Different expression of T-cell receptor beta-chain variable region genes in lymph nodes of lpr mice with different alleles of the major histocompatibility complex.

In order to search for a possible role of abnormally proliferating T cells in developing autoimmune disease in lpr mice, and to define the difference of the T cells among various lpr-congeneic mice with different clinicopathological findings, the T-cell receptor (TcR) V beta gene expression in the enlarged lymph nodes (LN) of C3H/HeJ-lpr/lpr (C3H-lpr), C57BL/6-lpr/lpr (B6-lpr) and MRL/Mp-lpr/lpr (MRL-lpr) mice was analysed. A RNA blot analysis using several V beta-specific probes showed that the V beta 3 gene, whose products are important for recognizing Mlsb/a, was used in B6-lpr and MRL-lpr with the Mlsb/b but not in C3H-lpr with the Mlsb/a. The V beta 5 gene, which is selectively related to I-E molecules, was predominantly used in B6-lpr(I-E-) but not in C3H-lpr(I-E+) nor MRL-lpr(I-E+). Similarly, the V12 gene was also expressed in B6-lpr but not in C3H-lpr. To compare in detail in V beta repertoire among lpr mice with different major histocompatibility complex (MHC) backgrounds, the V beta gene sequences in the cDNA libraries from LN cells of C3H-lpr were analysed, following the recent investigation of B6-lpr mice (Ohga et al., 1989). Eleven beta-chain cDNA out of 32 beta cDNA in B6-lpr and 24 beta-chain cDNA out of 55 beta cDNA in C3H-lpr were found to contain sequences with open reading frames that potentially encode functional TcR beta-chain. The frequencies of the messages in the cDNA libraries from these mice were consistent with the RNA blot analysis using V beta 3- and V beta 5-specific probes. It was notable that 36% of the functional beta-chain mRNA in B6-lpr and 50% of the beta mRNA in C3H-lpr expressed the V beta 8 gene family. When the TcR V beta gene expression was compared between the LN cells in C3H-lpr, B6-lpr and MRL-lpr, as reported by Singer et al. (1986), the usage of V beta genes other than the V beta 8 gene family in B6-lpr (H-2b) LN cells differed significantly from those in C3H-lpr (H-2k) and MRL-lpr (H-2k). The results presented here indicate that the usage of V beta genes is heavily influenced by the genetic background of lpr mice, similar to normal mice, but with preferential usage of the V beta 8 gene family as a common structural feature in lpr gene-induced cell populations.     

Roles of CD4+ and CD8+ T cells in discordant skin xenograft rejection

An essential role of murine CD4+ T cells in immune reactivity and skin graft rejection in discordant xenogeneic combinations have been reported. Our study was conducted to further clarify the roles of CD4+ and CD8+ T cells in discordant skin xenograft rejection, by using CD4 and CD8 knockout [C57BL/6 Cr Slc (B6; H-2b) background] mice. When human skins were grafted on CD8 knockout mice or B6 mice, both hosts rejected human skin grafts within 12 days after grafting. By contrast, survival of human skin grafts was significantly prolonged in CD4 knockout mice (mean survival times=19.3+/-(SD) 1.6 days; median 19 days). Fully allogeneic C3H/He Slc (H-2k) skin grafts were rejected within 14 days in CD4 knockout mice, suggesting that non-CD4+ T cells in CD4 knockout mice were immunocompetent for allograft rejection. In spleens of these recipient mice, CD8+ T cells seemed to be activated 10 days after human skin grafting. Immunohistological analysis revealed the infiltration of CD8+ T cells at the site of transplanted human skin on CD4 knockout mice. To further examine the role of CD8+ T cells in CD4 knockout mice, human skin grafting was performed on day 0 followed by administration of anti-CD8 monoclonal antibody on days 0, 5, and 14. The administration of anti-CD8 monoclonal antibodies caused the significant prolongation of human skin graft survival. These results indicate the following two conclusions: (1) CD4+ T cells have an essential role in rejecting discordant human skin xenografts rapidly and (2) however, CD8+ T cells also are capable of rejecting discordant human skin xenografts.     

IL-1β and TNF-α produced by peripheral blood mononuclear cells before and during interferon therapy in patients with chronic hepatitis C

We investigated the spontaneous and phytohemagglutinin-stimulated production of interleukin-1 (IL-1) and tumor necrosis factor- (TNF-) by peripheral blood mononuclear cells in patients with chronic hepatitis C during treatment with interferon- (IFN-). Spontaneous productions of these were significantly higher in patients with chronic hepatitis C than in healthy subjects. For patients prescribed interferon, stimulated production of TNF- was significantly higher in complete responders than in partial responders, but the differences were small between the other cytokine levels and outcome of IFN treatment. Spontaneous production of these cytokines was higher in patients with genotype III with complete response than in genotype III patients with a partial response, but this was not the case in patients with genotype II. There was a negative correlation between these cytokines and histological activity index. Spontaneous production of cytokines was decreased only in complete responders after the administration of interferon. These data suggest that the elevated production of cytokines in patients with chronic hepatitis C may be due to host response to the virus, and monitoring cytokines along with alanine aminotransferase and hepatitis C virus RNA during treatment may provide more precise information of the effectiveness of therapy.     

LAPAROSCOPIC CHOLECYSTECTOMY WITH AND WITHOUT ABDOMINAL PROPHYLACTIC DRAINAGE

Aim: As techniques in laparoscopic cholecystectomy (LC) have improved, the role of routine prophylactic abdominal drainage may be limited. A retrospective review was carried out of patients undergoing elective LC to evaluate the benefit of routine drainage in simple uncomplicated procedures. Methods: This study of 295 patients with cholecystolithiasis or gallbladder polyp included 145 patients who underwent LC with drainage and 150 patients who underwent LC without drainage between 2003 and 2007. Allocation to drain or not to drain was non‐randomized and based on surgeon preference according to intraoperative findings. Patient characteristics, operative results, and postoperative outcomes were compared between the two groups with univariate analysis. Results: Time to first flatus and length of postoperative hospital stay in the LC without drainage group were shorter than in the LC with drainage group. There was no significant difference between the two groups with respect to postoperative complication rate. No complications were noted due to the lack of drain placement. Conclusion: The use of drain after simple elective uncomplicated LC could safely be limited to appropriate patients as judged by the operating surgeon.     

RE‐EPITHELIALIZATION OF SQUAMOUS EPITHELIUM FOR A RADIATION‐INDUCED RECTAL ULCER WHILE GIVING AN ECABET SODIUM ENEMA

The present patient developed a severe rectal ulcer more than 1 month after having received external beam radiation therapy for prostate cancer. Surveillance endoscopy every 3 months demonstrated healing of this rectal ulcer using a novel therapy. He was given enemas with ecabet sodium, which provides physical protection and promotes healing by increasing prostaglandin E₂, and this process induced squamous metaplasia that halted the progression of the ulcer of radiation proctitis as a late‐phase reaction. Intrapapillary capillary loops were visualized with magnified narrow band imaging at the healing ulcer site as seen via the esophagus and, moreover, demonstrated histologically.     

Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK alpha-dependent noncanonical NF-kappaB activation

Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1)-induced NF-kappaB activation is important for infected cell survival. LMP1 activates NF-kappaB, in part, by engaging tumor necrosis factor (TNF) receptor-associated factors (TRAFs), which also mediate NF-kappaB activation from LTbetaR and CD40. LTbetaR and CD40 activation of p100/NF-kappaB2 is now known to be NIK/IKKalpha-dependent and IKKbeta/IKKgamma independent. In the experiments described here, we found that EBV LMP1 induced p100/NF-kappaB2 processing in human lymphoblasts and HEK293 cells. LMP1-induced p100 processing was NIK/IKKalpha dependent and IKKbeta/IKKgamma independent. Furthermore, the LMP1 TRAF-binding site was required for p100 processing and p52 nuclear localization, whereas the LMP1 death domain-binding site was not. Moreover, the LMP1 TRAF-binding site preferentially caused RelB nuclear accumulation. In murine embryo fibroblasts (MEFs), IKKbeta was essential for LMP1 up-regulation of macrophage inflammatory protein (MIP)-2, TNFalpha, I-TAC, ELC, MIG, and CXCR4 RNAs. Interestingly, in IKKalpha knockout MEFs, LMP1 hyperinduced MIP-2, TNFalpha, and I-TAC expression, consistent with a role for IKKalpha in down-modulating canonical IKKbeta activation or its effects. In contrast, LMP1 failed to up-regulate CXCR4 and MIG RNA in IKKalpha knockout MEFs, indicating a dependence on noncanonical IKKalpha activation. Furthermore, LMP1 up-regulation of MIP-2 RNA in MEFs was both IKKbeta- and IKKgamma-dependent, whereas LMP1 upregulation of MIG and I-TAC RNA was fully IKKgamma independent. Thus, LMP1 induces typical canonical IKKbeta/IKKgamma-dependent, atypical canonical IKKbeta-dependent/IKKgamma-independent, and noncanonical NIK/IKKalpha-dependent NF-kappaB activations; NIK/IKKalpha-dependent NF-kappaB activation is principally mediated by the LMP1 TRAF-binding site.     

Myocardial perfusion imaging using adenosine triphosphate stress multi-slice spiral computed tomography: alternative to stress myocardial perfusion scintigraphy.

BACKGROUND: The present study was designed to: (i) detect myocardial ischemia in contrast enhanced multi-slice spiral computed tomography (CE-MSCT) using adenosine triphosphate (ATP) pharmacological stress test; and (ii) evaluate the potential of ATP stress CE-MSCT in a clinical setting. METHODS AND RESULTS: Twelve patients underwent ATP stress CE-MSCT and stress thallium-201 myocardial perfusion scintigraphy (MPS) and 9 of the patients received conventional coronary angiography (CAG). Dual CE-MSCT scans were performed for stress and rest images, with and without intravenous infusion of ATP (0.16 mg.kg-1.min-1) at intervals of 20 min. Myocardial perfusion and coronary artery were visually evaluated using MSCT and compared the results obtained from MPS and CAG. Of 36 territories, stress images of CE-MSCT described 26 hypo-perfusion areas and MPS described 22 redistributions. The agreement between MSCT and MPS was 83% (30/36, p<0.05). In 141 coronary artery segments of 9 patients undergoing CAG, rest images of CE-MSCT, which had significantly higher assessability than stress images (89% vs 48%, p<0.05), described 76% (13/17) of culprit coronary stenoses. CONCLUSIONS: Although CT-angiography should be currently assessed using rest images, ATP stress CE-MSCT can describe both ATP-induced myocardial ischemia and coronary artery stenoses in patients with coronary artery disease.     

Disease-specific screening for deep venous thrombosis and pulmonary thromboembolism using plasma <Emphasis Type="SmallCaps">d</Emphasis>-dimer values after total knee arthroplasty

We prospectively evaluated the disease-specific features of the early postoperative plasma D: -dimer value and the relationship with deep venous thrombosis and/or pulmonary thromboembolism (DVT/PE) in 95 patients following total knee arthroplasty. Patients in whom DVT/PE was highly suspected were diagnosed by high-resolution multi-detector row computed tomography scanning (MDCT). Forty-nine knees in 46 patients with rheumatoid arthritis (RA, 24 knees) or osteoarthritis (OA, 25 knees) were finally recruited. DVT/PE was detected in 28 (57.1%) of the 49 cases examined by diagnostic MDCT: 12 (50.0%) of the 24 cases of RA, and 16 (64.0%) of the 25 cases of OA. Of these, PE was found in 11 cases (39.2%), but none of them showed clinical symptomatic signs of dyspnea or chest pain. In both RA and OA cases, there were statistically significant differences in the D: -dimer value on postoperative day 3 (P = 0.027) and after day 28 (P = 0.037) between the groups with and without DVT/PE. In OA cases, there were significant differences between the two groups on postoperative days 1 (P = 0.034), 3 (P = 0.020), 5 (P = 0.005), and 7 (P = 0.045), respectively. At the baseline, perioperative D: -dimer levels in the RA group without DVT/PE were higher than in the OA group. However, multivariate logistic regression analysis showed that RA was not a significant risk factor of DVT/PE in comparison with OA. In conclusion, individual evaluation of the D: -dimer level between RA and OA should provide a more precise predictive indicator of early postoperative DVT/PE.