Biomedical subjects

S Shigeta

Publications and source records attributed to S Shigeta.

At least 73 records · Page 4Linked to original sources

PubMed1998

Upregulation of HIV-1 replication in chronically infected cells by ingenol derivatives.

We have previously reported that ingenol derivatives are highly potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in acutely infected cells. In this study, however, we have found that some ingenol derivatives strongly enhance the replication of HIV-1 in chronically infected cells at nanomolar concentrations. One of the derivatives could activate nuclear factor kappa B (NF-kappa B), a potent inducer of HIV-1 replication, through the activation of protein kinase C (PKC). Whereas another derivative, which affected neither PKC nor NF-kappa B, significantly enhanced HIV-1 replication, suggesting that a PKC-independent mechanism may also exist in ingenol derivative-induced HIV-1 upregulation.

Butyrates↗

PubMed1998

The cooperative effect of interferon-alpha and ribavirin on subacute sclerosing panencephalitis (SSPE) virus infections, in vitro and in vivo.

We studied the effects of two antiviral agents, human interferon-alpha (IFN-alpha) and ribavirin, on subacute sclerosing panencephalitis (SSPE) virus infections in hamsters. By intracranial administration, IFN-alpha alone improved the survival of infected hamsters by 20% at a dose of 6 x 10(4) IU/kg every other day for 10 days. When the dose of IFN-alpha was increased incrementally to 6 x 10(6) IU/kg, the survival rate increased by 70% in a dose-dependent manner. The combination of IFN-alpha and ribavirin had a synergic inhibitory effect on the replication of SSPE virus in cell culture. Combination of IFN-alpha (at a dose of 6 x 10(5) IU/kg) with ribavirin (at a dose of 1 mg/kg) completely prevented mortality. This was significantly better than either IFN-alpha or ribavirin monotherapy (p < 0.05). Under the conditions used, IFN-alpha did not enhance the toxicity of ribavirin in hamsters. Intraventricular administration of high dose IFN-alpha and ribavirin may have potential usefulness in the treatment of patients with SSPE.

Animals↗

PubMed1998

RD6-2198, a novel betain-type fluoroalkylated oligomer, inhibits the replications of human immunodeficiency virus type 1 and other enveloped viruses.

We have examined a novel betain-type fluoroalkylated oligomer, RD6-2198, for its inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses, including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively) and respiratory syncytial virus (RSV) in cell cultures. We have found that the compound is a potent and selective inhibitor of these viruses. RD6-2198 inhibited the replication of HIV-1IIIB at a concentration of 0.85 microg/ml with a selectivity index greater than 59 in MT-4 cells. Furthermore, its 50% effective concentration (EC50) values for HSV-1, HSV-2 and RSV, were 0.51, 0.94 and 3.0 microg/ml, respectively. We found that the RD6-2198 suppressed the gp120-CD4 interaction (as monitored by an enzyme-linked immunosorbent assay (ELISA) method). RD6-2198 also inhibited the binding of anti-gp120 monoclonal antibody to gp120 expressed on MOLT-4/IIIB cells (MOLT-4 cells chronically infected with HIV-1IIIB). However, the compound did not inhibit the interaction of anti-CD4 antibody with CD4. These results suggest that RD6-2198 interacts with the viral envelope glycoprotein and thereby inhibits the viral adsorption process. In addition, RD6-2198 was also found to suppress the proliferation of MOLT-4/IIIB cells. When applied topically, RD6-2198 at a concentration of 10 mg/ml completely protected mice from an intravaginal HSV-2 infection.

Animals↗

PubMed1998

Altered antigenicity of M-177, a 177-kDa allergen from the house dust mite Dermatophagoides farinae, in stored extract.

BACKGROUND: A high molecular weight allergen, M-177 (177 kDa) was isolated from Dermatophagoides farinae using a specific antibody raised to an allergenic clone Mag 3, which was obtained by immunoscreening a mite cDNA library. The potent IgE reactivity of M-177 is comparable with that of Der f 2. OBJECTIVE: The aim of this study was to analyse the molecular characteristics and the allergenic activity of M-177 in stored mite extracts. METHODS: Antigens were analysed by immunoblotting and enzyme-linked immunosorbent assay (ELISA; inhibition). Allergenic activity was estimated from IgE reactivity and the results of a histamine release assay. RESULTS: The intact M-177 molecule was present in high concentrations in fresh extract obtained from purified mite bodies, but was only detected in small amounts in stored extracts. Instead of the intact molecule, anti-Mag 3 antibody detected various cross-reactive antigens in the stored preparations. Studies of a stored liquid extract showed that these cross-reactive antigens were produced by the degradation of M-177, and that this change was suppressed by the addition of protease inhibitors. Interestingly, the allergenic activity of the fragmented M-177 (sM-177) isolated from the stored extracts was greater than that of the intact antigen. Specific IgE reacted with sM-177 in 84.2% of 38 sera samples from patients allergic to mites, while 65.8% were positive for M-177-specific IgE. Similarly, the histamine release test showed that sM-177 had greater allergenic activity in vitro. ELISA inhibition indicated that the increased allergenic activity resulted from alteration of the antigenicity with the degradation of M-177. CONCLUSIONS: M-177 is a protease-sensitive allergen. The breakdown products of M-177 provoked higher allergenic activity than the intact allergen.

Animals↗

PubMed1998

Detection and sequence analysis of borna disease virus p24 RNA from peripheral blood mononuclear cells of patients with mood disorders or schizophrenia and of blood donors.

Borna disease virus (BDV) p24 RNA was detected in the peripheral blood mononuclear cells (PBMCs) of psychiatric patients and blood donors by nested reverse transcriptase PCR (RT-PCR). The prevalences of BDV p24 RNA in patients with mood disorders (4%) and schizophrenia (4%) were not significantly different from that in blood donors (2%). This finding was inconsistent with previous reports that showed either a high prevalence or absence of BDV p24 RNA in patients with psychiatric disorders. The differences in BDV p24 RNA prevalence in these studies may be due to differences in the criteria for positivity, the number of PBMCs used for RNA extraction, or the amount of RNA tested for nested RT-PCR or to laboratory contamination. Sequence analysis of BDV p24 RNA from the PBMCs of patients and blood donors showed a high nucleotide sequence conservation but definite nucleotide mutations compared with horse BDV p24 RNA sequences. In comparison with human BDV p24 RNA sequences previously reported from Japan and Germany, there were several positions with silent nucleotide mutations among these clones.

Adult↗

PubMed1998

Approaches to antiviral chemotherapy for acute respiratory infections.

The causative agents of acute respiratory infections (ARI) in infants and children are mostly thought to be viruses. Some ARI in adult patients may be caused by bacteria but most often the causes are virus infections. When ARI affect immunocompromised patients or the elderly the mortality rates are significantly higher than in immunocompetent individuals. Many types of viruses cause ARI. Among them, influenza viruses A and B and respiratory syncytial virus (RSV) are thought to be the most important because of the severity of illness after infection and their high communicability in the human population. Recently, several novel antiviral drugs against ARI have been developed and some are proceeding in clinical trials. This review covers current investigations into antiviral compounds targeted at several points in the virus life-cycle. This includes PM-523, which broadly inhibits ortho- and paramyxo-viruses, two neuraminidase inhibitors for influenza virus, neutralizing antibody to RSV and chimeric soluble ICAM-1-IgA molecules targeted against rhinoviruses.

Acute Disease↗

PubMed1998

Inhibitory effects of podophyllotoxin derivatives on herpes simplex virus replication.

Podophyllotoxin and its derivatives were examined for inhibitory effects on the replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), including acyclovir-resistant virus and clinical isolates. Deoxypodophyllotoxin (RD4-6266) proved to be a highly potent and selective inhibitor of all HSV strains in MRC-5 cells. EC50 values of RD4-6283 (in which the methylenedioxy ring A is modified) for HSV-1 and -2 were inferior to those of deoxypodophyllotoxin. However, podorhizol (RD4-6277) and 5'-methoxy-podorhizol (RD4-6276), in which ring C is absent, did not inhibit HSV replication. Moreover, RD4-6266 also inhibited the production of infectious virus particles of HSV-1 KOS strain and HSV-2 G strain. In contrast, none of the podophyllotoxin derivatives were found to have an antiviral effect against influenza A virus, respiratory syncytial virus or human cytomegalovirus in doses not toxic to the cells.

Antiviral Agents↗

PubMed1998

Inhibition of human cytomegalovirus proteinase by salcomine derivatives.

Salcomine, N,N'-bis(salicylidene)ethylene diamino-cobalt (II), and its derivatives were evaluated for their ability to inhibit selectively human cytomegalovirus (HCMV) proteinase activity. The 50% inhibitory concentration (IC50) of salcomine was 1.4 microM for HCMV proteinase, but > 200 microM for three other serine proteinases (trypsin, > 250 microM; chymotrypsin, 206 microM; and elastase, > 250 microM). Two salcomine derivatives also inhibited HCMV proteinase with IC50 values under 2 microM. Studies of the structure-activity relationship of salcomine-related compounds showed that the phenyl moiety and the spacer moiety (distance between the two amines) were instrumental in the inhibition of HCMV proteinase. Moreover, salcomine inhibited the growth of laboratory strain AD169 and three clinical isolates at a 50% effective concentration (EC50) range of 1.92-2.89 microM. These results show that salcomine derivatives are potent and selective inhibitors of HCMV proteinase and HCMV replication in cell culture. Salcomine derivatives appear to be worth pursuing as candidate drugs for the chemotherapy of HCMV infection.

Antiviral Agents↗

PubMed1998

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996). I. Susceptibility distribution].

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 680 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period of June 1996 to May 1997. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.4% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 69.6% and most of them were Escherichia coli. Susceptabilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90S of 2 micrograms/ml. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA Arbekacin (ABK) and VCM showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90S of them were 1 or 2 micrograms/ml. The others except minocycline (MINO) had low activities with the MIC90S of 32 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and VCM showed the strongest activities against S. epidermis isolated from patients with UTIs. The MICs for all strains were equal to or lower than 2 micrograms/ml. Cefazolin (CEZ), cefotiam (CTM) and cefozopran (CZOP) were also active with the MIC90S of 4 micrograms/ml. Compared with antimicrobial activities of cephems is 1995, the MIC90S of them had changed into a better state. They ranged from 4 micrograms/ml 16 micrograms/ml in 1996. 4. Streptococcus agalactiae All drugs except MINO were active against S. agalactiae. ABPC, CZOP, IPM, and clarithromycin (CAM) showed the highest activities. The MICs for all strains were equal to or lower than 0.125 micromilligrams. Tosufloxacin (TFLX) and VCM were also active with the MIC90S of 0.5 micromilligrams. 5. Citrobacter freundii Gentamicin (GM) showed the highest activity against C. freundii isolated from patients with UTIs. Its MIC90 was 0.5 micrograms/ml. IPM and amikacin (AMK) were also active with the MIC90S of 1 microgram/ml and 2 micrograms/ml, respectively. Cefpirome (CPR) and CZOP were also active with the MIC90S of 8 micrograms/ml. The MIC90S of the others were 16 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 0.5 microgram/ml. The MIC90S of ciprofloxacin (CPFX) and TFLX were 1 microgram/ml, the MIC90 of AMK was 2 micrograms/ml, the MIC90S of CZOP, GM and ofloxacin (OFLX) were 4 micrograms/ml. The MIC50S of cephems except CEZ, cefmetazole (CMZ) and cefaclor (CCL) had changed into a better state in 1996, compared with those in 1995. 7. Escherichia coli All drugs except penicillins and MINO were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MIC90S of them were 0.125 microgram/ml or below. Among E. coli strains, those with low susceptibilities to cephems except CEZ, cefoperazone (CPZ), latamoxef (LMOX) and CCL have increased in 1996, compared with those in 1995. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with the MIC90S of 2 micrograms/ml or below. CPR had the strongest activity, the MICs for all strains were equal to or lower than 0.25 microgram/ml. Flomoxef (FMOX), cefixime (CFIX), CZOP and carumonam (CRMN) were also active with the MIC90S of 0.125 microgram/ml or below. 9. Pseudomonas aeruginosa All drugs except quinolones were not so active against P. aeruginosa with the MIC90S were 32 micrograms/ml or above. Quinolones were more active in 1996 than 1995. The MIC90S of them were between 4 micrograms/ml and 8 micrograms/ml, and the MIC50S of them were between 1 microgram/ml and 2 micrograms/ml. 10. Serratia marcescens GM showed the highest activity against S. marcescens. Its MIC90 was 1 micro

Anti-Bacterial Agents↗

PubMed1998

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996). II. Background of patients].

Clinical background was investigated on patients with urinary tract infections (UTIs) from whom 752 bacterial strains were isolated in 10 hospitals during the period from June, 1996 through May, 1997. 1. Distribution of age and sex of patients and type of infections. Among males, those with ages 40 years or older were more frequent, the higher the ages of them. Among females, those with ages in the 60's were the most frequent (24.6%), and those with ages in the 20's, 40's and 50's were about 13%. With regard to type of infections, more than a half of infections among males with ages 30 years or older were of complicated types, but most of infections among females were of uncomplicated types, especially among females of ages less than 60 years. 2. Ages of patients and types of pathogens. The higher the ages of patients, the lesser became the isolation frequencies of Escherichia coli, but the higher were those of Pseudomonas aeruginosa and Klebsiella spp. 3. Effect of antibiotic use on isolation frequencies of pathogens. Use of antibiotics decreased pathogens isolated from patients with uncomplicated UTIs drastically (231 isolates before antibiotics compared to 60 after). Even isolated pathogens from patients with complicated UTIs decreased drastically with the use of antibiotics when indwelling catheters were not in use (193 isolates before antibiotics compared to 75 after), but when indwelling catheters were in use, antibiotics apparently failed to decrease the isolation frequency. 4. Surgical procedures and types of causative organisms for UTIs. From cases of uncomplicated UTIs, E. coli was the most frequently isolated, followed by Enterococcus Faecalis and Klebsiella spp. E. coli was the most frequently isolated organism from complicated UTIs without indwelling catheters. When a surgical procedures were not done, E. coli was isolated most frequently. From cases of complicated UTIs with indwelling catheters, P. aeruginosa, E. coli and E. faecalis were the organisms that were mainly isolated, with isolation frequencies of 23.2%, 15.2, 12.2, respectively. When no surgical procedures were used, isolation frequencies of P. aeruginosa, E. faecalis and Enterobacter spp. were 17.2%, 13.8%, 13.8%, respectively.

Adolescent↗

PubMed1998

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996), III. Secular changes in susceptibility].

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 10 hospitals during June 1996 to May 1997, and the results were compared with those obtained during the same period in earlier years. 1. E. faecalis Among E. faecalis strains, those with high susceptibilities to ampicillin and minocycline appeared to have decreased in the latest study period. 2. S. aureus To almost antimicrobial agents, S. aureus isolated from uncomplicated UTIs showed low susceptibilities. But the MIC50s of those agents for S. aureus from complicated UTIs have changed better state. Particularly, the MIC50s of imipenem and clindamycin were 0.125 microgram/ml or below in the latest period for the first time in our history. 3. E. coli The susceptibilities to piperacillin and quinolones of E. coli isolated from uncomplicated UTIs were better than those isolated from complicated UTIs. 4. Klebsiella spp. The susceptibilities to almost antimicrobial agents of Klebsiella spp. have been better during the latest period, compared to those during period of 1995-1996, but to ofloxacin and ciprofloxacin have appeared to have been lower. 5. P. aeruginosa The susceptibilities to quinolones of P. aeruginosa have been better during the latest period compared those during periods of 1995-1996. But, the susceptibilities to cefozopran, carbapenems and monobactams of P. aeruginosa isolated from complicated UTIs appeared to have been lower. These susceptibility changes should be utilized in determining clinical treatments.

Anti-Bacterial Agents↗

PubMed1997

Novel hepatitis C virus protease inhibitors: thiazolidine derivatives.

This study evaluated the inhibitory effects of thiazolidine derivatives on hepatitis C virus (HCV) protease and other human serine proteases. The inhibition efficacy was tested with a reversed-phase high-performance liquid chromatography (HPLC) assay system using a NS3-NS4A fusion protein as the HCV protease and a synthetic peptide substrate that mimics the NS5A-5B junction. Nine thiazolidine derivatives showed more than 50% inhibition at 50 microg/ml. The most potent derivative was RD4-6250, with 50% inhibition at a concentration of 2.3 microg/ml; this concentration was lower than those of other protease inhibitors reported previously. The most selective derivative was RD4-6205, with 50% inhibition at a concentration of 6.4 microg/ml, a lower concentration than those on other serine proteases (chymotrypsin, trypsin, plasmin, and elastase). These results suggest that the RD4-6205 skeleton is an important structure for inhibitory activity on the HCV protease NS3-NS4A.

Enzyme Inhibitors↗

PubMed1997

Stavudine selectively induces apoptosis in HIV type 1-infected cells.

We evaluated the cytotoxic effects of various human immunodeficiency virus (HIV-1) reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine, stavudine, and nevirapine) on HIV-1-infected and uninfected T cell lines. Among the compounds, only stavudine (not the others) proved to be more cytotoxic to MOLT-4/IIIB cells (MOLT-4 cells chronically infected with HIV-1) than to uninfected MOLT-4 cells. Its 50% cytotoxic concentrations were 59.8 and 2.2 microM for MOLT-4 and MOLT-4/IIIB cells, respectively. Stavudine was also more cytotoxic to CEM/ROD (CEM cells chronically infected with HIV type 2) than to uninfected CEM cells. Microscopic analysis revealed that stavudine induced apoptosis in MOLT-4/IIIB cells. Apparent chromatin condensation in the nucleus was observed by electron microscopy. Furthermore, a DNA fragmentation ladder was detected by agarose gel electrophoresis. Addition of thymidine to the culture medium could rescue the cells from stavudine-induced apoptosis. The expression of anti-apoptotic protein Bcl-2 was partially downregulated in MOLT-4/IIIB cells after treatment with stavudine. This downregulation was not identified in MOLT-4 cells. These results indicate that stavudine selectively induces apoptosis in HIV-1-infected T cells and may have potential as a novel strategy for effective chemotherapy of the acquired immune deficiency syndrome (AIDS).

Anti-HIV Agents↗

PubMed1997

Risk of cytomegalovirus infection after peripheral blood stem cell transplantation.

From 1992 to 1995, 105 patients received PBSCT in our hospitals and we observed no incidence of CMV-pneumonia. To clarify whether activation of CMV occurs in these patients shell vial cultures, CMV antigenemia and PCR (DNA-PCR and RT-PCR) were used as detection methods for CMV. Bronchoalveolar lavage (BAL) samples, MNC and PMN samples from peripheral blood leukocytes, and urine samples were taken from 17 patients on day 35 after PBSCT. CMV was detected in one urine specimen but not detected in any of the BAL, MNC or PMN specimens by shell vial culture. CMV antigenemia provided no positive data. Nine of the 74 samples taken from the 17 patients proved positive by DNA-PCR, but all CMV-mRNA results were negative by RT-PCR. We performed CMV antigenemia and PCR on MNC and PMN specimens from six patients every 1 to 2 weeks after transplantation to determine whether and when CMV was activated. Two patients tested positive transiently by DNA-PCR but negative throughout by both antigenemia and RT-PCR. These results suggest that the risk of CMV infection is low because the incidence of CMV activation in patients receiving PBSCT is low.

Adolescent↗

PubMed1997

Human T cell responses to recombinant mite antigens of Dermatophagoides farinae.

We studied T cell responses to four glutathione S transferase (GST)-fused mite antigens prepared in our laboratory using peripheral blood lymphocytes from mite-sensitive patients with bronchial asthma. Of the four recombinant antigens, purified GST-Mag3 had the strongest ability to cause patients' lymphocytes to proliferate, and its potency was almost comparable to that of crude mite bodies (Dfb) and faeces (Dff) antigens and a purified major antigen, Der f 2. The responder lymphocytes were mainly T cells, because the proliferative response was depleted by the treatment of lymphocytes with anti-CD3 antibody and complement, but not with anti-CD20 antibody and complement. The responsiveness of lymphocytes to GST-Mag3 correlated with that to Der f 2, but GST-Mag3 displayed slightly higher activity to stimulate lymphocytes than Der f 2. Simultaneously, the levels of Dff- and GST-Mag3-specific IgE antibodies correlated with the responsiveness of lymphocytes to GST-Mag3. These results suggest that Mag3 is a new valuable antigen for the response of T cell proliferation in mite-sensitive patients.

Allergens↗

PubMed1997

Thiadiazole derivatives: highly potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replications in vitro.

We have recently reported that thiadiazole (TDA) derivatives are highly potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication. These compounds belong to the family of nonnucleoside reverse transcriptase inhibitors (NNRTIs). In an attempt to develop more effective and pharmacologically favorable compounds, novel TDA derivatives have been synthesized and examined for their anti-HIV-1 activity in vitro. Among them, RD4-2217 was found to be the most potent inhibitor of HIV-1 replication. It inhibited replication of the HTLV-IIIB strain in MT-4 cells at a concentration of 6 nM. RD4-2217 was also inhibitory to clinical isolates and zidovudine-resistant mutants of HIV-1. The combination of RD4-2217 with zidovudine or the protease inhibitor A-75925 synergistically inhibited HIV-1 replication. Studies on the emergence of drug-resistant mutants revealed that, although much higher concentrations (1-10 microM) were required, RD4-2217 completely suppressed the breakthrough of HIV-1 in the supernatants during long-term culturing of infected cells. Furthermore, RD4-2217 at low concentrations (10 or 100 nM), in combination with zidovudine, also completely inhibited viral breakthrough. In addition, RD4-2217 had lower lipophilicity and improved protein binding as compared to its congener RD4-2024 and loviride. These results suggest that RD4-2217, one of the TDA derivatives, is worth pursuing as a candidate drug for the treatment of HIV-1 infections.

Anti-HIV Agents↗

PubMed1997

Identification of T-cell epitope sequences on an important mite antigen.

BACKGROUND: T-cell epitopes on Der 1 and Der 2 groups, the major mite allergens, have been intensively analysed, while those on the other important allergens remain to be elucidated. We have cloned four cDNAs coding for important mite allergens on the basis of frequency and capacity of IgE binding. Stimulatory action of glutathione S-transferase-fused Mag1 on lymphocytes from mite-allergic patients was relatively high among them. OBJECTIVE: To identify T-cell epitopes on Mag1, we studied the stimulating activity of truncated Mag1 proteins and synthetic peptides on proliferative response of lymphocytes from mite antigen-immunized mice and mite-sensitive patients. METHODS: Truncated Mag1 proteins were expressed as a fusion protein with beta-galactosidase in Escherichia coli pop2136 carrying a variety of deleted Mag1 inserts. Murine T-cell epitope regions were estimated by the truncated antigen-induced lymphocyte proliferation assay. Overlapping peptides covering the whole sequence of the presumed T-cell epitope regions were synthesized to identify the epitope core sequences using murine and human Mag1-specific T-cell lines. RESULTS: Amino acid range 56-70 on Mag1 molecule showed remarkable stimulatory action on murine T cells, while amino acid ranges 51-65 and 86-100 had potent stimulatory activity on human T cells. CONCLUSIONS: These results suggest that Mag1 is a valuable antigen suitable for studies on T-cell responses and T-cell epitopes in mice and humans.

Animals↗

PubMed1997

Synergistic anti-influenza virus A (H1N1) activities of PM-523 (polyoxometalate) and ribavirin in vitro and in vivo.

A Kegin-type polyoxometalate, PM-523, in combination with ribavirin, was tested for its therapeutic effectiveness against influenza virus (FluV) A (H1N1) infection in tissue culture and in mice. PM-523 [(PriNH3)6H [PTi2W10O38(O2)2] x H2O, where Pri is isopropanol] and ribavirin individually inhibited FluV A-induced cytopathic effects in Madin-Darby canine kidney (MDCK) cells at median effective concentrations (EC50s) of 30 and 34 microM, respectively, and at 70% effective concentrations (EC70s) of 48 and 72 microM, respectively. On the other hand, a combination of PM-523 and ribavirin at a ratio of 1:16 exhibited lower EC50s and EC70s than each compound used singly, and combination indices were less than 1. A wide range of combinations of PM-523 and ribavirin at ratios of from 1:128 to 1:1 exhibited additive or synergistic anti-FluV effects in MDCK cells. When these compounds were tested for their anti-FluV A activities in vivo by aerosol exposure of mice which had been infected with a lethal dose of FluV A by an intranasal route, a 1:16 combination of PM-523 and ribavirin was found to have a significantly better therapeutic effect than a single dose of either compound used singly with respect to both the survival rate of the mice and the virus titer in the lungs of the infected mice. PM-523 was effective for the treatment of experimental FluV infection, and in combination with ribavirin, PM-523 exhibited enhanced anti-FluV effects in vitro and in vivo compared with the effect of PM-523 alone.

Animals↗