Relationship between urinary excretion of modified nucleosides and rheumatoid arthritis process

The levels of the five methylated nucleosides pseudouridine (psi-Urd), 1-methyladenosine (1-MeAdo), 4 acetylcytidine (4-AcCyd), 1 methylinosine (1-Melno) and 7 methylguanosine (7-MeGuo) resulting from RNA degradation were examined in the urine of rheumatoid arthritis (RA) patients. Of these five, 1-MeAdo and psi-Urd were correlated with the active phase of the disease, while two others (4-AcCyd and 1-Melno), which require further evaluation, appeared to be linked to the prognosis of the disease. As RNA turnover is closely associated with cell proliferation, including that of lymphocytes in RA, there may be a hitherto unsuspected benefit in measuring 1-MeAdo and psi-Urd as biochemical markers of RA disease activity.      

Opposite effects of tumor necrosis factor alpha on the sphingomyelin- ceramide pathway in two myeloid leukemia cell lines: role of transverse sphingomyelin distribution in the plasma membrane

Tumor necrosis factor alpha (TNF alpha) mediates proliferation, functional activation, and apoptotic cell death depending on the target cell type. Although sphingomyelin (SPM) hydrolysis and ceramide generation may function as an important mediator in TNF alpha signaling, the molecular mechanisms of the signaling pathway(s) are still not well understood. The aim of the present study is to compare the effect of TNF alpha on SPM metabolism and cell growth in two myeloid leukemic cell lines (U937 and KG1a) that differ in their sensitivity to TNF alpha. Our results show that TNF alpha induced apoptosis in U937 but not in KG1a cells. TNF alpha triggered in KG1a cells neither SPM hydrolysis nor ceramide generation, but induced SPM synthesis and ceramide breakdown as well as dose-dependent cell proliferation. In contrast, TNF alpha induced in U937 SPM hydrolysis and ceramide generation as well as dose-dependent cell death. Synthetic cell permeant ceramide, as well as natural ceramide, generated by treatment with bacterial sphingomyelinase (SPMase), all induced apoptosis in both U937 and KG1a cells. These findings indicate that the SPM-ceramide pathway is altered in KG1a cells upstream of the ceramide generation. Analysis of the transverse distribution of SPM in the plasma membrane showed that the SPM pool involved in cell signaling (inner leaflet) was markedly reduced in KG1a cells; it is 7-fold lower than that found in the inner leaflet of U937 cells. Therefore, our study strongly suggests that the different responses induced by TNF alpha in myeloid cells are dependent on the SPM plasma membrane transverse asymmetry.     

Cutaneous T-cell infiltrates: analysis of T-cell receptor gamma gene rearrangement by polymerase chain reaction and denaturing gradient gel electrophoresis

In cutaneous T-cell infiltrates, the demonstration of a clonal T-cell receptor (TCR) gene rearrangement has been considered helpful to distinguish Cutaneous T-cell lymphomas from reactive lymphoproliferation. Hence, a polymerase chain reaction (PCR) method using GC-clamp primers and denaturing gradient gel electrophoresis has been developed in our laboratory to analyze the TCR gamma locus configuration. Two hundred eleven cutaneous samples from 155 patients were analyzed. A detectable clonal TCR gamma rearrangement was significantly associated with cutaneous T-cell lymphomas as defined by morphologic and immunologic criteria. A clonal TCR gamma rearrangement was also detected frequently in lymphomatoid papulosis, never in reactive lymphocytic infiltrates and B-cell lymphomas, and rarely in parapsoriasis en plaque and cutaneous lymphoid hyperplasia. Forty five patients had both a cutaneous and a peripheral blood sample. Fifteen had a detectable clonal rearrangement in the two samples and 22 were negative. Six patients had a positive skin sample and a negative blood sample, whereas two patients had a positive blood sample and a negative skin sample. Four lymph node samples were analyzed and the PCR results were the same as in the skin. Finally, 21 patients had sequential samples of recurrent skin lesions. The PCR results were concordant in all and, when detectable, the clonal TCR gamma rearrangement remained unchanged in a given patient. Because of its simplicity and accuracy, the newly designed PCR procedure improves the monitoring of diagnosis, staging, and follow-up in cutaneous T-cell infiltrates.     

Apoptosis induced by polyclonal antilymphocyte globulins in human B- cell lines

Antilymphocyte and antithymocyte globulins (ALG) are currently used as immunosuppressive agents in clinical transplantation and for the treatment of severe aplastic anemia. ALG contain a mixture of antibodies that recognize T- and B-cell-specific antigens but mostly nonlineage-specific molecules. We reported previously that ALG could inhibit the proliferation of activated B cells and B cell lines (Bonnefoy-Berard et al, Blood 79:2164, 1992). We show here that ALG induce apoptosis of several human hematopoietic cell lines, as shown by nuclear condensation and fragmentation in fluorescence and electronic microscopy and by double-strand DNA breaks shown by DNA electrophoresis. Apoptosis was achieved without elevation of intracellular Ca2+ and requirement for mRNA and protein synthesis. Most of the B-cell lines tested (Epstein-Barr virus [EBV]-transformed lymphoblastoid cell lines, EBV-negative and groups I/III EBV-positive Burkitt's lymphoma cell lines, as well as other B-lymphoma cell lines) were susceptible to ALG-induced cytotoxicity. Myelomonocytic and T-cell lines were much less susceptible than B-cell lines. Susceptibility to ALG-induced cytotoxicity was not correlated with intracellular Bcl-2 level. Most cell lines that express high levels of Fas/Apo-1 antigen were susceptible to ALG. However, several lines of evidence support the conclusion that, in addition to Fas/Apo-1, other cell surface molecules can mediate ALG-induced apoptosis. The cytotoxic activity could be fully removed by adsorption on susceptible cell lines but not on a resistant cell line, indicating that it was mediated by antibodies specific for surface antigens expressed only on susceptible cell lines. Apoptosis was triggered by ALG F(ab')2 fragments as well as by intact ALG. This cytotoxic property of ALG may account for their antiproliferative effect and might contribute to some extent to the relatively lower risk of posttransplant lymphoproliferative disorders previously reported in ALG-treated patients.     

共病致大肠癌漏诊情况分析55例

目的:总结共病状态下大肠癌漏诊的具体原因.方法:回顾性分析55例漏诊大肠癌的临床资料,对率的比较采用卡方检验.结果:被漏诊的疾病中,大肠癌合并痔疮18例,合并消化性溃疡10例,合并结直肠息肉7例,合并急性阑尾炎5例,合并缺铁性贫血5例,合并慢性胆囊炎4例,合并溃疡性结肠炎3例,合并慢性盆腔炎2例,合并阑尾周围脓肿1例.结论:不少临床医师拘泥于“一因论”的思维模式而忽视了共病的存在,这是导致共病状态下大肠癌漏诊的主要原因.