Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

关于空腹血糖、空腹胰岛素乘积的倒数在流行病学研究中应用的补充说明

高胰岛素正糖钳夹技术可以测定活体的胰岛素敏感性,但它并不适用于大规模流行病学研究。流行病学研究需要简单的胰岛素抵抗测定法。本文补充报告在空腹血糖(FPG)(75～306mg/dl或4.2～17.1mmol/L)及空腹胰岛素(FIns)(9.7～120mU/L)范围很宽的Pima印第安人群中,正糖钳夹技术测定的胰岛素介导的葡萄糖代谢率(M)与涉及FPG、FIns的多种复合的胰岛素敏感指数的相关性:胰岛素作用指数(IAI)=1/(FPG×FIns)在非糖尿病人群及2型糖尿病人群都与M显著正相关(r>0.7,P=0.0001),而且这两者的相关性强于M与其他指数如FIns或FPG/FIns比值的相关性,也不弱于M与糖负荷后3～5个时间点的血糖、胰岛素曲线下面积乘积的相关性。IAI的五分变量分布情况表明有90.4%的IAI落在所预测的M值五分变量区域或与之相邻的一个五分变量区域之内。1/FPG×FIns虽相对简单但确实与机体的胰岛素敏感性密切相关,它可以做为胰岛素敏感指数在流行病学研究中应用。     

Regulation of stimulated integrin surface expression in human neutrophils by tyrosine phosphorylation

The control of the adhesive properties of human neutrophils is an essential element of their defense function. One level at which this control is exerted involves the upregulation of the surface expression of beta 2-integrins. In this study, we have examined the potential involvement of tyrosine phosphorylation in the latter process. Two inhibitors of tyrosine kinases with differing modes of action, erbstatin and herbimycin A, were found to inhibit the expression of CD11b and CD18 stimulated by chemotactic factors (fMet-Leu-Phe or leukotriene B4) or growth factors (tumor necrosis factor alpha). This inhibition was not shared by an inactive analog of erbstatin or by the protein kinase C inhibitor Ro 31-8330. Erbstatin also inhibited the unveiling of activation-specific neoepitopes detected by antibody CBRM1/5. Pretreatment of neutrophils (but not of endothelial cells) with erbstatin inhibited the stimulation of neutrophils' adherence to endothelial cells induced by fMet-Leu-Phe. Augmentation of tyrosine phosphorylation by inhibiting tyrosine phosphatases using hydroperoxyvanadate led to an increased surface expression of CD11b and CD18 and enhanced the adhesion of neutrophils to endothelial cells. Finally, the leumedin NPC 15669, which had previously been shown to inhibit stimulated CD11b expression and neutrophil adherence to endothelial cells and to exhibit anti-inflammatory properties in various in vivo models of inflammation, inhibited the stimulation of tyrosine, phosphorylation induced by fMet-Leu-Phe. Taken together, these data establish a strong correlation between tyrosine phosphorylation and integrin upregulation in stimulated human neutrophils.     

Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon

Idiotypes are distinct clonal markers for B-cell lymphomas. Previously we reported the use of anti-idiotype antibodies in the therapy of patients with B-cell malignancies. Because synergy was demonstrated with the addition of alpha interferon to anti-idiotype antibodies in a murine lymphoma model, we performed a clinical trial combining these two agents. Here we provide an update of the original trial of anti-idiotype antibodies alone and report the outcome of the new combination trial. In 16 treatment courses of anti-idiotype antibodies alone there were seven partial responses and one complete response. In 12 courses of combination anti-idiotype antibody and alpha interferon there were two complete responses and seven partial responses. Substantial tumor regressions occurred with minimal toxicity in both trials even in patients refractory to conventional chemotherapy. Tumor specimens obtained at the time of disease progression often contained a preponderance of idiotype-negative lymphoma cells, suggesting that anti-idiotype antibody treatment exerted a strong antitumor effect against antigen-positive cells. Anti-idiotype antibodies have reproducible objective antitumor activity in B-cell lymphoma. The addition of alpha interferon may improve the initial rate of response to this treatment. Strategies that deal effectively with idiotype-negative lymphoma cells should improve the extent and duration of these responses.     

Effects of disease-modifying therapy on peripheral leukocytes in patients with multiple sclerosis

Journal of Neurology - Modern disease-modifying therapies (DMTs) in multiple sclerosis (MS) have variable modes of action and selectively suppress or modulate the immune system. In this review, we...