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Biomedical subjects

R Zeller

Publications and source records attributed to R Zeller.

At least 55 records · Page 3Linked to original sources
PubMed1995

Limb deformity proteins during avian neurulation and sense organ development.

The nuclear Limb deformity (Ld) proteins (formins) are expressed during the avian primitive streak stages. Initially, they are detected predominantly in cells of the forming notochord, scattered mesodermal precursors and the induced neural plate. No expression is detected in endodermal cells. The subsequent graded distribution of Ld positive cells along the anterior-posterior axis of the neural tube follows the antero-posterior progression of its differentiation. The Ld proteins are also differentially expressed during induction and development of both the inner ear and eye. An unequal distribution of Ld proteins along the dorso-ventral axis of the otic vesicle is observed during its initial patterning. In the eye, the Ld proteins are expressed by the optic vesicle during secondary induction of the lens placode. Following induction, the proteins are also expressed by the newly formed lens placode, a process which is reminiscent of homeogenetic induction. During differentiation of the retina and lens, the Ld domains seem to demarcate territories, giving rise to specific eye structures. A comparative analysis of the Ld distribution and BrdU incorporation in the two sense organs indicates that the proteins are predominantly expressed by committed and/or differentiating (post-mitotic) cells. In general, expression of Ld proteins is induced during determination and remains during differentiation of particular cell-types. This study implies that the nuclear Ld proteins are involved in morphogenesis of both neuro-ectodermal and mesodermal structures.

Animals↗
PubMed1995

Differential effects of retinoic acid and a retinoid antagonist on the spatial distribution of the homeoprotein Hoxb-7 in vertebrate embryos.

An antibody raised against the recombinant Xenopus laevis Hoxb-7 protein (López and Carrasco [1992] Mech. Dev. 36:153-164) recognizes the 30 kDa translation product of the Hoxb-7 gene in X. laevis and the cognate nuclear protein in chicken embryos. The X. laevis Hoxb-7 protein was expressed maternally and zygotically. Treatment of X. laevis and chicken embryos with either all-trans retinoic acid (RA) or the retinoid antagonist Ro 41-5253 (Ro; Apfel et al. [1992] Proc. Natl. Acad. Sci. U.S.A. 89:7129-7133) during early development induced malformations of the neural tube and complementary changes in the expression domain of the homeoprotein Hoxb-7. Treatment of X. laevis embryos with retinoic acid during gastrulation induced an anterior shift of the Hoxb-7 expression domain and was correlated with an enlargement of rhombomere r7. In addition to a reduction in rhombomere numbers and of forebrain size, various malformations involving all three germ layers were observed. Treatment of X. laevis embryos with the antagonist Ro before or during gastrulation caused a progressive reduction of the Hoxb-7 domain and also dose-dependent malformations of all three germ layers. RA or Ro treatment of chicken embryos from the beginning of gastrulation caused changes of the Hoxb-7 expression domain very similar to those observed in X. laevis. In particular, either a dose-dependent loss of the Hoxb-7 protein in the neural tube or an ectopic expression in the forebrain region was observed. The results of this study indicate that endogenous retinoids regulate the spatial expression of homeobox-containing genes in vertebrates.

Animals↗
PubMed1995

Nucleo-cytoplasmic translocation and secretion of fibroblast growth factor-2 during avian gastrulation.

The expression and distribution of the fibroblast growth factor-2 (FGF-2 or bFGF) proteins during early avian embryogenesis has been analysed in detail. Three FGF-2 protein isoforms of 18.5, 20.0 and 21.5 kDa are expressed during gastrulation of chicken embryos. Using whole mount immunohistochemistry, these proteins were found to be predominantly nuclear in prestreak blastodiscs during mesoderm induction. Distribution of positive cells in the epiblast was mosaic, whereas all cells of the forming hypoblast expressed the FGF-2 proteins. During primitive streak formation, the proteins started to translocate to the cytoplasm in epiblast cells but remained nuclear in the hypoblast. The FGF-2 proteins became predominantly cytoplasmic in all cells during the subsequent developmental stages. Their highest levels were detected in endodermal cells underlying Hensen's node and the newly formed notochord, the dorsal apex of all epiblast cells and, most interestingly, in the extra-cellular basal lamina separating the epiblast from newly formed mesoderm. Heparin and suramin treatment of these advanced embryos (stage 4) revealed a dose-dependent inhibition on the regression of Hensen's node and formation of mesodermal derivatives such as somites. The results are discussed with respect to current models on FGF-mediated functions during vertebrate mesoderm induction and regionalization.

Animals↗
PubMed1995

The limb deformity mutation disrupts the SHH/FGF-4 feedback loop and regulation of 5' HoxD genes during limb pattern formation.

Mutations in the murine limb deformity (ld) gene disrupt differentiation of the Apical Ectodermal Ridge (AER) and patterning of distal limb structures. However, initial outgrowth of the limb bud is not affected, suggesting that early and late functions of the AER are uncoupled. Similarly, activation of the 5' members of the HoxD gene cluster (Hoxd-11 to Hoxd-13) is not affected in ld mutant posterior limb bud mesenchyme, but the subsequent anteriorization of 5' HoxD domains is delayed by about 12 hours and is associated with reduced levels of polarising activity. These results indicate that the ld gene products act upstream of 5' HoxD genes during patterning of the autopod. Expression of the signalling molecule Sonic hedgehog (Shh) in the posterior limb bud mesenchyme is initiated normally, but ceases prematurely indicating a defect in maintenance of Shh by the ld mutant AER. Furthermore, no Fgf-4 transcripts are detected in the ld mutant AER, whereas Fgf-8 transcripts remain expressed. However, Shh expression can be rescued by heterospecific grafting of ld mutant posterior mesenchyme under a wild-type chicken AER. These studies show that the AER defect in ld homozygous limb buds causes disruption of the FGF-4/SHH feedback loop and support the proposed essential role for FGF-4 in maintaining Shh expression during limb pattern formation.

Animals↗
PubMed1995

[Distal intra-articular resection of the calcaneus in the treatment of severe or recurrent congenital clubfoot].

INTRODUCTION: Secondary adaptive bone changes and joint distorsions in clubfoot may present a barrier to adequate correction of the deformity. The purpose of our study is to show how the lateral excision of the calcaneus distal part as described by Lichtblau, in combination with an appropriate medial release allows better correction of forefoot deformity, with less recurrence rate. MATERIAL AND METHODS: Between 1974 and 1982, 43 feet in 38 patients underwent this type of surgery. Lateral excision o the calcaneus was decided preoperatively in 34 feet, for recurrence of the forefoot deformity following previous surgery. In the remaining 9 feet, this lateral excision was decided intraoperatively, because of an uncomplete correction of the fore part of the foot, despite an adequate posteromedial release. The resected angle from the distal intra-articular part of the calcaneus varied from 10 to 30 degrees with an average of 15 degrees. RESULTS: All our results were evaluated at end of growth. Mean age at follow-up was 15 years and 4 months, with an average period of 10 years and 7 months following surgery. The average forefoot adduction moved from 21 degrees preoperatively to 1 degree at last follow-up. The clinical calcaneocuboid mobility was preserved in 37 cases. Four types of complications were encountered in 7 patients: pain in 5 cases, calcaneocuboid fusion in 6 cases, recurrence of deformity in 2 cases, and overcorrection in 5 cases; this last complication was related to intraoperative overcorrection rather than a progressive deterioration of the result, and had no clinical significance. No overcorrection was seen after calcaneocuboid fusion. We have found no relation between age at surgery, and the incidence of calcaneocuboid fusion, but the two cases operated on children under one year old, ended up with a bad result. DISCUSSION: The resection of a single side of a joint may permit normal joint function to be retained. The resected cartilage is replaced by a fibrocartilage that resembles the original articular cartilage, provided the resected defect is deep enough to allow vascularization from the underlying bone. CONCLUSION: The success of this method depends on an accurate surgical technique, as described by its promoter. It can be of great help in severe and complicated clubfeet. It achieves the goal with a calcaneocuboid function often preserved.

Calcaneus↗
PubMed1994

Cell-type-specific nuclear translocation of fibroblast growth factor-2 isoforms during chicken kidney and limb morphogenesis.

Analysis of the fibroblast growth factor-2 (FGF-2 or bFGF) proteins during chicken embryonic pattern formation and organogenesis revealed that three isoforms (18.5, 20.0, and 21.5 kDa) were synthesized by alternative translation initiation from one coding region. A highly specific antiserum was raised and used for studying the temporal and spatial distribution of the FGF-2 isoforms during chicken embryogenesis. The distribution of FGF-2 proteins during limb pattern formation has been unraveled. Their presence in both ectodermal and mesenchymal cells is consistent with an involvement in regulating the balance of growth and differentiation. High levels of FGF-2 proteins were furthermore detected in all epithelial cells of the developing kidney from the pronephric stage onward. The proteins were in general predominantly cytoplasmic, but a specific subpopulation of limb mesenchymal cells and kidney epithelial cells (podocytes) showed a striking nuclear localization. Nuclear translocation of the FGF-2 proteins occurred in differentiating podocytes of meso- and metanephric glomeruli and was maintained in adult kidneys. These results, in contrast to previous in vitro studies, revealed that nuclear accumulation of FGF-2 proteins is restricted to few specific cells during embryogenesis.

Amino Acid Sequence↗
PubMed1994

[Ischio-vertebral dysplasia (a dangerous syndrome for the spinal cord)].

PURPOSE OF STUDY: A previously unreported condition is defined, diagnostic features identified, and clinical course and treatment modalities presented. MATERIAL AND METHODS: This is a retrospective study of 11 patients with ischio-vertebral dysplasia (IVD), accomplished by record and radiographic review. RESULTS: 11 patients were included in the study group, age at presentation from 1 day to 33 yrs. Follow-up ranged from 5-30 yrs. Involvement of 3 successive generations (grandmother, mother and daughter) with similar findings was present in 1 family. Common features of IVD include: peculiar facies incomplete ossification of the ischial ramus, and a dysplasic scoliosis with a significant kyphotic element, constituting a rotatory dislocation. 2 patients followed from birth demonstrated the natural history of the condition, beginning without spinal deformity, and progressing to significant deformity. The spinal deformity was manageable surgically. The scoliosis ranged from 10 degrees to 235 degrees, and the kyphosis from 0 degrees to 200 degrees (the 10 and 0 being at day 1 of age). 6 patients incurred neurological sequelae, either spontaneously or associated with surgical treatment. 2 patients died, 1 due to cardiopulmonary failure at age 33; the 2nd was an infant with severe neurologic and cardiopulmonary complications due to the spinal deformity. Multiple surgical approaches to the problems were employed. Analysis of results permitted formulation of a logical and successful approach to the problem. Pre-op mean kyphosis = 112 degrees, post-op at maximum follow-up = 67 degrees. Deformity stabilization and neurologic normalcy was produced in every patient operated but 1. DISCUSSION: The characteristics of the syndrome are clear, as is the progressive nature of the deformity. The very high risk of neurologic involvement is emphasized. Before age 10, circumferencial fusion prevents progression and neurologic deterioration. Older patients require gradual correction by skeletal traction, followed by anterior concave strut stabilization and posterior fusion (with or without instrumentation). Extreme care is necessary for protection of the particularly vulnerable neurologic structures. Early stabilization and correction is recommended for prevention of the deterioration of cardiopulmonary function.

Abnormalities, Multiple↗
PubMed1994

[A new technique of osteotomy for femoral varisation in the management of hip dislocation and paralytic subluxation of the hip].

PURPOSE OF THE STUDY: Severe valgus deformity of the upper femur is a frequent feature of the unstable paralytic hip. Thus, the insertion of the osteosynthesis material during a varization osteotomy can be technical demanding. Risks and benefits of a modified femoral varization osteotomy were evaluated in a retrospective follow-up study. MATERIAL: 53 paralytic hips (33 patients) have been operated from September 1989 to april 1993. Mean age at surgery was 6 years. The etiologies were Spinal Amyotrophy in 12 hips, Cerebral Palsy in 31 hips and miscellaneous neurologic diseases in 10 hips. The average neck-shaft angle before surgery was 162 degrees. The mean Reimers' Index was 58 per cent. METHODS: The upper femoral shaft was exposed by subperiosteal dissection in a circumferential manner. An intertrochanteric osteotomy was carried out. The direction of the femoral neck was identified. An AO 100 degree blade plate was then introduced under direct visual control through the cancellous osteotomy surface of the proximal fragment. Radiological and clinical outcome were assessed at last follow-up. Mean follow-up was 16 months. RESULTS: Solid fusion was obtained in all patients. The mean postoperative neck-shaft angle was 104 degrees. The mean Reimers' Index was 17 per cent at last follow-up. Two infections were noted. Voluminous calcifications under the femoral neck have been observed in 6 cases. Recurrence of the valgus deformity was noted in 9 hips at last follow-up. DISCUSSION: This simplified varization technique permits a large amount of varization. The medialization diminishes the problem of protruding hardware. The complications rate appears to be low without any femoral head necrosis in this series despite subperiosteal dissection of the femoral neck. CONCLUSION: The authors think that this modified varization technique may deserve consideration in the treatment of the unstable paralytic hip.

Adolescent↗
PubMed1994

[Traumatic scapulo-humeral dislocation in children and adolescents. Apropos of 9 patients].

From 1974 to 1989, 9 children or adolescents, with an average age of 12 years and 4 months were seen for traumatic dislocation of the shoulder. All patients were followed for a minimal period of 2 years following the primary dislocation. Six patients were treated with closed reduction and immobilization for 3 weeks followed by a rehabilitation program. The recurrence rate was 71%. The authors insist on the fact that traumatic glenohumeral dislocation is a rare pathology in pediatric traumatology. The recurrence rate following the initial episode is higher however than for the adult population. These patients should be followed until consolidation of their lesions.

Adolescent↗
PubMed1993

Expression of alternatively spliced bFGF first coding exons and antisense mRNAs during chicken embryogenesis.

We have identified eight different basic fibroblast growth factor (bFGF or FGF-2) transcripts which can be grouped into three classes expressed during chicken embryogenesis and in specific adult organs. Three of them encode the evolutionarily conserved bFGF proteins. Two additional mRNAs are structurally homologous to the previously isolated Xenopus laevis bFGF antisense transcripts. Their expression during embryogenesis and the inversely proportional amounts of sense and antisense transcripts in several adult organs provide further evidence for a possible regulatory role of the antisense transcripts. Unexpectedly, a novel class of three alternatively spliced bFGF transcripts expressed predominantly during embryogenesis was isolated. Alternative splicing of exon 1 of the open reading frame creates a predicted bFGF isoform containing a completely novel amino-terminal domain. This is the first report describing alternative splicing of the coding region of bFGF. Similar levels of alternatively spliced (alt-bFGF) and canonical bFGF transcripts are expressed during embryogenesis, but in adult organs alt-bFGF transcripts are far less abundant, which suggests roles for the predicted novel bFGF isoform during morphogenesis.

Alternative Splicing↗