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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 1,063 records · Page 59Linked to original sources

Phenytoin potentiates methamphetamine-induced behavior in mice.

We demonstrated that stereotyped behavior and tremor induced by methamphetamine (MA) were potentiated by pretreatment with phenytoin (PNT) in mice. Similar enhancing effects were obtained by pretreatment with carbamazepine. Gas chromatographic study demonstrated that pretreatment with PNT increased MA concentrations in the brain to approximately 2.5 times of control level. The increased MA concentrations were thought to be a major factor for the observed potentiation of MA-induced behavior by PNT. However, all MA-induced behavior were not equally potentiated; tremor was enhanced more than stereotypy. These results suggest that central neuronal mechanisms may also be involved in PNT-potentiated MA-induced behavior in mice.

Animals↗

Role of the pudendal nerves on the dynamics of micturition in the dog evaluated by pressure flow EMG and pressure flow plot studies.

The role of the pudendal nerves on the dynamics of micturition was studied using 16 decerebrated dogs. The voiding cycles were analyzed by pressure flow EMG and pressure flow plot studies under 3 conditions: control, after unilateral, and after bilateral pudendal nerve transection. In the control condition, highly reproducible reflex micturition with bladder contraction and spasmodic rhythmic sphincter contractions was demonstrated. Two patterns were noted following pudendal nerve transection: reflex micturition and overflow incontinence. Even though reflex micturition could be achieved in 9 out of 16 dogs after bilateral transection, there was decreased bladder emptying as well as absence of spasmodic rhythmic sphincter contractions. Overflow incontinence developed in the remaining 7 dogs (5 dogs after bilateral transection and 2 dogs after unilateral transection). It appears that the pudendal nerves play an important role in emptying the bladder of the dog.

Animals↗

Purification and characterization of a tuberculin-active substance from Mycobacterium bovis BCG.

A new tuberculin-active substance, designated TAS-1D3, has been purified from the extract of Mycobacterium bovis BCG by precipitation at pH 4.2, ethanol fractionation, and column chromatography involving CM-cellulose, QAE-Sephadex A-25, Sephadex G-100, and Sephadex G-75. TAS-1D3 was homogeneous in polyacrylamide gel electrophoresis and positive in both Coomassie brilliant blue and periodic acid-Shiff staining, suggesting that TAS-1D3 is a glycoprotein. The molecular weight of TAS-1D3 was estimated to be 26,000 by gel filtration. In amino acid analysis, TAS-1D3 was distinctive in having proline as a dominant amino acid, and in that it lacked basic amino acids, sulfur-containing amino acids and aromatic amino acids. Moreover, TAS-1D3 was almost devoid of absorption at around 280 nm. In guinea pigs sensitized with BCG vaccine, the tuberculin activity of TAS-1D3 was about forty times more potent than that of purified protein derivative (PPD).

Amino Acids↗

Basal cell adenoma with parallel tubules in stromal cells of the parotid gland.

A case of basal cell adenoma in the right parotid region of a 51 years old male was reported. The tumor measured 2.5 cm x 3 cm, was spherical and covered with a fibrous capsule. Histologically, it was a tubular monomorphic adenoma with scant edematous interstitial tissue. The stromal cells stained positively by the PAP method using anti-S-100 protein serum. Electron microscopically, the tumor cells forming tubular had many microvilli at the luminal surface, many filaments in the cytoplasm and well developed desmosomes in the intercellular junctions. Ordinary intracellular organelles of the tumor cells were small in number, and their nuclei were oval with shallow indentation. In the dilated rough endoplasmic reticulum of the stromal cells, many straight parallel tubules were found. The tubules measured from 15 nm to 25 nm thick and 3.5 micrometers long in the longitudinal sections and from 25 nm to 30 nm in diameter with electron lucent core and poor coat in the cross sections. Other cell organelles of the stromal cells were small in number, and filaments and dense attachments were found in the ectoplasm. Around the stromal cells there was a discontinuous basement membrane.

Adenoma↗

Monoclonal antihuman thyroglobulin antibodies.

Six murine hybridomas secreting monoclonal antihuman thyroglobulin (Tg) antibodies (TAK 1-6) were established by cell fusion techniques. Solid phase RIA was employed to detect the anti-Tg antibody in culture supernatants of hybridomas. The characteristics of these monoclonal antibodies were analyzed by radioimmune blocking assay using rat Tg, human glycoproteins, thyroid hormones, and various preparations of Tg obtained from patients with thyroid disease as inhibitors. In the same system, competitive inhibition studies between 125I-labeled and unlabeled monoclonal antibodies were carried out to determine whether these antibodies recognized the same antigenic determinant. TAK 2 and 3 reacted with human Tg specifically and had equal binding activity using various preparations of human Tg. The other four monoclonal antibodies (TAK 1, 4, 5, and 6) cross-reacted with xenogeneic Tg (rat Tg) and their affinity for human Tg increased as the iodine content of Tg increased. Tg binding to TAK 1 and 4 was inhibited by T4, whereas Tg binding to TAK 5 and 6 was not inhibited by any thyroid hormone or their precursors. In conclusion, we prepared six monoclonal antihuman Tg antibodies. One group is specific for human Tg and recognizes the framework structure unmodified by iodination; the second group reacts with iodination-related epitopes other than iodoamino acids, and the third group recognizes determinants consisting of T4. These monoclonal antibodies provide important probes to detect the polymorphism of human Tg.

Animals↗

Alterations of hepatic delta-aminolevulinic acid synthetase, heme oxygenase, microsomal cytochrome content and drug metabolism in rats bearing ascitic tumors AH 13, AH 66 and AH 414 and a 3-methylcholanthrene induced tumor.

Hepatic microsomal drug-metabolizing enzyme activities, cytochrome content, delta-aminolevulinic acid (ALA) synthetase and heme oxygenase activities were studied in rats bearing ascitic tumors AH 13, AH 66 and AH 414 and a primary, 3-methylcholanthrene (3-MC)-induced, tumor. Hepatic microsomal drug-metabolizing enzyme activities and cytochrome content were decreased in rats transplanted intraperitoneally with 1-2 x 10(6) cells of ascitic tumor cell lines AH 13, AH 66 and AH 414. The extent of the decrease of the microsomal cytochrome content and enzyme activities were dependent on the tumor-bearing periods after inoculation. Hepatic microsomal heme oxygenase activity was significantly increased concurrently with the decrease of microsomal drug-metabolizing enzyme activities and cytochrome content. Hepatic ALA synthetase was not changed appreciably in these tumor-bearing rats. Similar alterations of microsomal enzyme content and activities were observed in the livers of rats transplanted subcutaneously with AH 66 tumor cells and in rats bearing a primary tumor initiated by the subcutaneous injection of 3-MC. When the tumor was surgically removed from the rats bearing AH 66 subcutaneously, these hepatic microsomal parameters returned to normal levels. Microsomal drug-metabolizing enzyme activities and cytochrome content in these ascitic tumor cells were found to be at very low levels. From these results, if appears that there is an inverse relationship between the increase of microsomal heme oxygenase activity and the decrease of cytochrome P-450 and b5 as well as drug-metabolizing enzymes in the liver of tumor bearing rats.

5-Aminolevulinate Synthetase↗

Effects of chronic haloperidol and chlordiazepoxide treatment on lateral hypothalamic self-stimulation behavior in rats.

The effects of chronic administration of haloperidol and chlordiazepoxide for 14 days on self-stimulation behavior were investigated in rats with electrodes chronically implanted in the lateral hypothalamus. Haloperidol produced a prominent decrease in self-stimulation behavior during chronic treatment, followed by a significant increase in the lever-pressing rate during a 2 week withdrawal period, with a return to the control level about 5 weeks after drug withdrawal. Chlordiazepoxide produced a significant increase in self-stimulation behavior during chronic treatment. However, the lever-pressing rate was not significantly different from the control level during a 3 week observation period following drug withdrawal. These results indicate an increase in the sensitivity of central dopaminergic receptors following chronic haloperidol treatment, but not following chronic chlordiazepoxide treatment.

Animals↗

[Role of the striated urethral sphincter in the voiding cycle of the decerebrated dog].

The role of the striated urethral sphincter on the dynamics of micturition was studied using 4 decerebrated dogs. The voiding cycles were analyzed by pressure flow EMG and pressure flow plot studies before and after the administration of suxamethonium. In the control condition, highly reproducible reflex micturition with bladder contraction and spasmodic rhythmic sphincter contractions was demonstrated. After the administration of suxamethonium reflex micturition occurred, but there was decreased bladder emptying as well as absence of spasmodic rhythmic sphincter contractions. The striated urethral sphincter would seen to play an important role in bladder emptying of decerebrated dogs.

Animals↗

Determination of low affinity platelet factor 4 in frozen and thawed human platelets by the newly developed enzyme immunoassay system.

By the use of a newly developed sandwich enzyme immunoassay method for low affinity platelet factor 4 (LA-PF4), the effects of repeated freeze-thawing on the contents of this protein in platelets were determined and compared with those of Triton-X 100 lysed platelets. The assay system consisted of polystyrene balls covered with immobilized antibody fragments F(ab')2 and the same antibody Fab' labeled with beta-D-galactosidase from E. coli. The assay was specific to LA-PF4 with no significant cross-reactivity with platelet factor 4. Coefficients of variation within-run and between-run for the assay of LA-PF4 were less than 12%. The results obtained with this enzyme immunoassay correlated well with those of a radioimmunoassay of beta-thromboglobulin which is immunologically identical with LA-PF4 (r = 0.961, slope = 1.056, y-intercept = -3.739 ng/ml; n = 22). The contents of LA-PF4 per 10(9) Triton-X 100 lysed platelets in platelet-rich plasma were 23.65 +/- 3.14 micrograms (mean +/- S.D.). The contents of LA-PF4 in platelets were increased from 46% to 95% of Triton-X 100 values by repeated freezing and thawing 1 to 7 times. The present data indicate that the freeze-thawing technique should be done carefully to obtain the reliable determination of LA-PF4 in platelets.

Blood Coagulation Factors↗

High yield of platelet-rich plasma from CPD blood compared to ACD blood.

The yields of platelet-rich plasma (PRP) obtained by centrifugation of CPD (citrate-phosphate-dextrose) blood and ACD (acid-citrate-phosphate) blood were compared. The volumes of PRP from 5 ml blood in test tubes and 200 ml blood in bags were larger by 4% and 4.5%, respectively, when CPD was used as an anticoagulant. In addition, the number of platelets in PRP from CPD blood was higher than that from ACD blood. These data suggest that the optimal centrifugal condition for CPD blood should be different from that for ACD blood.

Blood Platelets↗

High yield of platelet-rich plasma from CPD blood compared to ACD blood.

The yields of platelet-rich plasma (PRP) obtained by centrifugation of CPD (citrate-phosphate-dextrose) blood and ACD (acid-citrate-phosphate) blood were compared. The volumes of PRP from 5 ml blood in test tubes and 200 ml blood in bags were larger by 4% and 4.5%, respectively, when CPD was used as an anticoagulant. In addition, the number of platelets in PRP from CPD blood was higher than that from ACD blood. These data suggest that the optimal centrifugal condition for CPD blood should be different from that for ACD blood.

Blood Platelets↗

[Effects of psychotropic drugs on lateral hypothalamic self-stimulation behavior in rats: correlation between self-stimulation behavior inhibition and striatal dopaminergic blockade by neuroleptic drugs].

The effects of neuroleptic drugs on self-stimulation behavior were investigated in rats with electrodes chronically implanted in the lateral hypothalamus. Except for sulpiride and carpipramine, the neuroleptic drugs chlorpromazine, thioridazine, perphenazine, haloperidol, floropipamide, pimozide, clocapramine and oxypertine all suppressed self-stimulation behavior dose-dependently. The anti-anxiety drugs chlordiazepoxide, diazepam, clotiazepam and etizolam facilitated this behavior. The antidepressant drugs imipramine and amitriptyline suppressed this behavior slightly at the dose of 40 mg/kg. The alpha-antagonist phenoxybenzamine also suppressed this behavior, but the slope of its dose-response curve was gentle compared with those of the neuroleptic drugs. The inhibition produced by the neuroleptic drugs is considered to be mediated primarily at the dopaminergic receptors. Turning behavior induced by methamphetamine in rats with unilateral 6-hydroxydopamine lesions of the caudate nucleus was used to assess the striatal dopaminergic blocking potency of the neuroleptic drugs. No correlation was found between the ED50 values for the turning behavior inhibition and the ED50 values for the self-stimulation behavior inhibition produced by these drugs, so the dopaminergic receptors in the striatum are apparently not involved in the mediation of self-stimulation behavior.

Animals↗

Effect of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)-benzimida zole difumarate (KB-2413), a new antiallergic, on chemical mediators.

Effects of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazol e difumarate (KB-2413) on chemical mediators were investigated in vitro and in vivo. Antihistaminic activity of KB-2413 in vitro was about 2, 7 and 5 times more potent than those of chlorpheniramine, diphenhydramine and clemastine, respectively, and equipotent to that of ketotifen. This antihistaminic activity of KB-2413 was competitive antagonism to histamine. In the study preventing histamine-induced mortality in guinea pigs, the antihistaminic potency of KB-2413 (p.o.) was about 39, 780, 68 and 3 times more potent than those of chlorpheniramine, diphenhydramine, clemastine and ketotifen, respectively. In the study preventing histamine-induced increase in vascular permeability, the antihistaminic potency of KB-2413 (p.o.) was about 27 and 4 times greater than those of chlorpheniramine and ketotifen, respectively. The preventing activity of KB-2413 (i.v.) on histamine-induced increase in airway resistance was about 10 and 2 times more potent than those of chlorpheniramine and ketotifen, respectively. These results indicate that the antihistaminic potency of KB-2413 is stronger than that of chlorpheniramine and that of ketotifen which has the strongest antihistaminic activity of all reference drugs. On the other hand, KB-2413 had only very weak anticholinergic, antibradykinin and antiserotonin activity in the study in vitro or in vivo, so that KB-2413 had selective antihistaminic activity. Therapeutic index of KB-2413 calculated from the antihistaminic potency on histamine-induced mortality and acute toxicity in guinea pigs was about 110 times greater than that of chlorpheniramine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Antiasthmatic effect of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidaz ole difumarate (KB-2413), a new antiallergic.

Effects of KB-2413 on experimental asthma and respiration were examined in comparison with ketotifen and chlorpheniramine in guinea pigs. Anaphylactic bronchoconstriction in guinea pigs were measured by two methods. One is the method measuring increase of airway resistance and the other is the method measuring change of volume and rate of respiration. KB-2413 (0.003-0.1 mg/kg p.o.) showed a dose-dependent inhibition on antigen-induced increase in airway resistance in passively sensitized guinea pigs. The ED50 value of KB-2413 was 0.012 mg/kg p.o. and the inhibitory effect of KB-2413 was 24.9 and 3.3 times more potent than those of chlorpheniramine and ketotifen, respectively. On the other hand, disodium cromoglycate did not show any inhibitory effect on this reaction at a dose of 30 mg/kg i.v. KB-2413 (0.003-0.03 mg/kg p.o.) also showed a dose-dependent inhibition on antigen-induced disorder of the respiration in passively sensitized guinea pigs. KB-2413 itself did not induce respiratory disorder at doses of 1 and 3 mg/kg i.v. and 30 mg/kg i.d. On the other hand, ketotifen and diphenhydramine induced respiratory disorder distinctly at a dose of 1 mg/kg i.v. Thus, KB-2413, by oral administration, has a very strong inhibitory effect on anaphylactic bronchoconstriction, and does not induce respiratory disorder even at about 2500 times the dose as that which showed a 50% inhibitory effect on anaphylactic bronchoconstriction.

Airway Resistance↗

Influence of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidaz ole difumarate (KB-2413), a new antiallergic, on ciliary movement.

Influence of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazol e difumarate (KB-2413), a new antiallergic agent, on tracheal ciliary movement of pigeons and its local anaesthetic effect were investigated in comparison with reference drugs. KB-2413 (0.3 and 3 mg/kg i.v.) did not affect ciliary movement, but ketotifen, diphenhydramine, chlorpheniramine, lidocaine and tetracaine showed a significantly inhibitory effect on ciliary movement at a dose of 3 mg/kg i.v. KB-2413 (4% solution) did not inhibit corneal reflex in guinea pigs, but ketotifen, diphenhydramine and chlorpheniramine inhibited corneal reflex at 1%, 1% and 4% solution, respectively. KB-2413 (5 X 10(-4) mol/l) did not inhibit action potentials of desheathed frog sciatic nerve fiber, but ketotifen, chlorpheniramine and diphenhydramine inhibited significantly action potentials at 5 X 10(-4) mol/l. These results suggested that KB-2413 did not influence tracheal ciliary movement because of having no local anaesthetic effect.

Action Potentials↗

Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity.

A fraction extracted from Mycobacterium bovis strain BCG, which was composed of 70.0% DNA, 28.0% RNA, 1.3% protein, 0.20% glucose, and 0.1% lipid and of no detectable amounts of cell wall components such as alpha, epsilon-diaminopimelic acid and hexosamine, was found to possess strong antitumor activity. Repeated intralesional injection of this fraction, designated MY-1, without attachment to oil or a single intralesional injection of MY-1 emulsified in mineral oil caused the IMC carcinoma of CDF1 mice and line 10 tumor of strain 2 guinea pigs to regress and/or prevented metastasis very effectively. MY-1 after digestion with RNase, which contained 97.0% single-stranded DNA with a guanine-cytosine content of 69.8%, was more effective than undigested MY-1 against IMC and line 10 tumor, while MY-1 digested with DNase, which contained 97.0% RNA, had reduced activity, suggesting that the DNA from BCG possessed strong antitumor activity under certain conditions. Details of the extraction procedures and physicochemical characterization of MY-1 were also described.

Animals↗

Antiallergic effect of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidaz ole difumarate (KB-2413).

Antiallergic effects of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazol e difumarate (KB-2413) were investigated in immediate type hypersensitivities. KB-2413 (0.005-0.04 mg/kg p.o.) showed a marked inhibition on lethal anaphylaxis in guinea pigs induced by anti-egg albumin rabbit serum, and it was 30 and 1.6 times more potent than chlorpheniramine and ketotifen, respectively. KB-2413 (0.003-0.1 mg/kg p.o.) showed a dose-dependent inhibition on vascular permeability increase induced by 48 h homologous passive cutaneous anaphylaxis (PCA) and histamine in guinea pigs, being about 10-30 times and 3 times more potent than chlorpheniramine and ketotifen, respectively. All drugs did not completely inhibit 4 h heterologous PCA in guinea pigs induced by the anti-egg albumin rabbit serum in the doses used here, but KB-2413 was more effective than chlorpheniramine and ketotifen. No difference in inhibitory effect on the vascular permeability increase between the single and daily oral administration for 4 weeks of KB-2413 could be found. KB-2413, as well as chlorpheniramine and ketotifen, showed a dose-dependent inhibition on 48 h homologous PCA in rats at doses of 1-10 mg/kg p.o., and showed a concentration-dependent inhibition on Schultz-Dale reaction at 10(-8) - 10(-7) mol/l. KB-2413 (10(-5) - 10(-3) mol/l) showed a concentration-dependent inhibition of anaphylactic histamine release from isolated rat peritoneal mast cells which were passively sensitized by rat IgE. KB-2413 also inhibited compound 48/80-induced histamine release from rat peritoneal mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗

Hereditary deficiency of OKT4-positive cells: studies for mode of inheritance and lymphocyte functions.

Two Graves' patients were found to have no OKT4+ cells in their peripheral blood lymphocytes (PBL). However, the reactivity of their lymphocytes with T4(T4A) and anti Leu-3a was normal and no autoantibodies to the OKT4 determinant were found in their sera. Cytofluorographic analysis of PBL from their family members showed three types of immunofluorescence profiles with OKT4. The first type was the complete OKT4+ cell deficiency, the second was the normal percentage of OKT4+ cells with half immunofluorescence intensity and the third was the normal staining pattern with OKT4. Phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) induced blastogenesis; PWM induced IgG synthesis, autologous and allogeneic mixed lymphocyte reaction, and Interleukin-2 (IL-2) production of their PBL were also normal. These results suggest that (i) the expression of determinant to OKT4 is transmitted as autosomal incomplete dominant trait and (ii) OKT4+ cell deficiency is not accompanied by a lack of the inducer/helper subset of T cells.

Antibodies, Monoclonal↗