The child of uncertain sex: 17 years of experience

Objective: To review the common clinical presentations, investigations and final diagnosis of children presenting with genital ambiguity. Methodology: Retrospective search of the Royal Children's Hospital, Brisbane, Australia, medical records and personal medical database of one of the authors (MJT) between 1982 and 1999. Results: Fifty-one children aged 0.1-;14 (mean 3.9) years were identified. Twenty-two cases had a 46XX karyotype, and commonly presented with an enlarged phallus (77.2%), urogenital sinus (63.6%) and labioscrotal fold(s) (40.9%). Congenital adrenal hyperplasia (CAH) was the most common final diagnosis (72.7%) . Twenty-nine cases of genital ambiguity had a 46XY karyotype and commonly presented with palpable gonad(s) (75.8%), undescended testes (51.7%), penoscrotal hypospadias (51.7%) and a small phallus (41.3%). Androgen insensitivity and gonadal dysgenesis were the commonest final diagnosis both occurring at a frequency of 17.2%. Conclusions: The results emphasize the importance of CAH as the most common diagnosis in 46XX cases presenting with ambiguous genitalia. Those with 46XY had a wider range of diagnoses. Despite thorough investigation, 23.5% had no definite final diagnosis made.

Specificity of 17 beta-oestradiol and benzo[a] pyrene oxidation by polymorphic human cytochrome P4501B1 variants substituted at residues 48, 119 and 432

1. Eight human cytochrome P4501B1 (CYP1B1) allelic variants, namely Arg(48)Ala(119)Leu(432), Arg(48)Ala(119)Val(432), Gly(48)Ala(119)Leu(432), Gly(48)Ala(119)Val(432), Arg(48)Ser(119)Leu(432), Arg(48)Ser(119)Val(432), Gly(48)Ser(119)Leu(432) and Gly(48)Ser(119)Val(432) (all with Asn(453)), were expressed in Escherichia coli together with human NADPH-P450 reductase and their catalytic specificities towards oxidation of 17 beta -oestradiol and benzo[a]pyrene were determined. 2. All of the CYP1B1 variants expressed in bacterial membranes showed Fe2+. CO versus Fe2+ difference spectra with wavelength maxima at 446 nm and they reacted with antibodies raised against recombinant human CYP1B1 in immunoblots. The ratio of expression of the reductase to CYP1B1 in these eight preparations ranged from 0.2 to 0.5. 3. CYP1B1 Arg(48) variants tended to have higher activities for 17 beta -oestradiol 4-hydroxylation than Gly(48) variants, although there were no significant variations in 17 beta -oestradiol 2-hydroxylation activity in these eight CYP1B1 variants. Interestingly, ratios of formation of 17 beta -oestradiol 4-hydroxylation to 2-hydroxylation by these CYP1B1 variants were higher in all of the Val(432) forms than the corresponding Leu(432) forms. 4. In contrast, Leu(432) forms of CYP1B1 showed higher rates of oxidation of benzo[a]pyrene (to the 7, 8-dihydoxy-7,8-dihydrodiol in the presence of epoxide hydrolase) than did the Val(432) forms. 5. These results suggest that polymorphic human CYP1B1 variants may cause some altered catalytic specificity with 17 beta -oestradiol and benzo[a]pyrene and may influence susceptibilities of individuals towards endogenous and exogenous carcinogens.

The gene encoding the immunoregulatory signaling molecule CMRF-35A localized to human chromosome 17 in close proximity to other members of the CMRF-35 family

The immunoregulatory signaling (IRS) family includes several molecules, which play major roles in the regulation of the immune response. The CMRF-35A and CMRF-35H molecules are two new members of the IRS family of molecules, that are found on a wide variety of haemopoietic lineages. The extracellular functional interactions of these molecules is presently unknown, although CMRF-35H on initiate an inhibitory signal and is internalized when cross-linked. In this paper, we described the gene structure for the CMRF-35A gene and its localization to human chromosome 17. The gene consists of four exons spanning approximately 4.5 kb. Exon 1 encodes the 5' untranslated region and leader sequence, exon 2 encodes the immunoglobulin (Ig)-like domain, exon 3 encodes the membrane proximal region and exon 4 encodes the transmembrane region, the cytoplasmic tail and the 3' untranslated region. A region in the 5' flanking sequence of the CMRF-35A gene, that promoted expression of a reporter gene was identified. The genes for the CMRF-35A and CMRF-35H molecules are closely linked on chromosome 17. Similarity between the Ig-like exons and the preceding intron of the two genes suggests exon duplication was involved in their evolution. We also identified a further member of the CMRF-35 family, the CMRF-35J pseudogene. This gene appears to have arisen by gene duplication of the CMRF-35A gene. These three loci-the CMRF-35A, CMRF-35J and CMRF-35H genes-form a new complex of IRS genes on chromosome 17.

Mouse Sox8 is located between, not within, the t-complex deletions t(w18) and t(h20) on chromosome 17

The SOX family of developmental transcription factors is known to play critical roles in cell lineage specification, fate determination and differentiation during development in diverse phyla. Their importance is underscored by their involvement in a number of human diseases and mouse mutants, and by targeted mutation in mice. SOX8 is broadly expressed during development and is located on human chromosome 16p and within the t-complex on mouse chromosome 17, in the vicinity of two mutations t(w18) and t(h20). Here we analyse mutant genomic DNA to show that the Sox8 gene locus lies outside the deletion regions of both t(w18) and t(h20) and between these deletions. These data exclude Sox8 from contributing to the t(w18) and t(h20) phenotypes, and provide an additional marker for structural characterization of this complex genomic region. Copyright (C) 2001 S. Karger AG, Basel.

A????es premiadas no 17?? Concurso Inova????o na Gest??o P??blica Federal 2012

Este livro traz os relatos das 10 iniciativas premiadas no 17?? Concurso Inova????o na Gest??o P??blica Federal. Iniciativa da ENAP, em parceria com o MP, o Concurso conta com o apoio, para as premia????es, das embaixadas da Fran??a, da Noruega e da Nova Zel??ndia; da Coopera????o Alem?? para o Desenvolvimento (GIZ); e da Ag??ncia Brasileira de Coopera????o (ABC). Ao longo de 17 anos, o Concurso tem cumprido seu objetivo de estimular a implementa????o de iniciativas inovadoras de gest??o em organiza????es do governo federal; dissemin??-las e valorizar servidores p??blicos que atuam de forma criativa em suas atividades

Texto para discuss??o 17: controle interno e paradigma gerencial

O interesse no estudo do tema ???controle??? surge num contexto de reforma administrativa com vistas adequar o aparelho do Estado ??s novas demandas do desenvolvimento econ??mico e social. O projeto de reforma administrativa de iniciativa do Minist??rio da Administra????o Federal e Reforma do Estado tem por base um diagn??stico de crise fiscal e de crise do modelo de administra????o burocr??tica caracter??stico do Estado nacional-desenvolvimentista e interventor, vigente entre os anos 30 e final da d??cada de 80 no Brasil. Tendo cumprido o seu papel no passado, o modelo burocr??tico torna-se obsoleto por seu car??ter excessivamente formalista e r??gido, hierarquizado e pouco comprometido com resultados. A alternativa a este modelo ?? denominada administra????o gerencial ou administra????o por resultados

Programa do curso de forma????o para o cargo de Analista de Planejamento e Or??amento (APO) 17?? edi????o - 2012

Proposta Pedag??gica do Curso de Forma????o inicial para Analista de Planejamento e Or??amento 2012 (17?? Edi????o), segunda etapa do concurso p??blico para provimento do referido cargo

Palestras do curso de forma????o para o cargo de Analista de Planejamento e Or??amento: 17?? edi????o

Palestras e semin??rios sobre temas atuais da agenda governamental, nos quais foram abordadas dimens??es pertinentes aos valores e compet??ncias requeridos para o exerc??cio profissional dos Analistas de Planejamento e Or??amento

Portaria n?? 181, de 17 de julho de 2013: aprova a Pol??tica Editorial da Escola Nacional de Administra????o P??blica e institui a Comiss??o Editorial da Enap

O objetivo da portaria ?? instituir a Comiss??o Editorial da ENAP.

Portaria n?? 181, de 17 de julho de 2013

A pol??tica editorial da Escola Nacional de Administra????o P??blica (ENAP), ?? regulamentada pela Portaria n?? 181, de 17 de julho de 2013.