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Prenat Diagn ; 39(5): 361-368, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30740743


OBJECTIVES: To determine the association between medications intake in early pregnancy and variation in the fetal fraction (FF) in pregnant women undergoing cell-free DNA (cfDNA) testing. METHODS: We performed a retrospective cohort study of women (n = 1051) undergoing cfDNA testing at an academic center. The exposed group included women taking medications (n = 400; 38.1%), while the nonexposed group consisted of women taking no medications (n = 651; 61.9%). Our primary outcome was FF. We performed univariate and multivariate analyses as appropriate. RESULTS: The FFs were 8.8% (6.6-12.1), 8.7% (6.3-11.6), and 7.7% (5.1-9.3) among women taking 0, 1, and two or more medications, respectively (P < 0.01). Using multivariable linear mixed effects model, the mean FF was significantly lower among those taking two or more medications compared with the nonexposed group. FF was directly correlated with gestational age at the time of cfDNA testing and inversely correlated with maternal obesity. Exposure to metformin was associated with 1.8% (0.2-3.4) lower mean FF when compared with the nonexposed group (P = 0.02). Obesity and intake of two or more medications were associated with higher hazard ratio of having a low FF less than 4%. CONCLUSIONS: Exposure to metformin or two or more medications was associated with decreased FF, and obesity is associated with delay in achieving adequate FF percentage. These findings should be considered while counseling patients on test limitations.

BJPsych Bull ; 39(6): 305-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26755992


Treatment resistance occurs in approximately 30% of individuals with schizophrenia and is commonly treated with clozapine. Nodular sclerosing Hodgkin's lymphoma is a subtype of Hodgkin's lymphoma predominantly affecting those under 50 years of age. In this case report, an individual with treatment-resistant schizophrenia developed nodular sclerosing Hodgkin's lymphoma and is treated with concurrent clozapine and systemic chemotherapy. The aim of this case report is to act as guidance for clinicians and to outline the difficulties of treating individuals with psychiatric illness under the Mental Capacity Act 2005 when the proposed treatment could lead to high levels of morbidity and mortality.

Oncogene ; 24(45): 6820-9, 2005 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-16007143


The integrin beta4 subunit has been shown to be involved in various aspects of cancer progression. The aim of the present work was to evaluate the expression of beta4 in primary colon cancers and to investigate the occurrence of a previously identified intestinal nonfunctional variant of beta4 (beta4ctd-) for adhesion to laminin. Immunodetection of beta4 using a panel of antibodies and RT-PCR analyses were performed on series of paired primary colon tumors and corresponding resection margins. The beta4 subunit was found to be significantly overexpressed in cancer specimens at both the protein and transcript levels. Surprisingly, beta4 levels of expression were closely correlated with those of the oncogene c-Myc in individual specimens. In vitro studies of c-Myc overexpression showed an upregulation of beta4 promoter activity. Finally, the beta4ctd- form was identified in the normal proliferative colonic cells but was found to be predominantly absent in colon cancer cells, both in situ and in vitro. We concluded that the beta4ctd- form is lost from colon cancer cells, while the level of the wild-type form of beta4, which is functional for adhesion to laminin, is increased in primary tumors in relation with the expression of c-Myc.

Neoplasias Colorretais/metabolismo , Expressão Gênica , Genes myc , Integrina beta4/metabolismo , Regulação para Cima/genética , Sequência de Bases , Linhagem Celular Tumoral , Primers do DNA , Humanos , Integrina beta4/genética , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase Via Transcriptase Reversa
Am J Physiol Gastrointest Liver Physiol ; 284(6): G1053-65, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12571085


The purine metabolic gene adenosine deaminase (ADA) is expressed at high levels in a well-defined spatiotemporal pattern in the villous epithelium of proximal small intestine. A duodenum-specific enhancer module responsible for this expression pattern has been identified in the second intron of the human ADA gene. It has previously been shown that binding of the factor PDX-1 is essential for function of this enhancer. The studies presented here examine the proposed roles of GATA factors in the enhancer. Site-directed mutagenesis of the enhancer's GATA binding sites crippled enhancer function in 10 lines of transgenic mice, with 9 of the lines demonstrating <1% of normal activity. Detailed studies along the longitudinal axis of mouse small intestine indicate that GATA-4 and GATA-5 mRNA levels display a reciprocal pattern, with low levels of GATA-6 throughout. Interestingly, gel shift studies with duodenal nuclear extracts showed binding only by GATA-4.

Adenosina Desaminase/genética , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Duodeno/metabolismo , Elementos Facilitadores Genéticos/genética , Elementos de Resposta/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional/genética , Animais , Animais Geneticamente Modificados , Sequência de Bases , Sítios de Ligação , DNA/genética , Duodeno/enzimologia , Fator de Transcrição GATA4 , Mucosa Intestinal/enzimologia , Mucosa Intestinal/metabolismo , Camundongos , Dados de Sequência Molecular , Mutação , Especificidade de Órgãos , Ligação Proteica