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Biomedical subjects

S Shigeta

Publications and source records attributed to S Shigeta.

At least 163 records · Page 9Linked to original sources
PubMed1993

Differences in response of patient's blood cells with bronchial asthma to diverse house dust mite allergens by histamine release assay.

A HPLC method was developed for the determination of histamine released from washed blood cells of allergic patients after exposure to allergens in the presence or absence of plasma. The blood cells used were preserved in a vital state at 4 degrees C during at least 6 hours after blood-collecting. The responses of blood cells to an appropriately diluted series of a mite feces extract (Dff) solution were evaluated in three patient's groups (68 cases of hyposensitized, 59 cases of newly visited and 44 cases of the others) with bronchial asthma. Washed blood cells from the hyposensitized groups had a tendency to release histamine easily even with lower concentration of the Dff solution. Both the sensitivities of washed blood cells to Dff or mite body extract (Dfb) and the responses of the cells to diverse antigens in neither extract differed largely in individual cases. The titer of blocking antibody could be expressed as the amount proportional to the concentration of Dff or Dfb.

Allergens↗
PubMed1992

Synthesis and antiviral activity of deoxy analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.

The effect of substitution in the acyclic structure of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) on anti-HIV-1 activity was investigated by synthesizing a series of deoxy analogs and related compounds. Preparation of 1-[(2-alkyloxyethoxy)methyl]-6- (phenylthio)thymine (2-4) derivatives was carried out based on alkylation of HEPT with primary alkyl halides. Preparation of the 1-[(alkyloxy)methyl]-6-(phenylthio)thymine (26-31) and 1-[(alkyloxy)methyl]-6-(arylthio)-2-thiouracil (32-45) derivatives was carried out on the basis of LDA lithiation of 1-[(alkyloxy)-methyl]thymine (9-14) and 1-[(alkyloxy)methyl]-2-thiouracil (15-25) followed by reaction with diaryl disulfides. The oxidative hydrolysis of the 2-thiouracil derivatives gave 1-[(alkyloxy)methyl]-6-(arylthio)uracil derivatives (46-57). 1-Alkyl-6-(phenylthio)thymine (59-61) derivatives were prepared on the basis of alkylation of 6-(phenylthio)thymine (58). Methylation of the hydroxyl group of HEPT did not affect the anti-HIV-1 activity of HEPT. Substitution of the 1-(2-hydroxyethoxy)methyl group by ethyl, butyl, methoxymethyl, (propyloxy)methyl, and (butyloxy)-methyl groups somewhat improved the original anti-HIV-1 activity of HEPT. Substitution with ethoxymethyl and (benzyloxy)methyl groups further potentiated the activity [EC50: 1-(ethoxy-methyl)-6-(phenylthio)thymine (27), 0.33 microM; 1-[(benzyloxy)methyl]-6-(phenylthio)thymine (31), 0.088 microM]. When the 5-methyl group of 27 and 31 was replaced by an ethyl or an isopropyl group, the anti-HIV-1 activity was improved remarkably [EC50: 5-ethyl-1-(ethoxymethyl)-6-(phenylthio)-uracil (46), 0.019 microM; 5-ethyl-1-[(benzyloxy)methyl]-6-(phenylthio)uracil (52), 0.0059 microM; 5-isopropyl-1-(ethoxymethyl)-6-(phenylthio)uracil (55), 0.012 microM; 5-isopropyl-1-[(benzyloxy)methyl]-6-(phenylthio)uracil (56), 0.0027 microM]. Introduction of two m-methyl groups into the phenylthio ring also potentiated the activity.

Antiviral Agents↗
PubMed1992

Structure-activity relationships of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine analogues: effect of substitutions at the C-6 phenyl ring and at the C-5 position on anti-HIV-1 activity.

The effect of substitution on the pyrimidine moiety of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiothymine (HEPT-S) on anti-HIV-1 activity was investigated by synthesizing a series of 5-methyl-6-(arylthio) and 5-substituted-6-(phenylthio) derivatives. Preparation of the 5-methyl-6-(arylthio) derivatives was carried out based on either LDA lithiation of 1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]thymine (3) and 1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]-2-thiothymine (4) followed by reaction with diaryl disulfides or an addition-elimination reaction of 1-[[2-(tert-butyldimethylsiloxy)ethoxy]-methyl]-6- (phenylsulfinyl)thymine (31) with aromatic thiols. Preparation of the 5-substituted-6-(phenylthio) derivatives was carried out based on either C-5 lithiation of the 1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]-6-(phenylthio)uraci l (41) with LTMP or the LDA lithiation of 5-alkyl-1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]-2-thiouraci l derivatives 45-47. Substitution at the meta position of the C-6-(phenylthio) ring by the methyl group improved the original anti-HIV-1 activity of HEPT, and introduction of two m-methyl groups to the phenylthio ring further potentiated the activity [EC50: 6-[(3,5-dimethylphenyl)thio]-1-[(2-hydroxyethoxy)methyl]thymine (28), 0.26 microM; 6-[(3,5-dimethylphenyl)thio]-1-[(2-hydroxyethoxy)methyl]-2-thiothymin e (30), 0.22 microM]. When the 5-methyl group was replaced by an ethyl or an isopropyl group, the anti-HIV-1 activity of HEPT was also improved remarkably [EC50: 5-ethyl-1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiouracil (48), 0.11 microM; 5-isopropyl-1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)-2-thiouracil (50), 0.059 microM; 5-ethyl-1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiouracil (54), 0.12 microM; 5-isopropyl-1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiouracil (56), 0.063 microM]. 6-[(3,5-Dimethylphenyl)thio]-5-ethyl-1-[(2-hydroxyethoxy)methyl]thymine derivatives 51 and 57 and 6-[(3,5-dimethylphenyl)thio]-5-isopropyl-1-[(2- hydroxyethoxy)methyl]thymine derivatives 52 and 58 inhibited the replication of HIV-1 in the nanomolar concentration range.

Antiviral Agents↗
PubMed1992

Establishment of stable cell lines producing anti-Pseudomonas aeruginosa monoclonal antibodies and their protective effects for the infection in mice.

Human-human hybridomas producing monoclonal antibodies (MoAbs) specific for five major serotypes of Pseudomonas aeruginosa were developed by fusing P. aeruginosa primed and Epstein-Barr virus-transformed cells with human myeloma P109 cells using polyethyleneglycol. The MoAbs which were produced by the hybridomas were protective against lethal intraperitoneal (i.p.) challenge of P. aeruginosa (10 LD50) in mice. The 50% effective dose (ED50) values of MoAbs ranged from 0.5 to 10.2 micrograms/mouse and were 26 to 240 times more protective than a commercial human IgG preparation. MoAb administration to mice promoted bacterial clearance in peritoneal cavity, and prevented bacterial invasion into blood in the way of increasing both the number of bacteria trapped by a macrophage and the ratio of macrophages that trapped bacteria. MoAbs also showed protective effects against lethal infection of P. aeruginosa in the mice which were decreased in polymorphonuclear cells (PMN) by cyclophosphamide (CY). All MoAbs showed serotype-specific binding to the clinical isolates of P. aeruginosa as well as to the immunized strains. The hybridoma cell lines maintained their capacity to produce MoAb continuously for more than 12 months and produced 10 to 60 micrograms MoAbs per 10(6) cells in 24 hr. It is practicable to use these cell lines for large-scale production of anti-P. aeruginosa MoAbs and such MoAbs must be useful for the therapeutics of patients with P. aeruginosa infection.

Animals↗
PubMed1992

In vitro drug combination of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil with anti-human immunodeficiency virus or anticancer nucleosides.

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and E-5-(2-bromovinyl)uracil, a metabolite of BV-araU, did not affect either the anti-human immunodeficiency virus activity or the cytotoxicity of azidothymidine in MT-4 and MOLT-4 cells. Similarly, the bromovinyl compounds did not affect the in vitro antitumor activities of arabinosylcytosine, 5-fluorouracil, and 5-fluoro-2'-deoxyuridine. The anti-varicella-zoster virus activity of BV-araU was not influenced by azidothymidine, 2',3'-didehydro-2',3'-dideoxythymidine, or arabinosylcytosine, whereas relatively high concentrations of fluorinated antitumor agents enhanced the anti-varicella-zoster virus activity.

Antiviral Agents↗
PubMed1992

Antiviral activities of ribavirin, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide, and 6'-(R)-6'-C-methylneplanocin A against several ortho- and paramyxoviruses.

5-Ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) and 6'-(R)-6'-C-methylneplanocin A (TJ13025) are two novel antiviral agents which are targeted against IMP dehydrogenase and S-adenosylhomocysteine hydrolase, respectively. These compounds have been examined for their activities against various strains of orthomyxoviruses (influenza virus) and paramyxoviruses (parainfluenza virus, mumps virus, measles virus, and respiratory syncytial virus) in vitro. EICAR was 10- to 59-fold more active than ribavirin and TJ13025 was 32- to 330-fold more active than ribavirin against parainfluenza virus types (2 and 3), mumps virus, and measles virus. EICAR was also more active than ribavirin against respiratory syncytial virus and influenza virus, whereas TJ13025 was virtually inactive against these viruses. The 50% virus-inhibitory concentrations of EICAR and TJ13025 were generally within the 0.1- to 1-microgram/ml range. Although the compounds did not prove cytotoxic to stationary host cells (HeLa, Vero, MDCK, and LLCMK2) at a concentration of 200 micrograms/ml, concentrations of 4 to 13 micrograms/ml inhibited the growth of dividing cells. EICAR and TJ13025 should be further pursued as candidate drugs for the treatment of ortho- and paramyxovirus infections.

Adenosine↗
PubMed1992

Effects of protease inhibitors on replication of various myxoviruses.

We studied the effects of eight protease inhibitors on the multicycle replications of various orthomyxoviruses and paramyxoviruses. Among the compounds, nafamostat mesilate, camostat mesilate, gabexate mesilate, and aprotinin, which are widely used in the treatment of pancreatitis, inhibited influenza virus A and B replication at concentrations that were significantly lower than their cytotoxic thresholds in vitro. None of the protease inhibitors had activity against respiratory syncytial virus, measles virus, or parainfluenza virus type 3 at the highest concentrations tested. Camostat mesilate was found to be the most selective inhibitor. Its 50% effective concentration for influenza virus A replication was 2.2 micrograms/ml, and the selectivity index, which was based on the ratio of the 50% inhibitory concentration for host cell proliferation to the 50% effective concentration for influenza virus A replication, was 680. When the in ovo antiviral activity of the compounds was tested by using chicken embryos, camostat mesilate at a dose of 10 micrograms/g markedly reduced the hemagglutinin titers of influenza viruses A and B.

Amino Acid Sequence↗
PubMed1992

Synthesis and anti-human immunodeficiency virus type 1 (HIV-1) activity of 3-substituted derivatives of 3'-azido-3'-deoxythymidine (AZT), and inhibition of HIV-1 reverse transcriptase by their 5'-triphosphates.

Various 3-substituted 3'-azido-3'-deoxythymidine analogs (2a-i) were prepared by the reaction of 3'-azido-3'-deoxythymidine (1), AZT with N,N-dimethylformamide dialkylacetal or alkyl bromide in the presence of base and their activities against human-immunodeficiency virus type-1 (HIV-1) were evaluated. The corresponding 5'-triphosphate analogs (9) were also synthesized in order to examine inhibition of HIV-1 reverse transcriptase activity. Beyond expectation, some N3-derivatives of AZT were found to reserve the anti-HIV-1 activity to some extent. Among the compounds (2a-i) obtained, 3-allyl-AZT (2e) was the most active against HIV-1 replication in MT-4 cells in vitro with an EC50 value of 0.9 microM. 3-Allyl-AZT 5'-triphosphate (9e), however, exhibited no inhibition of HIV-1 reverse transcriptase activity.

Antiviral Agents↗
PubMed1992

Behavioral effects of repeated aluminum administration in the rat.

Behavioral effects of repeated aluminum administration during prenatal periods were studied in THA rats. Four groups of pregnant rats were administered a daily dose of 0, 90, 180 or 360 mg/kg of aluminum chloride from the 8th day to 20th day of gestation by gavage. No differences were observed between the aluminum treated offspring and controls in terms of body weight. Delays in pivoting, longer latency and more rearings in an open field test were observed in the 360 mg/kg treated group, but no other developmental alterations were found. Urination in the open field test in the 180 mg/kg and 360 mg/kg treated groups was significantly more frequent than in the other two groups of rats. These results suggest that repeated doses of aluminum chloride during the prenatal period affects neuromotor maturation and emotionality in rats.

Aluminum↗
PubMed1992

[W-probe for microdialysis method in freely moving rat brain].

Measurements of neuropeptides, neurotransmitters and amino acids in freely moving rat brain were performed by microdialysis method. Recently, despite the different methods of measurement for each of those compounds, there have been attempts to measure them simultaneously from the same sample of brain dialysate, without measuring each compound from different samples. However, more sophisticated techniques and highly sensitive devices are required, to manage smaller volume samples obtained with this recent method. In our study, we present W-probe consisting of two probes with cylindrical dialysis membrane with 3 mm length and 0.222 mm outer diameter, intending to improve this method of analysis, without decreasing the recovery rate and sample volume compared with U-probe and permitting a clear analysis of acetylcholine and monoamine metabolites, even with the use of eserine. The results demonstrated that sample volume did not decrease even with slow perfusion rate (2 microliters/min). Thus, the sampling interval could be shorter than the previous microdialysis method, permitting the measurement of neurotransmitter releasing variation.

Acetylcholine↗
PubMed1992

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). I. Susceptibility distribution].

Isolation frequencies and sensitivities to antibacterial and antibiotic agents were investigated on 801 bacterial strains isolated from patients with urinary tract infections in 9 hospitals during the period of June to November 1988. Of the above total bacterial population, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus spp. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. 1. Enterococcus faecalis: Vancomycin was most active with its MIC90 < or = 0.78 microgram/ml. Ampicillin, piperacillin, ofloxacin (OFLX), ciprofloxacin (CPFX) and imipenem (IPM) were also active. 2. Staphylococcus aureus: Arbekacin and minocycline were most active with their MIC90s 0.39 microgram/ml and 1.56 micrograms/ml, respectively. Among penicillins, dicloxacillin was the most active. Activities of cephems were considerably lower. 3. E. coli: Most of the agents were tested active. Particularly the second and third generation cephems were active in a range of < or = 0.10-0.20 microgram/ml. Carumonam (CRMN), IPM, OFLX and CPFX were also active with MIC90s < or = 0.10 microgram/ml. 4. Klebsiella pneumoniae CRMN and IPM were highly active. Penicillins generally showed lower activities. Cephems and new quinolones had high activities with their MIC90s in a range of 0.39-0.78 microgram/ml. 5. Proteus mirabilis: The third generation cephems were active with their MIC90s in a range of < or = 0.10-0.20 microgram/ml. CRMN, OFLX and CPFX were also active with their MIC90s < or = 0.10 microgram/ml, 0.39 microgram/ml and 0.20 microgram/ml, respectively. 6. Pseudomonas aeruginosa: IPM and tobramycin were active with their MIC90s 1.56 micrograms/ml and 3.13 micrograms/ml, respectively. CRMN and new quinolones showed MIC80s of 25-100 micrograms/ml. Most of penicillins and cephems were not active. 7. Other Gram-negative rods: Against Citrobacter freundii, Enterobacter cloacae and Serratia marcescens, IPM, CPFX and OFLX were active. Penicillins and cephems were not so active. CRMN was active against S. marcescens with its MIC80 at 6.25 micrograms/ml.

Anti-Bacterial Agents↗
PubMed1992

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). II. Background of patients].

Clinical background was investigated on 916 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period from June to November, 1988. 1. Distribution of sexes, ages and infections: Among males, fifties and older were most frequent and most of them had complicated UTIs. Among females, most cases among twenties or thirties were uncomplicated UTIs. Forties and older cases were most frequent and complicated UTIs were more frequent among them than among patients in twenties and thirties. 2. Distribution of sexes, ages and pathogens isolated from UTIs: In males, Pseudomonas spp. and Enterococcus spp. were frequently isolated. In contrast, in females, Escherichia coli was the most frequent. In thirties, E. coli was not the most frequently isolated bacterium. Frequency of Pseudomonas spp., other non-fermented Gram-negative rods and Enterococcus spp. were greater among patients with higher ages. 3. Administration of antibiotics and pathogens isolated from UTIs: (1) Before administration: In uncomplicated UTIs, E. coli accounted for the majority of causative organisms. In complicated UTIs, particularly in those cases with indwelling catheter, Enterococcus spp. and Pseudomonas spp. were rather frequently isolated. (2) After administration: In complicated UTIs, higher number of pathogens were isolated. Pseudomonas spp. and Enterococcus spp. were the most frequent. Distribution of pathogens isolated from complicated UTIs without indwelling catheter was similar to that before antibiotic administration.

Adult↗
PubMed1992

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). III. Secular changes in susceptibility].

Sensitivities to various antibacterial and antibiotic agents of strains of Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Serratia marcescens and Pseudomonas aeruginosa isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June to November 1988 were compared with those in the same period of previous year according to a classification, uncomplicated UTIs, complicated UTIs without indwelling catheter, and complicated UTIs with indwelling catheter. No remarkable changes were found in sensitivities of E. coli, Proteus spp., Citrobacter spp. and S. marcescens. The sensitivity of Klebsiella spp. to cephems decreased in complicated UTI without indwelling catheter and increased in complicated UTI with indwelling catheter. The sensitivity of Enterobacter spp. to third generation cephems decreased in complicated UTI with indwelling catheter. Sensitivities of P. aeruginosa to aspoxicillin and cefsulodin increased. The number of resistant strains to new quinolones increased slightly.

Anti-Bacterial Agents↗
PubMed1991

Further characterization of allergenically active oligosaccharitols isolated from a sea squirt H-antigen.

Complete primary structures of five allergenically active oligosaccharitols (HPG-beta 2-N5a, -N6, -N7a, -N7b, and -N9) derived from a sea squirt H-antigen were studied. Structural characterization was carried out by a new method in which products of limited periodate oxidation, followed by derivatization with p-aminobenzoic acid ethyl ester, were analyzed by a combination of HPLC, fast atom-bombardment mass spectrometry, sequential glycosidase digestion, methylation analysis, and 500-MHz 1H NMR. Established structures of GalNAc beta 1-4 (GalNAc alpha 1-2Fuc alpha 1-3) GlcNAc beta 1-3GalNAc-ol, GalNAc beta 1-4GlcNAc beta 1-3 (GalNAc beta 1-4GlcNAc beta 1-6) GalNAc-ol, GalNAc beta 1-4GlcNAc beta 1-3[GalNAc beta 1-4 (Fuc alpha 1-3) GlcNAc beta 1-6] GalNAc-ol, GalNAc beta 1-4 (Fuc alpha 1-3) GlcNAc beta 1-3[GalNAc beta 1-4 (Fuc alpha 1-3) GlcNAc beta 1-6] GalNAc-ol, and GalNAc beta 1-4 (GalNAc alpha 1-2Fuc alpha 1-3)GlcNAc beta 1-3 [GalNAc beta 1-4 (GalNAc alpha 1-2Fuc alpha 1-3)GlcNAc beta 1-6]GalNAc-ol are represented by HPG-beta 2-N5a, -N6, -N7a, -N7b, and -N9, respectively. These structures have not been encountered previously. Oligosaccharide units GalNAc alpha 1-2Fuc alpha 1-, GalNAc beta 1-4GlcNAc beta 1-, and Fuc alpha 1-3GlcNAc beta 1- are considered to be the allergenically specific epitopes. Partial assignments of 500-MHz 1H NMR spectra of these novel O-linked oligosaccharitols were attempted.

Allergens↗
PubMed1991

An application of tetrazolium (MTT) colorimetric assay for the screening of anti-herpes simplex virus compounds.

A rapid and sensitive procedure was developed for in vitro evaluation of anti-herpes simplex virus (HSV) agents. The procedure is based on spectrophotometrical assessment for viability of virus- and mock-infected cells via in situ reduction of a tetrazolium dye MTT, which has already been used for the detection of anti-human immunodeficiency virus (HIV) agents (Pauwels et al., 1988). Monolayer cells such as human embryonic fibroblast, VERO, or HeLa cells were not suitable for this purpose. Among the non-adherent cell lines examined for susceptibility to HSV type 1 (HSV-1), a B-lymphoblastoid cell line NC-37 was found to be the most sensitive. The cell line was found to have a good correlation between the viable cell number and the reduction of MTT. In addition, centrifugation of the virus-infected cells resulted in further increase of the sensitivity of NC-37 cells to HSV-1. After optimization, the method proved to be as sensitive as plaque reduction. The system simplifies significantly the assay procedures and thus permits the evaluation of larger numbers of compounds for anti-HSV-1 activity.

Animals↗
PubMed1991

Synergistic inhibition of human immunodeficiency virus type 1 (HIV-1) replication in vitro by 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT) and recombinant alpha interferon.

1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) has recently proved to be a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. Combinations of HEPT and recombinant alpha interferon (IFN-alpha) synergistically inhibit the replication of HIV-1 in MT-4 cells at non-toxic concentrations. Synergistic inhibition of HIV-1 replication has also been observed in peripheral blood lymphocytes. These results indicate that the combination of HEPT with IFN-alpha should be further pursued in the treatment of retrovirus infections [i.e. acquired immune deficiency syndrome (AIDS)].

Acquired Immunodeficiency Syndrome↗