RESUMO
Small, incidental testicular lesions are often benign, but in the past have usually been treated by orchidectomy. An alternative is an operative excision biopsy, with localization by ultrasound if necessary, and characterization of the lesion by frozen section analysis. The present review summarizes the indications for the procedure, lists the likely diagnoses, and describes the technique. Frozen section is accurate for distinguishing benign from malignant lesions, testicular function is usually preserved, and there is no evidence that oncological safety is impaired. Such testis-preserving surgery is a rewarding ground for collaboration between urologists, radiologists, and pathologists.
Assuntos
Biópsia/métodos , Orquiectomia/estatística & dados numéricos , Doenças Testiculares/patologia , Testículo/patologia , Procedimentos Desnecessários , Adulto , Diagnóstico Diferencial , Secções Congeladas/métodos , Humanos , Achados Incidentais , Imageamento por Ressonância Magnética , Masculino , Doenças Testiculares/diagnóstico por imagem , Doenças Testiculares/cirurgia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/cirurgia , Testículo/diagnóstico por imagem , Testículo/cirurgia , Ultrassonografia de Intervenção/métodos , Adulto JovemRESUMO
AP-1, an immediate-early transcription factor comprising heterodimers of the Fos and Jun proteins, has been shown in several animal models, including Drosophila, to control neuronal development and plasticity. In spite of this important role, very little is known about additional proteins that regulate, cooperate with, or are downstream targets of AP-1 in neurons. Here, we outline results from an overexpression/misexpression screen in Drosophila to identify potential regulators of AP-1 function at third instar larval neuromuscular junction (NMJ) synapses. First, we utilize >4000 enhancer and promoter (EP) and EPgy2 lines to screen a large subset of Drosophila genes for their ability to modify an AP-1-dependent eye-growth phenotype. Of 303 initially identified genes, we use a set of selection criteria to arrive at 25 prioritized genes from the resulting collection of putative interactors. Of these, perturbations in 13 genes result in synaptic phenotypes. Finally, we show that one candidate, the GSK-3beta-kinase homolog, shaggy, negatively influences AP-1-dependent synaptic growth, by modulating the Jun-N-terminal kinase pathway, and also regulates presynaptic neurotransmitter release at the larval neuromuscular junction. Other candidates identified in this screen provide a useful starting point to investigate genes that interact with AP-1 in vivo to regulate neuronal development and plasticity.
Assuntos
Proteínas de Drosophila/genética , Drosophila/enzimologia , Drosophila/genética , Quinase 3 da Glicogênio Sintase/genética , Neurônios/enzimologia , Transmissão Sináptica/genética , Fator de Transcrição AP-1/metabolismo , Animais , Drosophila/crescimento & desenvolvimento , Proteínas de Drosophila/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Imuno-Histoquímica , Larva/metabolismo , MAP Quinase Quinase 4/metabolismo , Neurônios/metabolismo , Fenótipo , Transdução de Sinais , Fator de Transcrição AP-1/genéticaRESUMO
Remarkably anisotropic Mn L2,3 x-ray magnetic circular dichroism spectra from the ferromagnetic semiconductor (Ga,Mn)As are reported. States with cubic and uniaxial symmetry are distinguished by careful analysis of the angle dependence of the spectra. The multiplet structures with cubic symmetry are qualitatively reproduced by calculations for an atomiclike d5 configuration in tetrahedral environment, and show zero anisotropy in the orbital and spin moments within the experimental uncertainty. However, hybridization with the host valence bands is reflected by the presence of a preedge feature with a uniaxial anisotropy and a marked dependence on the hole density.
Assuntos
Clonagem Molecular/métodos , Impressões Digitais de DNA/métodos , Enzimas de Restrição do DNA/metabolismo , Polimorfismo Conformacional de Fita Simples , Bactérias , Primers do DNA , Proteínas de Ligação a DNA/genética , Humanos , Peso Molecular , Mutação , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Proteína Smad4 , Transativadores/genéticaRESUMO
Temozolomide (8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4-(3H)-one) has shown promising activity in Phase I trials against some brain (glioma) and skin (melanoma, mycosis fungoides) cancers. Temozolomide and lomustine (CCNU) showed parallel toxicity in seven human tumour cell lines and this generally correlated (correlation coefficients 0.87 and 0.92 respectively) with the level of expression of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase, EC 2.1.1.63). Pretreating cells with the ATase inhibitor, O6-benzylguanine (BG), potentiated cytotoxicity to a similar degree with both drugs, but did not sensitise a cell line (ZR-75-1) expressing very low levels of this protein. When BG pretreatment was combined with repeat doses of temozolomide a dramatic potentiation (300 fold) was seen in MAWI cells, which express high levels of ATase, but not in a cell line (U373) expressing lower levels of ATase. [14C]-labelled temozolomide uptake was similar in sensitive and resistant lines. Human ATase-cDNA transfected xeroderma pigmentosum (XP) fibroblasts were more resistant than XP control cells to temozolomide and the related chloroethylating agent mitozolomide and although BG completely suppressed ATase activity in these cells, resistance was still greater than in control cells.