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BACKGROUND: Well defined reference intervals are central to the utility of serum C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP), designated as reference markers in osteoporosis, and useful for monitoring therapeutic response in that condition. This study reports the reference intervals for plasma CTX and serum P1NP in a multi-ethnic Malaysian population. METHODS: Ethnic Malay, Chinese or Indian subjects aged 45-90 years old were recruited from Selangor, Malaysia from June 2016 to August 2018. Subjects with known medical conditions (e.g., bone disorders, malnutrition, immobilisation, renal impairment, hormonal disorders) and medications (including regular calcium or vitamin D supplements) that may affect CTX and P1NP were excluded. Additionally, subjects with osteoporosis or fracture on imaging studies were excluded. The blood samples were collected between 8 a.m. and 9 a.m. in fasting state. The CTX and P1NP were measured on Roche e411 platform in batches. RESULTS: The 2.5th-97.5th percentiles reference intervals (and bootstrapped 90%CI) for plasma CTX in men (n = 91) were 132 (94-175) - 775 (667-990) ng/L; in post-menopausal women (n = 132) 152 (134-177) - 1025 (834-1293) ng/L. The serum P1NP reference intervals in men were 23.7 (19.1-26.4) - 83.9 (74.0-105.0) µg/L, and in post-menopausal women, 25.9 (19.5-29.3) - 142.1 (104.7-229.7) µg/L. CONCLUSION: The reference intervals for plasma CTX and serum PINP for older Malaysian men and post-menopausal women are somewhat different to other published studies from the region, emphasising the importance of establishing specific reference intervals for each population.
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Colágeno Tipo I , Osteoporosis , Fragmentos de Péptidos , Procolágeno , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pueblo Asiatico , Biomarcadores/sangre , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Valores de Referencia , Colágeno Tipo I/sangreRESUMEN
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.
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Antagonistas del Receptor de Neuroquinina-1/síntesis química , Piperidonas/síntesis química , Biomasa , Cristalografía por Rayos X , Furaldehído/química , Conformación Molecular , Antagonistas del Receptor de Neuroquinina-1/química , Piperidonas/químicaRESUMEN
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.
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Virus de la Influenza B/genética , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/diagnóstico , Nucleoproteínas/genética , Anciano , Preescolar , Errores Diagnósticos , Técnica del Anticuerpo Fluorescente , Humanos , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Mutación , ARN Viral/genética , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , SingapurRESUMEN
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.
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Infecciones por Paramyxoviridae/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Estaciones del Año , Clima Tropical , Adolescente , Asma/epidemiología , Niño , Preescolar , Femenino , Gastroenteritis/epidemiología , Humanos , Humedad , Incidencia , Gripe Humana/epidemiología , Masculino , Análisis Multivariante , Estudios Retrospectivos , Singapur/epidemiología , Infecciones Urinarias/epidemiologíaRESUMEN
[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.
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[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).
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Lactonas , Sesquiterpenos , Compuestos de Espiro/síntesis química , Química Orgánica/métodos , Indicadores y Reactivos , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Plantas Tóxicas , SemillasRESUMEN
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.
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Adaptación Fisiológica , Anticuerpos Antivirales/inmunología , VIH-1/inmunología , VIH-1/fisiología , Pruebas de Neutralización , Vacunas contra el SIDA/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/inmunología , Secuencia de Bases , Línea Celular , Cartilla de ADN , Cobayas , Proteína gp120 de Envoltorio del VIH/inmunología , Humanos , Inmunoglobulinas Intravenosas/inmunología , Datos de Secuencia Molecular , Replicación ViralRESUMEN
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.
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Genes Reguladores , Virus de la Leucemia Murina de Moloney/genética , Secuencias Repetitivas de Ácidos Nucleicos , Animales , Secuencia de Bases , Línea Celular , Exodesoxirribonucleasas , Regulación de la Expresión Génica , Datos de Secuencia Molecular , Mutación , Sondas de Oligonucleótidos , ARN de Transferencia/genética , Mapeo Restrictivo , Teratoma , TransfecciónRESUMEN
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.
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ADN Viral/genética , Regulación de la Expresión Génica , Células Madre Neoplásicas/microbiología , ARN Viral/biosíntesis , Retroviridae/genética , Animales , Secuencia de Bases , Unión Competitiva , Células Madre de Carcinoma Embrionario , Elementos de Facilitación Genéticos , Virus de la Leucemia Murina de Moloney/genética , Provirus/genética , Caperuzas de ARN , Recombinación Genética , TransfecciónRESUMEN
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.