Biomedical subjects

T Obata

Publications and source records attributed to T Obata.

At least 127 records · Page 7Linked to original sources

PubMed1996

[Expression of Fas/Fas ligand and proto-oncogenes in rheumatoid synovial tissues].

Expression of Fas antigen and Fas ligand (-L) were observed in synovial tissue from rheumatoid arthritis (RA) patients, whereas in only a few cells expressed these molecule osteoarthritis synovial tissue. Fas-L was expressed on CD45RO, CD4, CD8 or CD56 positive cells in RA synovial tissue. Moreover, 10 to 30% of synovial cells expressing Fas antigen were observed to be identical with apoptotic synovial cells and Fas expression was closely related to c-fos and c-myc. These findings suggest that activated T cells and natural killer cells infiltrating into the RA synovium may play an important role in the induction of apoptosis of RA synovial cells through Fas/Fas-L interactions.

Apoptosis↗

PubMed1996

Monoamine oxidase released into plasma treated with the hepatotoxin allyl formate.

Monoamine oxidase (MAO) released from the rat liver into plasma and the activity levels of lipid peroxide (LPO) and superoxide dismutase (SOD) in liver tissue were investigated after pretreatment of rats with the perilobular hepatotoxin allyl formate (AF). When 3H-pargyline was given to AF-pretreated rats, the levels of 3H-pargyline labelled MAO in rat plasma were increased to 38% (p < 0.01 vs control), but the radioactivity was decreased to 35% (p < 0.05 vs control). The molecular weight of MAO subunits in plasma was similar to that of MAO subunits in liver (about 60,000) as determined by SDS electrophoresis. Liver tissue LPO levels in these rats were increased, whereas SOD activity was decreased. These results suggest that MAO in liver mitochondria was released into plasma as a consequence of membrane disorder.

Animals↗

PubMed1996

Role of adenosine in blood flow in the rat intestine.

We examined the relation between adenosine production and increased blood flow. For this purpose, we used a sensor holding system with a laser Doppler blood flowmeter. The elevation of blood flow was observed by administration of adenosine. Therefore, when AMP was administered to the rats, the elevation of blood flow rate was observed. These results suggest that AMP is rapidly transported to the adenosine active site by ecto-5'-nucleotidase.

5'-Nucleotidase↗

PubMed1996

In vivo monitoring of .OH generation on jejunal ischemic injury by dialysis technique.

We applied an in vivo microdialysis technique to examine free radical generation following ischemic injury in the rat jejunum. For this purpose, we used a microdialysis probe holding system. The salicylate reacts with hydroxyl free radical (.OH) and generates 2,3-dihydroxybenzoic acid (DHBA), which can be measured electrochemically in picomole amounts by high-performance liquid chromatography (HPLC). Therefore, the former was used for trapping the .OH formation. Reperfusion of the jejunum produced progressive elevations in the levels of 2,3-DHBA achieving the maximums at 20 min, after which they decreased progressively to the baseline. These elevations were significant only after 10 min- and 20 min-ischemia. However, this change was not significant in the case of 30 min-ischemia. Ischemia-reperfusion of rat intestine caused morphological changes. These results suggest that .OH production is significantly reduced after 30 min-ischemia providing thus the possibility for more severe intestinal damage. In conclusion our dialysis probe can be useful for the measurement of .OH generation following ischemia-reperfusion injury.

Animals↗

PubMed1996

[Evaluations of a specified number of inhalations and how to assess the contents in metered-dose inhalers].

Many kinds of Metered-Dose Inhalers (MDI) have been clinically available for bronchial asthma. Although manufacturers demonstrate the specified number of inhalations per canister on an attached document or on a plastic bag, the information provided are usually inadequate and inconsistent. They provide no information on the problems of the Metered-Dose Inhalers beyond the maximum specified number of actuations and the time when to exchange for a new one. We examined the technique how to evaluate the contents of MDI and their accuracy. Patients and their parents depended on inaccurate methods, such as shaking the inhalers to listen to the sound of contents, estimating the weight of the canisters and the size of emissions, and only a half of them were able to distinguish between 1/3 and 2/ 3 of remaining doses. Three Metered-Dose Inhalers with anti-inflammatory drugs and one MDI with beta-stimulant supplied consistent doses until they reached the maximum specified number. The 4 MDIs floated in the water in different ways and provided information when to replace for new ones in some MDIs.

Adolescent↗

PubMed1995

Blood flow rate in jejunal ischemia-reperfusion injury.

We examined changes in the blood flow rate in the course of jejunal ischemic injury using a laser Doppler flowmeter. For this purpose, we designed a sensor holding system, which involved the fixation of the sensor to the jejunum and allowed their movements to be synchronized. When the jejunum was reperfused after 10 min of ischemia, the blood flow rate markedly increased and then gradually decreased to the initial level. A 30-min period of ischemia produced the slowest recovery of the blood flow rate. This system could be useful for monitoring the blood flow rate in different anatomical regions.

Animals↗

PubMed1995

Photodynamic therapy of photofrin II and excimer dye laser on experimental tumors.

Photodynamic therapy (PDT) by combination of photofrin II and excimer dye laser was evaluated for its usefulness in experimental tumors. High antitumor effects of PDT on sarcoma 180 solid type were obtained when PDT was performed with laser irradiation at an energy of 50 or 100 J/cm2 (40 or 80 Hz, 4 mJ/pulse) 48 h after i.v. administration of photofrin II at a dose of 25 mg/kg. Under the same conditions, the antitumor effects of PDT on murine Lewis lung carcinoma, human fibrosarcoma HT-1080 and human bladder transitional cell carcinoma KK-47 were also observed. These results suggest that clinical application of PDT with photofrin II and excimer dye laser might be useful.

Animals↗

PubMed1995

Intracranial microdialysis of salicylic acid to detect hydroxyl radical generation by monoamine oxidase inhibitor in the rat.

The effect of pargyline, a monoamine oxidase inhibitor, on the generation of hydroxyl free radicals (OH) was investigated using striatal microdialysis. Salicylic acid in Ringer's solution (0.5 nmol microliter-1 min-1) was infused through a microdialysis probe to detect the generation of hydroxyl radicals (OH) as reflected by the formation of dihydroxybenzoic acid (DHBA) in the striatum. When pargyline (100 nmol microliter-1 min-1) was infused in rat brain, the level of 3,4-dihydroxyphenylacetic acid (DOPAC) gradually decreased in a time-dependent manner. In addition, a marked elevation of DHBA was observed. The present results indicate that accumulation of dopamine (DA) in the extracellular fluid elicited by pargyline can be auto-oxidized, which in turn leads (possibly by an indirect mechanism) to the formation of cytotoxic OH free radicals.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Deuterium magnetic resonance imaging of rabbit eye in vivo.

We used deuterium magnetic resonance imaging (2H MRI) to visualize water movement in the rabbit eye. Dynamic 2H MRI was obtained every 3.5 min at 2 tesla by FLASH pulse sequence (TR, 300 ms; TE, 10 ms; alpha = 90 degrees) with a slice thickness of 10 mm using a surface coil (4 cm in diameter). After topical administration (0.2 ml D2O), only the aqueous chamber was imaged, and the signals decreased mono-exponentially. The flow rate was 0.113/min, in agreement with that already reported. After intravenous administration of deuterated saline (3 ml/kg), the aqueous chamber became visible first during imaging, then by the vitreous body. The signals around the lens were only faintly detected. Thus, deuterium MRI was determined to be useful for visualizing water movement in the eye.

Animals↗

PubMed1995

Clinical and laboratory characteristics in the families with diabetes and a mitochondrial tRNA(LEU(UUR)) gene mutation.

We identified three families having a mutation in the mitochondrial tRNA(LEU(UUR)) gene at bp 3243 in 300 patients with non-insulin dependent diabetes mellitus (NIDDM), who had first degree relatives of patients with NIDDM. We found six individuals with diabetes, one with impaired glucose tolerance (IGT), and five with normal glucose tolerance (NGT) among three families. Insulin secretory response to oral glucose load was impaired in six diabetics, but was normal in IGT and NGT, and the proportion of mutant DNA in the blood did not always associate with the severity of glucose intolerance. Furthermore, both gender and obesity may influence the clinical expression of diabetes in three pairs with an age-matched brother-sister relationship with similar high mutation rate in blood samples. Thus, although patients with mitochondrial gene mutation had a high frequency of diabetes, the proportion of mutant DNA evaluated by blood samples may not necessarily indicate glucose intolerance in the members with the mutation. Unidentified factors including gender, aging, and obesity may alter the clinical manifestation of diabetes.

Adolescent↗

PubMed1995

Myocardial microdialysis of salicylic acid to detect hydroxyl radical generation during ischemia.

We examined in vivo monitoring of hydroxyl radical (.OH) generation during myocardial ischemia for 30 min by occluding the left anterior descending (LAD) in dog heart using a microdialysis technique. The hydroxyl radical reacts with salicylate and generates 2,3- and 2,5-dihydroxybenzoic acids (DHBA) which can be measured electrochemically in picomole quantity by a high pressure liquid chromatography-electrochemical (HPLC-EC) procedure. When the premature ventricular contraction (PVC) occurred at almost 25 sec intervals, marked elevation of the levels of 2,3- and 2,5-DHBA was observed in the heart dialysate of 30-min ischemia. This study demonstrated the generation of .OH in the canine heart subjected to 30-min ischemic insult.

Animals↗

PubMed1995

Molecular cloning of CWP1: a gene encoding a Saccharomyces cerevisiae cell wall protein solubilized with Rarobacter faecitabidus protease I.

A yeast cell wall glycoprotein with a molecular weight of 40,000, named gp40, was solubilized from SDS-extracted cell wall of Saccharomyces cerevisiae by incubation with Rarobacter faecitabidus protease I, which is a yeast-lytic enzyme. Based on its amino acid sequence, we cloned and sequenced the gene encoding the precursor of gp40, named CWP1; cell wall protein gene. The DNA sequence of the CWP1 gene was identical to YKL443, an open reading frame identified in a genome sequencing program for yeast chromosome XI. This gene encoded a serine-rich protein of 239 amino acids with a molecular weight of 24,267. The presence of hydrophobic sequences in the N- and C-termini of the CWP1 protein suggests that it is secreted as a glycosylphosphatidylinositol-anchored protein and is subsequently integrated into the cell wall. Since a gene disruption experiment showed no growth defect, the CWP1 gene is not essential for growth. Mutant CWP1 protein deficient in the C-terminal hydrophobic sequence was secreted into the culture medium, not anchored to the cell wall, thereby indicating that this hydrophobic sequence plays a crucial role in anchoring to the cell wall. Homology between the CWP1 protein and TIP1 family of cold shock proteins suggests that they belong to a new family of cell wall proteins.

Amino Acid Sequence↗

PubMed1995

[Effects of feed and mating age on reproductive performance in Syrian hamsters].

In order to utilize Syrian hamsters in selection experiments, we investigated desirable conditions of feed and mating age for reproduction in females. Hamsters were subdivided into two groups, raised on pellet feed for herbivores (ZC-2) and breeding (MB-1), respectively. Half of the hamsters in each group were switched to the other feed, respectively, after mating. They were mated at 8 or 12 weeks of age. In the group that has been fed on ZC-2 before mating and MB-1 after mating, there was significantly more females giving birth and weaning, and exhibited the largest litter size and litter weight at 3 weeks of age (P < 0.01). The hamsters of the groups mated at 12 weeks of age exhibited a higher percentage of females giving birth and litter size and litter weight at birth than those at 8 weeks of age, but that was no significant difference in litter size and litter weight at 3 weeks of age. We conclude that Syrian hamsters raised by fibrous feed before mating gave optimal reproductive performance.

Aging↗

PubMed1995

Deuterium MR in vivo imaging of the rat eye using 2H2O.

In vivo deuterium MR imaging (2H MR) was investigated in rats after intraperitoneal administration of deuterated saline, and a dynamic study of the water movement in rat eyes was performed. Deuterium MR imaging was carried out by means of a gradient-echo (GRE) and a spin-echo (SE) pulse sequence. The rat eye was imaged in 2H MR more selectively by SE than by GRE, but a lower signal-to-noise ratio was obtained in 2H MR imaging using the SE sequence. The MR signal intensity of the rat eye was followed by a 3-compartment model, which enabled determination of the flow rate constant of the water in the eye (0.359/min). Deuterium MR imaging is useful to visualize the dynamic change of water in rat eyes using 2H MR at the same magnetic field (2 T) that can also be used for conventional MR imaging in humans.

Animals↗

PubMed1995

[Investigation into the therapeutic efficacy of continuous isoproterenol inhalation in relation to respiratory infections in asthmatic children].

In our Department, continuous isoproterenol inhalation therapy has been conducted on status asthmatics over the last 10 years. In the present study, we investigated whether there are any differences in the therapeutic efficacy of continuous inhalation of isoproterenol in the presence or absence of respiratory infections which may induce or aggravate asthma attacks. The treatment period was significantly longer in patients with pneumonia. Further prolongation of the treatment period was noted in patients with atelectasis. However, there were no apparent differences in therapeutic efficacy according to age or the severity of attacks. These findings suggest that continuous inhalation of isoproterenol is very effective for status asthmatics if respiratory infections are thoroughly controlled.

Administration, Inhalation↗

PubMed1994

In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia.

The in vivo generation of .OH free radicals in specific brain regions can be measured by intracerebral microdialysis perfusion of salicylate, avoiding many of the pitfalls inherent in systemic administration of salicylate. Direct infusion of salicylate into the brain can minimize the hepatic hydroxylation of salicylate and its contribution to brain levels of 2,5-DHBA. Levels of 2,5-DHBA detected in the brain dialysate may reflect the .OH adduct plus some enzymatic hydroxylation of salicylate in the brain. After minimizing the contribution of enzyme and/or blood-borne 2,5-DHBA, the present data demonstrate the validity of the use of 2,3-DHBA and apparently 2,5-DHBA as indices of .OH formation in the brain. Therefore, intracranial microdialysis of salicylic acid and measurement of 2,3-DHBA appears to be a useful .OH trapping procedure for monitoring the time course of .OH generation in the extracellular fluid of the brain. These results indicate that nonenzymatic and/or enzymatic oxidation of the dopamine released by MPTP analogues in the extracellular fluid may play a key role in the generation of .OH free radicals in the iron-rich basal ganglia. Moreover, a site-specific generation of cytotoxic .OH free radicals and quinone/semiquinone radicals in the striatum may cause the observed lipid peroxidation, calcium overload, and retrograde degeneration of nigrostriatal neurons. This free-radical-induced nigral injury can be suppressed by antioxidants (i.e., U-78517F, DMSO, and deprenyl) and possibly hypothermia as well. In the future, this in vivo detection of .OH generation may be useful in answering some of the fundamental questions concerning the relevance of oxidants and antioxidants in neurodegenerative disorders during aging. It could also pave the way for the research and development of novel neuroprotective antioxidants and strategies for the early or preventive treatment of neurodegenerative disorders, such as Parkinson's disease (Wu et al., this issue), amyotrophic lateral sclerosis, head trauma, and possibly Alzheimer's cognitive dysfunction as well. In conclusion, this in vivo free-radical trapping procedure provides evidence to support a current working hypothesis that a site-specific formation of cytotoxic .OH free radicals in the basal ganglia may be one of the neurotoxic mechanisms underlying nigrostriatal degeneration and Parkinsonism caused by the dopaminergic neurotoxin MPTP. Addendum added in proof: The controversy concerning possible neurotoxic and/or neuroprotective roles of NO. in cell cultures was discussed and debated at the symposium (Wink et al., this issue; Dawson et al., this issue; Lipton et al., this issue).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Determination of 9 alpha, 11 beta-prostaglandin F2 in human urine and plasma by gas chromatography-mass spectrometry.

Sensitive and specific assay methods for 9 alpha, 11 beta-prostaglandin F2 (9 alpha, 11 beta-PGF2) by gas chromatography-mass spectrometry with electron impact ionization are described. The mass spectrometric assay for 9 alpha, 11 beta-PGF2 was based on the use of the methyl ester-dimethylisopropylsilyl ether derivative, and pentadeuterated PGF2 alpha as a convenient internal standard. The calibration graph for 9 alpha, 11 beta-PGF2 was linear from 5 pg to 100 ng for both the standard and spiked biological samples. The limit of detection was 50 pg/ml for urine and 25 pg/ml for plasma (signal-to-noise ratio = 2.3). The method was applied to the determination of 9 alpha, 11 beta-PGF2 in urine and plasma samples from patients with bronchial asthma.

Adolescent↗

PubMed1994

Leukotriene and thromboxane antagonists.

It has been suggested that arachidonate metabolites, leukotrienes, and thromboxane may play important roles in the pathogenesis of bronchial asthma. Biologic activities of these mediators are much more potent than those of histamine and acetylcholine on a molar basis in inducing bronchoconstriction, increase in microvascular permeability, formation of mucosal edema, and mucus secretion, which are characteristic features of bronchial asthma. Furthermore, recent studies have demonstrated the presence of these mediators in plasma, BALF, and urine in asthmatic patients after allergen challenge. Therefore, the regulation of the activities of these mediators may provide a novel therapeutic approach for the treatment of bronchial asthma. A large number of 5-lipoxygenase inhibitors, peptide leukotriene antagonists, thromboxane synthase inhibitors, and thromboxane antagonists have been actively developed by the pharmaceutical industry, and there are increasing findings to demonstrate a clinical efficacy by these compounds. Among them, a thromboxane synthase inhibitor, OKY-046, first became available as an antiasthmatic agent in Japan. This is a significant step in the management of bronchial asthma. Preclinical and clinical results have suggested that these inhibitors and antagonists may be capable of inhibiting airway obstruction with airway inflammation and bronchial hyperresponsiveness, which are important characteristics of bronchial asthma. Further results from clinical studies with newly developed leukotriene and thromboxane antagonists are eagerly awaited.

Animals↗