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Biomedical subjects

T Shibuya

Publications and source records attributed to T Shibuya.

At least 397 records · Page 22Linked to original sources

Characterization of the early and late stages of myelomonocytic leukemia induced by Friend helper-independent virus F-MuLV: isolation and induction of Friend myelomonocytic leukemic cell lines.

With the use of cloned helper-independent Friend leukemia virus (F-MuLV), we have induced a high incidence (approximately 70%) of myelomonocytic leukemia in mice resistant (Fv-6rr or Fv-6rs) to erythroleukemia induction by this virus. The spleen cells from these mice (DBA/2 or BALB/c X DBA/2) were found to contain a high level of progenitor cells capable of forming granulocytic and macrophage colonies (CFU-GM). These CFU-GM, however, were different from those in the spleens of uninfected mice, as they were either very sensitive to or independent of conditioned medium. No erythroid progenitor bursts (BFU-E) or precursor (CFU-E) cells were detected in the spleens of these diseased animals. If these mice with myelomonocytic leukemia were kept alive by transfusion of red blood cells from uninfected mice, tumorigenic cell lines, capable of being transplanted, into adult mice can be isolated. Three such cell lines TTA-1, TTA-3, and TTA-9 have been established, and they retain their morphology of monocytes and macrophages as well as being positive for the monocyte-specific stain alpha-naphthyl-acetate esterase. These myelomonocytic leukemia cell lines can also be induced in culture by spleen cell-conditioned medium to differentiate into macrophages. Other conditioned media such as L-cell-conditioned medium, phytohemagglutinin-stimulated leukocyte-conditioned medium, and WEHI-3 conditioned medium were less effective in their abilities to stimulate differentiation in these myelomonocytic leukemia cell lines.

Animals↗

Modifying effects of the enzyme inducers, phenobarbital and 3-methylcholanthrene, on dominant lethal events induced by 7, 12-dimethylbenz[a]anthracene in mice.

The effects of pretreatment with either phenobarbital (PB) or 3-methylcholanthrene (MC) on the induction of dominant lethal events by 7, 12-dimethylbenz[a]anthracene (DMBA) in male mice were studied. DMBA induced dominant lethals in both post- and pre-meiotic germ cells of mice. The incidences of DMBA-induced dominant lethals were markedly reduced in pre-meiotic germ cells by the pretreatment with PB, whereas a significant reduction of the lethal events in post-meiotic germ cells was observed with MC. No significant reduction of living implants was detected in pre-meiotic germ cells on pretreatment with PB. The contents of liver microsomal cytochrome p-450 of mice pretreated with PB or MC were about twice those of non-treated mice.

9,10-Dimethyl-1,2-benzanthracene↗

A possible autonomic modulation of sinus node recovery time in overdrive suppression test.

The effect of blood pressure fall on sinus node recovery time (SNRT) was studied in 17 patients during the overdrive suppression test. Their maximal SNRT was less than 150% of the mean P-P interval of the control state (=SCL) and CSNRT (=SNRT-SCL) was less than 550msec. Blood pressure was found to fall in about a half of the patients at a high pacing rate. Concomitantly, SNRT was found to shorten in those who showed such a fall in blood pressure. The subjects were then divided into two groups; one with a shorter SNRT at 150bpm than at 90bpm of pacing rate and the other without such shortening. The changes in SNRT and CSNRT were both significant in the first group (p less than 0.02 and p less than 0.001, respectively). The fall in blood pressure at 150 bpm was significant in the group with shortened SNRT and CSNRT and it was larger than in the other group: 23 +/- 14mmHg vs. 1 +/- 5mmHg (p less than 0.001). This result suggests a possible modulation of SNRT by a fall of blood pressure via baroreflex.

Adult↗

Isolation and induction of erythroleukemic cell lines with properties of erythroid progenitor burst-forming cell (BFU-E) and erythroid precursor cell (CFU-E).

We isolated erythroleukemic cell lines arrested at different levels of the erythroid differentiation pathway. One cell line (CB5), established from mice infected with the helper-independent Friend murine leukemia virus (F-MuLV), exhibited properties similar to those of the normal erythroid progenitor burst-forming cell (BFU-E). Six erythroleukemic cell lines, which were established from the anemia-inducing Friend virus complex (FV-A)-infected mice, formed erythroid colonies similar to the erythroid colony-forming precursor cell (CFU-E) after induction with dimethyl sulfoxide or erythropoietin. Three lines that were established from the polycythemia-inducing Friend virus complex (FV-P)-infected mice also formed low proportions (2-5%) of CFU-E-like colonies after induction by these same inducers. These data, together with the earlier findings that F-MuLV induces an increase in the levels of BFU-E and that FV-A or FV-P stimulates enhancement of CFU-E early after infection, indicate that the erythroleukemic cell lines isolated late in the diseases are at the same levels of differentiation as the leukemic cells in the corresponding initial stages. These cell lines with properties of BFU-E and CFU-E can be induced to differentiate in culture and should add to our understanding of the nature of erythroid progenitor cells and their early differentiation programs.

Animals↗

A dose ranging study of atenolol in hypertension: fall in blood pressure and plasma renin activity, beta-blockade and steady-state pharmacokinetics.

The relationship between the oral dosage and plasma concentration of the long-acting cardioselective beta-adrenoceptor blocker atenolol and the antihypertensive response to the the degree of beta-adrenoceptor blockade and change in plasma renin activity (PRA) was evaluated in patients with mild-to-moderate essential hypertension in a double-blind, randomized, between-patient, dose-ranging (25, 50 or 100 mg once daily for 4 weeks) study. The optimum, or minimum, daily dose of atenolol to treat patients with mild-to-moderate hypertension was not clearly identified in this study. A between-treatment comparison did not demonstrate that all blood pressure falls were always less in the 25 mg group than in the other two groups. Calculation of beta-error or the power for the negative results between doses suggested that a large sample size is required to draw a conclusion that no dose-antihypertensive relationship of atenolol exists in the treatment of mild-to-moderate hypertension. A relatively flat plasma concentration-antihypertensive response relationship was observed. Steady-state plasma concentrations of atenolol were dose-related and renal drug clearance was well correlated with individual creatinine clearance. beta-adrenoceptor blockade was better correlated with plasma atenolol concentration. Correlations which were less strong were between plasma drug concentration and change in various blood pressures and between blood pressure falls and beta-adrenoceptor blockade. There was no relationship between the fall in blood pressure and change in PRA. Atenolol appeared to suppress PRA in an all-or-none fashion.

Adult↗

Quantitative analysis of the antiarrhythmic effect of drugs on canine ventricular arrhythmias by the determination of minimum effective plasma concentrations.

Antiarrhythmic effects and minimum antiarrhythmic plasma concentrations (min PC) were examined using three canine ventricular arrhythmia models, i.e., two-stage coronary ligation arrhythmia (Cor), halothane-adrenaline arrhythmia (Adr) and digitalis arrhythmia (Dig). Disopyramide suppressed these three arrhythmias and its min PCs were 5.3 +/- 1.8 (Cor), 4.2 +/- 1.1 (Adr) and 1.7 +/- 0.4 micrograms/ml (Dig). Procainamide suppressed coronary ligation arrhythmia and its min PC was 27.1 +/- 4.0 micrograms/ml, but was not effective on adrenaline arrhythmia. Aprindine was effective on three arrhythmias and its min PCs were 1.6 +/- 0.3 (Cor), 1.0 +/- 0.4 (Adr) and 0.8 +/- 0.4 micrograms/ml (Dig). Lidocaine was not effective on coronary ligation arrhythmia, but was effective on adrenaline arrhythmia and its min PC was 15 micrograms/ml. Phenytoin was effective on three arrhythmias and its min PCs were 9.8 +/- 2.0 (Cor), 12.1 +/- 3.1 (Adr) and 11.3 +/- 3.0 micrograms/ml (Dig). It was not specifically effective on canine digitalis arrhythmia. Propranolol and other beta-blockers were effective on adrenaline arrhythmia, but very high doses were necessary for suppressing coronary ligation and digitalis arrhythmias. Verapamil was only effective on adrenaline arrhythmia and its min PC was 0.03 +/- 0.01 microgram/ml. Canine min PCs of drugs were almost the same as those reported in man except for procainamide and lidocaine. Membrane stabilizing effects seem to be important for suppressing canine ventricular arrhythmias.

Animals↗

Effects of prostaglandins on late coronary ligation arrhythmias in the dog.

Effects of an intravenous injection of indomethacin, prostaglandins (PGs) E1, E2 and F2 alpha and prostacyclin were examined by the use of a model of two-stage coronary ligation arrhythmias in conscious dogs. Indomethacin had no effect on the arrhythmias occurring 48 hr after coronary ligation. PGs and prostacyclin were injected after the injection of indomethacin. PGs did not show any significant antiarrhythmic effects on the arrhythmias occurring 48 hr after coronary ligation, while prostacyclin showed a transient arrhythmogenic effect. From the foregoing results, both endogenous and exogenous PGs do not seem to play a significant role in the genesis of late coronary ligation arrhythmias in the dog.

Animals↗

Anti-inflammatory effect of diclofenac-sodium ointment (cream) in topical application.

This study was performed to develop a topical ointment of diclofenac-Na which has a potent anti-inflammatory activity by oral administration. At first, research was carried out on the ointment base which influences the external anti-inflammatory effect of the drug. Ointments of diclofenac-Na were prepared with three kinds of bases: lipophilic, emulsion (cream) and gel bases; and their anti-inflammatory effects were compared. The cream was found to have the most potent effect. Therefore, in the next experiment, an optimum concentration of diclofenac-Na in cream was determined comparing the anti-inflammatory effect among the cream preparations containing 0.5, 0.75, 1.0 and 1.5% of the drug. Obvious effects were observed with the cream containing 1.0% and 1.5% of the drug concentration, and there was no significant difference in the anti-inflammatory activities of these two concentrations. Based on these results, the cream preparation containing 1.0% of diclofenac-Na (DF cream) was adopted as the external ointment of the drug. The anti-inflammatory effect of this cream was compared with that of existing anti-inflammatory ointments, i.e., indomethacin gel (IM gel), bufexamac cream (BM cream) and mobilat ointment (ML ointment). DF cream produced obvious inhibition on increased vascular permeability and on acute edema and remarkable suppression of ultraviolet erythema. These activities of DF cream were similar to those of IM gel and more potent than those of BM cream and ML ointment. The inhibitory effect of DF cream on the proliferation of granulation tissue was almost equal to that of ML ointment and more distinguishable than that of IM gel and BM cream. In adjuvant arthritis, DF cream reduced the swelling remarkably in the treated paw and slightly in the untreated paw. The anti-adjuvant activity of DF cream was equal to that of IM gel and more potent than that of BM cream and ML ointment. In pain to pressure stimulation, an analgesic effect was observed in the early stage of DF cream application, and its activity was slightly stronger than that of the other ointments. These results show that DF cream has an obvious anti-inflammatory effect as an external preparation, and the activity is comparable or superior to that of similar existing anti-inflammatory ointments. This cream may be considered as useful in the clinical field as a topical anti-inflammatory preparation.

Administration, Topical↗

Split atrial activity in a man with brady-tachy syndrome.

A 74-year-old man with brady-tachy syndrome showed split atrial activities in electrophysiologic studies. The split intervals of atrial activities varied spontaneously or in response to electric stimulations. The shorter were the coupling intervals of atrial extrastimuli, the longer the split intervals of captured atrial activities. At a critical timing of atrial extrastimuli, atrial flutter-fibrillation was initiated reproducibly. During atrial flutter-fibrillation, the split activities showed Wenckebach-like phenomenon. These findings seem to result from depressed conductivity. The split atrial activity may reflect a diseased state of the atrium which predisposes to atrial arrhythmias.

Aged↗

Progression of Wenckebach type A-V block to high degree A-V block in aged man.

This case report describes a 60 years old male with Wenckebach A-V block which progressed to high degree A-V block. Syncope and dizzy attacks were attributed to high degree A-V block in the study of ambulatory ECG (Holter). Wenckebach point was low; 90 bpm when the right atrium was paced. At 140 bpm, 2:1 A-H block with intermittent alternating and high degree A-H block were induced. Furthermore, a very wide His potential was recorded during the electrophysiological study. He received a permanent pacemaking. Since Wenckebach type A-V block is usually regarded as benign, this case seems to be rare.

Atrioventricular Node↗

[Antibacterial potency of cefotiam based on the clinical effect, MIC and decrement of organisms in the sputum].

To evaluate the antibacterial potency of cefotiam (CTM) clinical and laboratory studies were carried out and the results were as follows. Clinical evaluation and adverse reaction CTM was given to total of 23 patients, 10 with bronchopneumonia, 10 with bronchitis and one each with cystitis, enteritis and suspected sepsis. Overall efficacy rate was 78.3% (18/23) (excellent 9, good 9, fair 3, poor 2). Only 1 case showed a side effect of slightly elevated GOT and GPT. Antibacterial activities MIC of CTM against isolates from sputum was investigated on those patients mentioned above and was compared with MIC of CEZ and CMZ. CTM showed superior antibacterial activity against almost all strains. Especially on Haemophilus and Klebsiella antibacterial activity of CTM was impressive. Organisms in sputum Four out of 8 causative bacteria disappeared and 1 out of 8 decreased after administration of CTM. Thus CTM is considered to be the useful drug for the treatment of respiratory infection.

Adult↗

[Fundamental and clinical studies on T-1982 (cefbuperazone) in the field of obstetrics and gynecology].

T-1982 (cefbuperazone), a new cephem antibiotic, was fundamentally and clinically studied in the field of obstetrics and gynecology. The following results were obtained. The concentrations of the drug in arterial and venous blood, and genitalia following intravenous drip infusion were measured. The results demonstrated favourable transfer of the drug into various internal genital organs. Eleven patients with bacterial infections were treated with T-1982. The therapeutic results were markedly effective in 2 and good in 9 cases, therefore the effective rate was 100%. No side effects were noted in any cases. It is therefore, presumed, that T-1982 is a useful drug for infectious diseases in the field of obstetrics and gynecology although the number of subjects was not so large in this study.

Adolescent↗

Erythroleukemia induction by Friend leukemia virus. A host gene locus controlling early anemia or polycythemia and the rate of proliferation of late erythroid cells.

This report confirms that the Fv-5 locus controls the types of erythropoiesis induced by Friend erythroleukemia virus (FLV) (21) and extends the study to investigate the mode of action of this locus. With the use of FLV obtained by a variety of procedures, we showed that the polycythemia spleen focus-forming component (SFFVp) was responsible for the contrasting changes of hematocrits observed in FV-Pp (polycythemia strain)-infected DBA/2 (Fv-5pp) or CBA (Fv-5aa) mice. These changes in hematocrits were found to be a direct result of the rise in circulating reticulocytes and erythrocytes in DBA/2 mice and a corresponding drop of these erythroid cells in CBA mice 2 wk after infection. Examination of the FV-P-induced cellular changes indicated that dramatic increase in erythropoietin (epo)-independent erythroid precursor (CFU-E*) cells was detected in the spleens and marrow of both strains of mice. The epo responsiveness of the CFU-E in the uninfected and FV-P-infected CBA and DBA/2 mice was also very similar. Similar to FLV-infected DBA/2 mice, the FV-P-infected CBA mice also developed tumorogenic cells (CFU-FV) relatively early after infection (4-6 wk). Study of the physiological and pathological changes in the marrows and spleens of these infected mice indicated that significant differences were found in the spleens of the two strains of mice. The percent of reticulocytes in the spleen cells of CBA mice remained between 10 and 20%, and level of the DBA/2 mice increased to approximately 50%. This higher rate of erythropoiesis was also reflected in the significantly higher rate of uptake of 59Fe in the spleens of the DBA/2 mice. These results suggest that the Fv-5 locus might control the hematocrit levels of these mice by regulating the rates of erythropoiesis in the spleen levels of these mice, probably by affecting the rate of proliferation of an erythroid cell or cells. The erythroid cell(s) affected is likely to be more mature than the erythroid progenitor, CFU-E, as the levels of CFU-E in these two strains of mice were similar. The hypothesis that Fv-5 may control the rates of proliferation of a late erythroid (cell(s) is also supported by the significantly higher spleen weights found in the infected DBA/2 (approximately 2.5 g/spleen) mice than in the CBA (approximately 1 g/spleen) strain.

Anemia↗