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Biomedical subjects

R Zeller

Publications and source records attributed to R Zeller.

At least 19 recordsLinked to original sources
PubMed2006

[Orthopedic treatment of spinal deformities in infancy and early childhood].

Surgical treatment of spinal deformities in infancy and early childhood (before age 6) is often very useful if the lesion is localized and curable by one unique surgery, such as hemivertebra resection and fusion. On the contrary, if the lesion, whether idiopathic or paralytic, is extended to a large part of the spine, early surgical treatment in infancy gives very disappointing results and often worsens the status of the child, especially respiratory function if the lesion is mainly thoracic. The goal of this paper is to explain in detail indications and management of non-surgical treatment of such lesions. These are variable according to localization, etiology, and associated anomalies, and are mainly based on proper casting (often repeated), bracing (often intermittent between casting) and proper respiratory equipment. From time to time, a surgical treatment is locally indicated, but most of the time results are disappointing and the best is to repeat non-surgical treatment until proper definitive arthrodesis can be performed. This approach is not very rewarding for the child and family, but is clearly better than sudden extensive surgery in early childhood with very severe and disastrous results in adulthood. It is our hope that the recommendations and thoughts presented in this paper will help readers to manage young children using the most efficient, non-aggressive, but long-lasting therapy.

Age Factors↗
PubMed2006

Factors influencing nurses' judgements about self-neglect cases.

From the perspective of the practising nurse self-neglect may best be understood in terms of a set of complex and often poorly defined clinical problems in which two key clinical issues are "how do I judge whether this person has the capacity to make decisions about their lifestyle?" and "do we need to treat this person using mental health legislation?" These are taxing questions as judging if a patient has the capacity to make decisions about their lifestyle choices is difficult for even the most experienced clinicians. Such determinations require nurses to form a judgement as to mental capacity of the patient. We do not know what patient characteristics and in what combination nurses use these when making these judgements. This factorial survey aimed to identify which patient characteristics influenced Registered Nurses' judgements on decision-making capacity and decisions on the use of interventions which require statutory interventions in cases of self-neglect. Judgements on decision-making capacity were overwhelmingly predicted by information of the patients' mental health status. Nurses place patients in one of three broad categories of no mental illness, minor mental illness and severe mental illness. This categorization appears to operate as a fast and frugal heuristic indicating that nurses may use mental status as a cognitive screen to work from in judging self-neglect. Although there is a correlation between the severity of mental illness and the capacity for making decisions they are not the same. This study shows the continued work that needs done in educating nurses not only about self-neglect but also about the role a patient's mental status may have in assessment of problems.

Adult↗
PubMed2003

Giant magnetic anisotropy of single cobalt atoms and nanoparticles.

The isotropic magnetic moment of a free atom is shown to develop giant magnetic anisotropy energy due to symmetry reduction at an atomically ordered surface. Single cobalt atoms deposited onto platinum (111) are found to have a magnetic anisotropy energy of 9 millielectron volts per atom arising from the combination of unquenched orbital moments (1.1 Bohr magnetons) and strong spin-orbit coupling induced by the platinum substrate. By assembling cobalt nanoparticles containing up to 40 atoms, the magnetic anisotropy energy is further shown to be dependent on single-atom coordination changes. These results confirm theoretical predictions and are of fundamental value to understanding how magnetic anisotropy develops in finite-sized magnetic particles.

Journal Article↗
PubMed2001

Strongly enhanced orbital moments and anisotropies of adatoms on the Ag(001) surface.

We present ab initio calculations for orbital moments and anisotropy energies of 3d and 5d adatoms on the Ag(001) surface, based on density functional theory, including Brooks' orbital polarization (OP) term, and applying a fully relativistic Korringa-Kohn-Rostoker-Green's function method. In general, we find unusually large orbital moments and anisotropy energies, e.g., in the 3d series, 2.57 mu(B) and +74 meV for Co, and, in the 5d series, 1.78 mu(B) and +42 meV for Os. These magnetic properties are determined mainly by the OP and even exist without spin-orbit coupling.

Journal Article↗
PubMed2001

FGF signalling is required for differentiation-induced cytoskeletal reorganisation and formation of actin-based processes by podocytes.

To examine the potential role of fibroblast growth factor (FGF) signalling during cell differentiation, we used conditionally immortalised podocyte cells isolated from kidneys of Fgf2 mutant and wild-type mice. Wild-type mouse podocyte cells upregulate FGF2 expression when differentiating in culture, as do maturing podocytes in vivo. Differentiating wild-type mouse podocyte cells undergo an epithelial to mesenchymal-like transition, reorganise their actin cytoskeleton and extend actin-based cellular processes; all of these activities are similar to the activity of podocytes in vivo. Molecular analysis of Fgf2 mutant mouse podocyte cells reveals a general disruption of FGF signalling as expression of Fgf7 and Fgf10 are also downregulated. These FGF mutant mouse podocyte cells in culture fail to activate mesenchymal markers and their post-mitotic differentiation is blocked. Furthermore, mutant mouse podocyte cells in culture fail to reorganise their actin cytoskeleton and form actin-based cellular processes. These studies show that FGF signalling is required by cultured podocytes to undergo the epithelial to mesenchymal-like changes necessary for terminal differentiation. Together with other studies, these results point to a general role for FGF signalling in regulating cell differentiation and formation of actin-based cellular processes during morphogenesis.

Actins↗
PubMed2000

The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome.

Turner syndrome is characterized by short stature and is frequently associated with a variable spectrum of somatic features including ovarian failure, heart and renal abnormalities, micrognathia, cubitus valgus, high-arched palate, short metacarpals and Madelung deformity. Madelung deformity is also a key feature of Leri-Weill syndrome. Defects of the pseudoautosomal homeobox gene SHOX were previously shown to lead to short stature and Leri-Weill syndrome, and haploinsufficiency of SHOX was implicated to cause the short stature phenotype in Turner syndrome. Despite exhaustive searches, no direct murine orthologue of SHOX is evident. SHOX is, however, closely related to the SHOX2 homeobox gene on 3q, which has a murine counterpart, Og12x. We analysed SHOX and SHOX2 expression during human embryonic development, and referenced the expression patterns against those of Og12x. The SHOX expression pattern in the limb and first and second pharyngeal arches not only explains SHOX -related short stature phenotypes, but also for the first time provides evidence for the involvement of this gene in the development of additional Turner stigmata. This is strongly supported by the presence of Turner-characteristic dysmorphic skeletal features in patients with SHOX nonsense mutations.

Adult↗
PubMed2000

[Neuromuscular scoliosis. Follow-up of treatment and therapeutic principles].

The therapy of neuromuscular scolioses has to be tailored to the needs to the individual patient; there are no universally valid schemes of treatment. Detailed knowledge of neuromuscular diseases and their course is essential. For this reason, an interdisciplinary team is desirable; only in this way can all medical and surgical aspects of the underlying disease--which interfere with the therapy of the scoliosis--be treated successfully. The continual improvement in medical treatment of neuromuscular disease in recent decades has led to a significant increase in life expectancy. In addition, the severe consequences of failure to treat spinal deformities have become clear. Neglect or inadequate treatment of neuromuscular scolioses can have dramatic consequences, including inability to sit and serious impairment of cardiorespiratory status. The goal of treatment is therefore to prevent the spinal deformities leading to a dangerous worsening of respiratory status. Moreover, the therapy should improve function, which in most cases means restoring a stable sitting position. From the mechanical viewpoint this means restoration of spinal balance with a vertical spinal axis at right angles to a horizontal pelvis.

Adolescent↗
PubMed1999

Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds.

Outgrowth and patterning of the vertebrate limb are controlled by reciprocal interactions between the posterior mesenchyme (polarizing region) and a specialized ectodermal structure, the apical ectodermal ridge (AER). Sonic hedgehog (SHH) signalling by the polarizing region modulates fibroblast growth factor (FGF)4 signalling by the posterior AER, which in turn maintains the polarizing region (SHH/FGF4 feedback loop). Here we report that the secreted bone-morphogenetic-protein (BMP) antagonist Gremlin relays the SHH signal from the polarizing region to the AER. Mesenchymal Gremlin expression is lost in limb buds of mouse embryos homozygous for the limb deformity (Id) mutation, which disrupts establishment of the SHH/FGF4 feedback loop. Grafting Gremlin-expressing cells into ld mutant limb buds rescues Fgf4 expression and restores the SHH/FGF4 feedback loop. Analysis of Shh-null mutant embryos reveals that SHH signalling is required for maintenance of Gremlin and Formin (the gene disrupted by the ld mutations). In contrast, Formin, Gremlin and Fgf4 activation are independent of SHH signalling. This study uncovers the cascade by which the SHH signal is relayed from the posterior mesenchyme to the AER and establishes that Formin-dependent activation of the BMP antagonist Gremlin is sufficient to induce Fgf4 and establish the SHH/FGF4 feedback loop.

Animals↗
PubMed1999

Biomechanical behaviour in vitro of the spine and lumbosacral junction.

Six fresh human specimens extending from the 9th thoracic vertebra (T9) to the pelvis were used to study the biomechanical behaviour of the long lumbopelvic segments, including mobility of the sacrum. The loads were applied at T9 using pure couples up to 5 Nm. The displacements were measured by an optoelectronic method (VICON 140). Stress-displacement curves were obtained for the three angular components of the vertebra studied according to the plane of the principal stresses and of the two other planes corresponding to the coupled mobilities. Mobility decreased from T9 to the sacrum. There was mobility of the sacrum in relation to the pelvis in flexion, with a mean of 1.28 degrees (0.5 to 2.8 degrees); 3 sacrums showed a mobility of the order of one degree for torsional stresses. There was no sacral mobility during stresses in lateral flexion. The use of this experimental protocol with low mechanical stresses should allow the evaluation of long osteosyntheses extending to the sacrum.

Biomechanical Phenomena↗
PubMed1999

Formin defines a large family of morphoregulatory genes and functions in establishment of the polarising region.

Formin was originally isolated as the gene affected by the murine limb deformity (ld) mutations, which disrupt the epithelial-mesenchymal interactions regulating patterning of the vertebrate limb autopod. More recently, a rapidly growing number of genes with similarity to formin have been isolated from many different species including fungi and plants. Genetic and biochemical analysis shows that formin family members function in cellular processes regulating either cytokinesis and/or cell polarisation. Another common feature among formin family members is their requirement in morphogenetic processes such as budding and conjugation of yeast, establishment of Drosophila oocyte polarity and vertebrate limb pattern formation. Vertebrate formins are predominantly nuclear proteins which control polarising activity in limb buds through establishment of the SHH/FGF-4 feedback loop. Formin acts in the limb bud mesenchyme to induce apical ectodermal ridge (AER) differentiation and FGF-4 expression in the posterior AER compartment. Finally, disruption of the epithelial-mesenchymal interactions controlling induction of metanephric kidneys in ld mutant embryos indicates that formin might function more generally in transduction of morphogenetic signals during embryonic pattern formation.

Amino Acid Sequence↗
PubMed1999

Gli3 (Xt) and formin (ld) participate in the positioning of the polarising region and control of posterior limb-bud identity.

During initiation of limb-bud outgrowth in vertebrate embryos, the polarising region (limb-bud organizer) is established upon activation of the Sonic Hedgehog (SHH) signaling molecule at the posterior limb-bud margin. Another hallmark of establishing anteroposterior limb-bud identities is the colinear activation of HoxD genes located at the 5' end of the cluster (5'HoxD genes). The unique and shared functions of Gli3 and formin in these determinative events were genetically analyzed using single and double homozygous Extra-toes (Xt; disrupting Gli3) and limb deformity (ld; disrupting formin) mouse embryos. Analysis of the limb skeletal phenotypes reveals genetic interaction of the two genes. In addition to loss of digit identity and varying degrees of polydactyly, proximal skeletal elements are severely shortened in Xt;ld double homozygous limbs. The underlying molecular defects affect both establishment of the polarising region and posterior limb-bud identity. In particular, the synergism between Gli3- and formin-mediated mesenchyme-AER interactions positions the SHH signaling center at the posterior limb-bud margin. The present study shows that establishment and positioning of the polarising region is regulated both by restriction of Shh through Gli3 and its positive feedback regulation through formin. Concurrently, Gli3 functions independently of formin during initial posterior nesting of 5'HoxD domains, whereas their subsequent distal restriction and anterior expansion depends on genetic interaction of Gli3 and formin.

Animals↗
PubMed1999

Perthes' disease after the age of twelve years. Role of the remaining growth.

In order to define the prognostic factors in Perthes' disease in children older than 12 years, we reviewed 15 patients at the end of growth who were aged 12.1 to 14 years at presentation. The patients with the worst long-term prognosis (Stulberg class V) were compared with the others for age, skeletal maturity and remaining growth (Oxford method), as well as Catterall and Waldenström classifications at presentation. A significant difference (p = 0.001) was found for remaining growth (25% in Stulberg class V and 35% in the others) and also for the results at the end of growth when the remaining growth was over 30%, since this allowed sufficient time for reformation and remodelling of the femoral head.

Adolescent↗
PubMed1999

Osteochondritis dissecans: a multicenter study of the European Pediatric Orthopedic Society.

To assess of the value of conservative and operative treatment of osteochondritis dissecans of the knee, a multicenter study was performed. In 12 European countries, 798 cases of osteochondritis of the knee have been collected from 44 hospitals. Results were based on 452 patients with 509 affected knees with minimum follow-up was 1 year (mean follow-up, 3 years and 11 months) and sufficient data for evaluation: 61% were male patients; 39% female patients; 318 affected knees were found in juvenile patients; 191 affected knees were in adult or premature patients. The localization was the medial femoral condyle on the lateral side in 51% (typical site) of patients. Various other sites were involved. Of the 509 affected knees, 154 were treated conservatively, 355 were treated surgically (many with multiple operations). For evaluation, the initial situation (at the time of the diagnosis) was favorable in 198 patients (no effusion, diameter of the lesion < 20 mm and no gross dissection on imaging) and unfavorable (one of the parameters did not meet these prerequisites) in 311 patients. The results were better in young patients than in adult patients. However, in the adolescent group, 22% of patients had abnormal knee at follow-up. The classical localization has a better prognosis than an unusual one. Patients with a favorable situation at diagnosis have significantly better results after conservative treatment than those who have undergone operation. When there are signs of dissection, the results are better after operative than after conservative treatment.

Adolescent↗
PubMed1998

Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice.

Fibroblast growth factor-2 (FGF-2) has been implicated in various signaling processes which control embryonic growth and differentiation, adult physiology and pathology. To analyze the in vivo functions of this signaling molecule, the FGF-2 gene was inactivated by homologous recombination in mouse embryonic stem cells. FGF-2-deficient mice are viable, but display cerebral cortex defects at birth. Bromodeoxyuridine pulse labeling of embryos showed that proliferation of neuronal progenitors is normal, whereas a fraction of them fail to colonize their target layers in the cerebral cortex. A corresponding reduction in parvalbumin-positive neurons is observed in adult cortical layers. Neuronal defects are not limited to the cerebral cortex, as ectopic parvalbumin-positive neurons are present in the hippocampal commissure and neuronal deficiencies are observed in the cervical spinal cord. Physiological studies showed that FGF-2-deficient adult mice are hypotensive. They respond normally to angiotensin II-induced hypertension, whereas neural regulation of blood pressure by the baroreceptor reflex is impaired. The present genetic study establishes that FGF-2 participates in controlling fates, migration and differentiation of neuronal cells, whereas it is not essential for their proliferation. The observed autonomic dysfunction in FGF-2-deficient adult mice uncovers more general roles in neural development and function.

Animals↗
PubMed1998

A GR-motif functions in nuclear accumulation of the large FGF-2 isoforms and interferes with mitogenic signalling.

Nuclear translocation has been documented for members of the fibroblast growth factor (FGF) family in addition to their roles as extra-cellular signalling molecules. Fusing different parts of the chicken FGF-2 open reading frame to pyruvate kinase shows that direct nuclear accumulation is mediated by the amino-termini of the two leucine initiated FGF-2 isoforms (Leu-isoforms; 21.5 and 20.0 kDa). An evolutionarily conserved glycine-arginine (GR)-motif is present in the 21.5 kDa Leu-isoform and a shorter GR-repeat in the 20.0 kDa Leu-isoform, whereas no such repeats are present in the 18.5 kDa FGF-2 isoform (Met-isoform). Expression in NIH3T3 fibroblasts shows that the 21.5 kDa Leu-isoform is predominantly nuclear, whereas the Met-isoform is predominantly cytoplasmic. Most importantly, insertion of the GR-motif into the Met-isoform results in a protein with characteristics similar to the Leu-isoforms, as shown by nuclear accumulation of the chimeric MGR-protein. Furthermore, only NIH3T3 fibroblasts expressing the Met-isoform proliferate under serum starvation conditions, whereas cells expressing either the MGR- or Leu-isoforms stay growth arrested. These studies show that the GR-signal mediates nuclear translocation of endogenous Leu-isoforms and blocks their mitogenic activity.

3T3 Cells↗
PubMed1997

Rearrangements of the cytoskeleton and cell contacts induce process formation during differentiation of conditionally immortalized mouse podocyte cell lines.

Mature podocytes are among the most complex differentiated cells and possess a highly branched array of foot processes that are essential to glomerular filtration in the kidney. Such differentiated podocytes are unable to replicate and culturing of primary podocytes results in rapid growth arrest. Therefore, conditionally immortalized mouse podocyte clones (MPC) were established, which are highly proliferative when cultured under permissive conditions. Nonpermissive conditions render the majority of MPC cells growth arrested within 6 days and induce many characteristics of differentiated podocytes. Both proliferating and differentiating MPC cells express the WT-1 protein and an ordered array of actin fibers and microtubules extends into the forming cellular processes during differentiation, reminiscent of podocyte processes in vivo. These cytoskeletal rearrangements and process formation are accompanied by the onset of synaptopodin synthesis, an actin-associated protein marking specifically differentiated podocytes. In addition, focal contacts are rearranged into an ordered pattern in differentiating MPC cells. Most importantly, electrophysiological studies demonstrate that differentiated MPC cells respond to the vasoactive peptide bradykinin by changes in intracellular calcium concentration. These results suggest a regulatory role of podocytes in glomerular filtration. Taken together, these studies establish that conditionally immortalized MPC cells retain a differentiation potential similar to podocytes in vivo. Therefore, the determinative steps of podocyte differentiation and process formation are studied for the first time using an inducible in vitro model.

Animals↗
PubMed1997

Dorso-ventral limb polarity and origin of the ridge: on the fringe of independence?

Molecular and developmental studies of limb pattern formation have recently gained widespread attention. The fact that vertebrate limbs are amenable to both genetic and embryological manipulations has established this model system as a valuable paradigm for studying vertebrate development. Limb buds are polarised along all three major axes and the establishment of the dorso-ventral (DV) polarity is dependent upon cues localised in the trunk, where a DV ectodermal interface is produced by confrontation of dorsal and ventral identities. By analogy to Drosophila imaginal disc development, this interface has been proposed to determine and position an ectodermal organising centre, the Apical Ectodermal Ridge (AER), controlling limb bud outgrowth. Recent fate mapping studies and studies of genes regulating DV limb polarity, AER formation and differentiation suggest, however, that DV patterning and AER induction, though coordinately regulated during limb bud outgrowth, may early on be more dissociated than expected.

Animals↗