PubMed Health⌕ Search

Biomedical subjects

Y Koyanagi

Publications and source records attributed to Y Koyanagi.

At least 19 recordsLinked to original sources
PubMed1992

Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I-associated myelopathy.

The polymerase chain reaction (PCR) method was used to determine the presence and amount of human T lymphotropic virus type I (HTLV-I) proviral DNA in central nervous system (CNS) tissue obtained at autopsy from 6 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), 1 patient with adult T-cell leukemia (ATL) and CNS infiltration of leukemic cells, and 9 control subjects with other neurological disorders. HTLV-I pX and env but not pol DNA were detected in CNS tissue from 5 of 6 patients with HAM/TSP. The ATL samples were positive for pX, env, and pol DNA by PCR. None of the control samples was consistently positive for HTLV-I by PCR, but all showed positive bands on beta-globin PCR. Quantitative PCR combined with histological studies showed no correlation between HTLV-I proviral DNA amounts and extent of perivascular mononuclear cell infiltration in the HAM/TSP CNS. Also, the amounts of pX and probably env DNA were greater in the HAM/TSP samples than in the ATL sample, although the extent of mononuclear cell infiltration was far less in the HAM/TSP samples than in the ATL sample. Therefore, in addition to infiltrating mononuclear cells, constituent cells of the CNS may harbor the HTLV-I genome, at least in the pX and env regions, in patients with HAM/TSP.

Base Sequence↗
PubMed1992

Development of a supersensitive polymerase chain reaction method for human T lymphotropic virus type II (HTLV-II) and detection of HTLV-II proviral DNA from blood donors in Japan.

A supersensitive polymerase chain reaction procedure was developed to detect human T-lymphotropic virus type II (HTLV-II) proviral genome. Six primer pairs covering the various regions of HTLV-II were compared and selected on the basis of specificity and sensitivity. Among them, one primer pair of the pol region of HTLV-II (II pol) was able to amplify and detect even 0.1 fg of the cloned plasmid HTLV-II DNA (seven copies) by regular ethidium bromide staining on polyacrylamide gel. By using this procedure, we screened 189 HTLV-I seropositive blood donors from Yamaguchi and Fukuoka Red Cross Blood Centers, Japan. There were four positive samples detectable with the HTLV-II-specific pol primer pair, as well as with the HTLV-I tax primer pair. The amplified DNAs of two specimens were cloned and sequenced. The sequences of the HTLV-I tax region from both specimens were identical to that of HTLV-I. On the other hand, those of the HTLV-II pol region were identical to that of HTLV-II, except for one base substitution in a clone from one subject. These results indicate that dual infection of HTLV-I and HTLV-II in the same persons occurs among Japanese blood donors.

Base Sequence↗
PubMed1992

Increased production of human immunodeficiency virus (HIV) in HIV-induced syncytia formation: an efficient infection process.

Syncytia or multinucleated giant-cell formation is one of the major cytopathic effects induced by human immunodeficiency virus (HIV) infection. Cell fusion results from the strong interaction of CD4 molecules on the surface of the uninfected T cells and gp120, an external envelope glycoprotein of HIV on the infected T cells. We studied the production of HIV in fusion cells between MOLT-4 and virus-infected MOLT-4/HIV cells and found that HIV production was enhanced up to three- to fivefold, which showed a good correlation with the appearance and extent of syncytia formation. Blocking the fusion by monoclonal antibody against a binding epitope of CD4 molecule to gp120 decreased the HIV production significantly. Enhancement of HIV production was observed by more than five-fold in comparison with chronically infected cells, which were fusion free 20 hr postcocultivation. Electron microscopic observation also showed the presence of abundant HIV particles inside the fused cells and on the outer surface. AZT blocked the HIV augmentation of fused cells in coculture completely. Southern blot analysis revealed that both integrated and unintegrated HIV DNA were highly accumulated in fusion cells, as compared with fusion-free MOLT-4/HIV cells. Among unintegrated DNA, circular and linear DNA were accumulated to a similar degree. Northern blot hybridization showed that rapid enhancement of all three species of HIV-specific RNA containing genomic (9.2 kb) and subgenomic (4.3 and 1.9 kb) RNAs were found 20 hr postinfection in fusion cells. These data suggest that syncytia formation is an extremely active infection process of HIV, by which multiple rounds of reinfection might take place.

Animals↗
PubMed1992

Antibody titers to HTLV-I-p40tax protein and gag-env hybrid protein in HTLV-I-associated myelopathy/tropical spastic paraparesis: correlation with increased HTLV-I proviral DNA load.

We studied the relationship between antibody titers to recombinant HTLV-I p40tax protein and gag-env hybrid protein in serum (by an enzyme-linked immunosorbent assay) and HTLV-I proviral DNA load in peripheral blood mononuclear cells (by a quantitative polymerase chain reaction method) in 18 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), 17 HTLV-I carriers without HAM/TSP and 16 HTLV-I uninfected controls. The IgG and IgA antibody titers to either of the proteins correlated significantly with the HTLV-I pX (coding p40tax protein) and pol DNA amounts in HTLV-I infected subjects. HAM/TSP patients had significantly higher titers of IgG and IgA antibodies to the HTLV-I proteins than did the HTLV-I carriers without HAM/TSP. While the IgM antibodies to the HTLV-I proteins were found in only 6% of HTLV-I carriers without HAM/TSP, they were found in 40% of HAM/TSP patients, especially those having both a high HTLV-I proviral DNA load and high titers of the IgG and IgA antibodies. HAM/TSP patients with the IgM antibodies had a tendency to deteriorate more frequently on the Kurtzke's disability status scale and magnetic resonance imaging of the brain (leukoencephalopathy) than did those without in the two-year follow-up. Thus, the presence of IgM antibody and high titers of IgG and IgA antibodies to the HTLV-I proteins, together with the increased HTLV-I proviral DNA load, appears to distinguish HAM/TSP patients from HTLV-I carriers without HAM/TSP.

Adult↗
PubMed1992

Anti-human immunodeficiency virus activity of a novel synthetic peptide, T22 ([Tyr-5,12, Lys-7]polyphemusin II): a possible inhibitor of virus-cell fusion.

More than 40 peptides associated with tachyplesin and polyphemusin, which are highly abundant in hemocyte debris of the horseshoe crabs Tachypleus tridentatus and Limulus polyphemus, were synthesized. Among these peptides, we found that a novel compound, which was called T22 ([Tyr-5,12, Lys-7]polyphemusin II), strongly inhibited the human immunodeficiency virus type 1 (HIV-1)-induced cytopathic effect and viral antigen expression. Its 50% effective concentration was 0.008 micrograms/ml, while its 50% cytotoxic concentration was 54 micrograms/ml. The anti-HIV activity of T22 was observed with several strains of HIV-1, including zidovudine-resistant strains, and with HIV-2 within the concentration range of 0.006 to 0.071 microgram/ml. T22 efficiently inhibited giant cell formation on the cocultivation of MOLT-4/HIV and MOLT-4 cells but modestly inhibited direct HIV binding. T22 did not inhibit reverse transcriptase activity. A time-of-addition study, which involved monitoring of the appearance of proviral DNA by using the polymerase chain reaction technique, found that T22 exerted its effect on a process, most probably virus-cell fusion or uncoating, immediately after virus adsorption.

Amino Acid Sequence↗
PubMed1992

Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type 1.

Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are produced by leukocytes and play a role in immune responses. They also function in normal brain physiology as well as in pathological conditions within the central nervous system, where they are produced by brain macrophages (microglia) and brain astrocytes. In this study, we document the ability of human immunodeficiency virus type 1 (HIV-1) to induce TNF alpha and IL-1 in primary rat brain cultures. While productive infection did not occur in these cells, it was not required for cytokine induction. Using monocyte/macrophage-tropic (JRFL) and T-cell-tropic (IIIB) strains of HIV-1, we were able to induce cytokines in both microglia and astrocytes. In addition to whole virus, recombinant envelope proteins also induced these cytokines. The induction of IL-1 and TNF alpha could be blocked by a panel of antibodies recognizing epitopes in the gp120 and gp41 areas of the envelope. Soluble recombinant CD4 did not block TNF alpha and IL-1 production. If TNF alpha and IL-1 can be induced in brain tissue by HIV-1, they may contribute to some of the neurologic disorders associated with AIDS.

Animals↗
PubMed1991

Immunogenicity of human T cell leukemia virus type-I (HTLV-I) antigens for cytotoxic T lymphocytes in the rat system.

We showed previously that WKA (rat MHC, RT-1k) and DA (RT-1a) rat CTL specific for human T cell leukemia virus type-I (HTLV-I) recognized the gag and pX gene-encoded Ag. In the present study, we explored HTLV-I Ag recognized by CTL from other MHC genotype (RT-1l) rats, LEW and F344, and examined whether HTLV-I Ag expressed by recombinant vaccinia viruses (rVV) could prime WKA and LEW rats for HTLV-I-specific CTL. Upon priming in vivo and repetitive stimulation in vitro with HTLV-I+ syngeneic T cells, HTLV-I-specific CD8+ CTL were demonstrated in LEW and F344 rat spleen cell cultures. Interestingly, these CTL were directed against HTLV-I env and pX gene products. Immunization of LEW and WKA rats with the env and gag gene-expressing rVV, respectively, resulted in generation of HTLV-I-specific CD8+ CTL. However, a pX-gene expressing rVV failed to prime either rat strain. In addition, HTLV-I-specific CD8+ CTL from F1 hybrid (WKA x LEW) rats generated by immunization and restimulation with HTLV-I+ syngeneic T cells showed gag and pX Ag specificity on WKA rat cells and env and pX Ag specificity on LEW rat cells. These results suggest that immunogenicity of HTLV-I gag and env Ag in induction of HTLV-I-specific CTL varies depending on MHC, and that the pX Ag expressed by rVV is not a potent immunogen for rats.

Animals↗
PubMed1991

Increased HTLV-I proviral DNA in HTLV-I-associated myelopathy: a quantitative polymerase chain reaction study.

Using the polymerase chain reaction, we quantitated the amount of human T-lymphotropic virus type I (HTLV-I) proviral DNA in peripheral blood mononuclear cells from 18 patients with HTLV-I--associated myelopathy/tropical spastic paraparesis; 17 HTLV-I carriers without HTLV-I--associated myelopathy/tropical spastic paraparesis, with or without other autoimmune or inflammatory diseases; and 19 seronegative control subjects. The HTLV-I proviral DNA was 10- to 100-fold higher in the patients and in the HTLV-I carriers without HAM/TSP who had autoimmune or inflammatory diseases than in the carriers without autoimmune or inflammatory diseases. The patients who had had onset of myelopathy at a younger age (15 to 39 years) had an extremely high level of HTLV-I proviral DNA in the early phase, as compared with findings in those with a late onset of myelopathy (at 44 to 61 years). The large increase in HTLV-I proviral DNA in peripheral blood mononuclear cells is presumably closely related to the development of autoimmune or inflammatory processes in HTLV-I carriers, including HTLV-I--associated myelopathy/tropical spastic paraparesis.

Adult↗
PubMed1991

Evaluation of anti-human immunodeficiency virus effect of recombinant CD4-immunoglobulin in vitro: a good candidate for AIDS treatment.

CD4 molecule, a surface marker of helper T lymphocytes, interacts with gp120 of human immunodeficiency virus (HIV) with a high affinity and, hence, serves as a virus receptor. Soluble chimeric CD4-immunoglobulin (Ig) possesses anti-HIV activity due to its binding activity to gp120. Furthermore, this recombinant molecule has unique Ig-like properties representing Fc receptor-binding activity and a long half-life in vivo. In this report we have thoroughly evaluated the effect of this compound on HIV infection using different in vitro systems. Treatment with 4 micrograms/ml of recombinant CD4-Ig after infection completely blocked the HIV-specific cytopathic effect, antigen expression, and virus release in MT-4 cells, a human T cell line which is highly susceptible to HIV. Similarly, this molecule blocked the HTLV-III/B and YU-1 strains of HIV infection in peripheral blood mononuclear cells even at 1 microgram/ml. Pretreatment of the Fc receptor-positive cell line U937 with this reagent resulted not in enhancement but again in blocking of HIV infection. About 95% of HIV infection was inhibited in U937 cells when cells were treated with this compound at the time of exposure to HIV. Recombinant-CD4-Ig also completely inhibited HIV-induced syncytia formation between MOLT-4 and MOLT-4/HIV and resulting virus release at 8 and 2 micrograms/ml, respectively. Due to its stability and long half-life, this compound could be a promising therapeutic agent against HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Latent HSV-I infection in rat vestibular ganglia.

The vestibular ganglia of rats having no clinical symptoms after inoculation of HSV-I were examined by Polymerase Chain Reaction (PCR) in order to prove latent HSV-I infection. The rats were divided into two groups: one inoculated with HSV-I into the middle ear cavity (m.i. group), and the other into the peritoneal space (i.p. group). In the m.i. group, 67% of the vestibular ganglia on the inoculated side and 0% on the opposite side were positive. In the i.p. group, 60% of the vestibular ganglia on both sides were positive. These data indicate that HSV-I can establish latent infection in the vestibular ganglia. Furthermore, we assumed that reactivation of HSV-I genomes in the vestibular ganglia might lead to disorders of the vestibular system.

Animals↗
PubMed1991

[Hepatic infusion-chemotherapy of liver metastases from stomach cancer--comparative study for intraarterial group and non-intraarterial group].

Metastasis to the liver was detected in 96 out of 1,825 patients with gastric cancer treated at our department from April 1980 to March 1990, and was respectively found to be synchronous and metachronous in 63 and 33 of the 96 patients. We compared survival durations among these 96 patients according to synchronous or metachronous metastasis by dividing them into the intermittent intra-arterial chemotherapy (FAM) group (18 patients) and non-intra-arterial chemotherapy group (78 patients). In the comparison between the intra-arterial and non-intra-arterial groups, the survival duration was determined to be significantly longer in the intra-arterial group by Wilcoxon generalized test and Cox-Mantel test (p less than 0.01). Among the patients with synchronous metastasis, a significantly longer survival duration was also observed in the intra-arterial group (p less than 0.01). The direct effect of intra-arterial chemotherapy through CT was seen in 56% of the patients in the intra-arterial group. These results indicated the usefulness of FAM hepatic infusion chemotherapy for the treatment of metastasis of gastric cancer to the liver. It is expected that therapeutic results will be much more improved by selecting more effective anticancer drugs in the future.

Aged↗
PubMed1991

[Study of intermittent intra-arterial infusion chemotherapy in liver metastases from squamous cell carcinoma].

There are few reports about the methods, amounts, and kinds of dosage about intermittent intra-arterial chemotherapy of liver metastases from primal pathological type's squamous cell carcinoma. Because they are less than liver metastases from adenocarcinoma of colon or stomach. Although it is important of other factors about the operative method of primary focus and metastases of the other parts, it is possible that those cases obtained the good prognosis and protected liver failure, if those liver metastases could be controlled well. In our department from January 1987 to December 1989, 9 cases of inoperative liver metastases of squamous cell carcinoma (esophagus: 4 cases, larynx: 3 cases and cervix of uterus 2 cases) were treated of intra-arterial infusion chemotherapy of FAM (5Fu 500 mg/week, ADM 30 mg/4 weeks and MMC 4 mg/2 weeks) and CDDP methods (only CDDP 10 mg/week). Cases of esophagus carcinoma were treated with FAM method. On the CT-scan one of the cases showed the reduction rate of more than 50% and was a Progressive Response (PC), and the SCC tumor marker decreased in 2 cases. However, 2 other cases died of liver failure. Cases of larynx were treated with FAM and CDDP methods. However, on the CT-scan all of the cases showed No Change (NC) nor decrease in SCC. But thinking of prognosis FAM was better than CDDP. Cases of cervix of uterus were treated with the FAM and CDDP methods. FAM was not different than the CDDP in the prognosis and effect.

Aged↗
PubMed1991

[Clinical observations and the planning of therapy for sacrococcygeal tumors].

Amongst sacrococcygeal tumors, teratoma is seen often while other histologic types are rare. It is apparent that the less obvious intrapelvic tumors can cause obstructive symptoms and are usually diagnosed late. Twenty cases of sacrococcygeal tumor, including 14 teratomas (9 benign, 5 malignant) and 6 others (3 benign, 3 malignant) were treated at Tokyo Medical College and Shizuoka Children's Hospital over the last 23 years. The majority of the benign tumors were readily excised, but one case of benign teratoma was difficult to excise and died of bleeding. The resectability of malignant tumors was low, but aggressive multiagent chemotherapy, radiotherapy and second look operation made it possible to increase the survival. One case is alive and has been disease free for 11 years. Recently combined therapy by chemotherapy and surgery has improved the survival rate although some problems still remain.

Child, Preschool↗