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Biomedical subjects

T Miyazaki

Publications and source records attributed to T Miyazaki.

At least 649 records · Page 36Linked to original sources

Pericardial prostaglandin biosynthesis prevents the increased incidence of reperfusion-induced ventricular fibrillation produced by efferent sympathetic stimulation in dogs.

This study tested the hypothesis that sympathetic neural stimulation increases the prevalence of reperfusion-induced ventricular fibrillation and explored the mechanisms by which this occurs and how it may be prevented. In anesthetized, autonomically denervated dogs, we examined the effects of bilateral ansae subclaviae stimulation (SS) and of induction of pericardial biosynthesis of prostaglandins, an intervention that reduces SS effects by acting at presynaptic sites. A 5-minute occlusion of the left anterior descending coronary artery distal to the first or second diagonal branch was performed during SS. Heart rate was maintained constant by atrial pacing. In the absence of SS, one of 23 dogs developed ventricular fibrillation during occlusion, and three of the remaining 22 dogs developed ventricular fibrillation upon reperfusion. SS did not increase the prevalence of occlusion-induced ventricular fibrillation (four of 23 dogs) but increased the prevalence of reperfusion-induced ventricular fibrillation (12 of the remaining 19 dogs, p = 0.01). SS did not affect occlusion-induced decrease in local electrogram amplitude recorded from the ischemic myocardium or myocardial blood flow to the ischemic myocardium during occlusion or reperfusion. SS, however, prevented occlusion-induced increase in diastolic excitability threshold. Instillation into the pericardial cavity of arachidonic acid solution (3 micrograms/ml) resulted in release of prostacyclin, measured by radioimmunoassay as a stable metabolite 6-ketoprostaglandin F1 alpha (63.1 +/- 11.3 ng/ml, n = 11, mean +/- SEM), and of prostaglandin E2 (7.0 +/- 0.9 ng/ml, n = 11). This pericardial solution blunted SS-induced increase in mean arterial blood pressure and reduced the prevalence of ventricular fibrillation during reperfusion (six dogs to one dog, p less than 0.05). Blood flow to the ischemic myocardium remained unaffected. Indomethacin, when added to the solution (3 micrograms/ml), reversed the effects of prostaglandin release and arrhythmia development. These data indicate that efferent sympathetic stimulation during a coronary occlusion and reperfusion sequence increases the prevalence of reperfusion-induced ventricular fibrillation that is reduced by pericardial biosynthesis of prostaglandins. Pericardial prostaglandin synthesis may serve as a unique antiarrhythmic function by regulating efferent cardiac sympathetic nerve effects.

Animals↗

Prostaglandins in the pericardial fluid modulate neural regulation of cardiac electrophysiological properties.

In response to various stimuli, the pericardium produces prostaglandins that might play a role in neural regulation of cardiac electrophysiological properties by modulating epicardial nerve effects. We determined the effects of various epicardial superfusates on efferent cardiac responses, induced by bilateral efferent ansae subclaviae (SS) and cervical vagal (VS) stimulation, and afferent cardiac reflexes elicited by intracoronary injections of bradykinin (25 micrograms) and nicotine (50 micrograms). Pericardial instillation of arachidonic acid in normal Tyrode's solution (3 micrograms/ml) increased the concentration of pericardial prostacyclin (PGI2), measured by radioimmunoassay as the stable metabolite 6-keto-PGF1 alpha, and of prostaglandin E2 (PGE2). Arachidonic acid superfusion reduced SS-induced shortening of sinus cycle length (SCL), atrio-His interval (AH), and effective refractory period (ERP) of the right and left ventricular myocardium and prevented intra-aortic angiotensin II (30 ng/kg/min) from augmenting SS effects on these variables. Pericardial arachidonic acid plus indomethacin (1 microgram/ml) eliminated the prostaglandin increase and restored the responses of SCL, AH, and ERP to SS and to angiotensin II infusion. Pericardial PGE2 (30 or 50 ng/ml) or PGI2 (50 ng/ml) reversibly suppressed SS-induced shortening of SCL and ERP. Pericardial arachidonic acid or PGI2, however, did not blunt the shortening of ERP induced by intravenous infusion of norepinephrine. Pericardial arachidonic acid did not affect VS-induced lengthening of ERP or the duration of sinus arrest, or arterial blood pressure and heart rate responses to bradykinin or nicotine. We conclude that an increase in the concentration of prostaglandins in the pericardial fluid inhibits efferent sympathetic nerve effects on cardiac electrophysiological variables and antagonizes the facilitatory action of angiotensin II on efferent sympathetic stimulation by acting at presynaptic sites. Increased concentration of pericardial prostaglandins in response to various stimuli may constitute a physiological negative-feedback control mechanism that regulates efferent cardiac sympathetic stimulation.

Animals↗

Presynaptic modulation of efferent sympathetic and vagal neurotransmission in the canine heart by hypoxia, high K+, low pH, and adenosine. Possible relevance to ischemia-induced denervation.

Ischemia in the dog produces denervation of myocardium apical to the ischemic area. To investigate the mechanism(s) of the denervation, we tested the effects of hypoxia and some components of ischemia including high K+, low pH, and adenosine on efferent cardiac autonomic responses. In anesthetized, open-chest dogs, we occluded a diagonal branch of the left anterior descending coronary artery and perfused it with hypoxic Tyrode's solutions (PO2 less than 50 mm Hg). We found that effective refractory period (ERP) shortening induced by bilateral ansae subclaviae stimulation at myocardium basal and apical to the perfusing area did not change during a 20-25 minute period of perfusion with hypoxic normal Tyrode's solution. During perfusion with hypoxic combined Tyrode's solution containing 12 mM K+, pH 6.8, and 10 microM adenosine, ERP shortening at basal sites induced by bilateral ansae subclaviae stimulation remained unchanged but was attenuated at apical sites (16 +/- 1 to 8 +/- 1 msec, mean +/- SEM, n = 35, p less than 0.001), and seven apical sites exhibited denervation (less than or equal to 2-msec shortening). The maximum extracellular K+ concentration of the perfusing area, measured with a K(+)-sensitive electrode, was 5.1 +/- 0.9 mM (N = 3 dogs) during perfusion with normal Tyrode's solution and was 11.8 +/- 0.1 mM (N = 3 dogs) during perfusion with hypoxic combined solution (p = 0.017). In a separate group of dogs, the effects of high K+, low pH, and adenosine in the absence of ischemia were examined. Oxygenated Tyrode's solutions were instilled into the pericardial cavity to superfuse epicardial nerves. The Tyrode's solutions containing high K+ (12 mM), low pH (6.4), or adenosine (10 microM), individually or combined, reduced ERP shortening induced by bilateral ansae subclaviae stimulation in the ventricular intramyocardium to 46%, 55%, 56%, and 33% of each control value obtained during superfusion with normal Tyrode's solution and reduced the magnitude of ERP lengthening induced by bilateral cervical vagal stimulation to 57%, 71%, 61%, and 39%, respectively. ERP responses of the test sites to infused norepinephrine and methacholine, however, remained unaffected by superfusion with combined Tyrode's solution. Thus, high K+, low pH, and adenosine each inhibit efferent sympathetic and vagal neurotransmission presynaptically in the canine heart and may contribute to the development of denervation during early ischemia.

Adenosine↗

Hematoma of the interatrial septum associated with complete atrioventricular block.

A 70-year-old man who had been treated for tongue cancer began to suffer from repeated syncopal attacks. His electrocardiogram indicated complete atrioventricular block. A permanent pacemaker was implanted. He was well for about 2 years after which time he developed dyspnea, suffered from general fatigue, and then suddenly died. A postmortem examination revealed a hematoma approximately 4 x 4. cm in size in the interatrial septum, connected to a noncoronary sinus and rupture of the noncoronary leaflet, which compressed the tricuspid and aortic valves. This hematoma might have been related to the conduction disturbance caused by destructive compression on the conduction system, and his death by the rupture of the noncoronary leaflet.

Aged↗

Further characterization of urinary aldosterone metabolities in the rabbit by fast atom bombardment mass spectrometry.

After the subcutaneous injection of a large amount of aldosterone into a male rabbit, urine was collected for 24 h. The preliminary separation of urinary aldosterone metabolites was carried out by means of DEAE-Sephadex A-25 column chromatography. Each fraction obtained was further purified by reversed phase high pressure liquid chromatography. Purified materials were then analyzed by fast atom bombardment mass spectrometry and infrared spectroscopy. Thus, tetrahydroaldosterone glucuronide and tetrahydroaldosterone sulfate were detected as urinary aldosterone metabolites. These results confirmed our previously published data, where the nature of conjugating groups was determined indirectly. Furthermore, hydroxyaldosterone was identified as a urinary aldosterone metabolite.

Aldosterone↗

Liposome-encapsulated amphotericin B in the treatment of experimental murine candidiasis.

The efficacy of liposome-encapsulated amphotericin B in treating experimental murine candidiasis was compared with that of the commercially available amphotericin B (Fungizone). The LD50 of liposomal amphotericin B in ddY mice exceeded 10.0 mg/kg while that of Fungizone was 3.0 mg/kg. Experimental candidiasis was induced by injecting a clinical isolate of Candida albicans strain 0925-107-01, through the tail vein. With the injection of 1.7 x 10(6) colony forming units, the number of colonies in the kidneys remained between 2.1 x 10(5) and 1.2 x 10(6), whereas the number of colonies in blood, liver, spleen, lungs and heart decreased rapidly. Histological examination revealed severe pyelonephritis with fungal infiltration and a mild invasion of the heart, lungs, liver and spleen. The survival rate of mice with experimental candidiasis treated with Fungizone at a dose of 0.8 mg/kg was 50% (the maximum tolerated dose without acute lethality), whereas all mice treated with the liposomal amphotericin B at a dose of 5.0 mg/kg were alive even 42 days after the inoculation (p less than 0.01). Using liposome as a carrier for amphotericin B decreased this drug's systemic toxicity making it possible to administer doses higher than feasible with the commercial preparation and thus obtaining better therapeutic efficacy.

Amphotericin B↗

[Visual hemifield differences in recognition of kanji and hiragana and its relation to hemispheric cerebral asymmetries].

Visual hemifield differences in recognition of kanji and hiragana were studied on forty male right handers. A letter of kanji or hiragana was presented unilaterally to the right or left visual hemifield on a CRT display for 123 msec. A hundred and twenty recognition trials were performed for each subject using 20 well-acquainted kanji, 20 unfamiliar kanji and 20 hiragana. Kanji was more accurately recognized in the left visual hemifield than in the right hemifield. This tendency was more prominent in unfamiliar kanji compared with well-acquainted kanji. There were no visual hemifield differences in recognition of hiragana. Learning effects were observed for the right hemifield on kanji and both hemifields on hiragana. The results were discussed in relation to cerebral asymmetries of function. Kanji might be processed in the right cerebral hemisphere as geometric forms. The results on hiragana may be explained by mental set. It is suggested that modes of processing may be different between kanji and hiragana.

Adolescent↗

[Anemia in the elderly].

We measured red blood cell counts, hemoglobin levels, hematocrit values, serum iron levels, total iron binding capacity, transferrin saturation, and serum ferritin levels in 364 elderly subjects in the eighth decade, who consisted of 283 subjects (171 males, 112 females) living in their own homes and 81 subjects (28 males, 53 females) living in an old-age home. The mean values of RBC, Hb, Ht, SI, s-Ft in both male and female subjects living in their own homes were 469 X 10(4)/microliters vs 439 X 10(4)/microliters, 14.6 g/dl vs 13.3 g/dl 44.3% vs 40.6%, 95.6 micrograms/dl vs 84.8 micrograms/dl, 50.2 ng/ml vs 42.6 ng/ml, respectively. On the other hand, the mean values of RBC, Hb, Ht, SI, s-Ft in both male and female subjects living in an old-age home were 421 X 10(4)/microliters vs 390 X 10(4)/microliters, 13.8 g/dl vs 12.6 g/dl, 39.9% vs 36.7%, 74.2 micrograms/dl vs 58.6 micrograms/dl, 98.8 ng/ml vs 69.1 ng/ml, respectively. All erythrocyte parameters were significantly lower in females than in males in both groups, and significantly lower in subjects living in an old-age home than in subjects living in their own homes. The erythrocyte parameters of subjects living in their own homes showed little difference compared with those of normal young adults. These results suggest that a sedentary lifestyle in the elderly people contribute to the tendency to have anemia and this is considered to relate to age-associated pathology such as inflammation. As anemia in elderly people often follows a underlying illness, we must always give attention to the factors which cause anemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Measurement of HbA1c as a method to diagnose diabetes mellitus in nursing home residents].

Measurement of HbA1c is widely used to control diabetes mellitus (DM) and is one of the methods to diagnose DM. We adopted the measurement of HBA1c in the annual medical examination of residents at a nursing home for the elderly in order to obtain the normal serum level of HbA1c in the elderly and analyze the influence of aging on HbA1c. HbA1c and the body mass index (BMI) were measured in 968 elderly. HbA1c was distributed from 3.7 to 12.5%. Mean and SD, were 5.03 +/- 0.61% and there was no difference of the serum level of HbA1c between males and females. HbA1c was below 6.0% in 95% of all subjects. There was no correlation between age and HbA1c. To determine data trends, we divided the elderly into 4 age groups of 60 to 69 years, 70 to 79 years, 80 to 89 years and 90 or more. With advancing age, HbA1c gradually increased but there was no significant difference of HbA1c among the 3 groups which were younger than the group aged 90 or more. HbA1c was 5.51 +/- 1.06% in the group aged more than 90 years and there was a significant difference in the value of HbA1c between the group aged 90 or more and other groups. Inversely, BMI gradually decreased with age and there was also a significant difference of BMI between the group aged 90 or more and the other groups. These results suggest that there is a difference of metabolic condition between the group aged 90 or more and the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[The effects of antihypertensive therapy on the aged--an intervention study in a home for the aged].

Excessive antihypertensive therapy can create a risk of brain damage in the aged. Furthermore, no conclusion has been reached regarding treatment goals for systolic blood pressure (SBP). Two hundred elderly people with hypertension (SBP greater than 170 mmHg, average age 74 years) were studied, among them 40 age-sex matched pairs (80 people) were selected for further examination. They were then divided into two groups, and antihypertensive therapy was conducted on each group with systolic blood pressure level goals of 140 mmHg and 160 mmHg, respectively. To set a goal for antihypertensive therapy, we examined Hasegawa's dementia rating scale (HDS) and bilateral common carotid arterial blood flow (CCF), which were measured using the Doppler method. In the group in which the blood pressure was reduced to 160 mmHg level, changes were observed only in right CCF, and there was no change in HDS, but in the group in which the blood pressure was reduced to the 140 mmHg level, changes were observed in both bilateral CCF and HDS. It is recommended that the systolic blood pressure should be set at the 160 mmHg level to maintain the psychological function in the elderly.

Aged↗

[Usage of chitosan as a pharmaceutical material effectiveness as an additional additives of sodium alginate].

Application of chitosan, a deacetylated compound of chitin obtained from shells of shrimps, was investigated with reference to the pharmaceutical excipient for directly compressed tablets. Several drugs were chosen as model compounds and their in vitro dissolution tests were carried out according to the JP XI dissolution test. When chitosan was used alone as an excipient, immediate-release tablets were obtained, as already reported. But when more than 5% of sodium alginate, 1000 cps, was added as excipient, tablets showed an extended-release property under the present experimental conditions.

Adjuvants, Pharmaceutic↗

[Treatment of aplastic anemia with KRN8601 (rhG-CSF)].

Thirty-nine patients with severe or moderate aplastic anemia received treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF). The first group of eight patients received rhG-CSF in doses of 100 to 400 micrograms/m2/d by a daily 30-minute intravenous infusion for one or two weeks. Doses up to 400 micrograms/m2/d were well tolerated and resulted in increases of neutrophil counts in 5 out of 8 patients. We gave rhG-CSF (400 micrograms/m2/d) to the second group of 26 patients by a daily 30-minute intravenous infusion for two weeks. The treatment resulted in an increase of neutrophil counts in 15 out of 26 patients (3.1 to 29.5 fold). Further, higher doses (800 or 1,200 micrograms/m2/d) were administered in 5 patients who did not respond to the dose of 400 micrograms/m2/d. The treatment increased the neutrophil counts in 3 out of 5 patients. The third group of five patients received rhG-CSF subcutaneously in doses of 20 to 400 micrograms/m2/d. An increase of neutrophil counts was noted in all five patients. Differential counts of bone marrow aspirate revealed an increase of myeloid: erythroid ratios. However, the responses were transient and neutrophil counts returned to basal levels within 1 approximately 2 weeks after discontinuing treatment. No severe toxicity due to rhG-CSF was observed. These results suggest that rhG-CSF is effective on stimulating granulopoiesis in patients with aplastic anemia. This treatment will be particularly useful for the patient with aplastic anemia suffering from bacterial or fungal infections.

Adolescent↗

[Clinical effect of recombinant human granulocyte colony-stimulating factor on aplastic anemia].

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutropenia was studied in 30 patients with aplastic anemia (AA). RhG-CSF was administered intravenously daily at a dose of 2, 5, 10, or 20 micrograms/kg/day for more than 7 days. In the patients whose absolute neutrophil counts (ANC) were more than 0.1 X 10(9)/l, the rhG-CSF injections at greater than or equal to 5 micrograms/kg/day caused rapid and selective elevation of ANC which maintained during the injection period. Most of the patients were well tolerated, and minor side effects were observed in only 3 patients. These findings suggest that daily injections of rhG-CSF at a dose of greater than or equal to 5 micrograms/kg/day may be an effective strategy for the treatment of bacterial and/or fungal infections in AA patients.

Adult↗

[The direct tensile test of composite resins using the small specimen--effect of the preparation of specimen, the size of specimen and the testing condition on the tensile properties].

The direct tensile test of composite resins using the specimen with the gauge length 10 mm has been developed by authors. In this study smaller specimens with the gauge length 5 mm and 2 mm were also investigated. As the gauge length became smaller, tensile properties such as the proportional limit, the proof stress, and the tensile strength showed the tendency to become higher. The effect of strain rate on the tensile properties appeared clearly when using the specimen with the gauge length 2 mm. The small specimen was found to have many advantages for the preparation, the cost of material and the handling during the tensile test.

Composite Resins↗

[Automatic polishing of dental prostheses. 1. Development of a centrifugal barrel finishing apparatus].

A centrifugal barrel finishing apparatus with a variable turn table rotational speed (250-1,000 rpm) was newly developed and barrel finishing of Ni-Cr casting plates (10 x 10 x 2 mm) was performed using alumina base chips. When using the sample with a mirror face the amount of polishing and the surface roughness increased and the surface gloss decreased with the increase in rotation speed. A high rotational speed was useful for coarse polishing and low rotational speed was useful for fine polishing. The continuous barrel polishing was trially performed using the sample prepared by the carborundum wheel under variable rotational speed. Automatic polishing to fine polishing could be done using this apparatus.

Dental Polishing↗

Radioprotective effects of dimethyl sulfoxide in golden hamster embryo cells exposed to gamma rays at 77 K. I. Radical formation as studied by electron spin resonance.

Formation of free radicals in golden hamster embryo (GHE) cells in the frozen living state by gamma irradiation has been studied by electron spin resonance spectroscopy at 4.2 and 77 K. The relative yields of H atoms, OH radicals, and organic radicals trapped in the irradiated GHE cells are 12, 72, and 16%, respectively, of total radical yields. When dimethylsulfoxide (DMSO) is added to GHE cells at 77 K, a large quantity of CH2SOCH3 radicals (DMSO radicals) are formed after gamma irradiation. The yields of OH radicals are not affected by the addition of DMSO. When the GHE cell-DMSO mixtures are irradiated with gamma rays at 77 K and then warmed to 111 K, the OH radicals decay, whereas the DMSO radicals do not increase complementarily. Moreover, the decay rates of the OH radicals at 111 K do not depend upon the concentration of DMSO. Thus OH radicals do not react with DMSO during warming of the irradiated sample. When H atoms are produced by gamma irradiation of acid ice at 60 K, the decay rates of the H atoms at 77 K increase with increasing DMSO concentration, indicating that DMSO reacts with H atoms (CH3SOCH3 + H----.CH2SOCH3 + H2) at 77 K by quantum-mechanical tunneling. When the GHE cell-DMSO mixture is irradiated with gamma rays at 77 or 4.2 K in the dark, DMSO ions are produced in addition to DMSO radicals. Therefore it is concluded that DMSO does not scavenge OH radicals, but does capture H atoms, holes and/or electrons in the gamma-irradiated cells, resulting in the remarkable formation of DMSO radicals. This scavenger effect of DMSO may be related to the radioprotection of DMSO against cell killing described in the companion paper (Watanabe et al., Radiat. Res., this issue).

Animals↗