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Biomedical subjects

A Tamura

Publications and source records attributed to A Tamura.

At least 397 records · Page 22Linked to original sources

[Multivariate analysis of acute leukemia].

The outcome of chemotherapy in patients of 150 cases of acute leukemia was investigated. Patients were divided into two groups, that is group I: 100 cases of acute leukemia treated between 1980-1984, group II: 50 cases of acute leukemia between 1985-1986. Complete remission was achieved in 66% of group I and in 82% of group II. Using multivariate analysis, the initial levels of FDP and WBC count and age were found to be important factors to induce complete remission. Female sex was suggestive of a longer remission duration and survival by discrimination analysis.

Acute Disease↗

[Response to antitumoral agents of a human medulloblastoma implanted into the chorioallantoic membrane of a chick embryo].

In a previous study the authors have reported on a correlation between the effects of drugs on gliomas grown in the eggs and in the nude mice, and in this study, they have observed the antineoplastic effects of ACNU or combined chemotherapy (CAP-cyclophosphamide, adriamycin, cisplatin) against a medulloblastoma applied onto the chorioallantoic membrane (CAM) of a chick embryo. In this model, ACNU was thought to be ineffective because of an intracerebral dissemination that occurred in spite of the administration of ACNU. ACNU also proved ineffective against the medulloblastoma that grew on the CAM. There seemed to be correlation between the results of this test and the clinical course of this model. Thus this sensitivity test is thought to be useful in the screening of drugs against gliomas.

Adolescent↗

[Changes in xanthine and uric acid in rat brain after middle cerebral artery occlusion].

Xanthine and uric acid, products of purine metabolism, were measured by reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection in rat forebrain following focal cerebral ischemia. Focal cerebral ischemia was induced in the rat by permanent occlusion of the left middle cerebral artery (MCA). Sprague-Dawley rats were anesthetized with halothane inhalation and left MCA was occluded via trans-retro-orbital approach. Normal and sham-operated rats were used as control animals. The animals were decapitated 2 (MCA = 5, Sham = 5), 4 (MCA = 7, Sham = 6), 8 (MCA = 5, Sham = 5), and 16 (MCA = 6, Sham = 6) hours or 1 (MCA = 5, Sham = 5), 2 (MCA = 6, Sham = 6), 7 (MCA = 7, Sham = 6), 14 (MCA = 6, Sham = 5), and 28 (MCA = 7, Sham = 5) days after the operation. The brains were removed and divided into right and left hemisphere. Each hemisphere was homogenized and centrifuged. The supernates were filtered with membrane filter. An aliquot of the filtrate was used for measurement of xanthine and uric acid in both of the ischemic and contralateral hemisphere by a HPLC system. In the normal group, xanthine and uric acid in the brain was 12.4 +/- 0.4 and 2.2 +/- 0.1 nmol/g tissue (mean +/- SEM), respectively. In the ischemic hemisphere, xanthine increased up to 57.7 +/- 5.2 nmol/g tissue 2 hours after MCA occlusion and reached a maximum value of 59.42 +/- 4.91 nmol/g tissue 4 hours following the induction of ischemia. Xanthine level was still high 8 hours after ischemia and then rapidly decreased to the normal value at day 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of phospholipases on Cl-ATPase in the rat brain.

We investigated the effects of phospholipases on the activity of microsomal Cl-ATPase in the rat brain, in reference to those on the activities of Na,K-ATPase and anion-insensitive Mg-ATPase. In the presence of phospholipase A2 or phospholipase C, which almost completely hydrolyzed microsomal phosphoglycerides, the activities of Cl-ATPase and Na,K-ATPase were decreased to 8-50% of the control, but anion-insensitive Mg-ATPase activity was not altered. On the other hand, with sphingomyelinase treatment, only anion-insensitive Mg-ATPase was slightly inactivated. On the addition of phospholipids (phosphatidylserine (PS), phosphatidylinositol (PI) and microsomal phospholipid mixture), Cl-ATPase activity slightly recovered only with PI, while Na,K-ATPase activity partially recovered with either phospholipid. These data suggest that Cl-ATPase requires intact membrane lipid conformation and especially PI for its maximal activity.

Adenosine Triphosphatases↗

Preventive effect of pravastatin sodium, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on coronary atherosclerosis and xanthoma in WHHL rabbits.

In this paper, we examined whether the development of atherosclerosis in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model of familial hypercholesterolemia in man, could be prevented by the reduction of serum cholesterol levels. Pravastatin sodium (the generic name of CS-514), a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was used as a cholesterol-lowering drug. The drug was administered orally to 12 WHHL rabbits (2-3 months old) at a dose of 50 mg/kg per day for 24 weeks, and 13 animals were given water as control. In the treated group, serum cholesterol, phospholipid and triacylglycerol levels were significantly reduced by 28%, 32% and 16%, respectively, as compared with those of the control group. Although the prevention of development of the aortic atherosclerosis was not significant, the progression of coronary atherosclerosis was significantly prevented. The incidence of atherosclerosis in four main coronary arteries was reduced from 42% (control group) to 19% (treated group, P less than 0.01), and the development of lesion of coronary arteries evaluated by area of lesion was reduced from 19.7% (control group) to 9.1% (treated group, P less than 0.05). Histopathological findings supported the above observations. In addition, development of xanthoma in digital joints was also reduced from 90.4% (control group) to 58.3% (treated group, P less than 0.005). These results suggest that the development of coronary atherosclerosis and xanthoma in WHHL rabbit was reduced by continuous reduction of serum cholesterol levels treated with pravastatin sodium.

Animals↗

Behavioral changes after focal cerebral ischemia by left middle cerebral artery occlusion in rats.

Behavioral changes after occlusion of the left middle cerebral artery (MCA) in rats were investigated for 16 weeks. Impairment of motor coordination and incidence of neurological deficits including hemiplegia and abnormal posture were present for the first 2 and 4 weeks after MCA occlusion, respectively. Learning behavior in one-trial passive avoidance task was disturbed for the entire 16-week period when rats were trained at days 3 after MCA occlusion. Reacquisition was also impaired when rats were retrained on 8 weeks after MCA occlusion. Except for synchronized EEG at days 2 after MCA occlusion, significant changes in spontaneous movement and EEG were not observed in the MCA-occluded group. These results suggest that this rat model of MCA-occlusion is useful for quantitatively measuring functional changes in chronic phase of focal cerebral ischemia.

Animals↗

Structure-activity relationships of 4'-O-substituted 1-benzylisoquinolines with respect to their actions on the cell membrane of blood platelets and erythrocytes.

4'-O-Substituted 1-benzyl-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines inhibited the collagen-induced activation (aggregation and ATP secretion) of rabbit platelets and transformed the shape of human erythrocytes in a dose-dependent manner. Both effects increased with increasing number of carbon atoms of the 4'-substituted hydrocarbon moiety. The incorporation of these compounds into the erythrocyte membrane was also dependent on the number of carbon atoms of the 4'-substituted radical. The most potent phenoxy derivative suppressed arachidonic acid release from membrane phospholipids but had no effect on arachidonic acid metabolism in platelets. This indicated that the effects are comparable to those of a natural bisbenzylisoquinoline, cepharanthine. These effects appear to be due to a perturbing action on the membrane lipid bilayer.

Adenosine Triphosphate↗

Internal motion of a tryptophan residue in Streptomyces subtilisin inhibitor: deuterium nuclear magnetic resonance in solution.

Deuterium NMR spectroscopy was used to study internal motions of a deuterium-labeled single tryptophan (Trp) residue (per subunit) of Streptomyces subtilisin inhibitor (SSI) in solution. The free inhibitor with the five ring protons of the Trp replaced with deuterons showed a narrow resonance component (56 Hz) of about one-quarter of the total intensity, in addition to the broad resonance component (about 600 Hz) at 25 degrees C, showing that it exits in an equilibrium mixture of two conformers, in one of which the tryptophan side chain is highly mobile. In analogy to the two structures of SSI found in the crystal, these two conformers were attributed to the one in which the contact between the alpha-lobe and the beta-lobe of the subunit is tight and the other in which the same contact is loose. When SSI forms a complex with subtilisin BPN', the broad component becomes invisibly broad, but the narrow component increases with even further narrowing, suggesting that the binding to the enzyme favors the "loose" conformer over the "tight" conformer.

Bacterial Proteins↗

Tyrosinases of murine melanocytes with mutations at the albino locus.

Tyrosinase (monophenol monooxygenase; monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1) is a key enzyme in the synthesis of melanin. Reduced levels of tyrosinase play an important role in albinism. The data described here show differences in the expression and characteristics of tyrosinase in cutaneous murine melanocytes grown in culture from normal wild-type strains (C/C); from three albino locus mutants: himalayan (ch/ch), chinchilla (cch/cch), and albino (c/c); and from the double-mutant heterozygous pink-eyed chinchilla (cchp/cp). Our results suggest that the diminished pigmentation in all mutants is due to abnormal posttranslational modification of the enzyme: the levels of mRNA for tyrosinase in wild-type, himalayan, and pink-eyed chinchilla melanocytes are similar; the himalayan mutation confers a deficiency in N-linked glycosylation, which results in an extremely unstable enzyme that is also temperature sensitive; the chinchilla and albino mutations confer susceptibility to proteolytic cleavage; the pink-eye dilution confers a reduction in the levels of immunoprecipitable tyrosinase, and what little enzyme there is fails to be translocated from the trans-Golgi network to melanosomes. The kinetics of activation and inhibition of the enzyme by the cofactor dopa are unique for the mutants tested and differ from those of tyrosinase from wild-type melanocytes. The findings support the conclusion that the albino locus in mice encodes the structural gene of tyrosinase.

Animals↗

Interaction of cellular hydrogenase, cytochrome c3, and desulfoviridin in Desulfovibrio vulgaris Miyazaki with their antibodies.

Anti-sera for hydrogenase, cytochrome c3, and desulfoviridin (abbreviated as anti-hyd, anti-c3, and anti-dvn, respectively) were raised in mice, and used to locate these antigens in cells of Desulfovibrio vulgaris Miyazaki. The activity of the intact cells to absorb H2 with methyl viologen or sulfite as an electron acceptor was cumulatively inhibited by treating the cells with anti-hyd and anti-c3 but unaffected by anti-dvn treatment. The activity of the intact cells to produce H2 from formate was also inhibited by anti-c3 treatment, but the inhibition by anti-hyd treatment was not significant. The fluorescent antibody technique applied to intact cells of D. vulgaris Miyazaki indicated that both hydrogenase and cytochrome c3 are localized on the surface of the cell. These results are not exactly in conformity with the hydrogen-cycling hypothesis for proton gradient formation in the energy metabolism in Desulfovibrio. The procedure described in the present paper provides a new technique to elucidate the roles of proteins by applying anti-sera to intact cells without destroying the cellular structure.

Antibody Formation↗

Electron microscopic observations of the embryo Leptotrombidium (Leptotrombidium) pallidum naturally infected with Rickettsia tsutsugamushi.

Embryos of Leptotrombidium (Leptotrombidium) pallidum mites naturally infected with Rickettsia tsutsugamushi were examined by electron microscopy. Rickettsiae were not found in eggs just after oviposition, but were easily detected in cells at the various parts of the embryos just before hatching, indicating that the rickettsiae are surely vertically transmitted from infected adult mites to the larvae through embryos, and the rickettsiae may multiply in situ during the developing process of the embryo.

Animals↗

Immunoblotting analysis of anti-rickettsial antibodies produced in patients of Tsutsugamushi disease.

The reactivity of sera from patients of Tsutsugamushi disease (scrub typhus) with the antigenic polypeptides of Rickettsia tsutsugamushi was analyzed by the immunoblotting method. The reactivity varied greatly among the sera of individual patients tested. IgG and IgM antibodies of most patients reacted with the 54-56 kilodalton (54-56K) polypeptide located on the rickettsial surface, suggesting that this polypeptide is a predominant antigen in the infection. Other polypeptides of 60K, 50-52K, 46-47K, 35K, and 21-25K were reactive with some but not all sera. From the reactivity of these polypeptides, it was suggested that the 54-56K polypeptide is both strain-specific and group-specific, the 60K polypeptide is group-specific, and the 35K and 21-25K polypeptides are subgroup-specific. IgG antibodies seem to be more cross-reactive with polypeptides of multiple strains than IgM antibodies and have a tendency of increased cross-reactivity that was observed in the sera obtained at the later stage of illness.

Antibodies, Bacterial↗

Xanthine and uric acid levels in rat brain following focal ischemia.

Changes of the xanthine and uric acid (UA) levels in rat forebrain following focal cerebral ischemia were studied by reversed-phase HPLC with electrochemical detection. Focal ischemia was induced by occluding the left middle cerebral artery in the rat. The xanthine level in the normal group was 11.50 nmol/g tissue. In the ischemic group, the xanthine concentration in the ischemic hemisphere progressively increased after occlusion and reached a maximum value of 59.42 nmol/g tissue 4 h after operation. The UA level in the normal group was 2.20 nmol/g tissue, whereas in the ischemic group the UA concentration in the ischemic hemisphere gradually increased after occlusion, reaching a value of 38.53 nmol/g tissue 24 h after ischemia. The concentration of UA remained elevated in the ischemic hemisphere until 48 h after occlusion, and reached a maximum value of 38.98 nmol/g tissue. The xanthine and UA levels in the contralateral hemisphere remained unchanged. The xanthine and UA concentrations in the sham-operated group did not show a significant increase after operation. The time course of xanthine and UA levels suggests that in ischemic forebrain UA is formed from xanthine as a product of purine metabolism.

Animals↗

In vitro and in vivo antibacterial activities of ME1207, a new oral cephalosporin.

ME1207 (pivaloyloxymethyl ester of ME1206) is a new oral cephalosporin. ME1206 is (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)- acetamido]-3-[(Z)-2-(4-methylthiazol-5-yl)-ethyl]-cephem-4-carboxy lic acid. The susceptibilities of about 1,600 clinical isolates to ME1206 were determined by the agar dilution method. ME1206 showed a broad spectrum of activity against gram-positive and gram-negative bacteria. ME1206 was more active than cefaclor, T-2525, and cefixime against Staphylococcus aureus and Staphylococcus epidermidis. Against gram-negative bacteria, the activity of ME1206 was comparable with that of T-2525, but ME1206 was less active than cefixime. Against Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae, ME1206 had high activity (MIC, less than or equal to 0.05 microgram/ml). ME1206 was stable against various beta-lactamases, except beta-lactamases from Providencia rettgeri, Pseudomonas cepacia, and Escherichia coli W3630 (Rms213). The 50% effective doses of ME1207 after oral administration against systemic infections in mice were comparable with those of T-2588 against gram-negative bacteria and about one-fourth that of T-2588 against Staphylococcus aureus Smith.

Administration, Oral↗

Effects of hypotension induced with sodium nitroprusside on the cerebral circulation before, and one week after, the subarachnoid injection of blood.

Cerebral blood flow (CBF) and mean arterial pressure (MAP) were monitored in six normal baboons and six further animals in which an artificial subarachnoid haemorrhage (SAH) had been induced one week previously. MAP was reduced by the infusion of sodium nitroprusside. In the normal animals with administration of sodium nitroprusside, CBF increased initially but started to decrease as MAP was reduced below 65 mm Hg and fell below its baseline value when MAP was less than 50 mm Hg. In the SAH group, there was no initial hyperaemic response and CBF fell below baseline values when MAP was reduced below 50 mm Hg. When, during the infusion of the sodium nitroprusside, MAP was returned to normal using angiotensin, CBF increased above its baseline value. These results suggest that the cerebrovascular effects of sodium nitroprusside are the net result of competition between direct cerebral vasodilatation, falling arterial blood pressure and the degree of impairment of the "autoregulatory" mechanism. Evidence of ischaemic brain damage was found in the arterial boundary zones of both groups of animals.

Animals↗

Indomethacin ameliorates ischemic neuronal damage in the gerbil hippocampal CA1 sector.

The purpose of our experiment was to examine whether the cyclooxygenase inhibitor indomethacin ameliorates neuronal injury in the gerbil hippocampal CA1 sector following 5 minutes of forebrain ischemia. Thirty minutes before bilateral carotid artery occlusion, Mongolian gerbils were injected intraperitoneally with 1 (n = 10), 2 (n = 10), 5 (n = 12), or 10 (n = 7) mg/kg of indomethacin. Seven days after occlusion, the gerbils were perfusion-fixed and neuronal density in the hippocampal CA1 sector was assessed. The mean +/- SEM neuronal density in nine unoperated normal gerbils was 307 +/- 9/mm, in 10 untreated ischemic gerbils 55 +/- 21/mm, and in seven vehicle-treated ischemic gerbils 15 +/- 9/mm. The mean +/- SEM neuronal density in ischemic gerbils treated with 1, 2, 5, or 10 mg/kg indomethacin was 132 +/- 28/mm, 154 +/- 29/mm, 176 +/- 30/mm, and 136 +/- 39/mm, respectively. Indomethacin at any dose significantly ameliorated ischemic neuronal damage in the gerbil hippocampal CA1 sector.

Animals↗