Biomedical subjects

S Shigeta

Publications and source records attributed to S Shigeta.

At least 199 records · Page 11Linked to original sources

PubMed1990

A rapid microassay for hemolytic antibody--its application to immunotoxicological study.

A rapid microassay for hemolytic antibody using an automatic spectrophotometer was developed. This microassay was parallel to hemolytic plaque forming cell (PFC) assay most commonly used to detect antibody formation. The former had more advantages than the latter did. The data obtained using arsenic and some metallic compounds as immunomodifiers suggested that this microassay was suitable for the screening of immunomodifiers in immunotoxicological and immunopharmacological studies which deal with a large number of samples within limited time.

Animals↗

PubMed1990

Conjunctival allergenicity-supporting factor (CASF) in DIIIa as the sea squirt antigen capable of inducing asthmatic attack and conjunctival reaction in sea squirt asthma.

Among three glycoproteins, DIIIa, Ei-M, and Gi-rep, isolated from sea squirt as antigens capable of eliciting skin reaction specific to sea squirt allergy, only DIIIa induces asthmatic attack and conjunctival reaction, whereas Ei-M and Gi-rep do not. Periodate oxidation eliminated not only the conjunctival allergenicity but also the skin allergenicity from DIIIa, suggesting that the conjunctival and skin allergenicity could both be ascribed to the epitope residing in the carbohydrate chains of DIIIa. On the other hand, proteolysis with Pronase E and chemical modifications of the carboxyl or amino groups by various methods eliminated the conjunctival allergenicity from DIIIa, whereas the skin allergenicity was still retained. Therefore, the expression of conjunctival reaction was expected to be supported by a relatively small structural factor residing in the protein moiety of DIIIa, which we have tentatively designated as conjunctival allergenicity-supporting factor (CASF). CASF might contribute to the permeability of the antigen into mucosa, enabling the carbohydrate epitope to interact with the allergy-specific IgE distributed in conjunctiva and bronchi . In specificity analysis of a rabbit anti-DIIIa serum, a periodate oxidation- and acid-stable but heat- and alkali-unstable epitope (type gamma) in the protein moiety of DIIIa was also characterized as a useful marker of the antigen. However, the type gamma epitope was apparently independent of CASF that was substantially stable to alkali and heat.

Animals↗

PubMed1990

Phosphonylmethoxyalkyl derivatives of purine as inhibitors of human hepatitis B virus DNA synthesis.

A selected number of antiviral compounds which have been previously shown to inhibit the replication of DNA viruses or retroviruses were examined for their inhibitory effects on human hepatitis B virus (HBV) DNA synthesis. The assay system was based on the use of a human hepatoblastoma cell line (HB611) that continuously synthesizes HBV DNA. The following phosphonylmethoxyalkyl-purine derivatives were found to inhibit HBV DNA synthesis: 9-(2-phosphonyl-methoxyethyl)-2',6'-diaminopurine (PMEDAP), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA). PMEDAP, HPMPA and PMEA not only inhibit HBV DNA synthesis in HB611 cells but also duck hepatitis B virus (DHBV) DNA and core antigen synthesis in primary duck hepatocytes.

Adenine↗

PubMed1990

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1987). I. Susceptibility distribution].

Since 1979, Ikemoto et al. have been retrospectively surveying the sensitivity of major species of bacteria isolated from patients with urinary tract infections to various antibacterial agents and antibiotics. Their findings for the past year are reported below. A total of 825 clinical strains of bacteria was investigated. Of this total, Gram-positive bacteria accounted for 28.0% (231 strains) and Gram-negative bacteria for 72.0% (594 strains). Taxonomically, Escherichia coli accounted for 34.7% (286 strains), Enterococcus faecalis for 14.3% (118), Pseudomonas aeruginosa for 11.0% (91), Klebsiella pneumoniae for 7.8% (64), and coagulase-negative staphylococci for 7.3% (60). Sensitivity spectra of these major bacteria to various drugs were as follows. 1. E. faecalis was sensitive to parenteral imipenem (IPM) and ampicillin and oral vancomycin. It was also sensitive to ofloxacin (OFLX) and ciprofloxacin (CPFX), which are new quinolones. Some strains were only slightly sensitive to second and third generation cephems cefmenoxime (CMX) and cefuzonam (CZON) aminoglycosides amikacin (AMK) and arbekacin (HBK), and erythromycin which is a macrolide. 2. Staphylococcus aureus was sensitive to dicloxacillin (MDIPC) which is a penicillin drug, cefotiam (CTM) which is a cephem, IPM, minocycline (MINO), and HBK. A fairly large number of strains were only slightly sensitive to cefazolin (CEZ), OFLX and CPFX. 3. Coagulase-negative staphylococci were sensitive to MDIPC which is a penicillin derivative, cephems CTM and CZON, IPM, HBK, clindamycin (CLDM) and MINO. Some strains, however, were only slightly sensitive to a majority of these drugs. 4. E. coli was sensitive to CTM, CMX, latamoxef (LMOX), ceftazidime (CAZ), CZON, and flomoxef (FMOX), all of which are second or third generation cephems. It was also sensitive to IPM, a carbapenem, carumonam (CRMN), a monobactam, and new quinolones, OFLX and CPFX. 5. K. pneumoniae was sensitive to cephems, viz. CTM, CAZ, CZON, FMOX and cefixime, CRMN which is a monobactam, IPM, a carbapenem and new quinolones, OFLX and CPFX. Some strains were only slightly sensitive to CTM, cefmetazole cefoperazone (CPZ), and FMOX. 6. Citrobacter freundii was sensitive to CRMN which is a monobactam, and new quinolones, OFLX and CPFX. Many strains were only slightly sensitive to cephems, viz. CEZ, CTM, CPZ and CAZ. 7. Enterobacter cloacae was sensitive to gentamicin and AMK which are aminoglycosides, but showed a bimodal pattern of sensitivity to CPZ, CAZ and CZON, all of which are cephems, and to quinolones, OFLX and CPFX.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

PubMed1990

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1987). III. Secular changes in susceptibility].

Sensitivity spectra of major species of bacteria (namely Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Serratia marcescens and Pseudomonas aeruginosa) which were among the clinical isolates mentioned in the first and second reports to various antibacterial and antibiotic agents and time courses of the spectra are reported below. 1. E. coli was sensitive to cefmenoxime (CMX), latamoxef (LMOX), ceftazidime (CAZ), cefzonam (CZON) and flomoxef (FMOX) which are third generation cephems, carumonam (CRMN) which is a monobactam, imipenem (IPM) which is a carbapenem, ofloxacin (OFLX) and ciprofloxacin (CPFX) which are new quinolones. Compared to the preceding 5-year period, sensitivities to most drugs have increased. 2. Klebsiella spp. were sensitive to CMX, CZON and FMOX which are third generation cephem antibiotics, CRMN which is a monobactam and gentamicin (GM) and arbekacin (HBK) which are aminoglycosides. Compared to the preceding 5-year period, the sensitivity on the whole has increased slightly. 3. Proteus spp. were sensitive to CMX, LMOX, CAZ and CZON which are third generation cephems, CRMN, a monobactam and OFLX and CPFX which are new quinolones. Compared to the preceding 5-year period, increased sensitivities, particularly to parenteral cephems, were found. 4. Citrobacter spp. were sensitive to CPFX which is a new quinolone antibiotic and CRMN, a monobactam. Compared to the preceding 5-year period, the sensitivity as a whole increased but there were still strains against which cefotiam, cefmetazole and, cefoperazone (CPZ) showed high MIC values. 5. Enterobacter spp. were sensitive to OFLX and CPFX, which are new quinolones, IPM, a carbapenem, and GM and HBK which are aminoglycosides. Compared to other bacteria, bacteria of this group were less sensitive to CPZ, CAZ, CZON, and FMOX which are third generation cephems. Compared to the preceding 5-year period, slight increases in sensitivity were found in cases of simple urinary tract infections. 6. S. marcescens as a whole was not very sensitive to antibiotics tested. Compared to the preceding 5-year period, sensitivities to CRMN and minocycline improved slightly. 7. P. aeruginosa was not very sensitive to any drug, as other bacteria were. Compared to the preceding 5-year period, sensitivities to new quinolones OFLX and CPFX and carbapenem IPM decreased slightly.

Anti-Bacterial Agents↗

PubMed1990

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1987). II. Background of patients].

In the retrospective survey of the sensitivity of clinical isolates reported in this journal, patients' backgrounds were also investigated. Some findings are summarized below. 1. Age distribution by sex: Patients with ages 50 years and older accounted for a majority, irrespective of their sexes amounting 67.6% for both sexes combined. 2. Annual distribution of sexes by age group: Females accounted for a majority in younger age brackets, but the proportion of males increased with age, accounting for a majority in patients 70 years or older. This pattern has been repeated practically every year. 3. Distribution of infection types by sex: Complicated urinary tract infections were predominant in males, while simple urinary tract infections were more frequent in females. 4. Annual distribution of sexes by type of infection: Complicated and simple urinary tract infections combined accounted for approximately 70% in both males and females. This pattern has been repeated practically every year. 5. Distribution of infection types by age: Patients of advanced ages were predominant as a whole but this trend was particularly pronounced in complicated urinary tract infection cases. 6. Annual distribution of infection types by age: The frequency of simple urinary tract infections among patients older than 20 years of age declined with age and this pattern has been repeated practically every year. Among patients older than 20 years of age, annual frequencies of complicated urinary tract infections have been on the decrease. 7. Distribution of isolated bacteria by sex: Escherichia coli was more frequent in females, while Enterococcus faecalis and Pseudomonas aeruginosa were more frequent in males. Compared with the previous year, the frequencies of coagulase-negative staphylococci, Enterococcus spp., and E. coli increased, while that of P. aeruginosa decreased. 8. Distribution of isolated bacteria by age: E. coli was most frequent on the whole, followed by E. faecalis, P. aeruginosa, Klebsiella spp., and coagulase-negative staphylococci, in that order. By age group, E. coli was frequent in younger patients and the frequencies of E. faecalis and P. aeruginosa increased with age. 9. Annual distribution of isolated bacteria by infection type: Coagulase-negative staphylococci increased as a whole and P. aeruginosa and Serratia marcescens decreased compared to 1986, but E. coli continued to be the most frequent. E. coli was isolated from a majority of simple urinary tract infection cases. The frequencies of E. faecalis and P. aeruginosa were high in cases of complicated urinary tract infections.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1990

Improvement in the therapeutic efficacy of an asthma-inducing sea squirt antigen termed DIIIa by its polymerization in hyposensitization of sea squirt allergy.

Polymerization using glutaraldehyde markedly improved the apparently low efficacy of an asthma-inducing sea squirt antigen, DIIa (MW 9,980), in hyposensitization therapy on patients with sea squirt allergy. A product (poly-DIIa-G) comparable to Gi-rep (MW 106,000) in MW-distribution showed high therapeutic efficacy comparable to the most effective therapeutic antigen, Ei-M, which was paralleled by a significant increase in the allergen-specific IgG titer in most of the successfully hyposensitized patients as assayed using Ei-M as the target antigen. Another product (poly-DIIa-E) comparable to Ei-M (MW 22,800) in MW also showed a high but slightly lower therapeutic efficacy relative to poly-DIIIa-G with an apparent increase in the specific IgG titer in some patients. However, no significant change in the IgG titer was detected in most patients unsuccessfully treated with intact DIIIa. On the other hand, no significant change was detected in the IgE titer specific to the target antigen in the patients, except in a few cases where the change was independent of the therapeutic effect. The apparent correlation between the increase in the specific IgG titer and the enhancement of the therapeutic effect suggested that polymerization enhanced the immunogenicity of DIIIa and resulted in a significant improvement in the therapeutic efficacy through an additional induction of the specific IgG capable of competing, as a blocking antibody, with the specific IgE for an asthma-inducing antigen, like DIIIa, in patients treated with the polymerized antigens.

Animals↗

PubMed1989

Sugar sequences of allergenically active oligosaccharide alcohols isolated from a large-molecular-size sea squirt antigen termed H-antigen.

O-Glycosidically linked oligosaccharide chains were liberated as oligosaccharide alcohols (HPG-beta 2) by beta-elimination treatment from a glycopeptide fraction (HPG, Mr ca. 10(5)) that was isolated from a Pronase digest of a large-size sea squirt antigen termed H-antigen (Mr 10(6)-2 X 10(7)). After HPG-beta 2 was divided into a neutral (HPG-beta 2-N) and an acidic (HPG-beta 2-A) fraction, 11 neutral saccharitols were isolated from HPG-beta 2-N, and their sugar sequences were determined by methylation/GC-MS, FAB-MS, and/or DI/EI-MS. By skin tests specific to patients with sea squirt allergy, it was found that six saccharitols were allergenically active but five were inactive. Furthermore, active saccharitols were all of branched structure containing two nonreducing terminal GalNAc (t-GalNAc) residues, whereas the inactive saccharitols contained one or no t-GalNAc. Since the allergic reaction in skin should depend on the crosslinking of IgE antibodies by certain allergens carrying two or more epitopes, three types of N-acetylgalactosaminyl disaccharide units, GalNAc1----2Fuc1----, GalNAc1----3/4GalNAc1----, and GalNAc1----3/4GlcNAc1----, were nominated as the major components of the allergy-specific epitopes in the active saccharitols. Such multiplicity of the epitope structures might reflect the polyclonality of the specific IgE antibodies.

Allergens↗

PubMed1989

Possible involvement of microfilaments in protein kinase C translocation.

We investigated the role of microfilaments in stimulus-induced translocation of protein kinase C (PKC) in polymorphonuclear leukocytes (PMNs) from C57BL/6 mice. Cytochalasin B and dihydrocytochalasin B almost completely inhibited PKC translocation induced by either TPA or Ca2+ ionophore after pretreatment of cells for 30 min. In addition, ML-9, a potent inhibitor of Ca2+/calmodulin-dependent myosin light chain kinase which regulate microfilament contraction, and a calmodulin antagonist W-7, also inhibited PKC translocation. These findings suggest the possibility that microfilaments are involved in the translocation of PKC.

Actin Cytoskeleton↗

PubMed1989

The thiol proteinase inhibitors improve the abnormal rapid down-regulation of protein kinase C and the impaired natural killer cell activity in (Chediak-Higashi syndrome) beige mouse.

Protein kinase C (PKC) is essential in intracellular signal transduction for various cell functions including natural killer (NK) cell activity. This enzyme is hydrolysed by calpain, which is Ca2+-dependent thiol proteinase. We showed here that in NK activity-deficient beige (bg/bg) mouse, the model of Chediak-Higashi syndrome, the translocated membrane-bound PKC activity declined rapidly in NK cell-enriched lymphocytes after TPA stimulation. However, the rapid decline was abolished by the pretreatment of cells with leupeptin (a thiol and serine proteinase inhibitor) or E64 (a thiol proteinase inhibitor). Furthermore, these reagents improved the impaired NK cell activity in beige mouse whereas they did not affect NK cell activity in C57BL/6 (+/+) and the heterozygous (+/bg) mice. Meanwhile, TPA stimulation induced only low levels in NK cytotoxic factors (NKCF) release from beige NK cells, but these reagents augmented the lowered NKCF release. These results suggest that the improvement of impaired NK cell activity in beige mouse by the thiol proteinase inhibitors may be due to the elimination of abnormal rapid down-regulation of PKC, resulting in the augmentation of the lowered PKC activity.

Animals↗

PubMed1989

Tumor necrosis factor enhances replication of human immunodeficiency virus (HIV) in vitro.

The effect of tumor necrosis factor (TNF) on the replication of human immunodeficiency virus type 1 (HIV-1) was investigated in several T4 lymphocyte cell lines. TNF markedly enhanced the cytopathogenicity of HIV-1, virion-associated reverse transcriptase (RT) activity in the cell culture supernatant, and viral antigen expression in MOLT-4 cells as early as 3 days after HIV-1 infection. A slight increase in RT activity was also observed in the supernatant of H9 cell cultures exposed to TNF. However, TNF did not increase either RT activity in MT-4 cell supernatants or viral antigen expression in HUT-78 cells. Thus, TNF is able to stimulate the replication of HIV-1 in de novo infected T4 cells although not all T4 cells seem to be sensitive to this stimulatory effect.

Antigens, Viral↗

PubMed1989

In vitro activity of mannan sulfate, a novel sulfated polysaccharide, against human immunodeficiency virus type 1 and other enveloped viruses.

Mannan sulfate, a novel sulfated polysaccharide, was prepared and investigated for its activity against human immunodeficiency virus type 1 (HIV-1) in vitro. Mannan sulfate completely inhibited HIV-1-induced cell destruction and viral antigen expression in HIV-1-infected Molt-4 (clone 8) cells at a concentration of 4 micrograms/ml. The 50% antiviral effective doses obtained with mannan sulfate in Molt-4 (clone 8) cells and in MT-4 cells were 1.5 and 9.3 micrograms/ml, respectively. No toxicity for Molt-4 (clone 8) cells or MT-4 cells was observed at a concentration of 4,000 and 2,500 micrograms/ml, respectively. Mannan sulfate was also inhibitory to other enveloped viruses, i.e. herpes simplex virus types 1 and 2, vaccinia virus and vesicular stomatitis virus. These results suggest that mannan sulfate may be useful for the chemotherapy of various viral infections, including those causing and associated with AIDS.

HIV-1↗

PubMed1989

Therapeutic effect and titers of the specific IgE and IgG antibodies in patients with sea squirt allergy (Hoya asthma) under a long-term hyposensitization with three sea squirt antigens.

Hyposensitization therapy with each of three sea squirt antigens, Gi-rep (molecular weight [MW] 106,000), Ei-M (MW 22,800), and DIIIa (MW 9980), have succeeded in 72%, 90%, and 36% of patients with sea squirt allergy, respectively, within the first year, and the effect has been maintained during subsequent 4-year maintenance therapy. All available sera from some of the hyposensitized patients were also examined for IgE and IgG titers against the most effective therapeutic antigen, Ei-M, and it was revealed that the Ei-M-specific IgG titer increased rapidly in the successfully hyposensitized patients, regardless of the therapeutic antigen used, except for a few patients. Furthermore, the high specific IgG titer, as well as the therapeutic effect, was maintained during the subsequent maintenance therapy. No such increase in the specific IgG titer was detected in all unsuccessfully hyposensitized patients. In contrast, the Ei-M-specific IgE titer was practically unchanged in all allergic patients, independent of the therapy. Therefore, the effect of the hyposensitization therapy was closely dependent on the induction of the specific IgG capable of competing with the specific IgE for a certain asthma-inducing antigen, like DIIIa. The apparently low therapeutic efficiency of DIIIa was attributed to its relatively low immunogenicity to induce the specific IgG.

Allergens↗

PubMed1989

Inhibitory effect of selected antiviral compounds on measles (SSPE) virus replication in vitro.

A variety of antiviral compounds were examined for their inhibitory effect on measles (SSPE) virus plaque formation in VERO cells. The following compounds inhibited SSPE virus (strain Niigata-1) replication at concentrations that were significantly lower than their minimum cytotoxic concentrations: neplanocin A, neplanocin C, carbocyclic 3-deazaadenosine, 9-(trans-2', trans-3'-dihydroxycyclopent-4'-enyl)adenine, 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-3-deazaadenine, (RS)-3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester, carbodine, cyclopentenyl cytosine, 3-deazaguanine, pyrazofurin, ribavirin and 6-azauridine. As the most selective inhibitors of SSPE virus replication emerged pyrazofurin, 3-deazaguanine, 6-azauridine and ribavirin. These compounds were further examined for their relative potency against a number of measles (SSPE) virus strains. Their order of (decreasing) potency was pyrazofurin greater than 6-azauridine approximately 3-deazaguanine greater than ribavirin. Amantadine, inosiplex and glycyrrhizin, that were also included in these assays, did not show appreciable activity against any of the measles (SSPE) virus strains.

3-Deazauridine↗

PubMed1989

Inhibition of natural killer cell-mediated cytotoxicity by ML-9, a selective inhibitor of myosin light chain kinase.

To investigate the role of microfilaments in natural killer (NK) cell-mediated cytotoxicity, general microfilament inhibitors, cytochalasins B,D and dihydrocytochalasin B, and a selective inhibitor of myosin light chain kinase (MLCK) which regulates microfilament contraction, i.e. 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) were examined in an NK assay system. ML-9 inhibited NK cell activity in a dose-dependent manner without affecting target cell binding, whereas cytochalasins suppressed the binding. The dextran suspension method revealed that ML-9 inhibits the programming for the lysis stage of the lytic process. In the single cell assay, the addition of ML-9 after target cell binding had occurred inhibited the lysis of bound target cells, whereas the addition of cytochalasins in a similar manner did not affect it. Thus, these results suggest the possibility that microfilament contraction is involved in the lytic mechanism of NK cell-mediated cytolysis. However, the mechanism whereby cytochalasins inhibit target cell binding remains unclear.

Actin Cytoskeleton↗

PubMed1989

N-acetylgalactosaminyl disaccharide terminals contained in presumed carbohydrate epitopes specific to sea-squirt allergy.

Using the methods of methylation/GLC, MS, and 1H-NMR analyses, a disaccharide structure of GalNAc alpha 1----2Fuc1---- was identified as one of the major structural units at non-reducing terminals of a highly branched and N-glycosidically linked carbohydrate on an allergenically active glycopeptide, Gp-2 (Mr ca. 8,000). Gp-2 was one of the major fractions in the Pronase digest of a sea-squirt antigen, Gi-rep, and is capable of eliciting the skin reaction specific to patients with sea-squirt allergy similarly to Gi-rep. An additional disaccharide structure of GalNAc1----(3/4)HexNAc1---- was also expected as the other major non-reducing terminal unit, though the anomeric configuration of the terminal GalNAc could not be identified. As Gp-2 carbohydrate was found to contain 3 mol each of the two types of terminal GalNAc-containing units, both were nominated as possible components of the IO4- oxidation-sensitive epitopes which are responsible for the allergenic activity in Gp-2 and its mother antigen, Gi-rep. A few moles of Fuc and Gal were also detected as minor non-reducing terminals in addition to the 6 mol of the GalNAc-containing units.

Acetylglucosamine↗

PubMed1989

Inhibitory effect of a lichen polysaccharide sulfate, GE-3-S, on the replication of human immunodeficiency virus (HIV) in vitro.

A sulfate (GE-3-S) prepared by chlorosulfonic acid treatment of GE-3, a partially acetylated beta(1----6) glucan of the lichen Umbilicaria esculenta, inhibited the cytopathic effect of human immunodeficiency virus (HIV) and suppressed the HIV-antigen expression in Molt-4 (clone 8) cells. GE-3-S also suppressed the giant cell formation of HIV-infected Molt-4 cells, and inhibited HIV-induced plaque formation by 50% at the dose of 19.5 micrograms/ml and completely at 250 micrograms/ml in MT4 cells. GE-3-S had no direct effect on the reverse transcriptase of HIV.

Antiviral Agents↗

PubMed1989

[The effects of prenatal trimethyltin exposure on development and learning in the rat].

Developmental effects of single prenatal trimethyltin exposure were examined in THA rats. Pregnant rats were injected on gestational day 12 with single dose of trimethyltin chloride (TMT) ip at either 0, 5, or 7 mg/kg. Significant differences between treated and control offspring rats could not be observed in terms of body weight, pinna detachment, incisor eruption, eye opening, surface righting, cliff avoidance, pivoting, negative geotaxis and auditory startle. Spontaneous motor activity and open field behavior in the rats were also not affected by TMT. In Sidman avoidance test, however, the avoidance rate of the treated offspring rats was lower when compared to that of the controls. These results suggest that prenatal TMT administration disrupts learning acquisition.

Animals↗