RESUMO
BACKGROUND: Congenital hypothyroidism is a frequent disease occurring with an incidence of about 1/1500 newborns/year. In about 75% of the cases, CH is caused by alterations in thyroid morphogenesis, defined "thyroid dysgenesis" (TD). TD is generally a sporadic disease but in about 5% of the cases a genetic origin has been demonstrated. Previous studies indicate that Dnajc17 as a candidate modifier gene for hypothyroidism, since it is expressed in the thyroid bud, interacts with NKX2.1 and PAX8 and it has been associated to the hypothyroid phenotype in mice carrying a single Nkx2.1 and Pax8 genes (double heterozygous knock-out). PURPOSE: The work evaluates the possible involvement of DNAJC17 in the pathogenesis of TD. METHODS: High-resolution DNA melting analysis (HRM) and direct sequencing have been used to screen for mutations in the DNAJC17 coding sequence in 89 patients with TD. RESULTS: Two mutations have been identified in the coding sequence of DNAJC17 gene, one in exon 5 (c.350A>C; rs79709714) and one in exon 9 (c.610G>C; rs117485355). The last one is a rare variant, while the rs79709714 is a polymorphism. Both are present in databases and the frequency of the alleles is not different between TD patients and controls. CONCLUSIONS: DNAJC17 mutations are not frequently present in patients with TD.
Assuntos
Biomarcadores/análise , Proteínas de Choque Térmico HSP40/genética , Mutação , Fator de Transcrição PAX8/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Disgenesia da Tireoide/genética , Fator Nuclear 1 de Tireoide/genética , Criança , Análise Mutacional de DNA , Feminino , Humanos , Fenótipo , Prognóstico , Disgenesia da Tireoide/diagnósticoRESUMO
We have presented prior evidence suggesting that fluid transport results from electro-osmosis at the intercellular junctions of the corneal endothelium. Such phenomenon ought to drag other extracellular solutes. We have investigated this using fluorescein-Na2 as an extracellular marker. We measured unidirectional fluxes across layers of cultured human corneal endothelial (HCE) cells. SV-40-transformed HCE layers were grown to confluence on permeable membrane inserts. The medium was DMEM with high glucose and no phenol red. Fluorescein-labeled medium was placed either on the basolateral or the apical side of the inserts; the other side carried unlabeled medium. The inserts were held in a CO2 incubator for 1 h (at 37 °C), after which the entire volume of the unlabeled side was collected. After that, label was placed on the opposite side, and the corresponding paired sample was collected after another hour. Fluorescein counts were determined with a (Photon Technology) DeltaScan fluorometer (excitation 380 nm; emission 550 nm; 2 nm bwth). Samples were read for 60 s. The cells utilized are known to transport fluid from the basolateral to the apical side, just as they do in vivo in several species. We used 4 inserts for influx and efflux (total: 20 1-h periods). We found a net flux of fluorescein from the basolateral to the apical side. The flux ratio was 1.104 ± 0.056. That difference was statistically significant (p = 0.00006, t test, paired samples). The endothelium has a definite restriction at the junctions. Hence, an asymmetry in unidirectional fluxes cannot arise from osmosis, and can only point instead to paracellular solvent drag. We suggest, once more, that such drag is due to electro-osmotic coupling at the paracellular junctions.
Assuntos
Fenômenos Eletrofisiológicos , Endotélio Corneano/fisiologia , Fluoresceína/metabolismo , Osmose , Transporte Biológico , Líquidos Corporais/metabolismo , Permeabilidade da Membrana Celular , Humanos , Modelos BiológicosRESUMO
BACKGROUND: Congenital hypothyroidism (CH) is a frequent disease occurring with an incidence of about 1/2500 newborns/year. In 80-85% of the cases CH is caused by alterations in thyroid morphogenesis, generally indicated by the term "thyroid dysgenesis" (TD). TD is generally a sporadic disease, but in about 5% of the cases a genetic origin has been demonstrated. In these cases, mutations in genes playing a role during thyroid morphogenesis (NKX2-1, PAX8, FOXE1, NKX2-5, TSHR) have been reported. AIM: This work reviews the main steps of thyroid morphogenesis and all the genetic alterations associated with TD and published in the literature.
Assuntos
Disgenesia da Tireoide/genética , Glândula Tireoide/embriologia , Animais , Hipotireoidismo Congênito/genética , Proteínas de Ligação a DNA/genética , Feminino , Fatores de Transcrição Forkhead/genética , Proteína Homeobox Nkx-2.5 , Proteínas de Homeodomínio/genética , Humanos , Masculino , Camundongos , Proteínas Nucleares/genética , Fator de Transcrição PAX8 , Fatores de Transcrição Box Pareados/genética , Receptores da Tireotropina/genética , Fator Nuclear 1 de Tireoide , Fatores de Transcrição/genéticaRESUMO
The corneal endothelium is a fluid-transporting epithelium. As other similar tissues, it displays an electrical potential of ~1 mV (aqueous side negative) across the entire layer [transendothelial potential difference (TEPD)]. It appears that this electrical potential is mainly the result of the transport of anions across the cell layer (from stroma to aqueous). There is substantial evidence that the TEPD is related linearly to fluid transport; hence, under proper conditions, its measure could serve as a measure of fluid transport. Furthermore, the TEPD is not steady; instead, it displays a spectrum of frequency components (0-15 Hz) recognized recently using Fourier transforms. Such frequency components appear due to charge-separating (electrogenic) processes mediated by epithelial plasma membrane proteins (both ionic channels and ionic cotransporters). In particular, the endothelial TEPD oscillations of the highest amplitude (1-2 Hz) were linked to the operation of so-called sodium bicarbonate cotransporters. However, no time localization of that activity could be obtained with the Fourier methodology utilized. For that reason we now characterize the TEPD using wavelet analysis with the aim to localize in time the variations in TEPD. We find that the mentioned high-amplitude oscillatory components of the TEPD appear cyclically during the several hours that an endothelial preparation survives in vitro. They have a period of 4.6 ± 0.4 s on average (n=4). The wavelet power value at the peak of such oscillations is 1.5 ± 0.1 mV(2) Hz on average (n = 4), and is remarkably narrow in its distribution.
Assuntos
Líquidos Corporais/metabolismo , Endotélio Corneano/fisiologia , Modelos Biológicos , Análise de Ondaletas , Animais , Simulação por Computador , Campos Eletromagnéticos , HumanosRESUMO
We are reporting a patient who presente with upper gastrointestinal bleeding which was in part caused by a wandering spleen. Endoscopy revealed erosions of gastric varices in the presence of gastric torsion. At surgical exploration the spleen was present in the pelvis. The twisted and elongated splenic pedicle resulted in a markedly dilated venous system of the proximal stomach and the engorged spleen. The literature of the wandering spleen is reviewed.