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Epidermal remodeling in psoriasis (II): a quantitative analysis of the epidermal architecture.

Hyperproliferative psoriatic epidermis was quantitatively analyzed using a geometric model of viable epidermis. Our model was based on hexagonally arranged cylindrical papillae, which allowed the determination of the total volume of the viable epidermis and the total area of the interface with the proliferative compartment based on several parameters, such as papillary height, papillary width, and distance between neighboring papillae. The analysis assumed that the total number of viable epidermal cells paralleled the proliferative compartment in a steady state of cell flow, so a quantitative relation could be made between both volume and interface of the viable epidermis. Multiple parameters of the psoriatic epidermal architecture were measured, and variations within psoriasis were predicted by the model. The results predicted were remarkably close to the observed values. The geometric model also indicated that psoriatic epidermis could be subdivided into two distinct types, with and without a granular layer; the latter having a shorter turnover time. This is consistent with the notion that the typical psoriatic epidermis (without the granular layer) represents the expanding hyperproliferative phase, whereas the psoriatic epidermis with a granular layer represents stationary or resolving states. The model of hexagonally arranged cylindrical papillae suggested that the architecture of the psoriatic epidermis is constructed by a simple mechanism, whereby the psoriatic angulated rete-papilla pattern was produced by a two-dimensional increase in the proliferative compartment and a three-dimensional increase in the total volume of the viable epidermis.

Epidermis↗

Quantitative analysis of surface atom positions in a thick crystal as determined by a reconstructed exit wave.

Atomic structures of an Au (110) 2 x 1 reconstructed surface were analysed quantitatively using an exit wave reconstructed by the three-dimensional Fourier filtering method in high-resolution transmission electron microscopy. To reconstruct the exit wave in a relatively thick crystal, a practical criterion was proposed in the present analysis. In the 'pseudo-exit wave' obtained by the proposed criterion, relaxation of surface atoms was clearly visible in the top three layers. The atoms' displacement was measured to be about 5-20 pm. For quantitative analysis of the atom column positions, image contrast calculations were performed using a structural model of the Au (110) reconstructed surface. Calculations confirmed that the reconstructed pseudo-exit wave could represent the atom column positions directly with an accuracy of several pm, even for a relaxed surface, provided the sample thickness was <7 nm.

Journal Article↗

[The lysosomal system of the hepatocytes during the development of extrahepatic cholestasis (a quantitative analysis)].

Electron microscopic and morphometric studies of the lysosomal system of hepatocytes with quantitative, informative and dispersion analysis of electron micrographs in healthy rats and rats with extrahepatic cholestasis have revealed the stage-like character of changes of the reaction of the liver subcellular structures in the processes of development of the pathologic process. At the first stage (12h-3 days) in parallel with the symptoms of injury (dilation of the lumen of bile canals with dystrophic alterations of epitheliocytes microvilli, depletion of the cytoplasm by glycogen, appearance of lipid inclusions, accumulation of the bile pigments) the initiation of urgent reactions of compensation was observed (using part of primary lysosomes in heterophagic processes, activation of autophagocytosis) as well as the beginning of the formation of long-term reactions with a somewhat increased amount of primary lysosomes and greater amount of small primary forms. There occur normalization of the ratio of primary and secondary forms. The 2nd stage (the 2nd half of the 1st week--the 2nd week) is characterized by the prevalence of compensatory adaptation reactions, underlaid by the formation of long-term reactions of compensation (considerable increase of the amount of primary lysosomes at the expense of intensification of their synthesis, active resorption of bile and lipid metabolites with the transformation of the latter in glycogen). The 3rd stage (the 3rd week) is characterized by depletion of reserves of the lysosomal system: sharp drop of the ability for self-renewal of the structures, change of the population composition of organelles expressed as prevalence of autophagosomes and residual bodies, transformation of the lysosomes in residual bodies.

Adaptation, Physiological↗

Spermatogenesis in XY, XYSxra and XOSxra mice: a quantitative analysis of spermatogenesis throughout puberty.

Adult XYSxra mice exhibit varying degrees of spermatogenic deficiency but are usually fertile, while XOSxra mice have severe spermatogenic failure and are always sterile. The present quantitative spermatogenic analysis documents when these anomalies first appear during puberty. The results demonstrate that in XYSxra mice there was increased degeneration of pachytene spermatocytes and, to a lesser extent, meiotic metaphase stages. On average, there were only one-half the number of spermatids compared with the XY controls. The defect in XOSxra mice appeared a little later, with an almost complete arrest and degeneration during the meiotic metaphases, so that the number of spermatids produced was only 3% of the control value. These results are discussed in relation to an hypothesis that links sex chromosome univalence during meiotic prophase with spermatogenic failure.

Animals↗

Quantitative analysis of electron energy-loss spectra from ultrathin-sectioned biological material. I. Optimization of the background-fit with the use of Bio-standards.

A computer program for quantitative spectral analysis is proposed for the elemental analysis of biological material by electron energy-loss spectroscopy in a conventional transmission electron microscope, the Zeiss EM902. Bio-standards are used to test the performance of this program. The application of a simplex optimization method for curve-fitting is proposed to separate the ionization edge from the background. Making use of Ce-, Ca- and Fe-bio-standards, this method is compared with Egerton's well-known two-area method.

Calcium↗

Probabilistic reliability analysis, quantitative safety goals, and nuclear licensing in the United Kingdom.

Although unpublicized, the use of quantitative safety goals and probabilistic reliability analysis for licensing nuclear reactors has become a reality in the United Kingdom. This conclusion results from an examination of the process leading to the licensing of the Sizewell B PWR in England. The licensing process for this reactor has substantial implications for nuclear safety standards in Britain, and is examined in the context of the growing trend towards quantitative safety goals in the United States.

Accident Prevention↗

A new quantitative analysis system for the evaluation of coronary bifurcation lesions: comparison with current conventional methods.

BACKGROUND: Objective conventional quantitative angiographic systems are designed to automatically follow the contours of straight vascular segments and not of bifurcations. Recently a new analysis method was specifically developed for bifurcation lesions, able to automatically divide the lesion into three separate segments. In this study, we aimed to assess whether the smaller interaction required by the analyst could reduce the analysis time and inter and intra observer variability when compared with a conventional analysis. METHOD: We used a dedicated system (QVA-CMS V. 6.0 with the Bifurcation Module, MEDIS, Leiden, The Netherlands) applying a minimum cost algorithm tuned to detect the contours of the proximal main vessel (PMV), distal main vessel (DMV), and side-branch (SB). We assessed the intra- and the interobserver agreement in measurements of minimal lumen diameter (MLD) and percentage diameter stenosis (%DS) of the PMV and DMV, as well as of the SB ostium in 30 angiograms of patients before and after percutaneous coronary angioplasty with stenting of both branches. The consensus between measurements by two observers and by the same observer was analyzed using the intra- and interclass correlation coefficient and the reliability coefficients for all measurements. Bland-Altman plots before and after PCI were also generated to assess the relationship between variability and absolute measurements. RESULTS: Before PCI, intra- and interobserver variabilities were consistently lower for the new QVA system, with a significant difference for lesion length in the SB. Post-PCI data showed a greater variability in the assessment of diameter stenosis with both techniques. The time for analysis was significantly lower both before and after PCI for QVA compared with quantitative coronary angiography (QCA) (4.7 +/- 1.1 min versus 6.2 +/- 1.3 min, P < 0.0001). CONCLUSION: Our results demonstrate that this new quantitative bifurcation analysis system can be consistently applied to the analysis of bifurcation lesions before and after angioplasty, with an intra- and interobserver reproducibility equal to or better than the conventional analysis system with a significantly shorter analysis time.

Aged↗

Quantitative analysis of CEA expression in colorectal adenocarcinoma and serum: lack of correlation.

Tissues and sera from 110 patients diagnosed with colorectal primary carcinoma, 20 patients with benign colorectal diseases and 31 healthy donors were subjected to quantitative CEA analysis. Multiple samples from tumor lesions and autologous histologically normal mucosa (10 cm from the tumor) were obtained at the time of surgery (cancer patients) or endoscopy (benign patients and healthy volunteers). CEA content was measured in protein extracts obtained from these tissues using a quantitative RIA method. A limit of normality for CEA content was established as 300 ng/mg of protein. When this was taken as cut-off, 104 of 110 (94.5%) tumor lesions and 51 of 110 (46.4%) autologous histologically normal colonic mucosa from cancer patients had elevated CEA levels. No correlation with stage of disease was found, while a correlation was observed with degree of tumor differentiation. A statistically significant difference between CEA content in tumor lesions and in histologically normal mucosa from cancer patients was observed (p = -0.001). Moreover, CEA content was statistically higher in the normal mucosa from cancer patients than in that from healthy donors (p = 0.005). CEA content in tissue specimens from benign lesions differed significantly from that in tissue from healthy donors (p = 0.005) and in carcinoma lesions (p < 0.001). The highest CEA content was observed in benign lesions with severe dysplasia. No statistical correlation between CEA content in carcinoma tissues and serum CEA levels (r = 0.195, p = .13) was found. Therefore, in considering diagnosis or therapy with anti-CEA MAbs for colorectal-carcinoma patients, or potential therapies with anti-CEA recombinant vaccines, serum CEA levels should not be taken as indicating CEA expression in tumor lesions.

Adenocarcinoma↗

Quantitative analysis of primary proliferative mesangial glomerulonephritis (PMGN) and diffuse form of idiopathic IgA nephropathy (IgAN). Variants of the same morphological process?

Fifteen renal biopsy specimens from patients with idiopathic diffuse IgAN and fifteen from patients with primary PMGN for whom both light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available were examined and compared quantitatively. Morphometric investigations were performed by means of a computer image analysis system to evaluate whether morphometric analysis could confirm morphological similarity of IgAN and PMGN as well as to study whether serum creatinine and changes in quantitatively analyzed glomeruli could correlate with the interstitial fibrosis in these glomerulopathies. The morphometric study revealed that there were no noticeable differences between the groups and the mean values of total glomerular area, total glomerular cells per total glomerular area, total glomerular cells per unit of glomerular area, mesangium (% of total glomerular area) and relative interstitial volume were similar in IgAN and MPGN (in all cases p > 0.05). Moreover, there were significant positive correlations between the width of the cortical interstitium and serum creatinine level as well as between the width of the cortical interstitium and glomerular changes in both IgAN and PMGN groups. In summary it should be noted that the results of quantitative analysis of IgAN and PMGN invariably lead to a conclusion that these glomerulopathies are immunological and clinical variants of the same morphological process.

Creatinine↗

Quantitative analysis of aphasic sentence production: further development and new data.

The narrative production of patients with Broca's aphasia and age-and education-matched control subjects was analyzed using the Quantitative Production Analysis (Saffran et al., 1989), a procedure designed to provide measures of morphological and structural characteristics of aphasic production. In addition to providing data for a larger number of subjects than in the original study, we provide data on interrater and test-retest reliability. The data were also submitted to factor and cluster analyses. Two factors characterized the data and the cluster analysis yielded four sets of patients who performed differently on these factors. In particular, there is evidence that agrammatic patients can differ in their production of free and bound grammatical morphemes, substantiating earlier claims in the literature.

Adult↗

Quantitative analysis of the fine vascular anatomy of articular ligaments.

An image analysis technique has been developed to quantitatively describe the fine vascular patterns observed in ligament tissue. The longitudinal orientational distribution and total vessel volume of India-ink-perfused blood vessel segments in normal and healing ligaments were determined. The methods involved special vascular preparation of adult rabbit knee medial collateral ligaments (MCL) by India-ink perfusion. Black and white microscope images of ink-perfused tissue sections were subjected to a thresholding procedure to binarize digitized ligament images, which were then skeletonized and analyzed for directional distribution based on the least-squares technique. Analysis of medial collateral ligaments in New Zealand White rabbits using this method has shown that scarred tissue is more vascular and has a more chaotic angular distribution of blood-vessel segments than normal ligament tissue.

Algorithms↗

Prognostic importance of quantitative analysis of coronary cineangiograms.

Many studies have shown the prognostic value of angiographic data, but few have examined quantitative parameters of wall motion and shape or coronary stenosis severity. To determine whether these parameters have prognostic importance, baseline angiograms of 283 patients with up to 11.2 years (mean 8.3) of follow-up were quantitated. Event-free survival curves were constructed using log-rank testing. These indexes were also considered in 2 predictive models (Cox regression models): 1 with ("clinical") and 1 without ("quantitative") subjective angiographic analysis and clinical information. Regional shape (anterior and inferior walls) and motion (anterior wall only) indexes were predictive of event-free survival when considered singly. But these parameters were not of independent prognostic importance in the regression models. The most important independent parameters in the quantitative model for predicting overall cardiac mortality or an initial lethal cardiac event were the ejection fraction and the percent diameter narrowing of each major coronary artery. Myocardial infarction was predicted by the percent diameter stenosis of the left main and left anterior descending arteries but not the ejection fraction. In the clinical model, the factors of overriding prognostic importance were the ejection fraction and the subjective determination of the number of vessels involved with "significant" stenoses. Quantitative coronary arteriography still contributed independent prognostic value. Thus, quantification of the ejection fraction and severity of coronary lesions were of independent, prognostic importance, whereas indexes of regional function and shape were not.

Adult↗

Informatics and quantitative analysis in biological imaging.

Biological imaging is now a quantitative technique for probing cellular structure and dynamics and is increasingly used for cell-based screens. However, the bioinformatics tools required for hypothesis-driven analysis of digital images are still immature. We are developing the Open Microscopy Environment (OME) as an informatics solution for the storage and analysis of optical microscope image data. OME aims to automate image analysis, modeling, and mining of large sets of images and specifies a flexible data model, a relational database, and an XML-encoded file standard that is usable by potentially any software tool. With this design, OME provides a first step toward biological image informatics.

Algorithms↗

Reexamination of Stewart's quantitative analysis of acid-base status.

To provide experimental verification to Stewart's quantitative approach to acid-base analysis, the effects of acute maximal treadmill exercise (VO2max test) on venous acid base status were studied in 17 male subjects aged 18-23 yr. Venous CO2 tension (PCO2) total plasma proteins ([PTOT]), [H+], and concentrations of strong ions [( Na+], [K+], [Cl-] and lactate ion concentration ([La-]) were measured before and within 1 min post-exercise. Mean post-exercise PCO2, [PTOT], [K+], and [La-] were significantly higher than the corresponding pre-exercise values (P less than 0.05), there was a strong tendency for a significant change in [Na+] (P less than 0.056), and no changes were found in [Cl-]. Changes in venous acid-base status were analyzed quantitatively by applying relevant physicochemical theory. Altered values measured in the independent variables ([PTOT], PCO2, and net strong ion difference, [SID]) were used to calculate the corresponding changes in the dependent quantities. Comparison of individual measured and calculated values for the only one of these that is normally measured, ([H+]), yielded the theoretically expected agreement. PCO2 and [SID] changes accounted for most [H+] changes. These results demonstrate the usefulness of the quantitative approach (i.e., [H+]-PCO2 diagram) in the analysis and in understanding of plasma acid base changes with exercise and in clinical situations.

Acid-Base Equilibrium↗

A quantitative analysis of the development of the pyramidal tract in the cervical spinal cord in the rat.

A quantitative electron microscopic analysis was undertaken of the development of the pyramidal tract, at the level of the third cervical spinal segment, in rats ranging in age from the day of birth to three months old. The axon number was calculated as the product of axon density, determined in a systematic random sample of electron micrographs, and tract area. During the first postnatal week the tract contains thin unmyelinated axons and growth cones. Growth cones are abundant in neonatal rats, but can still be observed occasionally at the end of the first postnatal week, indicating a continuous addition of pyramidal tract axons during the first postnatal week. Myelination starts around P10. By the end of the first postnatal month approximately 50% of the axons have already been myelinated. Myelination proceeds during further maturation, but in the three month old rat 28% of the axons are still unmyelinated. The total number of axons increases rapidly after birth up to 153,000 at the fourth postnatal day. Subsequently, the number of axons is reduced by nearly 50% to 79,000 in the adult rat. The axon loss is most prominent during the second postnatal week, when 32,000 axons are eliminated, but continues for several weeks at a slower rate.

Animals↗

Quantitative analysis of immune-mediated stimulation of tumor necrosis factor-alpha in macrophages measured at the level of mRNA and protein synthesis.

Expression of cytokines such as tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS) has been associated with inflammatory and regulatory immune reactions. Antigen-presenting cells, especially macrophages, play a central role in directing immune responses by synthesizing different cytokines. For the analysis of cytokine synthesis, we compared quantitative changes in mRNA and protein synthesis of TNF-alpha in RAW 264.7 cells stimulated with 0.1 ng/ml LPS. TNF-alpha mRNA was quantified using the LightCycler SYBR Green technology (Idaho Technology, Inc., Salt Lake City, Utah, USA). RAW 264.7 cells showed a basal TNF-alpha mRNA expression which increased approximately sixfold after 2 h of stimulation with LPS. TNF-alpha synthesis was analyzed at the protein level using a mouse-specific sandwich enzyme-linked immunosorbent assay (ELISA) and indicated a 56-fold increase in TNF-alpha protein concentration after 4 h. Thus, real-time polymerase chain reaction (PCR) is a sensitive and rapid method for quantitative determination of LPS-induced TNF-alpha expression. However, it requires extremely robust reaction parameters to be reliable for accurate quantification.

Actins↗

Quantitative analysis of trifluoroacetate in the urine and blood by isotachophoresis.

Trifluoroacetate (TFA), the major metabolite of halothane, was assayed by a newly developed isotachophoretic technique. This technique has several advantages over the presently used methods of analysis. It requires no special preparation of urine or blood samples. The sample volume is small (5--100 microliters) and the analysis time is short (30--90 min per sample). In addition, the method provides an analysis that is both qualitative and quantitative over a wide range of concentrations (from 2 nanomoles in 200 microliters to 200 nanomoles in 5 microliters). In this study, the assay was performed using HCl (0.001 M) in 1 per cent Triton X-100, titrated with beta-alanine to a pH value of 3.6--3.9 as the leading electrolyte and n-caproic acid (0.01 M) as the terminal electrolyte (50--100 muA migration current). Using this technique, daily urinary TFA excretion of seven patients was measured during halothane anesthesia and for 14 days postoperatively. The TFA values were highest on the second postoperative day (317--1,259 mg). The mean values of the urinary TFA excreted during the entire study (2,501 +/- 493 mg, mean +/- SEM) were much higher than those reported previously. The isotachophoretic technique provides a sensitive assay for future research into the biotransformation of halothane.

Biotransformation↗