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Biomedical subjects

R Zeller

Publications and source records attributed to R Zeller.

At least 73 records · Page 4Linked to original sources

Ectopic expression of genes during chicken limb pattern formation using replication defective retroviral vectors.

A gene transfer method to ectopically express genes during chicken limb pattern formation using replication defective retroviral vectors has been established. Spherical non-proliferating (mitomycin C treated) aggregates of clonal retrovirus producing cells were grafted directly into developing chicken wing buds. The cell aggregates had to be placed in direct contact with the highly proliferative cells of the wing bud to promote efficient in vivo infection of embryonic cells by the released retroviral particles. The majority of grafts resulted in widespread expression of a reporter gene (encoding bacterial beta-galactosidase) during limb pattern formation and early limb bud outgrowth without affecting morphogenesis. This method provides a novel approach to study the effects of ectopic gene expression on limb pattern formation. Possible future applications to study other developmental processes are discussed.

Animals↗

The chicken limb deformity gene encodes nuclear proteins expressed in specific cell types during morphogenesis.

The chicken limb deformity (ld) mutation affects morphogenesis of both limbs and kidneys and is one of few murine mutations for which the affected gene has been isolated. Analysis of the chicken homolog reveals evolutionary conservation of large parts of the encoded ld gene products. This is the first study of these proteins, their intracellular localization, and their temporal and spatial distribution during embryogenesis. A major 180-kD protein is expressed in chicken embryos and certain adult tissues. The proteins are localized in the nuclei of different embryonic cell types in a characteristic punctate pattern. In the developing chicken limb bud, they are expressed in the newly differentiated apical ectodermal ridge and the mesenchymal compartment, where an unequal distribution along the anteroposterior and, subsequently, the dorsoventral axes, is observed. During kidney morphogenesis, expression is initially restricted to the epithelial compartment of the pronephros and mesonephros. These results correlate well with the previous analysis of the murine ld phenotype and imply determinative roles for ld gene products during the morphogenesis of limbs and kidneys. Unexpected expression in the notochord, floor plate, and ventral horns suggests an involvement of the ld gene products in establishment of the dorsoventral polarity of the neural tube.

Amino Acid Sequence↗

An evaluation of AIDS education: a quasi-experimental exploration.

This study reports on a quasi-experimental study designed to evaluate the relationship between receiving classroom instruction and subsequent AIDS knowledge, behavior, and attitudes. Survey information was gathered from 61 students enrolled in an AIDS course and 68 students enrolled in "control" courses. Both groups were pretested at the beginning of the semester and again at the end of the semester concerning AIDS knowledge, behavior, and attitudes. The results obtained indicated that there was a widespread acceptance of the conventional wisdom concerning AIDS in both the experimental and control groups prior to the study. Few behavior changes were observed as a result of the AIDS curriculum. Three empirically distinct factors, "interaction," "constraint," and "testing," emerged from the attitude measures. Respondents were more accepting of interacting with persons with AIDS across time. Moreover, respondents in the experimental group were more reticent to advocate mandatory AIDS testing vis-à-vis those in the control group across time.

Acquired Immunodeficiency Syndrome↗

[Salter's single-stage bilateral pelvic osteotomy].

45 children (3 years 9 months old in average), suffering from congenital dislocation of the hip or acetabular dysplasia have sustained a bilateral innominate osteotomy in a single stage. Two different operative procedures have been used: "simultaneous osteotomy" (15 children) and "successive osteotomy" (30 children). The post-operative follow-up lasted 4 years 3 months. On both sides, the correction of acetabular deformity was obtained, the average value of the acetabular angle which was 36.6 in a pre-operative state, being 17.1 post-operative and 11.5 at the last follow-up. Complications were rare (3 superficial infections, 1 Kirschner wires migration and 2 hip instabilities which called for a capsulorraphy). The results were excellent for 83 hips, fair for 3 hips in 3 children (asymmetrical shift of the osteotomy) and poor for 4 hips in 3 children (who were contraindications of the Salter's osteotomy). The authors conclude that one-step bilateral innominate osteotomy is viable and simple. It makes a second operation unnecessary and results in a better angular gain compared to that obtained after unilateral osteotomy.

Blood Loss, Surgical↗

'Formins': proteins deduced from the alternative transcripts of the limb deformity gene.

Vertebrate limb formation is an evolutionarily conserved process programmed by an array of morphogenetic genes. As a result of transgene insertion, we previously identified a mutation at the mouse limb deformity (ld) locus that disrupts embryonic pattern formation, resulting in a reduction and fusion of the distal bones and digits of all limbs as well as variable incidence of renal aplasia. We have now characterized the ld locus at the molecular level. It contains evolutionarily conserved coding sequences that are transcribed in adult and embryonic tissues as a complex group of low abundance messenger RNAs created by alternative splicing and differential polyadenylation. The association of these transcripts with the gene responsible for the mutant phenotype was established by demonstrating that they are disrupted in two independently arising ld alleles. We have now deduced the structure of several novel proteins (termed formins) from the long open reading frames encoded by the various ld transcripts. The observation of these different RNA transcripts in different tissues suggests that the formins play a part in the formation of several organ systems.

Alleles↗

Disruption of formin-encoding transcripts in two mutant limb deformity alleles.

The recent identification of a gene residing at the mouse limb deformity (ld) locus permits us to test the hypothesis that disruption of this gene is responsible for an inherited anomaly affecting embryonic pattern formation. The gene gives rise to alternatively processed messenger RNAs that can be translated as a family of related protein products, termed the formins. We have now analysed transcripts from this gene in four independently isolated mutant alleles. In two of these, the ldHd allele (created by insertion of a transgene) and the ldIn2 allele (created by a translocation-inversion involving mouse chromosomes 2 and 17), a common subset of ld transcripts is abolished, but others are apparently unaltered. The correlation of altered transcripts in two independent ld mutants strongly supports the notion that one or more altered formins is responsible for the observed phenotype. That the defect is limited to the limb and kidney, despite expression of ld mRNA in other unaffected organs, suggests that these mutant alleles represent only partial loss of ld function.

Alleles↗