The mitogenic properties of rabbit anti-mouse brain serum

The mitogenic activity of heterologous rabbit anti-mouse brain sera (RAMB) was investigated. By complement-dependent cytotoxicity and indirect immunofluorescence, RAMB was T-cell specific. Mitogenic activity was assessed by determination of [³H]thymidine incorporation into DNA. RAMB was mitogenic for spleen cells for Thy 1.1- and Thy 1.2-positive mouse strains. Maximal mitogenic responsiveness to RAMB occurred on Day 3 of culture. The incorporation of [³H]uridine into RNA and [³H]leucine into protein and percentage of blast cells in culture were also significantly increased following RAMB stimulation. The mitogenic activity of RAMB was abrogated by adsorption of the sera with BALB/c or AKR thymocytes or brains or with RL♂ 1.3+, a Thy 1.2-bearing T-cell lymphoma of BALB/c origin. In contrast, the mitogenic activity was not removed when RAMB sera were absorbed with RL♂ 1.4?, a variant of RL♂ 1 which appears to specifically lack cell surface Thy 1 determinants. These data suggest that the mitogenic activity of RAMB is Thy 1 directed. RAMB mitogenicity is T-cell dependent. Spleen cells from normal and heterologous nu/+ mice respond to RAMB, while spleen cells from nu/nu mice do not respond. Normal thymocytes and cortisone-resistant thymocytes do not respond mitogenically to RAMB. The response of unseparated spleen cells to RAMB is also macrophage dependent. Nylon-wool column-purified splenic T cells respond to high concentrations of RAMB in the absence of exogenous macrophages but do not respond to lower concentrations of RAMB unless exogenous macrophages are added to the cultures. Nylon-wool-adherent cells, which are B-cell enriched and relatively T-cell depleted, also respond to RAMB, suggesting that in the presence of even small numbers of T cells, B cells can be recruited into the response.     

The regulation of hematopoietic stem cell proliferation and differentiation (CFU-S) during antigenic exposure

Hemopoietic stem cell (CFUs) proliferation is controlled by regulatory activities (stimulator and inhibitor) produced by bone marrow macrophages. Previously it has been shown that antigen administration stimulates CFUs proliferation. The data obtained in this study show the possible mechanism of antigen-induced stimulation of CFUs proliferation. 3-4 days after antigen injection bone marrow cells of BDF1 mice cease to produce inhibitory activity in contrast to similar cells of control animals. Therefore, increased CFUs proliferation in immunized mice can be due to decreased production of inhibitory activity and resulting abundance of stimulating factors. In BAlB/c mice CFUs proliferation is not changed after antigen injection and their bone marrow cells continue to synthesize inhibitory substances. Differentiation of CFUs into committed blood precursor cells may depend on the proliferation level in CFUs population since activation of CFUs proliferation in immunized BDF1 mice is accompanied by a decreased number of CFU-GM and CFU-M but an increased number of BFU-E. It should be noted that intact BAlB/c mice show a high level of CFUs proliferation similar to that of immunized BDF1 mice.     

Effect of anti-mouse brain serum on the CFUc in actively proliferating bone marrow

With hydroxyurea injected to donor mice a greater inhibition of splenic colony growth occurred after incubation of a bone marrow suspension with the rabbit antimouse brain serum (RAMBS), and restoration of the colony-formation by thymocytes was less pronounced than in normal bone marrow treated with the antibrain serum. The incubation of the bone marrow cells containing CFUc, which actively proliferate after irradiation or stimulation by vinblastine, with the antibrain serum sharply suppressed the splenic colony growth. In this case however, in contrast to normal bone marrow, the administration of thymocytes failed to exert a favourable action on the colony formation. It is suggested that functioning of accessory cells is not associated with the defined cell cycle stage of CFUc and that, in addition to the previously discovered accessory cell population, some other factors, inactivated by the RAMBS serum, are present in the bone marrow the analogue of which is absent in the thymus.     

The role of nicotine in regulation of lymphocyte proliferation

The effect of nicotine on both the expression of nicotinic acetylcholine receptors (nAChRs) and proliferation of hybridoma cells and normal mouse lymphocytes has been investigated. By means of immunoenzyme assay, nicotine was shown to regulate the number of nAChRs in both hybridoma cells and normal rat splenocytes. According to the data of triazolyl blue inclusion and ELISpot assay, nicotine stimulated proliferation of both hybridoma cells and normal plasma cells generated in the course of immune response in vivo. The cell sensitivity to nicotine depended on the number of nAChRs expressed on the membrane, as well as on their functional activity affected, in particular, by adhesive contacts. The use of the open channel blocker benzohexonium revealed that proliferative signal through nAChR in hybridoma cells was mediated by ion channel opening. The data obtained demonstrate the proproliferative role of nicotine for B lymphocytes, and may account for the development of lymphoproliferative disorders in tobacco smokers.     

The role of cells and their products in the regulation of in vitro stem cell proliferation and granulocyte development

In long-term marrow cultures haemopoiesis can be maintained in vitro for up to 6 months. Critical analysis of the cell populations produced has shown that the stem cells and their committed progeny have characteristics in common with the corresponding cell types in vivo. The maintenance of haemopoiesis in vitro is associated with the development of an appropriate inductive environment provided by bone marrow derived adherent cells. Analysis of the interactions between environmental and haemopoietic cells has been facilitated by the development of in vitro systems reproducing the naturally occurring genetic environmental defects and other systems where the development of a competent inductive environment shows a dependency upon corticosteroid hormones. Investigations have shown that stem cell proliferation may be controlled by production of opposing activities, one stimulatory for DNA synthesis, the other inhibitory. A model is proposed whereby modulation in the production of these factors is determined by the physical presence of stem cells in a proposed cellular milieu, within the adherent layer. The adherent layer, apart from acting at the level of stem cell proliferation, can also modify the response of differentiating cells (eg, GM-CFC) to exogenous stimulatory activities. Addition of GM-CSF or of CSF-antiserum has no effect on haemopoiesis in long-term cultures.     

The perturbed cell proliferation kinetics of the EMT6/M/AC tumour in mice treated with anti-mouse lymphocyte serum.

The cell proliferation kinetics of the EMT6/M/AC tumour were determined at two volumes, 6-3 mm3 and 180 mm3, in mice treated with anti-mouse lymphocyte serum, AMLS. Comparison of the growth curve with that obtained in non-AMLS treated animals showed a marked increase in the growth rate at all volumes in the treated group. In contrast, the cell cycle time and the intermitotic phase times were not significantly different in the treated and untreated groups at comparable volumes. The increase in the growth rate in AMLS treated mice was obtained in spite of decreases in both the rate constant for cell production and the growth fraction, and was due to a marked decrease in the rate constant for cell loss.     

Brain-associated theta antigen: reactivity of rabbit anti-mouse brain with mouse lymphoid cells

Immunization of rabbits with mouse brain (which is known to contain Θ antigen) results in a potent anti-Θ-like antiserum. This antiserum termed “anti-brain-associated Θ”, BAΘ, is cytotoxic to thymus cells but not marrow cells, inhibits the primary in vitro response to RBC, does not affect antibody-forming cells which are of marrow origin, and inhibits the graft-versus-host reaction. It serves as a convenient means of obtaining large quantities of anti-thymus antiserum.     

The role of histaminergic system of the brain in the regulation of sleep-wakefulness cycle

The structure and the morphological and neurochemical connections of the histaminergic system of the brain, which plays one of the most important roles in maintaining wakefulness, are considered. The biochemistry of histamine metabolism and histamine receptors is briefly described. The special role of the relation between the histamine system and orexin/hypocretin system is noted. Some examples of the effects of experimental manipulations with the histaminergic system on the wakefulness-sleep cycle are given.     

内源性CO对内皮素促大鼠主动脉平滑肌细胞增殖及MAPK活性的影响

血红素加氧酶（ｈｅｍｅ ｏｘｙｇｅｎａｓｅ,ＨＯ）是血红素分解代谢过程中的限速酶,它能使细胞内的血红素降解成胆绿素和一氧化碳（ｃａｒｂｏｎｍｏｎｏｘｉｄｅ,ＣＯ）,近来资料表明内源性一氧化碳对生理和病理状态下的血管张力有重要的调节作用,目前尚不不禁内源性ＨＯ／ＣＯ刘否参与平滑肌细胞增殖过程的调节,本实验在体内培养的大鼠主动脉平滑肌细胞模型上,用血色素加氧酶抑制剂卟啉锌－９（ｚｉｎｃ ｐｒｏｔｏｐｏ     

The role of DNA breaks in the regulation of cell proliferation, differentiation and aging

The published and author's data on the involvement of DNA breaks in cell proliferation, differentiation and senescence are reviewed. During senescence, exogenous unrepaired DNA breaks are irreversibly accumulated. During differentiation, DNA breaks are also accumulated, but against the background of active reparation processes in the cell on the principle of a dynamic equilibrium between DNA breakage and reparation. When modelling the state of cell quiescence, both types of DNA breaks may take place. It is suggested that DNA breakage in the replicative complex is specific for the state of quiescence.     

The role of tyrosine phosphorylation in the regulation of cell proliferation and differentiation in lower eukaryotes

The review summarizes current data on signaling transduction mechanisms in some unicellular eukaryotes, based on sequential translation of phosphotyrosine signals from the cell surface to the nucleus.     

The role of ERK-RSK signaling in the proliferation of intrahepatic biliary epithelial cells exposed to microcystin-leucine arginine

Microcystin-leucine arginine (MC-LR) is a potent specific hepatotoxin produced by cyanobacteria in diverse water systems, and it has been documented to induce liver injury and hepatocarcinogenesis. However, its toxic effects on intrahepatic biliary epithelial cells have not been invested in detail. In this study, we aimed to investigate the effects of MC-LR exposure on the intrahepatic biliary epithelial cells in the liver. MC-LR was orally administered to mice at 1 μg/L, 7.5 μg/L, 15 μg/L, or 30 μg/L for 180 consecutive days for histopathological and immunoblot analysis. We observed that MC-LR can enter intrahepatic bile duct tissue and induce hyperplasia of mice. Human primary intrahepatic biliary epithelial cells (HiBECs) were cultured with various concentrations of MC-LR for 24 h, meanwhile the cell viability and proteins level were detected. Western blotting analysis revealed that MC-LR increased RSK phosphorylation via ERK signaling. RSK participated in cell proliferation and cell cycle progression. Taken together, after chronic exposure, MC-LR-treated mice exhibited abnormal bile duct hyperplasia and thickened bile duct morphology through activating the ERK-RSK signaling. These data support the potential toxic effects of MC-LR on bile duct tissue of the liver.     

The effect of rabbit anti-mouse brain-associated theta serum on the immunologic responsiveness of AKR mice

Rabbit anti-C3H mouse brain-associated antiserum (BA-θ) was tested for its effect on the immunologic responsiveness of preleukemic and leukemic AKR mice to sheep erythrocytes. This BA-θ antiserum was cytotoxic in vitro for both C3H and for AKR thymocytes, and was immunosuppressive in vivo. Greater immunosuppression was effected by the antiserum in preleukemic AKR mice than in leukemic animals. Control rabbit serum also was cytotoxic in vitro and immunosuppressive in vivo, but this activity was removed by absorption with homologous erythrocytes and liver tissue, and with agarose. Conversely, absorption of the rabbit anti-BA-θ serum had no effect on either the in vitro cytotoxic activity, or on the in vivo immunosuppression.