RESUMO
Direct enzymatic assay of urinary sulfated bile acids is a sensitive, rapid, minimally invasive, and convenient method of detecting cholestasis in young infants. It may replace measurement of serum direct bilirubin for selective screening for biliary atresia and neonatal hepatitis syndrome at 1 month of age.
Assuntos
Ácidos e Sais Biliares/urina , Bilirrubina/sangue , Colestase/diagnóstico , Triagem Neonatal , Atresia Biliar/sangue , Atresia Biliar/diagnóstico , Atresia Biliar/urina , Colestase/sangue , Colestase/urina , Feminino , Hepatite/sangue , Hepatite/diagnóstico , Hepatite/urina , Humanos , Lactente , Recém-Nascido , Masculino , Sensibilidade e Especificidade , Sulfatos/urina , SíndromeRESUMO
Mice lacking functional T and B lymphocytes offer an in vivo animal model for the study of human immune functions. We have attempted to optimize the reconstitution of severe combined immunodeficiency (SCID) mice with human peripheral blood lymphocytes (PBL) using radiation, anti-asialo GM1 antibody or cyclophosphamide (Cy) treatment of the mice and in vitro stimulation of human PBL with interleukin (IL)-2 prior to their transfer to the mice. Total human IgG and tetanus-toxoid (TT)-specific human IgG responses of the mice were used as parameters of successful reconstitution. Treatment of the mice with anti-asialo GM1 antibody significantly enhanced total human IgG levels, but not TT-specific antibody responses, whereas irradiation or Cy treatment of the mice had no effect on human antibody production. In vitro treatment of human PBL with IL-2 prior to engraftment significantly decreased total human IgG responses of human PBL-grafted SCID mice. The immune responses of individual mice within a group were highly variable, which constitutes a major disadvantage of this model.
Assuntos
Linfócitos B/imunologia , Imunodeficiência Combinada Severa/imunologia , Animais , Anticorpos/farmacologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/efeitos da radiação , Ciclofosfamida/farmacologia , Modelos Animais de Doenças , Gangliosídeo G(M1)/imunologia , Humanos , Imunoglobulina G/imunologia , Interleucina-2/farmacologia , Camundongos , Camundongos SCID , Proteínas Recombinantes/farmacologia , Toxoide Tetânico/imunologia , Irradiação Corporal TotalRESUMO
When first tested for abnormal hemoglobins, a 2-year-old boy, appeared to have Hb F, Hb S and Hb A2. Confirmatory testing revealed a beta chain variant inherited from his father and beta S from his mother. Analysis of tryptic peptides in conjunction with automated DNA sequence analysis showed that the variant hemoglobin was Hb Shelby [beta 131(H9)Gln-->Lys (CAG-->AAG)]. Heat and mechanical stabilities of various liganded Hb Shelby tetramers were compared to those of Hb A and Hb S. Oxy-Hb Shelby precipitated more readily than oxy-Hb A, but was much more stable than oxy-Hb S during mechanical agitation. In contrast, oxy-Hb Shelby was much less stable than oxy-Hb A and oxy-Hb S following heat treatment. Met-Hb Shelby was most unstable compared to other liganded forms of Hb Shelby, while deoxy- and carbonmonoxy-forms of Hb Shelby showed similar heat-induced precipitation rates. These data indicate that heat instability of Hb Shelby is accompanied by heme oxidation, and that denaturation by mechanical agitation occurs in the absence of heme oxidation. Hb Shelby, like Hb A, can form hybrids with Hb S which participate in polymer formation in vitro. However, Hb S/Hb Shelby hybrids copolymerized with Hb S less than A/S hybrids. Since the patient's MCHC value is normal, this finding coupled with the elevated Hb A2 and Hb F levels, both of which are known to inhibit polymerization of Hb S, may contribute to the patient's mild clinical presentation.
Assuntos
Globinas/genética , Hemoglobinas Anormais/genética , Traço Falciforme/genética , Sequência de Bases , Pré-Escolar , Feminino , Hemoglobina Falciforme/química , Heterozigoto , Temperatura Alta , Humanos , Ligantes , Masculino , Dados de Sequência Molecular , Polímeros , Desnaturação Proteica , Solubilidade , Estresse MecânicoRESUMO
Wagenbach et al. (1991, BioTechnology, 9, 57-61) have recently developed a system for producing soluble recombinant tetrameric hemoglobin in yeast: hemoglobin begins to appear 4-5 h after induction with galactose, alpha- and beta-globin chains fold in vivo and endogeneously produced heme is incorporated into hemoglobin tetramers. We have further characterized the oxygen-binding properties, as well as the tetramer stability, of recombinant human Hb A made in yeast. After purification by ion-exchange chromatography, a single band at the same position as normal human Hb A was obtained using cellulose acetate electrophoresis. Although the oxy and deoxy forms of purified recombinant Hb A made in yeast were spectrophotometrically identical to native human Hb A, the oxygen-binding curve was shifted slightly left of that for native human Hb A. Further purification of recombinant hemoglobin by FPLC revealed two fractions: one (fraction B) with low cooperativity and high oxygen affinity, and the other (fraction A) with almost identical cooperativity and oxygen affinity compared with native human Hb A. The Bohr effect of fraction A was also identical to native human Hb A. Hemoglobin in fraction B with lowered cooperativity precipitated approximately 1.5 times faster than normal human Hb A during mechanical agitation, while hemoglobin in fraction A with normal cooperativity precipitated with kinetics identical to native human Hb A. These results suggest that some of the recombinant molecules made in yeast fold improperly, and that these molecules may exhibit decreased cooperativity for oxygen binding and decreased stability.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hemoglobinas/metabolismo , Oxigênio/metabolismo , Regulação Alostérica , Variação Genética , Hemoglobinas/química , Hemoglobinas/genética , Humanos , Concentração de Íons de Hidrogênio , Conformação Proteica , Desnaturação Proteica , Dobramento de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , TransfecçãoRESUMO
Thirteen asthmatic children were enrolled in a swimming program during five days. Pulmonary function test before and after swimming training was evaluated. Training did not change pulmonary function values, and asthmatic children improved swimming distance and enhanced swimming ability. No side effects were observed during study. After asthma can questionnaires indicated a high degree of enthusiasm and acceptance of the program by children and parents.
Assuntos
Asma/reabilitação , Natação , Adolescente , Asma/fisiopatologia , Criança , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Resistência FísicaRESUMO
Se incluyeron 13 niños asmáticos en un programa de natación durante cinco dias. se realizaron pruebas de función pulmonar antes y despúes de la práctica de natación . Durante el entrenamiento nom se encontraron cambios en las pruebas de función pulmonar y los niños aumentaron la distancia nadada y su habilidad en la nataciòn. Se efectuaron efectos secundarios durante el estudio. Al final del campeonato de niños asmáticos una encuesta indicó gran entusiasmo y aceptación por parte de los niños y sus padres.