Search PubMed⌕ Search

Biomedical subjects

T Tokunaga

Publications and source records attributed to T Tokunaga.

At least 199 records · Page 11Linked to original sources
PubMed1988

Gamma-aminobutyric acid and taurine antagonize the central effects of angiotensin II and renin on the intake of water and salt, and on blood pressure in rats.

Antagonism by neuro-amino acids of the central effects of angiotensin II and renin in rats was investigated. Angiotensin II (100 ng), injected into the preoptic area, stimulated the intake of water but not salt, to a lesser extent and with a shorter duration as compared with that induced by renin (5 mU), injected into the preoptic area. This angiotensin II-induced intake of water was markedly inhibited by [Sar1, Ile8]-angiotensin II, an angiotensin II receptor antagonist, but not by captopril, an angiotensin-converting enzyme inhibitor, previously administered through the same cannula. The angiotensin II-induced intake of water was also inhibited in a dose-dependent manner by gamma-aminobutyric acid (GABA) (50-100 micrograms), muscimol, a GABA agonist, (100-200 ng), taurine (100-200 micrograms) and hypotaurine (100-200 micrograms), administered into the cerebroventricle and by GABA (5-10 micrograms), muscimol (10-20 ng) and taurine (10-20 micrograms) injected into the preoptic area in smaller doses. Renin (5 mU), injected into the preoptic area, elicited a marked increase in the intake of water and salt, which lasted for about 3 days. The effect of renin was inhibited by [Sar1, Ile8]-angiotensin II (10 micrograms) and was eliminated by captopril (25 micrograms) injected into the preoptic area. This effect of renin was not influenced by the peripheral administration of captopril. The effect of renin was also inhibited by GABA, muscimol or taurine injected into the cerebroventricle, in larger doses, or into the preoptic area in smaller doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1988

Induction of calcium influx in immature T lymphocytes by anti-FT-1 monoclonal antibody.

The functional role of FT-1 antigen was investigated by measuring changes in intracellular [Ca2+]i after the addition of anti-FT-1 monoclonal antibody to murine T leukemic cells and embryonic thymocytes. Anti-FT-1 induced a rapid and sustained increase in cytosolic free [Ca2+]i and this effect was completely blocked by EGTA and La3+. These results suggest that FT-1 molecule is functionally associated with a plasma membrane calcium ion channel in embryonic thymocytes.

Animals↗
PubMed1988

A synthetic adjuvant effective in inducing antitumor immunity.

Guinea pigs which were injected repeatedly with a mixture of a 3M KCl extract of line 10 tumor and 6-O-(2-tetradecyl-hexadecanoyl)-muramyl-dipeptide (B30-MDP) rejected a tumor graft of line 10. Such an adjuvant effect of B30-MDP was also demonstrated when X-ray-treated line 10 cells were mixed with B30-MDP dissolved in phosphate-buffered saline and inoculated into the animals.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

In vitro augmentation of natural killer cell activity and production of interferon-alpha/beta and -gamma with deoxyribonucleic acid fraction from Mycobacterium bovis BCG.

A nucleic acid-rich fraction extracted and purified from BCG (MY-1) augmented natural killer (NK) cell activity of mouse spleen cells in vitro, and produced factor(s) which showed anti-viral activity and rendered normal macrophages cytotoxic towards tumor cells. These cellular responses were induced by the MY-1 digested preliminarily with RNase, but not by the MY-1 digested with DNase, indicating that DNA contained in MY-1 was essential for the responses. The function of the factor to activate macrophages was destroyed by treatment with a small amount of anti-interferon (IFN)-gamma antiserum or under acidic conditions (pH 2), but not by treatment with anti-IFN-alpha/beta antiserum, while the anti-viral activity was destroyed almost completely by treatment with anti-IFN-alpha/beta antiserum. It appears that DNA from BCG stimulated mouse spleen cells in vitro, resulting in augmentation of NK activity and production of IFN-alpha/beta and -gamma.

Animals↗
PubMed1988

A synthetic single-stranded DNA, poly(dG,dC), induces interferon-alpha/beta and -gamma, augments natural killer activity, and suppresses tumor growth.

When various synthetic double- or single-stranded DNAs were incubated with spleen cells from mice (BALB/c or CDF1) at 37 degrees for 20 hr, it was found that some of the DNAs augmented NK activity and produced factors in the culture supernatants which showed antiviral activity and activity to render mouse macrophages cytotoxic toward tumor cells. Poly(dG,dC) showed the strongest activities, when incubated with spleen cells from lipopolysaccharide-nonresponsive mice, C3H/HeJ. The activity of the culture supernatant to activate macrophages was completely abolished by a small amount of anti-IFN gamma antibody. On the other hand, the virus-inhibitory activity of the supernatant was mostly neutralized by anti-IFN alpha/beta. When IMC tumor cells (5 x 10(5) cells) were mixed with poly(dG,dC) (100 micrograms) and then inoculated intradermally into CDF1 mice, the tumor did not take, while tumors grew progressively and killed the mice in a control group inoculated with tumor cells alone. Direct cytotoxicity of poly(dG,dC) at a concentration of 1,000 micrograms/ml against IMC cells was not observed in vitro.

Animals↗
PubMed1988

Effects of procainamide and lidocaine on electrically inducible ventricular tachycardia studied with programmed ventricular stimulation in post myocardial infarction.

The effects of procainamide and lidocaine, representative of class IA and IB antiarrhythmic agents, on electrically inducible ventricular tachycardia (VT) were studied using programmed ventricular stimulation in 47 post myocardial infarction patients at an average of 1.5 months after the onset. The mean doses of administered procainamide and lidocaine were 1050 mg and 161 mg, and their mean plasma concentrations were 7.5 micrograms/ml and 3.1 micrograms/ml respectively. The induction of sustained VT was suppressed in 15 of 29 patients (52%) by procainamide, but in none by lidocaine. The induction of nonsustained VT was suppressed in 6 of 18 patients (33%) by procainamide, and in 1 of 8 patients (13%) by lidocaine. The efficacy rate of procainamide was significantly higher than that of lidocaine in suppression of VT induction (21/47 vs 1/14 p less than 0.01). Procainamide significantly prolonged the effective refractory period of the right ventricle as well as the HV and QRS interval, however lidocaine did not affect them significantly. On the other hand, the worsening effect which changed nonsustained VT inducible in the baseline into sustained VT inducible post drug administration was demonstrated in 8 of 18 procainamide cases (44%), and in 3 of 8 lidocaine cases (38%). Between the procainamide effective and ineffective or worsening patients, there were no differences found in the electrophysiologic variables either in the baseline or post procainamide administration. We concluded that procainamide was more effective than lidocaine for the prevention of potential life-threatening VT induction in post myocardial infarction patients, although its efficacy was considerably limited, and to confirm the effectiveness and exclude the worsening effects of the class IA and IB antiarrhythmic agents, drug testing using programmed ventricular stimulation appeared to be valuable.

Cardiac Pacing, Artificial↗
PubMed1988

[A case of male acromegaly with galactorrhea].

A 43-year-old man was admitted to our clinic with complaints of headache and nasal obstruction. He has noted increasing hand and foot size with decreasing libido and pollakiuria for ten years. On admission, he showed galactorrhea. His visual symptoms were slightly decreased. Endocrinological evaluation revealed high serum levels of GH and prolactin. A plain skull X-ray showed acromegalic features with remarkable destruction of dorsum sellae. A contrast enhanced CT demonstrated an intrasellar high density mass extending to the sphenoid sinus and the right ethmoidal sinus. A cerebral angiogram was nor.al. Surgery was then performed with the transsphenoidal approach. A soft reddish brown mass was found in the sphenoid sinus and the bilateral cavernous sinus extending from the sella turcica. Histologically the tumor was eosinophilic adenoma. There were numerous cells exhibiting immunostaining for both GH and PRL in the immunocytochemical study. Postoperative course was uneventful. His visual impairment improved soon after the operation. Serum GH and PRL levels decreased to 38 and 130 ng/ml. He was treated with conventional irradiation (500 rads), so remained galactorrhea and hyperhidrosis. One year after the operation, there is no regrowth of the residual tumor.

Acromegaly↗
PubMed1988

[A case of acute subdural hematoma associated with convexity meningioma].

A 61-year-old normotensive woman was admitted to our hospital with complaints of severe headache and nausea. She has had a limp due to the poliomyelitis in her childhood. Three days before admission, she had a headache without unconsciousness. On admission, she was almost alert. Her vital signs were normal. A mild monoparesis of the atrophic right lower extremity was evident. This impairment was due to her past poliomyelitis. There were no other motor palsy, sensory loss, nuchal rigidity, and papilledema. A plain CT scan showed a crescent high density zone adjacent to a round high density mass in the left convexity. A cerebral angiogram showed a vascular left temporoparietal mass supplied by a middle meningeal artery. A craniotomy was then immediately performed. The well encapsulated tumor was totally resected, and the adjacent subdural hematoma was also evacuated. Histologically, the tumor was transitional meningioma with areas containing thin-walled vessels and focal necrosis. Postoperative course was uneventful. The origin of hemorrhage in this case would seem to be the thin-walled blood vessel with loss of vessel support. The clinical significance and the mechanism of the hemorrhage from the meningioma were discussed.

Acute Disease↗
PubMed1988

Norepinephrine and adenosine triphosphate release in different ratio from guinea pig vas deferens by high potassium chloride, ouabain and monensin.

Release of norepinephrine (NE) and ATP from the guinea pig vas deferens evoked by ouabain in combination with monensin or by high KCl was measured by a high-pressure liquid chromatography-ECD and luciferin-luciferase assay, respectively. Ouabain (10-100 microM) induced a concentration-dependent liberation of NE, which was enhanced by 10 microM monensin, a Na+-ionophore. The marked NE release elicited by the combined administration of both the drugs was unaffected by Ca++-removal but was reduced by lowering Na+ from the medium. This NE release in the Ca++-free medium was diminished markedly after treatment with 6-hydroxydopamine or reserpine and in low-temperature (25 degrees C) medium. This release was also decreased by ruthenium red (10-30 microM), an uptake inhibitor of Ca++ to mitochondria, and carbonyl cyanide-m-chlorophenyl hydrazone (10 microM), a metabolic inhibitor. On the other hand, 100 mM KCl caused a moderate, extracellular Ca++-dependent release of NE. ATP-outflow from the tissue evoked by 100 microM ouabain plus 10 microM monensin was almost unaltered by Ca++-removal but was inhibited by 6-hydroxydopamine or prazosin (0.3 microM), whereas release induced by high KCl was reduced by 6-hydroxydopamine and Ca++-free medium but was unaffected by prazosin. ATP/NE ratios at respective maximum effluxes evoked by 100 mM KCl and ouabain plus monensin were 6.59 and 0.22, respectively. These findings suggest that there may be more than one site of corelease for NE and ATP. Ouabain plus monensin seems to produce an extracellular Ca++-independent neuronal release of NE and ATP from the cytoplasmic and vesicular storage sites which predominantly release NE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1987

Improvement in the basic technology of electrofusion for generation of antibody-producing hybridomas.

In order to define the optimum conditions of electrofusion technique for the generation of antibody-producing hybridomas, mouse spleen cells or EBV-transformed human B cells were fused with mouse myeloma cells (SP2/0) or human fusion partner cells (KR-4 or KR-12), respectively, by electric field pulse under various conditions. The results confirm reports that the presence of both Ca2+ and Mg2+ in fusion medium and pretreatment of mixed cells with proteases improve hybridoma yield. Moreover, the presence of liposome or hydrophobic protein in the fusion medium greatly enhanced the yield. Under optimum conditions, hybridoma yields of mouse cells and human cells were 2.5 X 10(-4) and 1 X 10(-4), respectively. These efficiencies were about ten times higher than those obtained by the conventional polyethylene glycol technique. Microscopic observation of the fusion-process revealed that in a human cell system 20%-50% of the cells were physically fused, although only one in 5000 physically fused human cells grew as a hybridoma after hypoxanthine-aminopterin-thymidine selection.

Animals↗
PubMed1987

Tumor cell detection method using complement-mediated cytolytic reaction and imaging sensor system.

A novel tumor-detection system consisting of complement-mediated cytolytic reaction and an image processing system was developed for the simple and rapid determination of tumor cells. The present system consists of a CCD image sensor, image memory board, personal computer, and microscope. When monoclonal antibody 3C4, which is specific to the guinea pig hepatoma L-10, was added to cell suspension, only L-10 cytolysis occurred. Cytolysis caused a decrease in brightness of the cells observed by phase-contrast microscopy. The phase contrast image of the cells before cytolysis was converted to a digitalized signal and stored in computer memory. After cytolysis, a brightness threshold above that of lysed cells was subtracted from the digitalized signal and compared to the signal stored before reaction. L-10 cells in mixed cell suspension were determined specifically by the system. Measurement time was only 2 sec and overall time, including reaction time, was approximately 30 min. Since this method does not require a cell washing process, automation of the whole system is possible.

Animals↗
PubMed1987

Beneficial effect of agar for the frozen storage of bisected embryos.

The effect of agar embedding on the viability of intact and bisected goat embryos during freezing and thawing was examined. Blastocysts or hatched blatocysts were bisected into haves by micromanipulation. After embedding with or without agar, they were stored by deep freezing. After thawing, undamaged and some partially damaged embryos were transferred into uteri of recipients. Of 22 demi-embryos embedded with agar, only one was undamaged, but of 58 demi-embryos embedded with agar, 29 were undamaged. Although one set of monozygotic twins was obtained after the transfer of 15 sets of frozen-thawed bisected embryos, the pregnancy rate (47%) and the proportion of young (27%) were lower than those obtained by transfer of frozen-thawed, intact embryos (67 to 80% for pregnancy rate, 45 to 53% for the young).

Journal Article↗
PubMed1987

High levels of soluble interleukin 2 receptors released from human retrovirus-infected cells.

Soluble interleukin 2 receptors (IL 2R) from human retrovirus-infected cells were analyzed. All the T cell lines integrated with human T cell lymphotropic virus (HTLV)-I and -II, or transfected with HTLV-I gag-pX gene, were found to release high levels of IL 2R constitutively. In contrast, this was not found in T cell lines in which HTLV-I was integrated but not expressed, human immunodeficiency virus (HIV)-infected T cell lines, or T cell, B cell, granulocyte and macrophage cell lines which were HTLV-I negative. These results raise the possibility that the pX-gene product might stimulate the generation of soluble IL 2R. In the sera from patients with adult T cell leukemia, large amounts of IL 2R were released, in contrast to sera from healthy carriers of HTLV-I. The molecular weight of IL 2R was determined to be about 50 KD by size-exclusion HPLC.

Cell Line↗
PubMed1987

Pharmacological effects of the antianxiety compound suriclone and its principal metabolites.

The pharmacodynamic effects of 4-methyl-1-piperazinecarboxylic acid ester with (+/-)-6-(7-chloro-1,8-naphthyridin-2-yl)-2,3,6,7-tetrahydro-7-h ydr oxy-5H-p- dithiino[2,3-c]pyrrol-5-one (suriclone, RP-31264) and its principal metabolites M1 and M2 on respiration, cardiovascular system, autonomic nervous system, smooth muscle and other physiological parameters were investigated in various animal species. Suriclone, 1 mg/kg i.v., increased the amplitude of respiratory movement, decreased the respiratory rate and blood pressure and increased the heart rate in conscious rabbits. The respiratory and depressor effects were more evident in pentobarbital anesthetized rabbits. In anesthetized dogs, suriclone, 0.05 or 0.5 mg/kg i.v., produced essentially the same effects as seen in the anesthetized rabbits. The ECG pattern was not significantly changed in any animal. Such effects on respiration and on the cardiovascular system of metabolites M1 and M2 in the rabbits were weak. In the isolated guinea-pig atria, suriclone, 10(-6) g/ml, had no effect but increased contractility and decreased heart rate at a high concentration of 10(-5) g/ml. Both M1 and M2 had weak effects. Suriclone had no action on flow rate of the perfusate through the blood vessels of the isolated rabbit ear. In anesthetized dogs, suriclone 0.5 mg/kg i.v., did not affect the responses to vagal stimulation or to pre- and postganglionic stimulation of cardiac ganglion. Suriclone instilled onto the eye or i.v. had no appreciable effect on pupillary diameter or the miotic response in rabbits, but an abnormal oculogyration was evoked when the drug was given i.v. at 1 mg/kg. M1 or M2 had no such effect. Suriclone did not exert analgesic effects in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Attempts to improve hybridoma technology for the production of human monoclonal antibodies].

The technology for producing hybridomas secreting human monoclonal antibodies has not been well established, contrary to the situation for mouse monoclonal antibodies. Therefore, we attempted to find better fusion partners using two EBV-transformed human B cell lines, C5TK1 and TAPC-30 (anti-SRBC IgM and anti-HBs IgG secretors, respectively; provided by Prof. Y. Ono, Nihon Univ. School of Med.). Fifteen partner cell lines available were fused with either of these lines by conventional PEG technique, and their fusion frequencies, cloning efficiencies, and levels and stabilities of specific antibody secretion were examined. Among the fusion partners tested, KR-12, SHM-D33 and 3HL3-6J lines appeared to be the best. Hybridomas with the KR-12 line were easily cloned and produced stable specific antibodies, although the level of Ig secretion was almost the same as the antibody-producing parental B-cell lines. SHM-D33 cells efficiently formed hybrids but the stability of their Ig production was low and cloning was laborious. Although the fusion frequency of 3HL3-6J cells was not so high, some hybrids were good producers of antibodies, and the levels of specific antibody reached levels greater than 10 micrograms/ml. Their cloning was relatively easy. Therefore, the 3HL3-6J line seemed to be the best fusion partner for EBV-transformed B cells. With regard to the low fusion frequency of human cells, we attempted to improve the efficiency using the electrofusion technique. Three to 10 times more hybridomas were obtained by this technique than by the conventional PEG method. Further investigations are under way.

Antibodies, Monoclonal↗