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Biomedical subjects

T Adachi

Publications and source records attributed to T Adachi.

At least 361 records · Page 20Linked to original sources
PubMed1993

Further study of effects of chelating agents on excretion of inorganic mercury in rats.

The effects of three chelating agents, N-benzyl-D-glucamine dithiocarbamate (BGD), 2,3-dimercaptopropanol (BAL) and D-penicillamine (D-PEN), on the excretion of mercury in rats exposed to mercuric chloride (HgCl2), the chemical forms of mercury compounds excreted in the bile and urine and the intestinal reabsorption of mercury compounds in the bile were studied. Rats were injected intraperitoneally with 203HgCl2 (300 micrograms Hg and 74 kBq of 203Hg/kg) and 24 h later, they were injected intraperitoneally with a chelating agent (a quarter of an LD50). The injection of the chelating agents significantly enhanced the biliary and urinary excretions of mercury. The enhancing effect of BGD on the excretions of mercury was almost the same as that of BAL and much larger than that of D-PEN. The major chemical form of mercury in the bile and urine of rats injected with BGD after HgCl2 treatment was Hg-BGD compounds. The chemical form of mercury in the bile and urine of rats injected with BAL after HgCl2 treatment was mainly Hg-GSH compound. The mercury after HgCl2 and D-PEN treatment was excreted mainly via the urine in the form of Hg-D-PEN compound. The intestinal reabsorption of mercury from the bile of rats injected with BGD or D-PEN was only 0.18% or 0.38% of the dose, respectively. The intestinal reabsorption of mercury from the bile of rats injected with BAL was 27.38% of the dose. It was suggested that the Hg-GSH compound excreted in the bile after HgCl2 and BAL treatment is partly degraded to Hg-cysteine (Cys) by the intestinal membranous enzymes and that the ligand of Hg-Cys is replaced by BAL in the bile, resulting in the effective reabsorption of Hg-BAL compound from the intestine.

Animals↗
PubMed1993

Binding of human xanthine oxidase to sulphated glycosaminoglycans on the endothelial-cell surface.

Much evidence has suggested that the superoxide generated by xanthine oxidase (XOD) within the endothelial cell triggers characteristic free-radical-mediated tissue injuries. Although it has been reported that XOD exists not only in the cytoplasm, but also on the outside surface of the endothelial cell membrane, it is not clear how XOD localizes on the outside of the plasma membrane. Purified human xanthine oxidase (h-XOD) had an affinity for heparin-Sepharose. The binding was largely independent of the pH over the physiological range, whereas it tended to increase at lower pH and to decrease at higher pH. Exposure of h-XOD to the lysine-specific reagent trinitrobenzenesulphonic acid or the arginine-specific reagent phenylglyoxal caused it to lose its affinity for heparin-Sepharose. The binding of h-XOD to heparin is apparently of electrostatic nature, and both lysine and arginine residues are involved in the binding. h-XOD was found to bind to cultured porcine aortic endothelial cells, and this binding was inhibited by the addition of heparin or pretreatment of the cells with heparinase and/or heparitinase. Intravenous injection of heparin into two healthy persons led to a prompt increase in plasma h-XOD concentration. These results suggest that XOD localizes on the outside surface of endothelial cells by association with polysaccharide chains of heparin-like proteoglycans on the endothelial-cell membranes. Superoxide extracellularly generated by XOD may injure the source-endothelial-cell membrane and also attract and activate closely appositional neutrophils, which themselves actually cause progressive oxidative damage.

Animals↗
PubMed1993

Gene structure and expression of rice seed allergenic proteins belonging to the alpha-amylase/trypsin inhibitor family.

Genomic and two novel cDNA clones for rice seed allergenic protein (RA) belonging to the alpha-amylase/trypsin inhibitor family were isolated and their nucleotide sequences determined. Ten cysteine residues deduced from nucleotide sequences were completely conserved among three cDNA clones including a clone, RA17, reported previously. One genomic clone, lambda 4, contained two RA genes, RAG1 and RAG2. Although RAG1 was cloned at the 5' portion only, two RA genes were arranged divergently. Nucleotide sequencing and DNA blotting analyses showed that RA are encoded by a multigene family consisting of at least four members. The transcriptional initiation site of RAG1 was localized at A, 26 bp upstream of the putative translational initiation codon, ATG, by the primer extension assay. The putative TATA box and CAAT box existed about 45 bp and 147 bp upstream of the transcription initiation site, respectively. A conserved sequence (ATGCAAAA) which was similar to the sequence (TGCAAAA) identified in rice glutelin promoters was observed in the 5' region of the two genes. In addition, RNA blotting analyses provided that RA genes specifically expressed in ripening seed and their transcripts accumulated maximally between 15 and 20 days after flowering.

Allergens↗
PubMed1993

Tumoricidal effect of human macrophage-colony-stimulating factor against human-ovarian-carcinoma-bearing athymic mice and its therapeutic effect when combined with cisplatin.

The effect of human macrophage-colony-stimulating factor (hM-CSF) on tumoricidal activity was examined in athymic mice bearing the human ovarian cancer cell line, HRA, injected intraperitoneally (i.p.). The survival period and survival rate in the groups treated daily with hM-CSF were significantly longer (P < 0.01) than in the untreated group. The peritoneal cell smears showed that ascitic tumor cells were markedly decreased in the hM-CSF-treated groups, and macrophages phagocytosed tumor cells, indicating a contact-mediated direct cytolysis. The combined therapeutic effects of cisplatin and hM-CSF on HRA-bearing athymic mice were also studied. The mean survival period was 25.4, 47.2, 42.4 and 67.4 days, respectively, in the untreated group, and in the groups treated with cisplatin alone, with hM-CSF alone, and with combined cisplatin and hM-CSF. The survival period and rate were significantly longer (P < 0.01) in the group treated with combined cisplatin and hM-CSF than in those treated with cisplatin or hM-CSF alone, indicating the therapeutic effectiveness of the combined use. Moreover, hM-CSF is effective against granulocytopenia due to bone marrow suppression caused by cisplatin. Our data demonstrate that hM-CSF administered i.p. has a tumoricidal activity in athymic mice bearing human ovarian cancer i.p., which is mediated by activated macrophages, and that the combined administration of cisplatin and hM-CSF has a significant therapeutic effect.

Agranulocytosis↗
PubMed1993

Selectivity and specificity in the recognition of tRNA by E coli glutaminyl-tRNA synthetase.

The specific recognition by Escherichia coli glutaminyl-tRNA synthetase (GlnRS) of tRNA(Gln) is mediated by extensive protein:RNA contacts and changes in the conformation of tRNA(Gln) when complexed with GlnRS. In vivo accuracy of aminoacylation depends on two factors: competition between synthetases, and the context and recognition of identity elements in the tRNA. The structure of the tRNA(Gln):GlnRS complex supports studies from amber and opal suppressor tRNAs, complemented by in vitro aminoacylation of the mutated tRNA transcripts, that the glutamine identity elements are located in the anticodon and acceptor stem of tRNA(Gln). Recognition of individual functional groups in tRNA, for example the 2-amino group of guanosine, is also evident from the result with inosine-substituted tRNAs. Communication between anticodon and acceptor stem recognition is indicated by mutants in GlnRS isolated by genetic selection with opal suppressor tRNAs which are altered in interactions with the inside of the L-shaped tRNA. We have also used genetic selection to obtain mutants of GlnRS altered in acceptor stem recognition with relaxed specificity for amber suppressor tRNAs, and a more extensive mutational analysis shows the importance of the acceptor binding domain to accurate recognition of tRNA.

Amino Acyl-tRNA Synthetases↗
PubMed1993

The nature of heterogeneous components of extracellular-superoxide dismutase purified from human umbilical cords.

Extracellular-superoxide dismutase (EC. 1.15.1.1., EC-SOD) is a secretory, tetrameric glycoprotein. This enzyme in plasma is heterogeneous with regard to heparin affinity and can be divided into at least three fractions approximately equally large: EC-SOD A, which lacks affinity; EC-SOD B with intermediate affinity; and EC-SOD C with high affinity. In this article, EC-SOD has been purified with a high yield from human umbilical cords. Of the umbilical cord EC-SOD, 0.8% behaved as subtype A, 1.9% as subtype B, and almost all as high heparin affinity subtype C. Purified native EC-SOD (n-EC-SOD C) showed a single band with enzymatic activity on polyacrylamide gel electrophoresis. It showed two bands with apparent molecular masses of 29.3 and 32.0 kDa on SDS-PAGE, while recombinant EC-SOD C (r-EC-SOD C) showed only one band with 32.0 kDa. By western blotting analysis with anti r-EC-SOD C antibody, two bands of n-EC-SOD C were detected at the same positions as in the gel stained with Coomassie blue. The appearance of two monomeric components with different molecular masses does not reside in the carbohydrate moiety, because the difference between the two components was not abolished by glycopeptidase F treatment; however, both bands were shifted to lower molecular weight ranges by this treatment. The two components could be clearly separated from each other by C4 reverse-phase high-performance liquid chromatography (HPLC).(ABSTRACT TRUNCATED AT 250 WORDS)

Amidohydrolases↗
PubMed1993

Effects of growth hormone on follicle growth, oocyte maturation, and ovarian steroidogenesis.

OBJECTIVES: To assess the effects of GH on follicle growth, oocyte maturation, ovulation, and ovarian steroidogenesis. DESIGN: In vitro perfused rabbit ovary. INTERVENTIONS: The rabbit ovaries were perfused with medium alone, with GH at 1, 10, 100, or 200 ng/mL, or with 50 IU hCG for 12 hours. MAIN OUTCOME MEASURES: The follicle diameter, the percent change in follicle diameter, the percentage of oocytes achieving germinal vesicle breakdown, and the production of P and E2 by the perfused rabbit ovaries. RESULTS: The addition of GH to the perfusate increased the follicle diameter at 12 hours after perfusion in a dose-dependent manner. The percent change in follicle diameter in GH-treated ovaries did not differ significantly from that in hCG-treated ovaries at each time point of perfusion. However, ovulation did not occur in either the control ovaries or the experimental ovaries treated with GH. Exposure to GH at a concentration of > 10 ng/mL significantly stimulated the resumption of meiosis, as compared with the contralateral control ovaries. Although the concentration of P in the perfusate did not differ significantly between GH-treated and control ovaries, GH stimulated E2 production by the perfused rabbit ovaries in a dose-dependent manner. CONCLUSIONS: Growth hormone acts on the rabbit ovary to stimulate follicle growth, oocyte maturation, and ovarian E2 production.

Animals↗
PubMed1993

Late reperfusion for acute myocardial infarction limits the dilatation of left ventricle without the reduction of infarct size.

BACKGROUND: While previous clinical studies have shown a possible beneficial effect of the reperfusion performed at a relatively late phase of acute myocardial infarction ("late reperfusion") in preventing left ventricular enlargement, the mechanism has not been clarified. METHODS AND RESULTS: Of 89 patients with an initial anterior myocardial infarction, reperfusion was successful in 69. These 69 were divided into three groups according to the time required to achieve reperfusion after the onset of symptoms: early-reperfused (< 3 hours from the onset to reperfusion; n = 22), intermediate-reperfused (3 to 6 hours from the onset to reperfusion; n = 28), and late-reperfused (> 6 hours from the onset to reperfusion; n = 19). The 20 patients whose infarct-related artery were occluded in the acute phase as well as 1 month later was classified as nonreperfused. Infarct size, evaluated as defect volume by 201Tl single-photon emission computed tomography 1 month after the onset, was 1593 +/- 652 units (mean +/- SD) in the late-reperfused group, significantly larger (P < .05) than that of the intermediate-reperfused (1066 +/- 546 U) or the early-reperfused groups (372 +/- 453 U) but not different from that of the nonreperfused group (1736 +/- 562 U). Wall motion abnormality index as well as global ejection fraction evaluated by left ventriculography 1 month after the onset showed that late reperfusion did not preserve the left ventricular wall motion and function. These results indicate that the earlier reperfusion decreased the size of the infarction and preserved left ventricular function, whereas late reperfusion (> 6 hours after onset) did not limit infarct size or preserve left ventricular function. In contrast, the end-diastolic volume index did not differ significantly among the early-reperfused (50 +/- 15 mL/m2), intermediate-reperfused (54 +/- 14 mL/m2), and late-reperfused (53 +/- 19 mL/m2) groups; those were significantly smaller than that of the nonreperfused group (68 +/- 12 mL/m2; P < .05). Left ventriculographic data obtained in both the acute and chronic phase in 39 patients showed that left ventricular volumes increased significantly during the course of myocardial infarction only in the nonreperfused group. CONCLUSIONS: Late reperfusion appeared to prevent ventricular dilatation acute myocardial infarction independent of the limitation of infarct size.

Adult↗
PubMed1993

Microbial hydroxylation of (-)-eburnamonine by Mucor circinelloides and Streptomyces violens.

(6R)-6-Hydroxy-, (6S)-6-hydroxy- and (18S)-18-hydroxyeburnamonines were obtained by microbial conversion of (-)-eburnamonine using Mucor circinelloides and Streptomyces violens. Their structures were determined by analyses of the mass, 1H- and 13C-NMR spectra. (-)-Eburnamonine and the three hydroxylated compounds showed cerebral protecting effects against potassium cyanide intoxication in mice.

Animals↗
PubMed1993

A secondary amyloidosis associated with systemic lupus erythematosus.

Secondary amyloidosis associated with systemic lupus erythematosus has rarely been reported. A 57-year-old female had been diagnosed as having possible systemic lupus erythematosus, although her clinical course was not typical. About one year after the diagnosis, treatment was begun with prednisolone because of progressive renal dysfunction, thrombocytopenia and low serum levels of complements. Recurrent diarrhea and gastrointestinal bleeding soon developed, then amyloidosis was revealed in the stomach and duodenum. Postmortem examination confirmed systemic amyloidosis. We discuss the significance of this rare association of systemic lupus erythematosus and secondary amyloidosis.

Amyloidosis↗
PubMed1993

Chemical modification of erythromycins. IX. Selective methylation at the C-6 hydroxyl group of erythromycin A oxime derivatives and preparation of clarithromycin.

Although erythromycin A contains five hydroxyl groups, regioselective methylation at the C-6 hydroxyl group was achieved to the extent of 90% when a 9-O-substituted erythromycin A 9-oxime was employed as substrate. The methylation and its selectivity are dependent on an O-protecting group at the 9-oxime, solvent, base, and methylating reagent. In particular, the use of a polar aprotic solvent is indispensable for the methylation. Among the 9-oxime derivatives, 2'-O,3'-N-bis(benzyloxycarbonyl)-N-demethylerythromycin A 9-[O-(2-chlorobenzyl)oxime] was the most important intermediate for the synthesis of clarithromycin (6-O-methylerythromycin A).

Clarithromycin↗
PubMed1993

[Effect of rG-CSF on the morphology and function of neutrophils in ovarian cancer chemotherapy].

The combined use of rG-CSF in ovarian cancer chemotherapy prevents a decrease in the number of neutrophils and promotes their recovery. rG-CSF also protects against infections, enhancing chemotherapeutic effectiveness. It is reported that neutrophils produced by rG-CSF not only increase in number but also in function. Some clinicians, however, doubt whether neutrophils mobilized or produced by rG-CSF have sufficient ability to function practically in clinical cases. We therefore examined, by means of flow cytometry, the neutrophils' phagocytosis and bactericidal ability and we found both normal. No morphological abnormalities were seen in these neutrophils. In our observations, moreover, no effect was exerted on the leukocyte-membrane antigen. It was concluded that (a) rG-CSF was very effective in protecting against the diminution of neutrophils by chemotherapy and (b) in promoting their recovery, and (c) also the function, morphology and leukocyte-membrane antigen of these neutrophils were normal.

Adolescent↗
PubMed1993

[A case uterine cervical squamous cell carcinoma successfully treated with preoperative carboplatin-based 5-drug-combined intraarterial infusion chemotherapy].

Preoperative 5-drug-combined intraarterial infusion chemotherapy using carboplatin as a main component was performed in a case of uterine cervical squamous cell carcinoma of Stage IIa. The regimen employed was as follows: carboplatin (100 mg/m2) on Day 4 and 5, vincristine (0.6 mg/m2) on Day 1, peplomycin (5 mg/body) on Day 1, 2, and 3, methotrexate (5 mg/m2) on Day 2 and 3, and doxorubicin (15 mg/m2) on Day 4. These drugs were administered into the right inguinal region through a residual catheter at 3-week intervals prior to operation. After completion of 3 courses, the patient achieved a CR confirmed by pathological analysis and diagnostic imaging followed by extended radical hysterectomy. Side effects observed, especially renal disturbance and myelosuppression, were all tolerable. Intraarterial infusion chemotherapy using carboplatin was thus suggested to be useful against malignant tumors in the gynecological field.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Concomitant intraperitoneal therapy with the antitumor polysaccharide Sizofiran and rG-CSF for ovarian cancer].

The concomitant administration of Sizofiran (a macrophage activator) and rG-CSF (which promotes neutrophil proliferation and activation) caused marked activation of intraperitoneal antitumor immunity. It promoted the induction of IL-2 receptor expression as well as the proliferation and activation of neutrophils, and also caused an increase in LAK and NK activity, which resulted in a clinical antitumor effect. Therefore, this concomitant regimen was found to be useful as maintenance therapy for ovarian cancer.

Drug Administration Schedule↗