ANALYSIS OF INTESTINAL CELL PROLIFERATION AFTER GUANETHIDINE-INDUCED SYMPATHECTOMY

Neonatal administration of guanethidine-sulfate results in an alteration of the cell proliferative pattern of the small intestinal epithelium of the young adult rat. Sympathectomy with guanethidine has previously been shown to depress mitotic, labelling, and total cellular migration indices while increasing the generation cycle time (T_C) of small intestinal crypt cells as measured by a stathmokinetic method. The present study showed that the G₁, S and G₂ phases of the crypt cell cycle are altered by sympathectomy, G₁ accounting for most of the increase in T_C. In addition, the percentage of [³H]-thymidine labelled crypt cells is reduced and the duration of crypt cell transit is lengthened by guanethidine-induced sympathectomy.     

ALTERATION OF NEONATAL RAT PAROTID GLAND ACINAR CELL PROLIFERATION BY GUANETHIDINE-INDUCED SYMPATHECTOMY

Newborn rats were injected with guanethidine-sulfate (20 μg/g body weight) every 48 hr from 12 hr after birth until day 14 (eight injections per animal). The guanethidine treatment resulted in an 86% absolute reduction in cell number in the superior cervical ganglia of 15 day old rats. The cells which remained after guanethidine treatment showed destruction of mitochondria and an extensive decrease in endoplasmic reticulum. Chemical sympathectomy with guanethidine induced a 3.1 hr lengthening of the acinar cell generation cycle time (17.4 hr to 20.5 hr), resulting from a longer G₁ period (6.9 hr in the control group as compared to 10.5 hr in the guanethidine-treated group), as well as a decrease in the mean percentage of [³H]thymidine-labeled acinar cells (22.3 ± 0.5% to 19.3 ± 0.5%) and mean acinar cell mitotic index (2.6 ± 0.2% to 2.1 ± 0.1%). A circadian rhythm was found to exist in parotid gland acinar cell mitotic activity of 15 day old rats and the amplitude of the rhythm was reduced from 26.5% to 14.9% in guanethidine-treated rats. This study indicates that the diminution of sympathetic influence on the developing parotid gland results in a slight, but significant alteration in acinar cell proliferation.     

CONTROL OF EPITHELIAL CELL PROLIFERATION IN THE SMALL INTESTINAL CRYPT

A heat labile factor which has been shown to inhibit proliferative activity in crypt epithelium both in rat jejunum in vivo and in explants of rat jejunum maintained in organ culture has been prepared from the soluble fraction of homogenized epithelial cells isolated from rat small intestinal crypts. The factor appears to have tissue specificity, for it has no influence on epithelial cell proliferation in colonic crypts, oesophagus or skin. Extracts of rat intestinal villous cells prepared using identical techniques were without effect on proliferative activity of small intestinal crypt epithelium.
Isoprenalin, which was also found to suppress cell proliferation, did not potentiate the effect of the factor and its effects were evanescent.     

EFFECT OF VILLUS LENGTH ON CELL PROLIFERATION AND MIGRATION IN SMALL INTESTINAL EPITHELIUM

For the interpretation of data supporting the hypothesis of a feedback regulation of proliferative activity in intestinal crypts by the functional villus cell compartment the life span and migration rate of epithelial cells on villi of experimentally reduced length should be known. Autoradiographic studies and scintillation counting of isolated villi at different time intervals after ³H-thymidine labelling were carried out 36, 48 and 60 hr intervals after X-irradiation. The results showed that the life span of epithelial cells in rat small intestine (36–48 hr) is independent of the villus length. In villi of reduced length the migration rate of the epithelial cells was found to be decreased compared with controls. Changes in the migration rate in turn seem to be dependent on the production of epithelial cells in the crypt. Comparative studies on the recovery of crypt and villus epithelium after various doses (300 and 700 R) of X-radiation support the hypothesis that increased proliferative activity in the crypt cell compartment is related to a reduction of the number of functional villus cells below a critical villus length. The importance of these findings in the interpretation of data on (micro) biochemical analyses of certain cell differentiation characteristics during increased proliferative activity is discussed.     

EXISTENCE OF TWO CHALONE-LIKE SUBSTANCES IN INTESTINAL EXTRACT FROM THE ADULT NEWT, INHIBITING EMBRYONIC INTESTINAL CELL PROLIFERATION

The inhibiting effect of tissue extract from fully differentiated intestinal mucosa of adult animals on proliferation kinetics of exponentially growing embryonic epithelial gut cell populations was studied in the newt Pleurodeles waltlii. Crude extract was fractionated by G-200 Sephadex chromatography and the effect of fractions on cell proliferation was studied using both mitotic index and ³H-thymidine incorporation methods. The inhibitions we obtained were then displayed by means of cytophotometric study of age distribution of intestinal gut cells around the cell cycle, measuring the Feulgen-DNA content. The results revealed the presence of two chalone-like substances in the intestine of adults. One (factor 1) is characterized by a molecular weight of between 120,000 and 150,000 and inhibits the cell cycle at the end of the G₁ phase, the other (factor 2) is characterized by a molecular weight lower than 2000 and inhibits the cell cycle in the course of the G₂ phase. The cells delayed in the G₂ phase escape from inhibition but the cells delayed in the G₁ phase do not, although availability time of both factor 1 and factor 2 is about 12 hr. It is thus thought that cells prevented from dividing in G₁ phase are indefinitely delayed in this phase and possibly differentiate.     

THE EFFECT OF CONTINUOUS IRRADIATION ON CELL PROLIFERATION AND MATURATION IN SMALL INTESTINAL EPITHELIUM

Autoradiographic studies and scintillation counting of crypt material after pulse labelling with ³H-thymidine showed that during continuous irradiation with 290 rads/day a reduced proliferative activity is present in the crypts of rat small intestine after 1 day of irradiation and of normal activity during the remaining period (5 days) irradiation. After cessation of irradiation an increase in proliferative activity can be observed after 1 day of recovery. From the time (36–48 hr after starting of the irradiation) that the number of villus cells is reduced an expansion of the proliferation zone in the crypt was observed. Both effects last until 1 day of recovery after cessation of irradiation. The process of crypt cell maturation and of villus cell function has also been studied during and after continuous irradiation by micro-chemical enzyme analyses in isolated crypts and villi. It was found that the expansion of the proliferation zone in the crypt is accompanied by a decrease in activity of only those enzymes (i.e. non-specific esterases) which normally become active during crypt cell maturation. The activity of enzymes normally present mainly in the functional villus cells remained relatively unaffected by changes in crypt cell kinetics. A hypothesis of different regulation mechanisms of the proliferative activity in the intestinal crypt and a possible explanation of the different behaviour of various enzyme activities as a result of changes in crypt cell proliferation is discussed.     

RGDS肽对大鼠主动脉球囊内膜剥脱后血管壁增殖的影响

在大鼠主动脉球囊内膜剥脱术后血管壁细胞过度增殖模型上,用合成的血小板膜纤维蛋白原受体（ｇｌｙｃｏｐｒｏｔｅｉｎⅡｂ／Ⅲａｃｏｍｐｌｅｘ,ＧＰⅡｂ／Ⅲａ）拮抗剂ＲＧＤＳ（Ａｒｇ－Ｇｌｙ－Ａｓｐ－Ｓｅｒ,５０μｍｏｌ·ｋｇ－１·ｄ－１）治疗可有效地抑制损伤血管壁的细胞计数增加和内膜增厚以及血管平滑肌细胞增殖,显著降低其血管组织３Ｈ－ＴｄＲ和３Ｈ－Ｌｅｕ的参入增加程度。实验结果提示ＲＧＤＳ肽作为血管成型术的辅佐剂,对于防治血管再狭窄可能具有潜在的临床应用前景。     

KINETIC ANALYSIS OF CELL SIZE AND DNA CONTENT DISTRIBUTIONS DURING TUMOR CELL PROLIFERATION: EHRLICH ASCITES TUMOR STUDY

In order to study the growth dynamics of proliferating and non-proliferating cells utilizing discrete-time state equations, the cell cycle was divided into a finite number of age compartments. In analysing tumor growth, the kinetic parameters associated with a retardation in the growth rate of tumors were characterized by computer simulation in which the simulated results of the growth curve, the growth fraction, and the mean generation time were adjusted to fit the experimental data. The cell age distribution during the period of growth was obtained and by a linear transformation of the state transition matrices, was employed to specify the cell size and DNA content distributions. In an application of the model, the time-course behavior of cell cycle parameters of Ehrlich ascites tumor is illustrated, and the parameters important for the transition of cells in the proliferating compartment to the non-proliferating compartment are discussed, particularly in relation to the G₁-G₀ and G₂-G₀ transitions of non-cycling cells as revealed by the variation of cell size distribution.     

VIP对气道平滑肌增殖的调节作用

为探讨血管活性肠肽（ＶＩＰ）对气道平滑肌增殖的影响及机制,我们以体外培养的犬气管平滑肌细胞为对象,以３Ｈ－ＴｄＲ掺入为指标,探讨了ＶＩＰ的作用,并分析了ＶＩＰ受体拮抗剂［４Ｃｌ－Ｄ－Ｐｈｅ６,Ｌｅｕ１７］ＶＩＰ,腺苷酸环化酶激活剂Ｆｏｒｓｋｏｌｉｎ,百日咳杆菌毒素（ＰＴｘ）和磷酯酶Ｃ抑制剂新霉素等对ＶＩＰ作用的影响。实验发现：ＶＩＰ对犬气道平滑肌细胞体外增殖有显著的抑制作用,且呈剂量依赖性。［４Ｃｌ－Ｄ－Ｐｈｅ６,Ｌｅｕ１７］－ＶＩＰ能完全阻断ＶＩＰ的作用,Ｆｏｒｓｋｏｌｉｎ则呈现出对ＶＩＰ的促进效应,ＰＴｘ和新霉素对ＶＩＰ作用无任何影响。上述结果提示：ＶＩＰ通过特异性受体在ＰＴｘ非敏感型Ｇ－蛋白介导下,激活ＡＣ,使平滑肌细胞内ｃＡＭＰ浓度增加,而发挥平滑肌细胞增生抑制效应     

鲤科（Cyprinidate）鱼肠道菌群分析

对江苏大纵湖区的草鱼、白鲢、团头鲂和鲤鱼等4种鱼肠道菌群中的好氧菌或兼性厌氧菌进行分离鉴定.对每种鱼的肠道中菌群数量和种类组成进行了分析,发现在上述鱼肠道中存在哈夫尼亚菌属、致病杆菌属、气单胞菌属、柠檬酸菌属、假单胞菌属、链球菌属、葡萄球菌属等.     

食管鳞癌Cyclin D1与细胞增殖关系的研究及意义

目的　探讨食管鳞癌细胞中细胞周期素D1(CyclinD1)表达与细胞增殖的关系及意义。方法　应用免疫组织化学和流式细胞术检测 48例食管鳞癌组织中CyclinD1蛋白表达及DNA倍体、S期细胞比值、G2 /M期细胞比值。结果　 48例食管鳞癌中CyclinD1阳性表达率为 45 8%(2 2 / 48) ;DNA异倍体检出率为 5 0 %(2 4/ 48) ,CyclinD1阳性表达的标本中DNA异倍体的检出率为 6 8 2 %(15 / 2 2 ) ,显著高于CyclinD1阴性表达的标本 (33 3%,9/ 2 7,P <0 0 5 )。CyclinD1表达阳性的肿瘤中细胞周期G2 /M期的比值也明显高于CyclinD1表达阴性的肿瘤 (分别为 5 98± 4 87和 4 12± 2 70 ,P<0 0 5 )。结论　从观察结果推测CyclinD1的表达可以加速肿瘤细胞增殖。分析食管鳞癌CyclinD1、DNA倍体及不同时相的细胞增殖有助于帮助分析和判断病人的预后。     

CD23McAb抑制活化B细胞增殖机制的初步探讨

本研究用ＣＤ２３单克隆抗体交联活化的人扁桃体Ｂ细胞,证明ＣＤ２３ＭｃＡｂ对Ｂ细胞呈双向调节效应,即：高浓度区抑制Ｂ细胞增殖,低浓度区促进Ｂ细胞增殖,继而,用对Ｂ细胞有抑制效应浓度的ＣＤ２３ＭｃＡｂ交联Ｂ细胞膜ＣＤ２３分子,通过研究抑制效应恢复条件,探讨了ＣＤ２３ＭｃＡｂ产生抑制效应的作用机制。结果显示：去除ＣＤ２３ＭｃＡｂ后,抑制作用不能恢复,用ＳＡＣ再次活化,使Ｂ细胞恢复增殖状态,用促Ｂ细胞增殖     

KINETICS OF MURINE HAEMOPOIETIC CELL PROLIFERATION IN DIFFUSION CHAMBERS

Murine bone marrow cells were cultured in cell impermeable diffusion chambers in the abdominal cavities of mice. The kinetics of granulocyte and macrophage formation were studied by stathmokinetic and autoradiographic techniques. During the period of most rapid growth of proliferative granulocytes, their generation time and its different phases were: t _c∽ 8 hr, t _G1∽ 1·5 hr, t _s∽ 5·5 hr, t _G2∽ 0·7 hr and t _M∽ 0·25 hr.
The generation time of macrophages and their precursors was approximately 8 hr. Formation of macrophages was significantly reduced when chamber inoculum was increased, as judged by ³H-TdR labelling index.