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Biomedical subjects

M Okabayashi

Publications and source records attributed to M Okabayashi.

9 recordsLinked to original sources
PubMed1993

Eradication of metastatic tumour cells from lymph nodes by local administration of anti-CD3 antibody.

The possibility of in vivo removal of metastatic tumour cells from lymph nodes by local intradermal administration of an anti-CD3 monoclonal antibody (mAb) was examined. Murine tumour cells in the lymph nodes were completely eradicated by intradermal injections of the mAb. This treatment was effective for removal of Lewis lung cancer cells from lymph nodes, but not for removal of subcutaneous tumours of this cell line. This treatment induced in vivo cytotoxicity in the regional lymph nodes against the syngeneic tumour cells. The following in vitro studies suggested that the cytotoxicity was probably mediated mainly by CD4+ T cells, with slight participation of CD8+ T cells. Normal lymph node and spleen cells showed cytotoxicity after in vitro incubation with the mAb for 2 days. Cell sorting with a fluorescein-activated cell sorter showed that CD4+ T cells developed during the incubation to lyse syngeneic tumor cells directly by themselves, macrophages not being involved in this tumour cell lysis. The lytic activity was detected in the cellular fractions, but not in the culture supernatants of these T cells. Furthermore, it was completely blocked by specific antiserum for tumour necrosis factor-alpha (TNF alpha). An immunoprecipitation study revealed that these T cells expressed TNF alpha molecules of 26 kDa, but not of 17 kDa, suggesting that tumour cell lysis was caused by membrane-integrated integrated TNF alpha molecules. These results strongly suggest that local administration of anti-CD3 antibody is a very effective and appropriate procedure for eradication of metastatic tumour cells from regional lymph nodes.

Animals↗
PubMed1993

Podofilox-induced regression of Shope papillomas may be independent of host immunity.

We tested the hypothesis that infiltrating leukocytes might contribute to papilloma destruction following podofilox treatment. New Zealand White (NZW) rabbits were inoculated with cottontail rabbit papillomavirus (CRPV) onto abraded areas of the dorsal skin. At 21 d after viral inoculation, 5.0% podofilox solution was applied to some papillomas, whereas others were used as controls. Three rabbits were sacrificed at each of three different periods after treatment initiation (1, 4, and 7 d). Four monoclonal antibodies (MoAbs), RG-16 (for B cells), L11/135 (specific for T cells), 2C4 (specific for class II antigen), and Ki67 (specific for proliferating cells), were used in an immunohistochemical study. All positive cells and total cells in the field were counted with an ocular grid. After 1 d of treatment, proliferation of papilloma cells was strongly suppressed in treated papillomas, but leukocytic infiltration was not altered. At 4 d and 7 d of treatment, there were substantial increases (about two to three times) in the numbers of B and T cells and class II-expressing leukocytes. The upper layers of the papillomas were highly necrotic and cell proliferation was absent in all layers. These data support the view that podofilox has a direct toxic effect on papilloma tissue. Leukocyte infiltration is not strongly associated with papilloma tissue and may not contribute to papilloma destruction.

Animals↗
PubMed1991

Morphometric analysis and identification of infiltrating leucocytes in regressing and progressing Shope rabbit papillomas.

Spontaneous regressions of papillomavirus lesions frequently occur in both human and animal infections. The mechanism by which this occurs is currently unknown. Mononuclear infiltrates are found in regressing human and rabbit papillomas. To assess the potential functional role of these infiltrates in regression, we have characterized and quantitated the cell types present in regressing rabbit lesions. Forty New Zealand white rabbits were inoculated with cottontail rabbit papillomavirus (CRPV) at 2 sites on the dorsal skin. All tumors on 6 rabbits markedly decreased in volume within 6 to 8 weeks of inoculation. Tumors on 4 of these 6 regressor rabbits were studied by immunohistochemistry. Regressor papillomas had conspicuous leucocytic infiltrates, most concentrated at the epithelial basement membrane, and often obliterating the basal cells of the germinal layer. Infiltrating leucocytes were also concentrated in the subjacent dermis immediately beneath the basement membrane. The infiltrates gradually lessened at increased depths in the dermis. In contrast, progressor papillomas contained fewer leucocytes, which were randomly distributed in the dermis. The phenotype of the infiltrating leucocytes was examined in 4 regressing and 12 progressing papillomas. In regressing papillomas, infiltrating leucocytes were predominantly T cells (68.0%), with relatively few B cells (7.4%). Progressing papilloma dermis contained fewer T cells and B cells than regressing papillomas. Most of the infiltrating T cells in regressing papillomas were labelled with a rabbit MHC-class-II-specific monoclonal antibody (MAb) (2C4), in contrast to only a small number in progressing papillomas. In addition to the leucocytic infiltrates, keratinocytes in regressing, but not in progressing, papillomas, frequently exhibited strong 2C4 staining. These results demonstrate that infiltration with T cells expressing rabbit class II is characteristic of regressing Shope papillomas and strengthens the assertion that cell-mediated immunity is the mechanism of Shope papilloma regression.

Animals↗
PubMed1989

Expression of human immunodeficiency virus type 1 (HIV-1) gag antigens on the surface of a cell line persistently infected with HIV-1 that highly expresses HIV-1 antigens.

MT-4 cells persistently infected with human immunodeficiency virus type 1 (HIV-1) (MT-4/HIV-1) were recently isolated (K. Ikuta, C. Morita, M. Nakai, N. Yamamoto, and S. Kato, Japan. J. Cancer Res. (Gann), 79, 418-423, 1988). Mouse hybridoma cell clones producing monoclonal antibodies (MoAbs) to HIV-1 gag p24 and p18, and pol reverse transcriptase (RT) were isolated by using this MT-4/HIV-1 cell line for the screening of MoAb production by the immunofluorescence (IF) test. By indirect IF tests of acetone-fixed cells with these MoAbs, the IF intensities in MT-4/HIV-1 cells were found to be higher than those in the other HIV-1 infected cells, such as MOLT-4/HIV-1, HL-60/HIV-1, and U937/HIV-1 cells. Cell surface expression of the HIV-1 gag p24 and p18 antigens examined by IF and radioimmune techniques with these MoAbs revealed the p24 and p18 antigens to be expressed strongly on the cell surface of MT-4/HIV-1 cells and faintly on the cell surface of MOLT-4/HIV-1 cells, respectively. However, monoclonal antibody isolated in the present study failed to detect pol RT antigen on the surface of MT-4/HIV-1 cells. These results indicate that the gag p24 and p18 antigens are expressed, at least in part, on the surface of HIV-1-infected cells.

Antibodies, Monoclonal↗
PubMed1987

Effect of a histamine H2-receptor antagonist, famotidine, on gastric secretion in healthy subjects.

The effects of 20 mg of famotidine or placebo on secretion of gastric juice and gastric acid were studied in ten healthy subjects in a randomized, crossover study. Gastric juice was aspirated and collected at hourly intervals for 24 hours after oral administration, and acid output was calculated based on gastric juice output and acid concentration. Secretion of gastric juice and acid output were lower after famotidine was administered than after placebo; over the 12-hour post-administration period, the hourly acid concentrations were significantly lower after famotidine than after placebo. During the 12 hours after famotidine or placebo, gastric juice output was 180.7 +/- 32.1 ml (mean +/- SE) in the placebo group and 64.7 +/- 9.1 ml in the famotidine group (P less than 0.01); acid concentrations were 49.3 +/- 3.8 mmol/L in the placebo group and 9.6 +/- 3.1 mmol/L in the famotidine group (P less than 0.01); acid output was 8.89 +/- 1.59 mmol in the placebo group and 0.55 +/- 0.17 mmol in the famotidine group (P less than 0.01). These results support the effectiveness of a 12 hour or possibly a 24-hour dosing interval for famotidine.

Administration, Oral↗
PubMed1978

Effects of diltiazem hydrochloride (CRD-401) on hepatic, superior mesenteric and femoral hemodynamics.

The effects of d-3-acetoxy-cis-2,3-dihydro-5-[2-(dimethylamino)ethyll-2-(p-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one hydrochloride (diltiazem hydrochloride; CRD-401) on the hepatic, superior mesenteric and femoral arteries were investigated in dogs. The results obtained were as follows: 1. At an i.v. dose of 100 microgram/kg, CRD-401 lowered the mean aortic blood pressure (-5%). It also decreased the diastolic aortic blood pressure (-11%) but did not affect the systolic aortic blood pressure. 2. The mean aortic blood pressure decreased after injection of CRD-401, but the blood flows in the hepatic, superior mesneteric and femoral arteries increased to 33%, 31% and 17%, respectively, more than did the control values and the vascular resistances of these arteries decreased by 25%, 27% and 17%, respectively. The present study obviously demonstrates that CRD-401 has vasodilating action on the hepatic, superior mesenteric and femoral arteries.

Animals↗
PubMedDate not supplied

Antitumor efficacy of two kinds of tumor vaccine modified with vaccinia virus.

We compared antitumor effectiveness of two types of tumor vaccine modified with vaccinia virus (VV). One type is UV-inactivated VV (UV-VV) -absorbed tumor cell vaccine (UV-VV TCV) produced by tumor cells that had been absorbed in vitro with UV-VV and subsequently X-irradiated with 10(4) rads. The other type is vaccinia oncolysate vaccine (VOV) from tumor cells that had been infected in vitro with live VV and subsequently sonicated. C3H/HeN mice were inoculated i.p. with UV-VV after whole body X-irradiation with 150 rads. After 3 weeks, the two kinds of vaccine were administered i.p. 3 times at weekly intervals. One week after the last injection, mice were challenged i.p. with syngeneic MH134 or X5563 viable tumor cells at different doses. The fifty percent tumor lethal doses (TLD50) of MH134 in mice treated with UV-VV TCV and VOV were 10(6.6) and 10(5.3), respectively, whereas the TLD50 of MH134 in non-treated mice was 10(0.6). The TLD50 of X5563 in mice treated with UV-VV TCV and VOV were 10(6.5) and 10(4.4), respectively, while the TLD50 of X5563 in non-treated mice was 10(0.5). These results show that UV-VV TCV is more effective than VOV. We suggest that the complete cell structure of the vaccine is more effective for enhancing tumor immunity.

Animals↗