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Nick Coleman

Publications and source records attributed to Nick Coleman.

4 recordsLinked to original sources
PubMed2006

Changes in gene expression during Wolffian duct development.

BACKGROUND: Wolffian ducts (WDs) are the embryonic precursors of the male reproductive tract. Their development is induced by testosterone, which interacts with the androgen receptor (AR). The molecular pathways underlying androgen-dependent WD development are largely unknown. We aimed to identify AR target genes important in this process. METHODS: RNA was isolated from rat WDs at E17.5 and E20.5. Affymetrix GeneChip expression arrays were used to identify transcripts up- or downregulated more than 2-fold. Regulation of seven transcripts was confirmed using quantitative PCR. RESULTS: Transcripts from 76 known genes were regulated, including modulators of insulin-like growth factor and transforming growth factor-beta signalling. By controlling these modulators, androgens may indirectly affect growth factor signalling pathways important in epithelial-mesenchymal interactions and organ development. Caveolin-1, also upregulated, may play a role in modifying as well as mediating AR signalling. Differentiation of WD epithelium and smooth muscle, innervation and extracellular matrix synthesis were reflected in regulation of other transcripts. Several genes were previously suggested to be regulated by androgens or contained functional or putative androgen/glucocorticoid response elements, indicating they may be direct targets of androgen signalling. CONCLUSION: Our results suggest novel cohorts of signals that may contribute to androgen-dependent WD development and provide hypotheses that can be tested by future studies.

Androgens↗
PubMed2006

Mcm-2 and Ki-67 have limited potential in preoperative diagnosis of thyroid malignancy.

OBJECTIVES: Minichromosome maintenance protein 2 (Mcm-2) is essential for DNA replication and serves as a useful biomarker of cell-cycle state in human tissue samples. Ki-67 is an established proliferation marker. Because Mcm-2 expression has not previously been assessed in thyroid tissue, the aim of this study was to assess the expression of both proteins in a range of thyroid lesions to determine their potential value as preoperative markers of thyroid malignancy. METHODS: Mcm-2 and Ki-67 protein expression were assessed by immunohistochemistry in formalin-fixed, paraffin-embedded thyroid tissues from 128 patients with histologic diagnoses of papillary carcinoma (n = 38), follicular carcinoma (n = 22), follicular adenoma (n = 33), and dominant nodules of multinodular goitre (n = 35). RESULTS: Mcm-2 and Ki-67-labeling indices (LIs) were both higher in follicular and papillary carcinomas than in follicular adenomas or dominant nodules. The Ki-67 LI discriminated better between follicular carcinomas and follicular adenomas (P < .0001) than Mcm-2 (P = .0273). However, the Mcm-2 and Ki-67 LIs overlapped widely between the four histologic groups, and the expression of these proteins was also noted to be heterogenous within these lesions. CONCLUSION: Neither Mcm-2 or Ki-67 can currently be reliably applied as preoperative markers to distinguish benign from malignant thyroid lesions.

Adenoma↗
PubMed2004

Residual activity of mutant androgen receptors explains wolffian duct development in the complete androgen insensitivity syndrome.

Development of the Wolffian ducts (WD) into epididymides and vasa deferentia is dependent on testosterone. Patients with the complete androgen insensitivity syndrome (CAIS) are therefore not expected to develop these structures. However, WD derivatives have been described in cases of CAIS. It is thought that these may be remnants. This study assesses the degree of WD development in 33 patients with CAIS and investigates whether this development was androgen dependent. Epididymides and vasa deferentia were identified in 70% of patients with substitution mutations in the androgen receptor ligand-binding domain. They were more developed than epididymides and vasa deferentia from 16- to 20-wk-old male fetuses, suggesting that the WD had been stimulated to grow, rather than failed to regress. Receptors with substitutions in the ligand-binding domain were normally expressed and showed residual response to androgens in transactivation assays. Patients with premature stop codons or frameshift mutations, which prevented androgen receptor expression, or DNA-binding domain mutations that abolished transcriptional activity did not have epididymides or vasa deferentia. We hypothesize that mutant receptors with residual activity in vitro respond to high local testosterone concentrations in vivo, thereby stimulating WD development. The classification of androgen insensitivity in such patients should be considered severe rather than complete.

Adolescent↗