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Biomedical subjects

T Kataoka

Publications and source records attributed to T Kataoka.

At least 217 records · Page 12Linked to original sources

New monoclonal antibodies specific for the guinea pig line 10 hepatocarcinoma.

Monoclonal antibodies reactive to line 10 (L10) hepatocarcinoma cells, but not to L2C leukemia cells, of strain 2 guinea pig were produced and characterized. Complement-mediated cytolysis assay and quantitative absorption analysis revealed that one of the monoclonal antibodies, 3C4 antibody (IgG2a), was highly specific for L10. Neither normal guinea pig tissues including adult and fetal liver, nor other hepatomas of strain 2 guinea pig, line 1 (L1) and Hepatoma III, were reactive with the 3C4 antibody. Another antibody, 2E4 (IgM), was reactive to the liver, kidney and spleen cells but not to the thymocytes, lymph node cells, brain and red blood cells of the guinea pig. The 2E4 antibody reacted to Hepatoma III but not to L1 cells. Therefore, 3C4 antibody is specific to a tumor-associated antigen of L10 hepatoma, and 2E4 antibody is cross-reactive with a certain differentiation antigen of normal tissues. The 3C4 antibody showed antibody-dependent cytotoxicity. Since 3C4 antibody was different in the isotype and the antigen recognized from a monoclonal antibody (D3) which was reported from the NIH in the USA, 3C4 is a new monoclonal antibody reactive with L10 hepatocarcinoma.

Animals↗

[Prostaglandin E2 and interleukin-1-producing activity of plastic-adherent cells from cancer patients as a result of modification by BRM therapy].

It is crucial to define the immunological characteristics of peripheral blood mononuclear cells in order to clarify the physiological state of cancer patients. In this study, we examined prostaglandin E2 (PGE2) and interleukin-1 (IL-1) production by plastic-adherent cells stimulated by lipopolysaccharide (LPS). The secretion of PGE2 and IL-1 into media depended on the dose of LPS. Although the addition of silica resulted in suppression of LPS-induced PGE2 production, it caused augmentation of IL-1 production. The effect of BRM therapy on IL-1 production was evaluated in five cancer patients. The results demonstrated that BRM therapy increased the levels of IL-1 at the late assessment point for 3 patients and their quality of life was improved. These findings suggest that production of IL-1 may be used as a monitor for the effectiveness of biotherapy. The association of PGE2 production with host antitumor response was evaluated in IFN-gamma therapy. The results showed that the PGE2 production ratio increased early in the therapy period and declined gradually, whereas the expression of HLA-DR antigen on monocytes and the level of IL-1 increased during the treatment. The exact mechanism by which BRM activates monocytes is unknown. It is possible that a distinct subpopulation of monocytes is responsible for this effect.

Biological Products↗

Rapid detection of leukemia cells by use of a complement-mediated cytolytic reaction and an imaging sensor system.

We describe a system for detection of leukemia cells involving complement-mediated cytotoxic reaction and an image processing system, consisting of a charge-coupled-device image sensor, an image memory board, a personal computer, and a phase-contrast microscope. Then added to a cell suspension, monoclonal antibody specific to the fetal thymus antigen-1 of the mouse leukemia GRSL cell produced cytolysis of only GRSL cells. This cytolysis decreased the brightness of the cells observed by phase-contrast microscopy. The remaining brightness was subtracted from that of the phase-contrast image of the cells before cytolysis, which had been converted to a digital signal and stored in computer memory. Measurement time is 2 s. The time course for complete GRSL cytolysis, as measured with this system, is 12 min; overall measurement time, including reaction time, is approximately 15 min. GRSL cells in a suspension of mixed cells were determined specifically by the system.

Cell Count↗

The Lyt phenotype of the T cells responsible for in vivo tumor rejection in syngeneic mice.

Spleen cells of BALB/c mice hyperimmunized with a transplantable methylcholanthrene-induced sarcoma Meth A (Meth A-Im-SPL) inhibited the growth of Meth A tumor in vivo in a tumor neutralizing test. Meth A-Im-SPL did not neutralize another antigenically distinct sarcoma, Meth 1, indicating that the antitumor activity is tumor specific. Lyt-1+2- cells of Meth A-Im-SPL (Im-Lyt-1+2-) were the effectors since in vitro treatment of Meth A-Im-SPL with anti-Thy 1.2 or anti-Lyt 1.2 antibody plus complement completely abrogated their neutralizing activity, whereas treatment with anti-Lyt 2.2 plus complement did not. To further confirm the effector activity of Im-Lyt-1+2- cells, T cell subpopulations were separated from Meth A-Im-SPL by the panning method. The purified Im-Lyt-1+2-, but not Im-Lyt-1+2+ cells neutralized the tumor in athymic nu/nu mice as efficiently as in +/+ mice, suggesting that the donor Im-Lyt-1+2- cells but not recipient T cells were primarily responsible for neutralizing the tumor. The present study, however, did not exclude the possible contribution of recipient T cells to the tumor neutralization and this is open to further investigation.

Animals↗

Antitumor, antiviral and natural killer-inducing activities of human recombinant interferon-alpha in the guinea pig.

It was found that human recombinant interferon-alpha (Hu rIFN-alpha) was biologically active in the guinea pig. Namely, intratumor injection of either Hu rIFN-alpha A or A/D regressed tumors and prevented metastasis of guinea-pig line 10 tumor. These rIFNs augmented splenic natural killer activity of the guinea pig and reduced the cytopathic effect of virus on guinea-pig cells. Hu IFN-gamma showed no such activity.

Animals↗

Mitomycin C-augmented production of I-A antigen-positive macrophages in tumor vaccine-primed mice.

Intraperitoneal inoculation of L1210 murine leukemia cell vaccine increased I-Ad antigen-positive and -negative macrophages in the peritoneal cavity of histocompatible mice. Mitomycin C, a poor producer of I-Ad antigen-positive macrophages, selectively augmented the production of I-Ad antigen-positive macrophages in L1210 vaccine-primed mice, since it did not augment the production of non-macrophage cells. Since our previous study showed that the priming of mice with L1210 vaccine and mitomycin C induced augmented antitumor response, we tested the feasibility of the association of mitomycin C-augmented I-Ad antigen-positive macrophages with the augmented antitumor response. Prostaglandin E2 suppressed the antitumor response in L1210 vaccine- and mitomycin C-primed mice and, consistent with this, it inhibited the production of I-Ad antigen-positive macrophages, although it inhibited the production of non-macrophage cells as well. This hypothesis was further tested by the use of silica. When L1210 vaccine- and mitomycin C-primed mice were further given silica on the day of and one day after live L1210 inoculation, their antitumor response was strongly suppressed, while a kinetic analysis of the cellularity of peritoneal cells showed that administration of silica resulted in a decrease of I-Ad antigen-positive macrophages, but not I-Ad antigen-negative macrophages or non-macrophage cells in these mice. These results strongly suggest, though they do not prove, the association of mitomycin C-augmented production of I-Ad antigen-positive macrophages with the antitumor response in L1210 vaccine- and mitomycin C-primed mice.

Animals↗

[Diagnosis of malignant thyroid tumor using high-frequency ultrasonography with piezoelectric transducer, soft X-rays and aspiration biopsy cytology].

Diagnosis of thyroid cancer has been based mainly on palpation and also soft X-rays because of its calcification. As the gland itself is very small and Aspiration Biopsy Cytology (ABC) has had a high level of diagnostic accuracy the clinical significance of ultrasonography did not become apparent for a long time. However, recently it has become possible to carry out detailed study and to detect suspect histological structures, following the remarkable progress which has been made in ultrasonography, using a high-frequency piezoelectric transducer. A single mechanical arch scanner, with a piezoelectric 7.5-MHz transducer (SAL-25A Toshiba Corp.) was employed for examination using the water bath method. The rates of correct diagnosis for each of the above methods among 847 nodular goiters including 184 malignant tumors which were microscopically examined were shown to be: ultrasonography 89.7%, soft X-rays 66.9% and ABC 86.4%. Ultrasonography was capable to revealing a few cases which could not be shown by ABC or soft X-rays. Using these three methods jointly, there was 1 false positive and no false negative cases. This study revealed that combined diagnosis with ultrasonography using a high-frequency piezoelectric transducer improved the accuracy of examination of malignant thyroid tumors.

Biopsy, Needle↗

[Elimination of suppressor macrophages in tumor-bearing mice by 6-mercaptopurine and its therapeutic contribution].

6-Mercaptopurine inhibited suppressor macrophages and induced antitumor monocytes in L1210-bearing mice. Although these antitumor monocytes did not neutralize L1210, they augmented the antitumor response in L1210 vaccine-primed recipient mice against a subsequent inoculation of live L1210. These results led to the trial of a novel immunochemotherapy regimen in which L1210 vaccine and 6-mercaptopurine in combination produced a synergistic therapeutic effect. In contrast, cyclophosphamide did not inhibit suppressor macrophages, nor did it induce antitumor monocytes in L1210-bearing mice. Consequently, the combination of L1210 vaccine and cyclophosphamide did not produce any further improvement in therapy. These results showed that modulation of macrophages and monocytes was associated with immunotherapeutic effect.

Animals↗

Non-cytotoxic activity of pyran copolymer-induced macrophages associated with potentiation of tumour vaccine in recipient mice.

Mice inoculated with both L1210 murine tumour vaccine and pyran copolymer were more resistant to L1210 than those inoculated with either of these agents alone. Rabbit anti-mouse thymocyte globulin and silica reduced the augmented resistance of these mice, suggesting the involvement of activated anti-tumour T cells and macrophages in the augmented resistance. We studied the activation of these two cells separately and examined the possible contribution of pyran copolymer-induced peritoneal cells to the augmented resistance to an inoculation of live tumour. Pyran copolymer-induced peritoneal cells endowed the tumour vaccine-primed mice, but not unprimed mice, with resistance to implanted L1210 and, among those peritoneal cell populations, macrophages but not T cells were responsible for this effect since the activity was associated with a cell population which was adherent to nylon wool columns, sensitive to silica and insensitive to anti-Thy 1.2 antibody plus complement. The pyran copolymer-induced peritoneal cells had very little antiproliferative activity when tested against L1210 in vitro and mice inoculated with these peritoneal cells did not survive a challenge of live L1210 cells much longer (less than 1 day) than L1210 inoculated control mice. Furthermore, the survival of L1210 vaccine-primed mice inoculated with one-tenth the amount of live L1210 (10(2)) was still much shorter than that of mice primed with L1210 vaccine plus pyran copolymer and challenged with ten times as many (10(3)) live L1210 cells. Therefore, direct tumoricidal activity was probably not a major factor in the in vivo immunological augmenting activity of the pyran copolymer-induced macrophages.

Animals↗

The antitumor effects of human lymphoblastoid interferon on human renal cell carcinoma in athymic nude mice.

The antitumor effects of human lymphoblastoid interferon (HLBI) on human renal cell carcinomas transplanted in nude mice, i.e., KU-2 and RCC-1, were investigated and compared with those on other human tumors, viz. HeLa (cervical carcinoma), KB (nasopharyngeal carcinoma), H.Ep#2 (laryngeal carcinoma), and MX-1 (breast cancer). A pharmacokinetic study on HLBI was also carried out in non-tumor-bearing nude mice. HLBI therapy was performed with a dose of 10(5) IU/mouse by daily SC or IT (intratumoral) injection for 2-4 weeks. Two renal cell carcinomas, KU-2 and RCC-1, proved to be highly sensitive to HLBI. The growth of these tumors was inhibited not only by IT but also by SC injection of HLBI. In contrast, HLBI exerted only a slight effect or none at all on the other human tumors, namely, MX-1, KB, H.Ep#2, and HeLa, even when given by IT injection. The data show that the antitumor effects of HLBI depend on the types of human tumors and may be relevant to the clinical observation that renal tumors are sensitive to HLBI. The serum HLBI reached a peak level of 4,390 U/ml 1 h after a single SC injection at a dose of 10(5) IU/mouse and declined with a half-life of 4 h to 128 U/ml 24 h later. This time-course was not affected by 10 consecutive daily injections of HLBI. In nude mice, the consecutive administration of HLBI at this dose level appears to result in neither accumulation nor rapid clearance due to antibody formation. From this range of serum HLBI levels and its in vitro anticellular activity, the in vivo antitumor effects of HLBI in nude mice seemed to depend on its direct anticellular action.

Animals↗

Diagnosis of breast lesions by aspiration biopsy cytology.

From November 1981 to the end of August 1984, 456 patients with breast lesions underwent aspiration biopsy cytology (A.B.C.). This study includes 109 for whom the diagnosis was histologically confirmed at surgical biopsy. Seventy-five lesions were histologically proven to be malignant and 34 were benign. The accuracy of diagnoses with A.B.C. was; true positive 86.7 per cent (65/75) of the time, true negative 82.6 per cent (28/34) of the time, false negative 5.3 per cent (4/75) of the time and false positive 5.7 per cent (2/34) of the time. Unsatisfactory or inadequate aspirated tissue made A.B.C. diagnosis difficult in 5.5 per cent (6/109) of the cases. Three out of 7 with malignant tumors, who were wrongly diagnosed as benign by A.B.C., had tumors with a diameter of 1.0 cm or less. Two benign cases which were falsely diagnosed as malignant also had small tumors about 1.0 cm in diameter. Although A.B.C. is more reliable than other conventional supplementary diagnostic techniques (mammography, ultrasonography, etc.), it is important to carefully follow clinically questionable cases which appear negative, using A.B.C..

Adult↗

DNA sequence and characterization of the S. cerevisiae gene encoding adenylate cyclase.

We have cloned CYR1, the S. cerevisiae gene encoding adenylate cyclase. The DNA sequence of CYR1 can encode a protein of 2026 amino acids. This protein would contain a central region comprised of over twenty copies of a 23 amino acid repeating unit with remarkable homology to a 24 amino acid tandem repeating unit of a trace human serum glycoprotein. Gene disruption and biochemical experiments indicate that the catalytic domain of adenylate cyclase resides in the carboxyl terminal 400 amino acids. Elevated expression of adenylate cyclase suppresses the lethality that otherwise results from loss of RAS gene function in yeast. Yeast adenylate cyclase, made in E. coli, cannot be activated by added RAS protein.

Adenosine Triphosphatases↗

Functional homology of mammalian and yeast RAS genes.

Yeast spores lacking endogenous RAS genes will not germinate. If such spores contain chimeric mammalian/yeast RAS genes or even the mammalian H-ras gene under the control of the galactose-inducible GAL10 promoter, they will germinate in the presence of galactose and produce viable haploid progeny dependent on galactose for continued growth and viability. These results indicate that the biochemical function of RAS proteins is essential for vegetative haploid yeast and that this function has been conserved in evolution since the progenitors of yeast and mammals diverged.

Animals↗