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Biomedical subjects

S Miyazaki

Publications and source records attributed to S Miyazaki.

At least 415 records · Page 23Linked to original sources

A variant form of hypobetalipoproteinaemia associated with ataxia, hearing loss and retinitis pigmentosa.

A six-year-old Japanese boy had ataxia, mental retardation, peripheral neuropathy, proximal myopathy, hearing loss, retinitis pigmentosa and deficiencies in apolipoprotein AI, B, CII and CIII. His clinical features except for hearing loss resembled those of abetalipoproteinaemia or symptomatic hypobetalipoproteinaemia, but his apolipoprotein abnormalities were distinct from these disorders. He had apolipoprotein B-100 with a normal molecular weight. Although most of his neurological manifestations were compatible with those of vitamin E deficiency, their early onset and the presence of hearing loss was unusual for that condition. There has been slight deterioration of ataxia during two years follow-up despite high-dose vitamin E supplementation. Other abnormalities in lipid metabolism might be associated with the neurological damage in this case.

Ataxia↗

The stimulative effect of diffusion potential on enoxacin uptake across rat intestinal brush-border membranes.

Evidence of a membrane potential dependence for enoxacin uptake by rat intestinal brush-border membrane vesicles has been found. The transient overshooting uptake of enoxacin disappeared in the voltage-clamped brush-border membrane vesicles in the presence of an outward H(+)-gradient. Momentary dissipation of the H(+)-gradient itself by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) did not affect the uptake of enoxacin. In contrast, enoxacin uptake was depressed by an interior positive K(+)-diffusion potential induced by valinomycin. Furthermore, not only the outward H(+)-gradient but also an inward Cl(-)-gradient caused a stimulating effect on enoxacin uptake, and the stimulation by the Cl(-)-gradient was dissipated by using voltage-clamped membrane vesicles. These results indicate that enoxacin transportation across the brush-border membrane is dependent on the ionic diffusion potential. On the other hand, neither Gly-Gly nor guanidine had any effect on enoxacin uptake by the membrane vesicles in the presence of an inward (for Gly-Gly) or outward (for guanidine) H(+)-gradient as a driving force for each transport system. Therefore, it seems that enoxacin transport through the intestinal epithelia does not participate in the carrier-mediated transport systems for Gly-Gly and guanidine.

Animals↗

[Bacteremia of in-patients of the department of urology].

Thirty cases of bacteremia out of 1512 patients who had been admitted to our Department between February 1988 and June 1991 were reviewed. They consisted of 22 males and 8 females and their age ranged from 32 to 88 years (mean 62.7). 25 of the patients (83.3%) had malignant diseases of which bladder cancer (15 cases) was predominant and 5 had benign diseases. Gram positive bacteria were isolated in 18 cases (56.2%) and fungi in 4 cases (12.5%) from blood culture. Of these MRSA was most prevalent: 6 cases (18.8%), followed by S. epidermidis: 4 cases (12.5%), P. aeruginosa: 3 cases: E. faecalis: 3 cases and Corynebacterium: 3 cases (9.4%). Analysing the onset of bacteremia for each case, in three cases urinary tract infections, in one case a surgical wound infection and in one case a skin infection were prominent before the diagnosis of bacteremia. From their background, 23 cases (76.7%) were so-called compromised hosts. A total of 7 cases had died, 6 cases of bladder cancer and one case of testicular cancer, five of them were on systemic anti-cancer chemotherapy. Of those cases who expired, P. aeruginosa was isolated in two cases, Candida in two cases, MRSA in one case and E. faecium in one case, Corynebacterium in one case. It was noteworthy that in two cases where blood cultures were positive for P. aeruginosa and one case where the blood culture proved positive for Candida, drastic decrease of the peripheral leukocyte number during anti-cancer chemotherapy was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vitro and in vivo antibacterial activities of KRM-1648 and KRM-1657, new rifamycin derivatives.

The in vitro and in vivo antibacterial activities of the new rifamycin derivatives KRM-1648 and KRM-1657 were compared with those of rifampin. Rifabutin, ciprofloxacin, and clarithromycin were also tested for reference. The respective MICs of KRM-1648 and KRM-1657 for 90% of the strains tested (MIC90S) were 0.016 and 0.0078 microgram/ml, respectively, for methicillin-susceptible Staphylococcus aureus, 0.016 and 0.0039 microgram/ml, respectively, for methicillin-resistant S. aureus, and 0.0625 and 0.016 microgram/ml, respectively, for methicillin- and quinolone-resistant S. aureus. These MIC90S of KRM-1657 were equal to or 2- to 64-fold lower than those of rifampin. KRM-1648 and KRM-1657 with MIC90S of between 0.002 and 0.078 microgram/ml were 2- to 128-fold more active than rifampin against Staphylococcus epidermidis and Streptococcus species, including Streptococcus pneumoniae and Streptococcus pyogenes. The MIC90S of KRM-1657 for Haemophilus influenzae and Neisseria gonorrhoeae were 0.25 and 0.1 microgram/ml, respectively; KRM-1657 was almost as active as rifampin and was 8- to 16-fold more active than KRM-1648 against these strains. The frequency of occurrence of spontaneous mutations to resistance to KRM-1648 and KRM-1657 was equal to that to rifampin. Against systemic infection with S. aureus in mice, the efficacies of KRM-1648 and KRM-1657 were comparable to that of rifampin.

Animals↗

Specific induction of LTC4 synthase by retinoic acid in rat basophilic leukemia-1 cells.

Overnight (10-16 h) incubation of retinoic acid (RA), a derivative of vitamin A, specifically induced LTC4 synthase activity (5 to 10-fold), but not LTA4 hydrolase activity in the lysate of rat basophilic leukemia-1 (RBL-1) cells. A time course study revealed that the increase of LTC4 synthase activity was time dependent and that the peak value was obtained after a 24-hour incubation with RA. The induction of enzyme activity was specifically localized to the microsomal fraction. Glutathione (GSH) S-transferase activity measured by using the same cell lysate as an enzyme source and 1-chloro-2,4-dinitrobenzene (DNCB) as a substrate was not influenced by RA treatment, indicating that the induction by RA is specific for membrane-bound LTC4 synthase. The induction of LTC4 synthase may be an important regulatory mechanism of peptide-LT synthesis in allergy and inflammatory diseases.

Animals↗

Coronary reperfusion enhances recovery of atrial natriuretic peptide secretion. Salvaging endocrine function in patients with acute right ventricular infarction.

BACKGROUND: The heart has been demonstrated not only to be a pumping organ but also an endocrine organ secreting atrial natriuretic peptide (ANP). We hypothesized that myocardial ischemia may affect ANP secretion and that reperfusion therapy for acute myocardial infarction can preserve endocrine function of the heart. METHODS AND RESULTS: Twenty patients with acute right ventricular infarction were examined who underwent reperfusion therapy on admission. These patients had proximal occlusion of the dominant right coronary artery involving the right atrial branches: 9 patients with successful reperfusion (SRP group) and the remaining 11 patients with unsuccessful reperfusion (URP group). Within 24 hours after the onset of infarction, a volume loading test was performed after reperfusion therapy with measurements for plasma ANP levels and hemodynamics. Before the volume loading test, the plasma ANP level and mean right atrial pressure were similar between these two groups. However, in the URP group, percent increase in ANP in response to volume loading was strikingly smaller (URP, 45 +/- 18% versus SRP, 133 +/- 25%; P < .01) despite similar percent increase in mean right atrial pressure (URP, 100 +/- 46% versus SRP, 86 +/- 23%). The peak ANP level occurred significantly later in the URP group (69 +/- 16 hours) than in the SRP group (28 +/- 9 hours, P < .001) after the onset of infarction. CONCLUSIONS: The response of ANP release to volume loading is attenuated in patients with right ventricular infarction without coronary reperfusion. However, successful reperfusion induces a rapid recovery of cardiac endocrine function as well as its mechanical function. A sufficiently elevated plasma ANP level may be a useful predictor of hemodynamic improvement in patients with right ventricular infarction.

Aged↗

Heart rate and force-frequency effects on diastolic function of the left ventricle in exercising dogs.

BACKGROUND: Previous studies from our laboratory have shown pronounced augmentation of the force-frequency relation on myocardial contraction during exercise, but the influence of this effect on diastole has not been investigated. METHODS AND RESULTS: Accordingly, the effect of changing heart rate on left ventricular (LV) relaxation, filling dynamics, and pressure-volume relations during exercise was studied in eight conscious dogs. The exercise heart rate was slowed from 208 +/- 21 (SD) to 163 +/- 11 beats per minute by injection of a specific sinus node inhibitor (UL-FS 49, or zatebradine, 0.6 mg/kg) during continuous exercise. Heart rate was then abruptly restored to the predrug level by atrial pacing during continued exercise. LV volume was calculated by use of implanted ultrasonic crystals, and LV pressure was determine with an implanted micromanometer. Comparing conditions after pacing back to a heart rate of 210 beats per minute with those obtained when the heart rate was slowed by atrial pacing, LV dP/dtmax was increased by 27% at the higher rate (P < .01), despite a marked decrease in LV end-diastolic pressure (24 +/- 4 versus 10 +/- 5 mm Hg, P < .01) and the time constant of isovolumic LV pressure decay (tau) was significantly shortened (19 +/- 5 versus 14 +/- 4 milliseconds, P < .01). The peak rapid filling rate in early diastole (PFR) was not significantly changed by increasing the heart rate, since it was maintained at the slower rate. During exercise, at the slowed heart rate the early portion of the diastolic pressure-volume curve was significantly shifted upward and to the right compared with that at the physiological heart rate, but the late portion of the curve was unchanged. CONCLUSIONS: These data indicate that the negative inotropic effect of the force-frequency relation when heart rate was slowed during exercise caused pronounced impairment of LV relaxation and early filling dynamics. Conversely, an important component of the pronounced improvement of diastolic ventricular function during normal exercise was shown to result from exercise-induced enhancement of the positive inotropic effects of the force-frequency relation on myocardial contraction and relaxation.

Animals↗

Inhibition by dexamethasone of retinoic acid-induced enhancement of leukotriene C4 synthesis in rat basophilic leukemia-1 cells.

We investigated inhibitory actions of dexamethasone (DEX) on retinoic acid (RA)-induced enhancement of leukotriene C4 (LTC4) synthesis in rat basophilic leukemia-1 (RBL-1) cells. Cultured cells were preincubated with RA for 16 h with or without DEX, and generation of LTC4 was measured by high performance liquid chromatography in cell-free and intact cell systems. RA (0.1 microgram/ml) significantly potentiated calcium ionophore-stimulated production of LTC4 synthesis. DEX inhibited the RA-induced enhancement of LTC4 synthesis by up to approximately 95% in intact cells when stimulated with calcium ionophore. RA-induced LTC4 synthase activity, which was determined by enzyme assay, was also inhibited by DEX by 65% in a cell-free system. This discrepancy of inhibition between the intact and cell-free systems was due to a partial inhibition of phospholipase A2 activity by DEX in the intact cells. These results indicate that the production of LTC4 is predominantly regulated at a level of LTC4 synthase. The induction of new LTC4 synthase activity by RA and inhibition of the RA-induced activity by DEX are important regulatory mechanisms of LTC4 synthesis.

Animals↗

Chitosan and sodium alginate based bioadhesive tablets for intraoral drug delivery.

Bioadhesive tablets for intraoral drug delivery were prepared by directly compressing the drug with a mixture of chitosan and sodium alginate in weight ratios of 4:1, 1:1 and 1:4, and the adhesion and release characteristics of the prepared systems were evaluated in vitro and in vivo. Ketoprofen was used as a model drug. The magnitudes of the adhesion force of chitosan/alginate tablets were observed to be comparable to that of Aftach, which is a typical commercial preparation of an oral mucosal adhesive tablet. Increasing the chitosan content in the tablets resulted in a decrease in the release rate of ketoprofen. When the tablets were administered to the sublingual site of rabbits, ketoprofen from the tablets with chitosan/alginate was rapidly absorbed without an initial sharp peak. Furthermore, the plasma concentration curves for the tablet with a 1:4 chitosan/alginate ratio showed a sustained release 3 h after administration. The data presented suggest that tablets prepared from chitosan and alginate are potential candidates for intraoral drug delivery.

Adhesiveness↗

[Enhancement of rectal absorption of rifampicin by sodium para-aminosalicylate dihydrate in human subjects].

The suppositories of rifampicin (RFP) containing sodium para-aminosalicylate dihydrate (PAS-Na) were prepared in order to enhance the rectal absorption of RFP. By the addition of PAS-Na, the in vitro release of RFP from the suppositories was enhanced and the hardness of the suppositories decreased. The rectal absorption of RFP from the suppositories containing no PAS-Na (control suppositories) was significantly lower compared to oral administration of it (26%) in human subjects. When PAS-Na was added to the suppository (300 mg), both the area under the plasma concentration-time curve (AUC) and the maximum plasma concentration (Cmax) increased significantly compared to those of the control suppositories. The rectal absorption of PAS-Na itself from the suppositories seemed to be fast. PAS-Na might increase the absorption of RFP dissolved in the rectal fluid from the suppositories, but not affect the undissolved RFP.

Administration, Oral↗

Erythromycin does not directly affect neutrophil functions.

To determine whether erythromycin could affect neutrophil functions, we measured N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced chemotaxis and superoxide generation of neutrophils in the presence of erythromycin at various concentrations. Erythromycin had no effect on either of them. We further confirmed that intracellular free calcium concentration ([Ca2+]i) was not influenced by FMLP stimulation in the presence of erythromycin. Our results indicate that erythromycin has no direct effects on neutrophil functions in vitro, although it is reported that erythromycin inhibits the local migration of neutrophils in the small airways of subjects with asthma.

Asthma↗

Simultaneous measurement of plasma 18-oxocortisol and 18-hydroxycortisol levels in normal man.

Plasma 18-oxocortisol (18-oxoF) and 18-hydroxycortisol (18-OH-F) were measured in 47 healthy subjects. Plasma 18-oxoF and 18-OH-F in the early morning were 0.827 +/- 0.04 nmol/l and 3.29 +/- 0.175 nmol/l, respectively. The plasma levels of both steroids correlated with each other and with cortisol, but not with aldosterone. Postural stimulation with or without furosemide administration increased 18-oxoF, 18-OH-F, aldosterone and plasma renin activity (PRA). Two hours after 2 mg of oral dexamethasone administration or after an overnight 2 mg of dexamethasone suppression cortisol, 18-oxoF and 18-OH-F decreased. Cortisol, aldosterone, 18-oxo-F and 18-OH-F increased after the intravenous administration of 250 micrograms of 1-24 ACTH. Changes in plasma 18-oxo-F and 18-OH-F levels correlated with PRA change during the posture studies and correlated with the change of ACTH during the dexamethasone studies. The ratios of post-/pre-test values of the postural stimulation and dexamethasone suppression in 18-oxoF and 18-OH-F were lower than that of aldosterone. Plasma 18-oxoF and 18-OH-F are more dependent on ACTH than on the renin-angiotensin system. The ratio of 18-OH-F/18-oxoF, which is between 4 and 5, remains constant during the various stimulation or suppression maneuvers.

Adrenocorticotropic Hormone↗

Assessment of left ventricular filling dynamics utilizing Doppler echocardiography in acute coronary syndrome.

To evaluate prolonged diastolic dysfunction in acute coronary syndrome, mitral inflow velocities and left ventricular wall motion were examined with pulsed-wave Doppler and two-dimensional echocardiography in 14 patients with successful reperfusion, 8 patients without reperfusion after acute myocardial infarction, and in 10 patients with prolonged angina. Early peak flow velocity and the ratio of early to atrial peak flow velocity increased gradually both after the onset of acute myocardial infarction with reperfusion and cessation of angina pectoris. However, in acute myocardial infarction without reperfusion, early peak flow velocity and the ratio of early to atrial peak flow velocity decreased significantly. Atrial peak flow velocity remained unchanged in acute myocardial infarction with reperfusion, while it was decreased in angina pectoris on the seventh day. Regional systolic dysfunction abated gradually in acute myocardial infarction with successful reperfusion, and regional systolic dysfunction was not detected in angina pectoris on the third day. Thus, abnormalities in left ventricular early diastolic filling persisted for several days after reperfusion in acute myocardial infarction or cessation of angina. Left ventricular late filling remained unchanged in acute myocardial infarction, whereas, in angina pectoris, a compensatory increase in late filling diminished gradually with an increase in early filling. These results indicate that there are different types of recovery process after diastolic filling abnormalities in patients with acute coronary syndrome.

Angina Pectoris↗

Does preconditioning affect recovery in stunned myocardium?

In this study, to determine whether preconditioning enhances the process of recovery from post-ischemic dysfunction, ultrasonic crystals were placed in 8 open-chest dogs to measure regional myocardial wall thickening in the ischemic area. A carotid-circumflex coronary artery bypass was created with an electromagnetic flow probe and a fixed stenosis was produced. Ventricular pacing was performed for 15 minutes at a rate of 190-220 bpm. After a 15 minutes rest period, a second pacing was performed in a similar manner. After cessation of the first pacing, circumflex wall thickening remained reduced significantly. Three minutes after cessation of the second pacing, circumflex thickening decreased further. After 15 minutes, wall thickening improved to the value recorded before the second pacing. The degree of improvement from 3 minutes to 15 minutes after the second pacing was greater than that after the first pacing. Thus, preceding demand ischemia modifies the rate of functional recovery from the next post-ischemic dysfunction, indicating that preconditioning of the ischemic myocardium enhances recovery from stunning.

Animals↗

In vitro and in vivo changes of serotype in Pseudomonas aeruginosa isolates by anti-pseudomonal drugs.

The present study was designed to clarify whether anti-pseudomonal drugs affected in vitro and in vivo changes in serotypes of Pseudomonas aeruginosa isolates. Forty-two isolates of P. aeruginosa belonging to different serotype groups were each incubated in Mueller-Hinton broth including piperacillin, cefsulodin, ceftazidime, imipenem, gentamicin or norfloxacin at 1 approximately 4 MICs at 35 degrees C for 20 hours. The bacterial cells in the media were serotyped after the incubation. In each experiment with these six drugs, serotypes of 4 (9.5%) to 8 (19.0%) of the 42 isolates changed to other different groups. There was no relationship between the serotypes of the variants formed with the anti-pseudomonal drugs and kinds of the drugs. In the case of P. aeruginosa TA-2 isolate, the different concentrations (1/2 MIC and 2 x MIC) of cefsulodin induced the distinct changes in serotypes such as the poly-agglutinable (M, G) and non-typable groups, respectively. The time course for the formation of the variant cells was investigated during the incubation of P. aeruginosa TA-2 isolate in the presence of cefsulodin, respectively. In this case, the variant cells appeared 6 hours after incubation and continued to grow together with the intact cells. On the other hand, the variant cells with anti-pseudomonal drugs (cefsulodin, imipenem and gentamicin) were also formed in the model infections in mice. The present results indicated that the co-existence of colonies with different serotypes in some isolates of P. aeruginosa was partially due to the alternation of serotypes with anti-pseudomonal drugs given to patients with infection.

Animals↗

Effects of a non-xanthine adenosine antagonist, CGS 15943, and a phosphodiesterase inhibitor, Ro 20-1724, in a light/dark test in mice.

We investigated the effects of a non-xanthine adenosine receptor antagonist, CGS 15943, and a non-xanthine phosphodiesterase inhibitor, Ro 20-1724, in a light/dark test in mice. CGS 15943 at a dose of 50 mg/kg had no significant effects on any parameter, although at 10 mg/kg it significantly antagonized decreases in locomotion and rearing behavior induced by treatment with A1 and A2 selective agonists, N6-cyclopentyladenosine and CGS 21680 respectively. On the other hand, Ro 20-1724 decreased locomotion and rearing behavior in the light and dark zones, number of shuttle crosses between both zones, and the time spent in the light zone dose-dependently at doses ranging from 1-10 mg/kg. In conclusion, the phosphodiesterase inhibitor decreased all parameters in the light/dark test, while the adenosine antagonist showed no effect.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Effects of xanthine derivatives in a light/dark test in mice and the contribution of adenosine receptors.

We investigated the effects of adenosine receptor antagonists, caffeine, theophylline, 8-phenyltheophylline, and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), in a light/dark test in mice. All antagonists decreased the time spent in the light zone in this test, which suggested that these compounds have anxiogenic effects. The anxiogenic effects of theophylline were reduced by pretreatment with CGS 21680, an A2-selective agonist, but not by N6-cyclopentyladenosine (CPA), an A1-selective agonist. However, the antagonism of the theophylline-induced anxiogenic effects by CGS21680 was only observed in the time spent in the light zone, and DPCPX-induced anxiogenic effects were neither reversed by CGS 21680 nor by CPA. Finally, it is notable that xanthine-derived adenosine antagonists tested here commonly showed anxiogenic effects in the light/dark test in mice. It is suggested that there is a minor contribution of adenosine receptors to these effects, although theophylline-induced anxiogenic effects were antagonized by an A2 receptor agonist.

Adenosine↗