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T Shimada

Publications and source records attributed to T Shimada.

At least 649 records · Page 36Linked to original sources
PubMed1992

Modulation of voltage-dependent Ca channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle.

The effects of arachidonic acid (AA) and other long-chain fatty acids on voltage-dependent Ca channel current (ICa) were investigated, with the whole cell patch clamp method, in longitudinal smooth muscle cells of rabbit ileum. 10-30 microM AA caused a gradual depression of ICa. The inhibitory effect of AA was not prevented by indomethacin (10 microM) (an inhibitor of cyclooxygenase) or nordihydroguaiaretic acid (10 microM) (an inhibitor of lipoxygenase). 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H7; 25-50 microM) or staurosporine (2 microM) (inhibitors of protein kinase C) did not block the AA-induced inhibition of ICa, and application of phorbol ester (a protein kinase C activator) (phorbol-12,13-dibutyrate, 0.2 microM) did not mimic the AA action. Some other cis-unsaturated fatty acids (palmitoleic, linoleic, and oleic acids) were also found to depress ICa, while a trans-unsaturated fatty acid (linolelaidic acid) and saturated fatty acids (capric, lauric, myristic, and palmitic acids) had no inhibitory effects on ICa. Myristic acid consistently increased the amplitude of ICa at negative membrane potentials. The present results suggest the possible role of AA, and perhaps other fatty acids, in the physiological and/or pathological modulation of ICa in smooth muscle.

Animals↗
PubMed1992

Cytochrome P450 2E1 and 2A6 enzymes as major catalysts for metabolic activation of N-nitrosodialkylamines and tobacco-related nitrosamines in human liver microsomes.

An acetyltransferase-overexpressing strain of Salmonella typhimurium (NM2009) has been used to investigate roles of human liver microsomal cytochrome P450 (P450) enzymes in the activation of carcinogenic nitrosamine derivatives, including N-nitrosodialkylamines and tobacco-smoke-related nitrosamines, to genotoxic products. Studies employing correlation of activities with several P450-dependent monooxygenase reactions in different human liver samples, inhibition of microsomal activities by antibodies raised against human P450 enzymes and by specific P450 inhibitors, and reconstitution of activities with purified P450 enzymes suggest that the tobacco-smoke-related nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and N-nitrosonornicotine (NNN) as well as N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) are oxidized to genotoxic products by different P450 enzymes, particularly P450 2E1 and 2A6. The activation of NDMA and NNN by liver microsomes was suggested to be catalyzed more actively by P450 2E1 than by other P450 enzymes because the activities were well correlated with NDMA N-demethylation and aniline p-hydroxylation in different human samples, and purified P450 2E1 had the highest activities in reconstituted monooxygenase systems. The relatively high contribution of P450 2A6 to the activation of NDEA and NNK was supported by the correlation seen with coumarin 7-hydroxylation in human liver microsomes, and antibodies raised against P450 2A6 inhibited both activities by approximately 50%. P450 3A4, 2D6 and 2C enzymes appear not to be extensively involved in the activation of these nitrosamines as judged by several criteria examined. Thus, this work indicates that several P450 enzymes, particularly P450 2E1 and 2A6, catalyze metabolic activation of nitrosamine derivatives including N-nitrosodialkylamines and tobacco-smoke-related nitrosamines in human liver microsomes.

Animals↗
PubMed1992

Contributions of human liver cytochrome P450 enzymes to the N-oxidation of 4,4'-methylene-bis(2-chloroaniline).

4,4'-Methylene-bis(2-chloroaniline) (MOCA) can produce tumors in rodents and dogs and an increased incidence of bladder tumors has been reported in exposed workers. It is therefore of interest to identify the human cytochrome P450 (P450) enzymes involved in MOCA N-oxidation, the primary reaction involved in the formation of an electrophilic product. Human liver microsomes were fractionated and MOCA N-oxidation activity was monitored through the procedure. The most active enzyme fraction corresponded to P450 3A4, as determined by immunochemical assays and N-terminal amino acid sequence analysis. Yeast recombinant P450 3A4 also had MOCA N-oxidation activity. Purified human liver P450 2A6 showed catalytic activity; however, anti-P450 2A6 inhibited less than 20% of the microsomal activity while anti-P450 3A4 inhibited up to 75%. Levels of marker activities of both P450 3A4 (nifedipine oxidation) and P450 2A6 (coumarin 7-hydroxylation) were measured in a set of human liver microsomes and both were correlated with MOCA N-oxidation rates. Gestodene and troleandomycin inhibited up to half of the microsomal MOCA N-hydroxylation activity but 7,8-benzoflavone showed only slight inhibition. Anti-P450 3A4 inhibited (up to 80% of) the microsomal transformation of MOCA to a product genotoxic as judged by bacterial SOS response. The work indicates that P450 3A4 makes a major contribution to human liver microsomal MOCA N-oxidation, and P450 2A6 has a minor role. P450 1A2, which catalyzes the hydroxylation of many arylamines, does not contribute to a great extent.

Benzoflavones↗
PubMed1992

Participation of rat liver cytochrome P450 2E1 in the activation of N-nitrosodimethylamine and N-nitrosodiethylamine to products genotoxic in an acetyltransferase-overexpressing Salmonella typhimurium strain (NM2009).

The possible roles of cytochrome P450 (P450) enzymes in the metabolic activation of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) by rat liver microsomes have been examined in a system containing the bacterial tester strain Salmonella typhimurium NM2009, a newly developed strain showing high O-acetyltransfer activities. The DNA-damaging activity could be determined by measuring expression of the umu gene in a plasmid containing the fused umuC-lacZ gene construct in the bacteria. The following lines of evidence support the view that both NDMA and NDEA are principally oxidized to reactive products by P450 2E1 in rat liver microsomes. First, NDMA and NDEA were activated by rat liver microsomes in a protein- and substrate-dependent manner and the former chemical was more active than the latter; both activities were induced in rats treated with P450 2E1 inducers such as ethanol, acetone and isoniazid and by starvation. Second, activation of NDMA and NDEA were both inhibited significantly by antibodies raised against rat P450 2E1 and by P450 2E1 inhibitors such as diethyldithiocarbamate and 4-methylpyrazole in rat liver microsomes. Finally, in reconstituted monooxygenase systems containing purified rat P450 enzymes, P450 2E1 gave the highest rates of the activation of both NDMA and NDEA; the addition of rabbit cytochrome b5 to the system caused about a 1.5-fold increase in both reactions. In separate experiments we also found that N-nitrosomethylacethoxymethylamine, a compound that reacts with DNA after ester cleavage, is more genotoxic in S.typhimurium NM2009 than in S.typhimurium NM2000, a strain that is defective in O-acetyltransferase activity. Part of the pathway involved in the activation of nitrosamines is suggested to be acetylation of alkyldiazohydroxides formed by P450 or acetylesterase, because the genotoxic activity of N-nitrosomethylacethoxymethylamine in S.typhimurium NM2009 could be inhibited by the O-acetyltransferase inhibitor pentachlorophenol. These results indicate that NDMA and NDEA are oxidized to gentoxoic products by rat liver microsomes and that a P450 2E1 enzyme plays a major role in the activation of these two potent carcinogens. The activation pathway of N-nitrosodialkylamines through acetylation by O-acetyltransferase has been proposed. This simple bacterial system for measuring genotoxicity should facilitate studies on the activation of N-nitroso alkylamines.

Acetyltransferases↗
PubMed1992

Detection and discrimination of Mycoplasma pneumoniae and Mycoplasma genitalium by the in vitro DNA amplification.

By using the primers designed on the bases of the sequences of the 16S rRNA genes of Mycoplasma pneumoniae and Mycoplasma genitalium, respectively, specific and sensitive in vitro DNA amplification assay system for the detection and discrimination of these two mycoplasmas was established. The detection limit of the assay was 100 cells for M. pneumoniae and 1,000 cells for M. genitalium. Neither other human mycoplasmas nor oral bacteria existing in human saliva showed any cross-reactions with these primers.

Base Sequence↗
PubMed1992

Serological cross-reaction between Yersinia enterocolitica O9 and non-O1 Vibrio cholerae bio-serogroup Hakata and antigenic analysis of their relationship by their lipopolysaccharides.

Cross-agglutination and cross-agglutinin absorption experiments were carried out on non-O1 Vibrio cholerae bio-serogroup Hakata (Hakata) and Yersinia enterocolitica O9 (O9). It was shown that the O-antigen of Hakata was closely related to that of O9 in an a, b-a, c type of relationship. The antigenic relationship between the O-antigens of the two bacteria was analyzed by passive hemolysis (PH) and passive hemolysis inhibition (PHI) tests by using their lipopolysaccharides (LPS) as antigen for sensitizing sheep red blood cells (SRBC) and, in the case of the latter, as an inhibitor in a PH system consisting of LPS-coated SRBC, guinea-pig complement and anti-Hakata or O9 antiserum, both unabsorbed and absorbed with the heterologous Hakata or O9 antigen. In the PH experiment, unabsorbed anti-Hakata antiserum had hemolytic titers of 126,100 and 2,600 against Hakata- and O9-LPS-coated SRBC, respectively, and anti-O9 antiserum had hemolytic titers of 19,400 and 38,800, respectively, against these SRBC. The PH experiment showed that anti-O9 antiserum contains a hemolysin reacting with the heterologous Hakata antigen at a high titer (19,400), while anti-Hakata antiserum contains a hemolysin reacting with the heterologous O9 antigen at a significant titer (2,600). The former was completely removed from anti-O9 antiserum with the Hakata antigen and the latter from anti-Hakata antiserum with the O9 antigen. Thus, serological cross-reactivity was demonstrated between the Hakata and O9 strains.

Agglutination↗
PubMed1992

Distribution of split 5.8S ribosomal RNA in Diptera.

Although the 5.8S ribosomal RNA (rRNA) of most eucaryotes consists of 155-170 nucleotides, in two dipterous species the 5.8S rRNA consists of two pieces, 123 and 30 nucleotides in length. The distribution of split 5.8S rRNA was studied in other Diptera and the most closely related order Siphonaptera to learn the origin of split 5.8S rRNA. Four species of mosquitoes, Culex tritaeniorhynchus, Culex pipiens molestus, Aedes albopictus, Anopheles sp. (Culicidae) had a single 5.8S rRNA consisting of approximately 154 nucleotides. A flea Ctenocephalides felis (Siphonaptera: Pulicidae) also had a single RNA of approximately 158 nucleotides. A crane fly (Tipulidae). a midge Orthocladius akamusi (Chironomidae), a robber fly (Asilidae), and a house fly Musca domestica (Muscidae), on the other hand, had divided 5.8S rRNA as did a fruit fly Drosophila melanogaster (Drosophilidae) and a dark-winged fungus gnat Sciara coprophila (Sciaridae). Three hypotheses are proposed on the relationship between the evolution of the 5.8S rRNA and the phylogeny of Diptera.

Animals↗
PubMed1992

[Enteropathogenicity and enteropathogenic toxin production of Vibrio mimicus].

Enteropathogenicity and enteroreactive-toxins were examined in 66 strains of Vibrio mimicus and the following results were obtained. Frequencies of enteropathogenic strains judged by the result of suckling mouse tests were 11/13 (85%) for clinical isolates and 37/53 (70%) for fish or environmental isolates. Frequencies of preservation of cholera toxin gene and NAG-ST gene were 2 and 15%, respectively, for 48 enteropathogenic strains, and 0 and 6%, respectively, for 18 non-enteropathogenic strains. Frequencies of production of NAG-rTDH, FAF and hemolysin were 4, 63 and 100%, respectively, for 48 enteropathogenic strains, and 6, 50, and 100%, respectively, for 18 non-enteropathogenic strains. No correlation between serovar and enteropathogenicity was observed in the suckling mouse test. Six out of 12 enteropathogenic strains produced hemolysin in ligated rabbit ileal loop, while 1 out of 12 non-enteropathogenic strains did so under the same condition. A significant inhibition of fluid accumulation in the ligated rabbit ileal loop test with viable cells was noted in rabbits immunized with hemolysin of non-O1 V. cholerae. These results suggest that approximately two-thirds of environmental isolates are enteropathogenic and that hemolysin is the most important toxin in the enteropathogenic mechanism of V. mimicus strains.

Animals↗
PubMed1992

[O serogroup and virulence factors of motile Aeromonas].

A total of 182 isolates of motile Aeromonas from patients with diarrhea and environmental sources was investigated for hemolytic activity to rabbit erythrocyte and cytotoxicity to HeLa 229 cell. Furthermore, the relation between O serogroup and virulence factors, which were lethal to mouse and autoagglutination, were investigated. There were many strains possessing both the hemolytic and cytotoxic activities in A. hydrophila from overseas traveller's diarrhea, suggesting that these activities were associated with intestinal pathogenecity. Although there was a clear correlation between hemolytic and cytotoxic activities in A. hydrophila from overseas traveller's diarrhea, the correlation was not found in A. hydrophila from domestic cases of diarrhea and A. sobria from overseas traveller's diarrhea. Especially, some A. hydrophila isolates from domestic case of diarrhea produced only hemolysin. These results indicated that there was a difference in specificity between the toxins accounted for hemolytic and cytotoxic activities, and more than two different toxins were developed. O serogroups 11, 34, 14, 16, and 35 in that order were the most frequent serogroups. About half of O11 and O34 strains possessed lethal activity to mouse. Autoagglutination phenomenon did not seem to be associated with the lethal activity. In O11 strains, high cytotoxic titer was more frequently found in lethal activity positive-strains than in the activity negative-strains, suggesting that cytotoxicity contributed preferentially to lethal activity to mouse. But such a correlation was not found in O34 strains, so other virulence factors than hemolysin and cytotoxin may be associated with the lethal activity.

Aeromonas↗
PubMed1992

Reassessment of the prevalence of heat-stable enterotoxin (NAG-ST) among environmental Vibrio cholerae non-O1 strains isolated from Calcutta, India, by using a NAG-ST DNA probe.

A collection of 521 environmental isolates of Vibrio cholerae which were previously examined by the suckling mouse assay and found to be negative for the heat-stable enterotoxin NAG-ST were reassessed by a recently developed DNA probe for NAG-ST. A total of 12 (2.3%) of the isolates hybridized with the NAG-ST probe. By using a cholera toxin (CT) DNA probe, the CT gene was detected in six of the strains in the collection, although none of the isolates of V. cholerae non-O1 hybridized with both of the toxin probes. All of the NAG-ST and CT probe-positive strains were hemolysin positive. Thirty-fold-concentrated supernatants of the three representative NAG-ST DNA probe-positive V. cholerae non-O1 strains gave positive fluid accumulation ratios in the suckling mouse assay even after heating (100 degrees C for 5 min) and also inhibited the binding of a NAG-ST monoclonal antibody to the bound NAG-ST in a competitive enzyme-linked immunosorbent assay (ELISA). Likewise, all six CT probe-positive V. cholerae non-O1 strains produced in vitro CT when examined by the CT bead ELISA. HindIII digest patterns of chromosomal DNA from the representative NAG-ST gene-positive strains were visually indistinguishable. Between the groups of NAG-ST probe-positive strains examined, there was a variation in the hybridizable fragments, with one group of strains exhibiting a hybridizable fragment similar to that of the NRT 36 reference strain; a smaller HindIII fragment hybridized with the NAG-ST probe in the other group of strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A block in full-length transcript maturation in cells nonpermissive for B19 parvovirus.

Vertebrate parvoviruses share a similar genomic organization, with the capsid proteins encoded by genes on the right side and nonstructural proteins encoded by genes on the left side. The temporal and cell-specific appearances of these two types of gene products are regulated by a variety of genetic mechanisms. Rodent parvovirus structural proteins, for example, are encoded by a separate promoter which is positively regulated by nonstructural-gene products. In contrast, for the human B19 parvovirus, the analogous structural-gene promoter is nonfunctional, and both left- and right-side transcripts originate from a single promoter and are highly processed. Using a combination of sensitive RNA analyses of wild-type and mutant templates, we have found that the relative abundance of these alternatively processed transcripts appears to be governed by unique postinitiation events. In permissive cells, the steady-state level of right-side structural-gene transcripts predominates over that of left-side nonstructural-gene transcripts. In nonpermissive cells transfected with the B19 virus genome, nonstructural-gene transcripts predominate. Removal of 3' processing signals located in the middle of the viral genome increases transcription of the far right side. Disruption of a polyadenylation signal in this region makes readthrough of full-length right-side transcripts possible. These results suggest that the abundance of B19 virus RNAs is determined by active 3' processing and is coupled to DNA template replication.

Animals↗
PubMed1992

A case report of Moyamoya disease: successfully treated with Chinese medicine.

The incidence of Willis' ring obstruction (Moyamoya disease) in Japan is higher than in Europe and North America. The therapeutic technique usually employed is either surgery or Western drug treatment. But these methods are still not satisfactory. We attempted to apply Chinese medicinal treatment to a patient with Moyamoya disease. This patient was referred to our department because of the ineffectiveness of Western drug treatment. The patient made satisfactory progress with Gui-Zhi-Fu-Ling-Wan and Xiao-Xu-Ming-Tang. We also noticed the improvement of the "stagnated blood condition." Whole blood viscosity was decreased and the blood flow rate in the bulbar conjunctiva was increased.

Blood Viscosity↗
PubMed1992

Influences of ciclosporin pretherapy on 90% hepatectomized rats.

We studied the effect of ciclosporin (Cs) on rats which underwent a 90% hepatectomy. Rats were divided into two groups: group 1 (without Cs pretreatment) and group 2 (with Cs pretreatment). Animals were given a 4-day treatment of Cs (10 mg/kg/day) prior to hepatectomy. The 1-week survival, serum biochemistry and parameters for hepatocyte proliferation (indices for mitosis and 5-bromo-2-deoxyuridine uptake) were serially investigated. Although Cs pretherapy significantly upregulated liver cell proliferation in group 2, there was no improvement in the survival rate of the immunosuppressed animals (group 2) compared to the controls (group 1). The implications of Cs pretherapy are discussed in the setting of extensive hepatectomy.

Animals↗
PubMed1992

Attenuation of dysfunction in the ischemia-reperfused liver by glycyrrhizin.

The present study evaluated the effect of glycyrrhizin (GR) on an injury of the liver caused by ischemia-reperfusion in rats. In the liver ischemia-reperfusion model, levels of serum GOT, GPT and LDH activities and lipid peroxides in the liver tissue were significantly increased. On the contrary, total glutathione content in the liver tissue and NADPH cytochrome P-450 reductase activity of liver microsomes were decreased. Pretreatment with GR 20 mg/kg, i.v. 10 min before induction of ischemia resulted in significant decreases in serum GOT, GPT, LDH activities and the lipid peroxide level and a higher tissue glutathione content during the period of reperfusion. Electron microscopic studies revealed various hepatocellular damages with an almost intact sinusoidal endothelium in ischemia-reperfused livers. However, the degree of damage was less severe in the livers from the rats pretreated with 20 mg/kg GR. The results indicate that GR is able to provide partial protection against ischemia-reperfused damage.

Animals↗
PubMed1992

Elucidation of catalytic specificities of human cytochrome P450 and glutathione S-transferase enzymes and relevance to molecular epidemiology.

A number of different approaches have been used to determine the catalytic selectivity of individual human enzymes toward procarcinogens. Studies with cytochrome P450 (P450) enzymes and glutathione S-transferases are summarized here, and recent work with pyrrolizidine alkaloids, aflatoxins, 4,4'-methylenebis(2-chloroaniline), and ethyl carbamate is discussed. In some cases a single enzyme can catalyze both activation and detoxication reactions of a chemical. The purification and characterization of human lung P4501A1 and the development of a noninvasive assay for human P4502E1 are also described.

Aflatoxin B1↗
PubMed1992

Changes of splenic lymphocyte subpopulation in mice inoculated with Babesia microti and Babesia rodhaini.

Changes of splenic lymphocyte subpopulation after Babesia microti and Babesia rodhaini inoculation in mice were examined by flow cytometric analysis. The B. microti inoculated mice showed a longer period of time from inoculation to the onset of increase or decrease parasitaemia (%), packed cell volume, total spleen cell numbers and surface immunoglobulin positive splenic cell numbers than respective periods in B. rodhaini inoculated mice. The Thy-1 positive cell numbers in B. microti inoculated mice and B. rodhaini inoculated mice pre-immunized with homologous parasites were significantly higher than that of B. rodhaini inoculated mice. The ratio of L3T4 positive cell/Lyt-2 positive cell after inoculation with B. microti was quite similar to that in B. rodhaini mice pre-immunized. However, the ratio in B. rodhaini inoculated mice revealed a lack of an increasing phase. These results suggested that the T-cell dependent early immune response, especially suppressor activity, was closely related to the difference in the course of infection between the non-lethal B. microti and the lethal B. rodhaini infection in mice.

Animals↗
PubMed1992

A case of primary hyperparathyroidism due to an oxyphil cell adenoma.

A 59-year-old woman with primary hyperparathyroidism was found to have a parathyroid adenoma behind the left clavicle. Preoperatively, it appeared as a hypoechoic mass on ultrasonography, as a hot nodule on thallium scintigraphy, and as a high signal on T2-weighted magnetic resonance imaging. Histological, immunohistochemical and ultrastructural studies of the surgically resected tumor revealed a parathyroid adenoma composed mainly of oxyphil cells with production of a parathyroid hormone. Moreover, a multilocular lesion of lymphangiectasia was contained. Hypercalcemia was alleviated postoperatively. These observations corroborated a functioning parathyroid oxyphil cell adenoma. This is the first case report of functioning oxyphil cell adenoma of the parathyroid gland with lymphangiectasia in Japan.

Adenoma↗