Matrix metalloproteinase induction in post-transplant obliterative bronchiolitis.

BACKGROUND: Epithelial cell injury, inflammation, fibrosis, and airway obliteration are associated in post-transplant obliterative bronchiolitis. Fibrosis is a consequence of fibroblastic activity and of collagen deposition after disturbances in the balance of protein formation and degradation. Proteolytic enzymes such as the matrix metalloproteinases mediate degradation. To assess matrix metalloproteinases during obliterative bronchiolitis development, we studied porcine, heterotopic bronchial allografts. METHODS: A total of 119 allografts or autografts were harvested serially at 3 to 60 days after transplantation and processed for histology and in situ hybridization for matrix metalloproteinases 2 and 9. Immunocytochemistry for vimentin and alpha-smooth-muscle-cell actin was performed with specific antibodies. RESULTS: Implants had initial ischemic injury to airway epithelium and to the bronchial wall. Recovery was rapid in autografts and in immunosuppressed allografts. In matrix metalloproteinase-2 mRNA activity in fibroblasts, correlation with endothelial expression and expression in macrophages occurred during intense fibroproliferation. We observed intense matrix metalloproteinase-9 positivity during onset of inflammation and fibroproliferation in endothelial cells (p < 0.01), fibroblasts (p < 0.05), macrophages (p < 0.05), and lymphocytes (p < 0.05). Matrix metalloproteinase-9 mRNA activity in fibroblasts correlated with that in endothelial and inflammatory cells and also proved predictive of early obliteration. CONCLUSIONS: Matrix metalloproteinase-2, and especially matrix metalloproteinase-9, gene activity was associated with onset of inflammation and fibroblastic proliferation in allografts, predicting early obliteration. Although this may be the case in the model described, its role in human-allograft post-transplant obliterative bronchiolitis requires further supportive data.     

Evaluation of frequency of clinical symptoms and signs within six months prior to death in patients with advanced solid cancers

This retrospective study documented the frequency of the clinical symptoms and signs that increase in advanced cancer patients as they move toward death in order to create a sum score and correlate it with survival. Of 572 adult patients who were treated in four selected hospitals and who died in 1998 and 1999, data at six, three, and one month(s) prior to death was available for 257. The results showed that the number of symptoms and certain clinical findings accelerated toward death, increasing the sum score. Younger patients obtained higher sum scores at one month prior to death than did elderly ones (p=0.014); this suggests that elderly patients die at a point where they show less worsening in their clinical condition than do younger patients. The score was independent of cancer type or gender. The results of this analysis provide data for further development of a clinical tool to predict long-term survival in palliative care settings.     

Single bolus antithymocyte globulin versus basiliximab induction in kidney transplantation with cyclosporine triple immunosuppression: efficacy and safety

BACKGROUND: The aim of this prospective randomized study was to examine the effect of induction immunosuppression and low initial cyclosporine (CsA) on the onset of graft function and its long-term consequences. METHODS: During 1999-2001, 155 patients were randomized to single 9 mg/kg dose antithymocyte globulin (ATG)-Fresenius (group A) or two 20-mg doses of basiliximab (group B) with reduced dose CsA or conventional CsA triple therapy without induction (group C). RESULTS: Delayed function (DGF) was lower in group A than in groups B or C (5.7% vs. 24.1% and 15.9%, P<0.025) and need of dialysis was less in groups A and B compared to C (10.3 and 10.4 vs. 20.0 days, P<0.05). Acute rejections occurred in 11.3%, 12.1% and 20.5%, and the mean (median) time to rejection was 16 (13), 97 (46) and 101 (35) days in groups A, B, and C, respectively (P<0.005). One-and 5-year graft survivals (GS) were 98.1% and 90.6% (group A), 96.6% and 96.6% (group B), and 93.2% and 84.1% (group C). Five-year GS was significantly better in group B than in group C (P<0.05). The death censored 5-year GS in groups A, B, and C were 94.3%, 96.6%, and 90.0% (P=NS). Single high-dose ATG induction was associated with hemodynamic and pulmonary disturbances without, however, serious or long-term consequences. CONCLUSIONS: ATG induction significantly reduced DGF. Both induction regimens together with low initial CsA led to significantly less posttransplant dialysis and excellent survival. The high dose ATG was associated with significant hemodynamic and pulmonary side effects during drug infusion.     

Non-occupational contact sensitization to epoxy resin of bisphenol A among general dermatology patients

Background. Sensitization to epoxy resins often results from occupational exposure in various fields of construction and industry. Non‐occupational sensitization sources and environments have remained overlooked. Objectives. To analyse non‐occupational and occupational contact sensitization to epoxy resin of bisphenol A among general dermatology patients. Special attention was paid to patients sensitized from non‐occupational sources. Patients and methods. During a 10‐year period, 6042 general dermatology patients were patch tested with epoxy resin (bisphenol A) in the Dermatology Clinic of Turku University Hospital. The clinical data and the sources of occupational and non‐occupational exposure to epoxy resin were analysed in sensitized patients. Results. Epoxy resin sensitization was found in 59 patients. Non‐occupational sensitization was found in 21 (35%) patients, whereas the number of occupational cases was 38 (65%). The most common sources of non‐occupational epoxy resin sensitization were materials used in domestic renovation and construction projects and in boat repair. Conclusions. Non‐occupational sensitization sources account for approximately one‐third of epoxy resin sensitization cases, and therefore represent an important risk among hobbies and leisure activities.     

O-glycosylation regulates LNCaP prostate cancer cell susceptibility to apoptosis induced by galectin-1

Resistance to apoptosis is a critical feature of neoplastic cells. Galectin-1 is an endogenous carbohydrate-binding protein that induces death of leukemia and lymphoma cells, breast cancer cells, and the LNCaP prostate cancer cell line, but not other prostate cancer cell lines. To understand the mechanism of galectin-1 sensitivity of LNCaP cells compared with other prostate cancer cells, we characterized glycan ligands that are important for conferring galectin-1 sensitivity in these cells, and analyzed expression of glycosyltransferase genes in galectin-1-sensitive, prostate-specific antigen-positive (PSA(+)) LNCaP cells compared with a galectin-1-resistant PSA(-) LNCaP subclone. We identified one glycosyltransferase, core 2 N-acetylglucosaminyltransferase, which is down-regulated in galectin-1-resistant PSA(-) LNCaP cells compared with galectin-1-sensitive PSA(+) LNCaP cells. Intriguingly, this is the same glycosyltransferase required for galectin-1 susceptibility of T lymphoma cells, indicating that similar O-glycan ligands on different polypeptide backbones may be common death trigger receptors recognized by galectin-1 on different types of cancer cells. Blocking O-glycan elongation by expressing alpha2,3-sialyltransferase 1 rendered LNCaP cells resistant to galectin-1, showing that specific O-glycans are critical for galectin-1 susceptibility. Loss of galectin-1 susceptibility and synthesis of endogenous galectin-1 has been proposed to promote tumor evasion of immune attack; we found that galectin-1-expressing prostate cancer cells killed bound T cells, whereas LNCaP cells that do not express galectin-1 did not kill T cells. Resistance to galectin-1-induced apoptosis may directly contribute to the survival of prostate cancer cells as well as promote immune evasion by the tumor.