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INFLUENCE OF EGF ON THE RELATIVE VOLUMES OF COLLOID, EPITHELIUM AND STROMA AND ON THYROCYTE NUCLEI SIZE IN RAT THYROID LOBES IN VITRO.

The epidermal growth factor (EGF) is believed to be a potent growth factor for the thyroid gland. In the present study, we have examined the relative volumes of the main histological compartments (colloid, epithelium and stroma) and the size of thyrocyte nuclei (the mean volume, the mean intersection area and the mean perimeter) in the rat thyroid lobes incubated in vitro for 18 hrs with EGF, applied in 5 different concentrations: 0.1, 1.0, 10, 100 and 1000 ng/ml. Morphometric evaluation was performed, using a computer image analysis system, developed by us. We found that EGF - in concentration of 100 ng/ml - increased the relative volume of stroma when compared to controls, as well as to all the other groups incubated in exposure to that growth factor (used in different concentrations); at the same time, EGF decreased the relative volume of epithelium in the thyroid gland (statistical significance has been recorded only vs. EGF concentrations of 10 ng/ml and 1000 ng/ml). On the other hand, we observed that EGF - in concentration of 100 ng/ml - significantly increased the mean nuclear volume and the mean intersection area of thyrocyte nuclei when compared to the controls, as well as to EGF in concentrations of 1 ng/ml and 1000 ng/ml. With regards to the mean perimeter, a significant increase of its length was noted in the EGF(100 ng/ml)-exposed group vs. the group incubated with an addition of EGF (1 ng/ml).

Journal Article↗

Biomechanics of hip dysplasia.

When walking, each hip alternately carries the body mass minus the supporting leg. This mass exerts a force K acting on the hip with a lever arm h'; it is counter-balanced by a force M exerted by the abductor muscles, which acts on the hip with a lever arm h. The hip joint transmits the resultant R of forces K and M. Force R evokes compressive stresses in the joint. In a normal hip, force R is exerted at the center of the force transmitting surface of the joint, and the stresses are evenly distributed over this surface. This is reflected by the narrow ribbon of subchondral sclerosis in the roof of the socket. The normal femoral neck is stressed in bending with shear. It has a medial bundle of cancellous trabeculae, stressed in compression, intersecting with a lateral bundle, stressed in tension. Dysplasia and an imbalance of the muscles may have similar mechanical consequences: a shortening of the lever arm h and a more vertical orientation of force M. Shortening of h results in an increase of the force M necessary to counterbalance the moment of force K; the change in direction of force M displaces the resultant R towards the edge of the socket. The result is an increased resultant force R which becomes unevenly distributed over a smaller surface. Subluxation of the femoral head due to a shallow socket will also result in an uneven distribution of force R on a smaller surface. The abnormal distribution of compressive stresses is reflected by the development of a triangular sclerosis at the edge of the socket. This is the beginning of subluxating osteoarthritis of the hip. In a coxa valga the femoral neck may be stressed in a pure compression. This appears in the structure of the cancellous bone of the neck. Coxa vara has opposite consequences: lengthening of the lever arm h of the abductor muscles and a more horizontal orientation of force M. This results in a decrease of the resultant force R, which is displaced medially over a larger surface, resulting into smaller compressive stresses in the joint. If the acetabular cartilage of the socket does not develop further medially, the distribution of compressive stresses may become uneven with a maximum medially, where a dense triangular sclerosis develops. This is the beginning of protrusive osteoarthritis of the hip. In coxa vara, the femoral neck is stressed in bending more than in a normal hip, which is reflected by more marked cancellous trabeculae which intersect at right angles in the femoral head. The medial bundle is stressed in compression, the lateral bundle in tension.

Biomechanical Phenomena↗

[Microfolds in the suprablastoporal zone of the frog gastrula and their relationship to the geometry and mechanics of gastrulation].

Spatial distribution and orientation of microfolds arising during invagination of the outer layer of suprablastoporal zone into the blastopore dorsal lip and changes of the lip shape were studied in Rana ridibunda embryos using statistical analysis of a normal individual variability. Active invagination of the cells into the lip correlated with deviation of the orientation of microfolds from the normal in the points of their intersection with the zone of dorsal lip inflection and their orientation is normalized upon transition of the cells across the inflection zone. Frequency distribution of the angle of microfold deviation from the normal is close to the exponential and, therefore, the angle of deviation is an analog of the potential energy of cells-components of the microfold: the bigger the deviation angle, the higher the potential energy. The minimum potential energy is observed at the normal orientation of microfolds, i.e., when it coincides with the radius of the dorsal lip curvature at the point of intersection with the microfold. The following mechanism of dorsal lip formation has been proposed: equatorial contraction of cells upon their invagination into the dorsal lip causes deviation of cell flux orientation from the normal orientation and the normal orientation is restored through an increase in the local curvature of dorsal lip. When the orientation of cell fluxes is normalized, invagination of cells in the dorsal lip ceases. The wave of normalization overtakes the wave of cell invagination into the dorsal lip at the lip angle length 120 degrees. At this moment, the archenteron roof is mechanically detached from the superficial cells of the suprablastoporal zone and lateral blastopore lips and this determines separation of the presumptive notochord.

Animals↗

[Analysis of genealogical structure of populations. II. The use od numerical pedigrees for calculation of inbreeding coefficient].

A method for calculation of inbreeding coefficient F in a numerical pedigree with no reference to its graphic representation is suggested. For calculation of F, a formula that does not take into account inbreeding coefficients of common ancestors and admits intersections in a loop is used. An advantage of this method is that it automatically finds all loops formed by paths to common ancestors. Detecting these loops via their tracing in a graphic pedigree with intersecting lines of descent creates a possibility of errors. A criterion of existence of at least one common link for two numerical paths is presented. It enables one to exclude pairs of paths to common ancestors that do not form loops. The methods considered for computing F in a given pedigree give exact values of the inbreeding coefficient for autosomal and sex-linked loci and generalize the known approximate approaches. The methods are illustrated by examples.

Female↗

[3-D direct matching interpolation for rotary scanning echo-cardial images].

In the present paper, a method of three dimension direct matching interpolation for a series of 2-D echo-cardial images with intersecting each other and arranging at an angle in space has been developed. It is different from the conventional interpolation. During the interpolation, sectional images are acquired and the 3-D spatial position of "empty voxel" in sectional images is located; secondly, the cubic volume is constructed, and the motion orbit of images between two windows where the nearest original image intersects to the volume is found up, passing through the "empty voxel"; In the end, based on the matching pixels, the "empty voxel" is interpolated. This method simplifies the two interopolating procedures of the conventional methods into one procedure, and overcomes the shortcoming of the overlap of image data. Experiments show that the accuracy and reasonability of interpolation can be improved by the proposed method.

Echocardiography↗

Assessment of left ventricular wall motion.

A new method for the assessment of left ventricular wall motion, using a polar analysis, is proposed. The percent shortening of several radii, labeled at 30 degrees intervals, were plotted against Theta (degrees) and an excellent numerical and visual display of wall motion was obtained. Two methods for correcting the systolic upward shifting of apex were tested. The simplest one uses the intersection of the major and minor axes to realign both the end-diastolic and the end-systolic silhouettes. In the other method ventricular outlines were realigned using anatomical internal markers (diaphragm, ribs, or vertebrae). The intersection of both long axes, whether inside or outside the ventricular silhouettes was used as a pivot point around which the long axes were rotated and the outlines realigned. The mid-point of the long axis was used as a common center. There was no statistical difference in the two methods. The data from 14 normal subjects composed a normal percent shortening vs. Theta graph, which can be used as a frame of reference as compared with abnormal hearts.

Cineangiography↗

The ultimate creativity machine. How BMW turns art into profit.

Many companies face the challenge of balancing art with commerce. The conflict between corporate pragmatism and artistic passion and quality is persistent: designers chafe under corporate requirements, budgets, and deadlines, and nondesigners struggle to understand the business value of artistic choices. At German carmaker BMW, the fanaticism about design excellence is matched only by the company's driving desire to remain profitable. Global design director Chris Bangle presides over the intersection of art and commerce at BMW, managing the often-strained relationships among the designers, engineers, and business managers. Bangle goes to great lengths to protect his designers from the unproductive commentary of others in the company, literally posting "Stop: No Entry" signs on the design studio doors. He also protects the design process, making sure that time-to-market pressures do not harm the designs by shifting the focus to engineering too soon. As a mediator, Bangle appeals to the core values of the company and a deeply held sense about BMW-ness--a pride of product shared by everyone in the company that expresses itself in the classic quality of the cars. Every employee, designer and nondesigner alike, understands that if a car doesn't meet this standard of excellence, it's simply not a BMW--and customers won't buy it. Managing at the intersection of art and commerce means translating the language of art into the language of the corporation. In this First Person account, the author describes his inventive techniques for getting the best from his artists--and getting his ideas across to corporate managers.

Art↗

Fine structure and mechanics of the anterior border of the primate iris: a scanning and transmission electron microscope study.

The morphology of the anterior border of the primate iris has been examined by transmission and scanning electron microscopy. The results confirm that the anterior iris is composed of heavily pigmented melanocytes, fibroblasts, and a loosely arranged network of collagen fibres. The melanocytes are slender, elongate structures, which show some branching in the peripheral iris. They run parallel to the surface and are filled with spindle-shaped pigment granules which are oriented in the long axis of the cell. In the miotic state, the peripheral iris melanocytes form a dense, interlacing network. As the pupillary margin is approached, the angles between intersecting melanocytes diminish; the melanocytes appear to be parallel and in close contact with one another.During mydriasis, the peripheral iris melanocytes are compressed and pupillary components are found to intersect at angles greater than 90%. The superficial fibroblasts are flattened cells, closely applied to the underlying melanocyte processes and in the mydriatic iris form a resonably continous monolayer over the anterior iris surface. Iris pores are present, exposing the underlying melanocytes and stromal collagen. During miosis, the surface fibroblasts become attenuated and the pores increase in size and number. This paper demonstrates the value of the scanning electron microscope in presenting an accurate three dimensional model of the iris.

Animals↗

The biological basis of epistasis between quantitative trait loci for flavone and 3-deoxyanthocyanin synthesis in maize (Zea mays L.).

A major weakness in our understanding of the genetic basis of complex traits has been that of defining the extent and biological basis of epistasis. Our research group has been studying the genetic control of the accumulation of maysin, a C-glycosyl flavone, in maize, Zea mays (L.), silks. Previously, we demonstrated the importance of the p1 locus as a QTL for maysin synthesis. The p1 locus often exhibits significant epistatic interactions with other loci. We developed a mapping population, (W23al x GT119)F2, specifically designed to test whether genes in an intersecting pathway might be detected as QTLs for maysin synthesis and result in epistatic interaction effects. The a1 gene is not required for the synthesis of flavones but is required for the synthesis of 3-deoxyanthocyanins, an intersecting pathway, in maize silks. The p1 locus (P < 0.0001) was a QTL for both flavones and 3-deoxyanthocyanins. The a1 locus was also highly significant (P < 0.0001) for both traits, as was the p1 x a1 epistatic interaction (P < 0.0001). Our results demonstrate that altering the flux of biochemical intermediates between pathways may be the biological basis of major QTL effects and epistatic interactions.

Alleles↗

[Theoretical and experimental approach to the problem of changes in functional capability of cells under the effects of adaptive doses of ionizing radiation].

It is concluded that a dose range from background dose to several cGy may be separated into two parts: a) first--the interval of small doses limited from above by D* which is determined from (1 g (D*/Doc)) < -0.51 g (n/2)), where Dse is an average dose of a single event, n--quantity of irradiated cells; in this interval only one track intersects a sensitive volume; b) second--the interval of low doses, in which in average one track intersects the volume and which is ranged from top D* to bottom Dse. Because events in this region qualitatively are similar to background events, cells in the dose range b) may be adapted to the influence of radiation. The first stage of the adaptive response of cells is associated with chromosome loci (centromere) movement in a cell nucleus and as we suggest the latter is the fundamental mechanism for repairing DSB DNA and switching of gene transcription. Because the movement of chromosome loci both in the resting cells under the adapting doses and in the normal dividing cells is much the same (but the latter lose their function characteristic for differentiated resting cells), it could be assumed that the resting cells under the adapting doses also lose their functional parameters. Under chronic exposure to low doses this functional changes can be principal for discussion on the influence of low doses on health.

Adaptation, Physiological↗

Metal and metal-ATP interactions with brain and cardiac adenylate cyclases.

Metal (Me) and MeATP interactions with adenylate cyclases associated with rabbit ventricular particles and with a detergent-dispersed preparation from rat cerebellum have been studied. data were simulated to fit kinetic models in which an inhibitor (HATP or ATP) is added in constant proportion to the variable substrate (MeATP). The specific models considered were that the enzyme binds (a) MeATP as the substrate; (b) MeATP as the substrate and HATP or ATP as an inhibitor; (c) MeATP as the substrate and free Me as an activator; and (d) MeATP as the substrate, free Me as an activator, and HATP or ATP as an inhibitor. Both equilibrium-ordered and random (rapid equilibrium assumption) types of sequential kinetic models were considered. The various models were tested using cardiac particulate adenylate cyclase in the presence of either a phosphoenolpyruvate-pyruvate kinase or a creatine phosphate-creatine kinase ATP-regeneration system. Although the enzyme with either system appeared to bind Mg2+ as an activator, one or both ATP-regeneration systems also seemed to interact directly with adenylate cyclase, making clear interpretations difficult. With the phosphoenolpyruvate-pyruvate kinase system, kinetic patterns on double reciprocal plots were linear as a function of MgATP, but with creatine phosphate-creatine kinase, kinetic patterns were concave downward. The kinetic models were further tested using the detergent-dispersed cerebellar enzyme, a preparation with low adenosine triphosphatase activity and not requiring the addition of an ATP-regeneration system. Reciprocal plots were linear and intersecting as a function of either MeATP or Me (Me = Mg2+ or Mn2+), and secondary replots of slopes and intersecting as function of either MeATP or Me (Me = Mg2+ or Mn2+), and secondary replots of slopes and intercepts also were linear. These data indicate that the brain detergent-dispersed enzyme conforms to a bireactant, sequential mechanism where free cation is a required activator and free ATP is not a potent inhibitor.

Adenosine Triphosphate↗

[Transformation of chemical energy in biomolecular systems with hydrogen bonds].

The mechanism underlying the excitation of the hydrogen bond with ATP hydrolysis was considered. Coulomb interactions of the proton of the hydrogen bond A-H...B with the electrical field of the covalent bond of ADP-P were calculated. It was shown that the electrical field of the covalent bond of ADP-P excites oscillations of the proton in the complex with the hydrogen bond A-H...B and displaces it from the equilibrium towards the covalent bond. The distortion of the potential curve depends on a change in the length of the covalent bond of ADP-P. Adiabatic potentials U0 and UN of the ADP-P system were calculated, which correspond to the ground and excited states of the H-bond proton. It was found that as the length of the bond of ADP-P (rho) increases, the branches of the adiabatic potential U0(rho) and UN(rho) intersect. At the intersection point, the system can transit to the branch UN(rho), which can lead to a reduction of the barrier and a break of the covalent bond of ADP-P. Presumably, this mechanism is universal for processes of transformation of the chemical energy of ATP to the energy of excited hydrogen bond, a mechanism for the maintenance of heat balance and reduction of entropy in a living organism.

Adenosine Diphosphate↗

Adjuvant influence on glyphosate efficacy in the presence of CA2+.

Calcium ion in the spray water diminishes the efficacy of glyphosate. Ammonium sulphate (AS) is long shown to be the most efficacious remedy to this antagonism. However, it is sometimes claimed that acidified lecithins or terpenic alcohols can also be used to this aim, and even ethoxylated amines (EA) provided that calcium concentrations are not higher than 5 mM. We investigated these claims by examining dose-response curves of barley plants treated with glyphosate at various calcium concentrations in the presence of these adjuvants. Calcium ion increased the slope of the curves and ED50 values, indicating a decrease in efficacy. Acidified lecithins and terpenic alcohols did not modify the response of barley to glyphosate observed in the presence of calcium ion. AS restored the ED50 and slope values observed in the absence of calcium ion. It was concluded that the inhibition of glyphosate efficacy by calcium ion was not relieved by terpenic alcohols and acidified lecithins but was completely reverted by AS. EA decreased ED50 and ED90 values of the response curves established in the presence of calcium ion without influencing the slopes (which remained high). As a consequence, at calcium concentrations up to 5 mM the response curves obtained with AS and EA intersected. It followed that in the presence of EA, ED50 values were higher than AS, whereas ED90 values were lower. By contrast, at 10 mM calcium the response curves did not intersect and consequently, in the presence of EA, ED50 and ED90 values were both higher than AS. Since ED90 relates to efficacies sought in the field, our experiments explain why at low calcium concentrations EA may appear as a better remedy than AS. Glyphosate formulations containing ammonium sulphate or a higher concentration in surfactants than usual glyphosate formulations were also studied. In the presence of calcium ion they behaved in a way which was in agreement with the above observations.

Alcohols↗

[A way to spatial irradiation planning. III. Further information on the procedure for obtaining dose homogeneity in noncoplanar ray beams and its experimental verification].

The method is based on the following principle: Single, initally unsettled parameters of irradiation are determined by explicit calculation in such a way that the dose gradient resulting from the dose gradients of the single ray beams in the point of intersection of their axes becomes zero. The separation or addition of components of the gradients is performed by use of co-ordinates for the ray beam as well as for the body. The following parameters can be determined explicitly: First, the weights of the partial doses which are to form the total dose in the point of intersection and/or second, the angles of the wedges and/or third, the rotational angles of the wedge filters, i. e. the angles of rotation of the wedge filters about an axis corresponding to the central ray. In the course of the following experimental verification of the method, maximally possible dose homogeneity results within the area of the crossing ray beams. Moreover, the advantages of field arrangements with different planes of incidence are coming into view.

Humans↗

Design and production of dental prosthetic restorations: basic research on dental CAD/CAM technology.

Dental prosthetic restorations (crowns and FPDs) are currently produced mainly by conventional dental technology methods. The automation of the production process can be achieved by the use of CAD/CAM techniques. In addition, it has become possible to use materials that previously could not be processed for technical reasons or could not be processed economically, especially high-performance ceramics. Although CAD/CAM methods for producing fixed restorations are of increasing interest, little information has been published about their mode of operation and functionality. To date, studies have focused mostly on special systems. However, basic studies are lacking. Basic research on the most important aspects of CAD/CAM fixed dental restorations from the viewpoint of production, information technology, and dentistry/dental technology are the subject of a current research project. The aim of this study is the presentation of preliminary results. The CAD/CAM process for fixed restorations was analyzed and broken down into single steps. In order to examine the influence of the single steps in the process chain, a computer test model with the teeth of the maxilla and mandible in static occlusion was developed and reverse engineered. While producing the test model, fundamental knowledge regarding the manufacturing of dental restorations with functional occlusal surfaces was gained. The intersection of the maxillary and mandibulary occlusal surfaces allows the qualitative analysis of occlusal contacts analogous to the conventional technique. Furthermore, a quantitative assessment of the size of the occlusal contacts and the measurement of intersection is possible.

Analog-Digital Conversion↗

[A model of the analysis of nursing knowledge].

We present an analysis based on the systemic idea where production, dissemination and utilization are constituting elements of knowledge, interdependent, allowing, in a global approach, identification of the interactions and areas of intersection. Each part, with its specific dynamism, interacts with the others, creating areas which contribute to growth. The concomitant intersection of the parts is characterized as the essence of knowledge and the dynamics of these seek the equifinality of the system: the incorporation of knowledge to practice.

Clinical Competence↗

Kinetic model of the epidermal growth factor (EGF) receptor tyrosine kinase and a possible mechanism of its activation by EGF.

The tyrosine kinase activity of the epidermal growth factor receptor (EGFR-TK) was determined at varying poly-Glu6Ala3Tyr1 (GAT) or [Val5]-angiotensin II (AT) and constant ATP concentrations and vice versa. With GAT as substrate, double reciprocal plots intersected practically on the abscissa following EGFR-TK pre-activation with EGF, but below the abscissa without EGF pre-activation. The EGFR-TK inhibitors App(NH)p (5'-adenylyl-beta, gamma-imidodiphosphate) and ADP were competitive with ATP and noncompetitive with GAT. Four families of 1/v vs. 1/[ATP] plots, constructed at different fixed concentrations of ADP and a different constant concentration of GAT for each family, yielded Slope1/ATP replots which intersected to the left of the ordinate and below the abscissa. GAT and AT, as cosubstrates, were competitive with each other and noncompetitive with ATP; 1/v vs. 1/[GAT] or 1/[AT] plots were hyperbolic and reached horizontal asymptotes when v was expressed as the rate of common product formation. All data were subjected to computer best-fit analysis by a program written especially for this purpose. We conclude that (i) the EGFR-TK reaction follows a Sequential Bi-Bi Rapid Equilibrium Random mechanism, and (ii) EGF induces conformational changes in the EGFR-TK active center which lead to marked decreases in the apparent dissociation constants of both substrates of the kinase reaction and a concomitant increase in initial velocities and Vmax (apparent).

Carcinoma, Squamous Cell↗

The pathogenic classification of glaucomas.

On the basis of a pathogenic definition, our classification distinguished for each of the first intersections a main--mostly determinant mechanism and a secondary mechanism, mostly modulating the damages: hydrodynamic alteration and tissue resistance alteration--for the second intersection, outflow block and hypersecretion--for the third. Reflecting the state of present knowledge, from the corresponding forms of the disease, only outflow block glaucoma is completely analysed, the exogenous, trabecular, pretrabecular and mixed glaucomas being described. In order to permit the correct framing of all pretrabecular block glaucomas, the posterior push forms (retrovitreal or parietal) were introduced besides the anterior already described forms (pupillary or angular). As for low tissue resistance glaucomas, genetic, cardiovascular, metabolic, haematologic and ocular influences are mentioned. This classification avoids the theoretical inadvertencies of previous classifications offering the synthetic frame of a coherent system, open to any new developments, all inclusive, terminologically clear and with direct therapeutic references.

Glaucoma↗