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Biomedical subjects

H Miyagawa

Publications and source records attributed to H Miyagawa.

At least 37 records · Page 2Linked to original sources

Dissociation of impairment between spatial memory, and motor function and emotional behavior in aged rats.

We investigated changes in learning and memory in aged rats, in relation to motor function and emotional behavior. Male Kbl Wistar aged rats (108-weeks-old) were divided into two groups, memory impaired and non-impaired, based on performance during six training trials in the Morris water maze task. Aged rats with a goal latency longer than the mean plus the 99% confidence limit of young rats, were regarded as memory impaired, whereas those with a goal latency within the range of the 99% confidence limit of the mean of young rats, were considered as memory non-impaired. Although the performance of the memory impaired aged rats in the standard test of the Morris water maze improved after six re-training trials to the level of the non-impaired aged rats and young rats, working memory impairment was evident. There were no differences in motor function and emotional behavior between the impaired and non-impaired aged rats. These results suggest that deficits of learning and memory in memory impaired aged rats can be dissociated from changes in motor function and emotional behavior.

Aging↗

X-ray crystal structure determination and molecular dynamics simulation of prophospholipase A2 inhibited by amide-type substrate analogues.

X-ray crystal structures of bovine pancreas prophospholipase A2 (proPLA2) inhibited by two amide-type inhibitors, [(R)-2-dodecanoyl-amino-1-hexanolphosphocholine (DAHPc) and (R)-2-dodecanoylamino-1-hexanolphosphoglycol (DAHPg)], were determined to R = 0.208 and 0.215 using reflections with up to 2.1 A resolution, respectively. Both complex crystals lacked defined electron densities for the prosequence of the N-terminal and for a loop region consisting of residues 65-70, retaining the disordered feature observed in free proPLA2 despite stabilization due to complex formation. The polar and nonpolar moieties of the amide-type inhibitors were located in the calcium-binding pocket and in the N-terminal alpha-helical hydrophobic region of the enzyme, respectively. As for the amide group of the inhibitor, which is lacking in the true substrate, a strong hydrogen bond was formed between the NH of the inhibitor and the unprotonated N(delta1) atom of His-48, resulting in the tight binding of the inhibitor to proPLA2, as well as to PLA2. The 20-30 times more potent inhibitory activity of DAHPg than DAHPc toward PLA2 could be explained by hydrogen bond formation between the glycol OH of DAHPg and the carbonyl O of Asp-49. The seven residues of the N-terminal prosequence of proPLA2, though disordered, block the access of a water molecule to Ala-1 of PLA2 or change the hydrogen-bonding property of Ala-1 alpha-amino group, resulting in breakage of the water-mediated hydrogen-bond network which is commonly formed in PLA2. The results of molecular dynamics (MD) calculation in an aqueous solution at 300 K indicate that this, rather than the close contact between the prosequence and the residues 65-70 loop region, is the main reason why the latter region becomes flexible in proPLA2, compared with in PLA2.

Animals↗

Endoscopic monitoring of operative procedures during cardiac surgery.

Both intracardiac repair and fine anastomotic procedures are hard to visualize in the sterile operative field. To overcome this problem, we have recently developed an endoscope video system for intraoperative monitoring in open heart surgery. The endoscope can be introduced into the cardiac cavity in a sterile fashion and thus be used to visualize intracardiac lesions as well as the operative procedures. This endoscopic video monitoring system is considered to be useful not only for thoracic surgery but also for cardiac surgery as well.

Adolescent↗

Regulation of androgen synthesis: the late steroidogenic pathway.

Studies of the regulation of androgen synthesis in steroidogenic cells have focused on both transcriptional and post-translational regulation of the proteins that catalyze these reactions: the P450c17 that catalyzes the production of DHEA or androstenedione in consecutive hydroxylase and lyase activities, and the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) that catalyzes the conversion of androstenedione to testosterone. Our studies of the regulation of the CYP17 lyase activity at the molecular level have utilized species- and tissue-specific differences to identify target regulatory sequences. Adenovirus infection of rat CYP17 promoter/luciferase reporter gene constructs in primary cultures of rat adrenal and rat Leydig cells revealed a rat-specific domain between-1 and -108 bp that cause inhibition of both basal and cAMP-induced CYP17 transcription in the adrenal, but not the Leydig cell. In contrast, similar promoter constructs from other species exhibited substantial cAMP-induced transcriptional activity in the rat adrenal. Mutagenesis of the conserved region of the rat and human proteins reveals significant differences in the amino acid domains required for hydroxylase and lyase activities within and between the two species, consistent with their differential regulation of lyase activity. The 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) reaction requires a viable glucose transporter system for optimal activity, and a high-energy phosphate was discovered to be the requisite product of glucose metabolism in 17 beta-HSD activation. These studies have provided insight into potential mechanisms of control of androgen synthesis in the late steroidogenic pathway, at the transcriptional and post-translational levels.

17-Hydroxysteroid Dehydrogenases↗

[Operative indication and risk factors for unruptured cerebral aneurysms].

Operative indication and risk factors for unruptured cerebral aneurysms were discussed. During the past 11 years, 38 aneurysms in 33 patients with a mean age of 54 years were operated on. All aneurysms were located in the anterior circulation; 16 were of carotid artery, 15 of the middle cerebral artery, 4 of the anterior communicating artery, and 3 of the distal anterior cerebral artery. Six cases (18.2%) developed neurological deficits postoperatively. The deficits were permanent in 3 cases (morbidity 9.1%). There was one operative death (mortality 3.0%). Operative risk factors were analyzed in 4 particular cases. Of these 4 cases, two cases had large aneurysms (14 and 16mm in diameter) located at carotid-ophthalmic and at the inferior wall of the carotid arteries, respectively. One developed unilateral blindness possibly due to operative manipulation, and the other showed hemiparesis with aphasia due to postoperative carotid stenosis caused by clipping. Of the rest 2 cases; one with multiple (carotid and middle cerebral) aneurysms developed hemiparesis because of postoperative stenosis of the atheromatous parent artery caused by clipping, and the other, with a large (17mm) aneurysm at the distal anterior cerebral artery, died of postoperative intracerebral hematoma. Both of these cases were associated with cerebral ischemic disease. All cases that developed postoperative neurological deficits had varying degrees of hypertension. Reviewing our series and other reports, it can be said that age is one of the most important factors that influence operative mortality. However, a lower risk of rupture develops as age increases. For those under 70 years of age, operation is considered safe in healthy individuals, especially among those without hypertension. However, in cases where there are large aneurysms, multiple lesions, less accessible locations and cerebral ischemic disease, operative risks should be kept in mind. Operative morbidity in these cases is relatively high compared to that found among others. Therefore, planning a meticulous surgical strategy and further careful operative manipulation are essentials, when surgical treatment is indicated.

Adult↗

Increased hypodense eosinophils after activation with PAF-acether and calcium ionophore in asthmatic subjects.

Eosinophils play a major role in the pathogenesis of bronchial asthma. In this study, we examined the density characteristics of blood eosinophils from 9 normal healthy individuals and 9 allergic asthmatic patients. Furthermore, the effect of platelet-activating factor, a potent mediator of inflammation, and calcium ionophore, A23187, on the density of normodense eosinophils (density > 1.085 g/ml) has also been examined. Initially, asthmatic patients had 27.0 +/- 1.1% eosinophils of lighter density (density < or = 1.081 g/ml), significantly greater than that in the normal individuals (7.5 +/- 0.5%). After exposure to platelet-activating factor (1 microM) or calcium ionophore (A23187, 1 microgram/ml), the normodense eosinophils switched to hypodense in both groups: 16.7 +/- 2.1% and 54.2 +/- 3.7%, respectively, in normal individuals, and 30.6 +/- 5.7% and 77.4 +/- 2.3%, respectively, in asthmatic patients. These data demonstrated that a certain percentage of normodense eosinophils from asthmatics and normal subjects switched to hypodense after activation with platelet-activating factor or calcium ionophore. Furthermore, eosinophils from asthmatics switched to a greater degree than in normal subjects, suggesting that the normodense eosinophils in asthmatics become primed probably by endogenously released mediators.

Adult↗

A special-purpose computer for molecular dynamics: GRAPE-2A.

Molecular dynamics simulations have been extensively used in research of proteins. Since these simulations are quite computer intensive, their acceleration is of main interest of the research. In molecular dynamics simulations, almost all computing time is consumed in calculating the forces between particles, e.g., Coulomb and van der Waals forces. We have designed and built GRAPE-2A (GRAvity PipE 2A), a special-purpose computer for use in simulations of classical many-body systems. GRAPE-2A calculates forces exerted on a particle from the other particles. GRAPE-2A can calculate force of an arbitrary functional form of a central force. The host computer, which is connected to GRAPE-2A through the VME bus, performs other calculations such as time integration. The peak speed of GRAPE-2A is 180 Mflops. We can also stimulate systems with periodic boundary conditions by the Ewald method, using GRAPE-2A and another special-purpose computer, WINE (Wave space INtegrator for the Ewald method).

Computer Simulation↗

Effect of cetirizine on human eosinophil superoxide generation, eosinophil chemotaxis and eosinophil peroxidase in vitro.

Cetirizine, a potent H1-antagonist, has been reported to inhibit eosinophil migration into human skin. We, therefore, further evaluated the effect of cetirizine on eosinophil function, including superoxide anion generation, chemotaxis, and eosinophil peroxidase (EP) release. In allergic subjects, superoxide anion generation 60 min after platelet-activating factor (PAF) activation was inhibited by concentrations of cetirizine ranging from 0.01 to 1 microgram/ml (2.612 x 10(-8) to 2.612 x 10(-6) M). No significant inhibition was observed in normal subjects. PAF (10(-6) M)-induced eosinophil chemotaxis was also inhibited by cetirizine. In allergic subjects, percent inhibitions were 47.5 +/- 6.1% at 0.01 microgram/ml, 50.8 +/- 5.1% at 0.1 microgram/ml and 58.9 +/- 6.4% at 1 microgram/ml of cetirizine. In allergic subjects, N-formyl-methionyl-lencyl-phenylalanine induced eosinophil chemotaxis was inhibited by cetirizine, although EP release was not. These results suggest cetirizine has effects on eosinophils which can not be explained by H1-blockade alone.

Adult↗

Total syntheses of (2S)-antafumicins A and B.

To clarify the absolute configurations of antafumicins A and B, which are antifungal substances from Aspergillus niger NH-401, the total synthesis of (2S)-antafumicins was accomplished by starting from (S)-malic acid in 12 steps. Based upon the physicochemical data of the synthetic samples, the absolute configurations of naturally occurring antafumicins A and B were determined as (2R,4S)- and (2R,4R)-4-(3-acetyl-2,6-dihydroxyphenyl)-2-methoxy-4-butanolide, respectively.

4-Butyrolactone↗

Clinical significance of coronary artery calcification.

Coronary artery calcification (CAC) was easily demonstrated by plain CT-scan. The aim of this study was to clarify the clinical significance of CAC in cardiovascular diseases. The subjects were 90 patients with ischemic heart disease (30 myocardial infarction, 50 exertional angina pectoris and 10 variant form of angina pectoris; 46 males and 44 females, 68 +/- 10 y/o) and 50 patients without ischemic heart diseases (30 hypertension, 10 arrhythmia, 3 valvular disease, 2 cardiomyopathy, 2 congenital heart disease and 3 others; 25 males and 25 females 65 +/- 9 y/o). CAC and calcification of thoracic aorta were evaluated by plain CT-scan (1 second scan time and 5 mm slice). The relationship between CAC and other clinical features (age, sex, hypertension, diabetes mellitus, hyperlipidemia, smoking, resting ECG, exercise stress ECG, aortic calcification and optic fundi) were studied. CAC were seen more frequently in patients with ischemic heart disease (63%), old age (67%), aortic calcification (70%) and positive exercise testing (64%). On the other hand, CAC were rare in variant angina (30%). In younger patients (under 70 y/o), CAC were seen more frequently in diabetic patients. But, in older patients, CAC were frequently in those with hyperlipidemia. These results suggested that CAC was associated with not only systemic arteriosclerosis, but also ischemic heart disease, except vasospastic angina. The prognostic value of CAC would be studied later.

Age Factors↗

[Nippon Telegraph and Telephone Corporation workplace smoking control--a questionnaire survey of male NTT workers in the Tokyo area].

A survey of NTT workers regarding smoking control in their workplaces was conducted utilizing a questionnaire administered at the time of routine employee medical examinations. The questionnaire was self-administered and anonymous. Subjects were 1918 men, almost all who were involved in office work in the Tokyo area. Responses were obtained from 1872 (20's and 30's year of age 13.2%, 40's 68.1%, 50's 18.8%) after excluding 106 for incomplete responses. The results were as follows; 1. Of the subjects, 43.4% reported that smoking control was already in effect in their workplace. As for the method of smoking control, smoking restricted to specified places was the most common (31.1%). 2. Of smokers, only 9.8% approved of smoking control in their workplaces, 9.8% were opposed, and 80.1% of smokers reluctantly complied to smoking control in their workplaces. 3. About 60% of subjects, without distinguishing smoking habit, supported smoking restricted to specified areas as the method of smoking control. 4. Over 95% of smokers replied that they can successfully refrain from smoking in prohibited places. 5. For locations where they smoke, smokers listed employee lounge (91.5%), lavatory (83.7%), personal room (75.5%), at own desk (75.3%), reception room (72.7%) and conference room (64.3%). More than half of non-smokers replied that they disapprove of smoking in these places. These results suggest that smoking restricted to only specified places is most appropriate as the method of smoking control in the workplace. However differences exist between smokers and non-smokers as to appropriate designation of smoking areas and non-smoking areas.

Adult↗

Effect of formoterol on superoxide anion generation from bronchoalveolar lavage cells after antigen challenge in guinea pigs.

It is well known that antigen challenge of sensitized subjects can induce an immediate and late asthmatic response, airway eosinophilia, and hyperreactivity. Using our modified guinea pig asthma model, we investigated the superoxide anion generation from eosinophils and macrophages recovered from bronchoalveolar lavage (BAL) 24 h after antigen (ovalbumin) challenge. We also investigated the effect of formoterol, a new long-acting selective beta 2-agonist, on these functions. Antigen challenge increased the total cell counts and the ratio of eosinophils in BAL. Eosinophils and macrophages were collected using discontinuous density centrifugation. Antigen challenge enhanced superoxide anion generation from eosinophils, from 5.39 +/- 1.08 to 13.19 +/- 1.95 nmol 60 min after phorbol myristate acetate (PMA) (1 ng/ml) activation, and 0.22 +/- 0.49 to 3.34 +/- 1.67 nmol 40 min after platelet-activating factor (PAF) (10(-6) M) activation. Formoterol treatment before antigen challenge prevented these enhancements. Superoxide anion generation from macrophages was also enhanced by antigen challenge, from 6.57 +/- 0.76 to 10.66 +/- 0.88 nmol 60 min after PMA activation, and 4.20 +/- 1.17 to 6.63 +/- 0.64 nmol 60 min after PAF activation. Formoterol, however, failed to inhibit enhancement of superoxide anion generation from macrophages. These results show antigen challenge of sensitized guinea pigs induces an increase of eosinophils and macrophages in BAL and enhances the functional characteristics of both cells. Formoterol had inhibitory effects on the enhancement of superoxide anion generation from eosinophils but did not have this effect on macrophages.

Analysis of Variance↗

[A survey of primary lung cancer among NTT workers in the Tokyo area. The incidence and mortality during the past 30 years and significance of radiologic screening].

An epidemiological study of primary lung cancer was conducted on NTT workers in the Tokyo area (about 40,000 persons). During the past 30 years (1960-1989), 77 cases (71 males and 6 females) of primary lung cancer were detected by routine medical examination (radiologic screening by radiophotography at their workplaces) or by clinical symptoms, of whom 59 (54 males and 5 females) were dead as of the end of December 1991. Standardized incidence rate and standardized death rate of the males by the direct method (5-yr age groups from 20 to 59 yr of age, per 100,000 population) were 4.5 in the 1960's, 9.9 in the 1970's and 9.8 in the 1980's, and 3.3 in the 1960's, 7.9 in the 1970's and 8.2 in the 1980's, respectively, with increase being observed from the 1970's. Standardized incidence ratio and standardized death ratio of the males by the indirect method (5-yr age groups from 20 to 59 yr of age) were 107 in the 1970's, 86.8 in the 1980's, and 53.8 in the 1960's, 99.4 in the 1970's and 98.5 in the 1980's, respectively. No significant difference could be observed when compared to the national average. By histological type, 44 cases of adenocarcinoma, 12 cases of squamous cell carcinoma, 8 cases of small cell carcinoma, 7 cases of large cell carcinoma and 6 cases of other or unclear types were detected. Excluding the 3 unclear cases, of the 77 cases, 54 cases were peripheral type and the remaining 20 cases were hilar type on radiophotography. Peripheral adenocarcinoma was the most common type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Density change of neutrophils from allergic subjects by granulocyte-macrophage colony stimulating factor.

We investigated neutrophil density change by platelet activating factor or granulocyte-macrophage colony-stimulating factor (GM-CSF). Although PAF significantly converted neutrophil density, there was no significant difference in density change between allergic subjects and normal subjects by platelet activating factor. Neutrophils from allergic subjects, however, were significantly converted by GM-CSF when compared with neutrophils from normals (P < .05). We conclude that neutrophils from allergic subjects are more sensitive to density change by GM-CSF than neutrophils from normal subjects. This might be due to preactivation or priming by biologic agents.

Adult↗

[A case of advanced hepatocellular carcinoma, in which the tumor almost disappeared by orally administered UFT].

A 59-year-old male with liver cirrhosis was admitted to our hospital for further examination of general fatigue. A huge tumor was found in the right lobe of his liver with abdominal ultrasonography and computed tomography (CT). The titers of serum AFP (14,055 ng/ml) and PIVKA-II (more than 50.0 AU/ml) were extremely high. A tumor embolus was observed in the portal vein with abdominal angiography. According to these findings, he was diagnosed as having advanced hepatocellular carcinoma (HCC). He was treated by oral administration of UFT (600 mg/day) as an unresectable case of HCC. Three months later, the clinical symptoms were greatly improved and HCC was almost diminished with abdominal ultrasonography and CT, although a small tumor embolus was found by angiography. The titers of AFP and PIVKA-II were reduced to the normal range. This case suggests the clinical effectiveness of UFT for the treatment of HCC.

Antineoplastic Combined Chemotherapy Protocols↗

[Results of initial bacteriology of pulmonary tuberculosis among male NTT employees in the Tokyo area--annual transition and influence of fiberoptic bronchoscopy].

A study was made on the annual changes in the positive rate for acid-fast bacilli (AFB) at the initial bacteriological examination of newly detected pulmonary tuberculosis among male NTT (Nippon Telegraph and Telephone Corporation) employees in the Tokyo area during a period of 32 years from 1960 through 1991. The influence on the changes of recent introduction of fiberoptic bronchoscopy for obtaining the specimen was also analyzed, and the following results were obtained. 1. Results obtained by the conventional bacteriological method using expectorated sputum or aspirated gastric juice as the specimens. (1) The annual incidence of bacteriologically positive (smear and/or culture positive) cases constantly decreased and reached the lowest in 1981, then ceased to decline and remained at the level of 1981. (2) The annual ratio of AFB positive by smear and the ratio of smear and/or culture positive cases to the newly detected cases of pulmonary tuberculosis were constant during the entire observation period. (3) The ratio of AFB positive by smear to the newly detected cases annually increased but did not increase when the observation period was limited to within 1976 to 1991. 2. Results obtained by fiberoptic bronchoscopy in combination with conventional bacteriological methods. (1) Both the annual incidence of smear and/or culture positive cases and the ratio of these cases to the newly detected cases of pulmonary tuberculosis showed a tendency to increase in both the 80's and 90's.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗