Biomedical subjects

T Shimada

Publications and source records attributed to T Shimada.

At least 451 records · Page 25Linked to original sources

PubMed1996

Treatment of aplastic anemia with antithymocyte globulin, cyclosporin A, methylprednisolone, danazol and recombinant human granulocyte-colony stimulating factor.

The main purpose of the present study was to determine the response rate to immunosuppressive therapy combined with recombinant human granulocyte-colony stimulating factor (rhG-CSF) and its efficacy for preventing infections in patients with severe aplastic anemia. The treatments included one course of antithymocyte globulin, cyclosporin A, methylprednisolone, danazole and rhG-CSF. Three patients had very severe aplastic anemia and two had moderate aplastic anemia. One patient relapsed 13 months following the first course of therapy and received a second course. Five patients received six courses of treatment and the response rate at 6 months was 83.3%. All patients achieved an absolute neutrophil count of greater than 1.0 x 10(9)/L within 40 days. All patients with a complete response are transfusion-free and doing well. All five patients are currently alive and have not had any episode of infection for 17-53 months. The results of the study indicate that this therapy may improve the poor prognosis of young patients with severe aplastic anemia. It has a good response rate and induces a rather rapid increase in the neutrophil count, which protects against life-threatening bacterial and fungal infections.

Adolescent↗

PubMed1996

[Rapid detection of the hemolysin genes in Aeromonas sobria by the polymerase chain reaction].

The hemolysin of Aeromonas sobria is one of the important virulence factors in this organism. Rapid detection and identification test for A. sobria is important for early and specific diagnosis of this infectious disease. We evaluated the polymerase chain reaction (PCR) for the rapid detection of A. sobria. Two pairs of synthetic oligonucleotide primers (ASA1-s and a; AerAAS-s and a) were used in PCR technique to detect the different hemolysin genes (ASA1 and aerAAS) in A. sobria. The PCR identified 91% of ASA1-positive and 23.4% of aerAAS-positive strains in beta-hemolytic A. sobria. Other species of Aeromonas, Plesiomonas shigelloides, Vibrio cholerae O1 and V. parahaemolyticus tested were negative in the PCR with two pairs of primers. The PCR technique for detection of two hemolysin genes suggested the possibility of application of this method for detection of A. sobria in A. sobria-associated infections.

Aeromonas↗

PubMed1996

Temporal shifts in traits of Vibrio cholerae strains isolated from hospitalized patients in Calcutta: a 3-year (1993 to 1995) analysis.

This study presents results of a surveillance on cholera conducted with hospitalized patients admitted to the Infectious Diseases Hospital, Calcutta, India, from January 1993 to December 1995. The O139 serogroup of Vibrio cholerae dominated in 1993 but was replaced by O1 as the dominant serogroup in 1994 and 1995. The isolation rate of V. cholerae non-O1 non-O139 did not exceed 4.9% throughout the study period, while the isolation rate of the O139 serogroup in 1994 and 1995 was below 9%. No temporal clustering of any non-O1 non-O139 serogroup was observed. With the exception of 1 strain, none of the 64 strains belonging to the non-O1 non-O139 serogroup hybridized with ctx, zot, and ace gene probes, while 97.3 and 97.7% of the O139 and O1 strains, respectively, hybridized with all the three probes. Multiplex PCR studies revealed that all the O1 strains belonged to the EIT or biotype. There was a progressive increase in the cytotoxic response on CHO and HeLa cells evoked by culture supernatants of strains of V. cholerae non-O1 non-O139 isolated during 1994 and 1995 compared with the response evoked by those isolated in 1993. Dramatic shifts in patterns of resistance to antibiotics between strains of V. cholerae belonging to different serogroups and within strains of a serogroup isolated during different time periods were observed. There was a discernible increase in the incidence of multidrug-resistant strains of V. cholerae O1 isolated in 1994 and 1995 compared with that in 1993. On the basis of the results of this study, we predict the possibility of newer variants of V. cholerae emerging in the future.

Drug Resistance, Multiple↗

PubMed1996

Phage specific for Vibrio cholerae O139 Bengal.

From the stool of a Vibrio cholerae O139 Bengal-infected patient, a phage that specifically lysed capsulated V. cholerae O139 strains only was isolated. The phage is useful for the confirmatory diagnosis of V. cholerae O139 infection and for the differentiation of variants that lack the capsule.

Bacteriophages↗

PubMed1996

Further studies on biochemical characteristics and serologic properties of the genus Aeromonas.

We characterized a collection of 268 Aeromonas isolates from diverse sources (clinical, animal, and environmental sources) for their species and serogroup designations. Overall, 97% of these strains could be identified to the genomospecies level by using an expanded battery of biochemical tests. Members of the Aeromonas hydrophila complex (A. hydrophila, HG2, and A. salmonicida), a group that has previously been difficult to separate biochemically, could easily be distinguished from one another by using a number of recently described phenotypic properties which included utilization of DL-lactate and urocanic acid. Differences in species distributions on the basis of the source of isolation were noted. Serogroup analysis of these 268 isolates plus a number of reference cultures indicated that (i) each genomospecies is serologically heterogeneous and individual serogroups can be found in more than one species, (ii) most type or reference strains for each hybridization group are not serologically representative of the genomospecies at large, (iii) serogroups O:11, O:34, and O:16 predominate clinically (48%), supporting previous studies indicating their importance in human infections, and (iv) most A. trota strains do not express the O139 antigen of Vibrio cholerae. The collective results suggest that both species and serogroup designations are important factors in establishing which isolates can cause human infections when they are acquired from nonclinical sources (foods, animals, and the environment).

Aeromonas↗

PubMed1996

Infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface.

The envelope protein, gp120, of human immunodeficiency virus type 1 (HIV-1) is heavily glycosylated and sialylated. The heavy sialylation greatly affects the physical properties of the protein, as it resolves into a wide acidic pH range despite the basic pI value predicted for its polypeptide backbone (B. S. Stein and E. G. Engleman, J. Biol. Chem. 265:2640-2649, 1990). However, the functional significance of the heavy sialylation remains elusive. Here, we show that desialylation of HIV-1 with neuraminidase greatly augments the initial virus-cell interaction, leading to remarkably enhanced viral replication and cytopathogenicity. This enhancement appeared to be a direct result of the removal of negatively charged sialic acids but not of the exposure of galactose residues or complement activation. Complementing these results, studies with inhibitors of mannosidase I and mannosidase II showed that the processing of HIV-1 oligosaccharides into the complex type to acquire the terminal sialic acid residues impeded the full replication capacity of the virus and that its prevention also enhanced virus replication and cytopathogenicity. Enhancement of infection by desialylation was found widely, with HIV-1 laboratory strains of different cell tropisms and primary isolates as well as HIV-2 and simian immunodeficiency virus. Thus, the sialylation catalyzed by host cell pathways appeared to reduce the infectivity of human and nonhuman primate lentiviruses. Our results further suggested that desialylation would help increase the titers of HIV-based vectors.

1-Deoxynojirimycin↗

PubMed1996

Isolation and characterization of restriction endonuclease in Plesiomonas shigelloides and Aeromonas species.

Five restriction endonucleases (ENases) and one ENase were found in a screen of 196 strains of Plesiomonas shigelloides and 147 strains of Aeromonas species. Plesiomonas and Aeromonas species are classified as Vibrionaceae, identified as food-poisoning bacteria, are closely genetically related to each other, and their ENases producing abilities have not bee reported. ENases were detected at relatively low frequencies in these species as compared to those in other species, such as Salmonella species and Vibrio parahaemolyticus. All Enases were shown to be isoschizomers of already known ENases. One of the Plesiomonas ENases, designated PshBI, recognizing the sequence 5'-AT/TAAT-3' should be useful, since PshBI ENase is produced at a high yield of 7000 units/g of wet cells. The specificities of other ENases are also described in this paper.

Aeromonas↗

PubMed1996

Effects of enalapril on the collagen matrix in cardiomyopathic Syrian hamsters (Bio 14.6 and 53.58).

The hereditary cardiomyopathic strain of Syrian hamster has been extensively studied as a model of cardiomyopathy of heart failure. We attempted to determine whether an angiotensin converting enzyme (ACE) inhibitor, enalapril, prevents the increase in extracellular collagen matrix which connects the myocytes in cardiomyopathy. Enalapril was administered at an average dosage of 10 mg/kg per day to 10- to 20-week-old hamsters with hypertrophic (Bio 14.6) and dilated (Bio 53.58) cardiomyopathy, as well as to control Syrian hamsters (F1 beta). Collagen concentration estimated by hydroxyproline concentration and the collagen type III:I ratio significantly increased in the hearts of the Bio 14.6 and Bio 53.58 strains at 20 and 40 weeks of age as, compared with those in age-matched F1 beta hamsters. When Bio 14.6 hamsters were given enalapril for 10 weeks from 10 to 20 weeks of age, the collagen concentration, the collagen type III:I ratio and type III collagen mRNA expression were significantly decreased, compared with those in untreated animals of the same strain. After the administration of enalapril, scanning electron microscopic examination also revealed a decrease in fibrillar collagen accumulation in the interstitium and the network surrounding the cardiac myocytes. These prophylactic effects were not observed in the Bio 53.58 strain. These results indicate that the administration of ACE inhibitor prevents type III collagen production in the Bio 14.6 strain but not in the Bio 53.58 strain of Syrian hamster.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Involvement of cytochrome P450, glutathione S-transferase, and epoxide hydrolase in the metabolism of aflatoxin B1 and relevance to risk of human liver cancer.

In recent years there has been considerable interest in the effect of variations in activities of xenobiotic-metabolizing enzymes on cancer incidence. This interest has accelerated with the development of methods for analyzing genetic polymorphisms. However, progress in epidemiology has been slow and the contributions of polymorphisms to risks from individual chemicals and mixtures are often controversial. A series of studies is presented to show the complexities encountered with a single chemical, aflatoxin B1 (AFB1). AFB1 is oxidized by human cytochrome P450 enzymes to several products. Only one of these, the 8,9-exo-epoxide, appears to be mutagenic and the others are detoxication products. P450 3A4, which can both activate and detoxicate AFB1, is found in the liver and the small intestine. In the small intestine, the first contact after oral exposure, epoxidation would not lead to liver cancer. The (nonenzymatic) half-life of the epoxide has been determined to be approximately 1 sec at 23 degrees C and neutral pH. Although the half-life is short, AFB1-8,9-exo-epoxide does react with DNA and glutathione S-transferase. Levels of these conjugates have been measured and combined with the rate of hydrolysis in a kinetic model to predict constants for binding of the epoxide with DNA and glutathione S-transferase. A role for epoxide hydrolase in alteration of AFB1 hepatocarcinogenesis has been proposed, although experimental evidence is lacking. Some inhibition of microsome-generated genotoxicity was observed with rat epoxide hydrolase; further information on the extent of contribution of this enzyme to AFB1 metabolism is not yet available.

Aflatoxin B1↗

PubMed1996

Effects of depletion of T cell subpopulations on the course of infection and anti-parasite delayed type hypersensitivity response in mice infected with Babesia microti and Babesia rodhaini.

To elucidate the role of T cell subpopulations in the protective cell-mediated immune response at the initial phase of infection with Babesia microti (BM) and B. rodhaini (BR), the changes in the course of infection and anti-parasite delayed type hypersensitivity (DTH) response after BM or BR inoculation were investigated in Lyt-2+ T cell or L3T4+ T cell-depleted mice. Depletion of Lyt-2+ T cells strongly enhanced the resistance to BM infection, whereas it increased the susceptibility to BR infection. In contrast, depletion of L3T4+ T cells increased susceptibility to BM infection, while it enhanced resistance to BR infection. The anti-parasite DTH response in BM-infected mice was significantly enhanced by depletion of Lyt-2+ T cells, while significantly reduced by depletion of L3T4+ T cells. No effects of depletion of either Lyt-2+ or L3T4+ cells on DTH response was observed in BR-infected mice. From these results, it was suggested that the roles of Lyt-2+ and L3T4+ T cells in the protective cell-mediated immune response at the initial phase of infection were different between BM- and BR-infected mice, resulting in the difference in their course of infection.

Animals↗

PubMed1996

The iothalamate clearance in cats with experimentally induced renal failure.

Plasma iothalamate (IOT) disappearance rates were measured after a single-injection of IOT (113.8 mg/kg, IV) in cats with experimentally induced renal failure. The disappearance rates especially fitted into the one compartment model. The mean value of plasma disappearance rates of IOT in these cats with induced renal failure (2.16 +/- 0.240 x 10(-3) micrograms/ml/min) was markedly lower than that of clinically healthy cats (4.10 +/- 1.00 x 10(-3) micrograms/ml/min). These results demonstrate that IOT clearance is available for evaluation of renal function in cats.

Animals↗

PubMed1996

The production of arthritis in beagles by an immunological reaction to bovine serum albumin.

Arthritis was produced in beagles by the immunological reaction to bovine serum albumin (BSA). Dogs immunized with BSA showed the development of delayed type-hypersensitivity response to BSA and the significant increase in the titer of serum anti-BSA antibodies. The development of arthritis and the increase in a number of nucleated cells in synovial fluid were observed by the injection with BSA into the knee joints of immunized dogs. The synovial membrane of BSA-injected joints revealed a remarkable villous hyperplasia of membrane, and an infiltration of lymphocytes and plasma cells around vessels, resulting in a lymphoid nodule-like formation. The depositions of IgG and C3 on the surface of the synovial membrane were also observed in BSA-injected joints. Histopathological and immunopathological findings indicated that the immune response to BSA in the knee joints could induce a rheumatoid arthritis like chronic synovitis in dogs.

Animals↗

PubMed1996

The intercalated disc of monkey myocardial cells and Purkinje fibers as revealed by scanning electron microscopy.

The intercalated discs of working myocardium and Purkinje fibers of the monkey heart were examined by scanning and transmission electron microscopy. The NaOH/ultrasonication technique resulted in the digestion of connective tissue and a separation of the intercellular junctions of intercalated discs, such that these could be visualized three-dimensionally. The intercalated discs of ventricular myocytes, atrial myocytes and Purkinje fibers vary considerably in number and configuration, as do the intercalated discs of the three different layers of the ventricular myocardium. Myocytes in the subepicardial, middle and subendocardial layers of the ventricle have 1-3, 4-5 and 5-6 intercalated discs at the end of these cells, respectively. Those in the endocardial layer are characterized by the presence of small laterally-placed intercalated discs. Atrial myocytes and Purkinje fibers usually only have 1-2 intercalated discs. Individual intercalated discs in ventricular myocytes have complicated stairs with 10-30 steps and corresponding risers, while those of atrial myocytes and Purkinje fibers have simple stairs with 1-3 steps and risers. Steps equivalent to the plicate segments are characterized by densely-packed microplicae and finger-like microprojections which greatly increase surface area in ventricular myocytes. Microprojections in atrial myocytes and Purkinje fibers are sparse by comparison. Risers equivalent to the interplicate segments containing large gap junctional areas are most numerous in left ventricular myocytes, followed by right ventricular myocytes, Purkinje fibers and atrial myocytes in decreasing order. The geometric arrangement of the various types of myocytes may be related with impulse propagation. Large intercalated discs of cell trunks and series branches may participate in longitudinal propagation, while small laterally-placed ones may be the site of transverse propagation.

Animals↗

PubMed1996

Effects of erythromycin and roxithromycin on oxidation of testosterone and nifedipine catalyzed by CYP3A4 in human liver microsomes.

Roxithromycin and erythromycin were incubated with rat and human liver microsomal or reconstituted cytochrome P450 (P450 or CYP) monooxygenase systems in the presence of an NADPH-generating system, and the effects of these chemicals on testosterone 6 beta-hydroxylation and nifedipine oxidation activities were compared with those of typical CYP3A4 inhibitors including ketoconazole, troleandomycin, and gestodene. Roxithromycin and erythromycin were found to be relatively weak inhibitors of testosterone 6 beta-hydroxylation and nifedipine oxidation activities by rat and human liver microsomes or by reconstituted systems containing CYP3A4/5. Formation of an inhibitory P450-metabolite complex was determined spectrally by incubating troleandomycin with human liver microsomes; the extents of the complex formation were lesser in liver microsomes of humans than those of rats treated with dexamethasone. Erythromycin and roxithromycin were also activated slightly by rat liver microsomes to form P450.Fe(II)-metabolite complex, although these chemicals caused very little or undetectable levels, respectively, of spectral changes by human liver microsomes even when a human sample which contained relatively high levels of CYP3A4 was used. These results suggested that roxithromycin and erythromycin were relatively less potent to inhibit CYP3A4-catalytic activities in human liver microsomes, because of their low capabilities to form P450.Fe(II)-metabolite complex.

Animals↗

PubMed1996

Ethnic-related differences in coumarin 7-hydroxylation activities catalyzed by cytochrome P4502A6 in liver microsomes of Japanese and Caucasian populations.

1. Interethnic differences in cytochrome P4502A6 (CYP2A6) levels and coumarin 7-hydroxylation activities were determined in liver microsomes of 30 Japanese and 30 Caucasians. 2. Although CYP2A6 levels and coumarin 7-hydroxylation activities varied very significantly in the 60 human samples examined, both CYP2A6 levels and coumarin 7hydroxylation activities were found to be higher in Caucasian than Japanese population. 3. Interestingly, eight of the 30 Japanese examined showed very low or undetectable levels of coumarin 7-hydroxylation activities as well as of CYP2A6 in liver microsomes. All of the Caucasians, however, had significant CYP2A6 levels and variable 7-hydroxylation activities. 4. Kinetic analvsis of coumarin 7-hydroxylation activities in liver microsomes of various human samples suggested that although there were 260-fold differences in Vmax's in 10 human samples examined, the Km's were very similar (2.1 + or - 107 mu M); a value consistent with that obtained (1.2 mu M) with purified CYP2A6 in reconstituted system. 5. The results suggest that CYP2A6 is actually involved in the 7-hydroxylation of coumarin in human liver microsomes, and that interethnic differences in coumarin 7-hydroxylation activities in Japanese and Caucasian population may be ascribed to the differences in expression of CYP2A6 protein.

Antibodies↗

PubMed1996

Effects of roxithromycin, erythromycin and troleandomycin on their N-demethylation by rat and human cytochrome P450 enzymes.

1. The effects of treatment of rat with roxithromycin, erythromycin and troleandomycin as well as other chemicals including typical cytochrome P450 inducers were examined in rat and human liver microsomes. 2. Erythromycin and troleandomycin but not roxithromycin caused slight increases in CYP3A1 levels and the N-demethylation of roxithromycin, erythromycin and troleandomycin and oxidation of nifedipine in rat, but none of these chemicals induced significantly CYP2B1 levels or benzphetamine N-demethylation activities. 3. Dexamethasone and pregnenolone 16 alpha-carbonitrile induced CYP3A1 levels and N-demethylation of roxithromycin, erythromycin and troleandomycin but not of benzphetamine, in rat liver microsomes. Treatment of rat with phenobarbital caused increases in both CYP2B1 and 3A1 levels and all of the N-demethylation activities examined. Phenytoin and metyrapone produced increases in contents of 2B1 and activities of benzphetamine N-demethylation as well as of roxithromycin, erythromycin and troleandomycin, although these two inducers did not induce 3A1 protein significantly. 4. In man, a liver sample that was high in CYP3A4 and nifedipine oxidation activity was found to be the most active in N-demethylation activities towards these substrates examined. In addition, recombinant 3A4 catalysed very efficiently the N-demethylation of roxithromycin, erythromycin and troleandomycin in reconstituted monooxygenase systems. 5. These data suggest that erythromycin and troleandomycin, but not roxithromycin, were able to induce CYP3A1 in rat liver microsomes, and that N-demethylation of roxithromycin, erythromycin and troleandomycin were catalysed mainly by 3A1 (and partly by 2B1) in rat and by 3A4 in man.

Animals↗

PubMed1996

New applications of bacterial systems to problems in toxicology.

Bacterial systems have long been of use in toxicology. In addition to providing general models of enzymes and paradigms for biochemistry and molecular biology, they have been adapted to practical genotoxicity assays. More recently, bacteria also have been used in the production of mammalian enzymes of relevance to toxicology. Escherichia coli has been used to express cytochrome P450, NADPH-cytochrome P450 reductase, flavin-containing monooxygenase, glutathione S-transferase, quinone reductase, sulfotransferase, N-acetyltransferase, UDP-glucuronosyl transferase, and epoxide hydrolase enzymes from humans and experimental animals. The expressed enzymes have been utilized in a variety of settings, including coupling with bacterial genotoxicity assays. Another approach has involved expression of mammalian enzymes directly in bacteria for use in genotoxicity systems. Particularly with Salmonella typhimurium. Applications include both the reversion mutagenesis assay and a system using a chimera with an SOS-response indicator and a reporter.

Amino Acid Sequence↗

PubMed1996

[Human gene therapy].

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Acquired Immunodeficiency Syndrome↗