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1.
Chemosphere ; 206: 1-8, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29723747

RESUMO

Bisphenol A is called as a endocrine-distrupting chemical because of the its steroid-like activity and it used in the construction of plastic containing materials. It is indicated that bisphenol A can pass the human serum, urine, follicular fluid, placenta and umblical cord as a result of the use of substances containing this agent. In this study, we aimed to investigate the effects of bisphenol A on the development of the thymus, a primary lymphoid organ which plays an important role in the specific immunity. The adult pregnant female rats were administered orally with bisphenol A (for 21 days) and postnatal thymus samples were obtained on day 21, 45 and 90 and were performed for histochemical and immunohistochemical staining for CD3, CD4, CD8 and CD79a and TUNEL assay for the apoptotic cells. Evaluation of all groups, CD3, CD4, CD8 and CD79a stainings were decreased in the experimental groups compared with control group. The apoptotic cells were determined in the all groups on day 90 as a result of the thymus involution. It is noted that there was not any histological and morphological damages in the rats prenatally exposed the bisphenol A. The effect of the bisphenol A is unknown in the future, but there is no problem in the adult rats.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Fenóis/efeitos adversos , Timo/anormalidades , Adulto , Animais , Humanos , Masculino , Ratos
2.
Prog. obstet. ginecol. (Ed. impr.) ; 61(2): 187-189, mar.-abr. 2018. ilus
Artigo em Espanhol | IBECS | ID: ibc-173674

RESUMO

Introducción: las anomalías de la vena innominada se observan habitualmente en pacientes con otras anomalías cardiacas o vasculares. La presencia de vena innominada intratímica es un hallazgo que puede plantear dudas tanto en su diagnóstico como en su manejo. Caso clínico: presentamos dos casos de venas innominadas intratímicas diagnosticados prenatalmente, una con diagnóstico a las 34 semanas y otra a las 21 semanas, y su seguimiento posnatal. Conclusión: el diagnóstico en una ecografía de un trayecto intratímico de la vena innominada no debería ser tan infrecuente, es sencillo de realizar y se considera una variante de la normalidad


Introduction: Abnormalities of the left braquiocephalic (innominate) vein are commonly observed in patients with other cardiac or vascular abnormalities. The presence of an intrathymic innominate vein may raise doubts both in its diagnosis and in its management. Clinical case: We present two cases of intrathymic innominate veins diagnosed prenatally, one at 34 weeks and another at 21 weeks, and postnatal follow-up. Conclusion: Diagnosis on ultrasound of an intrathymic innominate vein should not be uncommon, simple to perform, and considered a variant of normality


Assuntos
Humanos , Feminino , Gravidez , Adulto , Veias Braquiocefálicas/anormalidades , Veias Braquiocefálicas/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Timo/anormalidades , Timo/diagnóstico por imagem , Ecocardiografia/métodos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/fisiopatologia
3.
J Clin Ultrasound ; 46(6): 375-379, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29575022

RESUMO

PURPOSE: To assess the prevalence of ectopic thyroidal thymus tissue detected by sonography (US) in children and to analyze the US features. METHODS: We retrospectively reviewed images of 216 children who had undergone a thyroid or neck US examination from February 2015 to June 2015. Lesions within or adjacent to the thyroid gland that showed echopatterns consistent with thymic tissue were diagnosed as ectopic thyroidal thymus tissue. Lesions were reviewed according to their side, location, level, size, shape, echo pattern, internal content, and vascularization. RESULTS: A total of 216 children (119 girls, 97 boys) with a mean ± SD age of 8.6 ± 5.2 years were enrolled the study.Thirty children (13girls, 17 boys) (13.9%) had 35 lesions compatible with ectopic thyroidal thymus tissue.Nine children had intrathyroidal (4.2%) and 21 children had extrathyroidal (9.7%) ectopic thymus tissue.The mean ± SD ages of the children with and without ectopic thyroidal thymus tissue were 6.0 ± 3.6 years and 9.1 ± 5.2 years, respectively (P = .002). Twenty-five of the lesions were extrathyroidal and 10 were intrathyroidal. All extrathyroidal and most (8/9) intrathyroidal ectopic thymuses had fusiform shape with well demarcated contours. Ectopic thymuses were located either in the midportion (n = 23) or lower portion of the neck (n = 12). Both extrathyroidal and intrathyroidal ectopic thymuses showed typical hypoechoic (n = 22/25, n = 9/10, respectively) or hyperechoic (n = 3/25, n = 1/10, respectively) echo patterns with internal linear and punctate echoes. CONCLUSIONS: Ectopic thyroidal thymic tissue is common in children. Radiologists should be vigilant about the unique US features of ectopic thyroidal thymus, including a hypo- and hyper-echoic echo pattern with multiple linear and punctate echoes, a fusiform shape, well-demarcated contours, and middle or low-lying location to differentiate it from other neck or thyroid lesions.


Assuntos
Timo/anormalidades , Timo/diagnóstico por imagem , Disgenesia da Tireoide/diagnóstico por imagem , Ultrassonografia/métodos , Criança , Feminino , Humanos , Masculino , Prevalência , Estudos Retrospectivos
4.
Int J Pediatr Otorhinolaryngol ; 107: 53-55, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29501311

RESUMO

Two cases of anatomical variations of the thymus are presented with respect to the anatomical relations with the left brachiocephalic vein and found during the necropsy process. Less than 2 days after birth with Noonan Syndrome, when the left brachiocephalic vein was scanning behind the upper thymus horns, there were other adjacent lesions consisting of three supernumerary spleens and three hepatic veins. The second case was an 8-year-old infant with child malpractice who died from urinary sepsis due to obstructive uropathy, in which case the upper lobes of the thymus were fused and formed a ring through which the left brachiocephalic vein passed.


Assuntos
Veias Braquiocefálicas/anatomia & histologia , Síndrome de Noonan/diagnóstico , Timo/anormalidades , Variação Anatômica , Autopsia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Timo/anatomia & histologia
5.
Clin Genet ; 92(6): 664-668, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28657137

RESUMO

Otofaciocervical syndrome (OFCS) is a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies, and mild intellectual disability. Autosomal dominant cases are caused by deletions or point mutations of EYA1. A single family with an autosomal recessive form of OFCS and a homozygous missense mutation in PAX1 gene has been described. We report whole exome sequencing of 4 members of a consanguineous family in which 2 children, showing features of OFCS, expired from severe combined immunodeficiency (SCID). To date, the co-occurrence of OFCS and SCID has never been reported. We found a nonsense homozygous mutation in PAX1 gene in the 2 affected children. In mice, Pax1 is required for the formation of specific skeletal structures as well as for the development of a fully functional thymus. The mouse model strongly supports the hypothesis that PAX1 depletion in our patients caused thymus aplasia responsible for SCID. This report provides evidence that bi-allelic null PAX1 mutations may lead to a multi-system autosomal recessive disorders, where SCID might represent the main feature.


Assuntos
Síndrome Brânquio-Otorrenal/genética , Deficiência Intelectual/genética , Mutação , Fatores de Transcrição Box Pareados/genética , Imunodeficiência Combinada Severa/genética , Animais , Sequência de Bases , Síndrome Brânquio-Otorrenal/complicações , Síndrome Brânquio-Otorrenal/imunologia , Síndrome Brânquio-Otorrenal/patologia , Criança , Consanguinidade , Modelos Animais de Doenças , Exoma , Família , Feminino , Expressão Gênica , Genes Recessivos , Humanos , Lactente , Deficiência Intelectual/complicações , Deficiência Intelectual/imunologia , Deficiência Intelectual/patologia , Masculino , Camundongos , Marrocos , Fatores de Transcrição Box Pareados/imunologia , Linhagem , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/patologia , Timo/anormalidades , Timo/imunologia , Timo/metabolismo
6.
Pol J Vet Sci ; 20(1): 57-65, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28525344

RESUMO

Cranberries and cranberry-derived diet supplements are often recommended for the treatment of urinary tract infections, also during pregnancy. These products contain strongly anti-angiogenic chemical compounds which could not be indifferent to the developing fetus. In the present work we evaluated the effect of feeding pregnant and lactating mice American cranberry extract (daily dose 0.88 mg) on the morphology and some parameters of spleen and kidney function of their adult progeny. Six weeks after delivery the morphometry of spleen and kidney, cytometric analysis of spleen lymphocytes, evaluation of humoral response to SRBC (Sheep Red Blood Cells), and examination of serum creatinine/urea concentration, were performed in the offspring. Spleens of progeny from experimental (E) group differed from the spleens of progeny of control mice in the lower number of lymphatic nodules and their larger diameter. Cytometry of spleen cells from progeny of E mothers revealed more CD19+ and CD8+ lymphocytes than in the control group. No difference was seen in the response to immunization by red blood cells of sheep (SRBC) between control and E offspring. An increase in the diameter of glomeruli was observed in the kidneys of the experimental group in comparison with the control group. No abnormalities in creatinine and urea serum level were observed. A higher concentration of VEGF and bFGF in E offspring sera in comparison to the controls was seen. CONCLUSION: Although the observed differences between the control and experimental group were not large, caution is recommended in using cranberries and their extracts during pregnancy until more research will be done on this topic.


Assuntos
Anormalidades Induzidas por Medicamentos , Rim/anormalidades , Lactação/fisiologia , Extratos Vegetais/toxicidade , Baço/anormalidades , Vaccinium macrocarpon/química , Animais , Anticorpos , Eritrócitos/imunologia , Feminino , Rim/citologia , Rim/efeitos dos fármacos , Fígado/anormalidades , Fígado/efeitos dos fármacos , Camundongos , Extratos Vegetais/química , Gravidez , Ovinos/sangue , Baço/citologia , Baço/efeitos dos fármacos , Timo/anormalidades , Timo/efeitos dos fármacos
8.
Cancer Gene Ther ; 24(6): 259-266, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28429750

RESUMO

This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG group) and 293 healthy volunteers (negative control (NC) group) were enrolled in this study. Among the MG patients, there were 121 patients with thymoma-associated MG (T-MG group) and 184 without T-MG (NT-MG group). Enzyme-linked immunosorbent assay (ELISA) was used for the serum TNF-α level. Polymerase chain reaction-restriction fragment length polymorphism was conducted to determine genotype and allele frequencies of TNF-α gene promoter -1031T/C, -857C/T and -863C/A. The haplotype was analyzed with the SHEsis software. Logistic regression analysis was performed for correlations between TNF-α gene promoter polymorphisms and the risk of T-MG. The T-MG group had higher frequencies of the CT/TT genotype and T allele of -857C/T than the NT-MG and NC groups. The frequencies of the CC genotype and C allele of -1031T/C were higher in the T-MG group than in the NT-MG and NC groups, and higher in male patients in the T-MG group than in male patients in the NC group. TTA and TTC haplotypes exhibited lower frequencies in the T-MG group than in the NT-MG group. The ocular MG patients exhibited lower frequencies of the TT genotype and T allele of -857C/T than the generalized MG patients did. The TNF-α level was elevated in the T-MG group compared with that in the NC and NT-MG groups, indicating that the TC+CC and CT+TT genotypes were increased compared with the TT and CC genotypes in the -1031T/C and -857C/T, respectively. Logistic regression analysis suggested that expressions of anti-acetylcholine receptor antibodies, Osserman's classification, -1031T/C and -857C/T polymorphisms and the TTA haplotype were the independent risk factors for T-MG. These findings reveal that TNF-α -1031T/C and -857C/T polymorphisms and the TTA haplotype may be correlated with the occurrence of T-MG in a Northern Chinese Han population.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Miastenia Gravis/genética , Timo/anormalidades , Fator de Necrose Tumoral alfa/genética , Adulto , China , Feminino , Frequência do Gene/genética , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/patologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Fatores de Risco , Timo/patologia
9.
Int J Neurosci ; 127(4): 291-298, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27338803

RESUMO

BACKGROUND: The role of ß2-adrenergic receptor (ß2-AR) in the relapse of myasthenia gravis (MG) associated with thymus abnormality has not been fully identified. METHODS: Using polymerase chain reaction and gene sequencing method, we investigated the relationship of ß2-AR gene polymorphisms with different thymus pathology in MG patients. The role of ß2-AR gene polymorphisms in the relapse of MG was further investigated. RESULTS: Age of onset (p = 0.034), the onset symptom of ocular MG (OMG; p = 0.023), the first symptom of OMG second generalization (p = 0.040) were different in MG with thymoma from those in MG with normal thymus or thymus hyperplasia. Gene polymorphisms of ß2-AR on positions 16 and 27 showed no significant difference between relapsed and non-relapsed MG patients with thymus abnormality (thymus hyperplasia: position 16, p = 0.792; position 27, p = 0.664; thymoma: position 16, p = 0.226; position 27, p = 0.615). However, genotypes distribution on position 27 among MG patients with three thymus histology was significantly different (χ² = 8.153, p = 0.041). Furthermore, glucocorticoid can decrease relapse of MG with thymus hyperplasia (p = 0.021). CONCLUSIONS: MG patients with thymus abnormality differ from MG patients with normal thymus in age of onset, the onset symptom of OMG and the first symptom of OMG second generalization. ß2-AR gene polymorphisms had no relationship with the relapse of MG with thymus abnormality. Gene polymorphism of ß2-AR on position 27 was associated with different thymus histology of MG. Glucocorticoid was able to reduce the risk of relapse of MG with thymus hyperplasia.


Assuntos
Predisposição Genética para Doença/genética , Miastenia Gravis/genética , Miastenia Gravis/patologia , Polimorfismo Genético/genética , Receptores Adrenérgicos beta 2/genética , Timo/anormalidades , Adulto , Idade de Início , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas
10.
J Cardiovasc Med (Hagerstown) ; 18(5): 389-392, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-21107276

RESUMO

AIM: To establish a mouse model for the study of congenital defects, using exposure of pregnant females to the teratogen BMS-189453, a multiple retinoic acid competitive antagonist.We found not less than 60% of fetuses had transposition of the great arteries and l5% had other congenital heart defects such as double outlet right ventricle, tetralogy of Fallot, truncus and right aortic arch. Newborns exposed in utero to BMS-189453 were affected by thymus aplasia or hypoplasia, and severe congenital anomalies of the central nervous system due to neural tube defects. An anterior rotation of the right lung was also frequently present in our model. We also report a case of murine congenital diaphragmatic hernia associated with thymic aplasia and transposition of the great arteries. CONCLUSION: These findings support the hypothesis that the combination of diaphragmatic hernia and congenital heart defects may be related to an alteration of the retinoic acid signaling pathways.


Assuntos
Hérnias Diafragmáticas Congênitas/induzido quimicamente , Síndromes de Imunodeficiência/induzido quimicamente , Receptores do Ácido Retinoico/antagonistas & inibidores , Retinoides/toxicidade , Timo/anormalidades , Transposição dos Grandes Vasos/induzido quimicamente , Animais , Modelos Animais de Doenças , Feminino , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Exposição Materna , Camundongos , Gravidez
11.
Turk J Pediatr ; 58(2): 230-231, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27976570

RESUMO

Ectopic/aberrant cervical thymic tissue is a rare cause of neck mass and usually detected incidentally. Aberrant thymic tissue can occur anywhere in the course of thymic descent from the angle of the mandible to the superior mediastinum. We report a case of aberrant cervical thymus demonstrated by ultrasound.


Assuntos
Timo/anormalidades , Ultrassonografia/métodos , Pré-Escolar , Coristoma , Feminino , Humanos , Pescoço/diagnóstico por imagem , Timo/diagnóstico por imagem
12.
Horm Res Paediatr ; 86(5): 325-329, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27756075

RESUMO

BACKGROUND: During gestation, the primordial thymus migrates from the pharynx to the anterior mediastinum, thus thymic tissue can remain at any point along this path. Intrathyroidal thymic remnants are rare, and their sonographic patterns have only recently been described. This retrospective study presents the sonographic appearance of ectopic intrathyroidal thymus and emphasizes the role of sonography in order to avoid misdiagnosis. METHODS: The population consisted of 42 children, 3.5-14 years old, who had a thyroid sonogram performed due to a positive family history or symptoms indicative of thyroid disease, and ectopic intrathyroidal thymus was recognized. RESULTS: In all patients, the same pattern was revealed: a fusiform intrathyroidal lesion, with no mass effect, homogeneously hypoechoic, with diffuse bright internal echoes. The similarity to the characteristic sonographic pattern of the normal mediastinal thymus was crucial for the diagnosis of ectopic intrathyroidal thymic tissue. In 8 cases, a normal elongated thymus was found connected to the thyroid with an accessory lobe embedded in the lower thyroid pole. The above sonographic appearances mimicked a thyroid nodule. CONCLUSIONS: Awareness of the sonographic patterns of the ectopic intrathyroidal thymus is mandatory to avoid misdiagnosis. In most cases, further investigation is unnecessary, but sonographic follow-up should be recommended.


Assuntos
Timo/anormalidades , Timo/diagnóstico por imagem , Glândula Tireoide/anormalidades , Glândula Tireoide/diagnóstico por imagem , Ultrassonografia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos
13.
Biodemography Soc Biol ; 62(2): 208-21, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27337555

RESUMO

The thymus is critical for mounting an effective immune response and maintaining health. However, epidemiologic studies characterizing thymic function in the population setting are lacking. Using data from 263 adults in the Detroit Neighborhood Health Study, we examined thymic function as measured by the number of signal joint T-cell receptor excision circles (sjTREC) and assessed associations with established indicators of physiological health. Overall, increasing age and male gender were significantly associated with reduced thymic function. Adjusting for covariates, individuals with elevated levels of the pro-inflammatory biomarkers C-reactive protein (ß: -0.50 [95% CI: -0.82, -0.18] for moderate elevation, ß: -0.29 [95% CI: -0.59, 0.00] for high elevation) and interleukin-6 (ß: -0.60 [95% CI: -0.92, -0.28] for moderate elevation, ß: -0.43 [95% CI: -0.77, -0.08] for severe elevation) also had lower thymic function. Compared to individuals with a BMI < 25, individuals who were overweight (ß: 0.36 [95% CI: 0.07, 0.64]) or obese (ß: 0.27 [95% CI: -0.03, 0.56]) had higher thymic function. Differences by self-rated health were not statistically significant. Our findings underscore demographic- and health-related gradients in thymic function among adult residents of Detroit, suggesting thymic function may be an important biomarker of health status in adults at the population level.


Assuntos
Demografia/tendências , Nível de Saúde , Receptores de Antígenos de Linfócitos T/análise , Fatores Sociológicos , Timo/anormalidades , Adulto , Afro-Americanos/genética , Proteína C-Reativa/análise , Feminino , Humanos , Interleucina-6/análise , Interleucina-6/sangue , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/sangue , Receptores de Antígenos de Linfócitos T/genética , Inquéritos e Questionários , Timo/metabolismo
14.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. Impr.) ; 42(4): 254-259, mayo-jun. 2016. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-152909

RESUMO

Las alteraciones congénitas del cuello constituyen un desafío para los médicos de familia y los especialistas. Aunque algunas de ellas son diagnosticadas de forma intrauterina, la mayoría permanecen silentes y se manifiestan en el contexto de infecciones a lo largo de la vida. La localización anatómica, la consistencia y la edad son determinantes en la orientación del posible diagnóstico. Una masa cervical en línea media infrahioidea hará pensar en un quiste tirogloso. Si es lateral, descartaremos un quiste braquial. Los estudios complementarios por imagen son fundamentales, sin olvidar pruebas anatomopatológicas como punción aspiración de aguja fina (PAAF) (AU)


Congenital neck masses are a challenge for general practitioners and specialists. Although some of them are diagnosed in utero, most of them remain silent until complications appear in the adult age. The anatomical location, consistency and age are determinants in guiding the possible diagnosis. A midline infrahyoid mass may be a thyroglossal cyst, however a lateral neck mass is more possible to result in a brachial cyst. Complementary imaging studies are essential such as pathological tests like needle aspiration fine needle aspiration (FNA) (AU)


Assuntos
Humanos , Masculino , Feminino , Pescoço/anormalidades , Diagnóstico Diferencial , Região Branquial/anormalidades , Região Branquial/patologia , Cisto Tireoglosso/diagnóstico , Cisto Tireoglosso/terapia , Malformações Vasculares/diagnóstico , Malformações Vasculares/terapia , Malformações Vasculares , Medicina de Família e Comunidade/métodos , Vértebras Cervicais/anormalidades , Vértebras Cervicais/patologia , Tomografia Computadorizada de Emissão , Cisto Tireoglosso , Torcicolo/terapia , Teratoma/diagnóstico , Teratoma/terapia , Timo/anormalidades , Laringocele/diagnóstico
15.
Prenat Diagn ; 36(6): 561-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27061523

RESUMO

BACKGROUND: CHARGE syndrome is a multiple congenital anomaly syndrome caused by mutations in CHD7. Diagnostic criteria have been proposed to improve diagnosis in fetuses at clinicopathological survey, but no criteria exist for fetal diagnosis during pregnancy. METHOD: We collected prenatal findings of 12 children with CHARGE syndrome diagnosed in the first 3 months and a CHD7 mutation. We retrieved data on prenatal ultrasound (US) follow-up, fetal supplementary investigations, and results of postnatal evaluation. RESULT: Seven pregnancies were complicated by the identification of isolated or multiple congenital anomalies. CHARGE syndrome was suspected in three fetuses but could not be confirmed despite additional examinations. Retrospectively, several postnatal findings could have been seen if they had been specifically searched. Intrauterine growth restriction, previously proposed as an exclusion criterion, complicated two pregnancies and is thus compatible with the diagnosis. CONCLUSION: Diagnosis of CHARGE syndrome remains difficult during pregnancy. If the diagnosis of CHARGE syndrome is raised in utero, we suggest a careful US examination to identify typical external ears, choanal atresia, or microphthalmia. Fetal brain magnetic resonance imaging can be helpful, but a normal result does not exclude the diagnosis. When CHARGE syndrome is highly suspected, CHD7 molecular analysis must be proposed to confirm the diagnosis. © 2016 John Wiley & Sons, Ltd.


Assuntos
Síndrome CHARGE/diagnóstico por imagem , Ventrículos Cerebrais/anormalidades , Ventrículos Cerebrais/diagnóstico por imagem , Fenda Labial/diagnóstico por imagem , Anormalidades Craniofaciais/diagnóstico por imagem , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Orelha Externa/anormalidades , Orelha Externa/diagnóstico por imagem , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Defeitos dos Septos Cardíacos/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Rim , Masculino , Fenótipo , Poli-Hidrâmnios/diagnóstico por imagem , Gravidez , Estudos Retrospectivos , Timo/anormalidades , Timo/diagnóstico por imagem , Ultrassonografia Pré-Natal , Ureter/anormalidades , Ureter/diagnóstico por imagem , Anormalidades Urogenitais/diagnóstico por imagem
16.
Clin Immunol ; 163: 60-5, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26748374

RESUMO

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic autoimmune disease characterized by early-onset life-threatening multisystemic autoimmunity. This rare hereditary disorder is caused by loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor, which plays a key role in the differentiation and function of CD4(+)CD25(+) natural regulatory T cells (Tregs), essential for the establishment and maintenance of natural tolerance. We identified a novel mutation in the FOXP3 gene affecting the Phe367 residue of the protein (F367V) in a family with three male siblings affected by IPEX. Two other mutations affecting the FOXP3 Phe367 residue (F367L and F367C) have been described previously. This unique situation of three mutations affecting the same residue in FOXP3 led us to study the molecular impact of these mutations on the structure of FOXP3 protein. Structure analysis showed that Phe367 is involved in a rich interaction network related to both monomer and dimer structure stabilization, and is crucial for FOXP3 regulatory activity. The relevance of this location is confirmed by the results of SIFT and PolyPhen-2 pathogenicity predictions for F367V mutation. In summary, as assessment of the pathogenicity of a novel mutation is crucial to achieve a proper molecular diagnosis, we analysed the impact of mutations affecting the Phe367 residue using a combined approach that provides a mechanistic view of their pathogenic effect.


Assuntos
Diarreia/genética , Fatores de Transcrição Forkhead/genética , Doenças do Sistema Imunitário/congênito , Diabetes Mellitus Tipo 1/congênito , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diarreia/imunologia , Dimerização , Eczema/genética , Eczema/imunologia , Eosinofilia/genética , Eosinofilia/imunologia , Evolução Fatal , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Transtornos do Crescimento/genética , Transtornos do Crescimento/imunologia , Hemorragia/genética , Hemorragia/imunologia , Hepatomegalia/genética , Hepatomegalia/imunologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Imunoglobulina E/imunologia , Lactente , Infecções por Klebsiella/genética , Infecções por Klebsiella/imunologia , Leucocitose/genética , Leucocitose/imunologia , Pneumopatias/genética , Pneumopatias/imunologia , Masculino , Meningoencefalite/genética , Meningoencefalite/imunologia , Modelos Moleculares , Mutação , Fenilalanina/genética , Sepse/genética , Sepse/imunologia , Esplenomegalia/genética , Esplenomegalia/imunologia , Trombocitopenia/genética , Trombocitopenia/imunologia , Timo/anormalidades
17.
J Gynecol Obstet Biol Reprod (Paris) ; 45(4): 388-96, 2016 Apr.
Artigo em Francês | MEDLINE | ID: mdl-26096354

RESUMO

OBJECTIVES: In prenatal diagnosis of 22q11.2 microdeletion syndrome, without cardiac malformation or multiple associated congenital anomalies, we study the presence of polyhydramnios and its association with thymic dysgenesis. MATERIALS AND METHODS: This was a multicenter retrospective observational study. It was performed in two multidisciplinary centers for prenatal diagnosis in the south of France between January 1, 2010 and June 30, 2013. Inclusion criteria were prenatal diagnosis of 22q11.2 deletion syndrome. We excluded from the study any fetus with cardiac malformation or multiple associated congenital anomalies. RESULTS: During the inclusion period, eleven antenatal diagnoses of 22q11.2 microdeletion syndrome have been made. Six cases were excluded: 5 fetuses with cardiac malformation and one with multiple associated congenital anomalies. Therefore, five cases of isolated polyhydramnios were included. All 5 fetuses had a thymic dysgenesis: 3 had a thymic agenesis and 1 thymic hypoplasia diagnosed by sonography and 1 had a thymic agenesis diagnosed by retrospective reading of fetal MRI. CONCLUSION: When faced with a polyhydramnios, the presence of a thymic dysgenesis should be search for by ultrasound screening and would alert to the possibility of a 22q11.2 microdeletion syndrome. The confirmation of this is diagnosis by amniocentesis would enable improved antenatal support for parents and would enable early implementation of the multidisciplinary neonatal care that is required to avoid serious complications of this syndrome.


Assuntos
Síndrome de DiGeorge/diagnóstico , Doenças Fetais/diagnóstico , Poli-Hidrâmnios/diagnóstico , Diagnóstico Pré-Natal/métodos , Timo/anormalidades , Adulto , Feminino , Doenças Fetais/diagnóstico por imagem , França , Humanos , Gravidez , Estudos Retrospectivos , Timo/diagnóstico por imagem
18.
J Ultrasound Med ; 34(12): 2263-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26573099

RESUMO

OBJECTIVES: The purposes of this study were to assess the feasibility of fetal thymus measurement between 13 and 16 weeks' gestation, to evaluate the potential difference using color Doppler sonography with the thy-box technique, and to construct normal percentile ranges. METHODS: This retrospective study included 287 healthy singleton pregnancies. The fetal thymus was shown in an axial plane of the upper mediastinum. Color Doppler imaging was applied to outline the thy-box: ie, the area between the brachiocephalic artery posteriorly and internal mammary arteries laterally. Measurements of the lateral and anteroposterior diameters of the thymus with and without color Doppler imaging were compared. RESULTS: The thymus was shown in 95% of the cases (273 of 287) between 13 and 16 weeks' gestation. The mean lateral thymus diameter ± SD with color Doppler imaging (5.30 ± 0.7 mm) was significantly longer in comparison to the measurement without color Doppler imaging (5.06 ± 0.8 mm; P < .001), whereas the anteroposterior diameter was significantly shorter (3.19 ± 0.9 versus 3.26 ± 0.8 mm; P = .044). Normal percentiles of thymus measurements for gestational age were constructed. CONCLUSIONS: The fetal thymus can be clearly and accurately shown as early as 13 weeks' gestation by using the thy-box. Measurements with color Doppler imaging were significantly different from those without and hence are preferable, as color Doppler imaging can delineate the thymus borders more accurately.


Assuntos
Algoritmos , Interpretação de Imagem Assistida por Computador/métodos , Timo/anormalidades , Timo/diagnóstico por imagem , Hiperplasia do Timo/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Estudos de Viabilidade , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Variações Dependentes do Observador , Gravidez , Segundo Trimestre da Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Timo/embriologia
19.
Dev Biol ; 407(2): 195-210, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26434918

RESUMO

Fibronectin (Fn1) is an evolutionarily conserved extracellular matrix glycoprotein essential for embryonic development. Global deletion of Fn1 leads to mid-gestation lethality from cardiovascular defects. However, severe morphogenetic defects that occur early in embryogenesis in these embryos precluded assigning a direct role for Fn1 in cardiovascular development. We noticed that Fn1 is expressed in strikingly non-uniform patterns during mouse embryogenesis, and that its expression is particularly enriched in the pharyngeal region corresponding with the pharyngeal arches 3, 4, and 6. This region bears a special importance for the developing cardiovascular system, and we hypothesized that the localized enrichment of Fn1 in the pharyngeal region may be essential for cardiovascular morphogenesis. To test this hypothesis, we ablated Fn1 using the Isl1(Cre) knock-in strain of mice. Deletion of Fn1 using the Isl1(Cre) strain resulted in defective formation of the 4th pharyngeal arch arteries (PAAs), aberrant development of the cardiac outflow tract (OFT), and ventricular septum defects. To determine the cell types responding to Fn1 signaling during cardiovascular development, we deleted a major Fn1 receptor, integrin α5 using the Isl1(Cre) strain, and observed the same spectrum of abnormalities seen in the Fn1 conditional mutants. Additional conditional mutagenesis studies designed to ablate integrin α5 in distinct cell types within the Isl1(+) tissues and their derivatives, suggested that the expression of integrin α5 in the pharyngeal arch mesoderm, endothelium, surface ectoderm and the neural crest were not required for PAA formation. Our studies suggest that an (as yet unknown) integrin α5-dependent signal extrinsic to the pharyngeal endothelium mediates the formation of the 4th PAAs.


Assuntos
Sistema Cardiovascular/embriologia , Sistema Cardiovascular/metabolismo , Fibronectinas/metabolismo , Integrina alfa5beta1/metabolismo , Especificidade de Órgãos , Transdução de Sinais , Animais , Animais Recém-Nascidos , Região Branquial/embriologia , Região Branquial/metabolismo , Região Branquial/patologia , Sistema Cardiovascular/patologia , Linhagem da Célula , Embrião de Mamíferos/patologia , Feminino , Proteínas com Homeodomínio LIM/metabolismo , Camundongos Knockout , Modelos Biológicos , Morfogênese , Mutação/genética , Crista Neural/metabolismo , Crista Neural/patologia , Faringe/embriologia , Faringe/metabolismo , Fenótipo , Gravidez , Células-Tronco/citologia , Células-Tronco/metabolismo , Proteínas com Domínio T/metabolismo , Timo/anormalidades , Timo/irrigação sanguínea , Fatores de Transcrição/metabolismo
20.
J Autoimmun ; 65: 90-100, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26385063

RESUMO

Multiple receptors that control cell growth and inflammation activate the NFκB pathway that comprises of two pathways. Dysfunction of the classical pathway leads to impaired adaptive and innate immunity in humans. In contrast the exact role of the alternative NFκB pathway mediated by RelB in humans remains largely elusive. We have recently identified deleterious mutations in RelB in patients with combined immunodeficiency and autoimmunity. We studied here the biological effects of RelB deficiency on the immune system. We show that the thymus in this patient is dysplastic and consequently new thymus emigrants are rare and there is an accumulation of CD45 RO(+) T cells with an increase in CD62L(+) central memory cells. The TCR repertoire of these cells appears skewed with selective clonal expansion. In vitro responses to T cell mitogens were markedly depressed and so were PHA induced IL2 and IFNγ production. In addition, the TH1 promoting T bet and STAT1 were reduced. In contrast, hyper-activation was seen in response to anti-CD3 and CD28. T cell dependent antibody responses were low to absent in all patients. We found that BAFF-R was reduced and CD40 signaling aberrant. Critically, CD27(+) memory cells were absent. We have shown here for the first time the role of RelB on lymphocyte development in humans. In the absence of RelB, B cells development is arrested, resulting in poor production of immunoglobulins and specific antibodies. T cell maturation in the thymus appears altered with reduced output and production of a skewed T cell repertoire with expansion of clones which are likely the cause of the autoimmune features observed in these patients.


Assuntos
Linfócitos B/fisiologia , Subpopulações de Linfócitos T/fisiologia , Timo/anormalidades , Fator de Transcrição RelB/imunologia , Autoimunidade , Diferenciação Celular/genética , Proliferação de Células , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Interleucina-2/imunologia , Masculino , Subunidade p50 de NF-kappa B/imunologia , Transdução de Sinais/imunologia , Timo/imunologia , Timo/patologia , Fator de Transcrição RelB/genética
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