Proliferation and production of hemopoietic cells in two stages of disease: Preleukemia and overt leukemia

Summary The kinetics of erythropoietic and granulocytopoietic cell proliferation have been investigated in the same patient at two distinct stages: firstly in preleukemia presenting as pancytopenia with ineffective erythropoiesis, and secondly 2 years later in acute myelogenous leukemia. The method of investigation is based on determining the DNA synthesis rate of individual cells by means of quantitative¹⁴C-autoradiography after short-term incubation with¹⁴C-thymidine and fluorodeoxyuridine.Erythropoiesis was equally ineffective in the two stages, the rate of proliferation, however, slowed down towards the leukemic state. The production rate of myeloblasts was markedly reduced in preleukemia accompanied by a very low labelling index. In leukemia on the other hand the production rate was increased to such a degree that the leukemic myeoblast compartment is to be considered as prevailingly self-reproductive. The proliferation rate of myeloblasts was reduced already in preleukemia, and there was a further decrease in leukemia. From the point of view of cell kinetics the manifestation of leukemia in this patient is explained best by a change in the mode of proliferation: the myeloblasts change from steady state growth to behaving like an exponentially expanding population.Study performed under the association contract for hematology between EURATOM and GSF no. 089-72-I-BIAD Supported by the Deutsche Forschungsgemeinschaft: SFB 51/E-3     

Induction of erythroid differentiation in K562 cells and natural killer cell-mediated lysis: distinct effects at the level of recognition and lysis in relation to target cell proliferation

The erythroleukemic K562 cell line was induced to erythroid differentiation by a variety of agents, including hemin, bleomycin, and cytosine arabinoside. The sensitivity of induced cells to binding and lysis by non-sensitized peripheral blood mononuclear cells (MNC) in agarose was studied in relation to the target cell division rate. Differentiated K562 cells formed a lower proportion of conjugates with MNC, when compared with non-induced controls. The reduction correlated significantly with the level of differentiation, irrespective of the inducer and the proliferative status. The differentiation-induced alterations of lysis, however, were strongly influenced by the modification of target cell growth rate which was caused by the differentiating agent. These data suggest that target cell differentiation has distinct effects upon the steps of recognition and lysis by natural killer cells.     

T淋巴细胞自稳增殖对器官移植的影响

T淋巴细胞自稳增殖(HP)是指在没有外源性抗原刺激作用下,T细胞减少症的宿主体内残存的淋巴细胞或输注的淋巴细胞所发生的分裂增殖.其机制尚不完全清楚,但研究表明,T细胞数减少是驱动淋巴细胞HP的前提条件,T细胞HP很大程度上受到与两个配体接触的信号通路(即自身MHC/肽复合物和细胞因子或化学因子)的调控.HP的T细胞具有类记忆细胞的特点,这是对器官移植产生免疫耐受的一种障碍.     

Production of transforming growth factor-beta 1 (TGF-beta1) by blood monocytes from patients with different clinical forms of leprosy

In the present study, the concentration of TGF-beta1 secreted by adherent cells isolated from human peripheral blood mononuclear cells (PBMC) and either stimulated with PGL-1 or lipopolysaccharide (LPS) or left unstimulated was determined by ELISA. The cells were isolated from untreated patients with different clinical forms of leprosy and healthy individuals. The adherent cells exhibited spontaneous release of TGF-beta1 in all clinical forms of leprosy and in healthy individuals; however, lepromatous leprosy/borderline leprosy (LL/BL) patients presenting erythema nodosum leprosum (ENL) displayed significantly higher concentrations of TGF-beta1 than either the other patients studied or the controls. These high TGF-beta1 levels were consistently observed when LL/BL ENL cells were stimulated with phenolic glycolipid (PGL-1) or LPS, and even in the absence of a stimulus (P < 0.01). The most significant differences in TGF-beta1 levels were observed when comparing the results in the presence of PGL-1 from ENL with, in order of significance: tuberculoid leprosy (TT) patients (P < 0.001), LL/BL patients without ENL (P < 0.01), healthy individuals (P < 0.01) and borderline-borderline/borderline-tuberculoid (BB/BT) patients with reversal reaction (RR) (P < 0.01). The BB/BT patients produced equivalent levels of TGF-beta1 compared with LL/BL patients without ENL, for all types of stimuli (P > 0.05). In contrast, TT patients produced the lowest levels of TGF-beta1 among all the subjects studied (both patients and healthy controls), especially following PGL-1 stimulation (P < 0.001, and P < 0.05, respectively). In conjunction with our previous data regarding TGF-beta1 expression in dermal lesions, it appears that TGF-beta1 probably plays different roles in leprosy: (i) to mediate a suppressive action locally, associated with the presence of PGL-1, and (ii) to induce proinflammatory effects when secreted systemically by monocytes, thereby acting as a modulatory cytokine in the acute inflammatory reactions of ENL and associated with the Th2 immune response in multibacillary forms of leprosy.     

大剂量胸腺肽对肿瘤放疗病人T细胞亚群的影响

观察４６例肿瘤病人，分析疗加胸腺和药组和单纯放疗组（对照组）。用药组每日静点胸腺肽１６０ｍｇ，连续１０ｄ后用流式细胞仪检测外周血Ｔ细胞亚群的变化。结果表明，用药组放疗后ＣＤ４／ＣＤ８比值、ＣＤ４、ＣＤ２５（ＩＬ－２Ｒ）和ＣＤ５６（ＮＫ）阳性百分率均明显高于本组放疗前及单纯放疗组放疗后水平。提示，大剂量胸腺肽可在短期内提高肿瘤放疗病人机体的免疫功能。     

钙调素对微管组装的调节作用

利用我们建成的钙调素表达可调细胞模型－ＲＣ３细胞，对ＣａＭ高表达时微管组装行为进行了研究，当用生理剂量的地塞米松处理ＲＣ３细胞，细胞内ＣａＭ水平提高，而管蛋白浓度没有变化，造成钙调素／管蛋白比值上升，ＭＴ解聚，但同时加入ＣａＭ拮抗剂三氟拉嗪处理时，则可抑制ＭＴ的解聚，Ｃ３Ｈ１０Ｔ１／２转化细胞ＣａＭ含量的增加是引起ＭＴ解聚的主要因素，ＴＦＰ处理可恢复ＭＴ组装。ＲＣ３细胞ＣａＭ高表达导致ＭＴ解聚的实     

Interactions between normal and tumoral tissues at the boundary of human anterior pituitary adenomas

We studied the boundary between adenoma and peritumoral anterior pituitary tissues in order to understand their mutual interactions during tumour progression. We selected 18 adenomas of different secretory type, grade and invasiveness in which fragments of peritumoral anterior pituitary were still attached to the adenoma. Immunohistochemistry was performed on serial sections with markers of the basement membranes (type IV collagen), the hormone-producing cells of the normal and neoplastic anterior pituitary, and the folliculo-stellate cells (S-100 protein). In passing from tumour to gland, localized areas of passive compression of the normal gland were seen in only 3 cases. In all the tumours, the boundary consisted partly or solely of a transitional zone characterized by the presence of enlarged cell-cords. Openings in the basement membrane of these enlarged cell-cords were seen in contact with the tumour tissue. Normal and neoplastic cells intermingled in the transitional zone. Normal residual cells could be seen in the central area of the tumour but no adenomatous cells were observed in the gland around the tumour. Folliculo-stellate cells were concentrated in the vicinity of the transition zone. These findings favour the existence of an active process of adenoma expansion within the normal parenchyma, without noticeable infiltration of tumour cells into surrounding gland.     

Involvement of K+ channels in the quercetin-induced inhibition of neuroblastoma cell growth

The effects of the flavonoid quercetin on cell proliferation and voltage-dependent K⁺ current were studied on mouse neuroblastoma×glioma hybrid cells. In the presence of 1 % fetal calf serum, quercetin inhibited both cell proliferation and K⁺ current with effective doses inducing half-maximum effects of 10 M and 70 M respectively. Valinomycin (1 nM) antagonized 80 % of the growth-inhibitory effects of 10 M quercetin. The results suggest that at least a part of the antiproliferative effect of quercetin is mediated by a K⁺ channel blockade. They further confirm a role for K⁺ channels in mitogenesis and cell proliferation.