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2.
Chem Commun (Camb) ; 50(61): 8324-7, 2014 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-24940819

RESUMO

An efficient synthetic route towards tosyl-protected (2S)-phenyl-3-piperidone, a common intermediate for many drugs, has been developed in 5 steps in 54% yield from biomass derived furfural. The synthetic utility of the piperidone core structure was demonstrated with the synthesis of a NK1 receptor antagonist.


Assuntos
Antagonistas do Receptor de Neuroquinina-1/síntese química , Piperidonas/síntese química , Biomassa , Cristalografia por Raios X , Furaldeído/química , Conformação Molecular , Antagonistas do Receptor de Neuroquinina-1/química , Piperidonas/química
6.
Euro Surveill ; 16(33)2011 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-21871229

RESUMO

A new influenza B variant was discovered in Singapore in April 2011 during diagnostic testing of a 3-year-old boy with respiratory symptoms. Influenza B virus was isolated from culture and confirmed by standard immunofluorescence testing, but was not detected by the routine, in-house influenza screening reverse-transcription polymerase chain reaction assay that targets the nucleoprotein (NP) gene. Subsequent sequencing investigations demonstrated that several other published assays targeting NP could also fail to detect this novel variant.


Assuntos
Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Influenza Humana/diagnóstico , Nucleoproteínas/genética , Idoso , Pré-Escolar , Erros de Diagnóstico , Imunofluorescência , Humanos , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Mutação , RNA Viral/genética , Sensibilidade e Especificidade , Análise de Sequência de DNA , Singapura
7.
Epidemiol Infect ; 139(12): 1884-94, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21226981

RESUMO

Weekly (August 2003-December 2008) numbers of five common paediatric diseases and the incidence of respiratory viruses were obtained from a children's hospital in Singapore and correlated with climate data using multivariate time-series techniques. Upper respiratory tract infections were positively correlated with the incidences of influenza A, B, respiratory syncytial virus (RSV) and parainfluenza viruses (types 1-3 combined). Lower respiratory tract infections were positively correlated with only the incidence of RSV. Both upper and lower respiratory tract infections were negatively correlated with relative humidity. Asthma admissions were negatively correlated with maximum temperature and positively correlated with the incidence of influenza B and increasing hours of sunshine. Although sporadic cases of adenovirus infection were identified, not enough cases were available for a more detailed analysis. Gastroenteritis and urinary tract infections, included as control diseases, were not correlated significantly with any climate parameters. These correlations are compatible with current understanding of respiratory virus survival under certain climate conditions and may assist the prediction of disease burdens and hospital resource planning in such tropical environments.


Assuntos
Infecções por Paramyxoviridae/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologia , Estações do Ano , Clima Tropical , Adolescente , Asma/epidemiologia , Criança , Pré-Escolar , Feminino , Gastroenterite/epidemiologia , Humanos , Umidade , Incidência , Influenza Humana/epidemiologia , Masculino , Análise Multivariada , Estudos Retrospectivos , Singapura/epidemiologia , Infecções Urinárias/epidemiologia
8.
Org Lett ; 3(17): 2669-72, 2001 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-11506605

RESUMO

[reaction: see text]. A novel In(OTf)3-catalyzed (3,5) oxonium-ene type cyclization for the facile construction of various multisubstituted tetrahydrofurans and tetrahydropyrans was successfully developed. Further mechanistic investigations unveiled an In(OTf)3-catalyzed skeletal reorganization of the tetrahydrofuran to its thermodynamic isomer under thermal conditions.

9.
J Am Chem Soc ; 123(10): 2450-1, 2001 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-11456905
10.
Org Lett ; 3(2): 279-81, 2001 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-11430054

RESUMO

[figure: see text] An efficient strategy to construct the congested C-7a quaternary chiral center of anisatin was developed, by way of an Eschenmoser-Claisen rearrangement. Conversion of the resultant amide to Kende's epsilon-lactone intermediate 3 in four steps completed a concise formal synthesis of (+/-)-8-deoxyanisatin (2).


Assuntos
Lactonas , Sesquiterpenos , Compostos de Espiro/síntese química , Química Orgânica/métodos , Indicadores e Reagentes , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Plantas Tóxicas , Sementes
11.
J Virol ; 69(1): 39-48, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7983734

RESUMO

Seven diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) were examined and found to be refractory to neutralization by antisera to recombinant gp120 (rgp120) protein from HIV-1 MN. This stands in marked contrast to the sensitivity exhibited by certain laboratory-adapted viruses. To understand the difference between primary and laboratory-adapted viruses, we adapted the primary virus ACH 168.10 to growth in the FDA/H9 cell line. ACH 168.10 was chosen because the V3 region of gp120 closely matches that of MN. After 4 weeks, infection became evident. The virus (168A) replicated in FDA/H9 cells with extensive cytopathic effect but was unchanged in sensitivity to antibody-mediated neutralization. Thus, growth in cell lines is not sufficient to render primary virus sensitive to neutralization. The 168A virus was, however, partially sensitive to CD4 immunoadhesin (CD4-Ig). Adaptation was continued to produce a persistently infected FDA/H9 culture that displayed minimal cytopathic effect. The virus (168C) was now sensitive to neutralization by MN rgp120 vaccine sera and by MN-specific monoclonal antibodies and showed increased sensitivity to HIVIG and CD4-Ig. 168C encoded three amino acid changes in gp120, including one within the V3 loop (I-166-->R, I-282-->N, G-318-->R). MN-specific monoclonal antibodies bound equally to the surface of cells infected with either neutralization-resistant or -sensitive virus. The coincidence of changes in neutralization sensitivity with changes in cell tropism and cytopathic effect suggests a common underlying mechanism(s) acting through the whole of the envelope protein complex.


Assuntos
Adaptação Fisiológica , Anticorpos Antivirais/imunologia , HIV-1/imunologia , HIV-1/fisiologia , Testes de Neutralização , Vacinas contra a AIDS/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Sequência de Bases , Linhagem Celular , Primers do DNA , Cobaias , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Imunoglobulinas Intravenosas/imunologia , Dados de Sequência Molecular , Replicação Viral
12.
Mol Cell Biol ; 10(8): 4045-57, 1990 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2370861

RESUMO

A negative regulatory element (NRE) spanning the tRNA primer-binding site (PBS) of Moloney murine leukemia virus (M-MuLV) mediates repression of M-MuLV expression specifically in embryonal carcinoma (EC) cells. We precisely defined the element by base-pair mutagenesis to an 18-base-pair segment of the tRNA PBS and showed that the element also restricted expression when moved upstream of the long terminal repeat. A DNA-binding activity specific for the M-MuLV NRE was detected in vitro by using crude EC nuclear extracts in exonuclease III protection assays. Binding was strongly correlated with repression in EC cells. Mutations within the NRE that relieved repression disrupted binding activity. Also, nuclear extracts prepared from permissive, differentiated EC cell cultures showed reduced binding activity for the NRE. These results indicate the presence of a stem cell-specific repressor that extinguishes M-MuLV expression via the NRE at the tRNA PBS.


Assuntos
Genes Reguladores , Vírus da Leucemia Murina de Moloney/genética , Sequências Repetitivas de Ácido Nucleico , Animais , Sequência de Bases , Linhagem Celular , Exodesoxirribonucleases , Regulação da Expressão Gênica , Dados de Sequência Molecular , Mutação , Sondas de Oligonucleotídeos , RNA de Transferência/genética , Mapeamento por Restrição , Teratoma , Transfecção
13.
J Virol ; 62(11): 4086-95, 1988 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3172339

RESUMO

An intragenic region spanning the tRNA primer binding site of a Moloney murine leukemia virus recombinant retrovirus was found to restrict expression specifically in embryonal carcinoma (EC) cells. When the inhibitory domain was present, the levels of steady-state RNA synthesized from integrated recombinant templates in stable cotransformation assays were reduced 20-fold in EC cells but not in C2 myoblast cells. Transient-cotransfection assays showed that repression of a template containing the EC-specific inhibitory component was relieved by an excess of specific competitor DNA. In addition, repression mediated by the inhibitory component was orientation independent. This evidence demonstrates the presence of a saturable, trans-acting negative regulatory factor(s) in EC cells and suggests that the interaction of the factor(s) with the intragenic inhibitory component occurs at the DNA level.


Assuntos
DNA Viral/genética , Regulação da Expressão Gênica , Células-Tronco Neoplásicas/microbiologia , RNA Viral/biossíntese , Retroviridae/genética , Animais , Sequência de Bases , Ligação Competitiva , Células-Tronco de Carcinoma Embrionário , Elementos Facilitadores Genéticos , Vírus da Leucemia Murina de Moloney/genética , Provírus/genética , Capuzes de RNA , Recombinação Genética , Transfecção
14.
Mol Cell Biol ; 7(10): 3775-84, 1987 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3683398

RESUMO

Embryonal carcinoma (EC) cells are nonpermissive for retrovirus replication. Restriction of retroviral expression in EC cells was studied by using DNA transfection techniques. To investigate the activity of the Moloney murine leukemia virus (M-MuLV)enhancer and promoter sequences, the M-MuLV long terminal repeat and the defined long terminal repeat deletions were linked to neo structural gene sequences that encode resistance to the neomycin analog G418. Transient expression data and drug resistance frequencies support the findings that the M-MuLV enhancer is not active in EC cells but that promoter sequences are functional. In addition, a proviral DNA fragment that encodes the leader RNA sequence of a M-MuLV recombinant retrovirus was found to restrict expression specifically in EC cells. Deletion analysis of the leader fragment localized the inhibitory sequences to a region that spans the M-MuLV tRNA primer binding site. It is not known whether restriction occurs at a transcriptional or posttranscriptional level, but steady-state RNA levels in transient expression assays were significantly reduced.


Assuntos
Transformação Celular Viral , DNA Viral/genética , Vírus da Leucemia Murina de Moloney/genética , Teratoma/fisiopatologia , Células Tumorais Cultivadas/microbiologia , Animais , Linhagem Celular , Análise Mutacional de DNA , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Camundongos , Regiões Promotoras Genéticas , Sequências Repetitivas de Ácido Nucleico , Fatores de Transcrição/fisiologia , Transcrição Genética
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