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Biomedical subjects

H Yasui

Publications and source records attributed to H Yasui.

At least 109 records · Page 6Linked to original sources
PubMed1999

Vasorelaxation and inhibition of the voltage-operated Ca2+ channels by FK506 in the porcine coronary artery.

Using fura-2 fluorometry, the effects of FK506, an immunosuppressant, on changes in cytosolic Ca2+ concentrations ([Ca2+]i) and tension were investigated in porcine coronary arterial strips. The effects of FK506 on the activity of voltage-operated Ca2+ channels were examined by applying a whole cell patch clamp to the isolated smooth muscle cells of porcine coronary artery. FK506 inhibited the sustained increases in both [Ca2+]i and tension induced by 118 mM K+ depolarization and 100 nM U46619 in a concentration-dependent manner (1-30 microM). The extent of inhibition of the K+-induced contraction was greater than that of the U46619-induced contraction. The increases in [Ca2+]i and tension induced by histamine and endothelin- in the presence of extracellular Ca2+ were also inhibited by 10 microM FK506. FK506 (10 microM) had no effect on Ca2+ release induced by caffeine or by histamine in the Ca2+-free solution. FK506 (10 microM) had no effect on the [Ca2+]i-tension relationships of the contractions induced by cumulative increases of extracellular Ca2+ during K+ depolarization or stimulation with U46619. In the patch clamp experiments, FK506 (30 microM) partially inhibited the inward current induced by depolarization pulse from -80 mV to 0 mV. In conclusion, FK506 induces arterial relaxation by decreasing [Ca2+]i mainly due to the inhibition of the L-type Ca2+ channels, with no effect on the Ca2+ sensitivity of the contractile apparatus.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Biologic roles of gangliosides G(M3) and G(D3) in the attachment of human melanoma cells to extracellular matrix proteins.

The biologic functions of gangliosides G(M3) and G(D3) in the attachment of human melanoma cells to extracellular matrix proteins (type I and IV collagens, fibronectin, and laminin) were investigated by using the G(D3)-deficient mutant clone (SK-MEL-28-N1) and the parent cell line SK-MEL28. SK-MEL-28-N1 (N1) (high G(M3) expression: G(M3), 97.3%; G(D3), 0%) was selected by treating SK-MEL-28 (high G(D3) but low G(M3): G(M3), 6.5%, G(D3), 93.5%) with an anti-G(D3) monoclonal antibody (R24) and rabbit complement and subsequent subcloning of the surviving cells. The N1 clone showed significantly higher ability to adhere to type I and IV collagens and laminin than the parent clone SK-MEL-28. In the N1 clone, the expression of alpha2beta1 and alpha3beta1 integrin receptors was increased, whereas in SK-MEL-28, their expression was very low or undetectable. The treatment with monoclonal antibodies directed specifically to G(D3) expressed on SK-MEL-28 inhibited the cell attachment to type IV collagen (33% inhibition of control), fibronectin (59%), and laminin (71%). These findings suggest that gangliosides G(M3) (by influencing integrin receptor levels) and G(D3) (by interacting directly with matrix proteins) might play some functional roles in attachment to extracellular matrix proteins and thereby enhance the metastatic potency of melanoma cells.

Animals↗
PubMed1999

In vivo L-band ESR and quantitative pharmacokinetic analysis of stable spin probes in rats and mice.

Free radical species in animals have been measured by X-band ESR spectrometric method on a block of organs or a portion of homogenized samples. However, a nondestructive in vivo ESR measurement has been realized by using a recently developed L-band ESR spectrometry. With this L-band ESR method, we measured ESR spectra in animals, who received stable nitroxide radicals. L-band ESR spectra were observed at the upper abdomen of mice as well as at the heads of mice and rats at various ages immediately after the intravenous injections of nitroxide radicals such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (4-hydroxy-TEMPO) and 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3-carbamoyl-PROXYL), in which ESR measurements of the radicals were performed noninvasively at the real time. On the basis of the observed time-dependent free radical clearance curves, the following important results were obtained: (1) Free radical clearances were able to analyze by the pharmacokinetic method. (2) The radicals at the head of mice, given 4-hydroxy-TEMPO, were determined quantitatively by a new analytical method using L-band ESR for the first time. (3) The elimination of the radical was found to be saturated in mice. (4) The clearance rate constant of 4-hydroxy-TEMPO detected at the head of mice was decreased in dose- and age-dependent manners. While, no age-dependent clearance rate constant of 4-hydroxy-TEMPO was observed at the upper abdomen of mice. (5) Ratios of the amount of the detected radicals to that of the administered radicals were decreased age-dependently, but they were independent of the dose of the radicals, suggesting the age-dependent decrease of distribution capacity ratio of the radical at the head of animals. (6) Clearance rate constants of 4-hydroxy-TEMPO and 3-carbamoyl-PROXYL, that were estimated by X- and L-band ESR for the collected blood of mice and rats, were found to be remarkably smaller than those in whole living animals observed by in vivo L-band ESR method. The results suggest that the clearance of the nitroxide radical is relevant to the alteration of the radical in animals following the change of organ distribution and metabolism. (7) Both the radical and its corresponding hydroxylamine, which is the reduced form of the radical, were detectable by X-band ESR method in the collected urine of mice and rats without and with an oxidizing agent, respectively. On the basis of the results on L-band ESR spectrometry, the first quantitative pharmacokinetic analysis of stable spin probes in animals is proposed.

Aging↗
PubMed1999

Protection against influenza virus infection of mice fed Bifidobacterium breve YIT4064.

Mice fed Bifidobacterium breve YIT4064 and immunized orally with influenza virus were more strongly protected against influenza virus infection of the lower respiratory tract than ones immunized with influenza virus only. The number of mice with enhanced anti-influenza virus immunoglobulin G (IgG) in serum upon oral administration of B. breve YIT4064 and oral immunization with influenza virus was significantly greater than that upon oral immunization with influenza virus only. These findings demonstrated that the oral administration of B. breve YIT4064 increased anti-influenza virus IgG antibodies in serum and protected against influenza virus infection. The oral administration of B. breve YIT4064 may enhance antigen-specific IgG against various pathogenic antigens taken orally and induce protection against various virus infections.

Administration, Oral↗
PubMed1999

Effect of HSP47 on prolyl 4-hydroxylation of collagen model peptides.

Prolyl 4-hydroxylation, the most important post-translational modification in collagen biosynthesis, is catalyzed by prolyl 4-hydroxylase, an endoplasmic reticulum-resident enzyme. HSP47 is a collagen-binding stress protein which also resides in the endoplasmic reticulum (Nagata, K. and Yamada, K.M. (1986) J. Biol. Chem., 261, 7531-7536). Both prolyl 4-hydroxylase and HSP47 interact with procollagen alpha-chains during their folding and/or modification in the endoplasmic reticulum. Recent study has revealed that a simple collagen model peptide, (Pro-Pro-Gly)n, is recognized by HSP47 as well as by prolyl 4-hydroxylase in vitro (Koide et al., manuscript submitted). In the present study, we investigated the effect of HSP47 on the prolyl 4-hydroxylation of such collagen model peptides. To monitor the enzymatic hydroxylation of the peptides, we developed a non-RI assay system based on reversed-phase HPLC. When HSP47 was added to the reaction mixture, substrate and less-hydroxylated materials accumulated. This effect depended on the peptide-binding activity of HSP47, because a mutant HSP47 without collagen-binding activity did not show any inhibitory effect on prolyl 4-hydroxylation. Kinetic analysis and other biochemical analyses suggest that HSP47 retards the enzymatic reaction competing for the substrate peptide.

Animals↗
PubMed1999

Acute type A aortic dissection involving the left main trunk of the coronary artery--a report of two successful cases.

This report describes 2 cases of a type A acute aortic dissection combined with myocardial infarction caused by a retrograde dissection into the left main trunk of the coronary artery. Successful surgical treatments, including the replacement of the ascending aorta, aortic valve resuspension and coronary artery bypass grafting, were performed in both patients, and they recovered well from cardiogenic shock. However, left ventricular function of both patients remained depressed postoperatively, which limited their quality of life. Because no definite method for salvaging infarcted myocardium has yet been established, either more timely surgery or the preoperative placement of a perfusion catheter in the left main coronary artery is mandatory.

Acute Disease↗
PubMed1999

[An autopsy case of multiple system atrophy presenting with rapid progression of autonomic disturbance].

We report an autopsy case of multiple system atrophy (MSA) presenting with rapid progression of autonomic disturbance. He was admitted to our hospital because of gait disturbance and dysarthria. The patient was a Japanese man, who first noticed gait disturbance and dysarthria at age 58, followed by syncope 3 months later. He developed urinary incontinence and frequency of urination 8 months after the disease onset. His gait disturbance, dysarthria, syncope, and urinary symptoms progressed, and he was admitted to the department of neurology 1 year after the onset of the disease. He was clinically diagnosed as having MSA and was followed in the outpatient office. He deteriorated rapidly and was readmitted to the department of neurology 19 months after the onset of the disease. Physical examination showed orthostatic hypotension. Neurological examination revealed nystagmus, dysarthria of cerebellar type, increased deep tendon reflexes, bilateral positive Babinski signs, ataxic and spastic gait, mild right hypesthesia and hypalgesia, impotence, constipation, and urinary incontinence. Routine blood examination showed slight anemia, elevated BUN, GOT, and blood sugar. Electrocardiography revealed sinus tachycardia and chest rentogenogram showed cardiac enlargement. Brain MRI showed atrophy of cerebellum and pons, and lacunae in basal ganglia. Autonomic function tests revealed abnormal in head-up tilt test, and CVR-R in May and November 1995. However 123I-MIBG myocardial scintigraphy showed normal uptake of MIBG in May 1995 and decreased uptake in November 1995. He deteriorated rapidly and died in May 1996. Autopsy findings revealed not only prominent olivopontocerebellar and slight striatonigral lesions, but also autonomic lesions with massive appearance of glial cytoplasmic inclusions. He was pathologically verified as having MSA. In the present patient, autonomic nervous system, especially cardiac sympathetic nerve, deteriorated rapidly, which might result in short duration of the illness.

3-Iodobenzylguanidine↗
PubMed1999

[Clinical results of mitral valve surgery in children].

The clinical results of mitral valve surgery in children were evaluated. Fifty children (age ranged between 1 month and 12 years) with mitral valve regurgitation have undergone valve surgery with low operative mortality (2%). Valve plasty using several techniques including annuloplasty have been performed with quite high success rate (92%), while valve replacement was required in four patients who had the prolapse of the anterior mitral leaflet (8%). Reoperation was required in 5 patients (10%), and there were 4 late deaths. Introduction of the reconstructive technique of the chordae tendinae using artificial chordae resulted 100% success rate of mitral repair for the prolapse of the anterior mitral leaflet without death and reoperation. The reoperation free rate and the actuarial survival rate at 15 years of the patients with mitral regurgitation were 70 +/- 12% and 85 +/- 7%, respectively. In ten patients with mitral valve stenosis (age ranged between 1 month and 5 years), 5 patients required valve replacement (50%), and 2 patients died (20%). The clinical results of the surgery for the mitral stenosis were still unsatisfactory, and the reoperation free rate at 2 years was 42 +/- 30% and the actuarial survival rate at 13 years were 32 +/- 18%.

Blood Vessel Prosthesis↗
PubMed1999

[Descending aorta perfusion through median sternotomy in primary repair of aortic interruption complex].

Circulatory arrest is frequently used in aortic arch reconstruction in pediatric cardiac surgery. However, risks of postoperative acute renal failure and neurological deficit can not be ignored. We performed primary repair of aortic interruption in one-month old girl. After commencing extracorporeal circulation with bicaval venous cannulae and with arterial cannulae into the pulmonary trunk and the innominate artery, the descending aorta was cannulated just superior to the diaphragm. The cannula in the pulmonary trunk was then removed. Arch reconstruction and closure of the ventricular septal defect were performed with continuous perfusion to the brain and the lower body. The extracorporeal circulation time and the aortic cross-clamp time were 117 min and 21 min, respectively. Postoperative renal function was excellent, and there was no finding of neurological deficit. Cannulation of the descending aorta is a simple and useful technique with safety, in arch reconstruction in infants.

Aorta, Thoracic↗
PubMed1999

[Epidemiological studies on drug-resistance patterns, coagulase types, and MRSA-phage types of MRSA isolates during 1990-1994].

We examined drug-resistance patterns, coagulase types, and MRSA-phage types of 125 MRSA strains isolated from clinical specimens during the period of January 1990 and December 1994. No vancomycin-resistant strain was isolated. Twenty one antibiotics were divided into three classes, low-intermediate- and high-isolation-frequency class, based on isolation frequencies of resistant strains. Minocycline, chloramphenicol, streptomycin, and imipenem were found to be included in low-isolation-frequency class (16.8-40%). In intermediate-isolation-frequency class (45.6-62.9%), cefmetazole, amikacin, gentamicin, and tetracycline were included. Oxacillin, ampicillin, piperacillin, ceftizoxime, cefoperazone, cefazolin, erythromycin, oleandomycin, kitasamycin, clindamycin, kanamycin, tobramycin, and ofloxacin belonged to high-isolation-frequency class (97.6-100%). MIC90s of vancomycin and minocycline (1.56 and 25 micrograms/ml) were lower than that of other 13 drugs. Comparing medical ward with dental ward, imipenem-, gentamicin-, and minocycline-resistant strains at medical ward, chloramphenicol- and streptomycin-resistant strains at dental ward were isolated dominantly on each ward, MRSA isolates were classified to 39 types by drug-resistance patterns. The isolation frequencies of coagulase type II and type IV strains were 65.6% and 29.6%, respectively. At dental ward, the isolation frequency of coagulase type IV strains was higher than that of coagulase type II strains during 1990-1992. However, coagulase type II strains were isolated considerably more than type IV strains during 1993-1994. By MRSA-phage typing, MRSA isolates were grouped into 18 MRSA-phage types. One hundred and twenty five MRSA isolates were divided into 56 types by using drug-resistance patterns, coagulase typing, and MRSA-phage typing. It was considered that such classification in combination of three methods is useful to make decision of epidemic by the same MRSA strain.

Anti-Bacterial Agents↗
PubMed1999

[Efficacy of intravenous administration of atrial natriuretic peptide after cardiac surgery in neonates and infants].

Intravenous infusion of alpha-human atrial natriuretic polypeptide (hANP) and furosemide was performed in 12 patients (4: TGA, 3: univentricular heart, 3: HLHS, 2: VSD) after cardiopulmonary bypass. Their mean age at the operation was 68 days (6 patients in neonate), the mean body weight was 3.3 kg. All patients were treated with nitroglycerin in dose of 2 micrograms/kg/min and chlorpromazine in dose of 2.8 micrograms/kg/min and catecholamine in mean dose of 6.5 micrograms/kg/min. The criteria of indication for hANP was poor effect of furosemide alone. The hANP was given for 6-144 hours in dose of 0.1-0.2 microgram/kg/min. With the hANP and furosemide infusion, urine volume increased from 85.0 +/- 14.2 ml/kg/day to 107.9 +/- 25.3 ml/kg/day (p < 0.05), whereas the systemic arterial pressure, the central venous pressure and the renal function were unchanged. We conclude that the combination of the hANP and the furosemide is very effective in neonates and infants.

Atrial Natriuretic Factor↗
PubMed1998

HTHQ (1-O-hexyl-2,3,5-trimethylhydroquinone), an anti-lipid-peroxidative compound: its chemical and biochemical characterizations.

Recently, it has become apparent that reactive oxygen species (ROS) play many important roles in biological systems. For example, relationships between many diseases, such as cancer, cardiac infarction and arteriosclerosis, and ROS have been found. It is also well known that anti-oxidative agents scavenge ROS in biological systems, which in turn prevents ROS-related diseases. In our previous efforts to develop effective anti-oxidative compounds, we found that 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), which is a hydroquinone monoalkyl ether, is a potent anti-oxidative agent. Here, the scavenging activities of HTHQ against ROS, such as superoxide anion radicals, hydroxyl radicals, t-butyl peroxyl radicals and singlet oxygens, were examined by the ESR (electron spin resonance)-spin trapping method. Among ROS, HTHQ scavenged t-butyl peroxyl radicals most effectively (IC50=0.31+/-0.04 mM), showing approximately twice the activity of a well-known lipophilic anti-oxidant, D,L-alpha-tocopherol (IC50=0.67+/-0.06 mM), as measured by IC50 values defined as the 50% inhibition concentration of the generated ROS. In addition, a relatively stable ESR spectrum of free radicals due to HTHQ was observed during the reaction of HTHQ and t-butyl peroxyl radicals, indicating a direct reaction of HTHQ and t-butyl peroxyl radicals. The free radicals due to HTHQ were more stable than those derived from D,L-alpha-tocopherol under the same conditions examined. On the basis of these results, we evaluated anti-lipid-peroxidative activity of HTHQ in three systems involving micelles, liposomes and rat liver microsomes. HTHQ exhibited a similar anti-oxidative activity to that of D,L-alpha-tocopherol against lipid peroxidation in linolate micelles initiated by addition of Fe2+. On the other hand, HTHQ exhibited approximately 4.8-fold higher anti-lipid-peroxidation activity than that of D,L-alpha-tocopherol against the peroxidation in phosphatidylcholine liposomes initiated by addition of Fe2+. Furthermore, HTHQ scavenged the lipid peroxides at a rate approximately 150 times higher than that of D,L-alpha-tocopherol against Fe3+ -ADP-induced lipid peroxidation in rat liver microsomes, indicating that the anti-lipid-peroxidation activity of HTHQ might be substantially elevated in biological systems in comparison with that of D,L-alpha-tocopherol. Based on these results, we suggest that HTHQ reacts directly with peroxyl radicals, such as t-butyl peroxyl radicals and peroxides of linolate micelles, liposomes and microsomes, by scavenging them to form stable free radicals. The resulting free radicals are presumed to be reduced by several reducing mechanisms in biological systems similarly to those of D,L-alpha-tocopherol, and then the lipid-peroxidation reactions will be terminated. In conclusion, HTHQ was found to be a potent anti-lipid-peroxidative compound and its antioxidation activity to be extremely elevated in biological systems, such as that of liver microsomes via the generation of stable free radicals. We propose that HTHQ is a potent anti-oxidative agent for use in future treatments for lipid-peroxide relevant diseases.

Animals↗
PubMed1998

Dominant lethality of the mouse skeletal mutation tail-short (Ts) is determined by the Ts allele from mating partners.

Mice with the Tail-short (Ts) mutation have a short, kinky tail and numerous skeletal abnormalities, including a homeotic anteroposterior patterning problem involving the axial skeleton. The viability of Ts heterozygotes varies dramatically, depending on the mouse strain crossed with the mutant strain. At the extremes, the heterozygotes are viable or lethal prenatally. In this study, we found that laboratory mouse strains could be divided into two groups. A cross with strains from the first group yielded viable Ts heterozygotes, whereas a cross with the second group resulted in dominant lethality in utero. We planned to map the gene(s) that controls strain differences in the viability of the Ts heterozygotes. The result clearly indicated that a single chromosomal region, genetically inseparable from the Ts locus, is responsible for these differences. This suggests that allelism at the Ts locus generates variable manifestation of the mutant phenotype. Morphological and histological analyses indicated that embryos from the lethal cross exhibit severe developmental defects from the gastrulation stage through the early fetal stage. In particular, the umbilical vein does not develop properly. All of these results suggest that the phenotype of the Ts mutant is modified by the Ts alleles of the mating partners.

Alleles↗
PubMed1998

Situs variation and cardiovascular anomalies in the transgenic mouse insertional mutation, inv.

The inv mouse was reported as a novel strain with situs inversus Yokoyama et al., '93), and a few cases with heterotaxy were found in homozygotes. The original report by Yokoyama et al. described the location of the heart and the stomach using the index of arrangement of body structure. We newly examined 40 homozygous offspring for phenotypes of visceroatrial situs and the incidence of cardiovascular anomalies making use of morphological details defined in each organ structure. According to the arrangement of each organ, which ranged from the almost complete form of situs inversus to left isomerism, visceroatrial situs was classified into four categories: Situs inversus (4 cases), "variation type" of situs (17 cases), "abdominal heterotaxy" (15 cases), and visceroatrial heterotaxy (4 cases). In offspring with situs inversus, only one had aortic stenosis (25%). Seven with the "variation type" of situs had cardiovascular anomalies, such as aortic stenosis, endocardial cushion defect, and posterior vena cava interruption (41%). All 15 offspring with "abdominal heterotaxy" had anomalies of the posterior vena cava, and three of them also had tetralogy of Fallot. The remaining four with visceroatrial heterotaxy had endocardial cushion defect, which was associated with outflow tract anomaly in two cases (i.e. tetralogy of Fallot in one case and transportation of the great arteries in the other). These results revealed that visceroatrial heterotaxy frequently occurred in the inv homozygotes, especially in the abdomen, and often showed a propensity to left isomerism with posterior vena cava interruption.

Animals↗
PubMed1998

Anomalous looping, atrioventricular cushion dysplasia, and unilateral ventricular hypoplasia in the mouse embryos with right isomerism induced by retinoic acid.

BACKGROUND: Visceroatrial heterotaxy syndrome is characterized by abnormality of visceral laterality and complex cardiovascular anomalies usually involving both the outflow and inflow tract. Morishima et al. (1995) showed that mouse embryos treated with all-trans retinoic acid at embryonic day 6.5 (primitive streak stage) induces this syndrome. METHODS: To investigate the morphogenetic process of visceroatrial heterotaxy syndrome, we examined retinoic acid-treated mouse embryos at embryonic days 9-15 using scanning electron microscopy. RESULTS: The sinoatrial connection was first distinguished for the determination of situs as early as at embryonic day 10.5. Normal visceroatrial situs was found in 57% of all treated embryos, and the rest had abnormal situs, in which right isomerism was found in 81%. In the right-isomeric mouse, the cardiac morphology was characterized by abnormal looping together with dysplasia of the inflow and outflow tract cushion; that is, the primitive right ventricle was usually deviated cranially to various degrees, the atrioventricular cushion appeared trilobed in a half of them, and unilateral ventricular hypoplasia was noted in about one-third of them after embryonic day 14.5. CONCLUSIONS: An anomalous relation between the atrioventricular cushions and the interventricular septum appeared to have caused a restrictive inflow to the unilateral ventricle, leading to ventricular chamber hypoplasia on the ipsilateral side. Thus, we clarified that retinoic-acid treatment at the primitive streak stage disturbed cardiac looping and formation of atrioventricular cushion development, which secondarily influenced ventricular chamber development.

Abnormalities, Drug-Induced↗
PubMed1998

Preparation and evaluation of micro-porous ethylcellulose capsule as oral sustained-release preparation of theophylline.

Micro-porous ethylcellulose (EC) membrane capsules were prepared by dissolving polyvinylalcohol (PVA) particles from membranes which were made of a mixture of EC (a water-insoluble polymer). The pore size was approximately 400 microns. Since the dissolution rate of theophylline from the micro-porous EC membrane capsules was fast, gel-forming polymer, poly(acyclic) acid (Carbomer), was incorporated inside the capsule at 10, 20 or 30 mg. Using test capsules containing 100 microns of theophylline, in vitro dissolution studies were performed. By including Carbomer in capsule formulations, the dissolution rate of theophylline was decreased. However, there were not significant differences in dissolution rates between preparations containing the three different amounts of Carbomer. In vivo evaluation studies using beagle dogs showed that AUC, Cmax and Tmax were inversely proportional to the formulated amount of Carbomer. The capsule containing 20 mg of Carbomer gave plasma theophylline concentrations between 5 and 15 micrograms mL-1, which reflect levels within the therapeutic window. The effect of food intake on the pharmacokinetics of theophylline was also studied with the same capsule. Food increased AUC, Cmax and Tmax, although plasma theophylline levels were maintained within the therapeutic range.

Administration, Oral↗