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K Shibasaki

Publications and source records attributed to K Shibasaki.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Serotypes and drug susceptibility of Pseudomonas aeruginosa isolated from clinical specimens].

Between January, 1982 and December, 1994, 236 Pseudomonas aeruginosa strains were isolated from clinical specimens at our division, and were tested for serotypes and drug-susceptibilities to 15 antibiotics. Serotype G strains were isolated at the highest frequency (32.6%), and followed by strains of serotype B (15.7%), A (11.9%), E (9.3%), I (7.2%), F and M (5.5%), non-typable (5.1%), D (3.4%), H (2.1%), C and K (0.8%). We examined the changes of isolation frequencies of different serotypes annually. Isolation frequencies of serotypes E and F showed tendency to decrease, whereas serotype I has been isolated increasingly year by year. MIC90's of the 15 antibiotics were as follows, tosufloxacin: 0.78 microgram/ml, biapenem (BIPM) and ofloxacin (OFLX): 3.13 micrograms/ml, imipenem (IPM), ceftazidime, cefozopran, cefsulodin and gentamicin: 6.25 micrograms/ml, aztreonam and amikacin: 12.5 micrograms/ml, piperacillin, cefoperazone and minocycline (MINO): 25 micrograms/ml, fosfomycin: > 100 micrograms/ml and chloramphenicol: > 200 micrograms/ml. MIC90'S of IPM, BIPM, MINO and OFLX increased 4-fold from stage I (1982-1987) through stage III (1992-1994) and the isolation frequency of drug-resistant strains increased year by year. In other words, antibiotic resistant strains appeared increasing with time. No relationship between serotypes and drug-resistance were observed.

Anti-Bacterial Agents↗
PubMed1995

Effect of the potassium channel opener YM934 on the contractile response to electrical field stimulation in pig detrusor smooth muscle.

PURPOSE: The effect of a potassium channel opener, YM934, on the contractile response to excitatory neurotransmitters was investigated in isolated pig detrusor smooth muscle. MATERIALS AND METHODS: Electrical field stimulation (EFS; 5 second trains, 50 V, 0.8 msec. duration), alpha, beta-MeATP (3 x 10(-7) to 10(-5) M.) or carbachol (3 x 10(-8) to 10(-6) M.) produced a contractile response in isolated pig detrusor smooth muscle. The effect of YM934 on the contractile responses was evaluated in comparison with the antagonism of the putative cotransmitters, acetylcholine and ATP. RESULTS: A tetrodotoxin-sensitive, frequency-dependent contractile response to electrical field stimulation was obtained. Atropine (3 x 10(-8) M.) significantly inhibited the contractile response at high frequencies, whereas alpha, beta-MeATP (5 x 10(-6) M.) (desensitizer of P2X-purinoceptors) significantly inhibited the response at low frequencies. YM934 (10(-8) to 10(-7) M.) dose-dependently inhibited the nerve-mediated contractile responses to all frequencies but preferentially at low frequencies, by analogy with alpha, beta-MeATP. A combination of YM934 (3 x 10(-8) M.) and atropine (3 x 10(-8) M.) reduced the response at all frequencies to between 10 and 20% of control, an effect similar to that obtained with alpha, beta-MeATP (5 x 10(-6) M.) and atropine (3 x 10(-8) M.). In addition, YM934 (3 x 10(-8) M.) markedly inhibited the contractile response induced by exogenously applied alpha, beta-MeATP (3 x 10(-7) to 10(-5) M.) but only slightly inhibited the contractile response induced by exogenously applied carbachol (3 x 10(-8) to 10(-6) M.). CONCLUSION: These results suggest that YM934 may hyperpolarize the membrane of pig detrusor smooth muscle through the opening of ATP-sensitive potassium channels and, as a result, may functionally inhibit the contractile response to purinergic nerve stimulation that elicits the membrane depolarization.

Adenosine Triphosphate↗
PubMed1994

Pharmacological properties of YM-26365, a low molecular weight, orally active renin inhibitor.

This report describes the pharmacological properties of a novel renin inhibitor (YM-26365: (3R)-3-[3-[(1S)-1-cyclohexylmethyl-2-hydroxy-3- [(1-methyl-5-tetrazolyl)thio]propyl]ureido]-1-methyl-5-phenyl- 2,3-dihydro-1H-1,4-benzodiazepin-2-one) with molecular weight 577 and no peptide bonds. YM-26365 inhibited human plasma renin with an IC50 value of 2.9 x 10(-6) M, but did not affect plasma renin from dogs, rabbits, and rats at 10(-4) M. YM-26365 inhibited not only human renin, but also cathepsin D with an IC50 value of 1.7 x 10(-5) M. This compound competitively inhibited the reaction between recombinant human renin and N-acetyl tetradecapeptide with a Ki value of 1.1 x 10(-6) M. In pithed spontaneously hypertensive rats, YM-26365 at 10 mg/kg i.v. significantly antagonized the pressor response to recombinant human renin, but did not affect responses to angiotensin II, angiotensin I, norepinephrine, or arginine vasopressin. Similarly, oral administration of YM-26365 (10 and 30 mg/kg) to pithed spontaneously hypertensive rats caused a shift to the right of the recombinant human renin dose-pressor response curve. Systemic bioavailability as determined on the basis of the ratio of the total area under the plasma concentration-time curve after 3 mg/kg i.v. and 30 mg/kg orally to rats was 9.6%. These results demonstrate that YM-26365 is a weak but orally absorbed, low molecular weight renin inhibitor.

Administration, Oral↗
PubMed1994

The role of extracellular Ca2+ in carbachol-induced tonic contraction of the pig detrusor smooth muscle.

The role of extracellular Ca2+ in the tonic-contractile response to muscarinic receptor stimulation was investigated in isolated detrusor smooth muscle from the pig urinary bladder. Carbachol (10(-8)-10(-5) M) produced a concentration-dependent contractile response in isolated pig detrusor smooth muscle strips consisting of an initial phasic component followed by a tonic component. During the plateau of the tonic contractions induced by carbachol at the submaximal concentration of 10(-6) M, the inhibiting effects of atropine, EGTA, nifedipine (a voltage-dependent calcium channel antagonist), H-7 [a protein kinase C (PKC) inhibitor] and YM934 (a potassium channel opener) on the contractions were evaluated. Atropine (10(-10)-3 x 10(-8) M) concentration-dependently inhibited the tonic contractions induced by carbachol. In the same experimental conditions, EGTA (4 mM) and nifedipine (10(-9)-3 x 10(-7) M) depressed the tonic contractions in a concentration-dependent manner as did H-7 (10(-5)-3 x 10(-5) M) and YM934 (10(-8)-10(-6) M). However, H-7 (10(-5)-3 x 10(-5) M) and YM934 (10(-6) M) were very weak in inhibiting the contractions induced by KCl (50 mM) in isolated pig detrusor smooth muscle strips. These results suggest that the tonic-contractile response induced by carbachol in pig detrusor smooth muscle strips is dependent mainly on depolarization of the cell membranes and an influx of extracellular Ca2+, and also suggest that this depolarizing response may be due to inactivation of ATP-sensitive potassium channels through muscarinic activation of PKC.

Animals↗
PubMed1994

Pharmacologic profiles of YM934, a novel potassium channel opener.

Pharmacologic profiles of YM934, a newly synthesized 1,4-benzoxazin derivative K channel opener were evaluated in in vitro and in vivo experiments. In isolated rat portal vein, YM934 and a benzopyran derivative K channel opener lemakalim inhibited the frequency of spontaneous rhythmic contractions concentration dependently, with IC50 values of 14 and 38 nM, respectively. These inhibitory effects were competitively antagonized by glibenclamide (an ATP-sensitive K channel blocker; 10(-7)-3 x 10(-6) M). In isolated rabbit aorta, YM934 (10(-8)-10(-6) M) and lemakalim (10(-8)-10(-6) M) relaxed the contractions induced by 20 mM KCl concentration dependently but were ineffective against the contractions induced by 50 mM KCl. YM934 (10(-8)-3 x 10(-6) M) and lemakalim (3 x 10(-8)-10(-5) M), but not the calcium antagonist nifedipine, relaxed the contractions induced by norepinephrine (NE 10(-6) M) or prostaglandin F2 alpha (PGF2 alpha 3 x 10(-6) M) in the aorta. In pentobarbital-anesthetized dogs, YM934 (1-10 micrograms/kg intravenously, i.v.) dose-dependently increased coronary artery blood flow (CBF), and decreased total peripheral resistance (TPR) and mean blood pressure (MBP). YM934 selectively increased CBF, but had little effect on vertebral, carotid, mesenteric, renal and femoral artery BF. These vasodilatory effects of YM934 were antagonized by glibenclamide. YM934 is a potent K channel opener and possesses potent vasodilatory effects, with particularly pronounced effects on the coronary artery. These effects of YM934 may, like lemakalim, be mediated by opening of ATP-sensitive K channels.

Anesthesia↗
PubMed1994

The influences of the buffer capacity of various substances on pH changes in dental plaque.

This study clarified the suitable pKa value for buffering substances against plaque pH fall in vitro and simultaneously estimated the effect of low molecular chitosan (LMCS) on plaque pH lowered by metabolized acids in vitro and in vivo. Five buffering substances with different pKa, aspartame (pKa: 7.8), phosphate buffer (7.1), LMCS (6.4), maleate buffer (6.2), and monofluorophosphate (4.8), were tested in this study. In the method using S. mutans cells, phosphate inhibited the pH fall from an initial pH of over 7.0, but phosphate exhibited no effect when the initial pH was 6.0. By the addition with lactic acid, LMCS and maleate exhibited more effective inhibition of the pH-fall than the others. These observations imply that pKa value is an important indicator of the ability of a buffering substance to reduce pH fall in dental plaque and that the optimum pKa value may be around pH 6.3. In the plaque pH measurement using ISFET electrode, LMCS showed an additional effect in inhibiting plaque pH fall following direct application of the glucose solution. The findings indicate that LMCS may be useful as a food additive to decrease the cariogenicity of foods.

Adult↗
PubMed1994

Effects of low molecular chitosan on pH changes in human dental plaque.

Effects of six kinds of low molecular chitosan (LMCS) on pH changes in dental plaque were compared in vitro and in vivo in order to clarify the relationship between their characteristics and effectiveness. Six LMCS with different molecular weights (MW) (500-3,000) and degrees of deacetylation (DAC) (50-95%) were prepared for this study. Evaluations using S. mutans cell suspensions in vitro showed that all samples had almost equal abilities to reduce pH fall in dental plaque. They were found to have no influence on the glycolytic activity of S. mutans. However, clinical evaluations of pH fall in dental plaque using an ion-sensitive field-effect transistor (ISFET) electrode showed unexpected results as follows; The most reduction in pH fall was obtained with the LMCS with a MW of 3,000 and a DAC of 50%, which had been presumed to be the most ineffective sample. The second ranked LMCS in this experiment had a MW of 500 and a DAC of 95%; it had been expected to be the most effective one. The findings indicated that LMCS has a high ability to inhibit pH fall in dental plaque and suggested that such properties as molecular weight and degree of deacetylation can have great influences upon its activity in clinical application.

Acetylation↗
PubMed1994

pH response of human dental plaque to chewing gum supplemented with low molecular chitosan.

The effects of low molecular chitosan (LMCS) on pH responses of human dental plaque following exposure to fermentable carbohydrates were investigated by an ion-sensitive field-effect transistor electrode system. After the plaque pH values were minimized by direct application of 5% glucose solution or consumption of sugared caramel, the subjects started chewing the test gums containing 0 (control), 1 or 3% (w/w) LMCS for three minutes. The pH response was monitored until it recovered to over pH5.5. In the case of the glucose solution, chewing 3% LMCS gum caused significantly more rapid pH recovery toward the resting level than did the control gum. Initial pH rising rate during gum chewing was faster with either of the two LMCS gums than with the control gum. In the case of caramel, additional effects of LMCS were observed numerically as LMCS content increased. The findings indicated that LMCS had a potential to promote recovery of plaque pH after acidogenic challenge and to maintain the plaque pH around neutrality.

Adult↗
PubMed1993

Antianginal effects of YM-16151-4 in various experimental angina models.

The antianginal effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in various experimental angina models and compared with those of nifedipine and propranolol. In anesthetized dogs, YM-16151-4 (0.3 and 1 mg/kg intravenously, i.v.) increased coronary blood flow and reduced myocardial oxygen consumption (MVO2). In isolated dog coronary arteries, YM-16151-4 concentration-dependently inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 91 nM. In anesthetized rats, YM-16151-4 also inhibited the ST-segment depression induced by vasopressin (0.5 U/kg i.v.) with an ED50 value of 29 mg/kg orally, (p.o.). Nifedipine was also effective in these models, but propranolol was not. In addition, YM-16151-4 (0.3 mg/kg i.v.) inhibited the ST-segment elevation in the epicardial ECG induced by coronary artery occlusion in anesthetized dogs. Propranolol (1 mg/kg i.v.) also inhibited this elevation, but nifedipine (0.003 mg/kg i.v.) did not. In anesthetized dogs, furthermore, the prolongation of PQ-interval induced by YM-16151-4 was almost the same as that induced by propranolol. These results demonstrate that YM-16151-4, in contrast to nifedipine and propranolol, is fully effective in these various types of angina models. Thus, YM-16151-4 is expected to prove a valuable antianginal agent in treatment of various types of angina pectoris, with these antianginal effects resulting from the sum of its calcium entry blocking and beta 1-adrenoceptor blocking activities.

4-Aminopyridine↗
PubMed1993

Cardiovascular effects of YM-16151-4: a novel calcium entry blocking and selective beta 1-adrenoceptor blocking agent in rats and dogs.

The cardiovascular effects of YM-16151-4 were evaluated in rats and dogs. In conscious rats, YM-16151-4 (3-30 mg/kg p.o.) produced a dose-dependent hypotensive effect without increasing heart rate (HR) and plasma renin activity (PRA). Nifedipine (3-10 mg/kg p.o.) produced a dose-dependent hypotensive effect but significantly increased HR and PRA. Atenolol (30 mg/kg p.o.) decreased PRA but did not decrease blood pressure and HR. The cardiovascular effects of the combination of nifedipine and atenolol were similar to those of YM-16151-4. It is interesting that the time course of the hypotensive effect of YM-16151-4 was similar to that of its beta 1-adrenoceptor blocking effect, although the time courses of these effects of the combination of nifedipine and atenolol were different. In conscious dogs, YM-16151-4 (0.3-10 mg/kg p.o.) also produced a long-lasting hypotensive effect with almost no effect on HR and PQ-interval. The time course of the beta 1-adrenoceptor blocking effect was similar to that of its hypotensive effect. Furthermore, during 10-day repeated oral administration, neither tolerance nor augmentation was observed in the hypotensive and beta 1-adrenoceptor-blocking effects. In conclusion, the present results indicate that YM-16151-4 is an effective and long-lasting hypotensive agent that does not increase HR and PRA. These effects of YM-16151-4 may be attributable to its calcium-entry-blocking and beta 1-adrenoceptor-blocking activities, and the ratio of two activities was constant after single and repeated oral administrations.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1992

Cardiovascular effects of a novel calcium entry blocking and selective beta 1-adrenoceptor blocking agent, YM-16151-4, in anesthetized and conscious dogs.

Cardiovascular effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in dogs. In anesthetized dogs, YM-16151-4 (0.01-1 mg/kg intravenously, i.v.) dose-dependently increased coronary blood flow (CBF) and decreased mean blood pressure (MBP), total peripheral resistance (TPR), dP/dtmax, double product, and left ventricular (LV) work without increasing heart rate (HR) and cardiac output (CO). YM-16151-4 increased vertebral blood flow as well as CBF, but had no effect on carotid, mesenteric, renal, and femoral blood flow. Coronary vasodilating activity of YM-16151-4 was also observed after intracoronary artery injection (i.a.). In anesthetized and vagotomized dogs, YM-16151-4 dose-dependently inhibited isoproterenol (0.2 micrograms/kg i.v.)-induced tachycardia and decrease in diastolic BP (DBP), with ED50 values of 0.039 and 0.52 mg/kg i.v., respectively. In conscious dogs, YM-16151-4 (0.1-1 mg/kg i.v.) produced a dose-dependent hypotensive effect with no effect on HR or PQ-interval. The hypotensive effect of YM-16151-4 (0.3 and 1 mg/kg i.v.) reached its maximum approximately 1-2 h after each dosing and lasted 6-8 h. These results suggest that YM-16151-4 actually behaves as a hybrid compound, combining calcium entry blocking and beta 1-adrenoceptor blocking activities, and that this compound could be a novel long-acting antianginal and antihypertensive agent.

Adrenergic beta-Antagonists↗
PubMed1992

Expansive laminoplasty with reattachment of spinous process and extensor musculature for cervical myelopathy.

Since 1986 we have performed expansive laminoplasty with reattachment of the spinous processes and extensor musculature in cases of cervical myelopathy, to avoid the late postoperative complications of extensive laminectomy. The operative procedure and results are given in detail. Forty cases (24 men, 16 women) were followed for a mean of 28 months. Postoperative results were satisfactory, with no major complications according to the evaluation criteria of the Japanese Orthopaedic Association. No instability or malalignment was seen on postoperative radiographs.

Adult↗
PubMed1992

[Age-related non-tumorous lesions in SPF C57BL/6 mice with special reference to amyloidosis].

Non-tumorous pathological changes in C57BL/6 CrSlc mice, which were reared under a barrier system and died spontaneously, were examined. At 3 months intervals 125 to 209 mice were purchased at 4 weeks of age and raised for the supply of aged animals. A large portion of the mice were used for various experiments between 3 and 30 months of age, while not a small number died spontaneously and were autopsied. The major non-neoplastic lesion was amyloidosis, with incidence of 55.5% and 74.4% for the autopsied female and male, respectively. The organs involved were the liver, kidneys, spleen, adrenal glands, ileum, heart and lungs. Skin ulceration and its scar, cerebral vascular calcification, glomerulosclerosis and sepsis in both sexes, distension of the seminal vesicles in males, fibroblast growth of the adrenal glands in females were commonly found. Incidence of spontaneous neoplastic lesions was 69.7% and 55.1% for the female and male, respectively.

Aging↗
PubMed1992

[Age-related incidence of spontaneous tumors in SPF C57BL/6 and BDF1 mice].

Incidence of spontaneous tumors in C57BL/6 NCrj (CR), C5BL/6 CrSlc (SL) and B 6 Crj x DBA/2 NCrj F1 (BD) mice, which were reared under a barrier system and died natural death, were examined. Cohorts of mice in 200 to 300 each were purchased at 4 weeks of age and raised under SPF conditions. A large portion of the mice were used for various experiments between 3 and 30 months old while not a small number died before use and were autopsied. Median survival periods of the female and male were estimated at 697 and 680 days for CR, 764 and 806 days for SL and 866 and 929 days for BD, respectively. Incidence of spontaneous neoplastic lesions in the autopsied animals were 77.4% and 79.2% of 535 female and 590 male CR, 69.7% and 55.1% of 502 female and 463 male SL, and 75.8% and 78.0% of 298 female and 346 male BD, respectively. In CR, histiocytic sarcoma was the most predominant tumor, accounting for 72.1% of all tumors. In SL, malignant lymphoma was the most prevailing, forming 62.3%, and, in male BD, hepatocellular carcinoma was the most frequent, accounting for 41.8% of all tumors.

Aging↗
PubMed1991

Inhibition of adsorption of oral streptococci to saliva treated hydroxyapatite by chitin derivatives.

This study estimated the effects of five chitin derivatives low molecular chitosan (LMCS), ethyleneglycol chitin (PEGT), carboxymethyl chitin (PCMT), sulphated chitosan (PSSS), and phosphorylated chitin (PPPT) on the adsorption of three oral streptococci to saliva-treated hydroxyapatite (S-HA). The adsorption was evaluated by measuring the optical density of the bacterial cell suspensions released from saliva-treated hydroxyapatite by 0.5 N HCl. The adsorption of test strains to S-HA progressively decreased in proportion to each additional volume of PEGT, PPPT, or PSSS. PPPT and PSSS quite effectively inhibited the adsorption of S. mutans onto S-HA, but were less effective against S. sanguis and S. mitis. PPPT, PSSS, and PCMT all markedly promoted the desorption of S. mutans cells pre-adsorbed onto S-HA. Pretreatment of S-HA with PPPT, PSSS, or PCMT significantly decreased the subsequent adsorption of S. mutans and S. mitis. Pretreatment of these cells with PEGT also decreased their adsorption to S-HA. These findings suggest that these chitin derivatives may change the ionic natures of the S-HA and the bacterial cell surface, resulting in a less favorable interaction.

Adult↗
PubMed1990

Pharmacological profiles of YM-16151-1 and its optical isomers: a novel calcium entry blocking and selective beta-1 adrenoceptor blocking agent.

The pharmacological properties of YM-16151-1 [(+/-)-dimethyl 4-[2-[4-(2-hydroxy-3-phenoxypropylamino)butoxyl]-5-nitrop hen yl]-2,6- dimethyl-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride] and its optical isomers were evaluated in in vitro studies and radioligand binding assay. In isolated tissues, YM-16151-1 produced a competitive antagonism of CaCl2-induced contraction in the isolated rabbit aorta with a pKca-1 value of 8.17, and also produced a competitive antagonism of isoproterenol-induced positive chronotropic responses in the isolated rat atria with a pA2 value of 8.47. In rat brain membrane preparations, YM-16151-1 produced dose-dependent inhibitions of [3H]nitrendipine and [3H]dihydroalprenolol bindings with pKi values of 7.21 and 8.07, respectively. Calcium entry blocking activity of YM-16151-1 was 7 times weaker and 3 times greater than nifedipine and diltiazem, respectively. Beta-1 adrenoceptor blocking activity of YM-16151-1 was 2 times weaker than that of propranolol. YM-16151-1 showed about 900-fold selectivity for beta-1 adrenoceptor. YM-16151-1 also showed a weak alpha-1 adrenoceptor blocking activity and its potency was about 13 times weaker than that of phentolamine. S-(-)- and R-(+)-isomers of YM-16151-1 showed the same potency of calcium entry blocking activity. However, in beta-1 adrenoceptor blocking activity, the S-(-)-enantiomer was about 13 to 22 times more potent than the R-(+)-enantiomer. Oral administration of YM-16151-1 produced a dose-dependent blood pressure lowering effect without increasing heart rate in conscious spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗