Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 379 records · Page 21Linked to original sources

PubMed1998

Biological significance of the side chain length of ubiquinone in Saccharomyces cerevisiae.

Ubiquinone (UQ), an important component of the electron transfer system, is constituted of a quinone structure and a side chain isoprenoid. The side chain length of UQ differs between microorganisms, and this difference has been used for taxonomic study. In this study, we have addressed the importance of the length of the side chain of UQ for cells, and examined the effect of chain length by producing UQs with isoprenoid chain lengths between 5 and 10 in Saccharomyces cerevisiae. To make the different UQ species, different types of prenyl diphosphate synthases were expressed in a S. cerevisiae COQ1 mutant defective for hexaprenyl diphosphate synthesis. As a result, we found that the original species of UQ (in this case UQ-6) had maximum functionality. However, we found that other species of UQ could replace UQ-6. Thus a broad spectrum of different UQ species are biologically functional in yeast cells, although cells seem to display a preference for their own particular type of UQ.

Alkyl and Aryl Transferases↗

PubMed1998

Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex.

Mitochondrial cytochrome bc1 complex performs two functions: It is a respiratory multienzyme complex and it recognizes a mitochondrial targeting presequence. Refined crystal structures of the 11-subunit bc1 complex from bovine heart reveal full views of this bifunctional enzyme. The "Rieske" iron-sulfur protein subunit shows significant conformational changes in different crystal forms, suggesting a new electron transport mechanism of the enzyme. The mitochondrial targeting presequence of the "Rieske" protein (subunit 9) is lodged between the two "core" subunits at the matrix side of the complex. These "core" subunits are related to the matrix processing peptidase, and the structure unveils how mitochondrial targeting presequences are recognized.

Amino Acid Sequence↗

PubMed1998

Molecular cloning and mutational analysis of the ddsA gene encoding decaprenyl diphosphate synthase from Gluconobacter suboxydans.

Decaprenyl diphosphate (decaprenyl-PP) synthase catalyzes the consecutive condensation of isopentenyl diphosphate with allylic diphosphates to produce decaprenyl-PP, which is used for the side chain of ubiquinone (Q)-10. We have cloned the synthase gene, designated ddsA, from Gluconobacter suboxydans and expressed it in Escherichia coli. Sequence analysis revealed the presence of an ORF of 948 bp capable of encoding a 33,898-Da polypeptide that displays high similarity (30-50%) to other prenyl diphosphate synthases. Expression of the ddsA gene complemented the lethality resulting from a defect in the octaprenyl diphosphate synthase gene of E. coli and produced Q-10, indicating that Q-10 can substitute for the function of Q-8. The His-tagged DdsA protein was purified to characterize its enzymatic properties. This enzyme required detergent (0.05% Triton X-100) and 10 mM Mg2+, for full activity. The Michaelis constants for geranyl diphosphate, all-E-farnesyl diphosphate and all-E-geranylgeranyl diphosphate were 7.00, 0.50 and 0.32 microM, respectively. Nine single-amino-acid substitutions were introduced upstream of conserved region II or VI. Most of the mutants showed a considerable decrease in catalytic activity or shortening of the ultimate chain length. However, the A70G mutant produced a longer-chain-length product than wild-type decaprenyl-PP synthase, and the A70Y mutant completely abolished the decaprenyl-PP synthase function, indicating that Ala70 is important for enzyme activity and the determination of the chain-length properties of DdsA.

Acetobacteraceae↗

PubMed1998

Role of endogenous endothelin in the development of graft arteriosclerosis in rat cardiac allografts: antiproliferative effects of bosentan, a nonselective endothelin receptor antagonist.

BACKGROUND: The purpose of this study was to determine whether endothelin-1 (ET-1) contributes to the development of graft arteriosclerosis and whether the orally active nonpeptide endothelin receptor antagonist bosentan, which blocks both ETA and ETB receptors, can protect against this pathologic damage. METHODS AND RESULTS: Recipient male Lewis rats were divided into three groups; group 1 received heterotopic heart transplantations from Lewis donors and groups 2 and 3 received transplantations from Brown-Norway donors; group 3 recipients also received bosentan orally at the dose of 20 mg/kg per day for 120 days. All recipients were given cyclosporine and were euthanized at examination 120 days after transplantation. Plasma ET-1 levels were significantly higher in group 2 than in group 1 (6.99+/-0.91 and 4.15+/-.83 pg/mL, respectively). Strong ET-1 immunoreactivity was seen in both the thickened neointima and the media of the coronary arteries in group 2 but not in group 1. The mean ratio of the coronary luminal area to the total vascular area in group 2 (19.0+/-11.7%) was significantly lower than that in group 1 (34.2+/-9.9%) and was significantly increased in group 3 (33.2+/-9.2%). CONCLUSIONS: These results show that local upregulation of ET-1, mainly in the thickened neointima and the media of the coronary arteries, may play an important role in the pathogenesis of graft arteriosclerosis by stimulating ETA receptors, ETB receptors, or both. Orally active bosentan might be a useful agent for the clinical prevention of graft arteriosclerosis.

Actins↗

PubMed1998

A lipoprotein lipase activator, NO-1886, improves endothelium-dependent relaxation of rat aorta associated with aging.

Endothelial function is closely related to development of atherosclerosis and is impaired with aging. The novel compound NO-1886, 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamid e, is a lipoprotein lipase activator and its long term administration protects against the development of experimental atherosclerosis in animals. The aim of this study was to ascertain whether NO-1886 ameliorates the impaired endothelium-dependent relaxation of rat aorta associated with aging. NO-1886 (50 mg/kg p.o.) was administered to 7-month old rats for 3 months. Plasma lipid, glucose and insulin levels in old control rats (10 months of age) were significantly higher than those of young rats (2 months of age). NO- 1886 decreased plasma triglyceride levels (old rats, 233+/-10 mg/dl; old rats + NO-1886, 172+/-16 mg/dl, P < 0.01) and increased plasma high density lipoprotein (HDL) cholesterol level (old rats, 72+/-6 mg/dl; old rats + NO-1886, 142+/-6 mg/dl, P < 0.001) in old rats, but had no effects on plasma glucose or insulin. The endothelium-dependent relaxation of the thoracic aorta caused by histamine was significantly impaired in old rats (% relaxation at 10(-5.5) M histamine: young rats 25.4+/-3.1%; old rats 14.1+/-1.9%, P < 0.01), an effect completely prevented by NO-1886 (old rats + NO-1886; 22.8+/-2.8%, P < 0.05 vs. old rats). In contrast, NO-1886 showed no effect on the endothelium-independent relaxation by sodium nitroprusside. These results indicate that NO-1886 improves impaired endothelium-dependent relaxation of rat aorta associated with aging, possibly by correcting lipid metabolism.

Aging↗

PubMed1998

X-ray polarimetry with the microstrip gas chamber.

A two-dimensional microstrip gas chamber (MSGC) with a 5 cm x 5 cm detection area has been developed. It has 254 anodes and 255 back strips, both with 200 micro m pitches. Using this MSGC, linear polarization of X-rays was successfully measured in the energy range 6-14 keV. In addition, the performance of the MSGC as an X-ray imaging polarimeter has been simulated using the EGS4 program (Electron Gamma Shower, Version 4) modified for this purpose. In this article, the results of both the polarization measurement and the simulation are reported.

Journal Article↗

PubMed1998

Granular Cell Tumor of the Breast: A Case Report Describing Dynamic MR Mammography.

A case of granular cell tumor of the breast in a 36-year-old woman is reported. The patient presented with a hard mass,1.5 cm in diameter in the upper-outer quadrant of the left breast. Physical examination and ultrasonography suggested the presence of breast carcinoma. An aspiration biopsy cytology(ABC)specimen wasevaluated as class II, and dynamic magnetic resonance(MR)mammography indicated a benign tumor. Granular cell tumor was finally diagnosed on examination of an excisional biopsy specimen. Granular cell tumor of the breast can mimic breast carcinoma on physical examination, mammography, ultrasonography, and even gross inspection. Dynamic MR mammography has the potential distinguish this condition from carcinoma. Awareness of this disease and prudent use of diagnostic procedures, including MR mammography, will help prevent misdiagnosis and unnecessary surgery.

Journal Article↗

PubMed1998

Determination of amphetamine and methamphetamine in human hair by headspace solid-phase microextraction and gas chromatography with nitrogen-phosphorus detection.

A simple and rapid method for the determination of amphetamine (AP) and methamphetamine (MA) in human hair was developed by headspace solid-phase microextraction (SPME) and gas chromatography with nitrogen-phosphorus detection (GC-NPD). The hair (1 mg) was dissolved in 0.2 ml of a 5 M sodium hydroxide solution in a tightly sealed vial by shaking at 75 degrees C for about 5 min. In order to adsorb AP and MA on the SPME fiber, 100 microm of polydimethylsiloxane fiber was exposed to the headspace of the vial, and the vial was heated at 55 degrees C for 20 min. Then the fiber was removed from the vial and inserted into the injection port of the GC-NPD system using a CBJ-17 capillary column. The compounds adsorbed on the fiber were analyzed by exposing the fiber at 220 degrees C for 30 s in the GC injection port. By using this method, AP and MA in human hair could be analyzed simply and rapidly without any interference from coexisting substances. The percentages of AP and MA extracted from human hair by the SPME method were 48 and 62%, respectively, and relative standard deviations were below 10% (n=5). The calibration curves for AP and MA were linear in the ranges of 0.4-15 and 4-160 ng/mg hair, respectively. The detection limits of AP and MA at a signal-to-noise ratio of three were 0.1 and 0.4 ng/mg hair, respectively. This method could be applied to the analysis of an abuser's hair sample.

Amphetamine↗

PubMed1998

Function and Conformation of Wild-Type p53 Protein Are Influenced by Mutations in Bovine Leukemia Virus-Induced B-Cell Lymphosarcoma

The mutations of the p53 gene previously represented one of several genetic changes involved in the development of bovine leukemia virus (BLV)-induced lymphosarcoma, while the effects of these mutations on the function of p53 are unknown. We identified four mutations of p53 gene in BLV-infected cattle with lymphosarcoma and demonstrated clearly the existence of two functionally distinct groups of mutants: (i) the mutant forms with substitutions at codons 241 and 242, which were mapped within an evolutionally conserved region and corresponded to the human "hot-spot" mutations, had completely lost the capacities for transactivation and growth suppression and gained transdominant repression activity in p53-null SAOS-2 cells; and (ii) the mutations at codons 206 and 207 were located outside the evolutionally conserved regions. These mutants partially retained the capacity for transactivation and growth suppression and failed to inhibit the transactivation activity of coexpressed wild-type p53, instead showing an enhancement of this activity. In addition, protein analysis using an antibody specific for the mutant form revealed that the mutations at codons 206 and 242 induced a "mutant" conformation of the bovine p53 proteins. Collectively, these results show that mutations of p53 gene in BLV-infected cattle with lymphosarcoma can potentially alter its physiological function and may play an important role in BLV-induced leukemogenesis. Copyright 1998 Academic Press.

Journal Article↗

PubMed1998

Function and conformation of wild-type p53 protein are influenced by mutations in bovine leukemia virus-induced B-cell lymphosarcoma.

Animals↗

PubMed1998

Automated preparation and analysis of barbiturates in human urine using the combined system of PrepStation and gas chromatography-mass spectrometry.

A system for an automatic sample preparation procedure followed by on-line injection of the sample extract into a gas chromatography-mass spectrometry (GC-MS) system was developed for the simultaneous analysis of seven barbiturates in human urine. Sample clean-up was performed by a solid-phase extraction (SPE) on a C18 disposable cartridge. A SPE cartridge was preconditioned with methanol and 0.1 M phosphate buffer. After loading a 1.5 ml volume of a urine sample into the SPE cartridge, the cartridge was washed with 2.5 ml of methanol-water (1:9, v/v). Barbiturates were eluted with 1.0 ml of chloroform-isopropanol (3:1, v/v) from the cartridge. The eluate (1 microl) was injected into a GC-MS system. The calibration curves, using an internal standard method, demonstrated a good linearity throughout the concentration range from 0.02 to 10 microg/ml for all barbiturates extracted. The proposed method was applied to several clinical cases. The total analysis time for 20 samples was approximately 14 h.

Adult↗

PubMed1998

Sinoaortic denervation produces sodium retention in Dahl salt-sensitive rats.

The role of the arterial baroafferent signals in sodium (Na) homeostasis was examined in salt-sensitive rats. Sodium balances, water balances, and systolic arterial pressure (SAP) were measured for 3 weeks in sinoaortic denervated (SAD) or sham denervated (Sham) Dahl salt-sensitive (S) and salt-resistant (R) rats fed a standard-salt diet (0.4% NaCl). In R rats, there was no significant difference in Na balance, water balance, or SAP between the SAD and Sham animals. In the S rats, urinary Na excretion was suppressed in the SAD but not in the Sham animals, resulting in Na retention. SAD significantly increased SAP and mean arterial pressure. High salt challenge (8% NaCl diet) markedly increased SAP and Na and water balances in both S-SAD and S-Sham rats. However, no significant difference was found in SAP or cumulative Na and water balances between S-SAD and S-Sham rats. These results suggest that the baroafferent signals may have some role on the regulation of Na balance in salt-sensitive animals under a standard-salt condition, although a high-salt load masked the baroafferent-dependent sodium excretion.

Animals↗

PubMed1998

The gain of the hepatorenal reflex in anesthetized dogs.

To determine the overall gain of the hepatorenal reflex, hypertonic NaCl solutions were infused into the portal vein or inferior vena cava of anesthetized dogs at a rate of 0.01 ml/kg/min for 30 min and the urinary Na excretion measured. Infusion of 2.25% NaCl into either the portal vein or inferior vena cava had no effect. Portal infusion of 4.5% or 9% NaCl produced an increase of 36 +/- 16 or 40 +/- 17 microeq/kg/30 min, respectively, while inferior vena caval infusion had no effect. With 13.5% NaCl infusion, a significant increase in the natriuretic response was seen with portal venous infusion, with no significant difference between portal venous and inferior vena caval infusion. Thus, the difference in the natriuretic response between portal venous and inferior vena caval infusion was dependent on the degree of input; when an appropriate input was given, natriuresis was induced only by portal venous infusion, probably mediated by the hepatorenal reflex. The gain of the hepatorenal reflex was calculated from the output divided by the input. When 4.5% or 9% NaCl was infused into the portal vein, the 2-h gain of the hepatorenal reflex was 0.38 +/- 0.15 or 0.34 +/- 0.14, respectively.

Animals↗

PubMed1998

Involvement of H2O2 production in cisplatin-induced nephrotoxicity.

The purpose of this study was to elucidate the involvement of H2O2 production in cisplatin-induced nephrotoxicity. The S3 cells were more sensitive than OMCT cells in cell viability and H2O2 production during cisplatin treatment. The cytotoxicity and H2O2 production induced by cisplatin were terminated by treatment with catalase. In conclusion, we emphasize the importance of the hydroxy radical in cisplatin nephrotoxicity.

Animals↗

PubMed1998

Long-term follow-up of the vascularized iliac bone graft.

We retrospectively studied four patients who were treated with vascularized iliac bone graft for reconstruction of the tibia. The average length of the graft was 9.8 cm. The follow-up period was 11-18 years (average, 14.8 years). Although two of them were osteomyelitis, no recurrence occurred. We also studied four patients who were treated with nonvascularized iliac bone graft for anterior spinal interbody fusion (average, 10.8 years). Cosmetic problem slightly exists because the vascularized iliac bone still showed the original shape, which was prominent from the tibial contour. The vascularized iliac bone marrow showed iso intensity in both T1 and T2 image of the MRI. However, nonvascularized iliac bone graft on the spine showed high intensity in both T1 and T2 imaging. Since the vascularized iliac bone graft does not present fatty degeneration, it shows strong resistance against infection.

Adult↗

PubMed1998

Combined coronary artery bypass, mitral valve plasty, and abdominal aneurysmectomy in an 80-year-old patient: report of a case.

An 80-year-old man suffering from angina on exertion due to stenosis of the left main coronary artery, heart failure due to mitral valve regurgitation, and an abdominal aortic aneurysm (AAA) was successfully operated on with simultaneous surgical procedures. A coronary cineangiography revealed 90% stenosis of the left main coronary artery in segment 5, and 99% and 90% stenosis in segments 2 and 4AV, respectively, of the right coronary artery. Left ventriculography and aortography showed moderate mitral valve regurgitation and the presence of a fusiform-shaped AAA with a maximum diameter of 6 cm. It was thought that insertion of an intraaortic balloon pump (IABP) would prove difficult due to AAA; therefore, simultaneous surgery combining triple coronary artery bypass grafting (CABG), mitral valve plasty, and prosthetic replacement of the AAA was undertaken. The patient's postoperative course was uneventful, and subsequent angiography showed good patency of all coronary bypass grafts and the abdominal prosthesis, along with the disappearance of mitral regurgitation. This patient's clinical course suggests that an extended surgical procedure is effective for the treatment of complicated cardiovascular disease, even in very elderly patients.

Aged↗

PubMed1998

[Tracheoplasty with an intercostal pedicle flap for tracheal neurilemmoma--a case report].

A 16-year-old woman suffering from suffocating tracheal neurilemmoma was admitted to our hospital. Endoscopic polypectomy and Nd:YAG laser therapy were performed. Then the symptom was disappeared. During the observation, bronchoscopic findings showed the tumor was still existence and the radical operation was performed. Because the tumor was benign and the residual tumor was noted only in membraneous site, we resected the residual tumor and performed the tracheoplasty with an intercostal pedicle flap. Clinical course was good without any complications. This method was considered to be effective for the treatment of limited benign lesion.

Adolescent↗

PubMed1998

Oculomotor sequence learning: a positron emission tomography study.

The purpose of this study was to identify the brain regions activated in relation to oculomotor sequence learning. Nine healthy subjects participated in the study, which consisted of three positron emission tomography scans. In the initial learning task, subjects were instructed to track a sequence of seven successive positions of visual targets and to memorize the order of the targets as well as their spatial locations. In the saccade task, subjects were instructed to track visual targets presented at random locations. In the control task, subjects were instructed to gaze at a fixation point. Fields showing significant regional cerebral blood flow change were determined from task-minus-control subtraction images. We determined that fields in the pre-supplementary motor area (pre-SMA), the intraparietal cortex, and the prefrontal cortex were activated not only in the learning-minus-control images but also in the learning-minus-saccade images. Although prefrontal and parietal activations were bilateral, pre-SMA activation was confined to the left hemisphere. The results indicate that these fields function as a part of the neural network involved in the learning of sequential saccadic eye movements.

Adolescent↗