Biomedical subjects

Y Koyanagi

Publications and source records attributed to Y Koyanagi.

At least 163 records · Page 9Linked to original sources

PubMed1989

[Various methods of catheter placement in hepatic arterial infusion--technique of catheter placement via a femoral artery].

A comparative analysis of the individual techniques was performed on a total of 106 cases undergoing various methods of catheter placement in hepatic infusion. The comparison of laparatomy (n = 44) with a percutaneous method (n = 62) disclosed a higher incidence of peptic ulcer in the latter. When two modes of percutaneous approach, including a trans-left subclavian arterial method (n = 36) and a trans-femoral arterial method (n = 26), were compared, a shorter average catheterization time (approximately 70 minutes) and a higher selective insertion rate (92.3%) were noted in the trans-femoral approach. For these reasons, our department adopts the trans-femoral method as the percutaneous method of choice. It is advisable for further studies to be made in order to clarify indications for the individual techniques and for anti-complication measures.

Catheterization, Peripheral↗

PubMed1988

Cytokines alter production of HIV-1 from primary mononuclear phagocytes.

Some strains of human immunodeficiency virus type 1 (HIV-1) can infect primary monocytes and monocyte-derived macrophages in vitro. In this report, the effect of cytokines on the production of one of these strains that shows a tropism for mononuclear phagocytes, designated HIV-1JR-FL, was studied. Primary peripheral blood mononuclear phagocytes infected with HIV-1JR-FL were treated with the hematopoietic factors: granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), macrophage colony-stimulating factor (M-CSF), and gamma-interferon (gamma-IFN). The M-CSF, GM-CSF, IL-3, and gamma-IFN were able to alter HIV-1 production under different conditions.

Biological Products↗

PubMed1988

[First pass effect by infusing 99mTc-human serum albumin into the hepatic artery].

The fundamental principles of intra-arterial infusion chemotherapy are thought to be increased local drug concentration and the "first-pass" effect. The concentration in the rest of the body can only be decreased if there is local elimination of the infused drug before reaching the systemic circulation. This is referred to as the "first-pass" effect. In the evaluation of "first-pass" effect, the uptake of liver after infusing 99mTc-human serum albumin (99mTc-HSA) in the hepatic artery by injecting the subcutaneously implanted silicon reservoir was compared with that obtained after intravenous administration of 99mTc-HSA. In order to remove the factor of portal infusion, each count of liver up take had been continued for only 24 seconds after starting the liver uptake. The results are as follows: for 24 cases excepting 6 cases with catheter obstruction, the mean i.a./i.v. ratio was 7.92 +/- 3.34 (range 3.25 to 17.25). Although the elimination rate of drugs in the liver varies with each drug, the infusion of intraarterial chemotherapy should be about 8 times more concentrative than intravenous administration on the "first-pass" effect.

Heart↗

PubMed1987

Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms.

Human immunodeficiency virus (HIV) is the causative agent of the acquired immune deficiency syndrome (AIDS). A large number of AIDS patients show evidence of neurologic involvement, known as AIDS-related subacute encephalopathy, which has been correlated with the presence of HIV in the brain. In this study, two genetically distinct but related viruses were isolated from one patient from two different sources in the central nervous system: brain tissue and cerebrospinal fluid. Both viruses were found to replicate in peripheral blood lymphocytes, but only virus from brain tissue will efficiently infect macrophage/monocytes. The viruses also differ in their ability to infect a brain glioma explant culture. This infection of the brain-derived cells in vitro is generally nonproductive, and appears to be some form of persistent or latent infection. These results indicate that genetic variation of HIV in vivo may result in altered cell tropisms and possibly implicate strains of HIV with glial cell tropism in the pathogenesis of some neurologic disorders of AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Clonal selection of human immunodeficiency virus (HIV): serological differences in the envelope antigens of the cloned viruses and HIV prototypes (HTLV-III B, LAV, and ARV).

Human T-cell lymphotropic virus type III B (HTLV-III B) derived from H9/HTLV-III cells was cloned by a plaque-forming assay. Cloned viruses showed different restriction cleavage patterns, suggesting that HTLV-III B is a mixture of several viruses. Using two different neutralization assay systems, we compared the envelope antigenicity of uncloned HTLV-III B, cloned viruses, lymphadenopathy-associated virus (LAV), and acquired immune deficiency syndrome (AIDS)-associated retrovirus (ARV). A diversity of viral envelope antigens was consistently found among the strains of these AIDS-related retroviruses. These results concur with the previous finding that genomic divergence of AIDS-related viruses is located mainly in the region of the viral envelope gene. Thus, this plaque assay is useful for the clonal analysis of the virus, which is essential for comparing the envelope antigen(s) of the virus.

Antibodies, Viral↗

PubMed1987

[High-risk group--colorectal cancer].

The environmental factor, pathogenic factor, host factor and others can be assumed as high-risk factors of colon carcinoma. Histopathologically, in most cases, colon carcinoma is recognized as an adenoma-carcinoma sequence that originates based on the adenoma. In this study, in addition to the adenoma and adenomatosis (familial polyposis, Gardner syndrome, Turcot syndrome), the hamartoma (Peutz-Jeghers syndrome, juvenile polyp), inflammatory bowel diseases (ulcerative colitis, Crohn's disease, fistel ani and others) and the origin of the carcinoma were examined. The oncogenesis based on the tubular adenoma, tubulovillous adenoma, villous adenoma and genetic adenomatosis of the large intestine could be found in many cases, thereby requiring a wide range of examinations and treatments. Concerning the oncogenesis of several kinds of inflammatory bowel diseases, much attention should be paid to diseases such as ulcerative colitis, Crohn's diseases, and fistel ani extending over a period of 10 years. In addition, it is necessary to study the connection and promotion among factors of the environmental, pathogenic and host factors.

Adenomatous Polyposis Coli↗

PubMed1987

Relationship of human cord blood mononuclear cell lines, established by the HTLV-I integration, to expression of T-cell phenotypes and the T-cell receptor gene rearrangement.

The HTLV-I integrated cell lines originated from human cord blood mononuclear cells were examined for the T-cell receptor beta chain gene rearrangement in conjunction with immunological phenotype analysis. Five of seven cell lines contained the rearranged T-cell receptor beta chain gene. Interestingly, most of the rearranged lines failed to express the T cell differentiation antigens, OKT 4 and 8, though their positive expression of Leu 1 antigen indicated the commitment to the T-cell lineage. On the other hand, two cell lines retained the germ-line configuration of the beta chain gene, while phenotypical examination revealed that the two cell lines have distinct T-cell antigens. Non-rearranged cell lines have proved to be nearly monoclonal from HTLV-I integration pattern and/or surface marker clonality. Thus, the relationship between the immunological phenotypes and the T-cell receptor gene rearrangement observed in the T-cell lineage is not strict and often dissociates. A possible involvement of HTLV-I infection on the dissociation between phenotype and genotype is discussed from the viewpoint of phenotypical modulation.

Antigens, Surface↗

PubMed1986

Tumor promoter, TPA, enhances replication of HTLV-III/LAV.

The incubation of Molt-4/HTLV-III cells, human T-lymphotropic virus type III (HTLV-III)/lymphadenopathy-associated virus (LAV)-producer cell line, with more than 0.5 ng/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 2 to 4 days stimulated virus-induced cell killing which resulted in a high production of HTLV-III/LAV. TPA significantly increased the number of plaque-forming viruses released from the cultures as well as viral RNA content. Interestingly, MT-4 cells freshly infected with HTLV-III/LAV treated for 4 days with 0.125 to 2.0 ng/ml of TPA were found to retain the capacity to grow, because TPA inhibited the induction of the virus-specific antigens and cytopathic effects. In contrast to the situation in infected MT-4 cells in liquid cultures, the addition of 0.125 and 0.25 ng/ml of TPA into agarose medium induced large plaques, suggesting that TPA basically enhanced the production of the virus from one infected MT-4 cell. Taken together, the data suggest that TPA enhances the replication of HTLV/III/LAV. These assay systems are shown to be useful for analyzing the induction or suppression of a virus infection by many drugs and other factors in vitro.

Antigens, Viral↗

PubMed1986

Sensitive assay for neutralizing antibodies against AIDS-related viruses (HTLV-III/LAV).

A sensitive assay for neutralizing antibodies (NA) against AIDS-related viruses (HTLV-III and LAV) was developed, using human T-cell lymphotropic virus type-I (HTLV-I)-bearing and HTLV-III-susceptible MT-4 cells. NA to HTLV-III in 21 patients with acquired immune deficiency syndrome (AIDS), 10 individuals with AIDS-related complex (ARC), 20 healthy male homosexuals, and 10 healthy male controls were titrated. Antibodies to HTLV-III were also detected by indirect immunofluorescence (IF). The assay was sensitive up to a dilution of 1:10 000. Sera from patients with AIDS showed a geometric mean titer (GMT) of NA of 1:475, whereas much higher GMTs (1:1318 and 1:1009) were observed in patients with ARC and healthy male homosexuals, respectively. Moreover, titers of NA significantly correlated with the levels of anti-HTLV-III antibodies detected by IF.

Antibodies, Viral↗

PubMed1986

Effect of HTLV-III on the macromolecular synthesis in HTLV-I carrying cell line, MT-4.

Upon infection of human T-cell leukemia virus type I (HTLV-I)-carrying human T-cell lines such as MT-4, HTLV-III, a probable etiologic agent of acquired immune deficiency syndrome (AIDS) caused fast and strong cytopathic effects leading ultimately to the death of the cells. Such effects were preceded by the rapid induction of HTLV-III antigens. Cell lines not infected with HTLV-I could, however, be subcultured after infection with HTLV-III, although they were also positive for HTLV-III antigens. To understand this cytopathogenicity of HTLV-III in HTLV-I bearing cells, macromolecular synthesis, including DNA synthesis and total protein synthesis, and also IL-2 receptor expression were investigated kinetically. In infected MT-4 cells DNA synthesis was markedly inhibited by HTLV-III after the HTLV-III antigen synthesis became evident. This inhibition occurred before cell damage was detected in terms of viable cell-growth, but after induction of HTLV-III antigen. Puromycin, at 40 micrograms/ml, caused no toxic changes in MT-4 cells over 3 days but prevented viral antigen synthesis and virus-induced cytopathic effect. Protein synthesis and IL-2 receptor expression were also inhibited at 4 and 5 days post infection. The degree of the effects and their kinetics suggest that they are the secondary effects of cytotoxicity by HTLV-III infection.

Cell Line↗

PubMed1986

Establishment of a high production system for AIDS retroviruses with a human T-leukemic cell line Molt-4.

A cell culture system was developed for the continuous and efficient production of acquired immune deficiency syndrome (AIDS) retrovirus. After infection of a human T-cell line Molt-4 with HTLV-III and LAV the cells grow permanently and produce large amounts of virus continuously. The yields of production of virus were assessed either with reverse transcriptase activity or a newly established biological quantitation assay of active virus. The amounts of virus with this cell system were much higher than those of the H9 cell system. This procedure enabled us first to compare the two viral isolates HTLV-III and LAV directly in the same cell line. Establishment of the culture system, allowing efficient production of AIDS retroviruses, provides a useful tool for the isolation of the virus from patients with AIDS and for more basic research, such as the mechanisms of immune destruction caused by the virus leading to the occurrence of various malignancies.

Cell Line↗

PubMed1986

Quantitative evaluations of the effect of UV irradiation on the infectivity of HTLV-III (AIDS virus) with HTLV-I-carrying cell line, MT-4.

The effect of UV irradiation on HTLV-III was quantitatively studied to evaluate the dosage of UV irradiation which inactivates the virus for sterilization of blood products and for laboratory decontamination. In order to estimate the biologic activity and quantitation of the virus, induction of HTLV-III-specific antigens and inhibition of DNA synthesis in MT-4 cells infected by UV-irradiated HTLV-III were detected by indirect immunofluorescence technique and proliferation assay using [3H]thymidine uptake, respectively. Furthermore, plaque-forming assay was performed to count the infectious viral particles. Results showed that HTLV-III was completely inactivated by 5000 J/m2 UV irradiation. Cloned UV-irradiated HTLV-III (UV-1) was obtained from a plaque that was formed by 2000 J/m2 UV-irradiated virus. When MT-4 cells were infected by the clone UV-1, ballooning degeneration of cells was predominantly induced. These ballooning cells were not usually observed in MT-4 cells infected by unirradiated HTLV-III. The resistance to UV was not different between clone UV-1 and unirradiated HTLV-III.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Serological differences between human T-lymphotropic virus type-I (HTLV-I) and HTLV-III/LAV.

Sera from each of five preselected groups of patients with acquired immune deficiency syndrome (AIDS), AIDS-related complex (ARC), hemophilia, adult T-cell leukemia (ATL), and healthy controls were examined for antibodies to human T-cell leukemia (T-lymphotropic) virus type-I (HTLV-I) and HTLV-III by indirect immunofluorescence (IF) and radioimmunoprecipitation (RIP) methods. All sera from five patients with AIDS, ARC, and hemophilia reacted at titers from 1 : 512 to 1 : 5,120 with fixed H9/HTLV-III cells by IF but not with fixed MT-1 cells carrying HTLV-I. Similarly, sera from patients with AIDS, ARC, and hemophilia precipitated HTLV-III-specific polypeptides of 120K, 46K, and 24K. In contrast, sera from five patients with ATL did not react with fixed H9/HTLV-III cells, but reacted with fixed MT-1 cells. Moreover, HTLV-I-specific polypeptides of 68K, 28K, and 24K were precipitated with sera from ATL-patients but not with anti-HTLV-III-positive sera. Recently, we infected HTLV-I-carrying MT-4 cells with HTLV-III and provoked strong cytopathic effects. This system enabled testing for neutralizing antibodies to HTLV-III. Neutralizing titers to HTLV-III of five anti-HTLV-III-positive sera ranged from 1 : 720 to 1 : 9,000. In contrast, all five seronegative controls showed no or only low reactivity to HTLV-III envelope (1 : 80 and 100). However, three out of five anti-HTLV-I-positive sera exhibited weak cross-reactivities with HTLV-III. The reactivities were expressed as less than 1 : 160, except for one case (1 : 720). They were considered to be nonspecific since they were negative for HTLV-III antibodies in the radioimmunoprecipitation studies.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Differential susceptibility to the acquired immunodeficiency syndrome retrovirus in cloned cells of human leukemic T-cell line Molt-4.

Cells of human leukemic T-cell line Molt-4 which were cloned in soft agarose from individual colonies were analyzed for the cytopathic effect and viral antigen expression after human T-cell lymphotropic virus type III infection. The induction of cytopathic effect and viral antigens by the infection varied significantly among the different cell clones. These clones did not show significant differences in the amount of OKT-4 antigen, a possible surface receptor for acquired immunodeficiency syndrome virus. Moreover, the virus-producing ability and the susceptibility to the virus of each clone appeared to be separable.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Detection and isolation of an acquired immune deficiency syndrome (AIDS)-related virus (HTLV-III/LAV) from a Japanese boy with AIDS-related complex.

We attempted to isolate acquired immune deficiency syndrome (AIDS) virus from a Japanese hemophiliac with AIDS-related complex (ARC). After cocultivation of leukocytes from his peripheral blood with those of a healthy adult, reverse transcriptase activity and AIDS viral antigens were detected by immunofluorescence and radio-immunoprecipitation methods, respectively. Moreover, an electron microscopic study revealed the presence of viral particles consistent with AIDS virus. These retroviruses were further propagated. We designated the first Japanese isolate of AIDS virus as YU-1.

Acquired Immunodeficiency Syndrome↗

PubMed1985

Infection of human T-lymphotropic virus type-I (HTLV-I)-bearing MT-4 cells with HTLV-III (AIDS virus): chronological studies of early events.

Early events in the infection of the human T-lymphotropic virus type-I (HTLV-I)-positive MT-4 cell line by the acquired immune deficiency syndrome (AIDS) retrovirus HTLV-III were investigated. The virus was adsorbed completely to the cells within 60 min incubation after inoculation of the virus. Then, infected MT-4 cells started to produce the HTLV-III-specific antigens between 12 and 24 hr postinfection. Synthesis of the viral antigens consisting of 120K, 46K, 24K, and 17K polypeptides was suppressed by the treatment of the virus-infected MT-4 cells with cytosine arabinoside (Ara-C) or by the treatment of the virus with anti-HTLV-III-positive sera. The progeny of the virus released from the infected MT-4 cells was titrated by a newly developed plaque-forming assay method and reverse transcriptase activity. The maximum activity of HTLV-III (3 X 10(5) PFU/ml) was observed on Days 4 and 5 p.i. Most of the viral activities in this preparation were ascribed to HTLV-III, and not to HTLV-I. No phenotypic mixing between HTLV-III and HTLV-I was discerned, although MT-4 cells were HTLV-I-producer cell line. Thus, HTLV-III-infected MT-4 cells are thought to be useful in further study of the interaction between host cells and the virus, and appear to be a good viral source for the analysis of the virus.

Adsorption↗

PubMed1985

Selective cytotoxicity of AIDS virus infection towards HTLV-I-transformed cell lines.

Previously, we reported that cells of the human T-cell lymphotropic virus type I (HTLV-I)-transformed lines MT-2 and MT-4 were extensively killed by infection with AIDS retrovirus HTLV-III. We have investigated this phenomenon more systematically using light and electron microscopy as well as immunofluorescence. The cell lines used in the present studies included 14 of those carrying not only human HTLV-I but also related simian agents and 6 HTLV-I-negative T- and B-cell lines. The results showed that the cytocidal effects occurred in the HTLV-I-transformed cell lines exclusively and were not present in further subcultures. In these cell lines the cytotoxic response was closely correlated with the induction of HTLV-III antigens after virus infection. However, cells of 6 HTLV-I-free lines were not killed to a marked extent by HTLV-III and were passaged as continuous producers of AIDS virus. Only 2 cell lines were resistant to the cytocidal effect of HTLV-III among 14 HTLV-I carrying cell lines. They were also resistant to the replication of infected HTLV-III. This AIDS virus-specific cytotoxic effect observed in HTLV-I-transformed cell lines did not appear to be associated with gene expression of the gag and pXs region of HTLV-I genomes. This result may indicate that HTLV-III specifically interferes with some steps of HTLV-I transformation.

Acquired Immunodeficiency Syndrome↗

PubMed1985

Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay.

The human T-cell lines MT-2 and MT-4 carry the human T-cell leukemia virus type I (HTLV-I). When MT-2 and MT-4 were infected with HTLV-III, the probable etiologic agent of the acquired immune deficiency syndrome (AIDS), rapid cytopathogenic effects and cytotoxicity were observed that made it possible to titrate the biologically active virus in a plaque-forming assay. The cytopathogenic effects were preceded by the rapid induction and increase of HTLV-III antigens as revealed by immunofluorescence and immunoprecipitation. Activities of HTLV-III were neutralized by the human antibodies against the virus when immunofluorescence and plaque assays were used. Essentially the same results were obtained with the lymphadenopathy-associated virus (LAV1).

Adult↗