COLONY FORMING CELLS IN THE LIVERS OF PRENATAL FLEXED (f/f) ANAEMIC MICE

The colony forming unit (c.f.u.) content of foetal livers of f/f and f /+ genotypes has been investigated. Although proportions of c.f.u. to nucleated liver cells do not vary with genotype, the total number of c.f.u. and erythroid cells per foetus is reduced in f/f embryos from 11 to 16 days of gestation. The differentiative capacity of f/f stem cells, measured by ⁵⁹Fe uptake into blood 7 days after transplantation of cells, was less than that of f /+ stem cells. An initially low growth rate of c.f.u. in early foetal liver and in young spleen colonies can explain several characteristics of flexed erythropoiesis.     

EXPRESSION OF CONGENITAL DEFECTS IN THE HAEMOPOIETIC MICRO-ENVIRONMENT: PRE-NATAL ERYTHROPOIESIS IN ANAEMIC 'STEEL'(SljSlj) MICE

The production of red cells by the livers of congenitally anaemic Sl^jSl^j foetal mice is reduced, so that the red cell concentration reaches only 0.4 × 10⁹/ml, compared to 2.3 × 10⁹/ml in normal littermates. The deficiency in haemoglobin concentration is not so severe (3 g/100 ml compared to 10 g/100 ml), because Sl^jSl^j red cells are macrocytic and normochromic. The number of erythroblasts in the livers of Sl^jSl^j foetuses is considerably less than in normal littermates, but the ratio of early erythroblasts to late erythroblasts is not altered. The cell cycles of Sl^jSl^j and normal early erythroblasts are similar, but the cycle time of Sl^jSl^j late erythroblasts is longer than that of the corresponding normal cells. Sl^jSl^j foetal liver cells have a restricted response to erythropoietin in vitro in terms of haem synthesis, whereas foetal liver cells of normal littermates are highly responsive until the 16th day of gestation. Mixtures of late 16 day Sl^jSl^j and normal foetal liver cells (both non-responsive alone) respond to erythropoietin in vitro.     

ERYTHROID AND GRANULOCYTE-MACROPHAGE PROGENITOR CELLS IN PRE-NATAL 'STEEL' (SlJ/SlJ) ANAEMIC MICE

The erythropietin sensitivities of dissociated cell cultures and explanted fragments of fetal livers of congenitally anaemic Sl^J/Sl^J mice, and their normal littermates, have been compared. The erythropoietin responsiveness of Sl^J/Sl^J foetal liver cells is deficient in both types of culture. The maximum liver complement of erythroid colony forming cells (CFUe) occurs on the 16th day of development when ‘normal’ livers contain approximately 6 × 10⁵ erythroid colony forming cells/liver. In Sl^J/Sl^J fetuses the maximum reached is only 1 × 10⁵. Granulocyte-macrophage colony forming cells (CFU_C) in Sl^J/Sl^J fetal livers are also reduced to approximately 60% of normal numbers. Erythroid colony forming cells are also reduced in the spleen and femoral bone marrow of Sl^J/Sl^J mice in the 2–3 days preceding birth. Granulocyte-macrophage colony forming cells are rare in the femoral marrow of pre-natal Sl^J/Sl^J mice, but their production in the Sl^J/Sl^J pre-natal spleen appears unaffected.     

DEFECT OF ERYTHROPOIESIS IN NON-LEUKAEMIC AKR MICE

The kinetics of the CFU population and of erythropoiesis were investigated in the AKR strain mouse prior to the onset of thymic leukaemias: haemopoiesis was compared in syngeneic AKR, semi-allogenic C3H and (C3H x AKR) F, mice injected with AKR stem cells. These experiments demonstrate that the reduction in the number of spleen colonies previously described by Perkins et al. (1971) in syngeneic hosts, as compared to semi-allogenic C3H hosts, is actually related to defective erythropoiesis resulting from a dysfunction of the AKR haemopoietic inductive microenvironment (HIM). Erythropoietin secretion is normal in AKR mice. the early haemopoietic events related to the stem cell: lodgement of the CFU (‘f’ factor) and doubling time, are not disturbed, but the onset of CFU proliferation is markedly delayed in the AKR strain. the main expression of the AKR HIM dysfunction is a significant reduction in the number of erythroid (E) colonies and an impaired output of red blood cells per E-colony in the syngeneic host as compared to the allogenic one. In addition, data indicate that a weakly histo-incompatible system, such as that in C3H and hybrid hosts, does not interfere with the stages of haemopoiesis except by lengthening the doubling time of the CFU. the results, on the whole, emphasize the prevalent influence of HIM.     

COLONY-FORMING ABILITY OF BONE MARROW CELLS OF W ANAEMIC MICE ON MACROPHAGE LAYER FORMED IN PERITONEAL CAVITY OF MICE

The colony-forming ability of haematopoietic cells of W anaemic mice was examined on the macrophage layer formed in the peritoneal cavity of mice. Bone marrow cells of W anaemic mice formed a considerable number of colonies on the macrophage layer, notwithstanding they did not form any colonies in the spleen of the same recipients. As the colony-forming ability of the bone marrow cells was not reduced by the incubation with ³H-thymidine, most of the cells which formed colonies on the macrophage layer seemed to stay in G₀ state. The interrelationship between the spleen colony-forming cells, the macrophage-layer colony-forming cells, and in vitro colony-forming cells was discussed.     

DAILY VARIATIONS OF MARROW AND SPLENIC ERYTHROPOIESIS, PINNA EPIDERMAL CELL MITOSIS AND PHYSICAL ACTIVITY IN C57Bl/6J MICE

Regular daily fluctuations in spontaneous physical activity and in the mitotic indices of marrow and splenic erythroid elements and pinna cells, were observed. Both male and female C57Bl/6J mice showed these rhythms. Of particular interest was the finding that the spleen and the marrow mitotic activity showed a reciprocal relationship. The role of several hormones and the biological clock in control of these rhythms are discussed.     

胎脑提取液对衰老小鼠海马神经元酶活性影响的实验研究

目的 观察胎脑提取液对衰老小鼠海马神经元酸性磷酸酶（ACP）和琥珀酸脱氢酶（SDH）活性的影响,探讨胎脑提取液的抗衰老作用。方法 选用健康昆明种小白鼠30只,随机分为3组;采用D-半乳糖制备亚急性衰老模型;酶组织化学方法结合显微图像分析。观察各组小鼠海马神经元ACP和SDH的活性。结果 衰老模型组与正常对照组相比,小鼠海马神经元ACP活性明显升高,SDH活性明显降低;给药组与衰老模型组相比,小鼠海马神经元ACP活性明显降低。SDH活性明显升高。结论 胎脑提取液可以延缓海马神经元的衰老进程,具有一定的抗衰老作用。     

THE MATING SYSTEM GENETICALLY AFFECTS OFFSPRING PERFORMANCE IN WOODHOUSE'S TOAD (BUFO WOODHOUSEI)

To determine if the nonrandom, non-resource-based mating system of Bufo woodhousei affects tadpole performance, I performed a series of controlled matings and reared the tadpoles to metamorphosis in the laboratory and field. I asked whether differences in paternal identity, mating status, or body size were related to differences in tadpole mass, larval period duration, metamorphic mass, or survival of offspring. Although both laboratory and field rearings indicated that male and female parentage affected most offspring traits, no correspondence existed between either laboratory and field metamorphic mass or laboratory and field survival of offspring sired by the same male. The lack of correspondence between sire breeding values in the laboratory and field for two of three traits raises doubts as to the validity of drawing conclusions concerning how evolution might be expected to work from laboratory studies. Paternal effects were more pronounced in the field than in the laboratory, despite what is usually presumed to be a greater amount of environmental variation in the field. In the laboratory neither sire body size nor mating status affected any trait, but in the field larger males produced offspring that were 10% heavier at transformation than offspring sired by small males. This predictable relationship between sire phenotype (body size) and offspring performance means that nonrandom mating based on male body size could have a directional effect on offspring performance. Because larger males mate disproportionately often in this population (Woodward, 1982a; Mitchell, unpubl.), the mating system may exert a directional effect on metamorphic body size.     

THE EFFECT OF GENETICALLY BASED DIFFERENCES IN SEED SIZE ON SEEDLING SURVIVAL IN ARABIDOPSIS THALIANA (BRASSICACEAE)

The relationship between genetically different seed sizes and seedling survival under severe nutrient deprivation was determined by comparing ten inbred lines of Arabidopsis thaliana. Seedlings were supplied with only sterile distilled water, and the number of days between germination and death (complete chlorosis) was recorded. Seedlings from genotypes with larger seeds survived longer than seedlings from genotypes with smaller seeds. These results suggest a genetically based adaptive significance of larger seed size resulting from a greater seedling tolerance of nutrient deprivation. This may confer a potentially important selective advantage when nutrient deprivation is the result of a low resource supply in the environment, or the result of nutrient depletion by neighbors.     

POLY(HPMA)-COATED LIPOSOMES DEMONSTRATE PROLONGED CIRCULATION IN MICE

Surface modification of liposomes with amphiphilic flexible polymers significantly prolongs their circulation time in blood and reduces uptake by cells of the reticuloendothelial system (RES). Several polymers have already been shown to provide steric protection to liposomes. Still more polymers are expected to serve this purpose, thus broadening the variability of properties of long-circulating liposomes. Poly[N-(2-hydroxypropyl)methacrylamide] (poly (HPMA)) seems to have some properties similar to polyethylene glycol (PEG), the most widely used polymer in liposome surface modification, including flexibility, hydrophilicity and low immunogenicity, which suggest that it may also function as an efficient steric protector of liposomes. Semitelechelic poly(HPMA) with single- or double-oleic acid hydrophobic terminus were synthesized and incorporated into the surface of liposomes composed of phosphatidylcholine and cholesterol. These poly(HPMA)-modified liposomes provided strong steric protection for liposomes, increasing their circulation time and decreasing liver accumulation in experimental mice. Poly(HPMA)-modified liposomes may become a useful addition to a family of long-circulating liposomes with potential to be used as a drug delivery system.     

CELL PROLIFERATION IN HAEMATOPOIETIC SPLEEN COLONIES OF MICE: DIFFERENCE BETWEEN COLONIES DERIVED FROM INJECTED ADULT BONE MARROW AND FOETAL LIVER CELLS

Cell proliferation in mouse spleen colonies, derived from injected foetal liver and young adult bone marrow, was studied by measuring incorporation of radio-iodine-labelled 5-iodo-2'-deoxyuridine (IUdR). Foetal liver-derived colonies incorporated significantly more IUdR than marrow-derived colonies on the 8th and 12th days after cell injection. The data are consistent with the view that foetal haematopoietic stem cells are capable, on average, of producing larger descendant populations than are stem cells from young adults.     

植物凝集素(PHA)对小鼠白细胞及血清乳酸脱氢酶同工酶的影响

本文就 PHA 在不同时间内对小鼠白细胞及血清 LDH,同工酶的影响进行了观察,结果表明,PHA 对小鼠白细胞及血清的 LDH 酶活性有一定的影响,24h,48h,72h 三个不同时间组均与对照组有显著性差异(P<0.01),其中以48h 组酶活性最强,同时淋巴细胞的酶活性明显高于粒细胞;血清同工酶谱也有明显的变化,LDH_(1-4)均低于正常(P<0.01),LDH_5明显增高(P<0.01),同时出现了 LDH_5(?)亚带.     

INHIBITION OF EHRLICH TUMOR GROWTH IN MICE BY ELECTRIC INTERFERENCE THERAPY (IN VIVO STUDIES)

A study of solid tumor growth retardation by employing extremely low frequency (ELF) electric fields has been carried out. ELF electric fields were generated in tumor tissue in mice by the interference of two high frequency sinusoidal waves with the beat frequency centered at the tumor core. The results indicated a pronounced decrease in tumor growth rate in animals exposed to a 5-Hz interferential frequency for 1 hr daily. The 1 hr/day treatment produced a greater retardation effect than the 1 hr/week treatment. This indicates that treatment duration at the applied field frequency appears to play an important role in tumor growth delay. The dielectric properties of the tumor cells showed higher permittivity and conductivity values than homologous normal tissue. The permittivity of tumor cells treated daily with 5 Hz reaches nearly the same value as control tissue. Moreover, histological studies show that tumor tissues treated daily with the same frequency undergo partial regression and shrinkage of the aggregates of neoplastic cells leaving very little of them. We conclude that this new interferential technique is promising for tumor treatment in which a resonating electric field affects cell-to-cell communication.     

顺天胶囊对小鼠免疫功能的影响

本文探讨了顺天胶囊(Shun Tian Capsule;STC)在体外对小鼠淋巴免疫功能的影响,实验结果表明,本品浓度在0.25～1.0μml~(-1)范围内明显促进ConA和LPS对淋巴细胞增殖反应,增强诱导淋巴细胞产生IL-2和INF-α。提示,本品具有明显增强免疫功能的作用,最适剂量为0.5～0.75 ug.ml~(-1),并呈浓度依赖性的双向作用。     

人抗药基因在小鼠ES细胞中的表达及嵌合体小鼠的研究

本文用磷酸钙沉淀法将含人mdrl 基因表达质粒(pHaMDR 1/A)转染到小鼠胚胎干细胞(ES-5),得到了四个能稳定地在含有200 ng/ml 秋水仙素培液中生长传代的细胞克隆。经Southern 印迹杂交及RNA 印迹杂交证明人mdrl 基因已整合到ES 细胞基因组,并有表达。其中两个克隆杂交信号较强,抗药基因可随秋水仙素浓度提高而扩增,表达量也随之增加。用抗该基因编码的p170糖蛋白抗体对ES-mdr 1细胞作免疫荧光染色,证实p170蛋白分布于细胞表面。未发现ES-mdr 1细胞的体内、外发育潜能与亲代细胞的有何差异。但是mdr1细胞不能被RA 和HMBA 化学药物诱导分化,表明这些细胞已与亲代ES-5细胞不同,具有拮抗化学药物诱导分化的作用,其机理尚待研究。因此,ES-mdr1细胞可作为在细胞水平研究p170糖蛋白作用机理的体系,也可用以建立体外筛选拮抗抗约基因作用新手段的模型。我们也得到了含人mdr1基因的嵌合小鼠,并对它们的嵌合情况作了分析。