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Biomedical subjects

T Aoyama

Publications and source records attributed to T Aoyama.

At least 163 records · Page 9Linked to original sources
PubMed1997

Fluorescence in situ hybridization mapping of the alpha and beta subunits (HADHA and HADHB) of human mitochondrial fatty acid beta-oxidation multienzyme complex to 2p23 and their evolution.

Mitochondrial fatty acid beta-oxidation multienzyme complex/trifunctional protein has an alpha4beta4 structure and catalyzes the second through fourth reactions of the fatty acid beta-oxidation cycle. The alpha and beta subunits (HADHA and HADHB) are members of the enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase families, respectively. We analyzed the localization of each of these two genes (HADHA and HADHB) by in situ hybridization and found that both can be assigned to human chromosome band 2p23. Since the distance between the two loci is quite short, the two genes seem to exist side by side, as do the two (A and B subunit) genes of the bacterial fatty acid beta-oxidation multienzyme complex. This is an important and interesting finding in that two entirely different genes, encoding two independent proteins forming a multienzyme complex, are adjacent on chromosome band 2p23.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1997

Medium chain 3-ketoacyl-coenzyme A thiolase deficiency: a new disorder of mitochondrial fatty acid beta-oxidation.

A Japanese male neonate died at 13 d of age after presenting at 2 d of age with vomiting, dehydration, metabolic acidosis, liver dysfunction, and terminal rhabdomyolysis with myoglobinuria. Multiple urine organic acid analyses consistently revealed a markedly elevated excretion of lactic acid, 3-hydroxybutyric acid, and saturated and unsaturated C6-C16 dicarboxylic acids, with predominant C12-C16 species. Oxidation of [1-14C]octanoic acid in cultured skin fibroblasts was significantly reduced (0.59 nmol/h/mg of protein; controls, 1.93 +/- 0.65), [1-14C]palmitic acid oxidation was 1.11 nmol/h/mg of protein (controls, 1.63 +/- 0.41). A systematic study of the catalytic activities of nine enzymes of the beta-oxidation cycle using the respective optimal substrate revealed a deficiency of a single enzyme not previously associated with a metabolic disorder, medium chain 3-ketoacyl-CoA thiolase (patient, 3.9 nmol/min/mg protein; controls (n = 6), 10.2 +/- 2.3). Immunoprecipitation with antibodies raised against medium chain 3-ketoacyl-CoA thiolase revealed a 60% decrease compared with controls.

Acetyl-CoA C-Acyltransferase↗
PubMed1997

Role of volume weighted mean nuclear volume for predicting disease outcome in patients with renal cell carcinoma.

PURPOSE: Histological grading of malignancy in renal cell carcinoma is based on qualitative, morphological examination and suffers from poor reproducibility. On the other hand, estimate of volume weighted mean nuclear volume, which was developed based on a stereological technique, is an easy method to perform with high reproducibility. Furthermore, it has been reported that mean nuclear volume is remarkably correlated with prognosis of bladder and prostate cancer. We compared mean nuclear volume to a histological grading method and TNM classification in determining the prognosis of renal cell carcinoma using a Cox proportional hazards model. MATERIALS AND METHODS: A retrospective, prognostic study was done of 65 patients with renal cell carcinoma diagnosed by radical nephrectomy or needle punch biopsy between January 1978 and November 1995. Unbiased estimates of mean nuclear volume were compared to TNM classification and histological grading to determine prognostic value. RESULTS: Univariate analysis indicated that all TNM classifications, histological grades and estimates of mean nuclear volume were significantly correlated with prognosis of renal cell carcinoma. However, multivariate analysis revealed that estimates of mean nuclear volume and metastasis at diagnosis were the 2 most powerful independent predictors of disease specific survival. CONCLUSIONS: Our results indicate that estimates of mean nuclear volume are prognostically superior to morphological grading of renal cell carcinoma. We recommend mean nuclear volume estimates as an adjunct to subjective histological grading in patients with this disease.

Carcinoma, Renal Cell↗
PubMed1997

Urinary kallikrein in Dahl-Iwai salt-sensitive and -resistant rats.

This study was designed to evaluate the differences between the renal kallikrein in newly established Dahl-Iwai rats under salt loading and that of Sprague-Dawley rats (SD). Urinary kallikrein quantity and activity was markedly lower in Dahl-Iwai rats than in SD even during the control period. Moreover, kallikrein quantity and activity in Dahl-Iwai salt-sensitive rats (SS) were clearly diminished in comparison with salt-resistant rats (SR). The kallikrein activity/ quantity ratio was also lower in SS and SR than in SD during the control period. After salt loading, systolic blood pressure increased only in SS. Kallikrein activity in SS and SR, and kallikrein quantity in SS were increased, whereas those in SD did not change. Although the kallikrein activity/quantity ratio in SR reached the same level in SD after salt loading, that in SS was lower throughout the experiment. These results suggest that Dahl-Iwai rats are less able hereditarily to produce renal kallikrein and that there may exist structurally abnormal kallikrein that may have a lower activity. Different kinetics of renal kallikrein between SS and SR by salt loading might be explained by kallikrein inhibitors or abnormal kallikrein or nonkallikrein kininogenase. These different kinetics of renal kallikrein may play some role on blood pressure elevation in SS.

Animals↗
PubMed1997

Significance of late redistribution thallium-201 imaging after rest injection for detection of viable myocardium.

UNLABELLED: The aim of this study was to determine whether late redistribution imaging after rest injection of 201Tl would provide further information on myocardial viability over conventional rest-early redistribution 201Tl imaging. METHODS: Twenty-nine patients with coronary artery disease and left ventricular dysfunction underwent rest, early (3-4 hr) and late (20-24 hr) redistribution 201Tl and gated blood pool studies. In 14 patients with successful revascularization, gated blood pool study was repeated after the coronary intervention. RESULTS: Nine of 29 patients showed early redistribution, and six additional patients showed further redistribution on the late images. Of 136 segments with initial 201Tl defects, 18 showed early redistribution, and 10 showed late redistribution. When a threshold of 60% of peak activity was used as an index of myocardial viability, only a small fraction (3%) of the initial 201Tl defects were additionally considered viable by the late images. In 14 patients who underwent revascularization, the positive (69%) and negative (87%) predictive values of the early redistribution images for functional recovery were similar to those obtained by the late images (68% and 86%, respectively). CONCLUSION: Although late redistribution after rest injection of 201Tl occasionally occurs, most of the clinically relevant information on myocardial viability may be obtained by conventional rest-early redistribution 201Tl imaging when the defect severity is considered an index of tissue viability.

Aged↗
PubMed1997

[A case of thymic cyst and thymoma with myasthenia gravis].

A case of 53-year-old male with thymic cyst was reported. We established diagnosis for myasthenia gravis. The chest CT and MRI demonstrated a cystic and mass lesion on the anterosuperior mediastinum. This finding suggested a thymic cyst and tumor with myasthenia gravis. The extended thymectomy was performed. Histological examination demonstrated the clear separation of the mixed type thymoma and the thymic cyst. The few reported cases of thymic cyst and thymoma with myasthenia gravis were reviewed.

Humans↗
PubMed1996

Molecular cloning of cDNA encoding rat very long-chain acyl-CoA synthetase.

The cDNA encoding rat very long-chain acyl-CoA synthetase (VLACS) was cloned, using degenerative primers synthesized according to the partial amino acid sequences of the peptide fragments of the purified rat liver enzyme. The longest cDNA insert was 2972 base pairs with a 1860-base pair open reading frame encoding 620 amino acids. The calculated molecular mass of 70,692 daltons was consistent with size of the purified enzyme. In Northern blot analysis, a single band was detected at the position of about 3 kilobases, corresponding to the size of the cloned cDNA. cDNA-directed expression in Escherichia coli resulted in accumulation of expressed protein, as an inclusion body. An antibody was raised using this expressed protein to characterize the cDNA and the enzyme. The subcellular localization of VLACS in peroxisomes and microsomes was demonstrated in Western blot analysis. The specific activity and the substrate specificity of the cDNA expressed enzyme in COS-1 cells were consistent with those of the purified rat enzyme. The predicted amino acid sequence of VLACS had a high sequence similarity to fatty acid transport protein (Schaffer, J. E., and Lodish, H. F. (1994) Cell 79, 427-436), and was considered to have domains for adenylation and thioester formation. The entire structure of VLACS was dissimilar to that of long-chain acyl-CoA synthetase (Suzuki, H., Kawarabayashi, Y., Kondo, Y., Abe, T., Nishikawa, K., Kimura, S., Hashimoto, T., and Yamamoto, T. (1990) J. Biol. Chem. 265, 8681-8685), except for the domains.

Amino Acid Sequence↗
PubMed1996

Formation of the enzyme complex in mitochondria is required for function of trifunctional beta-oxidation protein.

The first Japanese patient with mitochondrial trifunctional protein deficiency has been identified. The patient's alpha and beta-subunits were synthesized, transported into the mitochondria, and converted to the mature size, but rapidly disappeared. The newly synthesized mature alpha and beta-subunits in the control cells were incorporated into the enzyme complex, alpha4beta4, whereas those in the patient's cells were present as monomers. We propose that formation of the enzyme complex is required for stabilization of trifunctional protein.

Autoradiography↗
PubMed1996

Comparison of defect size between thallium-201 and technetium-99m tetrofosmin myocardial single-photon emission computed tomography in patients with single-vessel coronary artery disease.

Defect size on exercise-rest technetium (Tc)-99m tetrofosmin myocardial perfusion imaging was compared with that on exercise-reinjection thallium-201 imaging with 20 patients with 1-vessel coronary artery disease. In each patient, exercise-reinjection thallium-201 single-photon emission computed tomography (SPECT) and exercise-rest Tc-99m tetrofosmin SPECT imaging were performed. For visual analysis of the obtained SPECT images, the left ventricular myocardium was divided into 20 segments based on 3 short-axis slices from the apical, middle, and basal ventricular levels. For quantitative analysis, a square region of interest was placed on the center of each segment which was used for visual analysis, and relative regional activity to the normal reference region was calculated for each segment. By visual interpretation of the images, exercise Tc-99m tetrofosmin imaging showed a smaller defect size than exercise thallium-201 imaging (6.9 +/- 3.9 vs 8.8 +/- 3.0 segments, p <0.01). In contrast, rest Tc-99m tetrofosmin imaging showed a defect size similar to that on reinjection thallium-201 imaging (5.9 +/- 3.6 vs 5.6 +/- 3.9 segments, p = NS). Similarly, the mean defect sizes during exercise determined by quantitative analysis were smaller on Tc-99m tetrofosmin SPECT than those on thallium-201 SPECT at all tested threshold cutoff points ranging from 50% to 70%, whereas there were no significant differences in defect sizes between rest Tc-99m tetrofosmin and reinjection thallium-201 imaging. These data indicate that exercise Tc-99m tetrofosmin SPECT defect size determined either by visual analysis or by quantitative analysis may be smaller than on exercise thallium-201 SPECT.

Aged↗
PubMed1996

Detection of carbamazepine drug interaction by multiple peak approach screening using routine clinical pharmacokinetic data.

Multiple peak approach screening was used to detect the effects of other antiepileptic drugs on the population estimates of relative clearance of carbamazepine. Routine clinical pharmacokinetic data (N = 1,010) collected from 466 patients receiving carbamazepine were analyzed according to a simple steady-state pharmacokinetic model with the use of NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. NONMEM estimates indicated that carbamazepine clearance decreased nonlinearly with increasing total body weight (TBW) in the maturation process (over an age range of 5 months to 15 years) and increased nonlinearly with increasing daily dose (mg/kg) of carbamazepine. Concomitant administration of other antiepileptic drugs resulted in an increased in clearance of carbamazepine as follows: valproic acid alone (VPA), 7%; phenobarbital alone (PB), 16%; more than two antiepileptic drugs (POLY), 27%. Final regression model of relative clearance (Cl) for all data was: Cl (mL/hr/kg) = 64.9. TBW (kg)-0.336.DOSE (mg/kg/day)0.465 1.07VPA 1.16PB 1.27POLY.

Adolescent↗
PubMed1996

alpha-Fetoprotein-producing (hepatoid) carcinoma of the fallopian tube.

This report describes a case of alpha-fetoprotein (AFP)-producing carcinoma of the fallopian tube. The patient was a 52-year-old woman who presented with an abnormally high serum level of AFP. A left adnexal mass was discovered in the subsequent close examination. Hysterectomy and adnexectomy revealed a 3 x 3 x 4-cm tumor in the fimbriae of the left tube. Histologically and immunohistochemically, the tumor was diagnosed as an AFP-producing (hepatoid) carcinoma arising in the fallopian tube. To our knowledge, this is the first report of such a tumor appearing in the tube. This case supports the view that hepatoid cells may also arise from the müllerian epithelium.

Adenocarcinoma↗
PubMed1996

Pharmacokinetics and pharmacodynamics of methylphenidate enantiomers in rats.

We investigated the relationships between methylphenidate (MPD) enantiomers and endogenous dopamine (DA) levels in striatal extracellular fluid, and that between DA level and locomotor activity, after intravenous administration of racemic MPD (2, 5 or 10 mg/kg dose) or the individual enantiomers (2.5 mg/kg dose) to rats. MPD and DA levels in the extracellular fluid were measured by in vivo brain microdialysis. The maximum levels of MPD enantiomers in the striatal extracellular fluid were obtained within 15 min after administration. On the other hand, the mean maximum DA levels after administration of 2-10 mg/kg dose of racemic MPD were obtained within 10 min with values in the range of 3.0- to 8.6-fold higher than the basal DA level. The maximum DA level (4.2-fold of the basal level) after administration of (+/-)-MPD was greater than that (2.2-fold) of the same dose of (-)-MPD. A clockwise hysteresis was observed between MPD concentration and DA level in the extracellular fluid after MPD administration. Locomotor activity after administration of (+)-MPD was also greater than (-)-MPD. From these results, it was shown that the locomotor activity induced by MPD may be related to the increase of DA level in the extracellular fluid, and the degree of increase of the DA level by (+)-MPD was greater than that of the (-)-isomer.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Impaired fatty acid uptake in ischemic but viable myocardium identified by thallium-201 reinjection.

Iodine 123-labeled 15-iodophenyl-3-methyl-pentadecanoic acid (BMIPP) has been proposed as a potential myocardial fatty acid probe. We studied BMIPP uptake in ischemic myocardium identified by thallium reinjection. Fifty-five patients with coronary artery disease who had persistent defects on standard exercise-redistribution thallium imaging were investigated. Patients underwent exercise-redistribution-reinjection thallium and resting BMIPP imaging. BMIPP uptake less than that seen with thallium on reinjection imaging was observed in 105 (82%) of 128 myocardial segments with new fill-in after thallium reinjection and 87 (37%) of 238 segments with reversible thallium defects. In contrast, only 32 (19%) of 166 segments with no fill-in showed discordantly decreased BMIPP uptake. Quantitative analysis showed reduction in BMIPP activity compared with differential uptake of thallium, an index of resting myocardial perfusion, especially in the area of fill-in (53.5% +/- 15.0% vs 76% +/- 12.1% of peak; p<0.01). These observations are consistent with impaired fatty acid uptake in ischemic myocardium, particularly in the area of fill-in after thallium reinjection.

Adult↗
PubMed1996

Efficacy of short-term treatment of pertussis with clarithromycin and azithromycin.

The recommended treatment for pertussis is erythromycin, 40 to 50 mg/kg per day for 2 weeks. The newly developed macrolides, clarithromycin and azithromycin, have been demonstrated to be superior to erythromycin because of improved absorption and a longer half-life. As a result, we conducted two separate comparison studies to evaluate the efficacies of clarithromycin, 10 mg/kg per day, twice a day for 7 days, and azithromycin, 10 mg/kg per day, once a day for 5 days, compared with the standard erythromycin regimen. A total of 17 patients, including 10 infants 1 year of age or less, for whom pertussis had been confirmed by culture, were allocated to receive either clarithromycin or azithromycin treatment, and each patient was matched (age, sex, and immunization status) with historical control subjects who had been treated with erythromycin. Eradication rates examined at 1 week after treatment were as follows: 9 of 9 with clarithromycin versus 16 of 18 with erythromycin (psi M-H = 1.13), and 8 of 8 with azithromycin versus 13 of 16 with erythromycin (psi M-H = 1.23). No bacterial relapse after treatment was detected in either group. All isolated strains of Bordetella pertussis were susceptible to clarithromycin, azithromycin, and erythromycin, and no change in drug susceptibility has been confirmed for the past 20 years in Japan. Because of the very low incidence of pertussis resulting from widespread use of acellular pertussis vaccination, this study did not enroll a large number of patients; however we conclude that short-term treatment with clarithromycin or azithromycin is expected to be equal or superior to the standard long-term erythromycin regimen for pertussis.

Adolescent↗
PubMed1996

In-line filter occlusion during intravenous delivery of injectable menatetrenone (vitamin K2).

Filter occlusion during intravenous infusion of injectable menatetrenone in an electrolyte fluid was examined. The menatetrenone concentration and its emulsion droplet size were not changed by in-line filtration. However, particle counts in the admixed solution and examination of scanning electron micrographs of the surface of the filter membrane indicated that particle formation occurred immediately after the admixture of menatetrenone injection with Hicaliq No. 2, but not with 5% glucose injection. This may be due to the interaction of excess lecithin in the emulsion with the electrolyte. Filter occlusion also occurred with the admixture of menatetrenone-free emulsion and Hicaliq No. 2, but not with 5% glucose injection. These findings indicate that injectable menatetrenone should not be admixed with electrolyte fluids.

Drug Therapy, Combination↗
PubMed1996

Protective effect of ubiquinone (coenzyme Q9) on ascites in broiler chickens.

1. The effect of ubiquinone (CoQ(9)) on ascites in broiler chickens was investigated. 2. The commercial broilers were divided into 2 groups of 100 birds each; CoQ(9) treated group and non-treated group. 3. The chickens were grown in a positive-pressured house with double high efficiency particulate air filtered intakes and exhaust, and thus were strictly isolated from infectious agents. 4. The chickens (15 to 21 d old) were exposed to cold stress in order to induce ascites. 5. The number of birds with ascites in the CoQ(9)-treated group was significantly lower than in the non-treated group. 6. Survival and production rates were better in the CoQ(9)-treated group than in the non-treated group.

Animal Feed↗