Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats

Increased intrahepatic resistance in cirrhotic livers is in part caused by increased vascular tone. Several morphological abnormalities have been described in the sinusoidal endothelial cells of cirrhotic livers, but the functional impact of these abnormalities on the intrahepatic vascular tone has not been studied. The aim of this study was to investigate the intrahepatic endothelial function and the role of nitric oxide (NO) with regard to vascular tone in cirrhotic livers. Isolated rat liver perfusions were performed in cirrhotic rats (induced by chronic carbon tetrachloride inhalation) and weight-matched normal controls. After preconstricting the intrahepatic microcirculation with methoxamine (10(-4) mol/L), response to cumulative doses of receptor-mediated endothelial agonist, acetylcholine (10(-7) mol/L-10(-5) mol/L), was obtained. In another series, response to the receptor-independent endothelial agonist, calcium ionophore A23187 (10(-7) mol/L and 3 x 10(-7) mol/L), was obtained in the absence and presence of Nomega-nitro-L-arginine (NNA) and indomethacin. In a third series of rats, nitrate and nitrite production was measured in the perfusate of perfused normal and cirrhotic livers. There was significantly less vasorelaxation in cirrhotic livers as compared with normal livers in response to acetylcholine and calcium ionophore A23187 (P < .0001). The impaired vasorelaxation was a result of a decrease in both NO-mediated and non-NO-mediated components of vasorelaxation. Cirrhotic livers from ascitic rats had significantly less vasorelaxation as compared with livers from nonascitic rats (P < .005). There was significantly less production of nitrates and nitrites in cirrhotic livers (P < .05). The liver microcirculation of cirrhotic livers is characterized by endothelial dysfunction that results in impaired release of endothelial relaxing factors including NO.     

Characteristics of a Sector of the Endcap Hadron Calorimeter for the CMS Facility

The characteristics of the prototype of the endcap hadron calorimeter for the CMS facility have been measured. Using the relations between the measured calorimeter response to a radiation source, muons, and pions, it is possible to determine the energy scale of the data-acquisition electronics, which will be used in future experiments along with the calorimeter. The light yield in the calorimeter due to a minimum-ionizing particle was measured. The effect of various factors on the duration of the calorimeter signal is analyzed. The joint operation of the hadron and electromagnetic calorimeters was investigated. The possibility of adjusting the uncompensated system using the data from a scintillation counter inserted between the calorimeters is analyzed. It is shown that the presence of a structural material between the calorimeters will not lead to a noticeable degradation in the energy resolution of the hadron calorimeter.     

Prognostic implications of proliferating cell nuclear antigen (PCNA), AgNORs and P53 in non-Hodgkin's lymphomas

We investigated the prognostic value of proliferating cell nuclear antigen (PCNA) and p53 oncoprotein expression and of nucleolar organiser region (NOR) scoring, in relation to classic clinicopathological parameters, in a series of non-Hodgkin's lymphomas (NHL). Paraffin embedded tissue from 91 patients with NHL was stained immunohistochemically with the monoclonal antibodies PC-10 (PCNA) and DO-1 (p53) and histochemically with the AgNOR technique. The median follow-up was 48 (4 to 193) months. The impact of PCNA and p53 expression and of AgNOR number on survival was tested using univariate as well as multivariate analysis, in order to circumvent the heterogeneity in histologic grade, type and therapy. Univariate analysis identified seven variables related to overall survival: histologic type and grade, clinical stage, chemotherapy, p53 labelling index (LI), PCNA LI and AgNOR score, whereas only one parameter i.e. histologic grade influenced disease-free survival. In multivariate analysis stage, PCNA LI and AgNOR score predicted independently overall survival. PCNA was also the only independent predictor of post-relapse survival and histologic grade the most important indicator of disease-free survival. In conclusion, PCNA expression and AgNOR number may be better predictors of overall and post-relapse survival than histologic grade. The latter remains the most valuable prognostic indicator of disease-free survival.     

Partial characterization of the human retinal endothelial cell tight and adherens junction complexes

PURPOSE: In diabetic retinopathy and macular edema, the blood-retinal barrier fails to function properly, and there is transvascular leakage of proteins and solutes. The tight junction protein occludin and the adherens junction protein cadherin-5 have been shown to be critical to maintaining the endothelial barrier and regulating paracellular transport of large vessel endothelia. However, the expression and distribution of these junction proteins in the retinal endothelium is not well characterized. METHODS: Human and bovine retinal endothelial cells were isolated as described previously. Western blot analysis and flow cytometry techniques were used to assay for the presence of occludin, zonula occludens-1 (ZO-1), cadherin-5, and beta-catenin. The subcellular localization of the proteins was visualized by immunohistochemistry performed on cultured human retinal endothelial cells and cryosections of bovine retina. RESULTS: Western blot analysis and flow cytometry techniques found occludin, ZO-1, cadherin-5, and beta-catenin in cultured human retinal endothelial cells. Immunofluorescence staining of cultured retinal endothelial cells and cryosections of bovine retina showed junctional localization of occludin, ZO-1, cadherin-5, and beta-catenin. CONCLUSIONS: This report demonstrates the expression of occludin and cadherin-5 in retinal endothelial cells and their localization to sites of cell-cell contact. Expression of their respective regulatory proteins, ZO-1 and beta-catenin, at sites of cell-cell contact suggests that occludin and cadherin-5 play a role in maintaining the retinal endothelial barrier.     

Autocrine transforming growth factor beta stimulation of extracellular matrix production by fibroblasts from fibrotic human gingiva

The effectiveness of cancer screening depends crucially on two elements: the sojourn time (that is, the duration of the preclinical screen-detectable period) and the sensitivity of the screening test. Previous literature on methods of estimating mean sojourn time and sensitivity has largely concentrated on breast cancer screening. Screening for colorectal cancer has been shown to be effective in randomized trials, but there is little literature on the estimation of sojourn time and sensitivity. It would be interesting to demonstrate whether methods commonly used in breast cancer screening could be used in colorectal cancer screening. In this paper, the authors consider various analytic strategies for fitting exponential models to data from a screening program for colorectal cancer conducted in Calvados, France, between 1991 and 1994. The models yielded estimates of mean sojourn time of approximately 2 years for 45- to 54-year-olds, 3 years for 55- to 64-year-olds, and 6 years for 65- to 74-year-olds. Estimates of sensitivity were approximately 75%, 50%, and 40% for persons aged 45-54, 55-64, and 65-74 years, respectively. There is room for improvement in all models in terms of goodness of fit, particularly for the first year after screening, but results from randomized trials indicate that the sensitivity estimates are roughly correct.     

Algorithm of the zonal solution of radiation — conduction heat-transfer problems

A numerical method is proposed to compute the stationary radiation-conduction heat transfer in semitransparent materials on the basis of a zonal approach.Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 41, No. 6, pp. 1094–1102, December, 1981.