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Full-length sequences of the Epstein-Barr virus (EBV) gene for latent membrane protein (LMP)-1 from 22 nasopharyngeal carcinoma (NPC) biopsy specimens and 18 non-neoplastic counterparts (NPI) were determined. Relative to the B95-8 strain, the amino acid sequences of the toxic-signal and transformation domains were changed variably in NPC and NPI specimens; in contrast, no change was observed in the NF-kB (nuclear factor kB) activation domain. HLA typing revealed that 47 % of NPC and 31 % of NPI specimens were HLA A2-positive. A major A2-restricted epitope within LMP-1 (residues 125-133) was analysed. At residue 126, a change of LRF was detected in 91 % (20/22) of NPC and 67 % (12/18) of NPI specimens. In addition, a deletion at residue 126 was detected in one NPC sample from Taiwan. At residue 129, a change of MRI was observed in all samples, regardless of whether they were NPC or NPI. The changes in this peptide between NPC and NPI specimens, including mutation and deletion, are statistically significant (P<0?05). A recent report indicated that this variant sequence is recognized poorly by epitope-specific T cells. Genotyping results indicated that 96 % of NPC and 67 % of NPI samples carried a type A virus. By scanning the entire sequence of LMP-1, eight distinct patterns were identified. Detailed examination of these patterns revealed that type A strains are more prevalent in NPC than in NPI specimens and are marked by the loss of an XhoI site, the presence of a 30 bp deletion and the presence of a mutated, A2-restricted, T cell target epitope sequence. These results suggest that an EBV strain carrying an HLA A2-restricted 'epitope-loss variant' of LMP-1 is prevalent in NPC in southern China and Taiwan.

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Curcumin (CUR) has been shown to possess a preventive effect against various cancers and interfere with multiple-cell signaling pathways. We evaluated the protective effects of CUR in regression of UVB-induced skin tumor formation in SKH-1 hairless mice and its underlying early molecular biomarkers associated with carcinogenesis. Mice irradiated with UVB at 180 mJ/cm2 twice per week elicited 100% tumor incidence at 20 weeks. Topical application of CUR prior to UVB irradiation caused delay in tumor appearance, multiplicity, and size. Topical application of CUR prior to and immediately after a single UVB irradiation (180 mJ/cm2) resulted in a significant decrease in UVB-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells together with an increase in p53 and p21/Cip1-positive cell population in epidermis. Simultaneously, CUR also significantly inhibited NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) levels. The results suggest that the protective effect of CUR against photocarcinogenesis is accompanied by downregulation of cell proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, while upregulation of p53 and p21/Cip1 to prevent DNA damage and facilitate DNA repair.

BackgroundMultiple case definitions are in use to identify chronic fatigue syndrome (CFS). Even when using the same definition, methods used to apply definitional criteria may affect results. The Centers for Disease Control and Prevention (CDC) conducted two population-based studies estimating CFS prevalence using the 1994 case definition; one relied on direct questions for criteria of fatigue, functional impairment and symptoms (1997 Wichita; Method 1), and the other used subscale score thresholds of standardized questionnaires for criteria (2004 Georgia; Method 2). Compared to previous reports the 2004 CFS prevalence estimate was higher, raising questions about whether changes in the method of operationalizing affected this and illness characteristics.MethodsThe follow-up of the Georgia cohort allowed direct comparison of both methods of applying the 1994 case definition. Of 1961 participants (53 % of eligible) who completed the detailed telephone interview, 919 (47 %) were eligible for and 751 (81 %) underwent clinical evaluation including medical/psychiatric evaluations. Data from the 499 individuals with complete data and without exclusionary conditions was available for this analysis.ResultsA total of 86 participants were classified as CFS by one or both methods; 44 cases identified by both methods, 15 only identified by Method 1, and 27 only identified by Method 2 (Kappa 0.63; 95 % confidence interval [CI]: 0.53, 0.73 and concordance 91.59 %). The CFS group identified by both methods were more fatigued, had worse functioning, and more symptoms than those identified by only one method. Moderate to severe depression was noted in only one individual who was classified as CFS by both methods. When comparing the CFS groups identified by only one method, those only identified by Method 2 were either similar to or more severely affected in fatigue, function, and symptoms than those only identified by Method 1.ConclusionsThe two methods demonstrated substantial concordance. While Method 2 classified more participants as CFS, there was no indication that they were less severely ill or more depressed. The classification differences do not fully explain the prevalence increase noted in the 2004 Georgia study. Use of standardized instruments for the major CFS domains provides advantages for disease stratification and comparing CFS patients to other illnesses.