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Biomedical subjects

A Isobe

Publications and source records attributed to A Isobe.

At least 37 records · Page 2Linked to original sources

[Participatory action-research in the development of health policies for Izumo City, Japan].

The method of participatory action-research has been introduced in planning and implementing health and welfare projects for the elderly in Izumo City since 1993. Public health researchers have participated in the projects with other related administrative sectors, citizen and non-profit organizations. This study analyzes the establishment and implementation of health policies of Izumo from the following five aspects: policy-making, priority, education, intersectoral cooperation and community development. The participatory action-research method was useful for developing the ability of health-staff to work with citizens; for integrating community care and community development; for using community resources effectively for primary health care; and for developing community-based education of citizens, medical students and health staff. This method can be and should be adopted for strengthening the policy-making ability of public health researchers who learn through cooperation with citizens and non-profit organizations.

Community Participation↗

Effects of paraquat on mitochondrial electron transport system and catecholamine contents in rat brain.

The effects of paraquat on rat brain were studied. Activities of complex I (NADH: ubiquinone oxidoreductase) in mitochondrial electron transport system, lipid peroxidation and the amount of catecholamines in rat brain were measured after acute paraquat exposure. Complex I activities were significantly lower and lipid peroxides were higher in the brains of a paraquat-treated group than in those of a control group. Lipid peroxide in rat serum, however, did not increase after paraquat exposure. A study of the time dependency of paraquat effects disclosed that mitochondrial complex I activities in rat brain as well as those in rat lung and liver gradually decreased prior to the appearance of respiratory dysfunction. As compared to controls, the dopamine in rat striatum was significantly lower in the paraquat-treated group. These results suggest that paraquat after crossing the blood-brain barrier might be reduced to the radical in rat brain, which may damage the brain tissue, especially dopaminergic neurons in striatum. We therefore propose that cerebral damage should be taken into consideration on paraquat exposure. Patients may therefore need to be followed up after exposure to high doses of paraquat.

Animals↗

A case of tick bite from Amblyomma testudinarium on the glans penis.

A tick which bit the glans penis of a 40-year-old Japanese man was surgically excised together with the skin where the bite occurred. It was identified as Amblyomma testudinarium through the taxonomical investigation of its morphological characteristics. To our best knowledge, our patient is the sixth tick bite from this species of tick recorded in the Chugoku District of Japan.

Adult↗

Radical formation site of cerebral complex I and Parkinson's disease.

Paraquat was reduced to the paraquat radical via complex I in bovine cerebral mitochondria and accelerated lipid peroxidation. Thirty-kilodalton subunit of complex I was considered to be the radical formation site, because of its marked destruction by the paraquat radical. The lipid peroxidation by the paraquat radical was suppressed not only by superoxide dismutase (SOD) but also by mannitol. The destruction of complex I subunits via lipid peroxidation must have been caused by the hydroxyl radical which was formed from the superoxide radical. The same phenomenon was observed by using 1-methylnicotinamide (MNA), which contains the same partial structure as paraquat in itself and is metabolized from nicotinamide in a living body. We observed NADH oxidation by MNA via cerebral complex I (Km = 26.3 mM), and MNA destroyed some complex I subunits, especially 30-kilodalton protein. Paraquat might be useful for studying the pathogenesis of Parkinson's disease (PD) in vitro, and MNA is expected to be one of the causal substances of PD from the viewpoint of the oxidative stress theory.

Animals↗

The fatty acids of each lipid fraction and their use in providing energy source of the plerocercoid of Spirometra erinacei.

The fatty acid concentration of each lipid fraction of plerocercoids of Spirometra erinacei and the host snake serum was investigated. The major fatty acids of phospholipid of the plerocercoids were C18:1, C18:0 and C16:0, and those of the host snake serum were C16:0, C18:1 and C18:0, in order of amount in both cases. The changes of the fatty acid composition of phospholipid of the plerocercoids when they were incubated in physiological saline at 18 degrees C and at 37 degrees C for 24 h were investigated in both cases. Polyunsaturated fatty acids increased at 18 degrees C, and saturated fatty acids increased at 37 degrees C. Michaelis constants (Km) of beta-hydroxyacyl-CoA dehydrogenase (HAD), NADH: ubiquinone oxidoreductase (complex I) (NADH: ferricyanide reaction) and complex I (NADH: ubiquinone reaction) for NADH were 20.6, 50 and 13.3 microM, respectively. The ATP production in mitochondria of the plerocercoids was accelerated by adding ADP and inhibited by adding such electron transport system inhibitors as rotenone, antimycin A and sodium cyanide. These results suggested that the fatty acids in the plerocercoids played an important role in regulating the fluidity of membrane by changing the composition in membrane lipid corresponding with the change of temperature circumstance. The NADH reduced by HAD might be accepted by the complex I in the electron transport system, and thus the parasites were capable of ATP production in a classical pathway of the oxidative phosphorylation system.

Adenosine Triphosphate↗

Effect of orthovanadate on commitment of avian myoblasts transformed with Rous sarcoma virus to myogenic differentiation.

Myogenic differentiation of quail myoblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus (QM-RSV cells) depends on the temperature: at 35.5 degrees C, the permissive temperature for the virus, the transformed myoblasts proliferate, without fusion, but at 41 degrees C, the nonpermissive temperature, they become committed to myogenic differentiation until about 10 h and then myoblast fusion occurs within 24 h. This temperature dependency of the differentiation reaction is derived from protein kinase activity of src gene product. Thus, at 41 degrees C, the differentiation proceeds with dephosphorylation of the proteins. For further clarification of relationship between the protein phosphorylation and the control of differentiation, the events during differentiation were examined using inhibitors of tyrosine kinase and phosphatase, respectively. To examine the role of phosphotyrosyl protein phosphatases in skeletal muscle differentiation, these cells were treated with sodium orthovanadate, a potent inhibitor of the enzyme. The treatment with the drug inhibited myoblast fusion and creatine kinase activity of the cells at 41 degrees C, with inhibition of tyrosine dephosphorylation. Moreover, the treatment of the cells with vanadate for 12 h at 41 degrees C, followed by the removal of the drug resulted in myoblast fusion after the lag time about 12 h. On the other hand, herbimycin A was needed to acquire the fusion commitment at 35.5 degrees C. These results are suggestive evidence to reflect that tyrosine dephosphorylation is a key step in commitment of QM-RSV cells to myogenic differentiation. Examination of the tyrosine phosphorylated proteins indicated that vanadate mainly inhibited the dephosphorylations of 70-, 58-, and 38-kDa proteins, suggesting that these proteins may be closely associated with the steps involved in commitment to myogenic differentiation.

Animals↗

Mechanism of cytotoxicity of paraquat. III. The effects of acute paraquat exposure on the electron transport system in rat mitochondria.

The effects of acute paraquat exposure on mitochondrial function in rat lung were studied. The paraquat dose-response study and time-effective study were performed to prove our hypothesis, enzyme toxicity especially in electron transport system following lipid peroxidation of mitochondrial inner membrane. In dose-response study, lipid peroxidation was increased by high dose paraquat exposure (40 mg/kg body weight) in rat lung, but not by low dose exposure (10 mg/kg body weight). But paraquat inhibited NADH:ubiquinone oxidoreductase (complex I) activities, especially NADH:ubiquinone reaction (NQR), even in low dose exposure. The lipid peroxide concentration did not correspond to the damage of complex I activity. In paraquat time-effective study, both lung and blood lipid peroxides increased after 6 h of paraquat exposure, decreased after 12 and 24 h and increased again after 48 h. After first peak of lipid peroxidation, NQR velocity decreased earlier than NADH:ferricyanide reaction (NFR) velocity. From these results, the cytotoxicity via mitochondrial dysfunction by acute paraquat exposure might be caused by complex I toxicity following lipid peroxidation of mitochondrial inner membrane.

Animals↗

[Changes in ischemic findings in ECG, obesity and serum lipids in the residents of an agricultural area in Shimane Prefecture].

Changes in ischemic findings in ECG, obesity and serum lipids and the relations among them were investigated in Sada Town, a typical agricultural and mountaineous area in Shimane Prefecture, where the mortality rate from ischemic heart disease had increased. Compared with 1983, the percentage of ischemic findings in ECG in 1990 increased, and a marked elevation of total serum cholesterol level, and relative and absolute lowering of HDL cholesterol level were observed in 1990. By observing the relations of total serum cholesterol, HDL cholesterol and the atherosclerotic index to the ischemic findings in electrocardiograms (ECG), it was found that males showed a significantly lower HDL cholesterol level and higher atherosclerotic index than the control group. In males, a relation between obesity and ischemic findings in ECG was observed. In females, a relation between obesity and the atherosclerotic index was observed; however, no relations were observed between ischemic findings and obesity. These results support the hypothesis that a marked elevation of the total serum cholesterol level, relative and absolute lowering of the HDL cholesterol level and obesity have an effect on the recent increase of male deaths due to ischemic heart disease in Sada Town, Shimane Prefecture.

Aged↗

The metabolism of arachidonic acid to prostaglandin E2 in plerocercoids of Spirometra erinacei.

With a simplified method of extracting and purifying prostaglandins, trace prostaglandins (nanogram order) were detected by gas chromatography-mass spectrometry. Arachidonic acid was metabolized to prostaglandin E2 (PGE2) by plerocercoids of Spirometra erinacei, the PGE2 was detected in the medium after incubation with arachidonic acid, and the role of albumin in the absorption of free arachidonic acid by plerocercoids and in the release of its metabolite was investigated. Plerocercoids absorbed arachidonic acid-binding albumin and released PGE2 efficiently. PGE2 is known to suppress the functions of mononuclear cells of the host. The selective release of PGE2 may be related to the escape mechanism of plerocercoids of S. erinacei from the host immune system to become established larva migrans, i.e., sparganosis.

Absorption↗

Mechanism of cytotoxicity of paraquat. I. NADH oxidation and paraquat radical formation via complex I.

The mechanism of cytotoxicity by paraquat was studied focusing attention on its effect on the mitochondrial electron transport system. Paraquat inhibited both mitochondrial and cytoplasmic malate dehydrogenase activities. NADH oxidation was verified in NADH: ubiquinone oxidoreductase (complex I) reaction mixture in which paraquat was an only electron acceptor, and paraquat radical formation was observed as turning blue of the reaction mixture. A kinetic characteristic of this enzyme reaction was that Km was so high as 4.1 mM. The maximum reaction velocity was defined in the range over pH 9. NADH autoxidation with complex I, but without paraquat, was not observed in any pH range. The maximum reaction velocity of the NADH autoxidation by paraquat without complex I was observed in pH 8.5, but the figure was so small as to be negligible. With these results, we propose the hypothesis that paraquat does not promote the autoxidation with complex I, but accepts electrons via complex I to induce paraquat radical formation.

Animals↗

Inflammatory activity of polymeric photoproducts of chlorpromazine.

To confirm the inflammatory activity of polymeric photoproducts (CPZ-polymers) of chlorpromazine (CPZ), which were obtained by gel filtration of a UV-pre-irradiated CPZ aqueous solution, the histamine release from rat peritoneal exudate cells was studied and the paw-inflammation in mice induced by these CPZ-polymers was examined. CPZ-polymers induced a dose-dependent histamine release at concentrations of 1, 3 and 10 mg/ml. This effect was approximately one-tenth of that of compound 48/80. Furthermore, CPZ-polymers markedly induced lasting paw-edema in a dose-dependent manner, the swellings remaining for at least 96 h. When intraperitoneally injected into mice, CPZ-polymers induced a significant elevation of histamine release in the peritoneal cavity 0.5 h after the injection, compared with a control group. The histamine levels in the cavities returned to normal within the next 0.5 h, and remained normal for at least 23 h, indicating that histamine release may be caused only in the early stages of CPZ-polymer-induced inflammation. The inflammatory activity of the CPZ-polymers suggests that they are inflammatory substances formed from CPZ by UV-irradiation.

Animals↗

Immunogenicity of human T cell leukemia virus type-I (HTLV-I) antigens for cytotoxic T lymphocytes in the rat system.

We showed previously that WKA (rat MHC, RT-1k) and DA (RT-1a) rat CTL specific for human T cell leukemia virus type-I (HTLV-I) recognized the gag and pX gene-encoded Ag. In the present study, we explored HTLV-I Ag recognized by CTL from other MHC genotype (RT-1l) rats, LEW and F344, and examined whether HTLV-I Ag expressed by recombinant vaccinia viruses (rVV) could prime WKA and LEW rats for HTLV-I-specific CTL. Upon priming in vivo and repetitive stimulation in vitro with HTLV-I+ syngeneic T cells, HTLV-I-specific CD8+ CTL were demonstrated in LEW and F344 rat spleen cell cultures. Interestingly, these CTL were directed against HTLV-I env and pX gene products. Immunization of LEW and WKA rats with the env and gag gene-expressing rVV, respectively, resulted in generation of HTLV-I-specific CD8+ CTL. However, a pX-gene expressing rVV failed to prime either rat strain. In addition, HTLV-I-specific CD8+ CTL from F1 hybrid (WKA x LEW) rats generated by immunization and restimulation with HTLV-I+ syngeneic T cells showed gag and pX Ag specificity on WKA rat cells and env and pX Ag specificity on LEW rat cells. These results suggest that immunogenicity of HTLV-I gag and env Ag in induction of HTLV-I-specific CTL varies depending on MHC, and that the pX Ag expressed by rVV is not a potent immunogen for rats.

Animals↗

Purification and hydrolytic action of a chitosanase from Nocardia orientalis.

Chitosanase from the culture filtrate of Nocardia orientalis was purified to apparent homogeneity by precipitation with ammonium sulfate followed by CM-Sephadex chromatography, biospecific affinity chromatography on a Sepharose CL-4B with immobilized chitotriose and by gel filtration on Sephadex G-75. The enzyme specifically acted on chitooligosaccharides and chitosan to yield chitobiose and chitotriose as final products. The mode of action of the chitosanase on chitooligosaccharides and their corresponding alcohols suggests that the enzyme requires substrates with four or more glucosamine residues for the expression of activity and its shows maximum activity on chitohexaose and chitoheptaose. In the hydrolysis of chitosans of varying N-acetyl content, the enzyme cleaved about 30% acetylated chitosan with maximum activity and the enzyme activity decreased with increasing the degree of deacetylation of chitosans tested. The analysis of products formed from 33% acetylated chitosan shows the chitosanase is capable of cleaving between glucosamine and glucosamine or N-acetylglucosamine, but not cleaving between N-acetylglucosamine and glucosamine. On the basis of the results, the whole pathway of enymatic degradation of partially acetylated chitosan by a combination of chitosanase, exo-beta-D-glucosaminidase and beta-N-acetylhexosaminidase is proposed.

Acetylglucosamine↗

Activation of hyaluronidase by 8-methoxypsoralen-polyamine photoproducts.

Ultraviolet radiation of 8-methoxypsoralen (8-MOP) in the presence of various polyamines resulted in stable photoproducts that were very soluble in water and showed hyaluronidase-activating properties. Among them, the photoproducts obtained from the reaction systems of 8-MOP-spermine and 8-MOP-spermidine markedly activated hyaluronidase. The enzyme activity was not affected by 8-MOP alone and the photoproduct of 8-MOP (8-MOP-P). From these facts, it was suggested that the photoproducts with hyaluronidase-activating properties might play an important role in the onset of 8-MOP-induced photosensitivity.

Animals↗

Production of benzoylformic acid from phenylglycine by Saccharomycopsis lipolytica.

Microbial production of benzoylformic acid (BF), which can be used as a substrate of enzymatic synthesis of (R)-(-)-mandelic acid, was investigated. Among 145 strains of yeasts and actinomycetes, Saccharomycopsis lipolytica (IAM 4964) was the best producer of BF from DL-phenylglycine (DL-PG). Culture conditions for BF production by the organism were optimized. When 0.2% fructose as a carbon source and 0.7% Bacto-tryptone as a nitrogen source were used in the presence of 4% DL-PG, 14.5 mg/ml of BF was produced (about 37% molar yield) in 4 days of cultivation. BF was synthesized from the L-form of PG, but not from the D-form. The BF was isolated from culture broth in a crystalline form and physicochemically identified.

Anti-Inflammatory Agents, Non-Steroidal↗

Increased hexokinase activity in fetuses of rats developed under maternal hyperglycemia.

Hepatic and diaphragmatic hexokinase (HK) activities increased in fetuses of rats developed under maternal hyperglycemic conditions, compared to those in normal controls. In those organs, Type I and Type II hexokinase isozymes were detected by electrophoresis and densitometry with a chromatoscanner. Densitometric peak that corresponded to hepatic and diaphragmatic Type II hexokinase was also increased in the fetuses developed under hyperglycemia, compared to that of normal fetuses. These findings suggest that in the fetal liver, where significant activity of Type IV was absent, activity of Type II hexokinase varied depending on physiological state such as maternal hyperglycemia.

Animals↗

Two different types of apnea induced by focal cold block of ventral medulla in rabbits.

The respiratory effects of unilateral focal cold block of ventral medulla were examined in rabbits. Focal cooling of the paraolivar region in the caudal area of ventral medulla induced prolongation of the expiratory time, with little change in the tidal inspiratory activity amplitude, leading to 'temporal apnea'. Whereas focal cooling of the region ventral to the retrofacial nucleus in the rostral part of the ventral medulla induced depression of tidal phrenic nerve activity amplitude, leading to 'suppression apnea'. Thus, two different types and regions of apnea were demonstrated in rabbits.

Animals↗

Effects of high-frequency inflation (HFI) on expiratory activity.

It has been reported that triangular-shaped positive pressure pulses applied to the airway (high-frequency inflation, HFI) stimulates pulmonary stretch receptors and prolongs expiratory duration. In the present experiment, changes in the integrated curve of expiratory activity induced by HFI were investigated. Duration until the onset of the expiratory activity (E1 stage) was unchanged. In the E2 stage, the initial ascending slope became steeper and higher peaks were reached during HFI stimulation. The period from the onset of the slope to the peak, previously designated the stage of active expiration (Ea stage), showed no consistent change in duration and remained unchanged on average. The period after the peak until the onset of the following inspiratory activity was consistently prolonged. This period was designated the declining stage of expiration (Ed stage).

Afferent Pathways↗