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Biomedical subjects

F Padilla

Publications and source records attributed to F Padilla.

At least 37 records · Page 2Linked to original sources

Phase and group velocities of fast and slow compressional waves in trabecular bone.

This Letter is an extension to a multilayer model of porous bone first proposed by Hughes et al. [Ultrasound Med. Biol. 25, 811-821 (1999)]. Both slow and fast compressional waves propagate when the acoustic wave propagation is parallel to the trabecular alignment. However, a slow wave disappears at high refraction angles. To explain this phenomenon, the multilayer model is extended to compute group velocity surface and arrival times with an angle. Two major effects are highlighted as the refraction angle increases. First, the energy of the slow wave is refracted from the phase propagation direction. Second, the signals of fast and slow waves overlap. As a consequence, the slow wave may not be observed for a refraction angle greater than 40 degrees, which is in agreement with previous experimental data published by Hughes et al. and others.

Acoustics↗

The wave bivector formalism associated with circumferential leaky waves

It is shown that the circumferential internal waves propagating around an elastic cylinder can be locally seen as plane evanescent waves, at any observation point inside the surrounding fluid. This is done by direct calculation of the associated complex bivector. The exact anatomy of the wave is detailed and the phase propagation paths are found to be curved, as expected. The transition to the plane interface is achieved. Polarization ellipses associated with the acoustic displacement vector are described. The additional low evanescence assumption leads to conventional ray interpretation with identification of the ray tube divergence coefficients, and the wavefront is found to be the involute of a circle.

Journal Article↗

Immobilized dimers of N-cadherin-Fc chimera mimic cadherin-mediated cell contact formation: contribution of both outside-in and inside-out signals.

Cell adhesion receptors of the cadherin family are involved in various developmental processes, affecting cell adhesion and migration, and also cell proliferation and differentiation. In order to dissect the molecular mechanisms of cadherin-based cell-cell adhesion and subsequent signal transduction to the cytoskeleton and/or cytoplasm leading to adapted cell responses, we developed an approach allowing us to mimic and control cadherin activation. We produced a dimeric N-cadherin-Fc chimera (Ncad-Fc) which retains structural and functional properties of cadherins, including glycosylation, Ca(2+)-dependent trypsin sensitivity and the ability to mediate Ca(2+)-dependent self-aggregation of covered microbeads. Beads covered with either Ncad-Fc or anti-N-cadherin antibodies specifically bound to N-cadherin expressing cells. Both types of beads induced the recruitment of N-cadherin, beta-catenin, alpha-catenin and p120, by lateral mobilization of preexisting cell membrane complexes. Furthermore, cadherin clustering elicited by Ncad-Fc beads triggered local accumulations of tyrosine phosphorylated proteins, a recruitment and redistribution of actin filaments, as well as local membrane remodeling. These results support a model where the adhesion of cadherin ectodomains is followed by clustering of cadherin/catenin complexes allowing signal transduction affecting both cytoskeletal reorganization and cytoplasmic signal mobilization (outside-in signaling). Interestingly, bead-cell binding was altered by agents promoting microfilament and microtubule depolymerization or tyrosine phosphorylation, indicating a possible regulation of the adhesive properties of the extracellular domain of N-cadherin by intracellular factors (inside-out signaling).

Animals↗

Upregulation and redistribution of cadherins reveal specific glial and muscle cell phenotypes during wallerian degeneration and muscle denervation in the mouse.

In the present work, we investigated the expression of cadherin mRNAs in the adult neuromuscular system either under normal conditions or following experimental neurotomy. Cadherin-6, a marker of Schwann cell precursors, was not expressed in the adult peripheral nerve, while M-cadherin, cadherin-11, and N-cadherin were expressed both by glial and conjunctive cells. Moreover, the three transcripts were transiently upregulated in the distal stump of neurotomized sciatic nerve during Wallerian degeneration: N-cadherin was abundant in myelinating Schwann cells during myelin degradation, while M-cadherin and cadherin-11 may be upregulated in proliferating Schwann cells. M-cadherin, cadherin-11, and N-cadherin were also detected in myofibres and endomysium of adult gastrocnemius muscle. Following neurotomy, cadherin-11 was only transiently increased in denervated myofibres, while M-cadherin was increased and sustained for at least 21 days postoperation. In contrast, N-cadherin was not upregulated in denervated myofibres. Thus, we defined here a combination of cadherins expressed in the adult nerve and muscle, and modulated during Wallerian degeneration and muscle denervation. The comparison of the expression pattern of this combination of cadherins to the one previously described during embryonic development shows that chronically denervated Schwann and muscle cells do not reverse to embryonic state (recapitulative hypothesis), but present specific phenotypic features.

Animals↗

In vitro alpha1-adrenoceptor pharmacology of Ro 70-0004 and RS-100329, novel alpha1A-adrenoceptor selective antagonists.

It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the alpha1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms. The present study describes the alpha1-adrenoceptor (alpha1-AR) subtype selectivities of two novel alpha1-AR antagonists, Ro 70-0004 (aka RS-100975) and a structurally-related compound RS-100329, and compares them with those of prazosin and tamsulosin. Radioligand binding and second-messenger studies in intact CHO-K1 cells expressing human cloned alpha1A-, alpha1B- and alpha1D-AR showed nanomolar affinity and significant alpha1A-AR subtype selectivity for both Ro 70-0004 (pKi 8.9: 60 and 50 fold selectivity) and RS-100329 (pKi 9.6: 126 and 50 fold selectivity) over the alpha1B- and alpha1D-AR subtypes respectively. In contrast, prazosin and tamsulosin showed little subtype selectivity. Noradrenaline-induced contractions of human lower urinary tract (LUT) tissues or rabbit bladder neck were competitively antagonized by Ro 70-0004 (pA2 8.8 and 8.9), RS-100329 (pA2 9.2 and 9.2), tamsulosin (pA2 10.4 and 9.8) and prazosin (pA2 8.7 and 8.3 respectively). Affinity estimates for tamsulosin and prazosin in antagonizing alpha1-AR-mediated contractions of human renal artery (HRA) and rat aorta (RA) were similar to those observed in LUT tissues, whereas Ro 70-0004 and RS-100329 were approximately 100 fold less potent (pA2 values of 6.8/6.8 and 7.3/7.9 in HRA/RA respectively). The alpha1A-AR subtype selectivity of Ro 70-0004 and RS-100329, demonstrated in both cloned and native systems, should allow for an evaluation of the clinical utility of a 'uroselective' agent for the treatment of symptoms associated with benign prostatic hyperplasia.

Adrenergic alpha-1 Receptor Antagonists↗

Cadherins M, 11, and 6 expression patterns suggest complementary roles in mouse neuromuscular axis development.

As the result of a systematic search for cell adhesion molecules of the cadherin family expressed in the developing mouse neuromuscular system, we obtained cDNAs coding for eight molecules of the family, including cadherins M, 11, and 6. Northern blot and in situ hybridization analysis in the mouse embryo revealed a complementary expression of these transcripts. M-cadherin is found in embryonic somitic and nonsomitic striated muscles. As far as the hypaxial musculature is concerned, M-cadherin is expressed in committed but not in migratory precursor cells. Cadherin-11 is detected in mesodermal and conjunctive tissues and transiently in the ependymal germinative layer and in the motoneuron columns of the spinal cord. Cadherin-6 is found in embryonic spinal motoneuron columns and in Schwann cell precursors. In vitro experiments confirmed the muscular, glial, and fibroblastic origins of cadherins M, 11, and 6 transcripts, respectively. Altogether, these results suggest that various cadherins are differentially involved in muscle cell, Schwann cell, and motoneuron interactions and differentiation during neuromuscular development.

Animals↗

Heart failure after aortic valve replacement for aortic regurgitation: prospective 20-year study.

BACKGROUND: The objective of this study was to assess the probability of development of heart failure during a long-term follow-up in patients submitted for aortic valve replacement for aortic regurgitation on the basis of preoperative findings. METHODS AND RESULTS: Eighty-seven consecutive patients with pure aortic regurgitation and normal coronary arteries were submitted for aortic valve replacement and prospectively followed up. Clinical examination, echocardiography, and radionuclide ejection fraction were performed before surgery and at 1, 2, 5, and 10 years after surgery. Operative mortality rate was 2.2% (2 patients). The follow-up period was 1 to 12 years (mean 6 years). Overall survival rate was 87% at 5 years and 81% at 10 years. During follow-up, 19 patients had heart failure develop, and there were 14 deaths (6 caused by heart failure). Probability of heart failure was 16% at 5 years and 24% at 10 years. Age was the single independent preoperative predictor of both death and heart failure. Age >50 years (relative risk [RR] 10.4), preoperative ejection fraction <40% (RR 10.6), and end-systolic diameter >50 mm (RR 74) were independently related to the postoperative development of heart failure. CONCLUSIONS: Aortic valve replacement can be performed safely in patients with severe aortic regurgitation by following current recommendations. Age >50, end-systolic diameter >50 mm, and radionuclide ejection fraction <40% were independent preoperative predictors of postoperative heart failure. The only independent predictor of both postoperative death and heart failure was age >50 years.

Adult↗

[Cadherins, the development and regeneration of the neuromuscular axis].

Various cell adhesion molecules of the cadherin family characterize the neuromuscular system. During development, cadherins N and M are sequentially expressed by myogenic cells during the two waves of myoblast fusion. Two other cadherins, called 6 and 11, are also expressed during the embryonic musculature development. In adult muscle, cadherins N and M, whose expression is suppressed by muscle activity, persist only at the neuromuscular junction and are reexpressed at the surface of denervated fibers. Cadherins N, M and E are also expressed in adult peripheral nerves. Their differential localization at Schmidt-Lanterman clefts, Ranvier nodes and neuromuscular junctions suggest that these molecules contribute to the stabilization of specialized intercellular contacts. In conclusion, a combination of cadherins, the expression of which is spatially and temporally regulated, participates in the differentiation and maintenance of the organization of the various cellular and tissular components of the neuromuscular system.

Adult↗

Localized deposition of M-cadherin in the glomeruli of the granular layer during the postnatal development of mouse cerebellum.

M-cadherin is a Ca2+-dependent cell adhesion molecule of the cadherin family, initially localized at the areas of contact between myotubes during myogenesis, but also detected in the peripheral nerve and at the adult neuromuscular junction. In this study, searching for the expression of M-cadherin in the adult mouse brain, we observed a restricted expression of M-cadherin in one of the three layers of the cerebellar cortex: the granular layer. M-cadherin was accumulated in structures rich in synapses and other intercellular junctions where mossy fibers connect granule cell dendrites, the glomeruli. This molecule was not expressed in the cerebellum during the first steps of postnatal cerebellar neurogenesis: granule cell proliferation and migration and Purkinje cell alignment. M-cadherin expression was first detected at postnatal day (P) 11, after the establishment of the synaptic connections between mossy fibers and granule cell dendrites. It then accumulated in glomeruli during their phase of maturation which is characterized by the formation of puncta adherentia between granule cell dendrites. M-cadherin was undetectable in the cerebella of the weaver and staggerer mutants, lacking granule cells, and therefore mature glomeruli and puncta adherentia. Furthermore, other components classically associated with intercellular junctions, i.e., alpha-caterin, beta-catenin and actin filaments, closely paralleled M-cadherin appearance and colocalized with M-cadherin in the mature glomeruli. M-cadherin, which appears as a molecular marker of glomerulus maturation, might be implicated in the formation, and be the ligand, of adherens junctions encountered in this structure.

Actins↗

M-cadherin distribution in the mouse adult neuromuscular system suggests a role in muscle innervation.

M-cadherin belongs to the Ca(2+)-dependent cadherin family of cell adhesion molecules and was first isolated from a mouse muscle cell line cDNA library. It is specifically expressed in muscle tissue during development and is supposed to play an important role in secondary myogenesis. In the present study the expression of M-cadherin mRNA and protein and its localization were investigated in adult mouse skeletal muscle and peripheral nerve. The mRNA was abundant in embryonic legs from embryonic day (E)14 to E18. It remained expressed in new-born and adult muscles. In the adult muscle M-cadherin immunoreactivity was only detected at the neuromuscular junction, associated with perijunctional mononucleated cells and on intramuscular nerves. Peripheral nerves were also M-cadherin-positive. The molecule was found at the surface of myelinated nerve fibres where it was concentrated at the node of Ranvier. When a nerve was crushed and allowed to regenerate, M-cadherin was over-expressed at the site of nerve injury and in the distal stump. M-cadherin was also upregulated on the sarcolemma of denervated muscle fibres. Taken together, these observations point toward a much wider tissue distribution of M-cadherin than previously thought. M-cadherin might be involved not only in specific steps of myogenesis but also in some aspects of synaptogenesis, axon/Schwann cell interactions and node of Ranvier structural maintenance.

Amino Acid Sequence↗

[Frontal dementia-motor neuron disease: a case report and literature review].

The association between frontal dementia and motor neurone disease has been known for years now although its existence as a nosologic entity in its own right is still subject to debate. Lack of strict histological criteria and inspecificity in complementary tests which might otherwise lend weight to such a diagnosis prevent our considering it as much more than a mere clinical syndrome. We present here the case of a 56 year old female patient who developed a type of dementia with frontal characteristics associated with motor neurone disease. We discuss the clinical picture and review the relevant literature.

Dementia↗

[Neurological manifestations of fat embolism syndrome].

Fat embolism is a frequent complication of long bone trauma. Although neurological signs are key elements in the diagnosis of this syndrome, little attention to them has been paid in the spanish literature. We present a retrospective study of 13 patients with fat embolism syndrome in which we focused on neurological manifestations and alterations in computerized tomography (CT) of the head. The most frequent symptom was impairment of consciousness of varying degrees. Three patients out of the 13 also presented focal signs (hemiparesis and partial seizures). CT revealed edema (4/7) and multiple low density foci (1/7). All but one patient recovered without sequelae. Our study does not allow us to establish either the physiopathology of fat embolism syndrome or the most effective treatment.

Adolescent↗

Prostate cancer.

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Aged↗