Expression of blood group antigens including HLA markers in human adult liver

The localisation of the principal blood group antigens has been studied in human liver. These blood group antigens included the erythrocyte antigens and the antigen of the major histocompatibility complex. This study was performed by the indirect immunofluorescence technique using polyclonal antibodies of human or animal origin and monoclonal antibodies from hybridomas. This study has shown that the normal hepatocyte is lacking in blood group antigens. On the contrary, the biliary cell was rich in antigenic markers: the main antigens expressed were Lewis, Pr, HLA-A and B antigens. In Kupffer cells, only i and HLA-DR antigens were clearly expressed. The endothelial cells of blood vessels mainly show A, B, H, HLA-A and B antigens; HLA-DR and Pr are slightly expressed. HLA-DR antigens were more strongly expressed on veins than on arteries. Dendritic cells have been identified in the portal space of human liver. They bore i and HLA-DR antigens.     

Pharmacokinetics of cerivastatin in renal impairment are predicted by low serum albumin concentration rather than by low creatinine clearance

The influence of renal impairment on the clearance of the new HMG-CoA reductase inhibitor cerivastatin was evaluated. A single oral dose of 300 microg cerivastatin was given to 18 patients with different degrees of renal impairment and 6 healthy controls. Concentrations of total cerivastatin, its fraction unbound, and the total concentrations of the active metabolites M1 and M23 were measured in plasma. Serum concentrations of unbound cerivastatin were calculated for each individual from the concentration of total cerivastatin and cerivastatin's fraction unbound at t = 2.5 hours. In contradiction to what had been expected, renal impairment significantly influenced the pharmacokinetics of cerivastatin. The best correlation to the AUC and Cmax of unbound cerivastatin was found with serum albumin concentration. Also, serum albumin concentration was the only factor significantly correlated to t 1/2 of cerivastatin. Significant but slighter correlation with the AUC and Cmax of unbound cerivastatin was also observed for creatinine clearance and cerivastatin's fraction unbound, while no correlation was observed with total plasma protein. No significant correlation of creatinine clearance, serum albumin concentration, fu, or total plasma protein concentration with the AUC and Cmax of total cerivastatin or the AUC, Cmax or t 1/2 of M1 and M23 was observed. The authors conclude that low serum albumin concentration rather than low creatinine clearance predicts the pharmacokinetics of cerivastatin in renal impairment.     

Ewing’s肉瘤细胞X-射线照射后TNF-α和TGF-β mRNA表达的研究

 目的　研究Ewing’s肉瘤细胞系 (RM 82 )X 射线外照射后肿瘤坏死因子 (TNF α)和转化生长因子 (TGF β)mRNA表达水平的变化 ,探讨X 射线诱导内源性TNF α和TGF β产生的可能性及意义。 方法　应用实时荧光RT PCR ,检测接受不同剂量X 线照射 (2Gy ,5Gy ,10Gy ,2 0Gy ,30Gy ,4 0Gy)和受照后不同时间 (1h ,3h ,6h ,12h ,2 4h ,4 8h ,72h)。TNF α和TGF βmRNA表达水平的变化。 结果　RM 82细胞TNF αmRNA表达水平较外照射前显著升高。一方面受照后TNF αmRNA表达逐渐升高 ,照射剂量达 4 0Gy时TNF αmRNA表达水平达高峰 ,为正常对照组的 10 8倍 ;另一方面 ,照射后 3h后TNF αmRNA表达逐渐升高 ,6h达高峰 ,为正常对照组的 18倍。相反 ,TGF βmRNA表达水平X 射线照射前后无显著变化。结论　Ewing’s肉瘤细胞系 (RM 82 )接受X 线照射后TNF αmRNA表达明显升高 ,且呈现时间、剂量依赖性。放射治疗可诱导Ewing’s肉瘤细胞系 (RM 82...     

Erythromycin treatment for gastrointestinal dysmotility in preterm infants

To report our clinical experience on the use of oral erythromycin for the treatment of severe gastrointestinal dysmotility in preterm infants.

Methodology:

A case series study of seven preterm infants (six were very low birthweight) with severe intestinal dysmotility in a tertiary neonatal centre.

Results:

All responded favourably without adverse effects and tolerated full enteral feeding within 1–2 weeks of the commencement of the drug.

Conclusions:

As prolonged total parenteral nutrition carries significant risk of complications, this therapy could be considered in selected preterm infants who fail to establish enteral feeding after an extended period, and in whom an anatomically obstructive lesion of the gastrointestinal tract has been excluded. Meanwhile, we would caution against the widespread implementation of this therapeutic approach until formal evaluation by randomized controlled trials have established the exact role of erythromycin, or its analogues, in the treatment of intestinal dysmotility in preterm infants.     

Human burst-forming units-erythroid need direct interaction with stem cell factor for further development

To understand the factors that regulate the early growth and development of immature erythroid progenitor cells, the burst-forming units-erythroid (BFU-E), it is necessary to have both highly purified target cells and a medium free of serum. When highly purified human blood BFU-E were cultured in a serum-free medium adequate for the growth of later erythroid progenitors, BFU-E would not grow even with the addition of recombinant human interleukin-3 (rIL-3), known to be essential for these cells. However, the addition of recombinant human stem cell factor (rSCF), which supports germ cell and pluripotential stem cell growth, stimulated BFU-E to grow equally well in serum-free as in serum-containing medium. Limiting dilution studies showed that rSCF acts directly on the BFU-E that do not require accessory cells for growth. Furthermore, rSCF was necessary for BFU-E development during the initial 7 days of culture, until these cells reached the stage of the late progenitors, the colony-forming units-erythroid (CFU-E). These studies indicate that early erythropoiesis is dependent on the direct action of SCF that not only affects early stem cells but is continually necessary for the further development of committed erythroid progenitor cells until the CFU-E stage of maturation.     

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma

Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.     

Effects of Deletion of ERα in Osteoblast‐Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice

Estrogen receptor alpha (ERα) has been implicated in bone's response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed‐background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell–specific ERαKO mice. Therefore, we crossed ERα floxed (ERα^fl/fl) and osteocalcin‐Cre (OC‐Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC‐ERαKO) and littermate controls (LC). At 10 weeks of age, the left tibia was loaded in vivo for 2 weeks. We analyzed bone mass through micro‐CT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared with LC, female pOC‐ERαKO mice had decreased cortical and cancellous bone mass, whereas male pOC‐ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC‐ERαKO female L₅ vertebrae and with increased maximum moment in pOC‐ERαKO male femora. Female pOC‐ERαKO mice responded more to mechanical loading, whereas the response of pOC‐ERαKO male animals was similar to their littermate controls. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.