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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 127 records · Page 7Linked to original sources
PubMed2001

Double-Switch operation for congenitally corrected transposition.

Double-switch operation was performed in 76 patients with congenitally corrected transposition of the great arteries at the Heart Institute of Japan, Tokyo Women's Medical University. Detailed surgical techniques of Mustard and Senning procedures for inlet switch, as well as arterial switch operation, pulmonary reconstruction by direct right ventricular-pulmonary arterial anastomosis, and external conduit repair for outlet switch are described in detail.

Adolescent↗
PubMed2001

Studies on mechanisms of low emetogenicity of YM976, a novel phosphodiesterase type 4 inhibitor.

YM976 is a novel and selective inhibitor of phosphodiesterase type 4 (PDE4) with a different chemical structure from rolipram. Orally administered YM976 showed anti-inflammatory activity (ED(50) = 2.8 mg/kg) similar to rolipram (3.5 mg/kg). On the other hand, the emetogenicity of YM976, one of the main adverse effects of PDE4 inhibitors, was lower (maximal non-emetic dose = 10 mg/kg) than that of rolipram (1 mg/kg). The reasons for this low emetogenicity of YM976 remain unclear, and the present study endeavored to elucidate the mechanisms. Candidates for the possible mechanisms included 1) PDE4 subtype selectivity, 2) binding affinity for HAR-conformation, and 3) brain penetration. YM976 exhibited affinity for high affinity for rolipram-conformation (HAR-conformation) (IC(50) = 2.6 nM) identical to that of rolipram (1.2 nM), and failed to show significant selectivity for the individual PDE4 subtype. These results suggested that neither subtype selectivity nor the affinity for HAR-conformation may be related to the low emetogenicity of YM976. YM976 showed a minor effect on reserpine-induced hypothermia, in contrast to rolipram. To estimate brain penetration, we then measured cAMP contents in peripheral tissues (peritoneal macrophages) and in the brain. YM976 increased the cAMP content of peritoneal macrophages, but caused no significant increase in brain cAMP levels, while rolipram elevated the cAMP content of both tissues at the same dose. In conclusion, YM976 shows an apparent dissociation between its anti-inflammatory effects and emetogenicity, perhaps because of the poor brain penetration.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

[Tuberculosis control strategy in the 21st century in Japan--for elimination of tuberculosis in Japan].

Modern tuberculosis control programme has been launched in 1951 by the major revision of the previous Tb. Control Law in Japan. Main control measures were BCG vaccination programme for tuberculin negatives, annual screening of Tb. by miniature radiophotography (MMR), charge free diagnosis and treatment of Tb. patients, registration and case-holding at Health Centres throughout the country and so on. Thanks to the efforts of the Government and people concerned, Tb. incidence has decreased with the annual reduction rate of 11% during 1961 and 1977. However, Tb. decrease has stagnated after that, and it is increasing slowly in these 3 years since 1998. Moreover, regional variations of Tb. incidence are considerable, and Tb. is concentrated in specific risk groups such as elderly persons, homeless, foreign born individuals and so on. However, the present Tb. Control measures were introduced prior to the discovery of most major anti-Tb. drugs and all modern internationally accepted Tb. Control strategies, so that it is strongly desired to improve the present control programme from rather classical present Tb. control measures to global standard one to overcome the resurgence of Tb. in Japan. At first, the author stressed that the priority of Tb. Control Programme should be changed according to the development of science and the change of epidemiological situations. BCG vaccination and Tb. screening by MMR might be very important when the annual risk of Tb. infection was very high--about 4% in 1950. Now it is around 0.05% and the incidence of Tb. among 0-14 years of age is 1.1 per 100,000 so that the priority should be given on treatment of the detected cases instead of BCG vaccination or MMR. The doctors in the public health field should give more strong concern on clinical aspects of Tb. Control Programme at present. It was considered that the main urgent problems to be improved in the present Tb. control measures are as follows. 1. It is strongly recommended to spread the global standard regimen with 2HRZE/4HR (E) more widely and rapidly. Because the standard regimen is used in only 50% of new smear positive cases at present although 15.3% of Tb. patients are 80 years or more, or 56.3% of them are 60 years or more, and the side effects by PZA are higher among elderly patients. 2. Shortening of the hospitalization duration is required because 76.7% of newly detected bacilli positive cases are hospitalized at first, and the median of the period of hospitalization is 4 months, and 18.4% of them are hospitalized 6 months or more at present. 3. DOT treatment has been introduced for special groups in the big cities in 2000 for the first time in Japan, but it is needed to spread DOT treatment more widely, for example, by increasing health insurance payment for the institutions where DOT treatment is being implemented. 4. It is recommended to build special rooms to accept Tb. patient at general hospitals and/or university hospitals to avoid the neglect of Tb. by general medical doctors. 5. Follow-up of Tb. patients after treatment completion at Health Centres is not needed now, because the relapse rate is so low. 6. Indiscriminative screening programme for all the people aged 19 years old or more should be stopped, at least up to 39 years of age, because Tb. detection rate has become so low as 0.0069% at present. As Tb. decrease is so slow, or is increasing in some areas, that the contact surveys among the young aged 20 to 39 should be strengthened in the future. 7. As Japan Anti-Tb. Association is being carrying out mass screening programme extensively at present, so that the Association has started to discuss the future health check system. Because of the rapid and constant increase of the lung cancer, the Association is discussing the method to detect the lung cancer, too. In any way, it is needed to focus the screening programme for special high risk groups instead of indiscriminative screening. 8. BCG vaccination for infants should be continued a little more, because BCG vaccination can protect the development of 7 miliary Tb. and/or meningitis cases during 15 years if BCG is given 70% of the infants in 2000. However, it was strongly recommended to stop re-vaccination of BCG, because it is not so effective, and disturb the diagnosis of Tb. infection by tuberculin testing. 9. Treatment of latent Tb. infection will become more and more important, so that it's indication should be expanded to the adults in the future instead of the present indication up to 29 years of age. It is needed to revise Tuberculosis Control Low to improve control programme in Japan. The author hoped that the members of Japan Tuberculosis Society will promote the improvement and to support the Government to improve the Law.

Age Factors↗
PubMed2001

[Case report of CABG for progressive coronary artery stenosis after 22-year history of Kawasaki disease].

More than 30 years has passed since Kawasaki disease was recognized as an independent disease entity, but the cardiovascular complications of Kawasaki disease are still not well known. We report an 22-year-old woman who underwent triple coronary artery bypass grafting because of a coronary artery aneurysm and multiple coronary artery stenoses, 22 years after the diagnosis of Kawasaki disease. A 2 cm coronary artery aneurysm due to Kawasaki disease was diagnosed when she was 10 years old, when she first presented with the symptom of dyspnea on effort. Since then, she was followed at the outpatient clinic. When she was 19 years old, the first coronary catheterization was performed. Two years later, the second coronary catheterization revealed progression of coronary artery disease. Therefore, coronary artery bypass grafting was performed. This case is rare from the point of view of long-term progression of coronary artery disease.

Adult↗
PubMed2001

[QOL questionnaire version 2001 for pediatric patients with bronchial asthma and their parents or caregivers--preparation and evaluation].

We already reported that the QOL questionnaire for pediatric patients with bronchial asthma and their parents or caregivers reflects reliability (including test retest), factorial validity, and changes in paroxysmal attacks of asthma. In this study, we revised the questionnaire for use in routine medical care. We investigated the importance of questions for affected children and their parents or caregivers and selected and discarded questions on the basis of average ranks of the importance and medical standpoint so that the questionnaire might have physical and emotional domains. The QOL questionnaire version 2001 for pediatric patients with bronchial asthma and their parents or caregivers (hereafter to be abbreviated as the version 2001) includes 15 questions for patients under the age of 4 years and 20 questions for patients over the age of 4 years and 4 year-old. The "present" and "absent" groups, which were categorized with respect to the events (e.g., attack) that developed in 2 weeks prior to the QOL investigation, showed a significant difference (Mann-Whitney U-test) in terms of the total score of replies which constitute each domain, i.e., physical domain (p = 0.0052) in patients under the age of 4 years and physical domain (p < 0.0001) and emotional domain (p < 0.0001) in patients over the age of 4 years and 4 year-old. Regarding the average value of each reply which constitutes the domain as well, the physical domain showed a decrease in symptom instability and the "> or = 4 years" group showed a decrease in exertional load and mental load. Therefore, a QOL investigation like ours which investigates disorders in which attacks develop suddenly, e.g., asthma, should examine the presence or absence of all events prior to the investigation. The version 2001 was considered useful for affected children and their parents or caregivers to comprehend the content and severity of impairments which were provoked by asthma.

Asthma↗
PubMed2001

[Effect of probucol on the concentration of cyclosporin A in patients with nephrotic syndrome].

The first choice of therapy for nephrotic syndrome is steroid, and cyclosporin A(CyA) or other immunosuppressants are selected for steroid resistant or recurrent cases. Nephrotic syndrome accompanies hyperlipidemia for which HMG-CoA reductase inhibitors are mainly used. On the other hand, probucol is used in cases showing inadequate effects or some adverse reactions under treatment with HMG-CoA reductase inhibitors. Recently, we experienced several cases whose blood levels of CyA were decreased to about half that before the combined use of probucol, and concomitant administrations were discontinued. Based on these cases, we considered that the use of probucol should be prescribed in patients with nephrotic syndrome accompanying hyperlipidemia giving preference to CyA treatment. In cases of unavoidable usage of probucol, CyA dose adjustments are required on the basis of frequent CyA blood level monitoring.

Adult↗
PubMed2001

[HGF as a key molecule in cardiovascular diseases].

Hepatocyte growth factor(HGF) is focused as a powerful endothelial growth factor in the field of cardiovascular diseases. As its physiological role in atherosclerosis, restenosis, angiogenesis etc is very important, HGF-based new treatments for various diseases are expected. Clinical gene therapy for restenosis and ischemic diseases using VEGF gene have already performed in USA, and they could show beneficial effects of such strategies. In Japan, gene therapy using HGF gene for ASO has just begun in spring 2001. In near future, powerful therapeutic effects of HGF could applied to restenosis, graft failure, cardiomyopathy, cerebral vascular diseases, renal failure and so on.

Animals↗
PubMed2001

[An autopsy case of atypical Friedreich's ataxia with chronic idiopathic intestinal pseudo-obstruction].

We report a 58-year-old man with slowly progressive muscle atrophy and weakness in the four extremities, accompanying cerebellar ataxia and sensory impairment of all modalities. He was a product of consanguineous marriage. His neurological manifestations began in childhood. He was admitted to our hospital because of marked abdominal distension and pretibial edema with hypoalbuminemia and hyperlipidemia. Neuroimaging studies showed marked atrophy of the cerebellum and spinal cord. Nerve conduction studies presented with slowing and sural nerve biopsy revealed demyelination with onion-bulbs. Abdominal distension was interpreted to be caused by chronic idiopathic intestinal pseudo-obstruction (CIIP), leading to protein-losing gastroenteropathy and hypalbuminemia caused by the CIIP. He died of DIC by myelodysplasic syndrome and DIC, two years later. Postmortem study demonstrated with severe loss of anterior horn cells and gliosis in the spinal cord. The Clarke's column was also affected. There was symmetrical degeneration in the dorsal column and corticospinal tracts. The cerebellum showed atrophy of molecular layer, prominent loss of Purkinje's cells and sparse granular cell layer, but no obvious change in the dentate nucleus. Neuronal loss in the dorsal root ganglia was remarkable. There were no alternations in the cerebral cortex, striatum, thalamus, subthalamic nucleus, and pontine nucleus, except for mild changes in substantia nigra and inferior olivary nucleus. This case was clinically suspected either of variant of Friedreich's ataxia or an early onset ataxia associated with hypoalbuminemia (EOAHA), although marked autonomic dysfunction was atypical. But the postmortem study, demonstrated with marked neuronal loss in anterior horn cells and cerebellan cortex and rather suggested an independent category of this case.

Friedreich Ataxia↗
PubMed2001

Development of "Standards for the Evaluation of Hospital Infection Control Policies and Procedures, the Second Version".

The Japan Society for Quality in Health Care (JSQua) created "Standards for the Evaluation of Hospital Infection Control Policies and Procedures, the First Version" in 1998 and carried out third-party surveys. Through the experience of those surveys, we revised the standards and created a second version in 1999. The surveyors felt that in using the second version of the standards it would be easier to evaluate the quality of hospital care and that these standards would be more widely applied.

Cross Infection↗
PubMed2000

Chemical changes of polymeric surfaces after modification with multi-source cluster deposition.

A new process for surface modification of polymers with multi-source cluster deposition apparatus has been reported in our previous work. The apparatus simultaneously supplies reactant of ammonium sulfamate and activator of energetic Ar(+) ion. In this work chemical changes are analyzed on the basis of XPS spectra and the relations of contact angle and platelet adhesion with chemical changes are discussed. Polymer film, setting on a turning holder, was irradiated by Ar(+) ions during bombardment with ammonium sulfamate clusters. The Ar(+) ion source served for activation of polymer surface and a cluster ion source supplied ammonium sulfamate molecules to react with activated surface. After thorough washing with deionized sterile water, the modified surfaces were evaluated in terms of contact angle of water, elemental composition and binding state on XPS and platelet adhesion with platelet rich plasma (PRP). The modification of polysulfone decreased the contact angle of water on surfaces from 82.6 down to 34.5 degrees. The adhesion number of platelets were decreased to one-tenth of the original surface. Ammonium, amine, sulfate and thiophene combinations were formed on the modified surfaces. The primary studies showed successful modification of polysulfone with ammonium sulfamate by assistance of Ar(+) ion irradiation. The polar groups like N-sulfate were formed on surfaces and contribute to the decrease of surface contact angle and adhesion number of platelets. Since the same process can also be applied to other polymeric materials with various substrates, combining with the features of no solvent and no topographic changes, this method might be developed in a promising way for modification of polymers.

Journal Article↗
PubMed2000

Measurement of direct photon emission in K+-->pi(+)pi(0)gamma decay

We have performed a measurement of the K+-->pi(+)pi(0)gamma decay and have observed 2x10(4) events. The best fit to the decay spectrum gives a branching ratio for direct photon emission of (4.7+/-0.8+/-0. 3)x10(-6) in the pi(+) kinetic energy region of 55 to 90 MeV and requires no component due to interference with inner bremsstrahlung.

Journal Article↗
PubMed2000

High prevalence of spinocerebellar ataxia type 1 (SCA1) in an isolated region of Japan.

Autosomal dominant cerebeller ataxias (ADCAs) are a heterogeneous group of neurodegenerative disorders that differ in both the clinical manifestations and modes of inheritance. At present, eight different genes causing ADCAs have been found: spinocerebeller ataxia type 1 (SCA1), SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA8, SCA12 and dentatorubropallidoluysian atrophy (DRPLA). The relative prevalence of each mutation varies according to race and native place. We studied 117 unrelated ADCA families that originated from the Tohoku District in the northernmost part of Honshu Island in Japan (mainly Miyagi Prefecture in the central part of Tohoku District). The SCA1 mutation was the most frequent among the known disorders (24.8% of all such families). The relative prevalence of SCA1 in the Tohoku District is very high compared with the values already reported from other regions in the world. Because the population of this area had seldom moved, the alleles with SCA1 mutations (including alleles with an intermediate CAG repeat number) are assumed to have been present in this area for a long time.

Ataxin-1↗
PubMed2000

Ribozyme oligonucleotides against transforming growth factor-beta inhibited neointimal formation after vascular injury in rat model: potential application of ribozyme strategy to treat cardiovascular disease.

BACKGROUND: Because the mechanisms of atherosclerosis or restenosis after angioplasty have been postulated to involve an increase in transforming growth factor (TGF)-beta, a selective decrease in TGF-beta may have therapeutic value. Thus, we used the ribozyme strategy to actively cleave the targeted gene to selectively inhibit TGF-beta expression. METHODS AND RESULTS: We constructed ribozyme oligonucleotides (ONs) targeted to the sequence of the TGF-beta gene that shows 100% homology among the human, rat, and mouse species. The specificity of ribozyme against TGF-beta gene was confirmed by selective inhibition of TGF-beta mRNA in cultured vascular smooth muscle cells as well as balloon-injured blood vessels in vivo. Importantly, the marked decrease in TGF-beta resulted in significant inhibition of neointimal formation after vascular injury in a rat carotid artery model (P:<0.01), whereas DNA-based control ONs and mismatched ribozyme ONs did not have any inhibitory effect on neointimal formation. Inhibition of neointimal formation was accompanied by (1) a reduction in collagen synthesis and mRNA expression of collagen I and III and (2) a significant decrease in DNA synthesis as assessed by proliferating cell nuclear antigen staining. Moreover, we modified ribozyme ONs containing phosphorothioate DNA and RNA targeted to the TGF-beta gene. Of importance, modified ribozyme ONs showed a further reduction in TGF-beta expression. CONCLUSIONS: Overall, this study provides the first evidence that selective blockade of TGF-beta resulted in inhibition of neointimal formation, accompanied by a reduction in collagen synthesis and DNA synthesis in a rat model. We anticipate that modification of ribozyme ON pharmacokinetics will facilitate the potential clinical utility of the ribozyme strategy.

Animals↗
PubMed2000

Familial spinal arachnoiditis with secondary syringomyelia: clinical studies and MRI findings.

We report the clinical and MRI findings of two patients with familial spinal arachnoiditis. Although their initial symptoms were various, they both showed spastic paraparesis and sensory disturbance below the thoracic level. Cytokines and WBC in the CSF were studied, but they were not elevated at all. The spinal magnetic resonance images of each showed extensive arachnoiditis and a cystic structure. The other impressive features included: (i) an enhancement within the thickened arachnoid and an adhesion between the spinal cord and the dura mater, (ii) deformation of the thoracic cord where the arachnoid adhered, and (iii) secondary syrinx formation. Laminectomy may have an adverse outcome for such patients.

Arachnoiditis↗
PubMed2000

Isolation and characterization of a novel liver-specific gene, hepassocin, upregulated during liver regeneration.

By differential cDNA cloning coupled with Xenopus oocyte expression screening, we isolated a cDNA encoding a novel protein, termed 'hepassocin', the expression of which is upregulated in the regenerating rat liver. The cDNA contained a single open reading frame encoding a protein of 314 amino acids (ca. 34 kDa), including 24 amino acids of signal sequence. The protein expressed from the cDNA in Verots cells had activity to stimulate DNA synthesis in primary rat hepatocytes and was of 66 kDa or 34 kDa, under non-reducing or reducing conditions, respectively. Using an affinity column conjugated with the antibody raised against a peptide in a hydrophilic region, we purified hepassocin from the rat liver: it had a DNA synthesis-stimulating activity in hepatocytes. The hepassocin obtained here was 66 kDa, and the 34 kDa protein obtained under reducing conditions contained five cysteine residues, indicating that hepassocin is active as a homodimer. Northern blot analysis revealed that hepassocin mRNA (1.4 kb in length) occurred only in the liver, and in situ hybridization studies revealed its presence in parenchymal hepatocytes but not in endothelial cells. Furthermore, the expression of hepassocin mRNA was upregulated during compensatory hyperplasia after partial hepatectomy and regeneration after galactosamine treatment in the rat liver. These results suggest that hepassocin plays an important role in stimulating liver cell growth, through an autocrine mechanism.

Amino Acid Sequence↗
PubMed2000

Supersymmetric model with an extra U(1) gauge symmetry forbidding proton decay

In the standard model the proton is protected from decay naturally by gauge symmetries, whereas in the ordinary minimal supersymmetric standard model an ad hoc discrete symmetry is imposed for the proton stability. We present a new supersymmetric model in which the proton decay is forbidden by an extra U(1) gauge symmetry. Particle contents are necessarily increased to be free from anomalies, incorporating right-handed neutrinos. Both Dirac and Majorana masses are generated for neutrinos, yielding nonvanishing but small masses. The superpotential consists only of trilinear couplings and the mass parameter &mgr; of the minimal model is induced by spontaneous breaking of the U(1) symmetry.

Journal Article↗