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Biomedical subjects

S Shigeta

Publications and source records attributed to S Shigeta.

At least 235 records · Page 13Linked to original sources
PubMed1987

Inhibitory effect of glycyrrhizin on the in vitro infectivity and cytopathic activity of the human immunodeficiency virus [HIV (HTLV-III/LAV)].

Glycyrrhizin (GL), one of the plant extracts, was investigated for its antiviral action on the human immunodeficiency virus [HIV (HTLV-III/LAV)] in vitro, using cytopathic effect and plaque forming assay system in MT-4 cells (a HTLV-I-carrying cell line). Cloned Molt-4 cells (clone No. 8), which are sensitive to HIV and fuse to giant cells after infection, were also used as a parameter for cytopathic effect of HIV. GL completely inhibited HIV-induced plaque formation in MT-4 cells at a concentration of 0.6 mM, the 50% inhibitory dose being 0.15 mM. GL completely inhibited the cytopathic effect of HIV and the HIV-specific antigen expression in MT-4 cells at a concentration of 0.3 and 0.6 mM, respectively. Furthermore, GL inhibited giant cell formation of HIV-infected Molt-4 clone No. 8 cells. GL had no direct effect on the reverse transcriptase of HIV. Its mechanism of anti-HIV action remains to be elucidated.

Antiviral Agents↗
PubMed1987

Inhibitory effect of dextran sulfate and heparin on the replication of human immunodeficiency virus (HIV) in vitro.

The polyanionic substances dextran sulfate and heparin were investigated for their antiviral effect on the human immunodeficiency virus (HIV) in vitro. Dextran sulfate and heparin effected a 50% reduction in the cytopathogenicity of HIV for MT-4 cells at a concentration of 4.7 and 7.5 micrograms/ml, respectively. In Molt-4 (clone 8) cells, these values were slightly higher (14.1 and 15.6 micrograms/ml, respectively). No toxicity for the host cells was noted with these compounds at a concentration up to 400 micrograms/ml, so that the selectivity indexes, as based on the ratio of the 50% cytotoxic dose to the 50% antiviral effective dose, were well in excess of 100. These findings may have far reaching implications both diagnostically, when attempts are made to isolate HIV from heparinized blood samples, as therapeutically, to the extent that dextran sulfate or heparin may be useful in blocking HIV replication in vivo.

Cell Line↗
PubMed1987

Antiviral activity of glycyrrhizin against varicella-zoster virus in vitro.

One of the plant extracts, glycyrrhizin (GL) was investigated for its antiviral action on varicella-zoster virus (VZV) in vitro. When human embryonic fibroblast (HEF) cells were treated with GL after inoculation of virus (post-treatment), the average 50%-inhibitory dose (ID50) for five VZV strains was 0.71 mM, and the selectivity index (ratio of ID50 for host-cell DNA synthesis to ID50 for VZV replication) was 30. GL was also effective against VZV replication when HEF cells were treated 24 h before the inoculation (pretreatment). Furthermore, at a concentration of 2.4 mM GL inactivated more than 99% of virus particles within 30 min at 37 degrees C. In combination with other anti-herpes drugs (acyclovir, adenine arabinoside, bromovinyldeoxyuridine, and phosphonoformate) or human native beta-interferon, GL had an additive or slightly synergistic effect on VZV replication. The mechanism of anti-VZV action is still unclear. We postulate that GL inhibits the penetration, uncoating or release of virus particles.

Antiviral Agents↗
PubMed1987

Natural killer activity enhancing substance in normal human serum.

We studied the effect of normal human serum on natural killer (NK) activity of normal peripheral lymphocytes. Both fresh serum and heat-inactivated (56 degrees C, 30 min) serum significantly enhanced NK activity, in a dose dependent manner, the limit being reached with a final concentration of 5%. However, antibody dependent cell-mediated cytotoxicity (ADCC) was not affected by heat-inactivated serum, although it did show the effects of fresh serum as complement. The serum absorbed with target cells also enhanced NK activity, so it indicated that the enhancing effect of normal serum was not due to the natural antibody against target cells in the serum. The serum was fractionated by Sephadex G-200 into fractions I, II and III in the order of elution. The enhancing factor existed in fraction III. When fraction III was further separated by Cibacron Blue-Sepharose, which selectively adsorbs albumin from serum, the enhancing activity existed in the albumin-rich subfraction. In addition, commercial human albumins had the NK enhancing activity, whereas native transferrin, platelet-derived growth factor (PDGF) or plasminogen did not. These results therefore suggest that the substance enhancing NK activity in normal serum is serum albumin, which is considered to have no significant effect on immune reaction.

Adjuvants, Immunologic↗
PubMed1987

Enhancement of the immune response in vitro by arsenic.

We examined the effect of arsenic (As) on the immune response of mice to sheep erythrocytes, assaying the spleen for plaque-forming cells (PFC). The effect of As on the PFC response to sheep erythrocytes was dose-dependent. At high doses of As the PFC response was erythrocytes was dose-dependent. At high doses of As the PFC response was suppressed, whereas it enhanced the response at low doses. The suppression was due to the cytotoxic action of As against lymphocytes generally. On the other hand, enhancement was seen on the addition of As at the start of the culture or as a result of pretreatment of normal spleen cells with As. Even low doses of As were cytotoxic, to both B and T cells. They differed, however, in their susceptibility to As. When normal spleen cells were added to the culture of As-treated spleen cells, the enhancement of the PFC response was reversed. Suppressor-inducer B cells, in the normal spleen cells, could not induce suppressor T cells from As-treated spleen cells. And As did not affect suppressor T cells. These findings indicate that As deletes the precursors of suppressor T cells from normal spleen cells, and thus enhances the immune response.

Animals↗
PubMed1987

An epitope residing in carbohydrate chains of a sea squirt antigen termed Gi-rep.

O-Glycosidically linked oligosaccharides (Gp-1 beta-b) were liberated from a large size glycopeptide (GP) fraction (Gp-1) in a Pronase digest of a sea squirt antigen termed Gi-rep by the treatment with 0.1 N NaOH per 1 mol/L of NaBH4. Gp-1 beta-b as well as Gp-1 and the intact antigen was capable of inducing a remarkable erythema in the skin of patients with asthma with sea squirt allergy at its concentration of 10 micrograms/ml. N-Glycoside GP fractions (Gp-1 beta-a and Gp-2 beta) having the allergenic activity were also prepared as alkali-resistant GPs from Gp-1 and the other relatively small size GP fraction (Gp-2) of the Pronase digest, respectively, after the alkali treatment. Chemically, the three allergenically active preparations were rich in galactosamine, glucosamine, and fucose in common, although the N-linked carbohydrates were much larger in size than O-linked carbohydrates. Accordingly, it has been expected that the epitope of the sea squirt antigen corresponds to certain oligosaccharide units residing in both of the O- and N-linked carbohydrate chains of the antigen. This suggestion was consistent with the observation that the allergenic activity of Gi-rep was significantly unstable to the periodate oxidation but substantially stable not only to acid, alkali, and heat treatments but also to the enzymatic proteolysis with Pronase E.

Animals↗
PubMed1987

Synergistic antiproliferative effect of interferon-beta in combination with bleomycin or neocarzinostatin on HeLa cells in culture: additive effect when combined with adriamycin or mitomycin C.

Human fibroblast interferon (IFN)-beta was administered in combination with the free radical-generating antiproliferative agents bleomycin (BLM), neocarzinostatin (NCS), adriamycin (ADM), and mitomycin C (MMC) to HeLa cells in culture. IFN showed a true synergistic antiproliferative activity in the presence of BLM or NCS. These effects were observed regardless of the ratio of IFN to BLM or NCS concentrations. However, the effect of IFN in the presence of ADM or MMC was additive. The possibility that IFN-beta potentiates the antiproliferative effects of these free radical-generating agents in a different manner is also discussed.

Antineoplastic Agents↗
PubMed1987

Inhibiting effect of (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine on varicella-zoster virus replication in cell culture.

The activity and mode of action of the new nucleoside analog (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (2HM-HBG) against varicella-zoster virus (VZV) were determined. In cell culture, replication of different strains of VZV was inhibited to 50% by 0.4 to 0.7 microM 2HM-HBG, while 685 microM was required to inhibit 50% of the DNA synthesis in uninfected human lung fibroblasts. A thymidine kinase-negative VZV strain was not inhibited by 100 microM 2HM-HBG. Inhibition of VZV replication was not reversible after 7 to 14 days of incubation, depending on the multiplicity of VZV. 2HM-HBG was shown to be selectively phosphorylated by purified VZV thymidine kinase, with an inhibition constant of 32.5 microM. The antiviral activity of 2HM-HBG in cell culture was decreased by the addition of deoxythymidine and deoxycytidine but not by other ribo- or deoxyribonucleosides.

Antiviral Agents↗
PubMed1987

Selective inhibitory effect of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and 2'-nor-cyclic GMP on adenovirus replication in vitro.

The inhibitory effects of 20 selected antiviral compounds on the replication of adenoviruses (types 1 to 8) in vitro were investigated. While 18 compounds were ineffective, 2 compounds, namely (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] and 9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]guanine P-oxide (2'-nor-cyclic GMP), were highly effective against all adenovirus types assayed in human embryonic fibroblast cultures. Their 50% inhibitory doses were 1.1 microgram/ml for (S)-HPMPA and 4.1 micrograms/ml for 2'-nor-cyclic GMP. They were nontoxic for the host cells at the effective antiviral doses.

Adenine↗
PubMed1987

Inhibitory effects of antiviral compounds on respiratory syncytial virus replication in vitro.

We examined the inhibitory effect of 20 antiviral compounds, including ribavirin, on the replication of respiratory syncytial virus in HeLa and HEp-2 cell cultures. Of the compounds studied, pyrazofurin and 3-deazaguanine emerged as more potent inhibitors of respiratory syncytial virus than ribavirin. Based on their inhibitory effect on the cytopathogenicity of respiratory syncytial virus in HeLa cells, the average 50% effective dose of pyrazofurin and 3-deazaguanine for eight strains was 0.07 and 1.65 micrograms/ml, respectively; that of ribavirin was 5.82 micrograms/ml. The cytotoxicity of these compounds for HeLa cells was examined by monitoring the incorporation of radiolabeled uridine into cellular RNA. The selectivity indexes of pyrazofurin and 3-deazaguanine exceeded that of ribavirin by 70- and 11-fold, respectively. Pyrazofurin, 3-deazaguanine, and ribavirin inhibited both viral antigen expression and syncytium formation in HeLa cell cultures, as assessed by an indirect immunofluorescence assay. In these assays, pyrazofurin and 3-deazaguanine again proved more potent than ribavirin. 2,5-Diamidinoindole and carbodine were less potent than ribavirin. Various other compounds, i.e., 3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester, 3-deazauridine, 3'-C-methyluridine, 5'-deoxy-5-fluorouridine, 5-cyanoimidazole-4-carboxamide, and its ribofuranosyl derivative, did not inhibit the cytopathic effect of the Long strain of respiratory syncytial virus at concentrations greater than or equal to 125 micrograms/ml. Tubercidin, 5-chlorotubercidin, xylotubercidin, neplanocin A, thiosemicarbazone R, and 3-methylquercetine were too toxic to HeLa cells for their inhibitory effects on respiratory syncytial virus to be examined.

Antiviral Agents↗
PubMed1987

[An experimental study on the prediction of heat stress of workers in a hot environment, with special reference to the relation between wearing suits, work load and environmental temperature].

Hardly any practical approaches have been made on prediction of appearance of heat-stress hazard, although basic studies have extensively been made, including various heat-stress indices. Hence, in the present paper, an applicational prediction equation is presented with regard to the permissible working time without heat-stress hazard on the basis of experimental results. The purpose of this experiment was to examine the significant correlations between elevated rectal temperature, working conditions such as wearing suits, work load, and environmental temperature. The results obtained can be summarized as follows. (1) A critical level of environmental temperature exists. When this level is exceeded, physiological indices such as rectal temperature rapidly increased. According to experimental results, the critical level was about 30 degrees C and the heavier the work load, the lower was the critical level. (2) Moreover, the heavier the wearing suit, the lower became the temperature level. This finding indicated that it was important to choose a suitable apparel under a hot environment in order to keep the workers safe from heat-stress hazard. (3) A general prediction equation of raising the level of rectal temperature compared with that of initial condition was proposed by analysing each experimental condition (suit, work load, and environmental temperature) by use of second order multiple regression method. This equation showed that elevation of rectal temperature was assumed to be proportional to the logarithm of the working periods. (4) The predicted values by this equation corresponded with the experimental values within +/- 0.2-0.3 degrees C, and the correlation coefficient was 0.96. This equation suggests that heavier suits elevated the rectal temperature about 2-3 degrees C when the work load and environmental temperature were moderate. (5) It is possible to predict the permissible working period by this equation. This may be applied to the working plan effectively. Appropriate working conditions can be chosen with regard to apparel, environmental temperature, and work load.

Adult↗
PubMed1987

A new anti-human immunodeficiency virus substance, glycyrrhizin sulfate; endowment of glycyrrhizin with reverse transcriptase-inhibitory activity by chemical modification.

Glycyrrhizin sulfate (GLS) was synthesized and investigated for antiviral effect on the human immunodeficiency virus (HIV) in vitro in comparison with the parental anti-HIV compound glycyrrhizin (GL). In MT-4 cells after HIV infection, the virus-induced cytopathic effect and the expression of viral antigens were inhibited by 0.25 mg/ml (0.184 mM) of GLS. Moreover, GLS completely inhibited HIV-induced plaque formation in MT-4 cells at a concentration of 1 mg/ml (736 microM), the 50% inhibitory dose being 0.055 mg/ml (40 microM). GLS was found to be an efficient inhibitor of reverse transcriptase. The effect of GLS was 4 times stronger than that of GL in molar terms.

Antiviral Agents↗
PubMed1987

Incorporation of (E)-5-(2-iodovinyl)-2'-deoxyuridine into deoxyribonucleic acids of varicella-zoster virus (TK+ and TK- strains)-infected cells.

The incorporation of (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) into DNA of varicella-zoster virus (VZV)-infected human embryo fibroblasts was studied, using thymidine kinase-positive (TK+) and thymidine kinase-negative (TK-) VZV strains. [125I]IVDU was taken up by cells infected with TK+ VZV-, but not by TK- VZV- or mock-infected cells. [125I]IVDU was incorporated into both VZV DNA and cellular DNA of TK+ VZV-infected cells. When the cells were exposed to 0.3 microM IVDU, a more marked shift was noted in the buoyant density of viral DNA than of host DNA. In contrast, the DNAs isolated from TK- VZV- or mock-infected cells did not exhibit a detectable incorporation of [125I]IVDU. [125I] IVDU-labeled VZV DNA was purified from the viral nucleocapsids of TK+ VZV-infected cells. Substitution of no more than 0.1-1% of the thymidine residues in the VZV DNA by IVDU seemed to suffice to inhibit the replication of VZV.

Autoradiography↗
PubMed1987

Interferon-alpha enhances the production of leukotriene B4 in murine peritoneal macrophages stimulated by opsonized zymosan.

Murine peritoneal macrophages pretreated with interferon (IFN)-alpha and then stimulated by opsonized zymosan produced two to three times more LTB4 than untreated macrophages. However, PGE2 production was not changed by IFN-alpha. Meanwhile, IFN-gamma did not affect the production of LTB4 and PGE2. From the results it is considered that IFN-alpha can modulate inflammation or host defence through the production of LTB4.

Animals↗
PubMed1987

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1985). II. Background of patients].

We have investigated relationships between patients' backgrounds and isolates from urinary tract infections in reference to various conditions, such as sexes, age distribution by sex, species of causative organisms by sex, age distribution according to species and types of infections, species and infections before and after treatment with antibacterial agents, and species and detected places. As for the relationship between sexes and types of infections, although simple urinary tract infections were consistently found at about 20% in men and at about 80% in women between 1981 and 1983, these infections were seen at 24.4% in men and at 75.6% in women in 1984, and at 26.6% and at 73.4% in 1985, indicating slight decreases in the ratio of women. By contrast, complex urinary tract infections were found in men at about 60-70% from 1981 up to 1985, regardless of the presence or absence of indwelling catheter. There were no noticeable changes according to age during this 5-year period in incidences of infections including simple urinary tract infection and complex urinary tract infection with or without indwelling catheter. Thus, backgrounds of patients with urinary tract infections, including sex, age and simple or complex infections, were fairly consistent throughout this period, while there were relatively large changes in species of isolates. Enterococcus faecalis was isolated at about 8% of both men and women in 1982 and 1983, but its isolation rates were increased to 22.5% of men and 17.9% of women in 1984. In 1985 this species was isolated in 14.9% of men and 7.6% of women, and in 11.2% of all patients. Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp. and Enterococcus spp. were detected at rates of 3.2%, 8.1%, 0.7% and 1.0%, respectively, and 24.2% of isolated strains were Gram-positive organisms. When species of isolates before treatment with antibacterial agents and their isolation rates were analyzed, it was found that the isolation rate of E. faecalis increased dramatically in 1983, and that this tendency was still seen in 1984. The isolation rate of Gram-positive organisms was 25% in 1984 and 24.3% in 1985. Escherichia coli was consistently isolated at about 40%, but, as far as simple urinary tract infections are concerned, its isolation rate decreased by about 10% in 1985, compared to 1982 and 1983. These results suggested that causative organisms for simple urinary tract infections became similar to those for complex urinary tract infections. In other words, isolates obtained from complex urinary tract infections before treatment were similar to those of simple infections.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1987

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1985). I. Susceptibility distribution].

The results of determinations of sensitivities of bacterial strains to various antibiotics are summarized as follows: 1. Against Escherichia coli, ofloxacin (OFLX) showed the strongest activity among oral antibacterial and antibiotic agents. Its MIC90 was below 0.10 micrograms/ml. The next strongest activity was found in mecillinam (MPC), cefaclor (CCL) and pipemidic acid (PPA); MIC90's of these agents 3.13 micrograms/ml. Cefotiam (CTM), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX) and latamoxef (LMOX) had MIC90 below 0.39 micrograms/ml. MIC90's of cefmetazole (CMZ) and cefoperazone (CPZ) were 1.56 micrograms/ml. Aztreonam (AZT) and carumonam (CRMN) in the monobactam group showed strong activities with MIC90's at 0.20 micrograms/ml. 2. Although Klebsiella pneumoniae had a strong resistance to ampicillin (ABPC) and showed relatively low sensitivities to other oral antibacterial and antibiotic agents, OFLX maintained high activity against this species and showed MIC90 of 0.39 micrograms/ml. Among injectable antibiotics, third generation cephems showed the strongest activity to this species with MIC90 of CZX below 0.10 micrograms/ml, of CTX and CMX 0.20 micrograms/ml, and of LMOX 0.78 micrograms/ml. MIC90 of CPZ was 6.25 micrograms/ml, which was the same as those of cefazolin (CEZ) and cefoxitin (CFX). CTM had similar MIC90 to LMOX, namely, 1.56 micrograms/ml. MIC90 of CMZ was 3.13 micrograms/ml. Monobactams AZT and CRMN showed strong activities to this species; their MIC90's were below 0.10 micrograms/ml and 0.20 micrograms/ml. 3. Although Citrobacter freundii generally exhibited low sensitivities to antibacterial and antibiotic agents examined, it showed high sensitivity to OFLX, at MIC80 of 0.78 micrograms/ml. This species showed low sensitivities to MPC, nalidixic acid (NA), PPA, and sulfamethoxazole-trimethoprim (ST). Among injectable antibiotics, LMOX and CMX had activities against this species; namely, MIC80's were 6.25 and 3.13 micrograms/ml, respectively. Among monobactams, AZT showed MIC80 of 12.5 micrograms/ml, and CRMN had that of 6.25 micrograms/ml. 4. Against Enterobacter cloacae, the strongest antibacterial activity was found with OFLX which had MIC90 of 0.39 micrograms/ml. A relatively strong activity was seen with MPC. MIC80 of MPC was 1.56 micrograms/ml. Except to CTM, this species had poor sensitivities to injectable first and second generation cephems, and their MIC80's were over 200 micrograms/ml. MIC80 of CTM was 25 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗