ABSTRACT
Type-I diabetes is an autoimmune inflammatory disease in which pancreatic beta-cells are selectively destroyed by infiltrating cells. TNF-related apoptosis-inducing ligand [TRAIL] is a type-II membrane protein of the TNF superfamily which is expressed in different tissues, including pancreas and lymphocytes. In humans, TRAIL interacts with four membrane receptors. TRAIL-R1 and TRAIL-R2 have cytoplasmic death domains, and can activate both caspases and NF?B pathways. The other two receptors, TRAIL-R3 and TRAIL-R4, are decoy receptors not capable of activating caspase cascade but may activate NF-?B and block apoptosis. As human beta cells are sensitive to TRAIL induced apoptosis, signaling via these molecules is considered to be a probable way of beta cell destruction. These molecules also are important in suppression of autorective T cells and immunoregulation. To explore the importance of TRAIL and its receptors at pathogenesis of type-I diabetes, we compared expression of these molecules on T-cells of diabetic patients and healthy controls. In this study, expression of TRAIL and its receptors at protein and mRNA levels were studied in freshly isolated peripheral T cells of 55 type I diabetic patients and 50 healthy individuals by flowcytometry, western blot and RT-PCR. We found that expression of TRAIL and its receptors in peripheral T-cells at both protein and mRNA levels are significantly increased in patients [except for TRAIL-R2 mRNA which was slightly higher in controls] but increase in TRAIL, TRAILR3 [2.7% vs. >0.5%] and TRAIL-R4 [2.6% vs. >0.5%] is more considerable. sTRAIL in sera of patients was significantly lower than in controls [p=0.01]. Our results explain resistance of autoreactive T-cells to immunoregulatory mechanisms. Besides, increased expression of TRAIL in autoreactive T-cells may play an important role in betacell destruction. Lower level of sTRAIL in diabetic patients may be a reason for hyperactivation of autoreactive T-cells
ABSTRACT
Background: Lung cancer is the second common malignancy in human. Human papillomavirus [HPV] has a well established association with squamous cell carcinoma of anogenital region. This study was performed in Massih Daneshvari hospital, between 1999 and 2003 to evaluate association of human papillomavirus type 16 and 18 in squamous cell carcinoma of the lung among Iranian patients
Materials and Methods: Paraffin embedded block of pathology archive of Massih Daneshvari hospital with diagnosis of SCC were selected for determination of HPV DNA by semi-nested PCR. For each specimen, all hematoxyline-eosin stained slides were reviewed by two pathologists; if the initial slide was inappropriate, a new slide was prepared. All inadequate specimens were excluded from the study
Results: 18 out of 45 paraffin- embedded specimens with diagnosis of squamous cell carcinoma were selected. Six specimens were positive for HPV type 16, and 2 were positive for HPV type 18. None of the specimens was shown to have concurrent positivity of HPV types 16 and 18
Conclusion: The present study showed that high risk HPV was associated with squamous cell carcinoma of the lung and more prevalent type was HPV 16. We suggest further investigations to evaluate this relationship