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M Mucenski

Publications and source records attributed to M Mucenski.

4 recordsLinked to original sources

Antibodies to capsular polysaccharides of group B Streptococcus in pregnant Canadian women: relationship to colonization status and infection in the neonate.

In a cohort study of 1207 pregnant women in Alberta, Canada, the serotype distributions of vaginal-rectal group B Streptococcus (GBS) isolates were compared with all isolates from neonates with invasive GBS disease identified by population-based surveillance. Serum concentrations of Ia, Ib, II, III, and V capsular polysaccharide (CPS)-specific IgG also were determined, according to serotype of the vaginal-rectal colonizing GBS strain. GBS colonization was detected in 19.5% (235 of 1207) of women. Serotype III accounted for 20.6% (48 of 233) of colonizing strains available for typing but for 37% (27 of 73) of invasive isolates from neonates (P<.01). Maternal colonization with type III was least likely to be associated with moderate concentrations of III CPS-specific IgG. Serotype III GBS is more invasive than other serotypes in this population; this may be due, at least in part, to poor maternal type III CPS-specific antibody response.

Adult↗

Initiation of adult myelopoiesis can occur in the absence of c-Myb whereas subsequent development is strictly dependent on the transcription factor.

The c-Myb transcriptional regulator is crucial to the development and functioning of haemopoietic cells, so much so that mouse embryos homozygous for an inactivated c-myb allele die from anaemia at about day 15 of gestation. By analysing c-myb(-/-) chimaeras we show that no mature cells of any lymphoid or myeloid lineage can be detected in adult haemopoietic tissues. This demonstrates that the effects of c-myb ablation on haemopoiesis are cell autonomous and correlates with an absence in the c-myb(-/-) foetal liver of uni- and multilineage CFUs. Indeed, CFU assays performed on E8.5 yolk sac cells revealed that haemopoietic progenitors are already defective at this stage. However, although cells expressing high levels of c-Kit were absent, we could detect a high proportion of CD34+CD45+ cells in the c-myb(-/-) foetal liver. Examination of chimaeric embryos revealed that c-myb(-/-) donor-derived CD34+/Kit+ cells, representing committed definitive progenitors, initially populated the foetal liver, but are unable to expand like wild type progenitors. Our results showing no megakaryocytic CFUs and a reduction in the absolute numbers of megakaryocytes in the c-myb(-/-) foetal liver also refute early suggestions that megakaryopoiesis is unaffected by the absence of c-Myb.

Animals↗

In vitro differentiation of c-myb(-/-) ES cells reveals that the colony forming capacity of unilineage macrophage precursors and myeloid progenitor commitment are c-Myb independent.

Mice homozygous for an inactivated c-myb allele exhibit embryonic (primitive) blood formation but die at about day 15 of gestation because of a failure to generate adult (definitive) haemopoiesis. Recently, it has been shown that commitment to definitive haemopoiesis does occur in vivo, but that some point in the subsequent development towards the differentiated lineages is compromised. Here we have asked whether it is possible to demonstrate this same distinction between the development of primitive and definitive haemopoiesis during the in vitro differentiation of c-myb null ES cells, and whether this can be used to define more precisely at which developmental stage the absence of c-Myb blocks the adult haemopoietic lineages. We investigated the kinetics of progenitor formation and commitment to differentiation using a combination of colony forming assays and analysis of RNA and surface antigen expression. Primitive unilineage macrophage and erythroid precursor commitment could develop in the absence of c-Myb. No precursors characteristic of definitive haemopoiesis were detected; nevertheless, we could show the expression of a programme of transcription and surface antigens which is consistent with the appearance of definitive progenitors blocked at an early multipotential stage.

Animals↗