硬皮病皮损成纤维细胞整合素表达的免疫电镜观察*

目的：研究硬皮病皮损成纤维细胞整合素表达及细胞超微结构特征。方法：将培养的硬皮病皮损成纤维细胞置包被纤维粘连蛋白的培养瓶中作粘附培养,运用间接免疫胶体金技术在电镜下观察成纤维细胞表面整合素α5,β1亚基表达、分布特征及细胞超微结构变化。结果：硬皮病皮损成纤维细胞整合素α5,β1亚基表达均较正常成纤维细胞显著增加（P<0.01）,并呈簇集分布的特征;细胞内骨架成分微丝密集成束。结论：整合素α5,β1介导的纤维粘连蛋白与成纤维细胞相互作用在硬皮病时增强。     

Mean amplitude of intraocular pressure excursions: a new assessment parameter for 24-h pressure fluctuations in glaucoma patients

BackgroundIntraocular pressure (IOP) is important in the pathogenesis of glaucoma and its circadian fluctuations are important in the disease management; however, there are no adequate parameters to describe the fluctuations. This study investigates a new parameter, mean amplitude of intraocular pressure excursion (MAPE), and compares its ability in assessing 24-h IOP fluctuations with other ocular parameters.MethodsOnly the right eye was evaluated in each of the 79 healthy people and 164 untreated patients with primary open angle glaucoma (POAG). Each participant underwent 24-h IOP monitoring by measuring IOP every 2 h. IOP fluctuations were expressed as MAPE calculations and currently used parameters included mean IOP, standard deviation of IOP, max difference and area under the circadian IOP curve. Comprehensive ophthalmologic examinations were also performed. Associations between visual field deficits and IOP fluctuation parameters were investigated via partial least squares (PLS) regression. Diagnostic performance was evaluated with area under the receiver operating characteristic curves (ROC).ResultsCompared with healthy volunteers, the MAPE values in POAG patients were higher (4.16 ± 1.90 versus 2.45 ± 0.89, p < 0.01). In PLS regressions where visual field deficits were as dependent variable, MAPE had the highest score regarding variable importance in projection, and its standard regression coefficient was larger than other parameters. Diagnostic performance analysis showed the area under ROC of MAPE for glaucoma detection was 0.822 (0.768–0.868, p < 0.001).ConclusionsMAPE might be an effective parameter in clinic to characterise IOP circadian fluctuations.Subject terms: Medical research, Glaucoma     

Establishment of a Mouse IgA Nephropathy Model With the MBP‐20‐Peptide Fusion Protein

Here, we aimed to determine whether immunoglobulin‐A nephropathy (IgAN) could be induced in Balb/c mice by immunizing them with a fusion protein (MBP‐20 peptide) comprising the maltose‐binding protein (MBP) and a 20‐amino‐acid peptide derived from Staphylococcus aureus. A recombinant plasmid encoding the fusion protein was constructed and expressed in bacterial cells. The synthetic 20‐peptide was used to prepare the monoclonal antibody. Balb/c mice were immunized with the MBP‐20‐peptide fusion protein over a 21‐week course before renal histology was examined at the light and electron microscopic levels. Direct immunofluorescence staining with the anti‐20‐peptide monoclonal antibody was also performed using renal biopsy tissue from human IgAN patients as a comparison. IgA and IgG specific for the 20‐peptide in human and mice serum were detected. The IgAN experimental mice developed a clinical and pathological profile that closely resembled that of human IgAN patients, including the induction of hematuria and numerous histopathological features. Levels of IgA and IgG specific for the 20‐peptide were significantly increased in serum from the IgAN experimental mice and IgAN patients compared with control mice and non‐IgAN patients. In IgAN model mice, the anti‐20‐peptide antibody labeled glomeruli, while the antibody strongly labeled glomeruli and weakly labeled tubular epithelial cells in renal tissue from human IgAN patients. In conclusion, immunization with an MBP‐20‐peptide fusion protein is able to induce clinical and pathological features closely resembling IgAN in Balb/c mice, indicating a potentially useful role for the model in the study of IgAN and related diseases. Anat Rec 293:1729–1737, 2010. © 2010 Wiley‐Liss, Inc.     

Temperature-Acclimated Brown Adipose Tissue Modulates Insulin Sensitivity in Humans

In rodents, brown adipose tissue (BAT) regulates cold- and diet-induced thermogenesis (CIT; DIT). Whether BAT recruitment is reversible and how it impacts on energy metabolism have not been investigated in humans. We examined the effects of temperature acclimation on BAT, energy balance, and substrate metabolism in a prospective crossover study of 4-month duration, consisting of four consecutive blocks of 1-month overnight temperature acclimation (24°C [month 1] → 19°C [month 2] → 24°C [month 3] → 27°C [month 4]) of five healthy men in a temperature-controlled research facility. Sequential monthly acclimation modulated BAT reversibly, boosting and suppressing its abundance and activity in mild cold and warm conditions (P < 0.05), respectively, independent of seasonal fluctuations (P < 0.01). BAT acclimation did not alter CIT but was accompanied by DIT (P < 0.05) and postprandial insulin sensitivity enhancement (P < 0.05), evident only after cold acclimation. Circulating and adipose tissue, but not skeletal muscle, expression levels of leptin and adiponectin displayed reciprocal changes concordant with cold-acclimated insulin sensitization. These results suggest regulatory links between BAT thermal plasticity and glucose metabolism in humans, opening avenues to harnessing BAT for metabolic benefits.     

肿瘤坏死因子在重型肝炎发病中的作用

目的　探讨TNF α在肝炎发病中的作用及重症肝炎患者血清内毒素水平与TNF α活性水平之间的关系。方法　选择不同临床类型的肝炎患者 84人 ,正常对照组 18人 ,比较各型患者血清TNF α活性 ,并就血清内毒素水平与TNF α活性水平之间的关系进行了研究。结果　TNF α活性水平在各组间总的差别有显著性 (F =2 1.53,P <0 .0 1) ,呈现出重症肝炎 >CH(重 ) >CH(中 ) >CH(轻 ) >肝硬化 >AH ;且重症肝炎组明显高于其他各组 (P均 <0 .0 1) ,其它各组间差别无显著性。慢性乙肝 (重度 )合并G- 杆菌感染者和TNF α活性与内毒素水平呈正相关 (r =0 .9111,P >0 .0 5)。结论　TNF α可能参与了重症肝炎的发生 ,内毒素通过刺激单核巨噬细胞产生大量TNF α促进肝细胞的坏死。     

干扰素联合胸腺肽治疗慢性乙型肝炎62例

目的：观察干扰素α（ＩＮＦ－α）联合胸腺肽治疗慢性乙型肝炎（Ｃｈｒｏｎｉｃ Ｈｅｐａｔｉｔｉｓ Ｂ，ＣＨＢ）的疗效。方法：１２６例患者随机分为治疗组６２例，给ＩＦＮ－α３００万ＩＵ＋胸腺肽２０ｍｇ，均隔日１次；对照组６４例，单用ＩＮＦ－α３００万ＩＵ，隔日１次，疗程均为６个月。主要观察患者治疗前后症状、体征、病毒复制指标、肝功能指标的变化。结果：①两组患者在主要症状、体征方面改善明显（ｘ＾２＝７．４５，Ｐ〈０．０５）。②疗程结束时及１年后，治疗组患者ＨＢｅＡｇ及ＨＢＶ－ＤＮＡ的阴转率均显著高于对照组（ｘ＾２＝５．４７、ｘ＾２＝８．６１，Ｐ〈０．０５、Ｐ〈０．０１）。结论：两药联用能明显抑制ＨＢＶ复制，降低其反跳和病情复发。     

Photodynamic therapy inhibits p-glycoprotein mediated multidrug resistance via JNK activation in human hepatocellular carcinoma using the photosensitizer pheophorbide a

Background  

Multidrug resistance (MDR) is frequently observed after prolonged treatment in human hepatoma with conventional anti-tumor drugs, and photodynamic therapy (PDT) is a recently suggested alternative to overcome MDR. The therapeutic potential of PDT was evaluated in a multidrug resistance (MDR) human hepatoma cell line R-HepG2 with photosensitizer pheophorbide a (Pa).     

Adrenocortical function in critically ill patients 24 h after a single dose of etomidate

We compared the effects of single doses of etomidate and thiopentone on adrenocortical function in a randomised controlled clinical trial involving 35 critically ill patients who needed a general anaesthetic. Just before induction of anaesthesia, a baseline blood cortisol sample was taken. Twenty-four hours later we performed a short adrenocorticotrophic hormone stimulation test. No patient had a low cortisol level (< 160 nmol.l-1) at any time during the study. Baseline, pre-ACTH and post-ACTH cortisol levels were similar in the two groups. However, significantly more patients in the etomidate group had an ACTH-stimulated cortisol increment < 200 nmol.l-1. The clinical significance of these findings is not clear, but we conclude that single doses of etomidate may interfere with cortisol synthesis for at least 24 h in the critically ill.