Cooperation between IL-7 and the pre-B cell receptor: a key to B cell selection

Hematopoiesis is regulated by a variety of signals that either originate within a developing cell or are supplied by the surrounding environment in secreted- or contact-dependent forms. This review discusses the effects of one secreted factor, interleukin-7, on the development of B lymphocytes. We describe a molecular mechanism for a crucial checkpoint during B lineage maturation, based on the integration of signals mediated by the pre-B cell receptor, the interleukin-7 receptor, and the environment in which these signals are received.     

A 23-pS Ca2+-activated K+ channel in MCF-7 human breast carcinoma cells: an apparent correlation of channel incidence with the rate of cell proliferation

In studies on the apical membranes of cultured MCF-7 human breast carcinoma cells, we found two conspicuous K⁺ channel types with conductances of 23 and 70 pS, respectively. Of these, the 23-pS K⁺ channel was most conspicuous. In cell-attached patches with KCl in the pipette, it had a linear current/voltage (I/V) relation and was activated by depolarisation and in excised insideout patches it was highly selective for K⁺ over Na⁺ (permeability ratio of Na⁺ to K⁺, P _Na/P _K=0.02). Rubidium (Rb⁺) had a similar permeability to K⁺, although it was only conducted at 20% of the rate of K⁺, and cesium (Cs⁺) had a permeability less than 30% that of K⁺ and was not conducted at all. Both Cs⁺ and Rb⁺ acted as partial blockers when applied internally but the channel was not blocked by external tetraethylammonium (TEA, 10 mmol/l), quinidine (200 mol/l) or apamin (50 nmol/l). It was activated by Ca^{2 +} in the range 10^–7–10^–6 mol/l. In cell-attached patches at a pipette potential of 0 mV, the open-time histogram was described by a single exponential (time constant 1.6 ms) and the closed-time histogram by two exponentials (time constants 0.5 and 1.5 ms). The incidence of the 23-pS but not the 70-pS channel depended on the rate of cell proliferation. Thus, in studies on cell-attached patches from cells in the exponential growth phase, the 23-pS channel was observed in 78% of patches. However, when the proliferation rate was decreased, whether as a result of allowing the monolayer to reach confluence, or of cell treatment with an anti-oestrogen (tamoxifen, 10 mol/l), or a phorbol ester [phorbol 12-myristate 13-acetate (TPA), 2.6 nmol/l], the channel incidence was reduced to 42%, 60% and 42%, respectively. The activity of the 23-pS channel is not obligatory for cell division, however, since the rate of cell proliferation remained the same in MCF-7 cultures in which the channel was not expressed.     

医疗数据交换规格MML(Medical Markup Language)3.0汉化版的制作

MML(Medical Markup Language)是一套不同医疗设施间的数据交换规格。于1995年在日本被开发。MML从版本2.21开始使用XML(eXtensible Markup Language)作为标记语言。而最新版本3.0又遵循HL7Clincal Document Architecture(CDA),包含14模块和36个数据定义表格。目前在中国,还没有一个使用XML来结构整个病历内容的规格。鉴于MML的柔韧性,我们制作了一个基于3.0版本的汉化版。日本与中国虽然诊疗流程、病历记录的内容等都很相似,但是也有一些,比如民族的表现、中医诊断分类,医师资格分类等都是日本不存在的或者分类不同的信息。另外,因为国情不同,医疗保险制度也完全不同。为了使MML能在中国的医院适用,我们追加和更改了12个数据定义表格,并重新制作了医疗保险信息模块。MML汉化版不止是一个对原规格的翻译和说明,它还考虑了本地的需要。因此,使用MML汉化版在中国的医疗设施间进行医疗数据交换已经成为可能。     

Ex vivo stimulation of cord blood mononuclear cells by dexamethasone and interleukin-7 results in the maturation of interferon-gamma-secreting effector memory T cells

The effects of dexamethasone phosphate and interleukin‐7 upon the proliferation of T‐cells and the production of interferon‐γ in the newborn's cord blood mononuclear cell cultures were studied. The capability of dexamethasone to enhance T‐cell proliferation induced by anti‐CD3 with interleukin‐7 in some newborn cord blood mononuclear cell cultures was identified. Dexamethasone suppressed production of interferon‐γ in 68‐h cell cultures stimulated with anti‐CD3 both in the presence of interleukin‐7 and without it. However, a 68‐h cultivation of newborn blood cells with dexamethasone, anti‐CD3 and interleukin‐7 resulted in the accumulation of T‐lymphocytes capable of producing interferon‐γ after restimulation. As a result of it the amount of interferon‐γ producing CD7⁺ T‐cells and the concentration of interferon‐γ in cultural supernatants were maximal in the cell cultures incubated with anti‐CD3, interleukin‐7 and dexamethasone during the first 68 h and subsequently restimulated with phorbol 12‐myristate 13‐acetate and ionomycin. The stimulation of neonatal or adult blood cells by dexamethasone, anti‐CD3 and interleukine‐7 also causes a decrease in the number of naïve T‐cells and central memory cells and an increase in the number of effector memory CD7⁺CD45RA⁺CD62L^– cells in cultures. It is possible that these effects are caused by the influence of dexamethasone on IL‐7 receptor expression: it is known that IL‐7 receptor alpha‐chain gene is a glucocorticoid‐inducible gene.     

Effect of injury to the zone of the medial forebrain bundle and preoptic region on activity of an epileptiform focus induced by penicillin (on the phenomenon of the hyperactive determinant dispatch station)

Experiments on cats showed that injury to the medial forebrain bundle (MFB) and also partly to the preoptic region on the side of application of penicillin to the cerebral cortex (middle suprasylvian gyrus) causes depression of paroxysmal activity (spike potentials) in the penicillin focus, and also in a secondary mirror focus arising in the symmetrical zone of the opposite cortex. Injury to MFB on the side of the mirror focus causes depression of paroxysmal spike potentials only in that focus and does not affect activity in the primary epileptiform focus. The effects described are examined from the standpoint of views regarding the role of the determinant dispatch station (DDS) in the activity of the CNS: A primary epileptiform focus is a hyperactive DDS which induces the appearance of secondary foci, supports them, and determines the character of their activity. The results of the investigation suggests a role for MFB in the modulation of cortical epileptiform activity.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathophysiology, Academy of Medical Sciences of the USSR, Moscow. Laboratory of Electrophysiology, V. F. Filatov Odessa Research Institute for Eye Diseases and Tissue Therapy, Ministry of Health of the Ukrainian SSR. Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 82, No. 12, pp. 1413–1416, December, 1976.     

Subtyping of MRSA isolates belonging to a widely disseminated clonal group by polymorphism of the dru sequences in mec-associated DNA

During the past 7 years the "Berlin epidemic MRSA" has spread throughout whole Germany. SmaI macrorestriction patterns of this clonal group are rather stable as are the length polymorphisms at the 3' end of the coagulase gene and the x-region of spa. However, the dru region (direct repeat units) of mec-associated DNA exhibits a length polymorphism due to deletion of one or more direct repeat units. Five different subclones could be discriminated by dru region length polymorphism. Location of deletions and of a few point mutations allow a delineation of these subclones.     

Interaction of B7RP-1 with ICOS Negatively Regulates Antigen Presentation by B Cells

Stimulation of T cells through the T cell receptor is insufficient for optimal T cell activation. A second activation signal is necessary, being usually provided by the costimulatory molecule CD28. Recently, additional costimulatory pathways have been identified, including inducible costimulator (ICOS) and its ligand B7RP-1. We have examined the role of the B7RP-1/ICOS costimulatory pathway on antigen presentation by B cells, using the I-A^k and I-E^k-positive CH27 B cell line and several different T cell lines. We found that CH27 expressed B7RP-1 and PD-L1 whereas the T cell lines expressed ICOS and PD-1. In the presence of HEL, the T cell hybridomas C10 and 3A9 released IL-2, which is indicative of antigen-specific T cell activation by the CH27 cells. Unexpectedly, blocking antibodies for B7RP-1 and ICOS enhanced the IL-2 response in both T cells. As expected, an increase in the production of IL-2 was seen when blocking antibodies for PD-1 were used. Blocking with antibodies for I-A^k, CD28, B7.1, and B7.2 lead to a decrease in IL-2 production. Additionally we tested a Th1 and a Th2 T cell clone. Blockade of B7RP-1/ICOS lead to an increased IFN- response in Th1 cells (A.E7) and an increased IL-4 response in Th2 cells (D10.G4.1). Intracellular staining also showed an increase in cytokine production when the B7RP-1/ICOS pathway was blocked. In conclusion, the B7RP-1/ICOS pathway is negatively regulating T cell activation by B cells and may play a role similar to that of the PD-L1/PD-1 pathway.     

PLPP2: Potential therapeutic target of breast cancer in PLPP family

PLPPs (Phospholipid phosphatases) are widely expressed in different human tissues, regulate cell signal transduction, and are overexpressed in cancers such as gliomas, pancreatic adenocarcinoma, lung adenocarcinoma, and so on. As a member of the PLPP family, PLPP2 (phospholipid phosphatase 2) plays a vital role in the occurrence and development of breast cancer, but its mechanism is still unclear. Our research found that PLPP2 was overexpressed in breast cancer, and the higher expression level of PLPP2 showed a worse prognosis for breast cancer patients. Further analysis showed that overexpression of PLPP2 affected the expression of CDC34 (cell-division cycle 34), LSM7 (Like-Smith 7), and SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) through EMT (epigenetic-mesenchymal transition) related pathways to promote the occurrence and development of breast cancer. In vitro, silencing PLPP2 significantly reduced the proliferation, invasion, and migration abilities of human breast cancer cells MDA-MB-231. ER+ is a common subtype of breast cancer. Furthermore, we found that the overexpression of PLPP2 was significantly related to the poor prognosis of ER+ breast cancer. These results indicate that PLPP2 has value as a potential therapeutic target for breast cancer, especially for ER+ breast cancer.     

构建7q32区域鼻咽癌和正常鼻咽上皮细胞部分基因的表达图谱

目的构建７ｑ３２区域鼻咽癌细胞和组织及原代培养人正常鼻咽上皮细胞的部分基因表达图谱。方法通过差异ＲＴ－ＰＣＲ和Ｎｏｒｔｈｅｒｎ杂交的方法检测定位于７ｑ３２区域的２０个ＥＳＴ在鼻咽癌细胞和鼻咽癌组织及原代培养人正常鼻咽上皮细胞ｍＲＮＡ的表达水平。结果８个ＥＳＴ在鼻咽癌细胞ＨＮＥ１和原代培养人正常鼻咽上皮细胞中表达量较一致，７个ＥＳＴ在两种细胞中均无表达，３个ＥＳＴ（Ｗ７２６８８、Ｈ１９８３０、ＡＡ１３０６３０）在鼻咽癌细胞株中表达上调，而２个ＥＳＴ（ＡＡ０７０４３７、Ｈ９０８８２）在原代培养人鼻咽上皮细胞中表达上调。在１３例鼻咽癌活检组织中３０．７％（４／１３）的ＡＡ０７０４３７表达下调，７７％（１０／１３）的Ｗ７２６８８和７７％（１０／１３）的Ｈ１９８３０表达上升。结论构建了７ｑ３２区域鼻咽癌细胞和组织及原代培养人正常鼻咽上皮细胞部分基因表达图谱，并初步认为Ａ０７０４３７的表达下调和Ｗ７２６８８、Ｈ１９８３０的过表达与鼻咽癌的发生有关。