhibition of HIV/SIV replication by dominant negative Gag mutants.

There are several major strategies against HIV/AIDS. Of these, the gene therapy is a novel, challenging, and promising one. The target genes, which have been extensively studied for the potential gene therapy of HIV/AIDS, include those of cellular and viral origins. Especially, trans-dominant negative Tat, Rev, Env, Pol, and Gag mutants of HIV have currently attracted considerable attention. In this brief review, we summarize the nature of the HIV/SIV mutants of this category and discuss their future use for gene therapy with special reference to the dominant negative Gag mutants of HIV-1.

Genes, Dominant↗

PubMed1999

Host cell-dependent replication of HIV-1 gag MA, CA, and NC mutants are independent of the functions of Vif and Vpu.

We have previously shown that some gag gene mutants of human immunodeficiency virus type 1 (HIV-1) display a replication-defect in a cell-dependent manner. We and others have also demonstrated that the requirement of vif and vpu genes for HIV-1 replication is cell-dependent. To determine whether the cell-dependent growth of the HIV-1 gag mutants is related to the functions of Vif and Vpu, double mutants of gag-vif and gag-vpu were constructed, and monitored for their replication in various cell lines. The results obtained showed that the mutations in gag do not affect the cell-dependent functions of Vif and Vpu.

Capsid↗

PubMed1999

Exchangeability of accessory Vif and Vpu proteins between various HIV/SIVs (review).

Representative human and simian immunodeficiency viruses (HIV/SIVs) have been monitored for their Vif and Vpu activities in a wide variety of cells. In contrast to the prototype HIV-1, viruses of the other groups do not necessarily have these activities. Only HIV-2 and SIVmnd were clearly demonstrated to show the Vif and Vpu activities, respectively. The exchangeability of these accessory activities between viruses was then assessed to determine the relatedness of the viruses. Quite different from the results for Tat and Rev trans-activators, the activities are almost fully compatible between viruses. These results may facilitate the functional grouping of various HIV/SIVs.

Gene Products, vif↗

PubMed1998

Producer cell-dependent requirement of the Nef protein for efficient entry of HIV-1 into cells.

A proviral nef gene mutant of human immunodeficiency virus type 1 (HIV-1) was evaluated for its defective early replication step. Virus stocks were prepared from six CD4-positive and -negative cell lines transfected with wild-type (wt) or the nef mutant clone and inoculated into two target CD4-positive cell lines to monitor the efficiency of viral entry process. The nef mutant virions produced in one cell line exhibited a severe defect in the entry process, although those produced in the other five cell lines were only slightly less efficient than the wt virions at entering into cells. These results have demonstrated that the HIV-1 Nef is critical for efficient viral entry in a producer cell-dependent manner.

CD4-Positive T-Lymphocytes↗

PubMed1998

Early function of HIV-1 Gag proteins is cell-dependent.

Various gag gene mutants of human immunodeficiency virus type 1 (HIV-1) were monitored for their replication potentials and defective replication sites in various CD4-positive T-cell lines. Some matrix, capsid, and nucleocapsid mutants displayed a replication defect in a cell-dependent manner. The single-round replication assays demonstrated that these mutants were defective at an early infection phase also in a cell-dependent way. These results indicated that interaction of a cell factor(s) and Gag proteins is involved in an early process of HIV-1 replication.

CD4-Positive T-Lymphocytes↗

PubMed1998

Suppression of HIV-2 replication by HIV-1 gag mutants.

Gag gene mutants of human immunodeficiency virus type 1 (HIV-1) were analyzed for their potentials of inhibiting the replication of wild-type (wt) HIV-2, the second AIDS virus, in a single-round of viral replication. Of twenty-two HIV-1 gag mutants examined, seven were found to efficiently interfere with the replication of wt HIV-2. Some mutants, which can suppress the replication of wt HIV-1, did not show this inhibitory effect. These mutants were defective at the late phase of viral replication. A mutant designated NL-C1a was demonstrated to be very effective against the replication of HIV-1 and HIV-2 in monocytic cells as well as in lymphocytic cells.

CD4-Positive T-Lymphocytes↗

PubMed1998

The potential of various HIV-1 mutants to inhibit the replication of wild-type virus.

We have previously demonstrated that many of gag mutants of human immunodeficiency virus type 1 (HIV-1) inhibited the replication of wild-type (wt) HIV-1. In this study, various HIV-1 mutants were systematically analyzed with respect to their ability to suppress the replication of wt HIV-1. Sixteen mutants of all eight HIV-1 genes other than gag were evaluated for their inhibitory effects. Only an env mutant designated NL-Hi efficiently interfered with the replication of wt HIV-1 in a single round of infection. The NL-Hi did not affect the late replication processes of wt virus, including transcription, translation, and assembly/release. Virions produced in the presence of the mutant Env were defective for the viral entry process in the early phase of HIV-1 replication cycle.

Cell Line↗

PubMed1998

Inhibition of HIV replication by capsid mutant C6b.

A Gag capsid mutant of human immunodeficiency virus type 1 (HIV-1) designated C6b was biologically and biochemically characterized with respect to its ability to suppress the replication of wild-type (wt) HIV. The C6b efficiently interfered with the replication of wt HIV-1 in the cleavage of Gag precursor, and also in the early replication process before or during viral DNA synthesis after viral penetration. The C6b Gag appeared to be unable to form chimeric multimers with HIV-2 Gag and failed to inhibit the replication of wt HIV-2.

Blotting, Southern↗

PubMed1998

Mapping the genetic determinants of human immunodeficiency virus type 2 for cell tropism and replication efficiency.

Two distinct infectious molecular clones of human immunodeficiency type 2 (HIV-2) were analyzed for their biological properties in six cell lines. Fourteen chimeric and ten mutant viruses were constructed from these two viral genomes to localize the genetic determinants responsible for the phenotypes. Growth property of the viruses in the cell lines, together with the biochemical data, showed that a major determinant for the viral tropism resides in the env gene. In addition, in some cell lines, the accessory genes vif and nef affected the efficiency of virus replication. Thus, like HIV-1, mutations in the auxiliary and env genes of HIV-2 contributed much to the differences in virological characteristics.

Base Sequence↗

PubMed1998

Gag-Pol region determines the tropism of SIVagm for human cells.

Simian immunodeficiency virus isolated from African green monkeys (SIVagm) does not grow in many of human cell lines such as CEM x 174, H9, and MT-4, but could replicate in some human cell lines. Sequence of SIVagm responsible for its narrow host range was determined by making and monitoring growth potential of chimeric clones between SIVagm and human immunodeficiency virus type 1 (HIV-1). The results obtained indicated that the gag-pol region determines the observed narrow host range. By monitoring virus DNA synthesis and progeny virion production, the defect(s) of SIVagm in the replication in the restricted cells was demonstrated to be located at early phase.

Animals↗

PubMed1998

Complete inhibition of SIVmac replication by its capsid mutants.

Mutations were introduced into a genomic region encoding the C-terminal portion of Gag capsid protein of pathogenic simian immunodeficiency virus (SIVmac239). All the mutants generated were defective for virion production and were non-infectious for monkey cells. They all efficiently suppressed the replication of wild type SIVmac in monkey cells. These results were in good agreement with those obtained for human immunodeficiency virus type 1, showing the importance of SIV/monkey model system for studies on Gag.

Animals↗

PubMed1998

Enhancement of human immunodeficiency virus type 1 infectivity by Nef is producer cell-dependent.

The growth kinetics of wild-type and nef mutant viruses of human immunodeficiency virus type 1 were comparatively analysed in several human CD4+ cell lines. Delayed replication of nef mutant virus was observed in all cell lines examined. To determine the stage in the virus replication cycle that is affected by Nef, a single-round replication assay was performed. Initially, the expression of marker genes in transfected cells was examined in order to study the role of Nef in the late phase of infection. The results obtained indicated that Nef is dispensable during the transcription to virion production stage. Next, the effect of Nef on the early phase was investigated with a single-round infection. It was demonstrated that Nef is required in the early phase of the virus replication cycle, from virion adsorption to integration. Finally, the infectivity of virus stocks prepared from four cell lines was determined. The relative infectivity of the nef mutant from the four cell lines differed. Taken together, we conclude that Nef acts via modulation of viral particles to enhance virus infectivity in a cell-dependent manner.

Gene Products, nef↗

PubMed1998

Suppression of HIV replication by dominant negative mutants of HIV-1 (review).

Various gag mutants of human immunodeficiency virus type 1 (HIV-1) generated in vitro were evaluated for their potentials to suppress the replication of wild-type (wt) virus. A single-round of wt virus replication in the presence of various mutant proteins was quantitatively monitored by transfection and infection experiments. Out of 38 mutants examined, 15 were demonstrated to interfere with the replication of wt HIV-1 at early and/or late viral replication phase. Some of these mutants were also effective against the replication of wt HIV-2. In this review, we focus on the mutants, which are able to act against a wide variety of HIV, and are very useful for future gene therapy against AIDS.

HIV-1↗

PubMed1998

Functional roles of HIV accessory proteins for viral replication (review).

Numerous lentiviruses, including human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) of causative agents of human AIDS as representative, have been recently isolated from various species of primates. The fundamental and most prominent feature of the viruses is the presence of a number of accessory genes in their genomes. Extensive biological and biochemical studies have demonstrated that the accessory gene products are not essential for viral replication at least in certain types of cells. Quite surprisingly, some of these accessory proteins are absolutely non-essential in any types of cells so far examined. In this brief review, our systematic genetic studies on the importance of the accessory proteins of HIV-1 and HIV-2 for viral replication are described and discussed.

Animals↗