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Biomedical subjects

Y Koyanagi

Publications and source records attributed to Y Koyanagi.

At least 145 records · Page 8Linked to original sources

[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↗

[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↗

[Developments of automated cell counter and its clinical laboratory application].

A rapid development has taken place in recent years in the field of automatic cell counting and automatic differential machine for miscellaneous blood cells. In the present paper we concisely summarized the history on the development of these machines, then reported the results obtained using STKS-VCS (automatic blood cell counter and cell analyzer based on flow system). 1. The precision of the STKS was established as follows using the coefficient of variation, 0.39-3.96% for 5 CBC parameters. WBC differentials; under 1% for neutrophils and lymphocytes, 6 to 9% for monocytes and eosinophils, approximately 18% for basophils. 2. Time profile of CBC and WBC differential data by same machine, was almost unchanged until 24 hours from blood taking using both glass and plastic vials. 3. Good correlation was obtained as for white cell differential between data from VCS and by manual ones with 4 skilled technicians according to NCCLS method. 4. Predictive value of tests applied to normal and abnormal population, high true positive and negative ratio and low false positive and negative ratio, which results helped us, to share more times to observe abnormal samples more carefully. 5. So called "flags" which predicts presence of abnormal cells (e.g. immature granulocytes, atypical lymphocytes) was useful to screen abnormal cell population in VCS system.

Blood Cell Count↗

HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain.

Cells of the mononuclear phagocyte system are the predominant cell producing HIV-1 in most tissues including the central nervous system (CNS), spinal cord, lung and skin; infection is associated with dementia, neuropathy, pneumonitis, and dermatitis respectively. Different HIV-1 isolates vary markedly in their ability to infect mononuclear phagocytes productively. Here we describe molecular clones of a CNS-derived isolate, HIV-1(JR-FL), which can replicate efficiently in mononuclear phagocytes. Analysis by polymerase chain reaction of early events after infection indicates that the early phase of viral replication before reverse transcription determines tropism. Genetic mapping of the macrophage-tropic phenotype by construction of recombinant viruses indicates that mononuclear phagocyte infectivity can be determined by a 157-amino-acid region of the gp 120 glycoprotein of HIV-1(JR-FL). Significantly, this region is upstream from the previously defined CD4-binding domain. We propose that at least one determinant for mononuclear phagocyte tropism involves target cell interactions with regions of gp120 distinct from the CD4-binding domain.

AIDS Dementia Complex↗

Mycoplasma can enhance HIV replication in vitro: a possible cofactor responsible for the progression of AIDS.

Mycoplasma membrane protein (MMP) augmented HIV production from MOLT-4 cells chronically infected by HIV. A nearly 3-fold increase of HIV p24 antigen was detected in MMP-treated culture as compared to control culture at 100 micrograms/ml. MMP also augmented HIV production in different T cells chronically infected by HIV-1 and ARV-1. Kinetic experiment showed that HIV production was maximally elevated 24 hr after exposure to MMP. Similarly, MMP also augmented HIV-induced cell fusion and virus production in coculture. Hybridization experiment revealed that this augmentation was due to enhancement of HIV transcription.

Antibodies, Monoclonal↗

Mycoplasma and AIDS.

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Acquired Immunodeficiency Syndrome↗

Recognition of human T cell leukemia virus type I (HTLV-I) gag and pX gene products by MHC-restricted cytotoxic T lymphocytes induced in rats against syngeneic HTLV-I-infected cells.

We established rat T cell lines expressing human T cell leukemia virus type I (HTLV-I) Ag from inbred strains of rats, WKA/H, DA, and F344, to study CTL response against the HTLV-I-infected cells. HTLV-I-specific Ag expressed in these rat cells were HTLV-I gag Ag, p19, p24, and p15, and pX Ag, p40tax and p27rex, but not env Ag, as determined by immunofluorescence and immunoblot assays. By immunization of rats with syngeneic HTLV-I-infected cells, CTL against syngeneic HTLV-I-infected cells and antibodies to HTLV-I Ag were generated in WKA/H and DA rats. The bulk CTL cultures from WKA/H and DA rats lysed specifically syngeneic SV40-transformed kidney cells infected with recombinant vaccinia viruses (RVV) expressing HTLV-I gag and pX Ag, but not those infected with RVV expressing HTLV-I env Ag or a control vaccinia virus. From WKA/H rat CTL cultures, four CTL clones reactive with syngeneic HTLV-I-infected cells were isolated, three of which were specific for p27rex/p21x, but the Ag recognized by the other CTL clone was not defined with any RVV used. These results indicate that HTLV-I gag and pX gene products are recognized by MHC-restricted rat CTL specific for syngeneic HTLV-I-infected cells.

Animals↗

High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients.

In the host cell, retroviral DNAs exist in three main forms: unintegrated linear, unintegrated circular, and integrated (the provirus). High levels of unintegrated forms of retroviral DNA often correlate with superinfection and accompanying cytopathic effects, as, for example, in the case of feline acquired immunodeficiency. In culture, HIV-1 infection also results in high levels of unintegrated viral DNA although direct correlations with cytopathicity have not been made. The low frequency of HIV-1-infected cells in patients has made it difficult to determine the structure of the viral DNA in fresh tissue samples from AIDS patients by standard methods such as Southern hybridization. The PCR technique however, which allows the detection of viral DNA at levels far below that possible by other hybridization methods is, in its conventional form, of limited use for quantitative analysis. To study the amount and form of HIV-1 DNA in primary tissue of AIDS patients we have therefore modified the PCR method. Our results indicate that each of the three species of viral DNA are detectable in blood and brain of AIDS patients, and that in autopsy samples from patients with HIV encephalitis there is a considerably higher proportion of unintegrated viral DNA.

AIDS Dementia Complex↗

The phorbol ester TPA strongly inhibits HIV-1-induced syncytia formation but enhances virus production: possible involvement of protein kinase C pathway.

Cocultivation of MOLT-4 and MOLT-4/HIVHTLV-IIIB cells with more than 0.01 ng/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 20 hr strikingly inhibited HIV-induced syncytia formation resulting from cell to cell infection. Interestingly, the production of HIV-specific p24 antigen in the culture fluid was significantly enhanced by TPA. TPA down-modulated the expression of CD4. CD4 is essential for syncytia formation through interaction with viral envelope protein gp120 on the surface of MOLT-4 cells. The effects of TPA on syncytia formation and on CD4 expression were specifically interfered with by nontoxic doses of blockers of protein kinase C (PKC) such as staurosporine and H7. These data suggest that (1) TPA inhibits HIV-induced syncytia formation through down-modulation of CD4 molecules on the surface of MOLT-4 cells and (2) PKC may play an important role in cell to cell as well as in cell-free infection of HIV.

Alkaloids↗

Human immunodeficiency virus causes mononuclear phagocyte dysfunction.

There is compelling clinical evidence for dysfunction of the mononuclear phagocyte system in patients with AIDS, which is believed due in part to loss of T-cell cooperativity. The direct consequences of human immunodeficiency virus infection on macrophage function are unknown. To address this question we infected normal human macrophages in vitro with a monocytotropic strain of human immunodeficiency virus and performed assays to quantify their extra- and intracellular killing ability. Human immunodeficiency virus-infected macrophages were significantly less effective than control cells in mediating antibody-dependent cell-mediated cytotoxicity against leukemic cell targets and intracellular killing of Candida pseudotropicalis. The functional defects were profound, related temporarily to active virus production by the macrophages, and could not be overcome by granulocyte-macrophage colony-stimulating factor. Treatment of macrophages with 3'-azido-3'-deoxythymidine (AZT) 6 days after infection caused a marked decrease in virus production and prevented development of the intracellular killing functional defect. The results suggest that early antiviral therapy may be useful in preventing or mitigating some virus-induced mononuclear phagocyte dysfunction.

Antibody-Dependent Cell Cytotoxicity↗

Human immunodeficiency virus type 1 T-cell tropism is determined by events prior to provirus formation.

Different strains of human immunodeficiency virus type 1 (HIV-1) vary in the ability to replicate in cells that bear the HIV-1 receptor, CD4. The mechanism responsible for these cell tropism differences is unknown. We examined different isolates of HIV-1 with regard to replication in specific tumor-derived CD4-positive T-cell lines and normal peripheral blood lymphocytes. To investigate early events in the virus life cycle at low multiplicities of infection, we used a modification of the polymerase chain reaction method. Use of a molecularly cloned primary HIV-1 isolate, HIV-1 JR-CSF, restricted for replication in T-cell lines, demonstrated that little or no viral DNA or RNA was synthesized in nonpermissive cells after infection. However, transfection of proviral DNA resulted in efficient transient virus production from these cells. Therefore, we conclude that at least one block to infection for HIV-1 strains in nonpermissive T cells occurs at a point in entry or uncoating before provirus formation.

Base Sequence↗

[A study of low-dose intermittent intra-arterial infusion chemotherapy for liver metastasis in colorectal cancer].

Since 1985 we have performed low-dose intermittent intra-arterial infusion chemotherapy using an implantable device for inoperable liver metastasis derived from colorectal cancer. We estimated the efficiency of this treatment in terms of effective rates and survival period. We classified subjects into intra-arterial infusion group and general administration group for comparison. The former group was comprised of 54 cases (37 synchronia, 17 heterochronia) treated with low-dose intermittent intra-arterial infusion (FAM ia) from July 1985 to June 1989. The latter comprised 32 cases (17 synchronia, 15 heterochronia) treated with general chemotherapy (general administration of 5-FU and MMC) for three years before December 1986. Of the 37 cases (23 synchronia, 14 heterochronia) evaluated in the intra-arterial infusion group, we recognized 9 PR cases (24.3%; including 5 synchronia, 4 heterochronia). On the other hand, we found only 1 PR case in the general administration group. The 50% survival period in the intra-arterial infusion group was 370 days (380 days synchronia, 340 days heterochronia), against 260 days (270 days synchronia, 250 days heterochronia) in the general administration group. There were no statistically significant differences between the two groups. Although it was not possible for us to obtain satisfactory results in terms of the efficiency of intermittent low-dose intra-arterial infusion treatment, we have been conducting a randomized study considering drug types, drug administration methods, and background of patients to further investigate the efficiency of arterial infusion treatment.

Antineoplastic Combined Chemotherapy Protocols↗

[An unresectable colon cancer with a diffuse metastases that turned resectable following thermotherapy with chemoimmunotherapy].

Reported is the case of a 66-year-old woman who complained of a pain in the upper abdomen. A barium enema revealed a stenosis in the transverse and sigmoid colon and since her ileus worsened, an emergency operation was performed, which revealed an unresectable transverse colon cancer with a diffuse peritoneal metastases. After closing the wound, the patient was treated with local thermotherapy of the abdomen using an RF wave in combination with chemotherapy and immunotherapy. Later, since the tumor could not be palpated and the tumor markers dissipated, a reoperation was performed, and it was found that diffuse metastases had completely disappeared from the peritoneum. Further, a histopathological study did not disclose any tumor cells. Therefore, as the cancer was remarkably reduced, a partial transverse and descending colon colectomy was performed.

Aged↗

Effect of interleukin-1 on the augmentation of human immunodeficiency virus gene expression.

Among the cytokines tested here (IL-2, IL-3, IL-4, IL-5, IL-6, granulocyte colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF), interferon-alpha (IFN-alpha), interferon-beta (IFN-beta) and interferon-gamma (IFN-gamma] only interleukin 1(IL-1) augmented HIV-long terminal repeat(LTR) directed chloramphenicol acetyl transferase(CAT) activity in protein kinase C(PKC)-independent manner. However, a stimulation by IL-1 was not as efficient as that due to tumor necrosis factor and the HIV production was not significant. IL-1 was not cytotoxic to MOLT-4/HIV cells.

Alkaloids↗

Interleukin-1 and tumor necrosis factor alpha can be induced from mononuclear phagocytes by human immunodeficiency virus type 1 binding to the CD4 receptor.

Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are important in normal immune processes. In this study, we demonstrate that human immunodeficiency virus type 1 (HIV-1) virions induce normal peripheral blood mononuclear phagocytes to produce both IL-1 and TNF within a few hours after their exposure to virus. The induction of these cytokines by HIV-1 does not require a productive infection. Blocking studies with soluble CD4 indicate that the effect is mediated through the CD4 molecule. In addition, the treatment of mononuclear phagocytes with OKT4A monoclonal antibody mimics the effects of HIV-1. Thus, these results indicate that induction of IL-1 and TNF alpha can occur via signals mediated through the CD4 molecule on mononuclear phagocytes. TNF has been shown by other investigators to induce HIV-1 expression. Therefore, TNF alpha may play a role in autocrine and paracrine regulation of HIV-1 expression. In addition, the induction of IL-1 and TNF by HIV-1 may also contribute to some of the neurologic and physiologic disorders associated with acquired immunodeficiency syndrome.

Antibodies, Monoclonal↗

[Effect of diglyceride on phospholipase A2 activities in plasma membrane of guinea pig peritoneal macrophases].

The AA release from phospholipids is believed to be controlled by the activation of phospholipase A2 which are probably localized in the plasma membranes. And the considerable interest has been focused on the study of cells of the immune system including macrophages which metabolize arachidonic acid (AA) to prostaglandins, thromboxanes and leukotriens. Recently, it has been reported that phosphatidylinositol (PI) turnover plays an important role in the response to external stimuli in these cells. PI turnover has been accepted as being initiated by the hydrolysis of PI which is catalyzed by the phospholipase C and produced AA. Recently, we demonstrated that PI-specific phospholipase A2 in macrophage plasma membrane directly acted for AA release from PI. On the other hand, diglyceride, which is produced from PI by phospholipase C activation, is known to regulate the several cell functions with a protein kinase C activation. In this report, we examined the effect of diglyceride on phospholipase A2 activities in macrophage plasma membrane. PI-phospholipase A2 and PC-phospholipase A2 activities were stimulated by the addition of diglyceride. In contrast, PE-phospholipase A2 was not affected by diglyceride addition. The results suggested that phospholipase A2 activation was occurred with coupling the diglyceride production via the phospholipase C pathway.

Arachidonic Acid↗

[Liver transplantation for biliary atresia with special reference to the Japanese children who received liver transplantation in foreign countries].

Seven cases out of 8 Japanese children who received orthotopic liver transplantation (OLT) in foreign countries because of biliary atresia as of Oct 1988 are reported. Their clinical courses after OLT have been good. Despite being satisfied with the results, their parents and family feel anxiety such as long term postoperative care and side effects of immunosuppressive therapy. Cost and the handling of rejection or retransplantation were pointed out as the greatest problems related to receiving OLT in foreign countries.

Biliary Atresia↗