RESUMO
PURPOSE: Previous studies have shown that inactivation of the retinoblastoma tumor suppressor protein (pRb) can cause lens fiber cell proliferation and apoptosis. Because pRb is thought to block cell cycle progression by inhibition of E2F transcription factors, experiments were conducted to test whether overexpression of different E2F family members would be sufficient to induce fiber cell proliferation and subsequent apoptosis. The in vivo functions of the transcription factor E2F2 have not previously been analyzed or described in transgenic mice. METHODS: Human E2F1 and E2F2 cDNAs were linked to the alphaA-crystallin promoter. Transgenic mice were generated by microinjection. Changes in cell cycle regulation were assayed by immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) incorporation and by in situ hybridization. Cell death was assayed using the TdT-dUTP terminal nick-end labeling (TUNEL) assay. RESULTS: At embryonic day (E)15.5, strong expression of the E2F1 and E2F2 transgenes was detected in lens fiber cells with little or no expression in epithelial cells. BrdU incorporation and TUNEL assays showed that overexpression of either E2F1 or E2F2 in lens fiber cells was sufficient to cause cell cycle entry and subsequent apoptosis. Expression of either E2F1 or E2F2 was sufficient to induce the transcription of cyclins (A2, B1, and E), as well as p53 and Bax in the lens fibercells. CONCLUSIONS: Expression of either E2F1 or E2F2 can induce postmitotic lens fiber cells to re-enter the cell cycle. Inappropriate cell cycle entry is recognized by p53 in each case, and programmed cell death ensues.
Assuntos
Apoptose , Proteínas de Transporte , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/fisiologia , Proteínas de Ligação a DNA , Cristalino/citologia , Proteínas Proto-Oncogênicas c-bcl-2 , Fatores de Transcrição/metabolismo , Animais , Bromodesoxiuridina/metabolismo , Divisão Celular , Ciclinas/metabolismo , Primers do DNA/química , Fatores de Transcrição E2F , Fator de Transcrição E2F1 , Fator de Transcrição E2F2 , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Cristalino/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Gravidez , Proteínas Proto-Oncogênicas/metabolismo , Proteína 1 de Ligação ao Retinoblastoma , Fase S , Fator de Transcrição DP1 , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2RESUMO
The case of a 2-day-old male full-term newborn with myotubular (centronuclear) myopathy is reported. He presented with generalized hypotonia and muscle weakness, swallowing disturbance, and respiratory distress at birth. He had a typical myopathic face, high-arched palate, funnel chest, and mild bilateral ptosis. Deep tendon reflexes were absent. Serum creatine kinase was normal. The histologic examination of the muscle biopsy over the right rectus femoris muscle revealed an increased number of fibers with centrally placed nuclei, type 1 fiber predominance, type 1 fiber atrophy, and a peripheral halo in the sarcoplasm on NADH-TR staining. On electron microscopy, central nuclei were separated by strands of glycogen and mitochondria. His muscle strength showed clinical improvement at a 14-month follow-up. This case illustrates the need for a muscle biopsy and histochemical staining and/or electron microscopic investigation for a proper diagnosis in hypotonic newborns with respiratory distress.
Assuntos
Doenças Neuromusculares/complicações , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia , Biópsia , Humanos , Recém-Nascido , Masculino , Músculos/patologia , Doenças Neuromusculares/patologiaRESUMO
Epidermolysis bullosa (EB) is a group of inherited diseases, that are characterized by vesiculobullous lesions that arise in response to minimal trauma or friction. The three major groups of EB differ according to the ultrastructural level of cleavage namely: simplex (epidermolytic), junctional and dystrophic (dermolytic). The combination of EB and pyloric atresia in rare and there is a definite association between them. We report a baby boy who died epidermolysis bullosa complications despite successful surgical correction of this pyloric atresia.
Assuntos
Epidermólise Bolhosa Juncional/complicações , Piloro/anormalidades , Epidermólise Bolhosa Juncional/patologia , Humanos , Recém-Nascido , Masculino , Pele/patologiaRESUMO
Neonatal adrenal hemorrhage is frequently associated with large fetal size, birth trauma owing to difficult labor or delivery, perinatal asphyxia, fetal hypoxia, septicemia or coagulation defect. A case of giant baby with perinatal asphyxia and birth injury complicated with adrenal hemorrhage is presented. The baby was admitted at five days of life due to profound jaundice. Right adrenal hematoma was found by abdominal sonography. The hematoma resolved gradually under supportive management by three months of age as documented by serial sonography. No complication was found. We conclude that abdominal sonography is the modality of choice for initial diagnosis and follow-up of neonatal adrenal hemorrhage, and conservative management is the mainstay of treatment.
Assuntos
Doenças das Glândulas Suprarrenais/diagnóstico , Hematoma/diagnóstico , Doenças das Glândulas Suprarrenais/etiologia , Doenças das Glândulas Suprarrenais/terapia , Traumatismos do Nascimento/complicações , Diagnóstico Diferencial , Feminino , Hematoma/etiologia , Hematoma/terapia , Humanos , Recém-NascidoRESUMO
Vitamin K prophylaxis for all neonates has been recommended to prevent hemorrhagic disease of the newborn (HDN), but it is still an uncommon practice in most developing countries throughout the world. In the United States and Canada, where vitamin K injections continue to be recommended in the newborn period, HDN is not a major concern. The risk factors for HDN include inadequate vitamin K prophylaxis, exclusively breast-fed infants, diarrhea, and alternative causes of vitamin K deficiency, such as liver disease and cystic fibrosis. We present an exclusively breast-fed 3-week-old infant with diarrhea for 2 days who died from intracranial hemorrhage related to HDN despite having received a single intramuscular injection of 0.2 mg of vitamin K at birth. Hemorrhage in the infant from vitamin K deficiency should be a concern for pediatricians and obstetricians. We emphasize the importance of administering an adequate dosage of vitamin K for prevention of HDN, particularly in an exclusively breast-fed infant.
Assuntos
Sangramento por Deficiência de Vitamina K/prevenção & controle , Vitamina K/uso terapêutico , Aleitamento Materno , Humanos , Recém-Nascido , MasculinoRESUMO
Candida infection contracted in utero and manifested at birth is a rare event. Two newborn infants are presented with generalized maculopapular rashes at birth. The eruption soon became vesicles or pustules; no other manifestations were found. Candida albicans was isolated from the skin lesion. After topical antifungal application, the lesions became fine and desquamated in the recuperative period. No complication was noted during the course. The diagnosis of congenital cutaneous candidiasis relies on its clinical course and positive culture result of the skin lesion. No systemic antifungal therapy is recommended except for the high risk infants.
Assuntos
Candidíase Cutânea/congênito , Candidíase Cutânea/diagnóstico , Candidíase Cutânea/tratamento farmacológico , Humanos , Recém-Nascido , MasculinoRESUMO
We describe a Chinese infant with maple syrup urine disease (MSUD) who had acrodermatitis enteropathica-like skin manifestations, edema, anemia, and diarrhea due to inadequate intake of branched-chain amino acids (BCAAs). A BCAA supplementation resulted in resolution of the eruption. This observation suggested the importance of monitoring plasma amino acids' levels for infants with metabolic disease on special formula.
Assuntos
Acrodermatite/etiologia , Aminoácidos de Cadeia Ramificada/administração & dosagem , Doença da Urina de Xarope de Bordo/terapia , Acrodermatite/terapia , Feminino , Humanos , Lactente , Doença da Urina de Xarope de Bordo/complicaçõesRESUMO
BACKGROUND: Necrotizing enterocolitis (NEC) is the most significant acquired gastrointestinal (GI) emergency in the neonatal intensive care unit. METHODS: We sought to gain a clinical perspective on NEC by reviewing the records of NEC patients over a 9-year period. The case histories of 22 infants with NEC treated from September 1, 1986 to September 1, 1995 were reviewed. RESULTS: Mean gestational age was 32 weeks and mean birth weight was 1774 grams. Eighteen percent were full term babies and 82% were premature. Average age at the onset of NEC was 11 days. The most common clinical manifestations were abdominal distension (100%), gastric retention (64%), unstable vital signs (59%) and Guaiac-positive vomitus or stool (36%). Sixteen cases (73%) were classified as stage III NEC, which has the highest mortality and/or morbidity. CONCLUSION: Early identification and management are critical to improve the outcome of NEC.
Assuntos
Enterocolite Pseudomembranosa , Peso ao Nascer , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/fisiopatologia , Enterocolite Pseudomembranosa/terapia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Morbidade , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
During vertebrate embryogenesis, the neuroectoderm differentiates into neural tissues and also into non-neural tissues such as the choroid plexus in the brain and the retinal pigment epithelium in the eye. The molecular mechanisms that pattern neural and non-neural tissues within the neuroectoderm remain unknown. We report that FGF9 is normally expressed in the distal region of the optic vesicle that is destined to become the neural retina, suggesting a role in neural patterning in the optic neuroepithelium. Ectopic expression of FGF9 in the proximal region of the optic vesicle extends neural differentiation into the presumptive retinal pigment epithelium, resulting in a duplicate neural retina in transgenic mice. Ectopic expression of constitutively active Ras is also sufficient to convert the retinal pigment epithelium to neural retina, suggesting that Ras-mediated signaling may be involved in neural differentiation in the immature optic vesicle. The original and the duplicate neural retinae differentiate and laminate with mirror-image polarity in the absence of an RPE, suggesting that the program of neuronal differentiation in the retina is autonomously regulated. In mouse embryos lacking FGF9, the retinal pigment epithelium extends into the presumptive neural retina, indicating a role of FGF9 in defining the boundary of the neural retina.