RESUMO
A prior phenotype-based screen of mice derived from ethylmethanesulfonate-mutagenized embryonic stem cells yielded two mouse limb defect mutants. Animals heterozygous for the polydactyly ems (Pde) mutation display preaxial polydactyly of the hindlimbs, and homozygous syndactyly ems (sne) animals are characterized by a fusion of the middle digits of their hindlimbs and sometimes forelimbs. We now report that Pde is a new allele of the basic helix-loop-helix protein gene Twist. Sequencing the full-length cDNA and several hundred basepairs of genomic DNA upstream of the coding region failed to reveal a mutation, suggesting that the lesion may be in a regulatory element of the gene. sne is a new fused phalanges (fp) allele of the shaker-with-syndactylism deletion complex (sy), and we show that the genomic lesion is a small deletion removing an entire exon, coincident with the insertion of the 3' end of a LINE element belonging to the TF subfamily.
Assuntos
Metanossulfonato de Etila/farmacologia , Proteínas dos Microfilamentos/genética , Mutação/efeitos dos fármacos , Mutação/genética , Proteínas Nucleares/genética , Fatores de Transcrição , Alelos , Sequência de Aminoácidos , Animais , Sequência de Bases , Análise Mutacional de DNA , Éxons/genética , Fibrilina-2 , Fibrilinas , Genes Letais/genética , Teste de Complementação Genética , Genótipo , Elementos Nucleotídeos Longos e Dispersos/genética , Camundongos , Dados de Sequência Molecular , Mutagênese/efeitos dos fármacos , Mutagênese/genética , Proteínas Nucleares/química , Fenótipo , Mapeamento Físico do Cromossomo , Polidactilia/genética , Alinhamento de Sequência , Deleção de Sequência/genética , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Sindactilia/genética , Proteína 1 Relacionada a TwistRESUMO
Fibrillins are large, cysteine-rich glycoproteins that form microfibrils and play a central role in elastic fibrillogenesis. Fibrillin-1 and fibrillin-2, encoded by FBN1 on chromosome 15q21.1 and FBN2 on chromosome 5q23-q31, are highly similar proteins. The finding of mutations in FBN1 and FBN2 in the autosomal dominant microfibrillopathies Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCA), respectively, has highlighted their essential role in the development and homeostasis of elastic fibres. MFS is characterized by cardiovascular, skeletal and ocular abnormalities, and CCA by long, thin, flexed digits, crumpled ears and mild joint contractures. Although mutations arise throughout FBN1, those clustering within exons 24-32 are associated with the most severe form of MFS, so-called neonatal MFS. All the mutations described in CCA occur in the "neonatal region" of FBN2. Both MFS and CCA are thought to arise via a dominant negative mechanism. The analysis of mouse mutations has demonstrated that fibrillin-1 microfibrils are mainly engaged in tissue homeostasis rather than elastic matrix assembly. In the current investigation, we have analysed the classical mouse mutant shaker-with-syndactylism using a positional candidate approach and demonstrated that loss-of-function mutations outside the "neonatal region" of Fbn2 cause syndactyly in mice. These results suggest that phenotypes distinct from CCA may result in man as a consequence of mutations outside the "neonatal region" of FBN2.
Assuntos
Glicoproteínas/genética , Proteínas dos Microfilamentos/genética , Mutação , Sindactilia/genética , Sequência de Aminoácidos , Animais , Éxons , Fibrilina-1 , Fibrilina-2 , Fibrilinas , Heterozigoto , Camundongos , Camundongos Endogâmicos , Proteínas dos Microfilamentos/química , Dados de Sequência Molecular , Estrutura Secundária de Proteína , Deleção de Sequência , Fator de Crescimento Transformador beta/metabolismoAssuntos
Distrofias Musculares/reabilitação , Qualidade da Assistência à Saúde , Braquetes , Humanos , Distrofias Musculares/diagnóstico , Distrofias Musculares/fisiopatologia , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/fisiopatologia , Doenças Neuromusculares/reabilitação , Procedimentos Ortopédicos , Admissão e Escalonamento de Pessoal , Respiração com Pressão Positiva , Reabilitação/tendências , Estados UnidosRESUMO
Hearing impairment is a common human condition, but we know little about the molecular basis of cochlear function. Shaker-with-syndactylism (sy) is a classic deaf mouse mutant and we show here that a second allele, sy(ns), is associated with abnormal production of endolymph, the fluid bathing sensory hair cells. Using a positional candidate approach, we demonstrate that mutations in the gene encoding the basolateral Na-K-Cl co-transporter Slc12a2 (Nkcc1, mBSC2) cause the deafness observed in sy and sy(ns) mice. This finding provides the molecular basis of another link in the chain of K+recycling in the cochlea, a process essential for normal cochlear function.
Assuntos
Proteínas de Transporte/genética , Surdez/genética , Animais , Proteínas de Transporte/análise , Mapeamento Cromossômico , Cóclea/química , Cóclea/patologia , DNA/química , DNA/genética , Análise Mutacional de DNA , Surdez/metabolismo , Surdez/patologia , Feminino , Genes/genética , Imuno-Histoquímica , Deformidades Congênitas dos Membros/genética , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Camundongos Endogâmicos , Camundongos Mutantes , Mutação , Simportadores de Cloreto de Sódio-Potássio , Sindactilia/genéticaRESUMO
The present study was done to determine the effect of the modified Hall valvulotome technique on endothelial injury by measuring TxB2 and 6-keto PGF1alpha, the stable metabolites of thromboxane and prostacyclin, respectively. It was hypothesized that increased levels of these cyclooxygenase products would be an excellent indicator of vascular endothelial injury in the presence of the modified Hall valvulotome. Eight segments of human distal saphenous veins were obtained, each measuring approximately 4 cm in length, with diameters of approximately 2 to 3 mm. From these original vein segments, two groups of smaller vein segments were examined, with each group consisting of eight segments, each segment measuring 2 cm in length. The first group of vein segments was designated as the control group, and the second group of vessels had a modified Hall valvulotome (2.5 mm size) inserted into each segment to simulate valvulotomy. After this procedure, all vein segments were analyzed for levels of thromboxane and prostacyclin by a standard radioimmunoassay procedure. Results from the present study indicate that the modified Hall valvulotome technique in human saphenous veins does not significantly increase the levels of the cyclooxygenase metabolites thromboxane and prostacyclin relative to control conditions. However, the ratio of TxB2 formation 6-keto PGF1alpha production was increased in the valvulotomized vessel segments, indicating possible platelet release of thromboxane. Therefore, even though there was increased thromboxane production relative to prostacyclin levels in the modified Hall valvulotome technique, it still appears that this type of valvulotomy is relatively noninsulting to the endothelial cell lining.
Assuntos
Endotélio Vascular/lesões , Epoprostenol/análise , Veia Safena/química , Instrumentos Cirúrgicos/efeitos adversos , Tromboxanos/análise , Humanos , Veia Safena/lesões , Veia Safena/cirurgiaRESUMO
We report a case of an angiographically documented fistula between the circumflex coronary artery and a left strial appendage thrombus in a patient with mitral stenosis, flow from which can be demonstrated solely by a color doppler transesophageal echocardiogram. Evaluation of catheter derived hemodynamics and angiographic flow patterns reveals a heretofore undescribed physiologic property of coronary to atrial shunts in patients with mitral stenosis.
Assuntos
Doença das Coronárias/fisiopatologia , Fístula/fisiopatologia , Átrios do Coração , Estenose da Valva Mitral/fisiopatologia , Velocidade do Fluxo Sanguíneo , Angiografia Coronária , Doença das Coronárias/complicações , Ecocardiografia Transesofagiana , Feminino , Fístula/complicações , Cardiopatias/complicações , Cardiopatias/fisiopatologia , Humanos , Pessoa de Meia-Idade , Estenose da Valva Mitral/complicaçõesRESUMO
Use of valvulotomes in non-reversed venous conduits carries the potential of venous endothelial cell injury. Earlier studies have shown that there is a significant decrease in the number of endothelial cells present in the human saphenous vein when employing the circular (LeMaitre) valvulotome. The present study was performed to evaluate and compare the LeMaitre and modified Hall valvulotome techniques on vascular endothelial cells from human saphenous vein. The results of the present study indicate that while both valvulotomes caused a significant decrease in the number of endothelial cells, the modified Hall instrument was less damaging to the vascular endothelium than the LeMaitre valvulotome. These results suggest that the modified Hall valvulotome technique may be more beneficial in maintaining endothelial cell function when the use of a valvulotome is warranted.
Assuntos
Endotélio Vascular/lesões , Veia Safena/transplante , Instrumentos Cirúrgicos , Procedimentos Cirúrgicos Vasculares/instrumentação , Contagem de Células , Sobrevivência Celular/fisiologia , Endotélio Vascular/patologia , Humanos , Veia Safena/patologiaRESUMO
With increasing use of nonreversed saphenous vein as a bypass conduit (either in-situ or translocated) several techniques of valve ablation are used. The present study was designed to assess the extent of endothelial damage caused by a circular blade valvulotome.
Assuntos
Endotélio Vascular/lesões , Veia Safena/lesões , Instrumentos Cirúrgicos/efeitos adversos , Ferimentos e Lesões/etiologia , Contagem de Células , Endotélio Vascular/citologia , Desenho de Equipamento/normas , Estudos de Avaliação como Assunto , Humanos , Veia Safena/citologia , Veia Safena/transplante , Ferimentos e Lesões/patologiaRESUMO
Major vascular involvement by a bronchogenic cyst is rare; most large cysts cause respiratory symptoms. We present a case in which a large bronchogenic cyst was adherent to the left pulmonary artery. During removal of the cyst by right thoracotomy, the artery lacerated. Repair of the artery in such a situation taxes the surgeon's ingenuity and decision-making process.
Assuntos
Cisto Broncogênico/cirurgia , Complicações Intraoperatórias , Artéria Pulmonar/lesões , Toracotomia/efeitos adversos , Adulto , Cisto Broncogênico/diagnóstico por imagem , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
We have reported two instances requiring long term central venous access in which the more traditional access sites were no longer available. The use of the internal mammary vein has made it possible to easily obtain central venous access in these patients without thoracotomy. Also, based on the anatomy, we believe this to be superior to the intercostal venous approach, since the passage of the catheter is more direct, thus, avoiding the acute azygous arch angle and cumbersome positioning.
Assuntos
Mama/irrigação sanguínea , Cateterismo Venoso Central/métodos , Cateteres de Demora , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , VeiasRESUMO
This prospective randomized study was undertaken to determine intraoperatively the hemodynamic effects of local anesthesia of the carotid sinus nerve during carotid dissection in preparation for endarterectomy. Twenty carotid endarterectomy patients were divided into 2 groups: a control group of 10 patients, in whom ordinary saline solution was infiltrated into the carotid bifurcation; and a study group of 10 patients, in whom 5 mL of 2% lidocaine hydrochloride was infiltrated. To determine whether a nerve-sparing dissection might in itself be adequate to prevent the perioperative hemodynamic instability associated with carotid endarterectomy, we took scrupulous care in all patients to avoid injuring the carotid sinus nerve. After we had established baseline values for heart rate and blood pressure in each patient, we recorded heart rate and blood pressure again intraoperatively, every 2 minutes during a 10-minute period. Because the series was small, an analysis of variance showed no statistically significant changes in these values during carotid dissection in either group. However, intraoperative increases in systolic pressure (p < 0.0064) and mean pressure (p < 0.0028) were greater in the lidocaine group. Neither group experienced any deaths, or any neurologic or hemodynamic sequelae during 48 hours of postoperative observation. We conclude that local anesthetic injection of the carotid sinus nerve before carotid dissection and endarterectomy is unnecessary when nerve-sparing dissection is performed; and we conclude further that such injection might actually be deleterious to intraoperative systolic and mean blood pressures.