Effect of aminoglutethimide on murine fetal hepatic erythroid colony formation

Pretreatment of pregnant mice with aminoglutethimide phosphate, an inhibitor of glucocorticoid synthesis, increases the content of fetal liver erythroid colony-forming cells (CFU-E), as assessed by the formation of erythroid colonies in vitro by fetal liver cells in plasma clots containing exogenous erythropoietin. In addition, the inability of aminoglutethimide to influence erythroid colony formation in vitro suggests that endogenous glucocorticoids exert a suppressive effect on the number of functional CFU-E in the fetal liver.     

Systemic oxygen transport and erythropoiesis in the mouse

Summary Removal of 15% of blood volume in the mouse increases erythropoiesis by a factor of 2.2 when measured 12 h after bleeding. Exposure of normal mice to 40% reduced barometric pressure for the same period of time increases erythropoiesis only by a factor of 1.6. The response to hypoxia takes place in the presence of a 40% reduction of oxygen consumption and tissue-venous P_{o 2}, changes which are concomitant with a 5-fold increase in plasma erythropoietin activity. The larger response in anemic animals on the other hand occurs without any detectable change in these parameters. These results cast serious doubts about the interpretation of the quantitative homeostatic control of erythropoiesis based solely on the action of erythropoietin.Acknowledgments. This work was supported by a grant from the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina. We thank Isabel Zingariello for excellent technical assistance.     

Granulocytosis induced in vivo by a mouse marrow stromal cell line,BMA1, which produces colony stimulating factor

Summary Nude mice were inoculated with BMA1 cells. These are cells which produce granulocyte-macrophage colony stimulating factor (GM-CSF); They are derived from mouse bone marrow stromal cells transfected with adenovirus 5 DNA. Progressive neutrophilia developed as the tumor grew, but disappeared quickly after local tumor excision. Media conditioned with tumor cells had GM-CSF but neither erythropoietin, nor burst-promoting activity. In all the tumors which developed, focal areas of bone formation were found among fibrosarcomatous tissues.     

Granulocytosis induced in vivo by a mouse marrow stromal cell line, BMA1, which produces colony stimulating factor

Nude mice were inoculated with BMA1 cells. These are cells which produce granulocyte-macrophage colony stimulating factor (GM-CSF); They are derived from mouse bone marrow stromal cells transfected with adenovirus 5 DNA. Progressive neutrophilia developed as the tumor grew, but disappeared quickly after local tumor excision. Media conditioned with tumor cells had GM-CSF but neither erythropoietin nor burst-promoting activity. In all the tumors which developed, focal areas of bone formation were found among fibrosarcomatous tissues.     

Abnormal sensitivity to erythropoietin in the erythroblast precursors in Vaquez disease]

Marrow specimens of patients with polycythemia vera rise to erythrocytic colonies in vitro without addition of erythropoietin to the culture. This behavior was never observed with marrow cells of normal subjects or secondary erythrocytosis. These results indicate that the sensitivity of some erythrocytic progenitor cells to erythropoietin is altered in polycythemia vera.     

Shear-dependence of endothelial functions

Endothelial cells are subjected to shear forces which influence important cell functions. Shear stress induces cell elongation and formation of stress fibers, increases permeability, pinocytosis and lipoprotein internalization, is involved in the formation of atherosclerotic lesions, increases the production of tissue plasminogen activator, and enhances von Willebrand factor release and hence platelet aggregation. It decreases adherence of erythrocytes and leukocytes, and increases the release of prostacyclin, endothelium derived relaxing factor, histamine and other compounds, but decreases erythropoietin secretion. The mechanism of signal transduction to the endothelial cell is not known exactly; shear-sensitive ion channels seem to be involved. It is concluded that a better understanding of shear-dependent endothelial functions will influence pathophysiologic concepts and therapeutic interventions.     

Erythropoietin modulates the neural control of hypoxic ventilation

Numerous factors involved in general homeostasis are able to modulate ventilation. Classically, this comprises several kind of molecules, including neurotransmitters and steroids that are necessary for fine tuning ventilation under different conditions such as sleep, exercise, and acclimatization to high altitude. Recently, however, we have found that erythropoietin (Epo), the main regulator of red blood cell production, influences both central (brainstem) and peripheral (carotid bodies) respiratory centers when the organism is exposed to hypoxic conditions. Here, we summarize the effect of Epo on the respiratory control in mammals and highlight the potential implication of Epo in the ventilatory acclimatization to high altitude, as well as in the several respiratory sickness and syndromes occurring at low and high altitude. (Part of a multi-author review.)     

D-半乳糖致衰老小鼠学习记忆能力和睾丸的改变及延衰合剂的治疗作用

目的研究D-半乳糖所致亚急性衰老小鼠学习记忆能力和睾丸的变化,并观察延衰合剂对其的治疗作用。方法选昆明系雄性小鼠,用D-半乳糖建立亚急性衰老模型。应用Morris水迷宫实验测试衰老小鼠学习记忆能力的变化;电镜技术观察延衰合剂治疗后衰老小鼠睾丸的形态学改变;酶联免疫分析法检测血清睾酮的变化。结果衰老小鼠学习记忆能力下降,睾丸重量减少,生精细胞减少,结构紊乱,功能障碍,血清睾酮含量明显降低。在改变学习记忆能力上延衰合剂高剂量组作用明显优于延衰合剂低剂量纽（P〈0．05）,但与补肾益寿胶囊纽及延衰舍剂中荆量组差畀无显著性（P〉0．05）。结论延衰舍剂可以提高衰老小鼠学习记忆能力,改善睾丸生精小管的超微结构,抑制衰老小鼠血清睾酮含量的下降,具有一定的延缓衰老作用。     

Administration of D-alanine did not cause increase of D-amino acid oxidase activity in mice.

D-amino acid oxidase (DAAO) activity was not altered in the liver and kidney by oral administration of D-alanine to adult mice. The enzyme was apparently not induced by the enteric microflora either, since the enzyme activity in the liver and kidney of germ-free mice was not different from that of specific-pathogen-free mice. The times of appearance of DAAO activity and of free D-amino acids in the kidney were elucidated using suckling mice. DAAO activity started to increase 7 days after birth, and reached almost the adult level by 28 days. The content of free neutral D-amino acids also increased with age, in a similar fashion. A possible conclusion is that the enzyme activity normally increases during this period, to eliminate the free D-amino acids which have increased with age in the suckling mice. Consequently, the administration of D-alanine had no further effect in increasing enzyme activity.     

Nociception,neurogenic inflammation and thermoregulation in TRPV1 knockdown transgenic mice

Transgenic mice with a small hairpin RNA construct interfering with the expression of transient receptor potential vanilloid 1 (TRPV1) were created by lentiviral transgenesis. TRPV1 expression level in transgenic mice was reduced to 8% while the expression of ankyrin repeat domain 1 (TRPA1) was unchanged. Ear oedema induced by topical application of TRPV1 agonist capsaicin was completely absent in TRPV1 knockdown mice. Thermoregulatory behaviour in relation to environmental thermopreference (30 vs. 35°C) was slightly impaired in male knockdown mice, but the reduction of TRPV1 function was not associated with enhanced hyperthermia. TRPV1 agonist resiniferatoxin induced hypothermia and tail vasodilatation was markedly inhibited in knockdown mice. In conclusion, shRNA-mediated knock down of the TRPV1 receptor in mice induced robust inhibition of the responses to TRPV1 agonists without altering the expression, gating function or neurogenic oedema provoked by TRPA1 activation. Thermoregulatory behaviour in response to heat was inhibited, but enhanced hyperthermia was not observed.     

Administration of D-alanine did not cause increase of D-amino acid oxidase activity in mice

D-amino acid oxidase (DAAO) activity was not altered in the liver and kidney by oral administration of D-alanine to adult mice. The enzyme was apparently not induced by the enteric microflora either, since the enzyme activity in the liver and kidney of germ-free mice was not different from that of specific-pathogen-free mice. The times of appearance of DAAO activity and of free D-amino acids in the kidney were elucidated using suckling mice. DAAO activity started to increase 7 days after birth, and reached almost the adult level by 28 days. The content of free neutral D-amino acids also increased with age, in a similar fashion. A possible conclusion is that the enzyme activity normally increases during this period, to eliminate the free D-amino acids which have increased with age in the suckling mice. Consequently, the administration of D-alanine had no further effect in increasing enzyme activity.     

Drug susceptibility of PCA in WBB6F1-W/Wv mice

Our previous study revealed that passive cutaneous anaphylaxis (PCA) can be produced in congenitally mast cell-deficient WBB6F1-W/W^v (abbreviated as W/W^v) mice on sensitization with undiluted or slightly diluted allogeneic and xenogeneic antisera but not on sensitization with allogeneic monoclonal immunoglobulin (Ig)E and IgG1 antibodies regardless of the antibody concentration [1]. In view of these findings, the present study was conducted to characterize PCA in this strain from its drug susceptibilities using mast cell-bearing WBB6F1-+/+ (abbreviated as +/+) and B6D2F1 mice as references. PCA in W/W^v mice mediated by a low dilution (1  4) of hyperimmune serum to bovine serum albumin of the B6D2F1 mouse origin was markedly suppressed by CV-6209, an antagonist of platelet-activating factor (PAF), but not by antihistamines such as cyproheptadine and oxatomide. In contrast, PCA in +/+ and B6D2F1 mice mediated by a high dilution (1  128) of the anti-serum (virtually by IgG1 antibody) was nearly completely suppressed by antihistamines but not by CV-6209. A remarkable difference between PCA in W/W^v and reference mice was also observed in the susceptibility to monoclonal anti mouse granulocyte (Gr-1) antibody PCA in W/W^v mice was potently suppressed by the 1- to 3-day pretreatment with this antibody but that in references was not at all. Putting these present results together with the previous finding that anti-granulocyte antibody greatly reduces circulatory Gr-1⁺ leukocytes, 1 to 3 days after the treatment [2], it is highly probable that PCA in W/W^v mice mediated by some antibody isotypes other than IgE and IgG1 is produced by PAF mainly released from Gr-1⁺ cells, while IgG1 antibody-mediated PCA in mast cell-bearing reference mice is evoked by histamine derived from mast cells. PCA homologous to that in W/W^v mice could also be produced in the reference mice on sensitization with undiluted or slightly diluted antiserum, when generalized blueing due to excess IgG1 antibody was removed by the oxatomide treatment be fore the antigen challenge. Received 10 December 1997; received after revision 2 February 1998; accepted 23 February 1998     

延衰合剂对D-半乳糖诱导的亚急性衰老小鼠免疫功能影响的实验研究

目的 研究延衰合剂( yanshuai mixture,YSM)对D-半乳糖所致亚急性衰老小鼠胸腺、脾脏组织结构及白介素2水平的影响.方法 选昆明系小鼠,用D-半乳糖建立衰老模型.应用光镜、电镜技术观察延衰合剂治疗前后衰老小鼠胸腺、脾脏的形态学改变;检测胸腺指数及脾脏指数;酶联免疫分析法检测血清白介素2的变化.结果 衰...     

Galactose transfer and UDP-Galactose hydrolysis in urine from normal balb/c and Balb/c YC8 mice

Summary By chromatographic method we have shown the existence of a complex system for galactose transfer from UDP-galactose and for nucleotide hydrolysis in urines from Balb/c YC8 and normal Balb/c mice. By action of sera from normal and ascitic mice as source of enzyme, we have been able to detect transfer for galactose in urines from ascitic mice and an important inhibitory effect of the nucleotide sugar hydrolysis by the sera with urines from normal mice.     

Preferential excretion of glycated albumin in C57BL-Ks-J mice: effects of diabetes.

Urinary excretion of glycated albumin was quantitated in genetically hyperglycemic mice (C57BL-Ks-J, db/db mice), a model for non-insulin-dependent diabetes mellitus, and compared with their non-diabetic littermates. The data indicated a preferential excretion of glycated albumin in non-diabetic mice. This phenomenon of 'editing' of glycated albumin is decreased significantly in diabetic mice. Quantitative measurements of overall excretion of glycated albumin suggested that the loss of editing in diabetic mice is due to the dilution of glycated albumin by the unmodified albumin which is excreted in large amounts in diabetic mice. Therefore, the loss of editing observed in this model resembled the one we characterized in insulin-dependent diabetic humans and a streptozotocin-diabetic rat model.     

The influence of cold or isolation stress on resistance of mice to West Nile virus encephalitis

The effect of cold or isolation stress on mortality rate and brain virus level were investigated in mice infected with West Nile virus (WNV). Exposure of mice for 5 min/day to cold water (1 +/- 0.5 degrees C) for 8-10 days resulted in 92% mortality as compared to 47% in control mice (p less than 0.001). Mice housed in individual cages (isolation stress) were also more susceptible to WN viral infection, as shown by increased mortality rate reaching 85% as compared to 50% in mice housed 6 per cage (p less than 0.01). Cold or isolation stress increased blood brain and spleen virus levels as early as 2 days after inoculation. After 8 days of isolation or cold stress, mice inoculated with WNV had 8.9 and 9.0 log10 plaque forming units in the brain, respectively, as compared to 6.9 in the control (p less than 0.01-0.001). Furthermore, lymphoid organs such as spleen and thymus showed severe mass loss. These data suggest that physical or non-physical stress situations enhance WNV encephalitis by accelerating virus proliferation and increase mortality in mice.     

Effects of some GABAergic agents on quinine-induced seizures in mice

The effects of some GABAergic agents on seizures induced by quinine were studied in mice. Muscimol, AOAA, DABA and baclofen significantly protected mice against quinine-induced convulsions. Bicuculline effectively enhanced quinine-induced convulsions, and significantly attenuated the protective effects of muscimol, AOAA and DABA against convulsions induced by quinine. Diazepam and phenobarbitone significantly protected mice against convulsions induced by quinine. However, phenytoin did not affect quinine-induced seizures to any significant degree. These results indicate that the convulsant effect of quinine may be due to a disturbance in the status of the GABAergic system.