A Model for Transport and Dispersion in the Circulatory System Based on the Vascular Fractal Tree

Materials are distributed throughout the body of mammals by fractal networks of branching tubes. Based on the scaling laws of the fractal structure, the vascular tree is reduced to an equivalent one-dimensional, tube model. A dispersion–convection partial differential equation with constant coefficients describes the heterogeneous concentration profile of an intravascular tracer in the vascular tree. A simple model for the mammalian circulatory system is built in entirely physiological terms consisting of a ring shaped, one-dimensional tube which corresponds to the arterial, venular, and pulmonary trees, successively. The model incorporates the blood flow heterogeneity of the mammalian circulatory system. Model predictions are fitted to published concentration-time data of indocyanine green injected in humans and dogs. Close agreement was found with parameter values within the expected physiological range. © 2003 Biomedical Engineering Society. PAC2003: 8710+e, 8719Hh, 8719Uv     

Intracellular targeting and protein kinase C in vascular smooth muscle cells: specific effects of different membrane-bound receptors

Protein kinase C is an important second messenger system, which is translocated from the cytosol to the cell membrane upon cell stimulation. We used confocal microscopy to study the spatial distribution of protein kinase C isoforms after stimulation of cultured vascular smooth muscle cells with different agonists. First, we analysed the effects of angiotensin II and platelet-derived growth factor (PDGF). Confocal microscopy showed a rapid assembly of PKC α along cytosolic fibres followed by a translocation towards the nucleus with angiotensin II. PDGF engendered a similar, but much slower response; however, a cytoskeletal distribution was not observed. We then investigated the effects of thrombin and bFGF on nuclear translocation. bFGF induced a rapid translocation of the isoform towards the perinuclear region and into the nucleus. bFGF had a similar effect on PKC ?. In contrast, thrombin had a smaller effect on nuclear translocation of PKC α and did not influence PKC ?, but instead induced a rapid nuclear translocation of PKC ζ. Thus, tyrosine kinase receptor activation via bFGF induces a rapid association of PKC α and ? within nuclear structures. Our results show that agonists cause, not only a translocation of protein kinase C isoforms into the cell membrane but also into the cell nucleus. Lastly, we analyzed the nuclear immunoreactivity of the PKC isoforms α, δ,? and ζ in vascular smooth muscle cells during the cell cycle. Resting cells were stimulated with foetal calf serum (FCS, 10%), which translocated PKC α and ? to the perinuclear region and into the nucleus, while PKC δ and ζ showed no increase in nuclear immunoreactivity. After 4 h of FCS, the nuclear immunoreactivity for PKC α and ? was reduced to or below control values. At 8 h, increased nuclear expression of isoforms α,? and ζ was observed, while isoform δ was not affected. Our results demonstrate a complex spatial and temporal regulation of PKC isoforms in response to vasoactive hormones and growth factors. We suggest that protein kinase C may be important for nuclear signaling and demonstrate that nuclear translocation of PKC isoforms is differentially regulated during the cell cycle.     

Hypofluorescent spots in indocyanine green angiography of peau d‘orange and fundus

Purpose. Hypofluorescent spots were seen inindocyanine green (ICG) angiography of peau dorangefundus in eyes with angioid streaks. Origin of the hypofluorescentspots were examined with attention to their correlationwith a peau dorange appearance of the central fundususing a computer-assisted image comparison system. Methods. ICG angiography was performed in 5 patientshaving peau dorange appearance of fundus using ascanning laser ophthalmoscope (SLO) and a digitalvideo-fundus camera. The same central fundus areas corresponding to hypofluorescent spots in an ICGangiogram were then digitally identified in afluorescein angiogram and in a red-free picture in all10 eyes of the 5 patients. Monochromatic lightobservation was also performed with a dark fieldobservation using a SLO to see subretinal orintrachoroidal pigment clumping. Results. In no patient, the areas identified withhypofluorescent spots did show relevant changes ina fluorescein angiogram or a red-free picture. SLOexamination revealed not perfusion defect at the sameareas. The dark field observation showed no pigmentclumping at the peripapillary and papillomacularbundle regions where hypofluorescent spots were seen.Conclusions: Hypofluorescent spots seen in ICGangiograms did not show exact consistency with peau dorange changes in their location and shape. Perfusion defects or blocking by pigments were not acause of hypofluorescent spots. The scatteredhypofluorescent spots were considered to be relevantwith irregular affinity of the fundus to ICG dye.     

Ca2+ activation of hSlo K+ channel is suppressed by N-terminal GFP tag

The human slow poke (hSlo) K+ channel was tagged with GFP (green fluorescent protein) at the N-terminus of its alpha-subunit. The fusion protein was expressed transiently in HEK293 cells; it formed functional voltage-gated channels as shown by whole cell patch-clamp measurements. However, the tag lowered the voltage dependence of gating and it suppressed the typical left-shift of gating by intracellular binding of Ca2+. The location of the GFP-tagged N-terminus was confirmed to be on the extracellular side by application of a monoclonal antibody to nonpermeabilized cells. Structural interpretations of the effects are discussed.     

Prognostic value of galactose elimination capacity,aminopyrine breath test,and ICG clearance in patients with cirrhosis

Seventy-eight patients with cirrhosis were prospectively followed for up to 20 months, on the average. At entry into the study, galactose elimination capacity, aminopyrine breath test, and ICG clearance were measured. At the end of the study, 27 patients had died. Univariate analysis using the Kaplan-Meier method showed that both quantitative liver function tests (galactose elimination capacity:P<0.025; aminopyrine breath test:P<0.001; ICG clearance:P<0.005) and common clinical and biochemical data (encephalopathy:P<0.001; ascites:P<0.001; serum bilirubin:P<0.005; serum albumin:P<0.001; prothrombin index:P<0.05) were significant predictors of survival. To investigate whether quantitative liver function tests could contribute to a better definition of the prognosis, once Pugh score had already been taken into account, a multiple regression analysis according to the Cox model was performed. Pugh score and galactose elimination capacity resulted in the only independent prognostic covariates. From them a prognostic index was calculated, and the model was validated in an additional sample of 70 patients investigated according to the same protocol. The contribution GEC gave to the assessment of overall prognosis over that obtained using the Pugh score was slight, as estimated by the statistical parameters of the Cox's model, but was significant as assessed by a ROC curve analysis (P=0.05). These data show that all quantitative liver function tests were predictors of survival in cirrhosis, and that the galactose elimination capacity added some new prognostic information to those already available using the Child-Turcotte-Pugh classification.This study was supported in part by a grant from the Italian Ministry of Education (National Project Liver Cirrhosis). Part of this study was presented at the 22nd Meeting of the European Society for Clinical Investigation, Graz, Austria, April 20–23, 1988.     

老年性黄斑变性脉络膜新生血管的组织病理学特征

目的 观察老年性黄斑变性（AMD）脉络膜新生血管(CNV) 吲哚青绿血管造影(ICGA) 表现与其组织病理学变化的关系。 方法 ICGA检查确诊的AMD患者21 例21只眼，根据ICGA检查结果将CNV分成活动期、消退期、静止期，通过玻璃体切割手术取出CNV，光学显微镜、透射电子显微镜观察不同期CNV的组织病理学特征。 结果 活动期CNV9只眼，组织病理学特征为大量CNV，无色素性细胞和纤维组织或有少量色素性细胞将其部分包裹；消退期CNV9只眼，组织病理学特征为CNV较活动期减少，有较多色素性细胞、少量的纤维组织；静止期CNV3只眼，组织病理学特征为大量的纤维组织，无CNV或有极少CNV，无色素性细胞。 结论 渗出型AMD患者CNV的组织病理学特征与ICGA表现具有一定的相关性。 （中华眼底病杂志，2004，20：71-74）     

Green Tea Extract Containing Piper retrofractum Fruit Ameliorates DSS-Induced Colitis via Modulating MicroRNA-21 Expression and NF-κB Activity

The aim of the present study was to examine the effect of green tea extract containing Piper retrofractum fruit (GTP) on dextran-sulfate-sodium (DSS)-induced colitis, the regulatory mechanisms of microRNA (miR)-21, and the nuclear factor-κB (NF-κB) pathway. Different doses of GTP (50, 100, and 200 mg/kg) were administered orally once daily for 14 days, followed by GTP with 3% DSS for 7 days. Compared with the DSS-treated control, GTP administration alleviated clinical symptoms, including the disease activity index (DAI), colon shortening, and the degree of histological damage. Moreover, GTP suppressed miR-21 expression and NF-κB activity in colon tissue of DSS-induced colitis mice. The mRNA levels of inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were downregulated by GTP. Colonic nitric oxide (NO) and prostaglandin E2 (PGE2) production, and myeloperoxidase (MPO) activity were also lowered by GTP. Taken together, our results revealed that GTP inhibits DSS-induced colonic inflammation by suppressing miR-21 expression and NF-κB activity, suggesting that it may be used as a potential functional material for improving colitis.     

增强型绿色荧光蛋白原核表达载体的构建及表达

目的 构建以增强型绿色荧光蛋白(EGFP)为标记的原核表达栽体,并观察EGFP基因在大肠杆菌中的表达情况.方法 据已知的EGFP基因序列,设计引物,并引入Nde Ⅰ和Xho Ⅰ酶切位点.采用PCR技术从含有EGFP的质粒pEGFP-C1中克隆EGFP编码序列;将其亚克隆入表达载体pTWIN1,得到以EGFP为标记的原核表达载体pTWIN-EGFP.转化大肠杆菌ER2566菌株,IPTG诱导EGFP基因表达.结果 经过IPTG诱导后,细菌培养物在长波紫外线的照射下,发出明亮的绿色荧光.结论 成功构建了原核表达载体pTWIN-EGFP,为应用EGFP作为报告基因和筛选标记奠定了实验基础.     

人涎腺癌原位转移裸鼠模型的建立

光学成像技术与基因标记技术结合的非侵入性在体分子荧光成像可以实时监测肿瘤的发生发展过程。本研究利用绿色荧光蛋白（GFP）转染人涎腺癌细胞ACC-M，建立了GFP标记肿瘤原位转移模型，并对模型进行了整体荧光成像的初步研究。实验结果表明光学成像可以从时间和空间上反映肿瘤转移的过程，因而这种模型同在体光学成像的结合为研究肿瘤治疗药物的筛选提供了一种很好的平台。     

EDTA对γ—FeOOH制备过程的影响

ＦｅＳＯ４制备铁黄时，ＥＤＴＡ的存在能诱导γ－ＦｅＯＯＨ粒子的生成。