Airway inflammation and epithelial remodeling are two key features of asthma. IL-13 and other cytokines produced during T helper type 2 cell-driven allergic inflammation contribute to airway epithelial goblet cell metaplasia and may alter epithelial-mesenchymal signaling, leading to increased subepithelial fibrosis or hyperplasia of smooth muscle. The beneficial effects of corticosteroids in asthma could relate to their ability to directly or indirectly decrease epithelial cell activation by inflammatory cells and cytokines. To identify markers of epithelial cell dysfunction and the effects of corticosteroids on epithelial cells in asthma, we studied airway epithelial cells collected from asthmatic subjects enrolled in a randomized controlled trial of inhaled corticosteroids, from healthy subjects and from smokers (disease control). By using gene expression microarrays, we found that chloride channel, calciumactivated, family member 1 (CLCA1), periostin, and serine peptidase inhibitor, clade B (ovalbumin), member 2 (serpinB2) were up-regulated in asthma but not in smokers. Corticosteroid treatment down-regulated expression of these three genes and markedly up-regulated expression of FK506-binding protein 51 (FKBP51). Whereas high baseline expression of CLCA1, periostin, and serpinB2 was associated with a good clinical response to corticosteroids, high expression of FKBP51 was associated with a poor response. By using airway epithelial cells in culture, we found that IL-13 increased expression of CLCA1, periostin, and serpinB2, an effect that was suppressed by corticosteroids. Corticosteroids also induced expression of FKBP51. Taken together, our findings show that airway epithelial cells in asthma have a distinct activation profile and identify direct and cell-autonomous effects of corticosteroid treatment on airway epithelial cells that relate to treatment responses and can now be the focus of specific mechanistic studies.gene expression microarray ͉ serpinB2 ͉ CLCA1 ͉ FKBP51
The introduction of Onyx has improved the endovascular cure rate of DAVFs, particularly types III and IV. Advances in technology have made an endovascular approach the management of choice for the majority of DAVFs requiring treatment. Low complication rates are achievable.
The question of banking of fresh frozen human prostatic tissue is addressed by a group of authors who have compared its value with what they call “pseudobanked” tissue. They then validate their methodology by a number of methods, including expression of hepsin, which they found to be significantly higher in malignant than in benign tissue. The theme of prostate cancer is continued by an English group looking at recent trends in the use of radical prostatectomy in England, and they make a number of interesting comments about this. Again in relation to prostate cancer, a group from Boston assess the use of steroids after prostate brachytherapy to reduce the risk of acute urinary retention. Authors from McGill University, Montreal and Beth Israel in Boston, comment on the controversial areas of insulin‐like growth factor and prostatic intraepithelial neoplasia and their role in the genesis of prostate cancer. Other interesting areas such as testicular sparing surgery in testis cancer, and a comparison of hand‐assisted laparoscopic versus open radical nephrectomy, are also described in this section. OBJECTIVE To describe the establishment, methods, validation and use of a bank of fresh‐frozen human prostate tissue. MATERIALS AND METHODS On obtaining informed patient consent, protocols were followed for banking prostate tissue from any type of prostatectomy or cystoprostatectomy. A pseudobanking procedure was devised to determine the accuracy of assessing the histopathological status of the banked tissue. RNA was extracted, its quality assessed and used for quantitative real‐time reverse transcription‐polymerase chain reaction for the serine protease hepsin. RESULTS To date prostate tissue from 112 patients has been banked, with pseudobanking in 58. The histopathological assessment showed pseudobanked tissue matched adjacent unbanked tissue in 98% of cases for benign vs malignant diagnoses, and in 92% of carcinomas for the Gleason score. Hepsin expression was significantly higher in malignant than in benign tissues (P < 0.0001). CONCLUSION We established a validated method for banking human fresh‐frozen prostate tissue and applied it successfully. Hepsin expression can be used to differentiate malignant and benign prostate tissue, and as an indicator of tissue heterogeneity.
Purpose Children with cerebral palsy may have low bone density stemming from various etiologies and are, thereby, at risk for fractures. The treatment of femur fractures in children with cerebral palsy may need to be tailored to address the management of spastic muscle tone and multiple medical co-morbidities. Methods Our study is a retrospective review that evaluates the treatment of 47 femur fractures in children with cerebral palsy in both ambulatory and non-ambulatory patients.Results Thirty-two fractures in non-ambulators were treated non-operatively, 11 of which resulted in malunions and five developed pressure sores. Six fractures in nonambulators were treated operatively, one of which resulted in a malunion. In ambulators, five fractures were treated non-operatively; one of these fractures lost reduction after 2 weeks and required surgical intervention. One of four fractures in ambulators treated operatively developed a malunion. Conclusion Our study results suggest that femur fractures in children with cerebral palsy can be treated non-operatively; however, because of the high risk of malunion in this patient population, fracture alignment needs to be followed closely during healing. Careful attention during casting is necessary to prevent pressure sores. Strong consideration should be given to initial operative treatment in ambulatory patients in order to preserve function.
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