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Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 145 records · Page 8Linked to original sources
PubMed1998

The effect of L-ascorbic acid on age-related changes of pyridinoline in cartilage collagen of guinea pigs.

In order to elucidate the effect of L-ascorbic acid (AsA) on the formation of pyridinoline, a mature crosslink of collagen, its content in cartilage collagen of guinea pigs supplemented with and without AsA in the growing process (4-8 weeks of age) and in the period of maturity (10-14 weeks of age) was examined. The AsA-deficient animals, for four weeks during the growing process, had a significantly higher content of pyridinoline in their collagen than the AsA-supplemented group, indicating that the depletion of AsA induced increasing contents of pyridinoline. On the other hand, in the period of maturity, the pyridinoline content in the collagen decreased with age, whereas no difference between AsA-deficient and -supplemented groups was observed. Based on these results, it is assumed that AsA affects the formation of pyridinoline, especially in the growing period.

Adrenal Glands↗
PubMed1998

Prolonged hepatic warm ischemia in non-heart-beating donors: protective effects of FK506 and a platelet activating factor antagonist in porcine liver transplantation.

BACKGROUND: Prolonged warm ischemic injury in non-heart-beating donors (NHBDs) significantly affects hepatic allograft function after liver transplantation (LTx). METHODS: The effects of FK506 and the platelet activating factor antagonist E5880 on postoperative function of hepatic allografts procured from NHBDs were evaluated in porcine orthotopic LTx. In donors, livers were subjected to 90 minutes of warm ischemia and a subsequent 4-hour cold preservation. Group 1 (n = 6) was the untreated control group. In group 2 (n = 4), donors were pretreated with FK506 (0.3 mg/kg). In group 3 (n = 4), donors and recipients were treated with E5880 (0.3 mg/kg). In group 4 (n = 6), pigs were treated with both FK506 and E5880. RESULTS: All of the recipients in group 1 died within 12 hours. In groups 2 and 3, half of the recipients survived more than 12 hours. In group 4, all of the recipients survived more than 2 days (p < 0.01 compared with group 1). The improved survival seen in group 4 was associated with a reduction in the serum concentrations of glutamic oxaloacetic transaminase and lactate, and a restoration of hepatic energy charge. CONCLUSIONS: The present study suggests that FK506 and E5880 can improve the function of hepatic allografts subjected to prolonged warm ischemia in NHBDs, and that the protective effects of the two drugs seem to be synergistic.

Adenosine Triphosphate↗
PubMed1997

Gender difference in regulation of branched-chain amino acid catabolism.

Regulation of the activity state of the hepatic branched-chain 2-oxo acid dehydrogenase (BCODH) complex during the light-dark cycle differs markedly in male and female rats. Female rats exhibit a profound diurnal rhythm in the activity state of the complex that is not observed in male rats. Regardless of gender, most of the complex was dephosphorylated and active in the middle of the dark period and early in the light period, and this form of the complex predominated in male rats at the end of the light period. In contrast, most of the complex in female rats became phosphorylated and inactive by the end of the light period. Gonadectomy prevented the diurnal rhythm in females but was without effect in males, indicating that female sex hormones are required for this gender difference in regulation of the BCODH complex. Changes in levels of branched-chain 2-oxo acids, known regulators of BCODH kinase, do not seem to be involved; rather, an increase in BCODH kinase activity occurring between morning and evening is responsible for inactivation of the BCODH complex in female rats. The increase in kinase activity is due to an increase in the amount of kinase protein associated with the BCODH complex. Thus a marked diurnal variation in the amount of BCODH kinase and therefore its activity results in large swings in the activity state of the liver BCODH complex in female rats. This study provides the first evidence for a gender-specific difference in the regulation of branched-chain amino acid catabolism.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1997

Determination of acetaldehyde in biological samples by gas chromatography with electron-capture detection.

A simple specific assay was developed for the determination of acetaldehyde in biological samples. Acetaldehyde was derivatized to 2,4-dinitrophenylhydrazone, which was determined by gas chromatography with electron-capture detection. The use of this detection method is an important device to which no one drew notice. This procedure was very simple and so sensitive that as little as 500 fmol of acetaldehyde could be measured in aqueous solution. The calibration curve of acetaldehyde was linear at least up to 40 microM. Its recoveries from human plasma and rat liver homogenate were 96.5 and 95.7%, respectively.

Acetaldehyde↗
PubMed1997

Hepatic allograft procurement from non-heart-beating donors: limits of warm ischemia in porcine liver transplantation.

To investigate the tolerance to warm ischemia of liver grafts from non-heart-beating donors, porcine orthotopic liver transplantation was performed using grafts obtained at various periods after cardiac arrest. Graft viability was investigated in relation to changes in hepatic adenine nucleotide metabolism. In donors, livers were divided into four groups according to warm ischemic time after cardiac arrest (group 1: 0 min, n=3; group 2: 30 min, n=3; group 3: 60 min, n=5; group 4: 90 min, n=4). Thereafter, the livers were flushed and preserved for 4 hr using 4 degrees C Euro-Collins solution. After surgery, all of the recipients in groups 1, 2, and 3 survived more than 4 days, except for one pig in group 3 that died of bleeding from an arterial catheter on day 2. By contrast, all of the recipients in group 4 died within 12 hr. The serum glutamic oxaloacetic transaminase concentration at 4 hr after reperfusion of the graft was significantly higher in group 4 (mean+/-SE, 2563+/-556 IU/L) than in groups 1, 2, and 3 (298+/-29 IU/L, 1226+/-222 IU/L, and 1181+/-174 IU/L, respectively). The adenylate energy charge of the liver graft recovered at 1 hr after reperfusion of the graft to 0.852+/-0.013, 0.845+/-0.003, and 0.842+/-0.003 in groups 1, 2, and 3, respectively. The recovery was significantly suppressed in group 4 (0.796+/-0.011). The hepatic adenosine triphosphate concentration also was significantly lower in group 4 compared with the other groups. The present study suggests that liver allografts can be used from non-heart-beating donors subjected to warm ischemia for less than 60 min. Postoperative survival is associated with prompt recovery of the adenylate energy charge of the liver graft.

Adenine Nucleotides↗
PubMed1997

Acute myocardial infarction caused by thrombotic occlusion of a coronary aneurysm.

We encountered an unusual case of acute myocardial infarction due to obstruction of a coronary aneurysm in a 38-year-old Japanese man. Although thrombolysis and rescue percutaneous transluminal coronary angioplasty, performed in the acute phase, did not result in recanalization, serial angiography and intravascular ultrasonography showed spontaneous recanalization and partial thrombosis within the aneurysmal segment during 3 months.

Adult↗
PubMed1997

Differentiating between multiple system atrophy and Parkinson's disease by positron emission tomography with 18F-dopa and 18F-FDG.

Both the striatal 18F-dopa uptake and brain glucose metabolism were studied by PET with 6-L-[18F]fluorodopa (FD) and [18F]fluorodeoxyglucose (FDG) in 9 patients with multiple system atrophy (MSA) and 15 patients with idiopathic Parkinson's disease (PD). Five of the 9 MSA patients were diagnosed as having olivopontocerebellar atrophy, whereas 2 had striatonigral degeneration and 2 demonstrated Shy-Drager syndrome. The FD uptake ratios to the occipital cortex in the MSA patients at 120 min after the administration of FD were 2.07 +/- 0.31 (mean +/- SD) and 1.96 +/- 0.29 in the caudate and the putamen, respectively, and decreased compared to those in the controls (2.72 +/- 0.11, 2.71 +/- 0.10). The same ratios in the PD patients were 2.07 +/- 0.36 and 1.74 +/- 0.24, respectively, which also decreased, but the decreased uptake in the putamen was more prominent. The caudate-putamen index (CPI)(%), which was calculated by a formula based on the difference in the uptakes in the caudate and putamen divided by the caudate uptake, indicated 5.6 +/- 4.6 in the MSA patients and 14.8 +/- 5.4 in the PD patients. The CPI for all PD patients was more than 7.0, which was the mean + 2SD for the controls, but the CPI for 3 MSA patients was more than 7.0 (accuracy: 88%). The glucose metabolic rates for each region in the PD patients showed no difference from the normal controls. The frontal and the temporal cortical glucose metabolism and the caudate, the putaminal, the cerebellar and the brainstem glucose metabolism in the MSA patients decreased significantly in comparison to those in the controls. But, as the glucose metabolic rates in such regions of each patient overlapped in the two groups, the accuracy of the FDG study for differentiation was lower than that of the FD study. The putaminal glucose metabolic rates, for example, in 3 PD patients were less than 6.8 (mg/min/100 ml), which was the mean-2SD for the controls, while those in 3 MSA patients were more than 6.8 (accuracy: 75%). In addition, the combination of these two methods slightly improved the accuracy. The glucose metabolism is useful for evaluating the regional metabolic activity of the brain, and the FD study, which is specific to the dopamine system, seems to be more useful for differentiating between MSA and PD.

Adult↗
PubMed1997

Positron emission tomography (PET) in Machado-Joseph disease.

Positron emission tomography studies on the regional cerebral glucose metabolism (rCMRglc) and 18F-fluorodopa (18F-Dopa) uptake were performed in 3 patients with Machado-Joseph disease (MJD), a dominantly inherited degenerative disease in the cerebellum, brainstem and basal ganglia. The rCMRglc in MJD was found to be significantly decreased in the cerebellum, brainstem, striatum and whole cerebral cortex in comparison to that in normal subjects. These results of rCMRglc were different from those for dominantly inherited olivopontocerebellar atrophy (dOPCA) or cerebellar cortical degeneration (CCD), however they were similar to those for sporadic olivopontocerebellar atrophy (sOPCA) and multiple system atrophy (MSA). The 18F-Dopa uptake in MJD was found to be significantly decreased in the putamen and relatively spared in the caudate, which was different from that of MSA. In addition, these results indicate that MJD showed a dysfunction, not only in the regions with apparent pathological involvement such as cerebellum, brainstem and nigro-striatal dopaminergic system, but also in the cerebral cortex and the striatum where no pathology could be observed using conventional morphological techniques.

Adult↗
PubMed1997

Antibiotic delivery system using bioactive bone cement consisting of Bis-GMA/TEGDMA resin and bioactive glass ceramics.

A novel drug delivery system containing cephalexin (CEX) as a model drug using a new bioactive bone cement consisting of 15% bisphenol-alpha-glycidyl methacrylate (Bis-GMA), 15% triethylene-glycol dimethacrylate (TEGDMA) resin and 70% apatite- and wollastonite-containing glass-ceramic (A-W GC) powder was investigated. A-W GC powder containing CEX powder hardened within 5 min after mixing with Bis-GMA/TEGDMA resin, and furthermore its compressive strength was expected to be higher than that of polymethylmethacrylate cement. In vitro CEX release from bioactive bone cement pellets in a simulated body fluid at pH 7.25 and 37 degrees C continued for more than 2 weeks. The drug release rate increased with increasing amount of CEX in the mixture. All of the drug release profiles followed the Higuchi equation at the initial stage, but not at later stages. As hydroxyapatite was precipitated out on the cement surface, the drug release rate decreased. These results suggest that the CEX release rate from bioactive bone cement could be controlled by varying the amount of drug in the cement system.

Biomechanical Phenomena↗
PubMed1997

Tachykinin receptors on motoneurons in the spinal cords of neonatal rats, gerbils and hamsters.

As a step to clarify the profiles of tachykinin receptors in the mammalian central nervous system, we examined the effects of various tachykinin receptor agonists and antagonists on motoneurons in isolated spinal cord preparations from rats, gerbils and hamsters. After treatment with tetrodotoxin, potential changes were recorded extracellularly from lumbar ventral roots at 27 degrees C. Bath-application of tachykinin NK1, NK3 receptor agonists produced depolarizing responses of ventral roots. In contrast, selective NK2 agonists exerted no or only marginal depolarizing action. Neurokinin A (NKA), however, exerted a distinct depolarizing action on motoneurons. Tachykinin NK1 receptor antagonists antagonized the actions of SPOMe and NKA in a competitive manner. The present results suggest that tachykinin NK1 and NK3 receptors are present on spinal motoneurons of newborn rats, gerbils and hamsters, and that NKA acts on the NK1 receptors.

Animals↗
PubMed1997

Enzymatic inactivation of enkephalin neurotransmitters in the spinal cord of the neonatal rat.

The possible involvement of enzymatic degradation in the inactivation of enkephalins in the spinal cord of neonatal rats was investigated electrophysiologically and biochemically. In an isolated spinal cord-saphenous nerve preparation, electrical stimulation of the saphenous nerve evoked a slow depolarization lasting 20-30 s of the ipsilateral L3 ventral root. This slow depolarization was depressed by a mixture of peptidase inhibitors, consisting of actinonin (10 microM), thiorphan (0.6 microM), bestatin (10 microM), arphamenine B (10 microM) and captopril (10 microM). Naloxone (0.5 microM) not only reversed this effect of the mixture of peptidase inhibitors but also potentiated the slow depolarization beyond the pre-control level. In an isolated spinal cord preparation, electrical stimulation of a lumbar dorsal root evoked a slow depolarization of the contralateral ventral root of the same segment. This slow depolarization was depressed by application of [Met5]enkephalin in a dose dependent manner. This effect of [Met5]enkephalin was markedly potentiated by addition of the mixture of peptidase inhibitors. Among the five peptidase inhibitors, actinonin, thiorphan or bestatin alone potentiated the depressant effect of [Met5]enkephalin, whereas arphamenine B and captopril did not. Membrane fractions prepared from neonatal rat spinal cords showed degrading activities for [Met5]- and [Leu5]enkephalins and these activities were inhibited by the mixture of peptidase inhibitors. Among the five peptidase inhibitors, actinonin and thiorphan markedly inhibited the [Met5]enkephalin-degrading activity while bestatin was less effective. Arphamenine B and captopril were ineffective. The present results suggest that enzymatic degradation by peptidases plays a role in the termination of the transmitter action of enkephalins in the neonatal rat spinal cord. The present results, together with our previous results on the enzymatic degradation of tachykinins in a study in which we used the same preparations, suggest that similar but distinct combinations of peptidases are involved in the inactivation of enkephalin and tachykinin neurotransmitters.

Animals↗
PubMed1997

Synthetic inhibitors of regulatory proteins involved in the signaling pathway of the replication of human immunodeficiency virus 1.

NF-kappa B, HIV-EP1, Sp1, and E1A are transcriptional proteins involved in the long terminal repeat-directed expression of HIV-1. The inhibitory effect of 18 dimethylaminopyridine-based compounds against these regulatory proteins was studied. Experiments using NF-kappa B-beads showed that histidine-pyridine-histidine compounds and their zinc complexes are inhibitory not only for the NF-kappa B-DNA binding, but also for the binding of NF-kappa B with the inhibitory protein I kappa B. Discriminative inhibition of the DNA binding of two distinct C2H2 type zinc finger proteins HIV-EP1 and Sp1 was also attempted using the synthetic compounds. Whereas some compounds inhibited the DNA binding of both HIV-EP1 and Sp1 at 300 microM, others preferentially and completely inhibited HIV-EP1 without much suppression of Sp1. Mercapto compounds were more potent and uniformly inhibitory against both HIV-EP1 and Sp1 at 30 microM. Disulfide compounds were also remarkably inhibitory against HIV-EP1 and Sp1 also at 30 microM whereas the shorter-chain disulfides 7 and 9 were effective only for HIV-EP1. S-Alkyl derivatives preferentially inhibited HIV-EP1 at 300 microM. The dimethylamino compound was the sole compound inhibitory only against Sp1, being non-inhibitory against HIV-EP1. Relevant combinations of these inhibitors would allow us to inhibit NF-kappa B, HIV-EP1, and Sp1 in any combinations. Inhibition of the TBP binding of C4 type zinc finger protein adenovirus E1A was also examined. It was found that two compounds induced, at 50 mM concentration, effective inhibition of the TBP binding of E1A, demonstrating that it is possible in principle to inhibit the protein-protein interaction of zinc finger proteins.

HIV-1↗
PubMed1997

Effect of sodium bicarbonate amount on in vitro indomethacin release from self-setting carbonated-apatite cement.

PURPOSE: In the present study, to develop a drug delivery system with higher bioactivity in hard tissues by using the self-setting bioactive carbonate apatite cement, we have investigated the effects of sodium bicarbonate content on the in vitro drug release from a self-setting bioactive carbonate apatite cement containing indomethacin (IMC). METHODS: The cement powder systems constituted an equimolar mixture of tetracalcium phosphate (Ca4(PO4)2O) and dicalcium phosphate dihydrate (CaHPO4.2H2O), hydroxyapatite (HAP, Ca10(PO4)6(OH)2) seed crystals and sodium bicarbonate. Two types of 2% IMC loaded-cements were prepared as follows, one containing 0% HAP seed crystal and 0-10% sodium bicarbonate, and the other containing 40% HAP seed crystal and 0-10% sodium bicarbonate. The drug release profiles from 2% IMC loaded-cements were measured in simulated body fluid at pH 7.25 and 37.0 degrees C. RESULTS: The drug release profiles from the cement matrix systems with or without seed crystals were estimated using a moment analysis computer program. The mean drug release time (MDT) and the time required for 50% drug release of the cement containing 0 and 40% seed crystal decreased with an increase of sodium bicarbonate. Furthermore, after the drug release the total pore volume of the cement matrix, as measured by mercury porosimetry, increased with an increase of sodium bicarbonate. CONCLUSIONS: MDT and T50's were a function of adding the amount of sodium bicarbonate. The results of the relationship between the micropore distribution, total volume of pores after drug release and drug release supported the hypothesis that the variation in drug release from the cements resulting from the addition of sodium bicarbonate was mainly due to an increase in the diffusion of the drug in the micropores of the cement by dissolution or erosion of the cement matrix.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Effects of passive immunization against oestradiol-17beta and inhibin on the secretion of gonadotrophin in the cyclic golden hamster (Mesocricetus auratus).

To investigate the physiological importance of oestradiol-17beta and inhibin in the regulation of gonadotrophin secretion in the cyclic golden hamster, females were passively immunized against two hormones. When 200 microL antiserum against oestradiol-17beta (oestradiol-AS) was given on Day 3 (Day 1 = day of ovulation), the preovulatory gonadotrophin surge was completely blocked for 24 h and the length of the oestrous cycle was also prolonged for one day. In the group given 200 microL oestradiol-AS on Day 3, basal levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) increased slightly and superovulation (19.6+/-0.8, mean+/-s.e.m.) occurred. When 200 microL antiserum against inhibin (inhibin-AS) was given at 1100 hours on Day 3, a dramatic increase in plasma FSH and a slight increase in LH were noted, resulting in superovulation (38.2+/-2.6) on the expected Day 1. The present study indicates clearly that inhibin plays a major role in regulating the specific ovulation rate in the hamster through the control of FSH secretion. Present results also indicate that oestradiol-17beta suppresses basal LH secretion. Oestradiol-17beta may act as an indicator of the follicular maturation, and the high plasma concentration of oestradiol-17beta noted from Day 3 to Day 4 may play an important role in determining the timing of initiation of the preovulatory gonadotrophin surge.

Animals↗
PubMed1997

Temporal changes in inhibin, steroid hormones, and steroidogenic enzymes during induced follicular atresia in the hypophysectomized cyclic hamster.

The time course for loss of ability of Graafian follicles to secrete inhibin and estradiol was investigated during induced follicular atresia. Cyclic hamsters were hypophysectomized on Day 1 (estrus) and injected s.c. with 30 IU eCG. Thereafter, these animals were given a single i.p. injection of antiserum to eCG on the morning of Day 4 to induce follicular atresia in a rapid and predictable manner. A drastic fall in plasma levels of estradiol and testosterone was noted within 1 h, whereas relatively high levels of plasma inhibin were maintained until 12 h, followed by an abrupt decline by 24 h. The first histological signs of pyknosis in granulosa cells appeared by 4 h, and breakdown of the mural granulosa layer was observed in most follicles by 8-12 h after immunoneutralization of circulating eCG. According to immunohistochemical analysis, inhibin activity was unchanged in granulosa cells at 12 h followed by a slight decline by 24 h, whereas positive reaction for aromatase in these cells rapidly declined by 8 h. Immunoreactivity of 17alpha-hydroxylase/C17,20-lyase (CYP 17) was also reduced in theca cells by 8 h. These results indicate that granulosa cells continue to secrete inhibin during the process of follicular atresia, although these cells quickly shut off the secretion of estradiol, and theca cells shut off the secretion of testosterone. The present results indicate as well that a rapid decline of estradiol and testosterone in plasma is an early sign of atresia in antral follicles. These results, therefore, suggest that the loss of enzymatic activity of aromatase in granulosa cells and CYP 17 in theca cells is a part of the process of follicular atresia.

Animals↗
PubMed1997

A study of verbal and spatial information processing using event-related potentials and positron emission tomography.

The activated cerebral regions and the timing of information processing in the hemispheres was investigated using event-related potentials (ERP) and regional cerebral blood flow (rCBF) as the neurophysiological indicators. Seven men and one woman (age 19-27 years) were asked to categorize two-syllable Japanese nouns (verbal condition) and to judge the difference between pairs of rectangles (spatial condition), both tests presented on a monochrome display. In the electroencephalogram (EEG) session, EEG were recorded from 16 electrode sites, with linked earlobe electrodes as reference. In the positron emission tomography (PET) session, rCBF were measured by the 15O-labeled H2O bolus injection method. Regions of interest were the frontal, temporal, parietal, occipital and central lobes, and the entire cerebral hemispheres. When the subtracted voltages of the ERP in homologous scalp sites were compared for the verbal and spatial conditions, the significant differences were at F7.F8 and T5.T6 (the 10-20 system). The latencies of the differences at T5.T6 were around 200, 250 and 320 ms. A significant difference in rCBF between the verbal and spatial conditions was found only in the temporal region. It was concluded that early processing of information, that is, registration and simple recognition, may be performed mainly in the left temporal lobe for verbal information and in the right for spatial information.

Adult↗