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Biomedical subjects

T Tokunaga

Publications and source records attributed to T Tokunaga.

At least 217 records · Page 12Linked to original sources
PubMed1987

Restoration of lipopolysaccharide-mediated cytotoxic macrophage induction in C3H/HeJ mice by interferon-gamma or a calcium ionophore.

Proteose peptone-induced peritoneal exudate macrophages (PEM) from C3H/HeJ mice do not respond to lipopolysaccharide (LPS) in vitro in terms of activation for tumor cytotoxicity. This unresponsiveness of PEM was overcome by addition of culture supernatant of normal mouse spleen cells stimulated with insoluble concanavalin A. The supernatant component responsible for the restoration of PEM sensitivity to LPS was indicated to be interferon (IFN)-gamma, because pretreatment of the supernatant with anti-mouse IFN-gamma antiserum, but not with anti-IFN-(alpha + beta) antiserum, abolished the supernatant activity and because recombinant murine IFN-gamma (rIFN-gamma) could replace the supernatant effect. Not only the LPS activation of tumor cytotoxicity of PEM but also the sensitivity of PEM to the lethal toxicity of LPS was restored by rIFN-gamma. IFN-gamma action in restoring the LPS responsiveness of PEM was mimicked by a calcium ionophore, A23187, but not by phorbol 12-myristate 13-acetate. These results suggest that IFN-gamma can restore LPS responsiveness of PEM from C3H/HeJ mice and that elevation of the intracellular calcium level is involved in the action of IFN-gamma.

Animals↗
PubMed1987

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↗
PubMed1987

[Present status of studies on the application of immunology to the diagnosis and therapy of cancer, with emphasis on monoclonal antibodies and cytokines].

This paper describes the present state of research on application of immunology for cancer diagnosis and therapy, especially with emphasis on the recent progress of monoclonal antibody and recombinant cytokines technologies. In the history of immuno-diagnosis and- therapy of cancer, a new era has been coming because of the progress of these technologies, in addition to an increase of our knowledges on host-defense mechanisms against cancer and development of new types of instruments and chemical synthesis technology. A number of approaches of cancer diagnosis and therapy with monoclonal antibodies and cytokines in Japan were introduced in this paper, and problems of these trials to be solved in the future were discussed. Together with almost established surgical treatment, chemotherapy and physicotherapy, including radiation and hyperthermia, biotherapy, including immunotherapy and therapy with hormones and various biological response modifiers (BRM) are required for the purpose of complete cure of cancer. Further energetic and systematic efforts should be made in the future.

Antibodies, Monoclonal↗
PubMed1987

[The dumbbell shaped vertebral hemangioma developed in the pleural cavity and spinal canal].

A 44-year-old male patient visited our clinic complaining of back pain since January, 1984 and feeling of weakness at the lower extremities, sensory and vesicorectal disturbance since March of the same year. Hypesthesia and hypalgesia were observed at Th10 or below. The chest X-ray findings revealed an egg-sized tumor mass at the level of Th8. Metrizamide CT also demonstrated thoracic epidural mass. The characteristic findings of hemangioma showing delayed appearance of the tumor stain were also observed by angiography. The tumor was then confirmed as dumbbell-shaped hemangioma growing in the pleural cavity and the spinal canal. At the first surgical operation, total resection of the tumor in the spinal canal was performed by the postero-lateral approach. Although the second surgical intervention of total removal of the tumor in the pleural cavity had also been scheduled, the surgery was postponed because the patient had to return to work. The 2-year follow-up study revealed no recurrence of the tumor. And the tumor was found slightly diminished on chest X-ray. At present, the patient is still under observation. In this report, the authors discuss the therapeutic methods for thoracovertebral hemangioma including our case and reviewed in the literature related to this type of tumor.

Adult↗
PubMed1987

[Follow-up study of inaccessible giant aneurysms of the intracranial internal carotid artery].

Inaccessible giant aneurysms of the internal carotid artery had been treated with various methods. But these results are not always satisfactory. To determine the optimal treatment for these aneurysms, long-term follow-up study was carried out in 8 patients. They included 7 females and one male with ages ranging from 18 to 72 years. The aneurysms arose at the cavernous portion in 6 patients, at bifurcation of the posterior communicating artery and the ophthalmic artery in 2 patients. All but 2 patients had multiple cranial nerve palsies before admission. Those patients younger than 60 years had the ligation of the internal or common carotid arteries with or without EC-IC bypass. The others had conservative treatments including repeated Matas test. Follow-up period was 17 to 112 months after discharge. Follow-up results showed gradual decrease of the size of the aneurysms on CT scan and improvement of signs in all 3 operated cases. But only one aged patient who had repeated Matas maneuver had spontaneous improvement of her signs. There was no improvements in the others with conservative treatment. From the results of the present study, we would like to recommend carotid ligation with EC-IC bypass for the patients younger than 60 years after preoperative balloon occlusion test. When the patients were intolerable in temporary balloon occlusion of the internal carotid artery, detachable balloon embolization or electrothrombosis with copper wire also will be the treatment of choice. In the aged patients with high surgical risk, repeated balloon occlusion test or Matas test seems to be effective to promote intra-aneurysmal thrombosis.

Adult↗
PubMed1987

Pharmacodynamic effects of the sleep inducer zopiclone.

Pharmacodynamic effects of [6-(5-chloro-2-pyridyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin -5- yl]-4-methyl-1-piperazine-carboxylate (zopiclone, RP-27267), chemically unrelated to benzodiazepines and a potential new sleep inducer, on the peripheral system were investigated in several species of animals. The drug was dissolved in the vehicle of 0.01 mol/l HCl solution for intravenous administration or for addition to the bath medium and was suspended in 0.25% carboxymethylcellulose solution for oral administration. In unanesthetized rabbits, zopiclone, 0.5 mg/kg i.v., exerted no action and at 1 mg/kg slightly decreased respiration and heart rate without affecting blood pressure and ECG. Zopiclone at 10(-6) g/ml had no action in the isolated guinea-pig atria but at 10(-5) g/ml it produced a gradual and slight decrease in heart rate without affecting the contraction. In the isolated small intestine of rabbits and guinea-pigs, zopiclone at 10(-6) g/ml had no action but produced a slight inhibition in a dose of 10(-5) g/ml. Zopiclone, 10(-5) g/ml, did not affect the stimulatory effects of acetylcholine, serotonin, histamine and barium in the isolated guinea-pig intestine. Zopiclone, 1, 5 and 10 mg/kg i.v., exerted no action on rabbit intestinal movement in vivo. Zopiclone, 5, 10, 20 and 50 mg/kg p.o., had no effect on the propulsive motility of the mouse intestine. Zopiclone, 10(-5) g/ml, did not affect contractile movement of the uterus isolated from rabbits and did not influence the contractile response to epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

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↗
PubMed1986

I-J-positive cloned macrophages as accessory cells for the induction of suppressor T cells in vitro.

I-A+/I-J+ cloned macrophages, SL-1, played the role of APC in the in vitro induction of Ts against DTH to BCG. By treating SL-1 cells with various antibodies, it was shown that I-J antigens on SL-1 cells are essential for Ts induction, but not for the effector cell induction for DTH. Ia-negative cloned macrophages, SL-4, did not show any APC activity either in suppressor or effector cell induction. The precursors of the Ts were also I-J-positive, and I-J restriction resided between T cells and macrophages in the Ts induction. Thus, it is suggested that the pre-Ts recognizes the antigenic determinants of BCG presented on the APC in association with the I-J antigen and differentiates into the Ts. This pathway seems analogous to that of helper or effector T induction, where the antigenic determinant is recognized by a T cell in association with the I-A antigen on APC.

Animals↗
PubMed1986

Cell-cell interaction responsible for the induction of first order suppressor T cells in hapten-specific contact sensitivity reactions.

C3H/He mice were found to be low responders in the contact sensitivity response to ABA. Intravenous injection of ABA-coupled syngeneic spleen cells induced hapten-specific Ts in C3H/He mice. These cells were Ts1 because they acted on the inductive phase of the contact sensitivity. They could suppress the contact sensitivity in H-2-compatible CBA mice which were known to be high responders to ABA. Using in vivo and in vitro systems for the induction of Ts, it was shown that I-A-I-J+Thy-1- adherent cells were necessary as APC for the induction of Ts1.

Animals↗
PubMed1986

Inquiries into the structure-function relationship of ribonuclease T1 using chemically synthesized coding sequences.

The genes for ribonuclease T1 and its site-specific mutants were chemically synthesized and introduced to Escherichia coli. All enzymes were fusion products produced by joining the synthetic gene at specific restriction sites to the synthetic gene for human growth hormone in a plasmid containing the E. coli trp promoter. The fusion protein from this plasmid contained 66% of the amino-terminal sequences of the human growth hormone, which were recognizable immunologically. RNase T1 or its mutants were cleaved from the fusion protein with cyanogen bromide. The synthetic RNase T1 endowed with the revised wild-type triad Gly-Ser-Pro, residues 71-73, was fully functional, readily hydrolyzing pGpC bonds, whereas a mutant enzyme having the originally reported, erroneous triad Pro-Gly-Ser was totally inactive. Various amino acid substitutions were also introduced to the guanosine recognition region comprised of residues 42-45, Tyr-Asn-Asn-Tyr. Substitution of either of the tyrosine residues noted above with phenylalanine had no dramatic effect on the enzyme's function. Replacement of asparagine-43 with arginine or alanine also caused only a small change in the hydrolyzing activity--a mutant enzyme maintained greater than 50% of the wild-type activity. In sharp contrast, when aspartic acid or alanine was substituted for asparagine-44, the activity was dramatically reduced to a few percent of the wild-type activity.

Amino Acid Sequence↗
PubMed1986

The effect of calcium antagonists on the activation of guinea pig neutrophils.

The role of calcium ions in the activation of guinea pig neutrophil functions was examined by evaluating the effects of calcium antagonists. The data presented here show that calcium antagonists inhibit the activation of guinea pig neutrophil functions elicited by N-formyl-methionyl-leucyl-phenylalanine (FMLP) such as chemotaxis, superoxide anion generation and granule enzyme release in a concentration-dependent manner. The concentrations of calcium antagonists demonstrating the inhibition of neutrophil functions may be somewhat different for each function and higher than that of smooth muscle cells. Calcium ionophore A23187 (A23187) caused superoxide anion generation and granule enzyme release of the neutrophils. A23187 also potentiated the FMLP-induced superoxide anion generation and granule enzyme release of the neutrophils. On the contrary, A23187 neither elicited neutrophil chemotaxis nor affected FMLP-induced neutrophil chemotaxis. These results indicate the possibility that the inhibitory effect of calcium antagonists on the activation of neutrophil functions is probably not simply mediated by inhibition of calcium uptake but also by inhibition of a calcium-dependent intracellular target.

Acetylglucosaminidase↗
PubMed1986

Influence of chronic intake of new sweetener fructooligosaccharide (Neosugar) on growth and gastrointestinal function of the rat.

The influence of the chronic intake of a newly developed sweetener named "Neosugar" (fructooligosaccharide) on body weight gain, organ weight, serum lipids, fecal excretion and intestinal function was investigated in rats. The following results were obtained. Body weight gain was diminished more severely in rats fed on 20% Neosugar diet than in rats fed on 10% Neosugar diet. The wet weights of cecum and colon were greatly increased by Neosugar feeding. Fecal wet weight was significantly increased and gastrointestinal transit time was shortened by Neosugar feeding compared with those of the control group. Serum triacylglycerol levels were significantly lower in rats fed Neosugar, whereas serum cholesterol levels were similar to those of the control group. Fecal excretions of neutral sterol and volatile fatty acids were significantly increased by Neosugar feeding. These results were quite similar, with the exception of diarrhea to those obtained using a dietary fiber such as glucomannan. Therefore, Neosugar with a pleasant-tasting sweetness appears to be an unavailable oligosaccharide with a dietary-fiber-like action.

Animals↗
PubMed1986

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↗