Astrocytes enhance glioblastoma growth

Glioblastoma (GBM) is a deadly disease with a need for deeper understanding and new therapeutic approaches. The microenvironment of glioblastoma has previously been shown to guide glioblastoma progression. In this study, astrocytes were investigated with regard to their effect on glioblastoma proliferation through correlative analyses of clinical samples and experimental in vitro and in vivo studies. Co-culture techniques were used to investigate the GBM growth enhancing potential of astrocytes. Cell sorting and RNA sequencing were used to generate a GBM-associated astrocyte signature and to investigate astrocyte-induced GBM genes. A NOD scid GBM mouse model was used for in vivo studies. A gene signature reflecting GBM-activated astrocytes was associated with poor prognosis in the TCGA GBM dataset. Two genes, periostin and serglycin, induced in GBM cells upon exposure to astrocytes were expressed at higher levels in cases with high “astrocyte signature score”. Astrocytes were shown to enhance glioblastoma cell growth in cell lines and in a patient-derived culture, in a manner dependent on cell–cell contact and involving increased cell proliferation. Furthermore, co-injection of astrocytes with glioblastoma cells reduced survival in an orthotopic GBM model in NOD scid mice. In conclusion, this study suggests that astrocytes contribute to glioblastoma growth and implies this crosstalk as a candidate target for novel therapies.     

磁共振弥散加权成像鉴别脑脓肿和坏死囊变脑肿瘤

目的探讨磁共振弥散加权成像(DWI)鉴别诊断脑脓肿和坏死囊变脑肿瘤的价值.方法6例脑脓肿和13例脑肿瘤(8例胶质瘤和5例转移瘤),行常规MR和DWI检查.应用1.5 T磁共振机SE-EPI序列,取b*1000 s/mm2,b=0s/mm2获得DWI图像.同时测量感兴趣区的ADC值,行两个独立样本秩和检验.结果6例脑脓肿5例DWI图像表现为高信号,ADC值为(0.33±0.11)×10-3 mm2/s,13例脑肿瘤中12例坏死囊变部分DWI图像表现为低信号,ADC值为(2.46±0.49)×10-3 mm2/s.结论磁共振弥散加权成像能为鉴别诊断脑脓肿和坏死囊变脑肿瘤提供很有价值的信息,帮助提高诊断的正确性.     

大鼠急性肺栓塞后hnRNP-E1的表达及胶原代谢的变化

目的 研究大鼠急性肺栓塞模型肺组织中异源性核糖核蛋白E1(heterogeneous nuclear ribonucleoprote E1, hnRNP-E1)的表达变化及其对胶原代谢的影响.方法 建立大鼠急性肺栓塞模型,分别在急性肺栓塞后1、2、7和21 d开胸取出肺组织,然后提取肺组织的总RNA和总蛋白,以正常大鼠为对照组,采取半定量RT-PCR的方法研究hnRNP-E1在mRNA水平表达的变化;采用Western blot方法进一步验证hnRNP-E1在蛋白水平表达的变化.采用Northern blot法分析大鼠肺组织中Collagen α1(Ⅰ)(COL1A1)和Collagen α1(Ⅲ)(COL3A1)在肺栓塞后mRNA水平的表达变化;采用羟脯氨酸(HYP)和Masson染色观察急性肺栓塞3周后肺组织内的胶原沉积状况.结果 在大鼠急性肺栓塞后的不同时间点,hnRNP-E1的mRNA水平和蛋白水平的表达均有显著升高.大鼠急性肺栓塞后肺组织中COL1A1的mRNA表达水平有明显升高,但是COL3A1的mRNA表达水平无显著变化.HYP分析和Masson染色均显示急性肺栓塞3周后肺组织内的胶原沉积明显增加.结论 大鼠急性肺栓塞后肺组织内hnRNP-E1的表达升高,可能促进了COL1A1的蛋白表达和胶原在肺部的沉积.     

The use of MRI in the investigation of leg oedema.

Magnetic resonance imaging (MRI) was used in the diagnosis of various conditions giving rise to leg oedema, with special attention to the oedema after femoro-distal vascular reconstruction for obliterative atherosclerosis (n = 14). Patients with deep venous thrombosis (n = 6), chronic lymphoedema (n = 6) and closed muscular compartment syndrome (n = 2) were also investigated. Leg volume increase was measured according to the formula of a truncated cone. Interstitial fluid hydrostatic pressure (Pif) was recorded with the wick-in-needle technique. Spin echo series with 10 mm transverse slices were obtained with MRI. Following vascular reconstructions, leg volume increased 26% on the operated side. In the operated leg, no gradient in Pif was found between the posterior muscular compartment and the subcutaneous tissue. However, there was a significantly higher Pif in the subcutaneous tissue compared to the anterior muscular compartment (p less than 0.05). In the operated group, MRI revealed oedema around the entire circumference of the leg, mainly restricted to the subcutaneous tissue. In contrast, oedema of the leg muscles, particularly in the posterior compartments, was typical for patients having deep venous thrombosis. The group with chronic lymphoedema showed circumferential subcutaneous oedema alone or in combination with a fibrotic honeycomb pattern. Oedema of the affected muscular compartment was easily observed in patients who had a closed compartment syndrome. In conclusion, the use of MRI is promising in the investigation of conditions giving rise to leg oedema. It is likely that the formation of post-reconstructive oedema is taking place in the subcutaneous tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

The association between smoking and the prevalence of intermittent claudication

The objective of this study was to investigate the association between smoking and the prevalence of intermittent claudication (IC). Between 1995 and 1997, all residents aged 20 years or older in Nord-Tr?ndelag County, Norway, were invited to take part in the Nord-Tr?ndelag Health Study (Helseunders?kelsen i Nord-Tr?ndelag: HUNT 2). A total of 19748 participants aged 40-69 years attended. Responses to 12 questions on IC (including a Norwegian translation of the Edinburgh Claudication Questionnaire) had been previously tested against the ankle-brachial pressure index (ABPI < 0.9), and an algorithm of the best test properties was used to identify people with IC. Using logistic regression analysis we computed age-adjusted prevalence odds ratios (OR) for the association between smoking and IC. Both current (ORmen = 3.8, confidence interval (CI) 2.1-6.7, ORwomen = 2.2, CI 1.4-3.4) and former smokers (ORmen = 1.7, CI 0.9-3.2, ORwomen = 1.7, CI 1.1-2.7) had a higher prevalence of IC compared with those who had never smoked, and individuals who had stopped smoking more than 20 years previously had a substantially lower prevalence of IC (ORmen = 0.2, CI 0.1-0.5, ORwomen = 0.4, CI 0.2-0.8) than current smokers. We found no association between passive smoking and IC in either men or women. Current and previous smoking habits were positively associated with the prevalence of IC, and smoking cessation was negatively associated in men and women. Passive smoking was not associated with IC in this study.     

Endocrine systems in juvenile anadromous and landlocked Atlantic salmon (Salmo salar): seasonal development and seawater acclimation

The present study compares developmental changes in plasma levels of growth hormone (GH), insulin-like growth factor I (IGF-I) and cortisol, and mRNA levels of their receptors and the prolactin receptor (PRLR) in the gill of anadromous and landlocked Atlantic salmon during the spring parr-smolt transformation (smoltification) period and following four days and one month seawater (SW) acclimation. Plasma GH and gill GH receptor (GHR) mRNA levels increased continuously during the spring smoltification period in the anadromous, but not in landlocked salmon. There were no differences in plasma IGF-I levels between strains, or any increase during smoltification. Gill IGF-I and IGF-I receptor (IGF-IR) mRNA levels increased in anadromous salmon during smoltification, with no changes observed in landlocked fish. Gill PRLR mRNA levels remained stable in both strains during spring. Plasma cortisol levels in anadromous salmon increased 5-fold in May and June, but not in landlocked salmon. Gill glucocorticoid receptor (GR) mRNA levels were elevated in both strains at the time of peak smoltification in anadromous salmon, while mineralocorticoid receptor (MR) mRNA levels remained stable. Only anadromous salmon showed an increase of gill 11beta-hydroxysteroid dehydrogenase type-2 (11beta-HSD2) mRNA levels in May. GH and gill GHR mRNA levels increased in both strains following four days of SW exposure in mid-May, whereas only the anadromous salmon displayed elevated plasma GH and GHR mRNA after one month in SW. Plasma IGF-I increased after four days in SW in both strains, decreasing in both strains after one month in SW. Gill IGF-I mRNA levels were only increased in landlocked salmon after 4days in SW. Gill IGF-IR mRNA levels in SW did not differ from FW levels in either strain. Gill PRLR mRNA did not change after four days of SW exposure, and decreased in both strains after one month in SW. Plasma cortisol levels did not change following SW exposure in either strain. Gill GR, 11beta-HSD2 and MR mRNA levels increased after four days in SW in both strains, whereas only the anadromous strain maintained elevated gill GR and 11beta-HSD2 mRNA levels after one month in SW. The results indicate that hormones and receptors of the GH and cortisol axes are present at significantly lower levels during spring development and SW acclimation in landlocked relative to anadromous salmon. These findings suggest that attenuation of GH and cortisol axes may, at least partially, result in reduced preparatory upregulation of key gill ion-secretory proteins, possibly a result of reduced selection pressure for marine adaptations in landlocked salmon.