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Biomedical subjects

S H An

Publications and source records attributed to S H An.

At least 19 recordsLinked to original sources
PubMed2006

A review of recent unexpected animal disease events in Japan and Korea and the follow-up action taken.

In Japan, the need to improve countermeasures against biological weapons was recognised after the Aum Shinrikyo cult attempted to use biological weapons in 1995. This paper describes how the two relevant ministries in Japan worked together to cope with recent disease outbreaks, including cases of classical swine fever (CSF) and avian influenza, which evidence suggests might have been the result of the deliberate misuse of unauthorised vaccines that had been illegally imported. By implementing successful control measures the two ministries were able to eradicate all the diseases within very short periods. In the past few years, the Republic of Korea has also experienced outbreaks of foot and mouth disease, highly pathogenic avian influenza, and CSF, all of which had previously been absent (or had been eradicated) in Korea. A review of the historical background, major events of the outbreaks and the control measures which were implemented are presented here.

Animal Diseases↗
PubMed2001

Construction of recombinant swinepox viruses and expression of the classical swine fever virus E2 protein.

To explore the swinepox virus (SPV) as a potential live vector for immunization, a vector was developed for the construction of a recombinant SPV carrying foreign genes. In this system, a foreign gene placed under the strong vaccinia virus promoter P(11) can be inserted into the viral thymidine kinase (TK) gene, and the recombinant virus can be isolated in a non-selective medium by the co-expression of E. coli lacZ gene. Compared with the wild type virus, the TK(-)recombinant SPV showed a modest level of attenuation in porcine cells while more attenuation was observed in monkey or human cells. Using this system, a recombinant virus expressing the E2 glycoprotein of classical swine fever virus (CSFV) was produced. Engineered with the gX signal sequence of the pseudorabies virus, and transmembrane domain of E2, the E2 protein was expressed as a dimeric form in the cytoplasm of the infected cells.

Animals↗
PubMed2001

Traceback systems used during recent epizootics in Asia.

Traceback systems in most countries of Asia are not well developed, as indicated by responses to a questionnaire by veterinary officials in thirteen countries. Marking of animals for traceback is practised only in a limited number of countries in specific areas or zones and for specific purposes only. In Malaysia, traceback has been undertaken by marking farm code tattoos on pigs. This enables the identification of the farm of origin of pigs found to be infected by Nipah virus in sero-surveillance programmes. The origin of the foot and mouth disease (FMD) virus that surfaced in the Republic of Korea in March 2000 was investigated through several epidemiological studies of suspected sources of contamination such as imported hay, yellow sand, milk collection trucks and feed delivery trucks. None of these studies gave results that indicated the origin of the FMD virus. The origin of the FMD virus that was recorded in Japan in March 2000 was also investigated in epidemiological studies; in this case, imported wheat straw was incriminated as the most likely source of infection. Comparative studies of the pathogenicities of FMD (type O) viruses isolated in Taipei China, the Republic of Korea and Japan, suggest that these viruses might have originated as vaccine strains used in a third country.

Abattoirs↗
PubMed2000

High-level expression of canine parvovirus VP2 using Bombyx mori nucleopolyhedrovirus vector.

For the potential use as recombinant vaccine, canine parvovirus (CPV) major capsid protein VP2 was expressed using Bombyx mori nucleopolyhedrovirus (BmNPV) vector. CPV VP2 gene was introduced into polyhedrin-based BmNPV transfer vector pBmKSK3, and recombinant virus BmK1-Parvo was prepared. When anti-CPV.VP2 monoclonal antibody was employed in immunofluorescence staining, an intense signal was observed within BmK1-Parvo-infected Bm5 cells but not within uninfected cells or cells infected with a wild-type BmNPV-K1. In hemagglutination assay, the expression level of VP2 were 3.2 x 10(3) HA units/ml from infected Bm5 cells, 2.1x 10(5) HA units/larvae from infected larval fat body, and 1.6x 10(6) HA units/ml from infected larval hemolymph. These results suggested that BmNPV vector system using B. mori larva as host could be applied to efficient mass-production of recombinant vaccines.

Animals↗
PubMed1997

Expression of envelope protein (E2) of bovine viral diarrhea virus in insect cells.

The gene encoding the envelope glycoprotein (E2) of bovine viral diarrhea virus (BVDV) was expressed in a baculovirus. The expressed protein was detected on the surface of infected cells by immunofluorescence. Western blotting analysis showed the presence of the expressed protein of a similar molecular size to the E2 protein. The antigenicity of expressed protein were tested in guinea pigs and cattle. The immunized animals developed neutralizing antibodies against BVDV.

Animals↗
PubMed1993

Synthesis and antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugates of optical isomers of ether and thioether lipids.

Four 1-beta-D-arabinofuranosylcytosine conjugates (ara-C) (1a, b and 2a, b) of sn-1 and sn-3 isomers of 1-O-octadecyl-2-O-palmitoylglycerol and its 1-S-alkyl analogue have been synthesized, and their antitumor activity against L1210 lymphoid leukemia in mice were compared with those of the previous conjugates (3a, b) of racemates in order to determine the significance of chirality of the glycerol moieties for activity. Administration (i.p.) of a single dose (300 mg/kg) of conjugates of sn-1 (1a), sn-3 (2a) and rac (3a) isomers of the ether lipid increased lifespan of i.p. implanted L1210 lymphoid leukemic DBA/2J mice by 169, 175 and 236%, respectively. The sn-1 (1b), sn-3 (2b), and rac (3b) isomers of the thioether lipid with a single dose of 300 mg/kg produced an increase in lifespan values of 238, 263 and 250%, respectively. The results indicate that chirality of the glycerol moieties appears not to be critical for the activity, and racemates 3a and 3b are promising prodrugs of ara-C for further clinical investigations.

Animals↗
PubMed1989

2'-Fluorinated isonucleosides. 1. Synthesis and biological activity of some methyl 2'-deoxy-2'-fluoro-2'-pyrimidinyl-D-arabinopyranosides.

New reactions of methyl 2,2-difluoro glycosides are described that were utilized for synthesis of some novel nucleoside derivatives. Thus, treatment of methyl 2-deoxy-2,2-difluoro-3,4-O-isopropylidene-alpha (beta)-D-erythro-pyranoside (2) with anhydrous HCl resulted in selective displacement of one fluorine atom with chlorine to give a 2-deoxy-2-chloro-2-fluoro glycoside 3. Reaction of 3 with silylated uracil in the presence of SnCl4 provided a 2-deoxy-2-fluoro-2-uracil-substituted glycoside 4. 2-Fluoro-2-deoxy glycosides substituted with other pyrimidines at C-2 were prepared similarly by the reaction of acylated 2,2-difluoro or 2-fluoro-2-bromo derivatives (5 and 6, respectively) with silylated pyrimidines. The resulting 2'-fluorinated isonucleosides were evaluated for their antitumor and antiviral activities. Compounds 7a,b, 8a,b, and 10a,b demonstrated 50% tumor cell growth inhibition in vitro (IC50) at 10(-4)-10(-5) M. At similar concentrations no antiviral activity was observed in vitro. Therapeutic activity was obtained with 7a,b and 8a,b in DBA/2 mice with L1210 leukemia. Administration of 7a,b at 500 mg/kg, ip daily, for 5 consecutive days, resulted in a 55% increase in life span (% ILS) while administration of 8a,b in the same manner at 200 mg/kg caused a 29% ILS. Treatment with 7a,b to mice with drug-resistant L1210 sublines (5-FU and araC) resulted in 22 and 57% increases in life span, respectively. Lewis lung carcinoma and M5076 sarcoma in mice also responded to the administration of 7a,b with reductions in tumor growth for both tumors and significant increases in life span in mice with Lewis lung carcinoma. Although the mechanism of action of 7a,b is not known, it has been found to be a relatively fast-acting, cell-cycle nonspecific cytotoxic agent that decreases [3H]deoxyuridine incorporation, blocks L1210 cells at the G2 phase of the cell cycle, and is not reversed by exogenous thymidine. These 2'-fluorinated isonucleosides have demonstrated biological activity and may have potential as antitumor drugs.

Animals↗
PubMed1988

Nucleoside conjugates. 10. Synthesis and antitumor activity of 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-1,2-dipalmitins.

Three 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-1,2-dipalmitins from L-, D-, and DL-alpha-dipalmitoylphosphatidic acids have been synthesized and their antitumor activity against two ara-C2 resistant L1210 lymphoid leukemia sublines in mice were evaluated. These new prodrugs of ara-C include ara-CDP-L-dipalmitin, ara-CDP-D-dipalmitin, and ara-CDP-DL-dipalmitin. The L and DL isomers produced significant increase in life span (greater than 400%) and four to five long-term survivors (greater than 45 days) out of six animals bearing ip implanted partially ara-C resistant L1210 subline [L1210/ara-C (I)], while the D isomer displayed a marginal activity (ILS 100-121%). In contrast, the L isomer was completely ineffective against deoxycytidine kinase deficient ara-C resistant L1210 subline [L1210/ara-C (II)]. However, the results demonstrate that the L and DL isomers of ara-CDP-dipalmitin are promising new prodrugs of ara-C with improved efficacy.

Animals↗
PubMed1986

Nucleoside conjugates. 8. The preparation of 5-fluoro-2'-deoxyuridine conjugates of corticosteroids.

Three 5'-(steroid-21-phosphoryl)-5-fluoro-2'-deoxyuridines (VI-VIII) have been prepared and characterized by uv, ir, 1H-nmr, elemental analysis, chemical and enzymatic hydrolyses. These new compounds are 5-fluoro-2'-deoxyuridine conjugates of cortisol (VI), cortico-sterone (VII), and prednisolone (VIII). Besides the physical and analytical data, all of the conjugates were demonstrated to be enzymatically hydrolyzed to the corresponding steroid and 5-fluoro-2'-deoxyuridine 5'-monophosphate (III), and the latter was further shown to be hydrolyzed to 5-fluoro-2'-deoxyuridine (II) by phosphodiesterase I, 5'-nucleotidase, and acid phosphatase. However, they were shown to be resistant to hydrolysis by bacterial alkaline phosphatase.

Antineoplastic Agents↗
PubMed1986

Nucleoside conjugates. 7. Synthesis and antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugates of ether lipids.

Three new 1-beta-D-arabinofuranosylcytosine conjugates of ether lipids (alkyl glycerols) linked by a pyrophosphate diester bond have been prepared and evaluated against mouse leukemia L1210 and P388. These include ara-CDP-rac-1-O-hexadecyl-2-O-palmitoylglycerol (9a) (ara-CDP = 1-beta-D-arabinofuranosylcytosine 5'-diphosphate), ara-CDP-rac-1-O-octadecyl-2-O-palmitoylglycerol (9b), and ara-CDP-rac-1-O-octadecyl-2-O-methylglycerol (9c). Among them, conjugate 9a produced significant increase in life span (200-293%) in mice bearing ip and ic implanted L1210 lymphoic leukemia at a total dose of 400-500 mg (406-508 mumol/kg). Significant schedule dependence was not observed when the conjugate was given ip once daily on day 1, days 1, 5, and 9, and days 1-5. The new conjugates are water soluble by sonication.

Animals↗
PubMed1985

Synthesis of methyl 6-(ammonium 2-acetamido-2-deoxy-alpha-D-glucopyranosyl phosphate)-alpha-D-mannopyranoside and use of this compound for the determination of N-acetylglucosamine-1-phosphotransferase.

Methyl 6-(ammonium 2-acetamido-2-deoxy-alpha-D-glucopyranosyl phosphate)-alpha-D-mannopyranoside was synthesized and identified by 1H-n.m.r. and 13C-n.m.r. data, acid hydrolysis, and elemental analysis. It was utilized for the determination of UDP-N-acetylglucosamine-1-phosphotransferase in an assay procedure that employed methyl alpha-D-mannopyranoside as an acceptor. The assay product was identified and characterized by thin-layer chromatography with the title reference compound. The present technique does not require [32P]UDP-N-acetylglucosamine, but effectively uses commercially available UDP-[14C]GlcNAc.

Acetylglucosamine↗
PubMed1984

1-beta-D-arabinofuranosylcytosine-phospholipid conjugates as prodrugs of Ara-C.

The L-, D-, and D,L-isomers of 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-1,2-dipalmitin, new prodrugs of ara-C5, have been evaluated for antitumor activity in L1210 lymphoid leukemic mice. The L-isomer produced significant increase in life span (ILS), and longterm survivors among mice bearing i.p. and i.c. implanted L1210 leukemia and the maximal ILS values found were greater than 543 and greater than 374% with five and four 45-day survivors out of six mice, respectively, at the optimal single doses of 300 mg/kg and 125 mg/kg. The D- and D,L-isomers also displayed significant in vivo antitumor activity against both i.p. and i.c. implanted L1210 leukemia in mice with ILS range of 144-293% at a total dose of 125-250 mg/kg. Significant schedule dependency was not observed when the conjugates were administered i.p. once daily for 5 days, once every 4 days, or as a single dose, but single doses typically produced the best effects. The L-isomer was found to be a more effective prodrug of ara-C than its isomers and other lipophilic prodrugs, 5'-O-palmitoyl-ara-C and N4-acyl-ara-C. Unlike the latter prodrugs, the new conjugates are water soluble by sonication method.

Animals↗
PubMed1981

Synthesis of N-glycosylthioureas, N-glycosylrhodanines, and N-glycosyl-2-aminothiazoles and their antimicrobial activity.

A method for obtaining N-beta-D-glucopyranosylthioureas was found in the aminolysis of N-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-5-aralkylidenerhodan ines. Aminolysis of the triacetylated or tribenzoylated ribosylrhodanines generally did not give ribosylthioureas but resulted in glycosidic cleavage, although N-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)thioureas were obtained using morpholine and hydroxylamine. Ring closure of N-beta-D-glucopyranosylthiourea with ethyl bromopyruvate gave ethyl 2-(N-beta-D-glucopyranosyl)aminothiazole-4-carboxylate, and ammonolysis led to the corresponding 4-carboxamide. Antimicrobial screening against five microorganisms showed that N-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)rhodanine and the glucosylaminothiazole-4-carboxylate had the broadest spectrum of inhibitory activity, although the thioureas usually showed inhibition of some organisms.

Anti-Infective Agents↗
PubMed1981

Mitogen- and viral antigen-induced transformation of lymphocytes from normal mink and from mink with progressive or nonprogressive Aleutian disease.

Peripheral blood lymphocytes (PBL) from mink with progressive Aleutian disease (AD) were shown to be significantly less responsive to phytohemagglutinin, concanavalin A, and pokeweed mitogen than were PBL from normal mink and from mink with a nonprogressive form of AD. Response to the virus of AD was significantly greater in PBL cultures from mink with nonprogressive AD than in those from normal mink or mink with progressive AD. After experimental infection with AD virus, mink PBL were responsive to viral antigen only transiently. These findings suggest that lymphocyte responsiveness as indicated by transformation induced by mitogens or viral antigen may be an important aspect of host response to infection with the parvovirus of AD.

Aleutian Mink Disease↗
PubMed1978

Transmission of Aleutian disease from mink with inapparent infections.

In apparent or nonprogressive Aleutian disease virus infection was considered a subclinical but persistent viral infection in which infected mink did not develop tissue lesions, hypergammaglobulinemia, or high antibody titers. Transmission of Aleutian disease virus from mink with this type of infection was measured. Mink with inapparent Aleutian disease appeared healthy and had normal gamma-globulin values, but were capable of transmitting the disease by direct and indirect horizontal contact. The risk of direct or indirect horizontal transmission from mink with inapparent infection was less than from mink with progressive Aleutian disease. Infection also was directly transmitted from the dam to the kits, but again the risk of infection from dams with inapparent infection was less than from dams with progressive Aleutian disease. Mink infected from their dams before weaning developed the disease more slowly than mink which became infected after weaning.

Aleutian Mink Disease↗