Androgen receptor genotyping in a large Australasian cohort with androgen insensitivity syndrome; identification of four novel mutations

We genotyped the androgen receptor (AR) gene in 31 Australasian patients with androgen insensitivity syndrome (AIS). The entire coding region of AR was examined including analysis of polymorphic CAG and GGN repeats in all patients. AR defects were found in 66.7% (6/9) of patients with complete AIS (CAIS) and 13.6% (3/22) of patients with partial AIS (PAIS). A novel deletion (N858delG) leading to a premature stop codon was found in CAIS patient P1. CAIS patient P2 has a novel deletion (N2676delGAGT) resulting in a stop at codon 787. These mutations would result in inactivation of AR protein. A novel insertion of a cysteine residue in the first zinc finger of the AR DNA-binding domain (N2045_2047dupCTG) was found in CAIS patient P3. PAIS patient P4 has a novel amino acid substitution (Arg760Ser) in the AR ligand binding domain, which may impair ligand binding. Five patients were found to have previously reported AR mutations and no mutations were identified in the remaining patients

An exploratory study of Muslim adolescents' views on sexuality: Implications for sex education and prevention

<p>Abstract</p> <p>Background</p> <p>This paper describes the results of an exploratory qualitative study on Muslim adolescents' views on sexuality in the Netherlands.</p> <p>Methods</p> <p>Data were gathered from an Internet forum on which 44 Muslim and 33 non-Muslim adolescents discussed sexuality as it relates to Islam. These discussions were subsequently analyzed for content using Nvivo 2.0.</p> <p>Results</p> <p>Our analysis revealed several issues that are relevant for the design of future sex education programs targeting Muslim youth. Apart from some expected outcomes regarding, for example, taboos on sexuality, sex outside marriage, abortion, homosexuality and conservative gender roles, our analyses showed that in cases of disputes 1) discussions were polarized, 2) opponents used the same Qur'anic passages to support their views, and 3) the authority of an Imam was questioned when his interpretation of Qur'anic passages was not in line with the views of participants.</p> <p>Conclusions</p> <p>Our findings show that current approaches to sex education among Muslim youth are likely to be unsuccessful given the rigidity of sexual norms in Muslim society. In addition, we also identified new barriers to sex education among Muslim youth (e.g. lack of respect for an Imam who opposes a youth's views on sexuality).</p

Methionine restriction reduces the chemosensitivity of central nervous system tumour cell lines

The aim of this study was to investigate the effects of methionine depletion with cytotoxic agents that are potentially influenced by depletion of methionine, and are known to have a role in CNS tumour treatments for children. MATERIALS AND METHODS: Cytotoxicity studies and synergistic interactions were assayed by SRB assay. Glutathione levels were assayed by HPLC after derivatization with OPA. MGMT activity was determined by a restriction endonuclease inhibition assay. RESULTS: Methionine depletion causes a demonstrable increase in glutathione levels for medulloblastoma (Daoy) and glioma (D54) cells, with a decrease in MGMT activity for Daoy cells. For both cell lines, methionine depletion reduces their sensitivity to a range of chemotherapy agents that interface at the level of methionine metabolism, namely temozolomide, cisplatin and methotrexate. CONCLUSION: The results show that methionine depletion increases the resistance of tumour cells to the chemotherapeutic agents tested. However, in methionine-replete conditions, we have demonstrated synergistic activity for various combinations of chemotherapeutic agents that are hitherto unreported and may have clinical utility for the treatment of children with CNS tumours

Biochemical changes and cytotoxicity associated with methionine depletion in paediatric central nervous system tumour cell lines

The aim of this study was to investigate the importance of the extent and duration of methionine depletion as a cause of cytotoxicity for CNS tumour cell lines, and also to investigate the associated in vitro cellular biochemical responses. MATERIALS AND METHODS: Cell growth inhibition was assayed by the SRB assay. Intracellular methionine levels were measured by GC/MS following dervatization with MTBSTFA. After methionine depletion, methionine synthase and MGMT activities were also determined. Glutathione levels were assayed by HPLC after derivatization with OPA. RESULTS: Medulloblastoma (Daoy) and glioma (D54) cells were found to be methionine dependent and effects on proliferation, apoptosis and clonogenic survival were dependent on time and degree of methionine depletion. Methionine depletion also caused a demonstrable decrease in L-methionine levels and an increase in glutathione levels for both cell lines, with a decrease in MGMT activity for Daoy cells. CONCLUSION: Daoy and D54 cells are methionine dependent; the degree and duration of methionine depletion is related to cell death. The associated biochemical changes in MGMT and glutathione may be expected to modulate chemosensitivity and this will be investigated in future studies

The influence of expertise upon the designer&apos;s approach to studio practice and tool use

Industrial design is characterized by the embodiment of design intentions. From conceptualization through to design specification, the designer employs a variety of design tools to externalize and develop design solutions to often ill-defined design problems. Surveys of student and practicing designers synthesise existing theoretical and empirical studies of design practice to analyse designer attitudes towards tool use and effectiveness. The survey studies illustrate the influence of expertise upon the designer&apos;s attitudes towards tool use during studio practice. Results indicate a relationship between limited experience and the designer&apos;s perceptions of and approaches to iterative exploration and design divergence. The use of certain designerly tools appear to compound a tendency for design convergence and fixation.close0