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M G Chen

Publications and source records attributed to M G Chen.

At least 73 records · Page 4Linked to original sources
PubMed1983

The influence of choline chloride on murine hematopoiesis in vivo and in vitro.

We report here studies to further document the ability of cholinergic agonists to influence murine hematopoiesis. B6C3F1 mice were administered ultrapure choline (0.14, 1.4, and 7.0 mg/animal) i.p. for three days, then randomly sacrificed for assessment of hematological parameters. No significant change was observed in the packed red cell volume; however, the WBC was elevated significantly (85-400%) over noncholine administered controls during all days examined [1-12]. In vitro choline (10 mM) increased heterogeneous marrow-derived CFU-GM colony formation 210% above controls. Nonadherent marrow cell-derived CFU-GM produced a significant elevation in colony formation (36%), suggesting choline may influence directly a portion of the CFU-GM population. A twofold increase in the CFU-GM kill after 16 mM hydroxyurea exposure suggests choline can stimulate a subpopulation of CFU-GM not normally in cell cycle. In addition, choline (10 mM) was effective in stimulating CSF activity from marrow-derived conditioned medium. Dose-response studies demonstrated that choline was also stimulatory for megakaryocyte colony formation (CFU-Mk), 26% at 5 mM. Erythroid precursor stem cells, CFU-E/BFU-E, were reduced significantly (10-50%) at all choline concentrations tested (1-50 mM). These studies document the ability of choline to influence hematopoiesis, and provide further evidence that cholinergic mechanisms may be important in the control of steady-state hematopoiesis.

Animals↗
PubMed1983

Lithium stimulates the recovery of granulopoiesis following acute radiation injury.

Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radiotherapy protocols. In this report, we have examined bone marrow and spleen cells for their recovery patterns of CFUS, CFUGM, CFUE, BFUE and 59Fe-incorporation, along with the usual peripheral blood indices (packed red cell volume, WBC and differential) from mice administered Li after receiving 200 rad whole body irradiation. Li increased granulopoietic recovery as measured by significant elevations in both marrow and spleen derived CFUGM compared to those values obtained from radiation controls. Significant elevation in the WBC, consisting mainly of neutrophils, was also observed. Bone marrow and splenic derived erythroid stem cells (CFUE, BFUE) and % 59Fe-incorporation measured from peripheral blood, femur and spleen were all slightly reduced, but not to a significant degree to alter the packed red cell volume. The CFUS populations from both irradiated groups (control and Li-treated) were depressed when compared to normal non-irr controls and this degree of suppression was greater in the Li-treated group. These results document the ability of Li to stimulate the recovery of granulopoiesis after radiation-induced hematopoietic injury and suggest Li may be useful in ameliorating the neutropenia that can often develop after routine radiotherapy protocols.

Animals↗
PubMed1983

A retrospective survey on side effects of praziquantel among 25,693 cases of schistosomiasis japonica.

A retrospective survey involving 25,693 persons was carried out in four provinces and the city of Shanghai, China between December 1981 until May 1982 to document relatively serious side effects of praziquantel used in a mass treatment programme for schistosomiasis japonica. Only 122 or 0.47% of those participating in the study had experienced relatively serious side reactions to the drug. Most had only one kind of side effects but two or more were recorded in a few patients. Neuropsychiatric reactions were seen in 39 persons (0.15%,) cardiovascular reactions in 37 (0.14%), hepatic changes in four (0.02%), dermatological reactions in 18 (0.07%) and delayed reactions resulting in fatigue and inability to work in 29 (0.11%). Praziquantel remains the drug of choice for the treatment of oriental schistosomiasis, it is highly effective and although side effects are minimal, caution should be taken in the treatment of chronic disease with heart failure, ascites, poor hepatic compensation and renal failure.

Adolescent↗
PubMed1983

Lithium stimulated in vitro megakaryocytopoiesis.

We have investigated the effects of lithium on the proliferative potential of murine megakaryocyte stem cells (CFUMeg) in vitro and on circulating platelet levels in vivo. At optimal levels of megakaryocyte-colony stimulating factor (Meg-CSF) (10%) concentrations of 0.5, 1.0 and 3.0 meq/L augmented CFUMeg numbers. Significant increases of 133% and 125% over control levels were observed at 1.0 and 3.0 meq/L, respectively. At suboptimal concentrations of Meg-CSF (1.0%), Li effected a maximum increase of 200% over control levels at 1.0 meq/L suggesting a greater sensitivity of CFUMeg to stimulatory factors in the presence of Li. To better define the mode of action of Li, heterogenous bone marrow was separated into adherent and non-adherent cell populations and cultured in the presence of Li. Non-adherent cells cultured in the presence of 0.5, 1.0 and 3.0 meq/L Li showed significant increases in CFUMeg over non-adherent cells cultured without Li. These results suggest a direct effect of Li on CFUMeg. Cells cultured from the adherent cell population also responded to Li with enhanced CFUMeg numbers. This response may be a direct stem cell effect or an indirect effect via the production of endogenous Meg-CSF. One meq/L of Li when injected i.p., produced a thrombocytosis from days 4 through 15, with a maximum at 6 days post-Li treatment. These results suggest Li is an effective agent for stimulating megakaryocytopoiesis and has both direct and possibly indirect effects on the megakaryocyte stem cell.

Animals↗
PubMed1982

Cell kinetics of lithium-induced granulopoiesis.

Lithium has been shown to be an effective inducer of granulopoiesis. The mechanism of lithium action has been shown to influence CFU-s and CFU-c proliferation, increase colony-stimulating factor (CSF) production and reduce erythropoiesis. We report here evidence to show that lithium recruits CFU-c that are not normally in the cell cycle into active DNA synthesis, as measured by hydroxyurea and tritiated thymidine suicide techniques. Furthermore, lithium action is shown to be time-dependent, since the delay addition of lithium for 5 min to normal bone marrow removes the enhancement usually seen when lithium is given at time zero. The implications of these lithium-induced effects are described.

Animals↗
PubMed1982

Modulation of murine in vitro erythroid and granulopoietic colony formation by ouabain, digoxin and theophylline.

Ouabain has been shown to increase the number of clonally derived erythroid stem cells, CFUE and BFUE, from normal murine bone marrow. We report here that digoxin and theophylline also enhance erythroid stem cell colony formation, in the presence of suboptimal concentrations of erythropoietin (Ep) (0.01 IU/ml) in methylcellulose culture. Both digoxin and theophylline increased CFUE colony formation optimally at 10(-8) M (29-81% respectively). The increase in BFUE colony formation occurred at 10(-10) M (35-76% respectively), suggesting that BFUE are more sensitive to the enhancing properties of these compounds. In addition, digoxin theophylline and ouabain were effective inhibitors of clonally derived granulocyte-macrophage progenitor cells, CFUC, from normal murine marrow plated in double layer agar in the presence of 10% L-cell conditioned medium (LCM). The degree of reduction in colony formation by CFUC ranged from 11% to 100%. Digoxin and theophylline were inhibitory for CFUC in the range of 10(-2) to 10(-12) M; however, ouabain was inhibitory over a broader concentration range of 10(-4) to 10(-18) M, suggesting that ouabain has a greater influence on committed hematopoietic progenitor cell colony formation. Both ouabain and digoxin have the property of binding to Na+/K+ATPase. This may mediate the alteration of hematopoietic differentiation. Theophylline, an adenyl cyclase inhibitor, may act through alterations in cyclic nucleotide levels. These studies further indicate that digoxin, theophylline and ouabain may serve as useful tools in elucidating the underlying mechanisms of how specific growth factors influence hematopoietic growth and differentiation.

Animals↗
PubMed1981

Influence of lithium on proliferation of hematopoietic stem cells.

We studied the effect of lithium on normal marrow hematopoiesis by determining the numbers of pluripotential (CFUS) and committed stem cells (CFUC, CFUE and BFUE) after in vitro and in vivo exposure to lithium. In the presence of 1 meq/L lithium in vitro, marrow CFUS and CFUC were increased; higher concentrations (greater than or equal to 5 meq/L) were inhibitory. Marrow CFUE and BFUE were decreased at concentrations of lithium greater than or equal to 0.5 meq/L. In vivo (0.5-5.0 meq/L i.p.), lithium produced similar results to those obtained in vitro with striking CFUC enhancement. Serum from these lithium-treated mice contained increased colony stimulating factor (CSF). In the Dexter continuous marrow culture system, lithium stimulated increased CFUC production from the non-adherent fraction. These in vitro nd vivo studies document lithium's ability to modulate hematopoiesis by influencing pluripotential and committed stem cell proliferation and differentiation towards granulopoiesis, apparently at the expense of erythropoiesis. Mechanisms of this modulation are discussed.

Animals↗
PubMed1980

Acute hematological tolerance to multiple fraction, whole body, low dose irradiation in an experimental murine system.

Using a dose fractionation scheme patterned after the current regimen for treatment of disseminated non-Hodgkin lymphoma, the authors studied the effects of irradiation on progenitor and effector cells for hematopoiesis in five-month-old BC3F1 mice. Fractions of 20 or 50 rad (0.2 or 0.5 Gy) total body irradiation were given twice weekly to a final total dose of 200 or 500 rad (2 or 5 Gy), respectively. Weekly assays revealed a marked, sustained depression of stem cell activity, measured as numbers of spleen colony-forming units (CFU-S) and in vitro colony-forming cells (CFU-C), without corresponding depression of effector cells (red and white cells, and platelets). The lack of correlation between numbers of stem cells and peripheral elements is relevant to clinical assessment of marrow reserve.

Animals↗
PubMed1980

Modulation of murine pluripotential stem cell proliferation in vivo by lithium carbonate.

The effect of administering lithium in vivo on murine pluripotential stem cell proliferation was studied. Lithium was injected i.p. at various meq/liter concentrations (0.5-5.0 meq/liter). Data was obtained establishing that lithium increased the pluripotential stem cell population from normal mice as measured by the Till and McCulloch CFUs assay. Significant increases were demonstrated in: (1) bone marrow CFUs; (2) bone marrow organ cellularity, and (3) peripheral blood WBC. Marrow CFUs increase was maximum at 4 days post-lithium injection and greatest in the 1 meq/liter group (p < 0.001). Further increases in lithium concentration, i.e., 5 meq/liter, effectively reduced CFUs levels below normal, suggesting toxicity of the drug was apparent at this dose level. We conclude lithium may modulate granulopoiesis by increasing the CFUs stem cell compartment, thereby directly channeling differentiation into the granulopoietic pathway. This increases the committed progenitor stem cell (CFUc) population and ultimately peripheral blood end-stage cells.

Animals↗