In vivo imaging of leukocyte trafficking in blood vessels and tissues

Selective recruitment of blood-borne leukocytes to tissues and their proper positioning within them is crucial for the many integrated functions of the immune system. Intravital microscopy (IVM) techniques have been employed for more than a century to study these events at the single-cell level in living animals. Conventional video-based IVM allows the visualization of extremely rapid adhesion events at the interface between blood and tissue. Multiphoton IVM is a relatively new tool for imaging the slower dynamics of cell migration and cell-cell interactions in the extravascular space in three dimensions. Fueled by the burgeoning development of sophisticated fluorescent markers and increasingly powerful imaging tools, we are currently witnessing the emergence of a new field in immuno-imaging, in which leukocyte function and cell-cell communication is explored in a truly physiological context.     

Age, alcohol consumption, and all-cause mortality

PURPOSE: Numerous epidemiological studies on middle aged men suggest that moderate alcohol consumption lowers all-cause mortality. Uncertainty exists whether this finding also applies to younger adults. METHODS: The authors studied the age specific association between alcohol consumption and all-cause mortality in a cohort of 19,943 male employees in the German construction industry (age range 25-64 years) who underwent an occupational health examination between 1986 and 1992 and were followed with respect to vital status over an average period of 10 years. Information on alcohol consumption at baseline examination relied on self report and strongly correlated with biological markers of alcohol consumption. Covariates considered in the proportional hazard regression analysis included age, nationality, smoking status, and comorbidity. RESULTS: Age specific analysis revealed that the J/U-shaped association between alcohol consumption and all-cause mortality is limited to men aged 35 years and above. In contrast, a linear positive dose-response relationship was observed for men aged 25 to 34 years (p-trend=0.02). CONCLUSIONS: Recommendations regarding alcohol consumption and potential health benefits should not be generalized to all ages.     

The effect of CYP19 and COMT polymorphisms on exercise-induced fat loss in postmenopausal women

OBJECTIVE: To examine whether genetic polymorphisms in CYP19 [intron 4 (TTTA)n; n = 7 to 13 and a 3-base pair deletion, which is in strong linkage disequilibrium with the seven repeat] and COMT (Val108/158Met) modified the change in BMI, total and percentage body fat, or subcutaneous and intra-abdominal fat during a year-long exercise intervention trial. These genes metabolize estrogens and androgens, which are important in body fat regulation. RESEARCH METHODS AND PROCEDURES: A randomized intervention trial was used, with an intervention goal of 225 min/wk of moderate-intensity exercise for one year. Participants (n = 173) were postmenopausal, 50 to 75 years old, sedentary, overweight or obese, and not taking hormone therapy at baseline. RESULTS: Exercisers with two vs. no CYP19 11-repeat alleles had a larger decrease in total fat (-3.1 kg vs. -0.5 kg, respectively, p = 0.01) and percentage body fat (-2.4% vs. -0.6%, respectively, p = 0.001). Exercisers with the COMT Met/Met vs. Val/Val genotype had a smaller decrease in percentage fat (-0.7% vs. -1.9%, respectively, p = 0.05). Among exercisers, women with the COMT Val/Val genotype and at least one copy of the CYP19 11-repeat allele vs. those with neither genotype/allele had a significantly larger decrease in BMI (-1.0 vs. +0.1 kg/m2, respectively, p = 0.009), total fat (-2.9 vs. -0.5 kg, respectively, p = 0.004), and percentage body fat (-2.6% vs. -0.4%, respectively, p < 0.001). DISCUSSION: Genetic polymorphisms in CYP19 and COMT may be important for body fat regulation and possibly modify the effect of exercise on fat loss in postmenopausal women.     

Immunohistochemical study in dural arteriovenous fistula and possible role of ephrin-B2 for development of dural arteriovenous fistula

Background Although there were several clinical and experimental studies discussing the pathogenesis of dural arteriovenous fistula (DAVF), the pathological process leading to intracranial DAVF so far remains unknown. In this study, we investigated the expression of vascular growth factors in order to elucidate the possible role of these factors for the development of DAVF and to study the biological activity of this uncommon lesion.Methods We examined the histological features, proliferative and angiogenic capacities of the tissue specimens obtained from 6 patients who underwent surgery at our institution. Immunohistochemical staining for vascular endothelial growth factor (VEGF), its receptors FIk-1 and Fit-1, ephrin-B2, MIB-1 and proliferating cell nuclear antigen (PCNA) was performed using standard immunohistochemical techniques.Results A positive immunostaining was found for all antibodies studied except MIB-1, whereas nuclear endothelial expression of PCNA was observed in only 3/6 cases. VEGF stained positive in all of the available specimens (6/6). FIk-1 showed a positive immunoreaction in only 2/6 cases and Fit-1 in 4/6 cases. Ephrin-B2 was expressed in the majority (5/6) of the cases.Conclusions These results support the hypothesis that DAVFs might be acquired dynamic vascular malformations with low biological activity. Vascular growth factors like VEGF and ephrin-B2 might play a pivotal role in the formation of DAVF.     

己酮可可碱对外源性过敏性肺泡炎治疗作用的初步研究

目的　通过研究己酮可可碱 (POF)对外源性过敏性肺泡炎 (EAA)患者肺泡巨噬细胞(AM)产生的细胞因子的作用 ,探讨其治疗EAA的可能性 ,并与地塞米松 (DEX)的作用进行比较。方法　入选EAA患者 9例 ,通过支气管肺泡灌洗收AM ,并以 10 %RPMI为培养液或 10 %RPMI加内毒素 (LPS ,10 0 μg/L) ;或分别加入浓度为 0 0 1mmol/L、0 1mmol/L、1mmol/L的POF ;或加入 0 1mmol/LDEX进行AM培养 2 4h。用ELISA方法测定培养上清液中细胞因子含量。结果　POF可抑制EAA患者AM自发释放的TNFα和IL 10 ,此作用有剂量依赖关系 (P <0 0 0 1和P <0 0 5 )。POF对其他自发释放的细胞因子则无影响。 0 1mmol/LDEX只抑制自发释放的TNFα(P <0 0 5 )。除IL 1β和可溶性肿瘤坏死因子受体外 ,POF和 0 1mmol/LDEX均抑制LPS刺激的其他细胞因子的释放 (P <0 0 0 1或P <0 0 1或P <0 0 5 )。结论　POF对EAA的炎症有一定的抑制作用 ,然而POF治疗EAA及其他肺部疾病的临床价值 ,需要进一步的临床试验来评价。