The development of new blood vessels from pre-existing blood vessels (angiogenesis) is essential for normal tissue repair. However, neovascularization also contributes to the growth and dissemination of solid tumors and thus interfering with tumor angiogenesis presents much promise as a means to limit tumor growth and metastasis. 1,2Tumor-derived stimuli induce quiescent endothelial cells (ECs) to re-enter the cell cycle, express extracellular matrix-degrading proteinases, and up-regulate expression of adhesion molecules to allow migration.3-5 Vascular sprouts then resynthesize basement membranes (BMs), undergo capillary morphogenesis and withdraw from the cell cycle, and form mature quiescent vessels.To understand the complex temporal and spatial regulation of expression of proteinases, adhesion molecules, and extracellular matrix molecules during angiogenesis, we have been investigating the role of Homeobox (Hox) master regulatory genes. In addition to their roles in embryogenesis, Hox genes are also expressed in adult cells, including the vascular endothelium, and regulate expression of genes involved in cell-cell, cell-extracellular matrix interactions, and cell proliferation.6 -11 Previously we showed that HoxD3 induces an angiogenic phenotype and promotes EC migration and invasion via up-regulation of ␣v3 integrin and urokinase plasminogen activator (uPA) and that HoxB3 contributes to angiogenesis by increasing expression of ephrin A1 that facilitates capillary morphogenesis. 9,12The 40 class I vertebrate Hox genes are clustered in four linkage groups (A to D), on four different chromosomes with both the proangiogenic HoxD3 and HoxB3 being located toward the 3Ј end of these Hox gene clusters. During embryogenesis, 3Ј Hox gene expression is followed by the sequential activation of more 5Ј Hox genes, giving rise to nonoverlapping boundaries of expression.13 A similar 3Ј to 5Ј wave of Hox gene expression is also observed when adult hematopoietic progenitor cells are induced to differentiate, 14 while maturing cells attenuate expression of 3Ј Hox genes and begin to express high levels of 5Ј Hox genes such as HoxA10. 15,16 Together these observations suggest that 5Ј and 3Ј Hox genes control different aspects of cell or tissue phenotype.As the majority of adult ECs exist in a quiescent state, we reasoned that after angiogenesis maturing capillaries would begin to express 5Ј Hox genes, which in turn may help to maintain a quiescent, differentiated phenotype. Furthermore, we investigated whether sustaining expression of 5Ј Hox genes in an angiogenic environment could prevent acquisition of an angiogenic phenotype. Materials and Methods Cells, Transfections, and RNA IsolationImmortalized human dermal microvascular ECs HMEC-1 were a gift from T. Lawley, Emory University, Atlanta, GA.17,18 Cells were maintained and cultured on BMs as previously described.9 Primary human dermal microvascular ECs were purchased from BioWhittaker (San Diego, American Journal of Pathology, Vol. 161, No. 6, December 2002 Copyright © Am...
Illicit drug use constitutes a major health problem and may be associated with various thoracic complications. These complications vary depending on the specific drug used and the route of administration. Commonly abused drugs that may play a role in causing thoracic disease include cocaine, opiates, and methamphetamine derivatives. Intravenously abused oral medications may contain filler agents that may be responsible for disease. Thoracic complications may be categorized as pulmonary, pleural, mediastinal, cardiovascular, and chest wall complications. Pulmonary complications of drug abuse include pneumonia, cardiogenic edema, acute lung injury, pulmonary hemorrhage, and aspiration pneumonia. Filler agents such as talc may result in panacinar emphysema or high-attenuation upper-lobe conglomerate masses. The primary pleural complication of illicit drug use is pneumothorax. Mediastinal and cardiovascular complications of illicit drug use include pneumomediastinum, cardiomyopathy, myocardial infarction, aortic dissection, and injection-related pseudoaneurysms. Chest wall complications include diskitis and vertebral osteomyelitis, epidural abscess, necrotizing fasciitis, costochondritis, and septic arthritis. Categorization of thoracic complications of illicit drug use may facilitate understanding of these disorders and allow accurate diagnosis.
During a 7-year period 123 paired urethrographic and sono-urethrographic studies were performed on 101 patients with 110 urethral strictures. In all but 3 cases the urethra was subsequently evaluated either cystoscopically or at open operation. Sono-urethrography readily identified urethral calculi, diverticula and false passages. It correctly identified the stricture and its site in every case. There was a significant difference between stricture length as measured by urethrography compared to that measured by sono-urethrography (p < 0.003). However, if the strictures were grouped based on anatomical location, there was good correlation and no significant difference in the penile urethra (correlation coefficient = 0.94, p = 0.74) but poor correlation and the significant difference remained in the urethral bulb (correlation coefficient = 0.64, p < 0.007). Similarly, when urethrographic and sono-urethrographic stricture lengths were compared with operative lengths, in the penile urethra the correlation coefficients were close (correlation coefficient = 0.91 versus 0.98) but in the urethral bulb the poor correlation persisted (correlation coefficient = 0.69 versus 0.89). Although sono-urethrography certainly identifies periurethral tissue, it was unreliable in predicting the depth of spongiofibrosis when compared with full depth biopsies in 36 patients with histopathological correlation. Finally, in 16% of the patients sono-urethrography correctly indicated a reconstructive procedure different from that originally suggested by conventional urethrography. Sono-urethrography is a dynamic 3-dimensional study that accurately identifies stricture site, number and caliber. Compared with conventional urethrography, it more accurately measures stricture length and diameter, and identifies periurethral tissue, making it a valuable adjunct in the evaluation of patients with suspected anterior urethral strictures.
Primary pulmonary LELC is histopathologically identical to nasopharyngeal carcinoma. The radiographic, CT, and MRI features of primary pulmonary LELC are nonspecific, often resembling those of bronchogenic carcinoma. Primary pulmonary LELC usually presents as a poorly circumscribed, enhancing, peripheral solitary pulmonary nodule on CT; necrosis may be present and is considered a poor prognostic sign. MRI shows isointense to low-intensity signal on T1-weighted images and mildly increased signal on T2-weighted images; enhancement of abnormal tissue is typical. Most patients present with early-stage disease. Primary pulmonary LELC should be suspected in selected patients and requires differentiation from bronchogenic carcinoma and metastatic nasopharyngeal carcinoma.
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