83 resultados para VERTEBRATE LIMB

em BORIS: Bern Open Repository and Information System - Berna - Suiça


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The mechanisms by which cells obtain instructions to precisely re-create the missing parts of an organ remain an unresolved question in regenerative biology. Urodele limb regeneration is a powerful model in which to study these mechanisms. Following limb amputation, blastema cells interpret the proximal-most positional identity in the stump to reproduce missing parts faithfully. Classical experiments showed the ability of retinoic acid (RA) to proximalize blastema positional values. Meis homeobox genes are involved in RA-dependent specification of proximal cell identity during limb development. To understand the molecular basis for specifying proximal positional identities during regeneration, we isolated the axolotl Meis homeobox family. Axolotl Meis genes are RA-regulated during both regeneration and embryonic limb development. During limb regeneration, Meis overexpression relocates distal blastema cells to more proximal locations, whereas Meis knockdown inhibits RA proximalization of limb blastemas. Meis genes are thus crucial targets of RA proximalizing activity on blastema cells.

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Vertebrate limbs develop in a temporal proximodistal sequence, with proximal regions specified and generated earlier than distal ones. Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. We identify fibroblast growth factor (FGF) as the main molecule responsible for this AER activity and propose a model integrating the role of FGF in limb cell proliferation, with a specific function in promoting distalization through inhibition of RA production and signaling.

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Vertebrate limb induction is triggered in the lateral plate mesoderm (LPM) by a cascade of signaling events originating in the axial mesoderm. While it is known that Fgf, Wnt and retinoic acid (RA) signals are involved in this cascade, their precise regulatory hierarchy has not been determined in any species. tbx5 is the earliest gene expressed in the limb bud mesenchyme. Recently, another transcription factor, Prdm1, has been shown to be crucial for zebrafish forelimb development. Here, we show that Prdm1 is downstream of RA, Wnt2b and Tbx5 activity. We find that RA activity, but not Fgf signaling, is necessary for wnt2b expression. Fgf signaling is required for prdm1 expression in the fin bud, but is not necessary for the initiation of tbx5 expression. We propose a model in which RA signaling from the somitic mesoderm leads to activation of wnt2b expression in the intermediate mesoderm, which then signals to the LPM to trigger tbx5 expression. tbx5 is required for Fgf signaling in the limb bud leading to activation of prdm1 expression, which in turn is required for downstream activation of fgf10 expression.

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Vertebrate limbs grow out from the flanks of embryos, with their main axis extending proximodistally from the trunk. Distinct limb domains, each with specific traits, are generated in a proximal-to-distal sequence during development. Diffusible factors expressed from signalling centres promote the outgrowth of limbs and specify their dorsoventral and anteroposterior axes. However, the molecular mechanism by which limb cells acquire their proximodistal (P-D) identity is unknown. Here we describe the role of the homeobox genes Meis1/2 and Pbx1 in the development of mouse, chicken and Drosophila limbs. We find that Meis1/2 expression is restricted to a proximal domain, coincident with the previously reported domain in which Pbx1 is localized to the nucleus, and resembling the distribution of the Drosophila homologues homothorax (hth) and extradenticle (exd); that Meis1 regulates Pbx1 activity by promoting nuclear import of the Pbx1 protein; and that ectopic expression of Meis1 in chicken and hth in Drosophila disrupts distal limb development and induces distal-to-proximal transformations. We suggest that restriction of Meis1/Hth to proximal regions of the vertebrate and insect limb is essential to specify cell fates and differentiation patterns along the P-D axis of the limb.

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The development of zebrafish paired fins and tetrapod forelimbs and hindlimbs show striking similarities at the molecular level. In recent years, the zebrafish, Danio rerio has become a valuable model for the study of the development of vertebrate paired appendages and several large-scale mutagenesis screens have identified novel fin mutants. This review summarizes recent advances in research into zebrafish paired fin development and highlights features that are shared with and distinct from limb development in other main animal models.

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OBJECTIVE: Ectopic calcification and mediacalcinosis can be promoted by corticosteroid use. Aim of the present investigation is to describe macrovascular disease features in patients with long-term corticosteroid therapy and symptomatic lower limb peripheral arterial occlusive disease (PAD). METHODS: A consecutive series of 2783 patients undergoing clinical and angiographic work-up of PAD were screened for long-term (>5 years) corticosteroid use (group A). Comparison was performed to a randomly selected age-, sex- and risk factor-matched PAD control cohort from the same series without corticosteroid use (group B). Patients with diabetes mellitus or severe renal failure were excluded. Arterial calcification was evaluated by qualitative assessment on radiographic images. Severity of atherosclerotic lesions was analysed from angiographic images using a semi-quantitative score (Bollinger score). RESULTS: In general, 12 patients (5 males, mean age 78.5 +/- 9.0 years) with 15 ischaemic limbs qualified to be enrolled in group A and were compared to 23 matching control patients (6 2 males, mean age 79.5 +/- 6 years) with 32 ischaemic limbs. Incompressibility of ankle arteries determined by measurement of the ankle-brachial index was seen in 12 limbs (80%) in group A compared to 3 limbs (9%) in group B (p = 0.0009). No significant difference was found comparing group A and B for segmental calcification, whereas comparison of the atherosclerotic burden using the angiographic severity score showed a significantly higher score at the infragenicular arterial level in group A (p = 0.001). CONCLUSION: Findings suggest that the long-term corticosteroid therapy is associated with a distally accentuated, calcifying peripheral atherosclerosis inducing arterial incompressibility. This occlusion pattern is comparable to patients with renal failure or diabetes. Further research is required to support our observations.

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Objectives The purpose of this study was to assess the impact of renal insufficiency (RI) on the distribution pattern of peripheral arterial disease (PAD). We hypothesised that RI is associated with a distally accentuated involvement of the peripheral arterial tree. Design This is a retrospective analysis. Materials and Methods Analysis was based on a consecutive series of 2709 patients with chronic PAD of atherosclerotic origin undergoing primary endovascular treatment of lower-extremity arteries. Atherosclerotic pattern was grouped into femoropopliteal (n = 2085) and infragenicular (n = 892) disease according to target lesions treated while using iliac disease (n = 1133) as reference. Univariable and multivariable multinomial regression analyses were performed to assess relation with RI. Results are shown as relative risk ratio (RRRs) with 95% confidence intervals (95% CIs). A p < 0.05 was considered statistically significant. RI was defined as glomerular filtration rate (GFR) < 60 ml min−1 1.73 m−2. Results Presence of RI was an independent risk factor for a centrifugal lesion pattern (RRR 1.48, 95% CI: 1.17–1.86, p = 0.001). Moreover, a decrease in GFR by 10 ml min−1 1.73 m−2 was associated with an RRR of 1.08 for below-the-knee arterial disease (95% CI: 1.03–1.13, p = 0.003). Conclusion Presence and severity of RI are independent predictors of a distal obstructive pattern in patients with symptomatic PAD.

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Background Focal spasticity is a significant motor disorder following stroke, and Botulinum Toxin Type-A (BoNT-A) is a useful treatment for this. The authors evaluated kinematic modifications induced by spasticity, and whether or not there is any improvement following injection of BoNT-A. Methods Eight patients with stroke with upper-limb spasticity, showing a flexor pattern, were evaluated using kinematics before and after focal treatment with BoNT-A. A group of sex- and age-matched normal volunteers acted as a control group. Results Repeated-measures ANOVA showed that patients with stroke performed more slowly than the control group. Following treatment with BoNT-A, there was a significant improvement in kinematics in patients with stroke, while in the control group, performance remained unchanged. Conclusions Focal treatment of spasticity with BoNT-A leads to an adaptive change in the upper limb of patients with spastic stroke.

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BACKGROUND: Only few standardized apraxia scales are available and they do not cover all domains and semantic features of gesture production. Therefore, the objective of the present study was to evaluate the reliability and validity of a newly developed test of upper limb apraxia (TULIA), which is comprehensive and still short to administer. METHODS: The TULIA consists of 48 items including imitation and pantomime domain of non-symbolic (meaningless), intransitive (communicative) and transitive (tool related) gestures corresponding to 6 subtests. A 6-point scoring method (0-5) was used (score range 0-240). Performance was assessed by blinded raters based on videos in 133 stroke patients, 84 with left hemisphere damage (LHD) and 49 with right hemisphere damage (RHD), as well as 50 healthy subjects (HS). RESULTS: The clinimetric findings demonstrated mostly good to excellent internal consistency, inter- and intra-rater (test-retest) reliability, both at the level of the six subtests and at individual item level. Criterion validity was evaluated by confirming hypotheses based on the literature. Construct validity was demonstrated by a high correlation (r = 0.82) with the De Renzi-test. CONCLUSION: These results show that the TULIA is both a reliable and valid test to systematically assess gesture production. The test can be easily applied and is therefore useful for both research purposes and clinical practice.

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The authors present the long-term results in a series of 44 cases with post-traumatic bone defects solved with muscle-rib flaps, between March 1997 and December 2007. In these cases, we performed 21 serratus anterior-rib flaps (SA-R), 10 latissimus dorsi-rib flaps (LD-R), and 13 LD-SA-R. The flaps were used in upper limb in 18 cases and in lower limb in 26 cases. With an overall immediate success rate of 95.4% (42 of 44 cases) and a primary bone union rate of 97.7% (43 of 44 cases), and despite the few partisans of this method, we consider that this procedure still remains very usefully for small and medium bone defects accompanied by large soft tissue defects.

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The purpose of this study was to evaluate the anti-nociceptive activity of ketamine and isoflurane in horses using a limb withdrawal reflex (WR) model. Single and repeated stimulations were applied to the digital nerve of the left forelimb in ponies anaesthetised with isoflurane before, during and after intravenous administration of racemic ketamine. Surface electromyographic activity was recorded from the deltoid muscle. Higher stimulation intensity was required to evoke a reflex during ketamine administration. Furthermore, the amplitudes of response to stimulations were significantly and dose-dependently depressed and a flattening of the stimulus-response curves was observed. The reflex activity recovered partially once the ketamine infusion finished. The results demonstrated that the limb WR can be used to quantify the temporal effect of ketamine on the sensory-motor processing in ponies anaesthetised with isoflurane.

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Patients with critical limb ischaemia have a high rate of amputation and mortality. We tested the hypothesis that non-viral 1 fibroblast growth factor (NV1FGF) would improve amputation-free survival.

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Patients with renal insufficiency (RI) are frequently excluded from trials assessing various endovascular revascularization concepts in critical limb ischemia (CLI) although information on clinical outcomes is scarce.

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Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking.

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