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The article deals with stages of establishment and development of toxicologic studies in the Institute over 90 years. The authors stress the role of professor N.S. Pravdin and RAMSc Corresponding Member I.V. Sanotsky in formulation and solving major problems of toxicology, in specifying its methodologic background. Priority directions in theoretic and applied research are presented, main results are given.

The question of need for standardization and validation of the complex methods to establish the maximum concentration limit (MCL) ofbiotechnological strains in the water of water bodies is under discussion. On the basis of the experimental studies it has been shown that a unified quantitative criterion for safety could not to be recommended for biotechnological strains and therefore requires the study of each strain in order to substantiate the safe level in water of water bodies. Proposed biosafety program should include the study of pathogenic properties in acute experiments and specific effects in subchronic experiments to study the influence of strains on the process of water purification and a risk assessment of transformation products of chemicals and the justification of the safety factor when establishing MCL t in terms of the toxic effect.

The state-of-the-art of hygienic standardization of biotechnological strains of microorganisms is considered. The last century's investigations accumulated abundant experimental data on the estimation of the adverse effect of the strains, formulated main guidelines for evaluating the negative activity of producing strains, and proposed a schematic diagram for toxicological and hygienic investigations of new biotechnological strains. Further studies made it possible to elaborate their human hazard classification, to improve study programs, to substantiate a priority list, and to develop approaches to assessing the occupational microbiological risk.

Based on studies of action characteristics (pathogeneity, general toxicity, immunotropic and dysbiotic effects) of 28 biotechnologic strains assigned to various taxonomy groups (Gram-negative and Gram-positive bacteria, nocardial actinobacteria and actinobacteria, mold fungi and yeast-like fungi) and literature data, the authors suggested hygienic classification of microorganisms according to their jeopardy effects in the body and adjusted this classification to recommendations of international organizations (WHO, OECD).

By analyzing the findings and databases on the hygienic standardization of industrial microorganisms, the authors have improved a research program for industrial strains on substantiating their safe exposure levels in workplace and ambient airs. A shortened program is proposed to investigate gram-positive bacteria and nocardioformic actinomycetes (Lactobacillus, Micrococcus, Propionibacterim, Brevibacterim, Rhodococcus), which have no negative effect. It is necessary to study gram-negative bacteria and micromycetes (Pseudomonas, Alcaligenes, Acinetobacter, Arthrobacter, Aspergillus, Penicillum, Candida), which have pronounced immunotropic and dysbiotic properties by the full program, by including the evaluation of all observed negative effects. On the basis of this group, the priority microorganisms that confer a real danger to workers' health in developing allergic diseases have been listed.

A total of 90 images of male cranes from different groups of horizontal profiling (120 +/- 10 degrees, 140 +/- 10 degrees, 160 +/- 10 degrees) were studied in experiment with the coordinate-controlled complex for turning angle (from the position full face to the right and left by 14 degrees with spacing 2 degrees). Each image was marked according to the system of 18 control points. Precision of the angle fixation was 0.1 degrees. Calculation of the angles of horizontal profiling and turning of the crane were made according to a specially devised program INPUTTING. Statistic processing of the computer data base made it possible to calculate precision rates of marking points and regression equation describing the pattern of cranial control points in turning. It is shown that presicion of the turning angle estimation with reference to horizontal profiling is much higher than without it. Basing on the data obtained a method of zeroing of coordinates of the control points (placing in position for correct scaling of the objects of craniofacial identification) was devised. The method allows greater reliability of the results of personal craniofacial identification.

Reports the results of examination of the skeleton of Admiral F. F. Ushakov, carried out in connection with canonization in the Russian Orthodox Church. Heretofore unknown data on the somatic characteristics of F. F. Ushakov and his diseases are presented. Special attention is paid to uneven age involution of the skeleton and the hypoergic aging velocity. A detailed morphological similarity between the skulls of F. F. Ushakov and monk Feodor (Admiral's uncle, I. I. Ushakov) evidenced common features inherited through the masculine line. Modern computer technologies showed that the appearance of F. F. Ushakov, determined by the skull and postcranial skeleton, agree with his appearance on the life-time portrait, in spite of Professor M. M. Gerasimov's opinion (1949). In this connection, the possibility of repeated reconstruction of Admiral Ushakov's appearance is proven.

An improved method for computer-aided personality identification by the skull, based on the POSKID 1.1 software, consists in investigation of enlarged images of the skull and life-time photograph of the probable individual by coordinates of 49 anatomical points; independent quantitative evaluation of the aspect of each of the compared objects by the X, Y, and Z axes; formal evaluation of the results of comparative study of the skull-portrait by multidimensional discriminant analysis models. The proposed version differs from the POSKID 1.0 software in the method for evaluating the spatial position of the head on the portrait and adequate orientation of the skull in space, which necessitates the utilization of coordinate-regulated holder POSKID 1.1 method is based on multidimensional discriminant analysis and suggests a virtually reliable solution in 76.13-80.65% cases, a probable solution (positive and negative) in 11.61-18.06% cases, and motivated refusal from solution in 5.81-7.74% cases. In case of a probable or indefinite solution further investigations are recommended making use of life-time photographs with different aspects.

The aim of this study was to develop a "quantitative verbal portrait" method on the basis of universal measured signs of the face and skull. The database includes 90 cases with expert evaluation of photocompatibility with proven identity. Four groups of signs were investigated: DX and DY--the width and height between accurately fixed concrete craniometrical (facial) points and the so-called RX and RY indices--the ratio between distances within the framework of the same direction. The proposed scheme of evaluation helps compare the photograph of a live human and the skull. For evaluating the degree of identity, one should have a summary characterization of all selected signs for the skull and compare it with the sum on the photograph; sometimes it is possible to rule out the identity of the photograph and the skull by the absolute size, e.g., a very large skull cannot belong to a human with a very little face. The score for each group of signs is used for analysis of the information for detecting the similarities. Accumulation and comparative analysis of two information flows are possible: database on portraits of lost subjects and database on graphic images of the skulls of unidentified corpses.

A method for isolation of the KEX2-gene-encoded membrane-bound proteinase from alpha-cells of Saccharomyces cerevisiae yeast has been modified. The isolated enzyme hydrolyzes peptides and proteins with basic amino acid pairs which are cleaved at the C-ends of their peptide bonds. Because KEX2 proteinase is located within the Golgi compartment, it may be isolated by differential centrifugation of broken cells at 7000g for 15 min and at 20,000g for 15 min. By extracting the fraction that contains the active enzyme by a detergent solution, a protein has been obtained with specific activity 30 times higher than that of the membrane extract prepared according to the standard technique. This protocol decreases the number of steps required to isolate the enzyme. The effects of pH and inhibitors on KEX2 proteinase-catalyzed hydrolysis of Ac-Leu-Lys-Arg-pNA were studied. KEX2 proteinase can participate in peptide hormone processing because it cleaves human proinsulin at the peptide bond between Arg32 and Glu33. The KEX2 proteinase can specifically cleave large recombinant proteins, for example, a protein consisting of a gamma-interferon fragment linked to HIV1-proteinase via a Lys-Arg-containing peptide.

Experimental findings indicate that if the basic position of the skull is assessed visually (as is usually done in expert photocombination), various video images of the same skull never fully conform to each other, the deviations reaching 1.5 and more degrees. As a result of this, the accuracy of determining the reference points on the video image varies from 1.-1.5 to 4.0-4.5 mm (en face) and 1.5-2.0 to 6.0-6.5 mm (profile). The task of identification of two images of the skull is reliably solved in 87.7% cases, and in 12.3% cases the results may be false-positive or false-negative. The individuality of the skull, that is, the impossibility of its replacement during computer-aided photocombination is realized in the absence of aspect distortions and minimal errors of measurements. Hence, a new technology of studies is to be introduced: coordination-monitored stable complex of video camera and computer with metric monitoring of all parameters liable to change.

The paper presents clinical findings of 210 children with localized osteogenic sarcoma who have undergone various treatments. The authors consider neoadjuvant chemotherapy the method of choice, but by replacing tubular bone defects, endoprosthesis should be regarded the method of choice, which substantially reduces the time of rehabilitation and yields good (32.4%) and satisfactory (47.0%) functional results in most patients. In children with osteogenic sarcomas, the outcomes of treatment depend on its scope: 5-year survival was achieved in 68% of cases following multimodality treatment and in 36.2 and 14.0% after combined treatment and monotherapy alone, respectively. The retrospective analysis of treatment for morphologically verified Jung's sarcoma shows it expedient to implement a comprehensive program, including cyclic polychemotherapy, radiation of a damage focus in a dose of 57 Gy, obligatory surgical intervention into the operable sites, by assessing therapeutical pathomorphism and subsequent adjuvant polychemotherapy for at least 12-18 months.

Improvements in surgical technique and advances in myocardial protection have resulted in low rates of morbidity and mortality despite a greater incidence of high-risk patients. Noncardiac morbidity prolongs hospital stays and increases the costs of cardiac surgery. This study examines the preoperative predictors of stroke following isolated coronary bypass surgery. The clinical records of 3910 consecutive patients who underwent isolated coronary bypass surgery at the University of Toronto were reviewed. Stepwise logistic regression identified six independent predictors of stroke following CABG (percent in parentheses) and calculated factor adjusted odds ratios (OR) for each risk factor. Triple vessel coronary artery disease was the most important predictor (1.9%, OR 5.71), followed by normothermic systemic perfusion (3.8%, OR 4.85), age > 70 years (3.2%, OR 3.88), a previous history of transient ischemic attacks or stroke prior to surgery (6.1 %, OR 3.7), peripheral vascular disease (4.7%, OR 2.77), and diabetes mellitus (2.6%, OR 2.01). The mechanism of stroke is likely different between these high-risk groups and strategies to prevent postoperative stroke should focus on the mechanisms responsible in high-risk patients.

A new method of duodenal closure in stomach reconstructive resection in patients with pathologic disturbances after vagotomy with drainage operation is worked up. 6 patients have been operated. No postoperative complications were observed. All the method advantages are evident.

Radioimmunoassay was employed to determine basal levels of LH, FSH, prolactin, total testosterone and 17 beta-estradiol in plasma from 52 pre- or postmenopausal women with prosopalgia consequent to cervical osteochondrosis. The measurements were made before and after laser treatment. Different from the control, basal levels of the hormones and the trends in their changes due to laser therapy depended on the patients' age and the disease stage.

The author studied the condition of the esophagogastric junction in 376 patients with gastric and duodenal ulcer before and in the late-term periods after selective proximal vagotomy and distal resection of the stomach performed in combination with antireflux interventions on the cardia (fundoesophagorrhaphy, crurorrhaphy+fundoesophagophrenorrhaphy, fundoplication) or without such interventions. It is shown that reliable correction of the obturator mechanism of the cardia in selective proximal vagotomy may be achieved only by fundoplication. In gastric resection fundoplication is advisable in marked reflux esophagitis, distention of the hiatus esophageus of third degree, hernia of the hiatus esophageus, and cardiac ulcer. In all other patients with distal resection of the stomach crurorrhaphy+fundoesophagophrenorrhaphy is justified as a preventive measure.

Under analysis are results of transgastric vagotomy in 211 patients with ulcer disease of the duodenum operated upon at the period from 1979 to 1989. The transgastric selective proximal vagotomy (TSPV) was used in 150 patients, an original authors' extensive TSPV--in 33 patients, combined transgastric vagotomy (CTV)--in 28 patients. Long-term results of TSPV are recognized to be excellent and good in 79.1% of the patients, satisfactory--in 9.8%, unsatisfactory--in 11.1%. An analysis of causes of unsatisfactory results of TSPV is made. Advantages of the method of extensive TSPV were shown. The CTV is thought to be expedient in patients in urgent surgery and in patients with severe coexistent diseases.

The reactogenic properties and immunological potency of modified cholera chemical vaccine (choleragen-toxoid + O-antigens Inaba and Ogawa) were tested in 278 volunteers aged 18 years and over in comparison with those of a commercial batch of monovalent cholera vaccine (choleragen-toxoid + O-antigen Inaba). The cholera vaccine, enriched with O-antigen Ogawa, was found to be safe; vaccination with this vaccine was not accompanied by the development of systemic and local reactions whose frequency and intensity met the requirements for the reactogenic properties of commercial cholera vaccine. The immunological potency of the bivalent vaccine with respect to strain Inaba was not inferior to that of the commercial vaccine; at the same time in persons immunized with the new preparation the titers of vibriocidal antibodies to strain of serovar Inaba were five-fold higher. The conclusion on the expediency of using cholera chemical vaccine enriched with O-antigen Ogawa was made.

276 volunteers aged 19 years and over were placed under observation in the course of the trial of oral cholera vaccine in tablets, containing choleragen toxoid, O-antigens of serovars Inaba and Ogawa and a number of Vibrio cholerae exoenzymes, for safety, reactogenic properties and immunological effectiveness. The vaccine was found to produce no reactions in a dose of 1-4 tablets; the administration of 3 tablets (300,000 binding units of the toxoid and 10,000 units of O-antigens, serovars Inaba and Ogawa) was shown to induce the most intensive synthesis of both antitoxins and vibriocidal antibodies in the blood sera of volunteers, as well as IgA coproantibodies. The oral vaccine was found to have an advantage over parenteral vaccines due to the absence of reactogenic properties and the formation of local immunity: coproantibodies appeared in 80% and 9% of the vaccinees respectively.

The data on antibiotic sensitivity of 38 strains of S. pneumoniae isolated from children and 46 strains isolated from carriers are presented. The isolates from the carriers had significantly higher sensitivity to benzylpenicillin, ampicillin, methicillin, oxacillin, cefazolin, erythromycin, oleandomycin and lincomycin. Resistance to gentamicin was more frequent in the strains isolated from the carriers. Among the strains of S. pneumoniae isolated from the patients and carriers representatives of serovar K19 were more frequent. There were no statistically reliable difference in them by sensitivity to benzylpenicillin, ampicillin, cefazolin, lincomycin and rifampicin. Still, the isolates from the carriers were much more sensitive to methicillin, oxacillin, oleandomycin and erythromycin.

The influence of transgastric selective proximal vagotomy (TSPV) on the cardia functional state was studied in 120 patients with ulcer disease of the duodenum. It was established that seromyotomy in the zone of cardia and lesser curvature of the stomach when performing TSPV resulted in disturbance of the constrictor-valvar mechanism of the esophago-gastric passage. Fundoesophagography does not allow the insufficient closure of the cardia to be adequately corrected. The significance of fundoplication is stressed in order to restore the mechanism of cardia closure after TSPV.

An analysis of results of transgastric selective proximal vagotomy in 90 patients with ulcer disease of the duodenum enabled the authors to conclude that seromyotomy of the lesser curvature of the stomach when performing transgastric selective proximal vagotomy fails to ensure valuable parasympathetic denervation of the zone in question which results in a number of cases in preservation of uninterrupted gastric acid formation of high intensity and in the development of recurrent ulcer.

A total of 319 strains of S. aureus and 729 strains of S. epidermidis belonging to different biovars isolated from the skin and nasal mucosa of 349 persons representing 8 independent groups were tested. On the whole production of penicillinase was more often observed in the strains of S. aureus than in the strains of S. epidermidis. Within the first species this property was more often detected in the strains of biovar I as compared to the other biovars. However, the frequency of the penicillinase-producing strains within S. aureus and the biovars of S. epidermidis markedly varied.

Oral cholera chemical vaccine in the doses tested (2 and 3 tablets) proved to be areactogenic, harmless and immunologically effective in a controlled limited trial in 150 volunteers. By the results of titration of specific antitoxins and vibriocidal antibodies in the blood serum, as well as of coproantibodies a dose of 2 tablets was chosen as the optimal one.

The process of microfiltration carried out in the regimen of destruction of concentrational polarization layer decreases considerably the retention of admixture proteins in filtrational concentration of virus suspension. This allows the membrane technology to be used not only for concentration but also for profound purification of the virus-containing allantoic fluid for preparation of inactivated influenza virus. Using the microfiltration method, vaccine preparations of any influenza virus strain may be obtained without loss of biological activity. The resultant vaccine is highly immunogenic and safe for man. The filtration technology makes it possible to restore the preparations discarded because of low virus titres or excess protein content.

A primary culture of cells derived from uninvolved and atherosclerotic intima of human aorta was used to elucidate the role of cyclic nucleotides in atherogenesis. The cells cultured from fatty streaks and atherosclerotic plaques had a 2- to 8-fold lower cyclic AMP level and a 1.5- to 2-fold higher level of cyclic GMP compared with those of a grossly normal intima. Medial cells cultured from nonlesioned and atherosclerotic aortic segments showed no differences in the cyclic nucleotide concentrations. Reduction of the intracellular cyclic AMP with 2′-deoxyadenosine or a cyclic GMP elevation with its dibutyryl derivative, or liposomes containing cyclic GMP stimulated the uptake of [ 3 H]thymidine and protein synthesis in the cells cultured from unaffected intima. On the contrary, a rise of the intracellular cyclic AMP caused by adenylate cyclase activators, a phosphodiesterase inhibitor, dibutyryl cyclic AMP, and liposomes containing cyclic AMP inhibited cell proliferation and protein synthesis. Elevation of the intracellular cyclic AMP stimulated the hydrolysis of lipids which led to reduction of lipid levels in the cells cultured from atherosclerotic lesions. The results of this study corroborate the existence of a relationship between the alterations of intracellular cyclic nucleotide levels and the metabolic disorders occurring in atherosclerosis.

The surgical anatomy of vagus nerves was studied in 25 corpses and in protocols of operations-vagotomies in patients with ulcer disease of the duodenum. The authors consider incomplete vagotomy to be responsible for insufficiently decreased secretion of hydrochloric acid after operation in 24 (23.1%) of 104 patients examined. It was found that both the right and the left vagus nerves had different numbers of trunks and branches. The knowledge of variants of branching and disposition of the vagus nerve branches decreases the risk of incomplete and inadequate vagotomy.

Remote results within the terms of from 1 to 3 years in 60 patients and the working ability in 73 patients subjected to selective proximal vagotomy (SPV) or SPV with drainage of the stomach were studied. Functional disorders were observed much more rarely after the isolated SPV. The use of benzohexasonium and electrostitmulation of the stomach in the early postoperative period allows preventing the development of functional disorders. The SPV ensures an early recovery of the working ability.