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Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 415 records · Page 23Linked to original sources
PubMed1994

Intravenous extended infusion of recombinant human soluble thrombomodulin prevented tissue factor-induced disseminated intravascular coagulation in rats.

This study demonstrated that intravenous infusion of recombinant human soluble thrombomodulin (rhs-TM) could inhibit disseminated intravascular coagulation (DIC) caused by 4 hr infusion of tissue factor (TF) in rats. Extended infusion of TF reduced fibrinogen and platelet counts and elevated serum FDP level. Pretreatment and coinfusion of rhs-TM could block changes of these DIC-parameters without prolongation of APTT. Heparin, which is a potent anti-DIC drug, could also inhibit these changes with extra prolongation of APTT and PT. Thus, these results suggest thrombomodulin prevent DIC less bleeding tendency than heparin.

Animals↗
PubMed1994

Antithrombotic effects of recombinant human soluble thrombomodulin (rhs-TM) on arteriovenous shunt thrombosis in rats.

We examined the antithrombotic effect of recombinant human soluble thrombomodulin (rhs-TM) using an arteriovenous shunt thrombosis model and its influence on hemostasis in rats. Intravenous administration of rhs-TM (0.5-4 mg/kg) significantly inhibited thrombus formation and prolonged ex vivo activated partial thromboplastin time (APTT) in a dose-dependent manner. Thrombus formation was inhibited to the same extent in animals treated with heparin (25-200 U/kg) and in those treated with rhs-TM (0.5-4 mg/kg), but heparin had a much stronger effect on prolonging APTT. In the hemorrhagic study using the rat template bleeding time method, rhs-TM exhibited the prolongation of the bleeding time only at the highest effective dose (rhs-TM; 4 mg/kg) of the thrombosis experiments. Thus, rhs-TM exhibits the inhibitory effect on thrombus formation with less APTT prolongation in comparison with heparin and without significant pertubation of hemostasis.

Animals↗
PubMed1994

Increased Fas antigen expression in murine retrovirus-induced immunodeficiency syndrome, MAIDS.

The Fas antigen (Fas), which is a cell surface protein belonging to the tumor necrosis factor receptor family, mediates apoptosis. To assess the contribution of Fas to the pathogenesis of retrovirus-induced immunodeficiency, we examined the kinetics of Fas expression on the lymphocytes during the course of murine acquired immunodeficiency syndrome (MAIDS) induced by a defective LP-BM5 murine leukemia virus. The Fas-positive cells were increased in proportion both in alpha beta T cells and B cells with the progression of MAIDS. The appearance of Fas-positive cells in alpha beta T cells preceded those in B cells during the course of MAIDS. Among alpha beta T cells, about half of the Thy1.2+ alpha beta T cells were positive for Fas, while almost all of Thy1.2- CD4+ alpha beta T cells were of the Fas-positive phenotype. The Fas-positive cells in MAIDS mice, especially unique Thy1.2-CD4+ alpha beta T cells, were easily rendered apoptotic by stimulation via Fas, indicating that Fas expressed on the lymphocytes is functional. Furthermore, concomitant infection with Mycobacterium avium in MAIDS mice caused a marked increase in Fas-positive cells accompanied by a severely impaired T cell reactivity to polyclonal stimuli. Taken together, these results suggest that possible participation of the Fas system in the pathogenesis of retrovirus-induced immunodeficiency.

Animals↗
PubMed1994

Phylogenetic relationships among vertebrate visual pigments.

Genomic DNA fragments in exon 4 of chicken, goldfish and salmon visual pigments were amplified by polymerase chain reaction, using oligonucleotide mixtures as primers, and hypothetical phylogenetic trees were drawn up from the deduced amino acid sequences. The results suggest that vertebrate visual pigments have evolved along at least five lines, and that these lines diverged from an ancestral gene before the bony fishes diverged from the rest of the higher vertebrates.

Amino Acid Sequence↗
PubMed1994

Panic attacks and panic disorder in Japanese non-patient population: epidemiology and psychosocial correlates.

To investigate the prevalence rates of panic disorder and panic attacks in the general population of Japan, a set of questionnaires were administered to 207 people aged 18 or over, who were then interviewed. Seven (3.4%) had experienced one or more unexpected panic attacks in their lifetime. Two subjects (1.0%) had had panic disorder (DSM-III-R), and five (2.4%) had had panic attacks not meeting the criteria for panic disorder. Seventy percent of the persons with panic disorder or panic attacks had sought medical care. There was comorbidity with agoraphobia in two cases, and with major depression in five. Harsh discipline, frequent quarrel, between parents, and serious illness before the age of 16 were more frequent in individuals suffering from panic attacks, compared to those without.

Adolescent↗
PubMed1994

Phototoxicity and photoallergenicity of quinolones in guinea pigs.

Clinical reports indicate that the fluoroquinolone group of antibiotics can induce cutaneous photosensitivity reactions. In the present study, phototoxicity and photoallergenicity of quinolones including nalidixic acid (NA) norfloxacin (NFLX), ofloxacin (OFLX), enoxacin (ENX), ciprofloxacin (CPFX), lomefloxacin (LFLX), and tosufloxacin (TFLX) were experimentally examined in an in vivo system using the guinea pig. Phototoxicity of all quinolones tested was demonstrated after a single, oral administration of the drugs and subsequent exposure to long-wave ultraviolet (UVA) at a dose of 30 J/cm2. The phototoxic potencies were: ENX, LFLX > OFLX > NA, TFLX > NFLX, CPFX. Photoallergic reaction was also induced to LFLX and NA by pretreatment with cyclophosphamide, an immunoadjuvant. No cross-reactions in photoallergy were observed among quinolones. The photo-ingestion test was positive in photoallergically sensitized animals, while the photopatch test was negative. This is the first report which demonstrated experimentally the photoallergenicity of quinolones. Clinical features of the photosensitivity due to quinolones can be explained by the results of the present experiments.

4-Quinolones↗
PubMed1994

A comparison study of IFN-gamma, ADA, and CA125 as the diagnostic parameters in tuberculous pleuritis.

Adenosine deaminase in pleural fluid (pADA), CA125 in serum (sCA125), and IFN-gamma in pleural fluid (pIFN-gamma) were measured in patients with pleurisy of various causes to evaluate their diagnostic utility in tuberculous pleuritis (TBP). We studied 39 pleural fluid samples, including 11 TBP and 28 non-TBP. With both pADA and sCA125, although the median values were much higher in TBP than in non-TBP groups, there was considerable overlap between the two groups. The sensitivity, specificity, and diagnostic efficiency were 81.8%, 89.3%, and 87.2%, respectively, when pADA values of more than 45 U ml-1 were considered, and they were 100%, 75.0%, and 84.2%, respectively, when sCA125 values of more than 35 U ml-1 were considered. In contrast, pIFN-gamma values were significantly higher in TBP patients (5.8 +/- 3.0 IU ml-1; mean +/- S.D.) than those in non-TBP patients (< 0.3 IU ml-1), leading to both a sensitivity and a specificity of 100%.

Adenosine Deaminase↗
PubMed1994

Clinical application of microplate DNA-DNA hybridization procedure for rapid diagnosis of mycobacterial infections.

SETTING: As an alternative to biochemical analysis, microplate DNA-DNA hybridization was applied for rapid diagnosis of mycobacterial infection. OBJECTIVE: To assess how rapidly and correctly the microplate hybridization method can progress from clinical sample to final species identification of mycobacteria. DESIGN: Clinical samples (pooled sputa or bronchial lavage fluid) were obtained from patients. Depending on the estimated bacterial amounts, genetic identification was performed either directly or following primary culture. Extracted DNA labeled by photobiotin was hybridized in microdilution wells with type-strain DNAs from 4 species (Mycobacterium tuberculosis, M. avium, M. intracellulare, and M. kansasii), the identified on the basis of genetic relatedness, which was quantitated by colorimetric detection. RESULTS: With samples containing more than 10(8) colony-forming units [CFU] (5 cases), species identification was successfully performed on the day of sample preparation. With samples of not more than 10(7) CFU (14 cases), although 4-21 days' primary culture were necessary, species were also correctly identified by the microplate method. Furthermore, M. avium and M. intracellulare were distinctly identified. All the results precisely corresponded to those of biochemical analysis, which took 4-12 weeks to complete identification. CONCLUSION: We consider that microplate DNA-DNA hybridization is a dependable technique for rapid diagnosis of mycobacterial infection.

Bacterial Typing Techniques↗
PubMed1994

Sudden infant death syndrome in infants of cocaine using mothers.

A study of Sudden Infant Death Syndrome (SIDS) with maternal cocaine exposure was undertaken using the perinatal medical records at the University of Miami/Jackson Memorial Medical Center and case files of the Metropolitan Dade County Medical Examiner Department, Miami, Florida USA from 1988-1992. 78 SIDS cases were analysed. 18 infants were classified as cocaine-exposed SIDS infants with positive history of maternal cocaine abuse and/or positive urine toxicology; 50 infants were classified as cocaine-negative SIDS infants without the history and with negative toxicology. The incidence of SIDS among cocaine-exposed infants was estimated to be higher than that of cocaine-negative infants overall (p < 0.025), but statistical significance between the groups was not confirmed when controlled for ethnicity. No significant differences of birth weight, estimated gestational age, body and brain weights were observed at autopsy between the two groups. Cocaine-exposed SIDS cases included 6 infants born small for gestational age (p < 0.05). 10 of 18 cocaine-exposed SIDS infants had a positive result for urine toxicology at birth and died younger aged than cocaine-negative infants (p < 0.05). Toxicology tests of the specimens obtained from cadavers were all negative for cocaine metabolites.

Journal Article↗
PubMed1994

Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA.

Holocarboxylase synthetase (HCS) plays an essential role in biotin utilization in eukaryotic cells and its deficiency causes biotin-responsive multiple carboxylase deficiency in humans. We have cloned the human HCS cDNA and show that antiserum against the recombinant protein immunoprecipitates human HCS. A one base deletion resulting in a premature termination and a missense mutation (Leu to Pro) were found in cells from siblings with HCS deficiency. Human HCS shows homology to BirA, which acts as both a biotin-[acetyl-CoA-carboxylase] ligase and a biotin repressor in E. coli, suggesting a functional relationship between the two proteins. The human HCS gene maps to chromosome 21q22.1.

Amino Acid Sequence↗
PubMed1994

Polyamino acids that inhibit the interaction of yeast translational elongation factor-3 (EF-3) with ribosomes.

EF-3 is a translational elongation factor specific to yeasts and fungi. Its carboxy-terminal region contains three lysine-clusters and is very basic. The region has been reported to be responsible for the interaction with ribosomes [Ishiyama, A., Ogawa, K., & Miyazaki, M. (1992) in Abstracts of the 15th Annual Meeting of the Molecular Biology Society of Japan, p.190]. To find specific inhibitors for the interaction of EF-3 with ribosomes, the effects of two basic polyamino acids, poly-L-(Lys) and poly-L-(Arg), and two acidic polyamino acids, poly-L-(Asp) and poly-L-(Glu), were examined using two assay systems for ATPase of EF-3. One was for the ribosome-activated ATPase and the other for the intrinsic (ribosome-independent) ATPase of EF-3. Basic polyamino acids were expected to act as analogues of the carboxy-terminal region of EF-3, and acidic ones to interact with EF-3. The basic polyamino acids inhibited the ribosome-activated ATPase, but they also inhibited the intrinsic one more effectively. Acidic polyamino acids, poly-L-(Asp) and poly-L-(Glu), inhibited the ribosome-activated ATPase but not the intrinsic one. Thus, acidic polyamino acids could be specific inhibitors of the interaction between EF-3 and ribosomes. Furthermore, a system for detecting the binding of EF-3 to ribosomes was constructed. That is, ribosome-bound EF-3 was detected by measuring the ATPase on precipitated ribosomes after a mixture of EF-3 and ribosomes had been ultracentrifuged. Using this system, poly-L-(Asp) was shown to inhibit the binding of EF-3 to ribosomes directly.

Adenosine Triphosphatases↗
PubMed1994

A novel peptide probe for studying the transbilayer movement of phosphatidylethanolamine.

Ro09-0198 is a cyclic peptide isolated from Streptoverticillium griseoverticillatum which recognizes strictly the structure of phosphatidylethanolamine (PE) and forms an equimolar complex with the phospholipid on biological membranes. To use the peptide as a probe for analyzing the transbilayer movement of PE, we labeled the amino-terminal amino acid of the peptide with biotin without changing either the reactivity or specificity of the peptide. The amount of the peptide bound to the membrane was measured by enzyme linked immunosorbent assay (ELISA) after extraction of the peptide from the membrane. The peptide showed a strict temperature-dependent binding to human erythrocytes and the binding increased with increasing temperature. Since the peptide bound to PE in a temperature-independent manner and the binding to membrane PE is not affected by membrane proteins, the present temperature-dependent binding of the peptide to the cell membranes was likely to reflect temperature-dependent translocation of PE. The binding of the peptide to erythrocytes differed greatly among animal species. The peptide also showed temperature-dependent binding to a human histocytic lymphoma cell line, U937, suggesting that the peptide will provide a novel and convenient probe for analyzing the transbilayer movement of PE in eukaryotic cells.

Animals↗
PubMed1994

Clinical experience of lower urinary tract reconstruction using a urethral Kock pouch.

The operative procedure used in the present series involved a nerve-sparing radical cystectomy, with anastomosis of the urethra using a pouch made of detubularized ileum. The 36 patients who underwent this operation were all male with an average age of 58. No deaths resulted from the operation. As far as late complications were concerned, malfunction of the antireflux nipple valve was noted in 1 patient and stenosis occurred between the urethra and pouch in 2. One patient was found to have multiple stones in the pouch and reservoir decompensation was recognized in 2. Thus, the late complication rate was 17%. There were no cases of total incontinence, but nocturnal incontinence appeared in 11 out of 31 (35%). A total of 20 out of 25 patients (80%) recovered their erectile function during the postoperative follow-up period and the disease-free survival rate at 5 years was 78%. Therefore, the urethral Kock pouch combined with nerve-sparing cystectomy has proved to be a useful procedure as far as the quality of life is concerned.

Adult↗
PubMed1994

Synthesis and structure-activity relationships of a novel antifungal agent, azoxybacilin.

A new antifungal substance, azoxybacilin (an unusual amino acid with an azoxy moiety) and its derivatives have been synthesized from Boc-L-Asp-OtBu utilizing the Moss procedure for the preparation of the azoxy moiety. The ester derivative, Ro 09-1824, showed more potent antifungal activity and a broader antifungal spectrum than azoxybacilin did.

Aminobutyrates↗
PubMed1994

A new methionine antagonist that has antifungal activity: mode of action.

A new antifungal, azoxybacilin (an unusual amino acid with an azoxy moiety) was identified from Bacillus cereus, and its in vitro antifungal activity and mode of action were investigated. Azoxybacilin was active against a broad spectrum of fungi. It was especially active against mycelial fungi, such as Aspergillus, and did not show antibacterial activity. No cross-resistance with antifungals currently on the market was observed. The IC50 values of azoxybacilin antifungal activity against Saccharomyces cerevisiae were significantly greater when amino acids containing sulfur were added to the growth medium, whereas other amino acids were not effective at all. We, therefore, tested the effect of the intermediates involved in the synthetic pathway of these amino acids. The activity markedly diminished when one of the following four intermediates was present in the medium:homocysteine, cysteine, cystathionine or methionine. These four intermediates were the same as those required for the growth of the O-acetylhomoserine sulfhydrylase mutant, S. cerevisiae ONO726, indicating that azoxybacilin would inhibit a step or steps in the sulfur-fixation pathway.

Amino Acids↗
PubMed1994

Monte Carlo simulation of DNA strand breaks induced by monoenergetic electrons using higher-order structure models of DNA.

A new theoretical model for estimating yield of initial DNA strand break induced by several monoenergetic electrons is presented. It is based on the Monte Carlo track structure simulation and on new DNA structure models (one turn of double-strand DNA, nucleosome, solenoid), and links physical and chemical stages of radiation action. Direct and indirect effects are strictly distinguished. Some results of calculations indicated: (1) the number of single strand breaks per nucleus (6 microns in diameter) per Gy in pure water was about 10 times that in a cell environment (OH radical life time is assumed to be 8.7 ns). This is due to the difference in the time-dependent variation in the total number of the OH radical; and (2) the contribution of indirect effects to total damage decreased as the order of the DNA target model structure used in the stimulation increased (e.g. a one-turn model of double-strand DNA, approximately 98.4%; but the 30-nm solenoid model, approximately 86.1%). This was due to the protective effect of histone protein against OH radical attack. Double-strand breaks were scored if two single-strand breaks were located on the same base pair. The present study indicated that the information from morphological and biochemical examinations of the cell environment must be considered more carefully with computer simulation.

Computer Graphics↗