低通气量呼吸对犬左空心肌收缩性的影响

大量的研究表明,急性呼吸衰竭时多伴有心血管功能的损害,但有关急性呼吸衰竭对于左室心肌收缩性的影响所知甚少。本文对开胸麻醉犬在低通气引起呼吸衰竭时,左室心肌收缩性的变化进行了观测和分析。结果表明,在实验组(n=9)低通气呼吸(通气量小于160ml/min/kg,PaO_2小于60mmHg)时,心率(HR)、主动脉平均压(MOP)、左室收缩峰压(LV-SP)、左室内压最大上升速率(dP/dt_(max))、节段心肌发展张力(DT)及其最大发展速率(dT/dt_(max))均显著降低,心肌开始收缩至dp/dt_(max)的时间(t-dp/dt_(max))和至dT/dt_(max)的时间(t-dT/dt_(max))则显著增加,与低通气呼吸前比较均有统计学差异。而在对照组(n=5)保持正常通气(通气量大于450ml/min/kg,PaO_2大于70mmHg),观察45min,未见上述指标有明显改变。本研究表明,急性呼吸衰竭时左室心肌收缩性严重受损。     

High-dose mode of death in Tribolium

This study reports the first demonstration within a single insect genus (Tribolium) of both the acute, or lethal-midlethal, dose-independent pattern of mortality, and the hyperacute, dose-dependent pattern, after appropriate doses of ionizing radiation. This demonstration provides resolution of apparently contradictory reports of insect responses in terms of doses required to cause lethality and those based on survival time as a function of dose. A dose-dependent mortality pattern was elicited in adult Tribolium receiving high doses, viz., 300 Gy or greater; its time-course was complete in 10 days, before the dose-independent mortality began. Visual observations of heavily-irradiated Tribolium suggested neural and/or neuromuscular damage, as had been previously proposed by others for lethally-irradiated wasps, flies, and mosquitoes. Results of experiments using fractionated high doses supported the suggestion that the hyperacute or high-dose mode of death is the result of damage to nonproliferative tissues. Relative resistance of a strain to the hyperacute or high-dose mode of death is not necessarily correlated with resistance to the midlethal mode, which is believed to be the result of damage to the proliferative cells of the midgut.

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Résumé Les résultats de nombreuses études des réactions des insectes adultes de différents groupes à l'irradiation s'opposent quant à l'importance de la dose provoquant la létalité et quant aux modalités de la mort. Les diptères et les guèpes impliquent des doses très élevées,-des centaines de Gy-, ne présentent aucune période caractérisant la mort par irradiation, et décèdent de plus en plus tôt avec l'augmentation des doses. Beaucoup d'autres insectes succombent à des doses (milétalelétale) beaucoup plus faibles,-de quelques Gy à des dizaines-, et quelle que soit la dose meurent au bout d'un temps voisin.Au cours de cette étude, nous avons pu observer que ces deux types de mortalité peuvent être provoqués chez le même genre d'insecte (Tribolium), avec des doses convenables d'irradiation . Un syndrôme caractéristique a été provoqué avec des doses très élevées, de 300 Gy ou plus,-à ces doses la mort est obtenue en 10 jours après l'irradiation. L'absence de syndrôme caractéristique se produit avec des doses inférieures ou égales à 80 Gy; la mort a lieu alors entre 10 et 16 jours en fonction de la dose.Les différences entre les deux types de décès indiquent deux processus de mort par irradiation. La manifestation d'une désorientation et d'une perte de coordination motrice chez les Tribolium fortement irradiés suggère des altérations neurales et/ou neuromusculaires comme cause/s de ce type de mort provoquée par des doses élevées. L'implication de tissus sans prolifération a été confortée par les résultats d'expériences utilisant de hautes doses fractionnées. Le type de mort milétal est considéré après de nombreuses observations indépendantes, comme le résultat d'atteintes à la prolifération des cellules de l'intestin moyen.Les données contradictoires sur les réactions des insectes aux irradiations proviennent d'abord de l'absence de connaissances sur le lieu des dégâts. Les diptères sont connus maintenant, après différentes études, comme perdant complètement l'aptitude au renouvellement cellulaire, et présentent ainsi un type de mort avec dose élevée. Beaucoup d'autres insectes adultes ont un renouvellement cellulaire de l'intestin moyen limité, et ainsi présentent le type de mort milétal. Le type de mort, dit haute dose, peut être induit dans cette dernière catégorie d'insectes par une irradiation suffisamment forte, et, dans le cas du Tribolium le déroulement de la mort se produit alors de deux façons bien distinctes.

     

Natural killer (NK) activity of cultured S100β-positive T-leukemia cells

In order to clarify the function of human S100β- positive T-cells, S100β-positive T-leukemia cells (S100β TLC) were examined in vitro. S100β TLC were obtained from the peripheral blood of a patient with S100β-positive T-cell leukemia and enriched by an E-rosetting method. Two dimensional flow cytometric analysis indicated that the vast majority of the E-positive fraction were S100β TLC expressing CD3 and CD8 antigens. Although S100β TLC expressed CD3 antigen, they were negative for the α/β and γ/δ T-cell antigen receptor (TCR) defined by monoclonal antibodies (mabs) WT-31 and δ TCS-1, respectively. It was speculated that S100β TLC initially expressed α/β TCR but lost it during malignant transformation. When S100β TLC were cultured for 24 h, they acquired cytotoxic activity towards various NK-sensitive cell lines including K-562, Molt-3 and CEM-CCLF, but did not exhibit lysing activity towards NK-resistant cell lines including Raji, Daudi and MT-1. Despite the NK-activity of cultured S100β TLC, they lacked the morphological features of large granular lymphocytes (LGL). S100β TLC did not exhibit lymphokine-activated killer (LAK) activity. When S100β TLC were cocultivated with NK-sensitive cells or NK-resistant cells, they selectively bound to NK-sensitive cells, indicating that they lysed target cells by cell-to-cell contact. The finding that S100 β TLC lacked TCR molecules and their NK activity was not inhibited by mabs reactive with the CD3-TCR complex indicated that the CD3-TCR complex was not involved in their target recognition. These findings suggest that S100 β-positive T-cells are functionally similar to NK cells. We discuss the roles of S100 β-positive T-cells in the human immune system.     

Establishment of primate lymphoblastic cell lines by coculture with a simian T-cell leukemia virus-1 positive, hypoxanthine-guanine-phosphoribosyltransferase negative Japanese macaque cell line

A cell line (JAMH17+) resistant to 8-azaguanine was established from a human T-cell leukemia virus type 1 related virus (simian T-cell leukemia virus-1) positive Japanese macaque cell line. Lymphoblastic cell lines were established from the peripheral blood mononuclear cells of humans, hominoids, and several species of macaques by coculture with JAMH17+ in hypoxanthine-aminopterin-thymidine medium. HTLV-1 specific antigen was detected in some of the established cell lines. Phenotypic analysis showed that several cell lines of crab-eating macaques expressed Leu11a antigen, which is a marker of human natural killer cells.     

Induction of interdigitating reticulum cell-like differentiation in human monocytic leukemia cells by conditioned medium from IL-2-stimulated helper T-cells

Monocytic leukemia (MoL) cells were obtained from the peripheral blood of a patient in whom the leukemic cells infiltrating various lymphoreticular organs exhibited features intermediate between interdigitating reticulum cells (IDC) and ordinary phagocytic macrophages, whereas the leukemic cells in the peripheral blood were essentially monocytic and lacked such features. Peripheral blood CD4+ T-cells were established as an interleukin-2-dependent T-cell line. When the MoL cells were exposed for a few days to conditioned medium from the T-cell line, they extended several dendritic cytoplasmic projections and became intensely positive for HLA-DR antigen, cytoplasmic S-100β protein, and CD1 antigen. Functionally, the conditioned medium significantly down-regulated Fc-mediated and Fc-independent phagocytic activities, and the levels of lysosomal enzymes such as lysozyme and nonspecific esterase in the MoL cells. Moreover, the conditioned medium significantly up-regulated the accessory cell function of the MoL cells as measured by the primary allogenic mixed leukocyte reaction (MLR). Furthermore, the conditioned medium significantly down-regulated the expression of CD14 antigen. Biochemical analysis indicated that the factor responsible for these changes is a protein which is distinct from known human cytokines and whose molecular weight is approximately 31 kDa. These findings suggest that IDC are closely related the monocytic lineage and that helper T-cells play an important role in constructing the microenvironment of T-lymphoid tissues which is necessary for the differentiation and maturation of IDC.     

Seasonal variations in the responses of glycolytic intermediates of human erythrocytes to acute cold exposure

Seven male students were studied to observe the effects of acute cold exposure (at 10°C for 60 min) on erythrocyte concentrations of glycolytic intermediates in summer and in winter. The subjects shivered slightly but frankly in both experiments. Significant decreases were observed in the concentrations of pyruvate and lactate during body cooling in summer, but not in winter. The lactate concentration remained significantly reduced 15 min after cold exposure. After 60 min of cold exposure in summer, a negative crossover point appeared to exist between phosphoenolpyruvate and pyruvate and erythrocyte pyruvate kinase activity showed a significant decrease. No seasonal difference was observed in the initial control values of the intermediates measured. From these results and the fact that glucose, pyruvate and lactate are evenly distributed between erythrocytes and plasma, it is likely that erythrocytes and skeletal muscles need less fuel substrate, glucose during cold exposure in winter than in summer, suggesting that an increased economy of energy for homeostasis is achieved.     

人体急性缺氧性意识障碍

实验分为低压组(低压舱7,000米)与常压组(吸入7.6％低氧混合气),每组受试者各为12名,有7名参加了两组实验。每组各有4名平均经15分23秒发生了意识模糊或丧失(通称意识障碍)。障碍者的肺泡氧分压为29.9±0.8mmHg。障碍发生前,呈现严重无力,觉醒度降低,反应迟钝,脑波特征是高幅6波(100-300μV)占优势。障碍发生时,高幅δ波丧失节律,幅度衰减,波型不规则,额枕失同步;呼吸循环代偿功能增强程度明显高于障碍前。本工作对于预测和评价人体急性缺氧引起的意识障碍有意义。     

MSI2通过下调circRNA_001214促进急性髓系白血病细胞HL60生长

Musashi-2（MSI2）是一种RNA结合蛋白质,对维持造血干细胞功能具有重要作用。研究表明,MSI2高表达能促进急性髓系白血病（acute myelocytic leukemia, AML）进展,但其作用机制尚不明确。本研究稳定沉默HL60细胞MSI2后,第1、2、3、4 d对照组的相对细胞生长率分别为1.931 ± 0.027、3.070 ± 0.073、4.017 ± 0.092和4.215 ± 0.246;敲减组分别为1.927 ± 0.035、2.564 ± 0.090、2.825 ± 0.097和3.223 ± 0.182,两组相比具有统计学差异,P<0.001;细胞凋亡明显增加(7.967% ± 0.698% vs 3.400% ± 0.322%., P<0.01);G₀/G₁期细胞比例明显增高（67.430% ± 4.390% vs. 50.360% ± 2.160%, P<0.01）;NUMB蛋白明显上调,LEF1明显下降。环状RNA（circular RNA, circRNA）芯片筛选和荧光定量PCR验证显示,MSI2沉默组circRNA_001214表达水平是对照组3.48倍。这一结果也在NALM6细胞得到证实。进一步用生物信息学分析,显示circRNA_001214最可能与miR-1273a、miR-1273e和miR 5095结合,进而影响参与细胞凋亡相关基因（CYCS、AKT1、BAX、TNFRSF10A、TNFRSF10D）、Wnt信号基因（WNT4、WNT2B、WNT7B、 DKK2、SFRP1、CSNKE1和LEF1）以及参与细胞代谢相关基因（RPE, PGAM4, PGAM1, TAT, CBS、RPE、SUCLG2、PGAM4、PGAM1和 IDNK）。总而言之,MSI2可能通过干扰circRNA_001214生成,减少靶miRNA对凋亡、Wnt信号及细胞代谢相关基因表达的影响,促进细胞生长。