RESUMEN
Infectious complications are a leading cause of morbidity and mortality in patients with sickle cell disease. Several mechanisms are supposed to contribute to this susceptibility. The exact reasons for the susceptibility of sickle cell patients to infection are not clear and are still a matter of debate. Interferon gamma (IFNgamma) is a key cytokine involved mainly in the defence against intracellular pathogens. We investigated a possible association of an IFNgamma +874 T/A polymorphism and infectious complications in sickle cell patients. Seventy-two sickle cell patients were typed for +874 T/A IFNgamma polymorphism. Genotype frequencies were different between cases and controls. Indeed, the T allele frequency was significantly higher in patients with infections than in patients without infections (P = 0.014). Our results suggest that the +874 T/A IFNgamma polymorphism is associated with infectious complications in sickle cell patients. T allele could be involved in infections in sickle cell patients.
Asunto(s)
Anemia de Células Falciformes/genética , Infecciones Bacterianas/genética , Interferón gamma/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/inmunología , Infecciones Bacterianas/epidemiología , Estudios de Casos y Controles , Comorbilidad , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Martinica/epidemiología , Persona de Mediana Edad , Osteomielitis/epidemiología , Osteomielitis/genética , Osteomielitis/microbiología , Sepsis/epidemiología , Sepsis/genética , Sepsis/microbiología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/genética , Adulto JovenRESUMEN
The reaction of trypsin on the heavy chain of gizzard myosin and chymotryptic HMM was investigated under restricted fragmentation conditions. The three fragments of the head part with 29 kDa, 50 kDa and 26 kDa were isolated and identified. The 66 K heavy chain segment containing the S1-S2 junction was slowly but extensively degraded liberating a S1-like entity which lacked an intact COOH-terminal 26 kDa region; this isolated species displayed full intrinsic ATPase activities but little actin-binding ability. Tryptic HMM was also formed bearing a fragmented heavy chain and lacking the 20 kDa light chain. Its actin-activated ATPase was derepressed upon cleavage of the 66 kDa segment by papain. We propose that the integral 66 kDa heavy chain component is directly involved in the regulation of the gizzard actomyosin ATPase.
Asunto(s)
Actinas/metabolismo , Molleja de las Aves/metabolismo , Subfragmentos de Miosina/metabolismo , Miosinas/metabolismo , Fragmentos de Péptidos/metabolismo , Tripsina/metabolismo , Aminoácidos/análisis , Animales , Pollos , Quimotripsina/metabolismoRESUMEN
To probe the molecular properties of the actin recognition site on the smooth muscle myosin heavy chain, the rigor complexes between skeletal F-actin and chicken gizzard myosin subfragments 1 (S1) were investigated by limited proteolysis and by chemical cross-linking with 1-ethyl-3-[3-(dimethyl-amino)propyl]carbodiimide. Earlier, these approaches were used to analyze the actin site on the skeletal muscle myosin heads [Mornet, D., Bertrand, R., Pantel, P., Audemard, E., & Kassab, R. (1981) Biochemistry 20, 2110-2120; Labbé, J.P., Mornet, D., Roseau, G., & Kassab, R. (1982) Biochemistry 21, 6897-6902]. In contrast to the case of the skeletal S1, the cleavage with trypsin or papain of the sensitive COOH-terminal 50K-26K junction of the head heavy chain had no effect on the actin-stimulated Mg2+-ATPase activity of the smooth S1. Moreover, actin binding had no significant influence on the proteolysis at this site whereas it abolished the scission of the skeletal S1 heavy chain. The COOH-terminal 26K segment of the smooth papain S1 heavy chain was converted by trypsin into a 25K peptide derivative, but it remained intact in the actin-S1 complex. A single actin monomer was cross-linked with the carbodiimide reagent to the intact 97K heavy chain of the smooth papain S1. Experiments performed on the complexes between F-actin and the fragmented S1 indicated that the site of cross-linking resides within the COOH-terminal 25K fragment of the S1 heavy chain. Thus, for both the striated and smooth muscle myosins, this region appears to be in contact with F-actin.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Actinas/metabolismo , Músculo Liso/metabolismo , Miosinas/metabolismo , Adenosina Trifosfatasas/metabolismo , Animales , ATPasa de Ca(2+) y Mg(2+) , Pollos , Dimetil Suberimidato/farmacología , Etildimetilaminopropil Carbodiimida/farmacología , Molleja de las Aves/metabolismo , CinéticaRESUMEN
The yeast glycogen branching enzyme (EC 2.4.1.18) is shown to be induced in batch culture simultaneously with the onset of intracellular glycogen accumulation. The branching enzyme structural gene (GLC3) has been cloned. Its predicted amino acid sequence is very similar to procaryotic branching enzymes. Northern analysis indicates that GLC3 mRNA abundance increases in late exponential growth phase coincident with glycogen accumulation. Disruption of the branching enzyme structural gene establishes that branching enzyme activity is an absolute requirement for maximal glycogen synthesis.