A morphometric study of neovascularization in colorectal carcinoma

BACKGROUND: Neovascularization reportedly is correlated with metastasis, recurrence, and prognosis in some types of tumors. Microvessel quantification in so-called "hot spots" has been studied extensively as the only factor reflecting angiogenesis in various malignant tumors. The objective of this report was to evaluate multiple morphometric microvascular characteristics in addition to microvessel density (MVD) in colorectal carcinomas to provide a better approach to examining the relation between angiogenesis and clinicopathologic factors and prognosis. METHODS: Histologic sections from 106 colorectal adenocarcinomas and 17 adenomas, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, total vascular area (TVA), and microvascular branching, as well as several morphometric parameters related to the vessel size or shape. RESULTS: MVD gradually decreased with progressing Dukes stage. The vascular branching counts were significantly higher in carcinomas than in adenomas, and remained unaffected through progressing Dukes stages. Shape-related parameters showed significant differences between carcinomas and adenomas and between different grades of differentiation. Branching counts and TVA were the only factors found to be of prognostic significance. CONCLUSIONS: This study provides evidence that neovascularization is an early critical event in colorectal tumorigenesis, reaching a maximum level early in the malignant process. Its prognostic significance is better assessed by quantification of TVA and the branching pattern of microvessels, whereas MVD does not provide significant prognostic information for colorectal carcinoma patients.     

Natural killer cell cytotoxicity and paternal lymphocyte immunization in women with recurrent spontaneous abortions

Although cardiac function is depressed during endotoxic shock, it remains controversial whether the ventricular contractility and structure are altered during sepsis. To resolve this issue, rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). At 2, 5, and 10 h after CLP (i.e., the early, hyperdynamic stage of sepsis) or 20 h after CLP (the late, hypodynamic stage of sepsis, based on the depressed tissue perfusion), in vivo left ventricular contractility parameters such as maximal rate of the left ventricular pressure increase (+dP/dtmax) and decrease (-dP/dtmax), maximal rate of "pressure-normalized" change in ventricular pressure (dP/dtmax/P), and ventricular peak systemic pressure were determined using a Digi-Med Heart Performance Analyzer. In additional groups of animals, ultrastructure of the cardiac muscle in the left ventricle was examined at 5, 10, or 20 h after CLP, using a transmission electron microscope. The results indicate that +dP/dtmax and dP/dtmax/P increased significantly at 2-10 h after CLP. The values of -dP/dtmax and ventricular peak systemic pressure increased significantly at 2 and 5 h after the onset of sepsis, respectively. These in vivo ventricular contractility parameters, however, were not significantly different from shams at 20 h after CLP. Ultrastructural examination showed that enlarged T-tubules were prominent during the hyperdynamic stage of sepsis, which was correlated with the increased cardiac contractility. Although focal and moderate hypertrophy as well as expanded intermyocyte junctions could be observed occasionally, myocardial cells did not appear to be compromised at 20 h after CLP. Thus, the transition from the hyperdynamic to hypodynamic circulation during sepsis does not appear to be due to any depression in myocardial function because cardiac contractility and structure are not compromised even during the late, hypodynamic stage of sepsis. However, further investigation is required to determine whether cardiac function is depressed at the terminal stage of polymicrobial sepsis.     

Photodynamic antitumor agents: beta-methoxyethyl groups give access to functionalized porphycenes and enhance cellular uptake and activity

Porphycene photosensitizers bearing two or four methoxyethyl side chains were synthesized in nine steps from commercially available starting materials. Ether cleavage led to (hydroxyethyl)- and (bromoethyl)porphycenes that were converted to vinyl and benzo derivatives. Five of the side chain-functionalized porphycenes were biologically studied in comparison with two tetra-n-propylporphycenes. Porphycenes were incorporated in small unilamellar liposomes and incubated with cultivated SSK2 murine fibrosarcoma cells. Cellular uptake and phototoxicity 24 h after 5 J/cm2 laser light treatment were determined. The porphycenes tested were between 17 and 220 times more photodynamically active than the currently clinically used sensitizer Photofrin, although extinction coefficients of the porphycenes' irradiated bands are only approximately 10-fold higher. The LD50 concentration for SSK2 cells in the incubation medium was as low as (8.5 +/- 2.8) x 10(-9) M for tetrakis(methoxyethyl)porphycene. Two methoxy or hydroxy groups enhanced cellular uptake, three or four methoxy groups both enhanced and accelerated cellular uptake of tetraalkylporphycenes. Half-life times of the uptake processes varied between (0.14 +/- 0.04) and (14 +/- 4) h and cellular saturation levels between (1.2 +/- 0.2) and (26 +/- 3) pmol/10(5) cells. When individual uptake rates were accounted for, all porphycenes had a similar "cellular" phototoxicity, pointing toward a common mechanism of action. Evidence is presented for the assumption that cell membranes are the primary targets of the tested porphycenes and that membrane solubility may play a critical role in their photodynamic efficiency. The results show that nonionic polar side chain functionalities can strongly enhance cellular uptake and antitumor activity of lipophilic porphyrinoids and thus that the known lipophilicity/activity relationship can be reversed for very hydrophobic sensitizers.     

The Use of Kits in the Analysis of Tissue Lipids Requires Validation

The ready availability and ease of use of kits for the measurement of serum lipids has greatly facilitated these measurements. In many cases it would be convenient to use these kits in the determination of lipid concentrations in tissues. The successful application of serum kits in tissue analysis requires that two important issues be considered. First, the solvent system for the extraction of the lipids and the solvent used for analysis by the kit must be compatible with the reactions in the kit. Second, the concentration range in the analyzed solution must be within the range for which the kit is used. We report here that lipids in liver and adipose tissues may be significantly underestimated by the use of some kits. We recommend that the use of kits for tissue analysis of lipids be validated for the specific analysis.     

Residual strength of composite laminates containing scarfed and straight-sided holes

This investigation is motivated by the needs to quantify the load-carrying capacity of composite laminates with scarfed holes, a damage cut-out shape employed to achieve flush repairs of composites. Both experimental testing and analytical modelling were carried out to investigate the damage progression behaviour of composite laminates containing either straight-sided or scarfed holes. Hoop strains were recorded by strain gauges located along the scarf surface and the results indicate a much greater extent of damage progression than specimens containing straight-sided holes. Three different strength-prediction models were employed to quantify the residual strength, including an analytical cohesive zone model developed in this work, an analytical inherent-flaw fracture mechanics method and a finite element-based continuum damage model. Comparisons of the experimental results with the model predictions reveal that the continuum damage model, calibrated using data from coupons with straight-sided holes, provides promising correlation with experimental results.     

Factors controlling Hg levels in two predatory fish species in the Negro river basin, Brazilian Amazon

A number of environmental factors have been shown to influence the dynamics of Hg in aquatic ecosystems. Here we investigate the influence of fish size, pH, dissolved organic carbon (DOC), and the availability of potential methylation sites (floodplain forests and hydromorphic soils) on the concentration of total Hg in two carnivorous fishes: Cichla spp. and Hoplias malabaricus in the Negro River, Brazil. Fish and water samples for chemical analysis were collected from 33 sites in the Negro basin. The percentage of alluvial floodplains and hydromorphic soils (potential methylation sites) in the drainage basin upstream from each sampling point was estimated from radar imagery and existing soil maps with GIS. The average of Hg concentrations were 0.337 ppm (SD = 0.244) in Cichla spp. and 0.350 ppm (SD = 0.250) in H. malabaricus. Although the study area was geographically isolated from most major anthropogenic Hg sources, over 18% of Cichla spp. and 29% of H. malabaricus had Hg concentrations above 0.5 ppm, indicating naturally high background levels of Hg. Hg concentrations increased with size in both Cichla spp. (r² = 0.664, p = 0.000) and H. malabaricus (r² = 0.299, p = 0.000). Hg concentrations in H. malabaricus also increased with percent floodable area (p = 0.006), pH (p = 0.000) and DOC (0,063). In Cichla spp, Hg increased only in relation to percent floodable area (p = 0.000). Hydromorphic soils did not influence fish Hg.     

A conservative nodal variational multiscale method for Lagrangian shock hydrodynamics

A new method based on a continuous, piece-wise linear approximation of the equations for Lagrangian shock hydrodynamics is presented. Numerical instabilities are controlled by a stabilizing operator derived using the paradigm of the variational multiscale analysis. Encouraging numerical comparisons with existing methods in the case of quadrilateral and hexahedral elements indicate that the proposed method is capable of preventing hourglass patterns in the solution, while maintaining accuracy in regions of smooth flow. The proposed approach satisfies Galilean invariance properties and hinges upon the interpretation of the Lagrangian shock hydrodynamics equations as a system of nonlinear wave equations. A specific implementation in terms of a predictor/multi-corrector version of the mid-point time integrator guarantees global conservation of mass, momentum, and total energy for each iterate. Stability and formal order of accuracy are investigated applying the von Neumann analysis to the linearized shock hydrodynamics equations in one dimension. This approach yields tight bounds for stable time-step estimation, formal second-order accuracy of the method in time and space, and valuable indications on the choice of the most appropriate values for the stabilization parameters present in the formulation.     

An Enhanced Vacuum Cure Technique for On-Aircraft Repair of Carbon-Bismaleimide Composites

Carbon/bismaleimide (BMI) composite is increasingly employed in critical load carrying aircraft structures designed to operate at temperatures approaching 180°C. The high post-cure temperature (above 220°C) required to fully react the BMI resin, however, renders existing on-aircraft prepreg or wet layup repair methods invalid. This paper presents a new on-aircraft repair technique for carbon/BMI composites. The composite prepregs are first warm-staged to improve the ability to evacuate entrapped air. Then the patch is cured in the scarf cavity using the vacuum bag technique, followed by off-aircraft post-cure. The fully cured patch then can be bonded using a structural adhesive.     

Bonded repairs for carbon/BMI composite at high operating temperatures

The increased use of carbon reinforced polymer composite structures in civilian and military aircraft has produced new challenges for on-aircraft bonded repairs. Carbon/bismaleimide (BMI) composite structure provides an added complexity associated with the application of adhesively bonded repairs. Commercially available carbon/BMI composite usually requires a post-cure temperature in excess of 220 °C to achieve the high strength properties at elevated operating temperatures. Application of bonded repairs in situ often places an upper limit on the temperatures that can be employed for curing the adhesive at 177 °C. Consequently, the adhesive bond needs to achieve similar mechanical properties to the parent matrix material without the benefit of the high post-cure temperature. The current work examines a range of repair options that can be used to recover strength and the selection of adhesives and processes to successfully apply the repairs using vacuum assisted pressure.