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[Theoretical aspects of the quantitative study of the chemical structure-biological action relationship].

The study of the interrelationship between the chemical structure of the drug molecule and their biologic activity is one of the most modern aspects of current pharmacology and pharmacochemistry. The information, obtained by these studies, contributes for more precise and detailed understanding of the mechanisms of drug molecule interaction with some biologic structures, and this helps to clarify a series of biologic and physiological phenomena. The authors describe in this paper some methods, which are used, when the dependences between structure and action are search for as well as the basic physiocochemical and quantum -- chemical values, which determine the pharmacological effect of drugs.

Binding Sites

An integrated set of computer programs for processing electron micrographs of biological structures.

A set of computer programs is described which has been developed for processing electron micrographs of biological structures. The programs provide facilities for efficient image storage, enhancement and display. Extensive programs are available for analysis of images of structures with translational, rotational and helical symmetry, and for performing 3-dimensional reconstruction. The considerations which went into the design of the system are listed. A description is provided of the means of control of the main program, which performs the majority of the image processing operations, and an example is given to illustrate its use. These programs are compared with other program systems also developed for micrograph image processing.

Computers

Structured Biological Modelling: a method for the analysis and simulation of biological systems applied to oscillatory intracellular calcium waves.

In biology signal and information processing networks are widely known. Due to their inherent complexity and non-linear dynamics the time evolution of these systems can not be predicted by simple plausibility arguments. Fortunately, the power of modern computers allows the simulation of complex biological models. Therefore the problem becomes reduced to the question of how to develop a consistent mathematical model which comprises the essentials of the real biological system. As an interface between the phenomenological description and a computer simulation of the system the proposed method of Structured Biological Modelling (SBM) uses top-down levelled dataflow diagrams. They serve as a powerful tool for the analysis and the mathematical description of the system in terms of a stochastic formulation. The stochastic treatment, regarding the time evolution of the system as a stochastic process governed by a master equation, circumvents most difficulties arising from high dimensional and non-linear systems. As an application of SBM we develop a stochastic computer model of intracellular oscillatory Ca2+ waves in non-excitable cells. As demonstrated on this example, SBM can be used for the design of computer experiments which under certain conditions can be used as cheap and harmless counterparts to the usual time-consuming biological experiments.

Calcium

Aldehyde bisulfite-toluidine blue (ABT) staining as a topo-optical reaction for demonstration of linear order of vicinal OH groups in biological structures.

The aldehyde-bisulfite-toluidine blue reaction followed by poststaining stabilization with potassium ferricyanide (ABT) is described as a topo-optical, oriented staining reaction of the vicinal OH groups of complex carbohydrates in biological structures such as polysaccharides, glycoproteins and glycolipids. The birefringence as induced by the oriented dye binding as a result of ABT is indicative of linear order of the vicinal OH groups and, in turn, provides information on the ultrastructural pattern of carbohydrate moieties in biological substances, which pattern is often not demonstrable by other ultrastructural methods. The possibilities of this new approach to the ultrastructural analysis of complex carbohydrates with ABT in a great number of biological substances is demonstrated and its practical value in histopathology discussed.

Aldehydes

PIK3CA in Cancer: Structure, Biology, Alterations, and Actionability.

PIK3CA, which encodes the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), is one of the most frequently altered oncogenes in human cancer and a major driver of tumor initiation, progression, metastasis, and therapeutic resistance. Over the past two decades, advances in structural biology, cancer genomics, and translational research have substantially expanded our understanding of PIK3CA function and established the PI3K pathway as a clinically actionable therapeutic target. This review provides an overview of the structural organization and physiological functions of the PI3Kα complex, the molecular mechanisms underlying oncogenic activation, and the diverse spectrum of PIK3CA alterations across human malignancies. We also summarize the current landscape of PI3K-targeted therapies, highlighting both approved agents and emerging therapeutic strategies. Clinical evidence supports the rational integration of PI3K inhibitors with endocrine therapy, CDK4/6 inhibitors, MAPK pathway inhibitors, dual PI3K/mTOR inhibition, and immune checkpoint blockade. In addition, accumulating evidence indicates that PIK3CA plays a pivotal role in shaping the tumor immune microenvironment, providing a biological rationale for combining PI3K inhibition with immunotherapy. Finally, we discuss future directions in precision oncology, emphasizing integrated molecular profiling, liquid biopsy, single-cell and spatial technologies, functional genomics, and evolutionary approaches as complementary strategies to refine patient selection, overcome therapeutic resistance, and optimize clinical outcomes.

PI3K signaling

The application of an image analyzing computer (Quantimet 720) for quantitation of biological structures--the automatic counting of mast cells.

A Quantimet 720 image analyzer was utilized in order to 1) quantify mast cells automatically in gingiva and in doing so to 2) investigate the applicability and accuracy of the machine for quantitative analysis of biological structures. The mast cells of two hundred gingival sections were counted first by means of the Quantimet and then by manual count. Results indicated that a) mean counts of mast cells obtained by means of the Quantimet were comparable to that of the manual counts, b) although the spread was larger than by manual methods, the Quantimet automatic image analyzer performed quantitation more rapidly.

Animals

[Mechanisms and ways of regulation of lipoic acid penetration into biological structures].

Experimental evidence of the penetration of low doses (100--120 mkM) of lipoic acid (LA) into cells and mitochondria by means of transport systems, involving proteins was obtained. The functioning of those systems is regulated by hormones, is dependent of redox states, is disturbed in the presence of energy metabolism inhibitors and is stimulated by repeated injections of LA. The penetration of LA into erythrocytes is facilitated by a concentration gradient K+ and Na+ and the high activity of transport ATPases. In case of high (over 120 mkM) content of lipoate in the incubation medium, its penetration into the cells and mitochondria occurs largely due to ordinary diffusion. Such penetration of LA predominantly occurs also under conditions of transversely directed gravitational overloading (6g). The rate of LA penetration into the biological structures of the organism is regulated by complicated and efficient mechanisms, involving hormonal control of protein biosynthesis.

Adenosine Triphosphatases

Real-time imaging with a new ultrasonic camera: part I, in vitro experimental studies on transmission imaging of biological structures.

Results are described of in vitro biological experimentation using a new through-transmission ultrasonic camera system developed at the Stanford Research Institute. The camera system produces real-time focused, orthographic images of a 15 times 15 cm field. The in vitro studies, which demonstrate the diagnostic potential of the new technique, include transmission images of selected excised organs such as liver, kidney, spleen, and uterus. In addition, preliminary studies evaluating ultrasonic image quality and the effect of out-of-focus structures are discussed.

Animals

[A model of biological structure adequate for a dynamic organicist concept of psychiatry].

A "dynamic organicist" conception of the psychiatry is credible only with a pattern of biological encephalic structure corresponding with the complexity and lability of the psychology and psychopathology features. The author reports the results of researches of his group by electron microscopy concerning the human cerebral cortex, permitting to elaborate adequate pattern. The encephalic structures are very complex, changeable, labile, therefor her variations can correspond with the "psychologics" variations.

Adolescent

Structural biology and diabetes mellitus: molecular pathogenesis and rational drug design.

Emerging concepts in the aetiology and pathogenesis of Type 1 (insulin-dependent) diabetes mellitus may offer new opportunities for treatment and cure. Here we describe recent advances in structural molecular biology and molecular design relevant to rational drug discovery. Such approaches focus on the three-dimensional structures of macromolecules and their interactions. In the coming decade such techniques may be applied to a wide variety of diabetes-related targets.

Amino Acid Sequence

[The self-organization of biological structures (author's transl)].

Viruses played an important role in analysing macromolecular structures. Structure and function in living systems are arranged hierarchically. An important purpose of biology is to describe the correlation between the structural hierarchy and the observed assembly and to analyse the embryological program of the organism.

Adenylate Kinase

Coupling of Gaussian electromagnetic pulse into a muscle-bone model of biological structure.

The effect of angle of incidence on the transmission electromagnetic pulse with Gaussion character in biological material is studied. The model assumed is a layer of soft tissue over a semi-infinite medium of boney structure governed by alpha dispersion. The numerical results demonstrate that the transmitted pulse strength is the greatest when the pulse is incident normally on the air-tissue interface. The coupling efficiency for a one microsecond pulse is three times as big as that for a ten microsecond pulse.

Bone and Bones

[Correlative analysis of chemical structure - biological activity using Hansch's method: principles and development of the method].

The basic principles and developments on which the Hansch multiple parameter approach depends are described. A correlation analysis on the antibacterial activity of 2-Y-4-(X-phenyl)-3H-1,5-benzodiazepines is discussed. The use of indicator varioables is shown to greatly increase one's ability to formulate quantitative structure-activity relationships. This approach allows one to carry out objective studies of massive amounts of chemical and biological data.

Bacteria

The CD34 antigen: structure, biology, and potential clinical applications.

The diversity of function of mature circulating blood cells is reflected in their respective complements of cell-surface molecules and receptors. Although monoclonal antibodies have been instrumental in the identification and characterization of many cell-surface molecules on mature hematopoietic cells, the CD34 antigen represents to date, the only molecule, similarly identified, whose expression within the blood system is restricted to a small number of primitive progenitor cells in the bone marrow. Although its precise function remains unknown, the pattern of expression of the CD34 structure suggests that it plays an important role in early hematopoiesis. The availability of CD34 antibodies has greatly aided the development of techniques for the enrichment of primitive progenitor cells for studies of hematopoiesis in vitro. Additionally, the use of CD34 antibodies for the 'positive selection' of hematopoietic stem/progenitor cells represents and alternative strategy to 'negative selection' or purging for the large-scale manipulation of bone marrow cells prior to transplantation. The availability of pure populations of the most primitive hematopoietic progenitor cells may also facilitate the development of genetic techniques for the repair of specific blood cell disorders. In this article, we review the biology of the CD34 molecule and assess some of the roles for CD34 antibodies in immunopathology and for progenitor/stem cell purification in clinical applications.

Animals