Traditionally the evaluation of the cellular infiltrate and protein expression in skin tissue sections is done by manual quantification. However, for reliable evaluation of histology in the development of new anti-pso...Traditionally the evaluation of the cellular infiltrate and protein expression in skin tissue sections is done by manual quantification. However, for reliable evaluation of histology in the development of new anti-psoriatic treatments there is a need for a more time-efficient and reproducible method. To test the use of digital image analysis (DIA) in this situation we compared the assessment of immunohistochemically stained skin sections with themore traditionalmanual quantification (MQ) and semiquantitative analysis (SQA). The number of CD3+T cells and the expression of E-selectin were evaluated in stained paired skin biopsie s from 11 patients with chronic plaque psoriasis before and after initiation of anti-psoriasis therapy. We observed significant correlations between MQ and DIA for the number of T cells (epiderm is: r=0.88, P ≤0.01, dermis r=0.87, P ≤0.01). Both DIA and MQ were equally eff ective in detecting reductions of T-cell numbers in active-treated patients. M Q took 20 h, compared to 6 h for DIA.We also observed significant correlations b etween SQA and DIA for the expression of E-selectin (r=0.88, P ≤0.01), althoug h DIA was more sensitive than SQA to detect (early) changes. SQA took 10 h, comp ared to 4 h for DIA. In conclusion, the quantification of the inflammatory infil trate in psoriatic lesional skin by DIA generated similar results as MQ and SQA in a reliable, reproducible and higher time efficient fashion.展开更多
背景急性出血坏死型胰腺炎是临床常见的消化系统急症,肺损伤是其常见并发症和致死原因.黄芪注射液具有调节内分泌、增强免疫力、抑制病毒、抗炎、抗氧化应激等作用,但目前尚未见关于黄芪注射液在重症急性胰腺炎肺损伤中的相关研究.目的...背景急性出血坏死型胰腺炎是临床常见的消化系统急症,肺损伤是其常见并发症和致死原因.黄芪注射液具有调节内分泌、增强免疫力、抑制病毒、抗炎、抗氧化应激等作用,但目前尚未见关于黄芪注射液在重症急性胰腺炎肺损伤中的相关研究.目的分析黄芪注射液通过调控雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)/核糖体70S小亚基S6蛋白激酶(ribosome 70S small subunit S6 protein kinase,p70S6K)信号通路对急性出血坏死型胰腺炎(acute hemorrhagic necrotic pancreatitis,AHNP)肺损伤炎症反应的影响.方法48只成年SD大鼠简单随机化分为对照组、模型组、低、中、高黄芪注射液组、阳性对照组,各8只,记录各组胰腺与肺组织组织病理学变化,比较各组Schmidt评分、血清淀粉酶(amylase,AMS)Hofouaer评分、动脉血二氧化碳分压(PaCO_(2))、动脉血氧分压(PaO_(2))、炎症因子[肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)、白介素-6(interleukin-6,IL-6)]、mTOR/p70S6K信号通路蛋白[mTOR、p70S6K、p-p70S6K、p-mTOR、真核启动因子4E结合蛋白1(p-4E binding protein 1,4EBP1)]水平.结果对照组胰腺、肺组织无异常变化;模型组胰腺实质呈片状坏死、充血水肿,胰腺腺泡细胞与间质细胞大量破坏,小叶结构紊乱,大量炎症细胞浸润与红细胞溢出,肺泡结构排卵紊乱、间质水肿、炎性细胞浸润、肺泡间隔增宽、灶性或片状肺不张、出血;低、中、高黄芪注射液组胰腺与模型组相比,呈现出不同程度改善,且随黄芪注射液剂量增加,改善程度依次增加,其中高黄芪注射液组与阳性对照组组织病理呈现出相似特征;模型组Schmidt评分、AMS、Hofouaer评分PaCO_(2)均高于对照组,PaO_(2)均低于对照组(P<0.05);低、中、高黄芪注射液组Schmidt评分、AMS、Hofouaer评分PaCO_(2)依次降低,PaO_(2)依次升高(P<0.05);模型组TNF-α、IL-6高于对照组(P<0.05);低、中、高黄芪注射液组TNF-α、IL-6依次降低(P<0.05);模型组mTOR、p70S6K、p-p70S6K、p-mTOR、4EBP1高于对照组(P<0.05);低、中、高黄芪注射液组mTOR、p70S6K、p-p70S6K、p-mTOR、4EBP1依次降低(P<0.05).结论黄芪注射液可呈剂量依赖性改善AHNP血气指标、炎症反应、胰腺与肺组织病理状态,其机制可能是通过调控mTOR/p70S6K信号通路实现的,抑制mTOR/p70S6K信号通路可能为AHNP肺损伤的治疗提供了一个新思路.展开更多
目的:探讨胆总管结扎引起的胆汁淤积对小鼠肝脏细胞凋亡和炎性细胞浸润的影响。方法:采用胆总管结扎手术制备胆汁淤积小鼠模型;利用全自动生化分析仪检测小鼠血清肝脏生化指标水平;用末端核苷酸转移酶介导的脱氧三磷酸尿苷原位缺口末端...目的:探讨胆总管结扎引起的胆汁淤积对小鼠肝脏细胞凋亡和炎性细胞浸润的影响。方法:采用胆总管结扎手术制备胆汁淤积小鼠模型;利用全自动生化分析仪检测小鼠血清肝脏生化指标水平;用末端核苷酸转移酶介导的脱氧三磷酸尿苷原位缺口末端标记法(Terminal deoxynucleotidyl transferase-mediated dutp nick end labeling,TUNEL)检测小鼠肝脏细胞凋亡;用实时荧光定量PCR和免疫组织化学方法检测肝脏炎症相关基因表达情况。结果:通过胆总管结扎手术成功制备了梗阻性胆汁淤积小鼠模型;小鼠血清生化指标结果表明小鼠肝脏功能受损,胆总管结扎手术成功;胆总管结扎引起胆汁淤积后,肝脏细胞凋亡和坏死明显增加,炎症细胞浸润增强。结论:胆汁淤积导致肝脏细胞凋亡、坏死和炎症活动增强是胆总管结扎致肝纤维化过程中的重要表现。展开更多
炎症性肌病为一组少见的、慢性炎症性肌肉病变,与自身免疫紊乱相关,广义上分为多发性肌炎（polymyositis,PM）、皮肌炎（dermatomyositis,DM）与包涵体肌炎（inclusion body myositis,IBM）三类,以对称性四肢近端肌无力为典型表现,肌肉...炎症性肌病为一组少见的、慢性炎症性肌肉病变,与自身免疫紊乱相关,广义上分为多发性肌炎（polymyositis,PM）、皮肌炎（dermatomyositis,DM）与包涵体肌炎（inclusion body myositis,IBM）三类,以对称性四肢近端肌无力为典型表现,肌肉活检示肌肉内有炎症细胞浸润,并可累及肺脏、心脏等内脏器官。展开更多
Objective: To describe a series of 41 patients with fresh lesions of Sweet syndrome in which the histopathologic study demonstrated an inflammatory infiltrate mostly composed of histiocytoid mononuclear cells. Design:...Objective: To describe a series of 41 patients with fresh lesions of Sweet syndrome in which the histopathologic study demonstrated an inflammatory infiltrate mostly composed of histiocytoid mononuclear cells. Design: Histopathologic, immunohistochemical, and cytogenetic studies of the inflammatory infiltrate in a case series of histiocytoid Sweet syndrome. Setting: University departments of dermatology and a private laboratory of dermatopathology. Methods: Conventional histopathologic study as well as immunohistochemical investigations were performed using the alkaline phosphatase antialkaline phosphatase technique with a large panel of antibodies. In some cases, fluorescent in situ hybridization studies were performed to investigate the presence of the bcr/abl gene fusion. Results: Immunohistochemical studies demonstrated that most cells of the infiltrate showed immunoreactivity for CD15, CD43, CD45, CD68, MAC-386, HAM56, and lysozyme, which is consistent with a monocytic-histiocytic immunoprofile. However, intense myeloperoxidase reactivity was detected in most of the cells with histiocytic appearance, which raised the possibility of specific cutaneous involvement by myelogenous leukemia. Nevertheless, cytologic peripheral blood examinations, fluorescent in situ hybridization studies to investigate the bcr/abl gene fusion, and follow-up of the patients, taken all together, ruled out this possibility. Conclusions: This case series demonstrates that some fresh cutaneous lesions of Sweet syndrome are histopathologically characterized by an infiltrate mostly composed of cells that may be misinterpreted as histiocytes, when in fact they are immature myeloid cells. We named this histopathologic variant histiocytoid Sweet syndrome, which should not be mistaken with leukemia cutis or other inflammatory dermatoses that are histopathologically characterized by histiocytes interstitially arranged between collagen bundles of the dermis.展开更多
文摘Traditionally the evaluation of the cellular infiltrate and protein expression in skin tissue sections is done by manual quantification. However, for reliable evaluation of histology in the development of new anti-psoriatic treatments there is a need for a more time-efficient and reproducible method. To test the use of digital image analysis (DIA) in this situation we compared the assessment of immunohistochemically stained skin sections with themore traditionalmanual quantification (MQ) and semiquantitative analysis (SQA). The number of CD3+T cells and the expression of E-selectin were evaluated in stained paired skin biopsie s from 11 patients with chronic plaque psoriasis before and after initiation of anti-psoriasis therapy. We observed significant correlations between MQ and DIA for the number of T cells (epiderm is: r=0.88, P ≤0.01, dermis r=0.87, P ≤0.01). Both DIA and MQ were equally eff ective in detecting reductions of T-cell numbers in active-treated patients. M Q took 20 h, compared to 6 h for DIA.We also observed significant correlations b etween SQA and DIA for the expression of E-selectin (r=0.88, P ≤0.01), althoug h DIA was more sensitive than SQA to detect (early) changes. SQA took 10 h, comp ared to 4 h for DIA. In conclusion, the quantification of the inflammatory infil trate in psoriatic lesional skin by DIA generated similar results as MQ and SQA in a reliable, reproducible and higher time efficient fashion.
文摘背景急性出血坏死型胰腺炎是临床常见的消化系统急症,肺损伤是其常见并发症和致死原因.黄芪注射液具有调节内分泌、增强免疫力、抑制病毒、抗炎、抗氧化应激等作用,但目前尚未见关于黄芪注射液在重症急性胰腺炎肺损伤中的相关研究.目的分析黄芪注射液通过调控雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)/核糖体70S小亚基S6蛋白激酶(ribosome 70S small subunit S6 protein kinase,p70S6K)信号通路对急性出血坏死型胰腺炎(acute hemorrhagic necrotic pancreatitis,AHNP)肺损伤炎症反应的影响.方法48只成年SD大鼠简单随机化分为对照组、模型组、低、中、高黄芪注射液组、阳性对照组,各8只,记录各组胰腺与肺组织组织病理学变化,比较各组Schmidt评分、血清淀粉酶(amylase,AMS)Hofouaer评分、动脉血二氧化碳分压(PaCO_(2))、动脉血氧分压(PaO_(2))、炎症因子[肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)、白介素-6(interleukin-6,IL-6)]、mTOR/p70S6K信号通路蛋白[mTOR、p70S6K、p-p70S6K、p-mTOR、真核启动因子4E结合蛋白1(p-4E binding protein 1,4EBP1)]水平.结果对照组胰腺、肺组织无异常变化;模型组胰腺实质呈片状坏死、充血水肿,胰腺腺泡细胞与间质细胞大量破坏,小叶结构紊乱,大量炎症细胞浸润与红细胞溢出,肺泡结构排卵紊乱、间质水肿、炎性细胞浸润、肺泡间隔增宽、灶性或片状肺不张、出血;低、中、高黄芪注射液组胰腺与模型组相比,呈现出不同程度改善,且随黄芪注射液剂量增加,改善程度依次增加,其中高黄芪注射液组与阳性对照组组织病理呈现出相似特征;模型组Schmidt评分、AMS、Hofouaer评分PaCO_(2)均高于对照组,PaO_(2)均低于对照组(P<0.05);低、中、高黄芪注射液组Schmidt评分、AMS、Hofouaer评分PaCO_(2)依次降低,PaO_(2)依次升高(P<0.05);模型组TNF-α、IL-6高于对照组(P<0.05);低、中、高黄芪注射液组TNF-α、IL-6依次降低(P<0.05);模型组mTOR、p70S6K、p-p70S6K、p-mTOR、4EBP1高于对照组(P<0.05);低、中、高黄芪注射液组mTOR、p70S6K、p-p70S6K、p-mTOR、4EBP1依次降低(P<0.05).结论黄芪注射液可呈剂量依赖性改善AHNP血气指标、炎症反应、胰腺与肺组织病理状态,其机制可能是通过调控mTOR/p70S6K信号通路实现的,抑制mTOR/p70S6K信号通路可能为AHNP肺损伤的治疗提供了一个新思路.
文摘目的:探讨胆总管结扎引起的胆汁淤积对小鼠肝脏细胞凋亡和炎性细胞浸润的影响。方法:采用胆总管结扎手术制备胆汁淤积小鼠模型;利用全自动生化分析仪检测小鼠血清肝脏生化指标水平;用末端核苷酸转移酶介导的脱氧三磷酸尿苷原位缺口末端标记法(Terminal deoxynucleotidyl transferase-mediated dutp nick end labeling,TUNEL)检测小鼠肝脏细胞凋亡;用实时荧光定量PCR和免疫组织化学方法检测肝脏炎症相关基因表达情况。结果:通过胆总管结扎手术成功制备了梗阻性胆汁淤积小鼠模型;小鼠血清生化指标结果表明小鼠肝脏功能受损,胆总管结扎手术成功;胆总管结扎引起胆汁淤积后,肝脏细胞凋亡和坏死明显增加,炎症细胞浸润增强。结论:胆汁淤积导致肝脏细胞凋亡、坏死和炎症活动增强是胆总管结扎致肝纤维化过程中的重要表现。
文摘炎症性肌病为一组少见的、慢性炎症性肌肉病变,与自身免疫紊乱相关,广义上分为多发性肌炎（polymyositis,PM）、皮肌炎（dermatomyositis,DM）与包涵体肌炎（inclusion body myositis,IBM）三类,以对称性四肢近端肌无力为典型表现,肌肉活检示肌肉内有炎症细胞浸润,并可累及肺脏、心脏等内脏器官。
文摘Objective: To describe a series of 41 patients with fresh lesions of Sweet syndrome in which the histopathologic study demonstrated an inflammatory infiltrate mostly composed of histiocytoid mononuclear cells. Design: Histopathologic, immunohistochemical, and cytogenetic studies of the inflammatory infiltrate in a case series of histiocytoid Sweet syndrome. Setting: University departments of dermatology and a private laboratory of dermatopathology. Methods: Conventional histopathologic study as well as immunohistochemical investigations were performed using the alkaline phosphatase antialkaline phosphatase technique with a large panel of antibodies. In some cases, fluorescent in situ hybridization studies were performed to investigate the presence of the bcr/abl gene fusion. Results: Immunohistochemical studies demonstrated that most cells of the infiltrate showed immunoreactivity for CD15, CD43, CD45, CD68, MAC-386, HAM56, and lysozyme, which is consistent with a monocytic-histiocytic immunoprofile. However, intense myeloperoxidase reactivity was detected in most of the cells with histiocytic appearance, which raised the possibility of specific cutaneous involvement by myelogenous leukemia. Nevertheless, cytologic peripheral blood examinations, fluorescent in situ hybridization studies to investigate the bcr/abl gene fusion, and follow-up of the patients, taken all together, ruled out this possibility. Conclusions: This case series demonstrates that some fresh cutaneous lesions of Sweet syndrome are histopathologically characterized by an infiltrate mostly composed of cells that may be misinterpreted as histiocytes, when in fact they are immature myeloid cells. We named this histopathologic variant histiocytoid Sweet syndrome, which should not be mistaken with leukemia cutis or other inflammatory dermatoses that are histopathologically characterized by histiocytes interstitially arranged between collagen bundles of the dermis.
