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Biomedical subjects

F Padilla

Publications and source records attributed to F Padilla.

At least 19 recordsLinked to original sources

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

Cisplatin hydration with and without mannitol diuresis in refractory disseminated malignant melanoma: a southwest oncology group study.

In a prospective phase II randomized trial, a dose of 100 mg/m2 iv cisplatin every 3 weeks plus forced hydration with or without mannitol diuresis was tested in patients with previously treated advanced malignant melanoma. A total of 67 patients were evaluated: 33 not given mannitol and 34 in the mannitol arm. Two partial remissions (of 2+ and 6.5 months) were achieved in the no-mannitol arm and one complete response and four partial responses (of 1, 2, 2.5, 5.5, and 8 months) were seen in the mannitol arm. Moderate, severe, and life-threatening renal toxicity was less in the mannitol arm, and patients tolerated more doses of cisplatin. The renal toxicity occurred mostly after the first dose of chemotherapy and did not seem to be cumulative. Other side effects were comparable in both arms. We concluded that renal toxicity is less severe in patients treated with cisplatin, hydration, and mannitol and that the use of cisplatin alone or in combination with other active agent(s) should be considered for further evaluation in previously untreated patients with malignant melanoma.

Cisplatin

Phase II evaluation of ftorafur in previously untreated colorectal cancer: a Southwest Oncology Group Study.

Eighty-four previously untreated patients with metastatic adenocarcinoma of the large intestine received intravenous ftorafur at a dosage of 2.25 g/m2/day for 5 consecutive days. Courses were repeated every three weeks. Regressions were noted in 9 of 84 treated patients (11%). Median survival for all patients was 32 weeks. Responders survived only 5 weeks longer than nonresponders; 36 vs. 31 weeks. Central nervous system toxicity was a limiting factor occurring in one-third of patients. Ftorafur in a daily X5 schedule appears not to make a significant contribution to the management of disseminated colorectal cancer.

Adenocarcinoma