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Biomedical subjects

S Miyazaki

Publications and source records attributed to S Miyazaki.

At least 73 records · Page 4Linked to original sources
PubMed2001

Analysis of Mn(2+)/Ca(2+) influx and release during Ca(2+) oscillations in mouse eggs injected with sperm extract.

Repetitive Ca(2+) release from the endoplasmic reticulum (ER) is necessary for activation of mammalian eggs. Influx and release of Mn(2+) and Ca(2+) during Ca(2+) oscillations induced by injection of sperm extract (SE) into mouse eggs were investigated by Mn(2+)-quenching of intracellular Fura-2 after adding Mn(2+) to external medium. Mn(2+)/Ca(2+) influx was detected at the resting state. A marked Mn(2+)/Ca(2+) influx occurred during the first Ca(2+) release upon SE injection, and persistently facilitated Mn(2+)/Ca(2+) influx was observed during steady Ca(2+) oscillations. As intracellular Mn(2+) concentration ([Mn(2+)](i)) increased progressively, periodic [Mn(2+)](i) rises appeared, corresponding to each Ca(2+)transient but taking a slower time course. A numerical simulation based on continuous Mn(2+)/Ca(2+) influx-extrusion across the plasma membrane and release-uptake across the ER membrane in a competitive manner mimicked well the Mn(2+) oscillations calculated from experimental data, strongly suggesting that repetitive Mn(2+) release develops after Mn(2+) entry and uptake into the ER. In other experiments, a marked Mn(2+) influx occurred upon Mn(2+) addition to Ca(2+)-free medium after depletion of the ER using an ER Ca(2+) pump inhibitor plus repeated injection of inositol 1,4,5-trisphosphate (InsP(3)). No significant increase in Mn(2+) influx was induced by injection of SE, InsP(3), or Ca(2+), when Ca(2+) release was prevented by pre-injection of an antibody against the InsP(3) receptor. We concluded that Ca(2+) influx is activated during the initial large Ca(2+)release possibly by a capacitative mechanism and kept facilitated during steady Ca(2+) oscillations. The finding that repetitive Mn(2+) release is caused by continuous Mn(2+) entry suggests that continuous Ca(2+) influx may play a critical role in refilling the ER and, thereby, maintaining Ca(2+)oscillations in mammalian fertilization.

Animals↗
PubMed2001

Successful management of secondary aortoesophageal fistula with graft infection.

A 60-year-old woman was transferred to our institution after massive hematemesis and the diagnosis of secondary aortoesophageal fistula was made. Five months previously, she had undergone graft replacement from the origin of the left subclavian artery to midthoracic aorta for chonic type B dissection. After an extraanatomic bypass was performed through a sternotomy, the infected thoracic aortic graft was resected through a left thoracotomy. She remained well without evidence of infection.

Aortic Dissection↗
PubMed2001

A novel pharmacologic action of glucocorticosteroids on leukotriene C4 catabolism.

Leukotriene (LT) C(4), a potent chemical mediator in human bronchial asthma, is metabolized to less active LTE(4) via LTD(4) in 2 consecutive enzymatic reactions by gamma-glutamyl transpeptidases and dipeptidases. We examined whether this inactivation process of LTC(4) was affected by fluticasone propionate, beclomethasone dipropionate, disodium cromoglycate, and salbutamol sulfate in transformed human bronchial epithelial cells. Fluticasone propionate and beclomethasone dipropionate accelerated LTC(4) catabolism by inducing activity of a LTC(4)-degrading enzyme, gamma-glutamyl transpeptidase-related enzyme (gamma-GTPRE), in transformed human bronchial epithelial cells. The activation of gamma-GTPRE might be regulated transcriptionally. This is a novel regulatory mechanism by which glucocorticosteroids exert antiasthma activities.

Albuterol↗
PubMed2001

Dynamic locomotor function in normals and patients with vertigo.

Gait analysis was performed in patients with various vestibular systems using a tactile sensor. There were 4 patients with vestibular neuronitis, 6 patients with large acoustic neuroma and 6 patients with spino-cerebellar degeneration (SCD). Gait phase related parameters such as stance, swing and double support were studied to assess gait stability. Also the area ratio of trajectories of center of force during stance and progression of foot pressure were checked. The calculated value of each variable became high in pathological cases compared with normal controls, and the highest value was obtained in the SCD group. As regards the effect of visual deprivation on stability of gait, the most striking change was found in the large acoustic neuroma group. In a case with a unilateral lesion such as vestibular neuronitis and large acoustic neuroma, foot pressure was greater on the lesion side, especially during gait with eyes closed. As for the foot pressure progression curve, the SCD group showed the most irregular pattern in general, although there were some individual variations. Those results could reflect a functional disorder of the gait control system caused by each disease. Significance of gait analysis is also discussed.

Adult↗
PubMed2001

The in vivo activity of olamufloxacin (HSR-903) in systemic and urinary tract infections in mice.

The in vivo activity of olamufloxacin (HSR-903), a new fluoroquinolone, was evaluated and compared with ciprofloxacin, sparfloxacin and levofloxacin. Olamufloxacin was active against systemic infection in mice inoculated with both Gram-positive and -negative bacteria. Olamufloxacin had equal efficacy for experimental urinary tract infections in mice caused by Pseudomonas aeruginosa.

Animals↗
PubMed2001

Efficacy of azithromycin, clarithromycin and beta-lactam agents against experimentally induced bronchopneumonia caused by Haemophilus influenzae in mice.

Azithromycin is an azalide with potent activity against Haemophilus influenzae including ampicillin-resistant strains. We evaluated the efficacy of azithromycin, clarithromycin and three beta -lactams when used for 1 day only and for 3 days for the treatment of a murine model of bronchopneumonia, using three strains of H. influenzae, two of which were ampicillin resistant. MICs of azithromycin (1-2 mg/L) and clarithromycin (4-8 mg/L) were similar for the three strains. The MICs of cefdinir and cefcapene for beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae were 32 times higher than those for beta-lactamase-positive ampicillin-resistant and ampicillin-susceptible strains. The viable counts in the infected tissues of azithromycin-treated mice with bronchopneumonia caused by the susceptible strain TUM8, beta-lactamase-positive strain TUH36 and BLNAR strain TUH267 were less than the counts obtained with the other antibiotics used, irrespective of MIC. At a dose of 50 mg/kg, the area under the concentration curve and the half-life of azithromycin in the lungs were respectively three times higher and six times longer than those of clarithromycin. Our results indicate that azithromycin may be useful for both ampicillin-susceptible and ampicillin-resistant bronchopneumonial infections caused by H. influenzae.

Animals↗
PubMed2001

In vitro and in vivo activities of meropenem and comparable antimicrobial agents against Haemophilus influenzae, including beta-lactamase-negative ampicillin-resistant strains.

The in vitro activity of ampicillin, cefotaxime, meropenem, panipenem, imipenem and biapenem was assayed using ampicillin-susceptible, beta-lactamase-positive and beta-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae isolated recently in Japan. Against ampicillin-susceptible isolates, cefotaxime was the most potent (MIC(90) 0.016 mg/mL). Both cefotaxime and meropenem (MIC(90) of both, 0.5 mg/L) were the most potent against beta-lactamase-positive isolates. Against BLNAR isolates, meropenem (MIC(90) 0.5 mg/L) was the most potent. In murine bronchopneumonia caused by ampicillin-susceptible and BLNAR H. influenzae, cefotaxime showed the best efficacy, followed by meropenem. Our results indicate that meropenem could be a useful intravenous agent for infections caused by H. influenzae, including BLNAR strains.

Ampicillin Resistance↗
PubMed2001

Expression of a green fluorescent protein variant in mouse oocytes by injection of RNA with an added long poly(A) tail.

In oocytes, cytoplasmic 3' polyadenylation regulates translational activation of dormant mRNA during meiotic maturation. Thus exogenous proteins are hardly expressed after injection of conventional RNA. To circumvent this, we synthesized a long polyadenylated (approximately 250 A) tail to encode RNA with an enhanced yellow fluorescent protein targeted to mitochondria (EYFP-mito), and injected it into mouse oocytes at the germinal vesicle (GV) stage. From this transcript, EYFP-mito was clearly expressed in approximately 80% of oocytes, while scarce expression from a transcript with only 30 A was observed. In strongly expressing oocytes, fluorescence was detected within 1-3 h after RNA injection, increased linearly up to 12 h, and reached a maximum at 12-15 h. The distribution of EYFP-mito matched the staining of mitochondria in these oocytes. About 80% of these oocytes underwent GV breakdown and 60% matured in vitro, comparable to non-expressing or non-RNA-injected oocytes. Some of the oocytes which strongly expressed EYFP-mito remained at the GV stage. Thus, the expression was not always accompanied by meiotic maturation, nor did it suppress the maturation process. Mature oocytes expressing EYFP-mito possessed normal fertilizability associated with intracellular Ca(2+) oscillations, and developed into 2-cell embryos. Thus, polyadenylated RNA is a useful tool applicable to the expression of EYFP-fused functional proteins or of indicator protein probes for studies of mammalian fertilization.

Animals↗
PubMed2001

Activity of a sperm-borne oocyte-activating factor in spermatozoa and spermatogenic cells from cynomolgus monkeys and its localization after oocyte activation.

It is widely accepted that mature mammalian oocytes are induced to resume meiosis by a sperm-borne oocyte-activating factor(s) (sperm factor, SF) immediately after normal fertilization or intracytoplasmic sperm injection. The SF is most likely a soluble factor that is localized within the cytoplasm of mature spermatozoa, but the exact stage at which it appears during spermatogenesis and its localization after oocyte activation is not fully understood, except in the mouse. First, we injected mature spermatozoa and spermatogenic cells from cynomolgus monkeys into mouse oocytes to assess their oocyte-activating capacity. More than 90% of mouse oocytes were activated after injection of monkey spermatozoa. Round spermatids and primary spermatocytes (late pachytene to diplotene) also activated oocytes (93% and 79%, respectively). Injection of monkey spermatozoa and spermatids induces intracellular Ca(2+) oscillations in a pattern similar to that seen following normal fertilization. Most spermatocytes did not produce typical intracellular Ca(2+) oscillations. Second, we transferred pronuclei or cytoplasts from mouse oocytes that had been activated by monkey spermatozoa or spermatids into intact mature mouse oocytes by electrofusion in order to examine the localization of the SF after pronuclear formation. Some of the SF was localized within the pronuclei, but some stayed in the ooplasm. This study demonstrated that spermatogenic cells of cynomolgus monkeys acquire oocyte-activating capacity at much earlier stages than those of mice, and that the monkey SF has a pronucleus-directing nature, although to a lesser extent than the mouse SF.

Animals↗
PubMed2001

In vitro and in vivo antibacterial activities of L-084, a novel oral carbapenem, against causative organisms of respiratory tract infections.

L-084 (a prodrug of LJC 11,036 [L-036]) is a new oral carbapenem. Here we compared the in vitro and in vivo antibacterial activities of L-036 with those of imipenem, faropenem, ceditoren-pivoxil, cefdinir, amoxicillin, and levofloxacin. The MICs at which 90% of the isolates were inhibited of L-036 against methicillin-susceptible staphylococci, Streptococcus pneumoniae including penicillin-resistant organisms, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae including ampicillin-resistant organisms, Legionella pneumophila, and Moraxella catarrhalis were equal to or less than 1 microg/ml. In pharmacokinetics studies of L-084 in lungs of mice, the maximum concentration in serum, half-life, and area under the concentration-time curve of this drug were 9.09 microg/g of tissue, 6.18 h, and 31.0 microg. h/ml, respectively. In murine respiratory infection models of penicillin-susceptible and -resistant S. pneumoniae and H. influenzae, the efficacies of L-084 were better than those of reference drugs. Our results indicate that the in vitro high potency and good distribution in the lungs might be the underlying mechanisms of its efficacy in the murine model of pneumonia.

Animals↗
PubMed2001

In vivo efficacy of telithromycin (HMR3647) against Streptococcus pneumoniae and Haemophilus influenzae.

The in vivo activity of telithromycin against erythromycin A- and penicillin G-resistant Streptococcus pneumoniae was superior to that of azithromycin, clarithromycin, cefdinir, and levofloxacin. In respiratory tract infections caused by erythromycin A-susceptible S. pneumoniae or Haemophilus influenzae in mice, telithromycin was more effective than clarithromycin and comparable to azithromycin.

Animals↗
PubMed2001

Oral sustained delivery of theophylline from thermally reversible xyloglucan gels in rabbits.

Thermally reversible gels formed in-situ following the oral administration of dilute aqueous solutions of an enzyme-degraded xyloglucan to rabbits were evaluated as sustained-release vehicles for the delivery of theophylline. In-vitro release of theophylline from gels formed by warming xyloglucan sols (0.5, 1.0 and 1.5% w/w) to 37 degrees C followed root-time kinetics over a period of 4 h. Gels formed after oral administration to rabbits of chilled 1.5% w/w aqueous solutions of xyloglucan containing dissolved drug showed sustained-release characteristics with a maximum plasma concentration at 4.5 h. The theophylline bioavailability from a 1.5% w/w xyloglucan gel was 1.7-2.5 times that of commercial oral sustained-release liquid dosage forms containing an identical theophylline concentration. It was concluded that dilute solutions of the enzyme-degraded xyloglucan had suitable rheological properties and in-situ gelling characteristics for use as sustained-release vehicles for oral drug delivery. The in-vivo release characteristics of theophylline in a rabbit model suggested the potential for the use of these vehicles in humans for the oral delivery of this drug.

Administration, Oral↗
PubMed2001

Appropriate indications for the use of a percutaneous cardiopulmonary support system in cases with cardiogenic shock complicating acute myocardial infarction.

Percutaneous cardiopulmonary support (PCPS) is now available for hemodynamic support in patients with cardiogenic shock, but there are no guidelines for its use. The present study determined the appropriate indications for the use of the PCPS in patients with cardiogenic shock complicating acute myocardial infarction (AMI). Sixty-four consecutive patients with cardiogenic shock complicating AMI had hemodynamic support with an intraaortic balloon pump (IABP; n=38) and/or PCPS (n=26). The shock score (0-15) was calculated immediately before starting these support systems to quantify the severity of shock. Multivariate logistic regression analysis determined the clinical factors affecting in-hospital mortality. The relationship between in-hospital prognosis and the shock score was also examined in the 2 groups. The most significant factor related to the in-hospital prognosis was the shock score (p=0.0007; OR 2.16, 95% CI: 1.37-3.39). Another related factor was revascularization; however, this relationship did not reach statistical significance (p=0.069; OR 0.06). Among the 13 cases whose shock score was 4-8 (moderate shock), 5 survived in the PCPS group, but only 1 of 19 patients survived in the IABP group (p<0.05). None of the patients in either group whose shock score was more than 9 survived. The severity of shock is the most reliable independent predictor of in-hospital mortality in patients with cardiogenic shock complicating AMI. Using PCPS in patients with moderate cardiogenic shock may improve their in-hospital survival, but it must be used before the shock becomes severe.

Aged↗
PubMed2001

Late reperfusion (6-24 hours after onset) improves left ventricular function in patients with acute myocardial infarction.

The TAMI-6 trial has demonstrated that coronary reperfusion >6h after onset (ie, late reperfusion) in patients with acute myocardial infarction (AMI) does not improve left ventricular (LV) function during the chronic phase of infarction. However, the low patency rate (only 60%) of the infarct-related artery (IRA) during the chronic phase in the TAMI-6 trial raises a new hypothesis that late reperfusion with a higher patency rate may improve LV function during the chronic phase. Forty-four patients with AMI, who were admitted to hospital 6-24h after the symptom onset and in whom emergency coronary angiography revealed a total occlusion of the IRA, were randomly assigned to either the late reperfusion group (n=22) or the non-reperfusion group (n=22). The initial success rate of reperfusion therapy in the late reperfusion group was 86% and the chronic patency rate of the IRA was 91%. The improvements in ejection fraction and chord shortening in the infarct region from the acute phase to the chronic phase were significantly greater in the late reperfusion group than in the non-reperfusion group. Late reperfusion with a high patency rate of the IRA significantly improves LV global and regional function in patients with AMI.

Adult↗
PubMed2001

Is inflammation related to the clinical severity of unstable angina?

The present study determined the white blood cell (WBC) count and the serum C-reactive protein (CRP) level in 27 patients with coronary spastic angina, 16 with Braunwald class IB unstable angina (UA) and 13 with Braunwald class IIIB. The relationship between the clinical presentation of UA and the requirement for emergency percutaneous transluminal coronary angioplasty (PTCA) was examined, and in patients with medically refractory angina, the determining factor among the clinical manifestations of angina was also investigated. In the acute phase, the WBC count and the serum CRP level were significantly higher in patients with Braunwald class IIIB than in those with coronary spastic angina or Braunwald class IB UA (p<0.001). In the Braunwald class IIIB group, a significantly higher rate of patients required emergency PTCA than that of the coronary spastic angina group (p<0.01). Patients with medically refractory angina had a significantly higher WBC count and higher serum CRP level on admission, and the WBC count on admission was independently associated with medically refractory angina by multivariate analysis (p<0.05). Inflammation may play a major pathological role in the rapid development of acute coronary syndrome.

Angina, Unstable↗
PubMed2001

Initial experience with nifekalant hydrochloride (MS-551), a novel class III antiarrhythmic agent, in patients with acute extensive infarction and severe ventricular dysfunction.

Nifekalant hydrocholoride, a novel class III antiarrhythmic agent, was used as the treatment in 4 patients with extensive anterior infarction and severe ventricular dysfunction. The malignant ventricular tachyarrhythmia was effectively suppressed at a relatively low dose, without compromising the hemodynamics, indicating that this potent K+ channel blocker has therapeutic potential for acute myocardial infarction.

Aged↗
PubMed2001

Role of transesophageal echocardiography in the prediction of thromboembolism in patients with chronic nonvalvular atrial fibrillation.

The purpose of this study was to determine whether parameters derived from transesophageal echocardiography (TEE) could predict thromboembolism in patients with chronic nonvalvular atrial fibrillation (AF). Eighty-nine patients, mean age 66+/-9 years, who underwent TEE in 1996 to 1999 were studied. The clinical endpoint was a thromboembolic event, including transient ischemic attack (TIA). Sixty-seven patients (75%) were anticoagulated with warfarin after TEE. After a follow-up period of 29+/-10 months, 1 patient died suddenly, 4 had a thromboembolism, and 3 had a TIA; the annual embolic event rate was 3.3%. Left atrial appendage (LAA) thrombus (86% vs 17%, p<0.001), LAA dysfunction (LAA velocity <20 cm/s; 71% vs 25%, p=0.009), and severe LA spontaneous echo contrast (29% vs 2%, p=0.002) were more prevalent in patients with an embolic event than in those without. In patients with LAA thrombus, the annual event rate was 11% as compared with 1.2% in those without (p=0.004). On the Cox proportional hazards model analysis, LAA thrombus (chi-square 7.0, p=0.008), severe LA spontaneous echo contrast (chi-square 7.0, p=0.008), and LAA dysfunction (chi-square 5.9, p=0.015) were significantly related to thromboembolism. Multivariate analysis revealed that LAA thrombus (chi-square 5.5, p=0.019) and LAA dysfunction (chi-square 4.0, p=0.045) were the independent predictors. In conclusion, TEE parameters, particularly the presence of LAA thrombus, can be used to assess thromboembolic potential in patients with chronic nonvalvular AF.

Aged↗