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Biomedical subjects

T Kawamoto

Publications and source records attributed to T Kawamoto.

At least 343 records · Page 19Linked to original sources
PubMed1984

Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity.

Four mouse monoclonal antibodies specific for human epidermal growth factor (EGF) receptors have been prepared using EGF receptor protein from human A431 epidermoid carcinoma cells as immunogen. We have determined the effect of these antibodies on two known functions of the EGF receptor: EGF binding and tyrosine kinase. Three of these antibodies (225, 528, and 579) are inhibitors of EGF binding, whereas the fourth (455) does not compete for binding but immunoprecipitates the EGF receptor. Inhibition is of the mixed competitive and noncompetitive type. The three competing monoclonal antibodies are antagonists of EGF-stimulated tyrosine protein kinase activity assayed both in intact cells and using an exogenous peptide substrate in solubilized membranes. These immunoglobulins are partial agonists in self-phosphorylation of the EGF receptor in solubilized membranes but exhibit only antagonist activity for this reaction in intact cells. The three competing monoclonal immunoglobulins recognize receptors in variant A431 cells with the same efficiency as in parental A431 cells. Such antagonist monoclonal antibodies can be used to control the concentration of receptors which can be activated by EGF.

Animals↗
PubMed1984

Relation of epidermal growth factor receptor concentration to growth of human epidermoid carcinoma A431 cells.

The relation between the concentration of epidermal growth factor (EGF) receptor/kinase and effects of EGF on cell proliferation has been studied using variant A431 cells and antagonist anti-EGF receptor monoclonal antibodies. Clonal A431 cell variants selected for escape from the EGF-mediated growth inhibition of parental A431 cells all have reduced concentrations of EGF receptor/kinase; Harvey sarcoma virus-transformed A431 cells, which have escaped from EGF-mediated growth inhibition, also have reduced EGF receptors. Three clonal variants which have reacquired EGF-mediated growth inhibition have 2- to 4-fold more EGF receptor than their respective parent variant. A biphasic response with stimulation at low and inhibition at high concentrations of EGF was especially evident in revertants of clone 29. Three separate antagonist monoclonal anti-EGF receptor antibodies block the growth inhibitory effects of EGF and uncover EGF-mediated growth stimulation. These studies indicate that in A431 cell variants a continuum of ligand-activated EGF receptors determines proliferative responses from low concentrations of active receptors under basal conditions to intermediate concentrations causing growth stimulation to high concentrations, causing inhibition of cell proliferation.

Antibodies, Monoclonal↗
PubMed1984

Determination of sisomicin, netilmicin, astromicin and micronomicin in serum by high-performance liquid chromatography.

A high-performance liquid chromatographic method for monitoring serum levels of the aminoglycoside antibiotics sisomicin, netilmicin, astromicin, and micronomicin, using an amino acid analysis system is described. The procedure involves sample preparation with a CM-Sephadex column, and quantitation using internal standards chosen from each of the other aminoglycosides. The aminoglycosides were separated by reversed-phase ion-pair chromatography on Zorbax C8 and ODS columns, and detected by the post-column derivatization technique. The calibration curves of serum concentration for sisomicin, netilmicin, astromicin, and micronomicin were linear over the ranges 0.32-22.8 micrograms/ml, 0.17-11.6 micrograms/ml, 0.1-6.3 micrograms/ml, and 1.0-30 micrograms/ml, respectively. The coefficients of variation were 2.5, 2.8, 3.1 and 1.9%, at the serum concentrations of 1.3, 1.45, 1.58 and 2.5 micrograms/ml, respectively (n = 6). Determination by the internal standard method using another aminoglycoside gives accurate and reproducible results. This method is applicable also to other aminoglycoside antibiotics.

Aminoglycosides↗
PubMed1984

Experimental study on the pulmonary absorption and excretion of toluene.

Three exposure levels of toluene were inhaled by dogs for 1 h. Toluene concentrations in expired air, arterial blood and venous blood were repeatedly measured. Absorptions of toluene within one hour of exposure were 25, 56 and 74 mg/kg at 700, 1500 and 2000 ppm respectively (absorption ratio = 27%). The cumulative excretion one hour after exposure was 63% of the absorped material at all three exposure levels. Multiple regression analyses were performed to interconnect the independent variables.

Absorption↗
PubMed1984

[An experimental examination of extra-hepatic metabolism of trichloroethylene in dogs].

To investigate the extra-hepatic organs metabolism of trichloroethylene, the extra-hepatic circulation in dogs was established by operating on the portal vein-right femoral vein bypass and other locations. These dogs were exposed for one hour to trichloroethylene at concentrations of 700 ppm. Metabolite (trichloroethanol (F-TCE), trichloroacetic acid (TCA) and total trichloroethanol (T-TCE) changes in serum and urine were measured from the beginning of exposure until one hour after termination, and compared with previous data as control. The following results were obtained. This operation method gave a very slight invasion on dogs. About two hours after the operation, no abnormal findings were observed clinically or physiologically. This method was considered to be one of the best for study of the metabolism of chemical substances in the extra-hepatic organs of dogs. The produced ratios of F-TCE, TCA and T-TCE in extrahepatic organs were about 60, 10 and 30% exposure to trichloroethylene at 700 ppm, respectively.

Animals↗
PubMed1984

Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies.

Monoclonal antibodies (MoAbs) were raised against epidermal growth factor (EGF) receptors on a human epidermoid carcinoma cell line, A431. Administration of anti-EGF receptor MoAbs inhibited tumor formation in athymic mice by A431 cells and by another epidermal carcinoma cell line, T222. When one of the same MoAbs was used in therapy against Li-7 (a human hepatoma) and HeLa cells (a cervical carcinoma), tumor growth was not affected. The number of EGF receptors on A431 cells was about 100-fold higher than on T222, Li-7, and HeLa cells, suggesting that the number of EGF receptors may not be an important determinant in suppressing tumor growth. Three anti-EGF receptor MoAbs were used in the present studies. MoAbs 528 (immunoglobulin G2a) and 225 (immunoglobulin G1) are capable of competing with EGF for receptor binding and inhibit proliferation of A431 cells in culture. The other MoAb, 455 (immunoglobulin G1), is incapable of blocking the binding of EGF to its receptors and has no effect on the proliferation of cultured A431 cells. All three MoAbs inhibited A431 tumor growth in athymic mice, indicating that the antibody isotype and the site of binding on the EGF receptor are not the determinants of antiproliferative activity in vivo. The observation that MoAb against the receptor for EGF is cytostatic rather than cytocidal in vitro against A431 cells, yet completely prevents tumor growth in vivo, suggests that some host animal responses also may be involved in the antitumor effect. MoAbs against growth factor receptors could provide useful immunotherapeutic agents.

Animals↗
PubMed1984

[Peripheral vasodilator effect of 1,1,1-trichloroethane inhalation].

It is presumed that systemic hypotension resulting from high concentration of 1,1,1-trichloroethane (1,1,1-TCE) inhalation may be induced by functional depression of the central nervous system. However, it is still uncertain the possibilities that one of the site of action where 1,1,1-TCE acts in systemic hypotension existed in the portion without the central nervous system. The present experiment was performed to investigate the role of the peripheral vessels as a site of action in the systemic hypotension following 1,1,1-TCE inhalation. The right hindlimb of a dog anesthetized with sodium pentobarbital (25-30 mg/kg, intravenously) was amputated at the central level of the thigh bone leaving muscles and nerves. The isolated hindlimb was perfused with blood at a constant flow rate using a pump. Venous blood circulated in the isolated hindlimb was returned to the femoral vein. To measure the perfusion pressure of the isolated hindlimb, a small catheter was inserted into the artery and was connected to a pressure transducer (Nihon Kohden, MPU-0.5). In this perfusion experiment, the changes in perfusion pressure following 1,1,1-TCE inhalation are shown to be the reaction of peripheral vessels only as the site of action of 1,1,1-TCE. In other words, the effects of 1,1,1-TCE on central nervous system could be completely removed. Various concentrations of 1,1,1-TCE vapor, made by an inside circuit vaporizer, were inhaled during a period of approximately 2 min. Perfusion pressure was continuously recorded before, during and after the termination of inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1984

Cholesterol requirement of NS-1 mouse myeloma cells for growth in serum-free medium.

We have shown that NS-1 mouse myeloma cells, but not NS-1 hybridomas, required human low density lipoprotein (LDL) for survival and growth in serum-free cell culture (Kawamoto et al., 1983). Here we have further defined the lipid requirement of NS-1 cells by demonstrating that LDL could be replaced by cholesterol complexed with carrier bovine serum albumin (BSA). Cholesterol was the active component of this complex since BSA alone did not promote NS-1 survival or growth. Cholesterol was an absolute requirement of these cells, and it could not be replaced by mevalonolactone. In contrast to NS-1 cells a related mouse myeloma cell line, Sp2/0, did not require cholesterol or other lipids for growth in vitro. Finally, we propose that cholesterol-deficient medium may be an effective alternative to HAT medium for selecting NS-1 hybridomas.

Animals↗
PubMed1984

Effects of ethyl-2-(4-chlorophenyl)-5-ethoxy-4-oxazole acetate (Y-9738) on the serum lipids of patients with hyperlipidemia and/or hypo-HDL-emia.

With the view of examining the serum lipid metabolism-improving action of a new compound, ethyl-2-(4-chlorophenyl)-5-ethoxy-4-oxazole acetate (Y-9738), 900 mg was administered to 47 patients with various diseases associated with hyperlipidemia and/or hypo-HDL (high density lipoprotein)-emia for successive 16 weeks. Serum HDL-cholesterol increased significantly 4 weeks after the administration (mean 11.8%, p less than 0.01). In the patients with hypo-HDL-emia who showed the initial level of 50 mg/dl or less, the degree of increase was more remarkable (mean 16,4%, p less than 0.01), and a significant increase was noted until 12 weeks later. Further, a similar change was noted in respect to serum HDL-phospholipid. The main apoprotein of HDL, apoprotein A (I + II) began to increase significantly 4 weeks after the institution of the administration. At the end of the trial, it increased by mean 31% (p less than 0.01). Y-9738 did not exert any significant effect on serum total cholesterol, triglyceride and phospholipid, but it caused a reduction in so-called atherogenic indexes.

Adult↗