Lack of association between DNA base excision repair gene XRCC1 Gln399Arg polymorphism and risk of malignant lymphoma in Japan

Growing evidence suggests that the polymorphism of DNA base excision repair gene XRCC1 Arg399Gln is associated with altered DNA repair proficiency and subsequent cancer susceptibility; however, no evidence is available for malignant lymphoma. We therefore conducted a case-control study (372 cases, 500 controls) to evaluate links with malignant lymphoma risk in Japan. The risk was evaluated in terms of odds ratio (OR) and 95% confidence interval (CI) adjusted for age and sex in an unconditional logistic regression model. There was no statistical risk change with the Arg/Gln (adjusted OR 0.89; 0.65-1.23, P = 0.492) or the Gln/Gln (0.57; 0.27-1.17, P = 0.127) compared with the Arg/Arg of the XRCC1 Arg399Gln polymorphism. The results were unchanged in analyses according to histological subtype (diffuse large lymphoma, follicular lymphoma, low-grade lymphoma of mucosa-associated lymphoid tissue, and others). These data suggest that XRCC1 Gln399Arg polymorphism plays a limited role in lymphomagenesis. Further study on the interaction between the polymorphism and environmental exposure is required.     

The roles of soluble osteopontin using osteopontin-transgenic mice in vivo: proliferation of CD4+ T lymphocytes and the enhancement of cell-mediated immune responses.

We generated transgenic mice expressing osteopontin (OPN) under the control of the alpha(1)-antitrypsin promoter. These mice (OPN-T mice) expressed OPN mRNA in liver and kidney, and released a large amount of plasma OPN, which increased after stimulation with turpentine oil. Before sensitization, the number of CD4+ T cells in lymph nodes was significantly higher in OPN-T than nontransgenic mice, and that in spleen was slightly higher, whereas that of CD8+ T cells was no different between OPN-T and nontransgenic mice. After sensitization, the CD4+ T cell numbers in spleen increased significantly, while there were almost no changes in the CD8+ T cells in lymph nodes and spleen. The intensity of contact hypersensitivity responses to 2,4-dinitrofluorobenzene (DNFB) was obviously enhanced in OPN-T mice. In the delayed-type hypersensitivity (DTH) model elicited by DNFB, the number of CD8+ T cells among DNFB-2,4,6-trinitrobenzenesulfonic acid (TNBS)-peritoneal exudate cells was significantly higher in OPN-T than nontransgenic mice, while there was almost no difference in that of CD4+ T cells. Adoptive transfer experiments revealed that the enhanced reactivity is carried by CD4+ and CD8+ T cells, respectively, although the ability of transferring DTH was significantly lower in CD8+ than in CD4+ T cells. The enhancement of CD8+ T cell migration was observed in OPN-T mice. These results suggest that OPN induces a proliferation of effector CD4+ and CD8+ cells in cell-mediated reactions and plays a role in the migration of CD8+ T cells.     

Raman spectroscopic study of hydrogen bonding of poly(N-vinyl-2-pyrrolidone) in heavy water and dimethyl sulfoxide

The Raman spectra of solutions of poly(N-vinyl-2-pyrrolidone) (PVP; M?_w = 1 000, 10 000, 40 000 and 360 000) in D₂O and dimethyl sulfoxide (DMSO) were measured at various concentrations. PVP is hydrated by D₂O in a manner different from N-ethyl-2-pyrrolidone (NEP) and N-methyl-2-pyrrolidone (NMP), monomer analogues of PVP. The self-association of DMSO molecules in the solution of PVP was found to be different from that in the solution of NMP by using difference spectroscopy. These phenomena were attributed to a net-like structure of concentrated solutions of PVP.     

Terminal rearrangements in the genome of adenovirus type 12 mutants adapted to growth in two human tumor cell lines

After serial passage of adenovirus type 12 in cells of the human melanoma line Nki4 virus mutants with enhanced growth potential have been isolated which carry additional sequences of regularly increasing size at the right end of the genome. DNA sequence analysis was performed'to characterize these genomic alterations as well as those of the previously described Ad12 $\text{C}\text{4}\text{1}$ mutants adapted to growth in the human carcinoma cell line $\text{C}\text{4}\text{1}$ (I. Kruczek, E. Schwarz, and H. zur Hausen (1981)Int. J. Cancer27, 139–143). Duplication of the inverted terminal repetition (ITR) emerged as the common feature of the right terminal alterations of all the mutant genomes analyzed. The sequences present between the ITR repeats were of either right-end or left-end origin, the latter suggesting that left-end sequences comprising the ITR and parts of the adjacent unique sequences have been transferred to the right end of the genome. The different sizes of the additional sequences in Ad12 Nki-4 DNA could be explained by varying degrees of amplification of a basic additional sequence of 342 base pairs.     

Alteration of cell cycle regulators correlates with survival in epithelial ovarian cancer patients

The p16-cyclinD1/CDK4-pRb pathway (RB pathway) and p14ARF-MDM2-p53 pathway (p53 pathway) work at the G1-S checkpoint, and the ATM-chk2-CDC25-cyclinB1/cdk1 pathway works at the G2-M checkpoint. The disruption of these pathways is thought to be related to the prognosis of human cancer. In this study, we analyzed the status of these pathways in 107 epithelial ovarian cancer (EOC) patients by immunohistochemistry and evaluated the relationship of these results with chemotherapy response and the prognosis. Altered RB, p53, and G2 pathways were detected in 50.5% (54/107), 51.4% (55/107), and 33.6% (36/107) of cases, respectively. The overall survival (OS) of 77.3% for patients with a normal RB pathway was significantly higher than the OS of 50.0% for patients with an altered RB pathway (by Kaplan-Meier analysis, P = 0.0021). The OS of 66.2% for patients with a normal G2 pathway was significantly higher than the OS of 58.3% for patients with an altered G2 pathway (P = 0.0416). However, the status of the p53 pathway was not related to OS. By univariate and multivariate analyses, advanced stage, high histological grade, altered RB pathway, and altered G2 pathway were significant predictors of poor OS. However, there was no significant relationship between pathway status and chemotherapy response. The status of the RB pathway and of the G2 pathway were independent prognostic factors of EOC.     

Comparison of Single and Dual Monitoring during Carotid Endarterectomy

We compared the rate of selective shunt and pattern of monitoring change between single and dual monitoring in patients undergoing carotid endarterectomy (CEA). A total of 121 patients underwent 128 consecutive CEA procedures. Excluding five procedures using internal shunts in a premeditated manner, we classified patients according to the monitoring: Group A (n = 72), patients with single somatosensory evoked potential (SSEP) monitoring; and Group B (n = 51), patients with dual SSEP and motor evoked potential (MEP). Among the 123 CEAs, an internal shunt was inserted in 12 procedures (9.8%) due to significant changes in monitoring (Group A 5.6%, Group B 15.7%, p = 0.07). The rate of shunt use was significantly higher in patients with the absence of contralateral proximal anterior cerebral artery (A1) on magnetic resonance angiography (MRA) than in patients with other types of MRA (p <0.001). Significant monitor changes were seen in 16 (12.5%) in both groups. In four of nine patients in Group B, SSEP and MEP changes were synchronized, and in the remaining five patients, a time lag was evident between SSEP and MEP changes. In conclusion, the rate of internal shunt use tended to be more frequent in patients with dual monitoring than in patients with single SSEP monitoring, but the difference was not significant. Contralateral A1 absence may predict the need for a shunt and care should be taken to monitor changes throughout the entire CEA procedure. Use of dual monitoring can capture ischemic changes due to the complementary relationship, and may reduce the rate of false-negative monitor changes during CEA.     

Bullous pemphigoid in patients receiving peritoneal dialysis: a case series and a literature survey

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. Although several cases of BP in end-stage renal disease patients receiving peritoneal dialysis (PD) or hemodialysis have been reported, the incidence of BP in these patients remains unknown. We recently experienced three PD patients diagnosed with BP. The skin injury was likely to be a trigger of BP in all the three PD patients. Nifedipine and icodextrin exposures were possible factors directly or indirectly affecting the onset of BP, because they were common in the three cases. We also report that the incidence of BP in PD patients was 3/478.3 person-years in a single-center 10-year study. This case series with a literature survey describes that the skin and tissue injuries are potential triggers responsible for the onset of BP in dialysis patients and that the incidence of BP in these patients seems to be much higher than that in the general population.