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111.
Approximately half of the colony-forming units-culture (CFU-C) from normal peripheral blood are eosinophilic. The purpose of our study was to determine: (1) whether progenitor cells committed to eosinophil or neutrophil maturation would be differentially affected by feedback inhibition, and (2) whether mature eosinophils added to the feeder layers of the culture would inhibit the proliferation of CFU-C in a manner similar to that described for neutrophils. Concentrated eosinophils and neutrophils, obtained by separation on a metrizamide gradient, were added to feeder layers containing either 10(6) autologous whole mononuclear cells (WMNC) or 0.1 ml of leukocyte conditioned media (LCM). The average number of colonies was 123/10(6) nonadherent cells (NAC) cultured. When neutrophils or eosinophils were added to the WMNC feeder layer, the percent inhibition of growth was 40.2% +/- 1.6% (mean +/- SEM) and 42.3% +/- 5.4%, respectively, but the ratio of neutrophil to eosinophil colonies remained constant. No effect was seen when neutrophils or eosinophils were added to an LCM feeder layer. Thus, it appears that the differential control of neutrophil versus eosinophil production in vitro is not regulated through feedback inhibition by mature granulocytes. In addition, these studies suggest that eosinophils, as well as neutrophils, cause inhibition of CFU-C growth when intact cells are the source of colony-stimulating factor (CSF). 相似文献
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Amit Kumar Ram Balasubramaniyan Vairappan BH Srinivas 《World journal of gastroenterology : WJG》2020,26(45):7131-7152
BACKGROUNDAltered tight junction (TJ) proteins are correlated with carcinogenesis and tumor development. Nimbolide is a tetranotriterpenoid that has been shown to have antioxidant and anti-proliferative properties; however, its anticancer effects and molecular mechanism in hepatocellular carcinoma (HCC) remains obscure.AIMTo investigate the effect of nimbolide on TJ proteins, cell cycle progression, and hepatic inflammation in a mouse model of HCC. METHODSHCC was induced in male Swiss albino mice (CD-1 strain) by a single intraperitoneal injection of 100 mg/kg diethylnitrosamine (DEN) followed by 80 ppm N-nitrosomorpholine (NMOR) in drinking water for 28 wk. After 28 wk, nimbolide (6 mg/kg) was given orally for four consecutive weeks in DEN/NMOR induced HCC mice. At the end of the 32nd week, all the mice were sacrificed and blood and liver samples were collected for various analyses. Macroscopic examinations of hepatic nodules were assessed. Liver histology and HCC tumor markers such as alpha-fetoprotein (AFP) and glypican-3 were measured. Expression of TJ proteins, cell proliferation, and cell cycle markers, inflammatory markers, and oxidative stress markers were analyzed. In silico analysis was performed to confirm the binding and modulatory effect of nimbolide on zonula occludens 1 (ZO-1), nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB), and tumor necrosis factor alpha (TNF-α).RESULTSWe found nimbolide treatment at a concentration of 6 mg/kg to HCC mice reduced hepatic tumor size by 52.08% and tumor volume (P < 0.01), and delayed tumor growth in HCC mice with a concomitant reduction in tumor markers such as AFP levels (P < 0.01) and glypican-3 expression (P < 0.05). Furthermore, nimbolide treatment increased tight junction proteins such as ZO-1 and occludin expression (P < 0.05, respectively) and reduced ZO-1 associated nucleic acid binding protein expression (P < 0.001) in HCC mice liver. Nimbolide treatment to HCC mice also inhibited cell proliferation and suppressed cell cycle progression by attenuating proliferating cell nuclear antigen (P < 0.01), cyclin dependent kinase (P < 0.05), and CyclinD1 (P < 0.05) expression. In addition, nimbolide treatment to HCC mice ameliorated hepatic inflammation by reducing NF-κB, interleukin 1 beta and TNF-α expression (P < 0.05, respectively) and abrogated oxidative stress by attenuating 4-hydroxynonenal expression (P < 0.01). Molecular docking studies further confirmed that nimbolide interacts with ZO-1, NF-κB, and TNF-α.CONCLUSIONOur current study showed for the first time that nimbolide exhibits anticancer effect by reducing tumor size, tumor burden and by suppressing cell cycle progression in HCC mice. Furthermore, nimbolide treatment to HCC mice ameliorated inflammation and oxidative stress, and improved TJ proteins expression. Consequently, nimbolide could be potentially used as a natural therapeutic agent for HCC treatment, however further human studies are warranted. 相似文献
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DW Webb BH Bjornson MA Sargent J Hukin EE Thomas 《Archives of disease in childhood》1997,76(4):362-364
A 6 year old boy presented with meningoencephalitis and was found to have serological evidence of acute human herpes virus-6 (HHV-6) infection. He did not develop symptomatic seizures or the rash of exanthum subitum (roseola). His course was marked by severe spastic quadriparesis associated with radiological evidence of basal ganglia infarction. HHV-6 infection should be considered in any child with acute meningoencephalitis. 相似文献
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Objective : To report a new case of de novo 7q deletion distal to q35.
Methodology : Developmental, cytogenetic and audiological investigations were carried out in the assessment of this rare chromosomal condition.
Results : Moderate developmental delay, mild congenital microcephaly, growth retardation and conductive hearing impairment were found for this case of 46, XX, del(7)(q35).
Conclusions : The phenotype of 7q terminal deletion is highly variable. 相似文献
Methodology : Developmental, cytogenetic and audiological investigations were carried out in the assessment of this rare chromosomal condition.
Results : Moderate developmental delay, mild congenital microcephaly, growth retardation and conductive hearing impairment were found for this case of 46, XX, del(7)(q35).
Conclusions : The phenotype of 7q terminal deletion is highly variable. 相似文献