Current Concepts of Foot and Ankle Angioleiomyoma.

Angioleiomyoma is a benign tumor, which arises from the smooth muscle. It comprises approximately 4.4% of all benign soft tissues' neoplasms and they are commonly located at the lower extremities. They are most frequently found in middle-aged women. Angioleiomyoma is usually presented as a painful solitary lesion in the subcutaneous tissue. Due to the lack of evidence in the literature, the aim of this current concepts review was to provide foot and ankle surgeons the most updated and useful information for diagnosis and management of foot or ankle's angioleiomyoma. The possible diagnosis of angioleiomyoma is rarely thought of before surgery. X-ray, US, MRI, aspiration, scintigraphy, CT and EMG make part of the diagnostic tools available and angioleiomyoma's main characteristics in each of the exams are detailed. Angioleiomyoma cannot be neglected as consequence of delay or mistreatment increases morbidity and the potential risk to malignant transformation.

NR2F1 deletion in a patient with a de novo paracentric inversion, inv(5)(q15q33.2), and syndromic deafness.

In an effort to discover genes important for human development, we have ascertained patients with congenital anomalies and cytogenetically balanced chromosomal rearrangements. Herein, we report a 4-year-old girl with profound deafness, a history of feeding difficulties, dysmorphism, strabismus, developmental delay, and an apparently balanced de novo paracentric chromosome 5 inversion, inv(5)(q15q33.2). Molecular cytogenetic analysis of the inversion revealed the presence of microdeletions of approximately 400-500 kb at or near both breakpoints. The 5q15 microdeletion completely removes the nuclear receptor NR2F1 (COUP-TFI) from the inverted chromosome 5. We propose haploinsufficiency of NR2F1 to be the cause of the patient's deafness and many of the other associated anomalies based on striking similarity with the Nr2f1 null mouse. Additionally, this study further highlights the need for high resolution analysis of clinical samples with chromosomal rearrangements as associated deletions may be primarily responsible for the clinical features of these patients.

Gene expression microarrays: glimpses of the immunological genome.

Successful microarray experimentation can generate enormous amounts of data, potentially very rich but also very unwieldy. Bold outlooks and new methods for data analysis and presentation should yield additional insight into the complexities of the immune system.

Where CD4+CD25+ T reg cells impinge on autoimmune diabetes.

Foxp3 is required for the generation and activity of CD4(+)CD25(+) regulatory T (T reg) cells, which are important controllers of autoimmunity, including type-1 diabetes. To determine where T reg cells affect the diabetogenic cascade, we crossed the Foxp3 scurfy mutation, which eliminates T reg cells, with the BDC2.5 T cell receptor (TCR) transgenic mouse line. In this model, the absence of T reg cells did not augment the initial activation or phenotypic characteristics of effector T cells in the draining lymph nodes, nor accelerate the onset of T cell infiltration of the pancreatic islets. However, this insulitis was immediately destructive, causing a dramatic progression to overt diabetes. Microarray analysis revealed that T reg cells in the insulitic lesion adopted a gene expression program different from that in lymph nodes, whereas T reg cells in draining or irrelevant lymph nodes appeared very similar. Thus, T reg cells primarily impinge on autoimmune diabetes by reining in destructive T cells inside the islets, more than during the initial activation in the draining lymph nodes.

Progression to islet destruction in a cyclophosphamide-induced transgenic model: a microarray overview.

Type 1 diabetes appears to progress not as an uncontrolled autoimmune attack on the pancreatic islet beta-cells, but rather in a highly regulated manner. Leukocytic infiltration of the pancreatic islets by autoimmune cells, or insulitis, can persist for long periods of time before the terminal destruction of beta-cells. To gain insight on the final stage of diabetogenesis, we have studied progression to diabetes in a CD4(+) T-cell receptor transgenic variant of the NOD mouse model, in which diabetes can be synchronously induced within days by a single injection of cyclophosphamide. A time-course analysis of the gene expression profiles of purified islets was performed using microarrays. Contrary to expectations, changes in transcripts subsequent to drug treatment did not reflect a perturbation of gene expression in CD4(+) T-cells or a reduction in the expression of genes characteristic of regulatory T-cell populations. Instead, there was a marked decrease in transcripts of genes specific to B-cells, followed by an increase in transcripts of chemokine genes (cxcl1, cxcl5, and ccl7) and of other genes typical of the myelo-monocytic lineages. Interferon-gamma dominated the changes in gene expression to a striking degree, because close to one-half of the induced transcripts issued from interferon-gamma-regulated genes.