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The publications on the structural and functional features of the main molecular shaperon of li-chain were updated. In the 1990s the determination of molecular shaperon as a group of mutually unrelated protein molecules taking part in the assembly of other polypeptides was worked out. In humans the main isoform of li-chain is the protein with a mol. wt. of 31-33 kD. A great variety of functions of this shaperon is linked with definite amino acid sequences. In particular, the molecular shaperon of the molecules of the main histocompatibility complex-II has functions connected with the presentation of antigen and the differentiation of B lymphocytes.

Publications on C-lectin receptors, multifunctional surface molecules of antigen presenting cells are updated. The study of C-lectin receptors is stipulated by their role in antimicrobial protection. The importance of C-lectin receptors of dendrite cells in the system of the recognition of microbial carbohydrate as well as their properties of the targeted supply of tumor cell and other antigens to dendrite cells with the purpose of the formation of immunity against faintly immunogenic antigens is considered. Suggestion is made on the potential of their use as experimental preparations for immunotherapy.

The relative percentage of type III to type I collagen, the ratio of alpha 1(I) to alpha 2(I) collagen chains and the ratio of dimers (beta-chains) to monomers (alpha-chains) in type I collagen have been measured in solubilized collagen fractions from keloids and hypertrophic scars aged about 1-7 years after burn. In tissue samples the content of crosslink with structure of pyridinoline were analyzed and expressed as mole of crosslink per mole of collagen. A comparison between hypertrophic and keloid scars has shown that the young (about 1 year) hypertrophic scars have higher ratios alpha 1(I)/alpha 2(I) and beta 11 + beta 12/alpha 1(I) + alpha 2(I). The increased proportion of beta-chains in the younger hypertrophic scars approximated to the same level as in normal skin within 7 years after lesion. There was no decrease in the ratio dimers/monomers of collagen type I with age of keloid scar tissue. The relative amount of collagen type III in young keloid scars was found decreased as compared to age-matched hypertrophic scars (13 +/- 3 and 17 +/- 7 respectively), but was similar in the older scars. The average pyridinoline crosslinks content per mole of collagen in keloids was 2 times as high as in hypertrophic scars. The data support the suggestion that general, as well as peculiar disturbances of collagen metabolism are involved in the development of keloids and hypertrophic scars.

Imbalance between the synthesis and degradation of collagen is a common sign of tissues of hypertrophic and cheloid scars. The fact that the collagen of abnormal scars of the both types have a polyfunctional linkage with a structure of pyridinol and high amounts of a polyfunctional linkage with a structure of pyrrole (Ehlich's chromogen) in the collagen of cheloid scars support the assumption that the collagen synthesis-degradation imbalance may be due to the enhanced resistance of structurally unchanged collagen to collagenolytic enzymes. The comparative studies of the ratio of type 1 collagen homotrimers to heterotrimers, that of type 1 collagen dimers to monomers, and that of types 1 to type 3 collagen in the pepsin extracts of abnormal scars of various age and patients' intact skin suggest that there are certain differences in the magnitude and scar age-related changes in the expression of collagen genes and posttranslational collagen modifications in the tissue of hypertrophic and cheloid scars. It is suggested that age-specific time course of collagen metabolic and structural changes in the abnormal scars may result from their alterations of the population composition of fibroblasts with a different phenotype.

The changes in the content of mature crosslinks with pyridinoline structure and soluble/insoluble collagen ratio in the costal cartilage tissue of human beings aged from 1 month to 57 years were found to be age-dependent. The effect of the pyridinoline crosslink content on the soluble/insoluble collagen ratio in human costal cartilage tissue may constitute no less than 67% of the total influence of the sum of all factors. The pronounced nonlinearity of the studied dependencies points to a possible involvement of a factor(s) other than the pyridinoline crosslink content.

A comparative study has been made of glycosaminoglycan (GAG) accumulation in human fibroblasts with trisomy 7 and triploidy from spontaneous abortuses, fibroblasts with triploidy from induced abortuses, fibroblasts from patients with Down's syndrome and diploid fibroblasts from age-matched controls. The study demonstrated that the incorporation of [3H] glucosamine into hyaluronic acid by fibroblasts with trisomy 7 and triploidy, established from spontaneous abortuses, and from two out of three induced abortuses with triploidy, was 2.6-5.3 times lower than control incorporation. One strain of fibroblasts from an induced abortus with triploidy (IMG-1062) did not show any differences in GAG production when compared with diploid fibroblasts. However, the strains from children with Down's syndrome revealed normal or even increased levels of hyaluronic acid production. The data support the contention that the decreased hyaluronic acid synthesis in fibroblasts with an abnormal karyotype is related to spontaneous abortion.

Catabolism of collagen was studied in 25 children with keloid and hypertrophic scars by means of evaluation of total and polypeptide-bound hydroxyproline excreted with urine. Formation of postburn pathological scars led to an increase in excretion of collagen degradation products, the rate of the increase depended on area and age of scar. In hypertrophic cicatrization rate of collagen metabolites excretion correlated with the scar age reversely, demonstrating the tendency to decrease of the scar collagen metabolites with its ageing. Excretion of collagen metabolites with urine in patients with keloid scars depended on area of the scar and only slightly on its age. Besides, in patients with keloids rather high, statistically distinct correlation (r = 0.855) was found between the ratio macrophages/neutrophils under studies using "skin window" as well as between the ratio of hydroxyproline content in the polypeptide fractions with molecular mass above 1,500 and in the fraction containing oligopeptides and free hydroxyproline. This correlation was not found in patients with hypertrophic scars. Interaction of macrophages, neutrophils and, probably, eosinophiles appears to have a definite importance in regulation of collagen degradation, impairment of which may be substantial for scars formation.

Excretion of pyridinoline and polypeptide-bound hydroxyproline with urine was studied in 27 children with hereditary impairment of connective tissue. At the same time, effects of beta-adrenoblocking agents and vitamin complex, prescribed during preoperation period before thoracoplasty in hereditary chest deformation, were investigated. Clinical efficiency of the treatment depended distinctly on the initial value of ratios pyridinoline/creatinine and polypeptide-bound hydroxyproline/creatinine. Total positive effect of the therapeutic course, considering also echocardiographic examination and postoperational complications, was observed in 44% of patients with Ehlers-Dunlop syndrome and in 75% of patients with Marfan syndrome.

Increased rate of pyridinoline excretion with urine was detected in patients with focal sclerodermia: the ratio pyridinoline/creatinine was equal to 0.094 +/- 0.049 as compared with that of 0.073 +/- 0.049 in controls. Concentration of mature collagen cross-links involving pyridinoline structure in urine of patients with focal sclerodermia did not depend on the patients age and the disease duration. However, this pattern correlated distinctly with clinical form of the disease (0.073 +/- 0.049 in local form and 0.013 +/- 0.017 in generalized form of sclerodermia) as well as correlated reversely with the rate of activity of natural killer cells (r = -0.977).

Natural physiological alterations in excretion of pyridoline (total hydroxypyridoline and lysyl pyridoline) with urine were studied in children and adults depending on age (1-86 years old) and sex. Age-dependent alterations of pyridoline excretion with urine had apparently four phases: an increase, a decrease, stabilization and secondary increase. Distinct dissimilarity between men and women in the rate of pyridoline excretion was found only in the age group of 16-21 years old.

The protective activity of the sera of mice immunized with the preparations of native and detoxified N. meningitidis lipopolysaccharide (LPS), group A, as well as with monoclonal antibodies to N. meningitidis antigens, groups A and B, was studied on the mucin model of meningococcal infection. The study showed that the maximum level of anti-LPS antibodies in mice was observed on day 7 after the injection of LPS. Immune sera obtained from mice were capable of protecting the animals from fetal meningococcemia induced by N. meningitidis strains of homologous and heterologous groups. As shown by the results of this study, the alkaline treatment of N. meningitidis native LPS did not decrease the protective properties of antibodies. The monoclonal antibodies under study were found to possess high preventive activity in mice challenged with N. meningitidis, groups A and B. Anti-LPS monoclonal antibodies showed greater protective activity than antipolysaccharide monoclonal antibodies.

Degradation of short- and long-life proteins was studied in human embryonal fibroblasts with normal karyotype, trisomy and triploidy. Degradation of both short- and long-life proteins by means of lysosomal enzymes was elevated in fibroblasts with anomalous karyotype at the logarithmic phase of growth as compared with normal state, when lysosomotropic agent NH4Cl was used. In transition to stationary phase of growth participation of the lysosomal system in degradation of long-life proteins was increased in fibroblasts with normal karyotype, whereas degradation of these proteins in aneuploid fibroblasts maintained at the level found during the logarithmic phase of growth. Lysosomal enzymes did not participate apparently in degradation of short-life proteins in fibroblasts with normal and anomalous karyotype at both phases of growth. The data obtained suggest that chromosomal disbalance was related to impaired regulation of protein degradation as well as to possible alteration in the ratio of cytosol and lysosomal proteolysis.

Relative synthesis of collagen was studied in skin fibroblasts of children with funnel chest and of corresponding age children (control) in presence of ascorbic acid. In presence of ascorbic acid the rate of collagen synthesis was 2-2.4-fold lower that in corresponding controls both in proliferating and stationary cultures. At the same time, relative synthesis of collagen was quite similar both in the patient and control fibroblasts in presence of ascorbic acid. Estimation of the 14C-Hypro/14C-Pro ratio in collagens isolated from cultural media showed that there was no difference in the hydroxylation rate of collagens in control and patient fibroblasts. These data suggest that funnel chest is one of the forms of systemic connective tissue diseases, which impaired mainly the cartilages.

A new method of collagen-normalizing therapy has been worked out to prevent specific anesthesia-induced, operative and postoperative complications and to treat some symptoms in children with Ehlers-Danlos and Marfan's syndromes and with non-classified Marfan-like malformations. The technique involves a combined use of beta-adrenoblocker in the age-matched doses and vitamins C/0.03 g/(kg.day)/, B2/0.0004 g/(kg.day)/and B6/0.002 g/(kg.day)/ for 2.5 months before surgery and during the first 2 weeks of the postoperative period. The above therapy reduces the incidence of delayed recovery of the muscular tone and adequate respiration, spontaneous and recurrent pneumothorax, hemorrhagic and gastroenterologic complications, as well as the incidence and severity of intestinal paresis. The indexes of effective collagen-normalizing therapy are as follows: body weight increase, echocardiographic pattern of reduced diameter of the aorta and mitral valve prolapse, normalization of the urinary excretion of total and polypeptide-bound oxyproline. The efficacy of therapy depends on the baseline level of oxyproline excretion.

Collagens were analyzed in skin and rib cartilage of 9 patients with Ehlers-Danlos syndrome of the II type. Electrophoresis and CNBr-peptide mapping showed that extended inserts and deletions as well as rough impairments of post-translation processing were not detected in collagens of the I, II and III types from these patients. In the patients with Ehlers-Danlos syndrome of the II type distinct increase was observed both in the total ratio of collagens III/I (P = 0.95) and in the ratio of intact collagens III/I free of cross-links. A decrease in content of dimers beta 11 and beta 12 was found in two patients. The data obtained suggest that the Ehlers-Danlos syndrome of the II type involved deteriorations in the structure of collagens I responsible for decrease in stability and sometimes for impairments in cross-link formation. Increase in content of collagen II fraction, predisposed to proteolytic hydrolysis of terminal sites, as well as elevated sensitivity of collagen II to pepsin hydrolysis were found in collagens of rib cartilage from patients with the syndrome and with funnel chest deformation. This suggests the lowered stability of collagen II from rib cartilage in funnel chest deformation.

The ratio of collagens I/III was studied in human diploid, trisomic and triploid fibroblast strains. The following material was used in experiments: 5 strains obtained from human spontaneous abortuses (trisomy 7, trisomy 9, triploidy), 6 diploid embryonic strains, 4 strains from patients with Down syndrome, 3 strains from healthy children, 4 strains from healthy adult donors and 3 strains from very old persons (81-107 years old). Various types of collagen were separated by means of electrophoresis. Distinct ontogenetic alterations were not observed in content of collagen III in diploid and aneuploid human cultivated fibroblasts. However, considerable alterations in the ratio of collagens I/III correlated with genetic pathologies only in the patients examined.

A comparative study of the relative rates of intracellular total protein metabolism in diploid and aneuploid (with trisomy for chromosome 7) human embryo fibroblasts in the logarithmic and stationary growth phases was carried out. Using double labeling with [14C]proline (24 hrs) and [3H]proline (3 hrs), it was found that: the rates of intracellular protein metabolism during transition to the stationary phase of growth are increased in diploid cells and decreased in cells with trisomy for chromosome 7; the relative rate of protein metabolism in the logarithmic phase is higher in trisomic cells than in diploid ones. The intracellular degradation of procollagen in trisomic cells is increased approximately by 17% as compared to normal fibroblasts. Treatment of cell lysates with bacterial collagenase revealed the presence of procollagen incomplete degradation products in anomalous fibroblasts. The observed differences in the rates and mode of protein metabolism during transition of diploid and trisomic fibroblasts to the stationary phase of growth suggest that the odd autosome interferes with the normal coordinated activity of genes in chromosomes.

A method of isolating polynucleotidephosphorylase (PNPase) containing polyribosome fraction from rat liver is described. PNPase is found to be bind to RNA in polyribosomes with weak electrostatic bonds which are easily broken down in a weak alkaline medium with ionic strength more than 0.1 beta-22P-labelled ADP, GDP, UDP and CDP are found among the products of endogenous RNA degradation in the fraction of total polyribosomes in the presence of 32P-orthophosphate. A considerable change in the base composition of PNP-degraded RNA is observed at different incubation times of total polyribosomes with 32P-orthophosphate: G+C//A+U ratio increased from 2.3 to 3.1, and purines/pyrimidines ratio-from 0.47 to 1.06 with the increase of the incubation time. Specific activity of PNP in ribosome fractions obtained under ultracentrifugation of total polyribosomes in succrose density gradient (0.3-1.0 M) increased in the direction from the fraction of heavy polysomes to trimers and dimers and then dropped at the region of monomers (80 S particles). The data obtained give no possibility to determine the type of PNP-bound RNA in polyribomes of rat liver.

The degradation rate of long-lived and short-lived proteins was determined in diploid fibroblasts and fibroblasts with trisomy 7 derived from human embryos. Two fractions of proteins were detected in the exponentially growing diploid fibroblasts with half-lives (T 1/2) 37 and 19 hours. The rate of protein degradation increases in diploid fibroblasts as they approach confluence and protein fractions with T 1/2 30, 18 and 12 hours appear. The rate of protein degradation in trisomic fibroblasts does not change for the long-lived and short-lived proteins and is the same in both exponential (T 1/2 31 and 14 hours) and stationary phase (T 1/2 33 and 17 hours). The relative amount of the short-lived proteins in trisomic fibroblasts in the stationary phase decreased as compared with the one in diploid fibroblasts. It is apparent that a mechanism of regulation of protein catabolism in trisomic fibroblasts is impaired.

The tumorigenic capacity of mouse B-cell hybridomas in both cloned and primary cultures was studied. The cells were selected for inoculation from 24-well plates and introduced into the spleen of syngeneic mice. The cells took in 50% of the animals. The cells of hybridoma tumors induced as the result of intrasplenic inoculation, when subcultured in the second passage following the standard scheme, i.e. inoculated intraperitoneally in a dose of 1 X 10(7) cells into mice previously treated with vaseline oil or pristane, produced tumors in 100% of the animals.

A possible role of polynucleotide phosphorylase (PNPase) in the destruction of poly-A fragments located at the 3'-OH end of mRNA from rat liver polyribosomes was studied. Using hybridization of mRNP particles and mRNA with poly-U Sepharose 4B, it was found that polyribosomal PNPase in vitro destroys the poly-A sequences of approximately 25% of poly-A+ mRNA during the first minutes of incubation at a high rate. The destruction of the poly-A fragment of mRNA by PNPase is incomplete, since part of it is presumably protected by proteins firmly bound to the poly-A sequences of mRNA.

Study of the effects of pepsin treatment on soluble collagens type I of the skin and collagens type II of the costal cartilage of healthy subjects revealed the presence of two classes of molecules differing in the stability of their three-helical structure. In collagen molecules possessing a low stability (their number may amount to 20-30%) within the temperature range of 4-30 degrees C pepsin causes a split-off of N-terminal sites with the formation of short chains, i.e., alpha 1(I), alpha 2(II), and alpha 1(II), whereas at higher temperatures (33 degrees C for collagens type I and 37 degrees C for collagens type II) a complete degradation of these molecules takes place. It was found that collagens types I and II molecules contain a high number of three-helical sites with a high susceptibility to pepsin. The putative functional role of structural heterogeneity of collagen molecules is discussed.

The electrophoretical analysis and CNBr-peptide mapping of the collagens, isolated from the costal cartilage of 30 patients with non-classified and syndromal forms of pex excavatum (funnel chest) (27 patients) and pex carinatum (3 patients) was carried out. In case of one patient with the nonclassified form of funnel chest the electrophoretical mobility of CB 9.7-peptide was found to be decreased. The electrophoretical mobilities of other peptides are not markedly changed. The data obtained allow one to suggest the mutation causing the defect in the region about 160 amino acid residues distant from the C-end of alpha 1 (II) chain of type II collagen of the patient.

Localization, physico-chemical and catalytic properties and possible biological functions of polynucleotide phosphorylase (PNPase) from animal tissues are discussed. In animal tissue cells PNPase has multiple localization; the major amount of the enzyme is localized in the endoplasmic reticulum ribosomes. In the nuclei PNPase, similar to other endo- and exo-RNAses participates in the processing of precursor molecules of mature forms of RNA, whereas in the cytoplasm it is involved in the destruction of polyribosomes in the polyribosomes of rapidly growing tissues the activity of PNPase is extremely decreased. The mechanisms regulating the PNPase activity in rapidly growing tissues are discussed.

The immunogenic potency, toxicity, homologous and heterologous protective activity of lipopolysaccharide preparations obtained from serogroup A N. meningitidis (LPS A) were studied in animal experiments. These preparations were shown to possess very high protective activity. The alkaline treatment of native LPS A decreased the toxicity of the preparation almost 20 times and did not affect its immunogenic potency. Detoxified LPS A was capable of protecting mice from fatal meningococcemia resulting from infection with N. meningitidis strains, serogroups A, B and C; the adsorption of the preparation on aluminium hydroxide did not affect its protective activity. In view of the properties of detoxified LPS A revealed in this investigation, it may be regarded as a possible vaccinal preparation.

Content of collagen and relative content of unextractable collagen were increased by 35% and 50%, respectively, while the content of immobilized water was decreased in costal cartilage of children with the isolated form of funnel chest or with the deformation accompanied by Ehlers-Danlos syndrome. These anomalies may be considered as indicators of the cartilage premature ageing. In skin of the children with isolated form of funnel chest the ratio of collagen extracted with acetic acid was increased 2-fold.

Age-dependent alterations in excretion of hydroxyproline were studied in 62 healthy persons (3-78 years old) by means of analysis of the morning portion of urine after gel filtration on Sephadex G-10. With ageing the following patterns were decreased: content of total hydroxyproline (r = -0.78; P less than 0.001), the ratio hydroxyproline/creatinine (r = -0.80, P less than 0.001) and content of hydroxyproline in peptide fraction with MW greater than 700-1000 (r = -0.50; P less than 0.001). The reverse correlation was found between the contents of total and free hydroxyproline (r = -0.45; P less than 0.001) but total content of hydroxyproline correlated directly with its content in the peptide fraction (r = 0.92; P less than 0.001). At the same time, reverse correlation was observed between the contents of free hydroxyproline and of the peptide-bound amino acid (r = -0.58; P less than 0.001). Approximate ranges of normal excretion of hydroxyproline with urine were calculated in various age groups.

Effect of cAMP on the activity of polynucleotide phosphorylase (PNPase) was studied in polyribosome fraction of rat liver tissue. Intraperitonel administration of cAMP or of theophilline into rats distinctly decreased the PNPase activity in the polyribosome fraction. The cAMP (1-10(-4) M) inhibited the enzymatic activity only by 8% in polyribosome fraction in vitro, as it was estimated by the reaction of phosphorolysis of endogenous RNA and polyA added. Any attempts were proved to be uncucessful to reveal cAMP, ATP-dependent proteinkinase in rat liver, responsible for the decrease in the PNPase activity in the polyribosome fraction. The cAMP inhibited the increase in the PNPase activity, coupled with protein biosynthesis in polyribosomes. Moreover, cAMP caused a decrease in the PNPase activity in reaction of polyA phosphorolysis and did not affect the rate of endogenous RNA phosphorolysis in polyribosome fraction, isolated from postmitochondrial fraction after incubation for 15 min at 30 degrees. The 3',5'-cyclo AMP (2-10(-6)-2-10(-4) M) stimulated incorporation of 14C-leucine into acid-insoluble material, when postmitochondrial fraction was incubated under the same conditions. The data obtained suggest that cAMP either inhibits specifically the PNPase synthesis or represses the coupled with protein biosynthesis formation of active "heavy" type of PNPase from less active "light" type.

Secretion of procollagen was studied in human embryonal fibroblasts with diploid chromosomes as well as in fibroblasts obtained from fetuses after spontaneous abortion from patients with trisomy by chromosome 7. The rate of procollagen secretion was approximately similar in these cells; the protein was shown to accumulate in intracellular matrix of diploid fibroblasts, while it did not occur in the matrix of aneuploid fibroblasts. Content of polymeric tubulin was decreased in fibroblasts with trisomy as compared with diploid cells. Impairment of the intracellular matrix structure in the cells with trisomy appears to be responsible for deterioration of morphogenesis in human chromosome anomalies.

Relationship between the state of natural cytotoxicity and collagen catabolism were studied in patients with focal sclerodermia. In the impairment activity of natural killer cells (NK cells) was markedly altered depending on such clinical parameters as duration, severity, activity and distribution of the disease as well as it was related to definite transformations in catabolism of collagen proteins. Low rate of collagen production and intensive collagenolytic processes correlated with the high level of hydrolytic activity of NK cells at the early steps of systemic morphea guttata accompanied by highly progressive course of the disease. Under conditions of subacute forms of focal morphea guttata activity of NK cells was distinctly decreased down to 50% of that of normal state and was accompanied by alterations in the spectrum of collagenolytic enzymes as well as by considerable variations in collagen production and in posttranslational modification of collagen fibrils. During the chronic step of sclerodermia activity of NK cells was normalized and correlated with the lowered rate of collagen production as well as with the subsequent alterations in collagen proteins catabolism. Alterations in the level of natural cytotoxicity appear to correlate with the state of collagen metabolism in focal sclerodermia.

The type of RNA is studied, which is degraded by polynucleotide phosphorylase (PNPase) in the fraction of free ribosomes and ribosomes released from endoplasmic reticulum membranes with Triton X-100. Beta-32P labelled ADP, UDP, GDP and CDP are found among the degradation products of endogenous RNA of free and bound ribosomes in vitro in the presence of 32P-ortophosphate. An analysis of molar ratio of beta-32P-NDP isolated revealed that PNPase degrades RNA of GC type in both ribosome fractions. The amount of PNPase-degraded RNA in bound ribosimes is 4-fold as high as that in free ribosomes under the same conditions. Analysis of stable 32P-RNA and rapidly labelled 32-P-dRNA, isolated from bound ribosomes after the incubation with and without inorganic phosphate, revealed that PNPase attacks the 28S fragment of RNA, which consists of about 370 nucleotides, and dRNA having a sedimentation coefficient less than 12S. The rate of dRNA degradation is considerably higher than that of rRNA. 5'-RNAase, hydrolysing synthetic homopolyribonucleotides to oligonucleotides with free 3'-OH terminal group, apparently participates, together with PNPase, in dRNA and rRNA degradation.

Synthesis of nonribosomal RNA was increased 2-2.5-fold in nuclei of rat liver cells at early steps of regeneration /2 days after partial hepatectomy/under conditions of protein synthesis inhibition by means of cycloheximide within 3 hrs. Amount of mRNA, transferred from nuclei into cytoplasm, was also 2-fold higher under these conditions as compared with control cells. The mRNA, transferred from nuclei into cytoplasm under the conditions of cycloheximide treatment of liver cells at early steps of regeneration, did penetrate the polyribosomes although the protein synthesis did not occur on the polyribosomes formed. At the later steps of regeneration /within 5 days after partial hepatectomy/ under the conditions of protein synthesis inhibition by cycloheximide within 3 hrs, formation of nonribosomal RNA was decreased by 40% in liver cell nuclei; amount of mRNA, transferred into cytoplasm, was also decreased by 40%. When the cycloheximide treatment was carried out during 1 hr, synthesis of nonribosomal RNA was increased 1.5-fold in liver cell nuclei at the later steps of regeneration although the amount of mRNA, transferred from nuclei into cytoplasm, was decreased by 30% as compared with the control cells. The data obtained suggest that during rat liver tissue regeneration a change occurred in the molecular mechanisms linking translation, biosynthesis and nuclear-cytoplasmic transport of mRNA of "tumoral" type/at early steps of regeneration/ or "normal type"/ at later steps of regeneration.

In a group of women, which had children with hereditary isolated and syndromal chest deformations, acute respiratory diseases, tonsillitis or influenza occurred during pregnancy in 42.9 +/- 6.6% and 53.8 +/- 13.8% of cases, respectively, whereas in the control group only 17.8 +/- +/- 7.2% of the women were impaired with identical infectious diseases during pregnancy (P less than 0.02 and P less than 0.05, respectively). Excretion of hydroxyproline was distinctly dissimilar in 22 children with isolated and in 13 children with syndromal chest deformations depending on presence or absence of the above-mentioned infections during pregnancy. Under conditions of these infections the higher level of total hydroxyproline excretion was noted as well as relatively lower content of bound hydroxyproline was detected in those peptides, which appear to be responsible for the content of newly synthesized collagen. The data obtained suggest that acute respiratory diseases, influenza, chronic and acute tonsillitis may impair collagen metabolism in children with hereditary chest deformations as well as that these infectious diseases occurred during pregnancy may increase the risk of the pathology development in the children.

A releasing factor (RF) of polynucleotide phosphorylase (PNPase) isolated and purified from sarcoma M-1 of the rat is a protein with molecular weight of about 8000 and the isoelectric point at 4,0--4,2. The process of PNPase release from the polyribosomes of normal rat liver does not depend on the pH of the medium within the pH range of 7,2--9,0, on temperature within the interval of 0--400 degrees and on incubation time. Inhibition of phosphorolysis by endogenous RNA from normal rat liver polyribosomes requires considerable amounts of RF--approximately 170--800 molecules of RF per molecule of poly(A)+-mRNA. The data obtained suggest that PNPase release from the polyribosomes under the action of RF is not a catalytic process and is caused by competition between RF and PNPase for the binding sites on the mRNA molecule.

Collagen production was studied in human embryonal fibroblasts. Synthesis of collagen in the cells with trisomy 7 was decreased 2-fold as compared with diploid cells in spite of 50% increase of the collagen genes localized on the chromosome 7. Diploid and aneuploid cells synthesized collagens of the I and III types at similar weight ratios. At the same time, an increase in synthesis of type I collagen trimer was found in culture of cells with anomalous caryotype. A decrease of collagen production in cells with anomalous caryotype appears to be one of the reasons responsible for spontaneous abortion.

Excretion of hydroxyproline with urine was studied in 16 children with localized form of funnel chest deformation simultaneously with Marfan and Ehlers-Danlos syndromes, in 9 children with the localized form of deformation within 6-8 months after thorax surgical plastic operation as well as in 3 children with Ehlers-Danlos syndrome but without funnel chest deformation. Funnel chest deformation of the II-III degree, independently of its form, was accompanied by a decrease of total hydroxyproline in urine as compared with healthy children of the similar age. The hydroxyproline excretion was normalized after thoracoplastic operation in the children with localized form of the chest deformation. In Ehlers-Danlos syndrome, independently on presence or absence of the chest deformation, relative content of free hydroxyproline was increased in urine, while the peptide-bound amino acid was decreased (peptides with molecular mass above 700 daltons); this phenomenon appears to be a characteristic property of the syndrome.

Skin and rib cartilage collagens were studied in patient 1.I.K. with isolated form of pigeon chest as well as in a group of children without any impairments of connective tissue. Distinct decrease in stability of collagen I, an increase in the ration of alpha 1 (I)/alpha 2(I) chains and impairment in formation of beta 12 dimers were detected in the patient with pigeon chest. In the patient skin total ratio between collagens I and III, calculated from a content of BrCN-peptides, was similar to normal level, whereas the proportion was markedly increased between intact molecules of collagens III and I free of cross-links, which was calculated from the ratio of alpha 1(III)/alpha 2(I) chains. Presence of cross-links between alpha 1 (III) and alpha 2 (I) chains as well as between alpha 1 (III) and alpha 2 (I) chains was detected after peptide mapping of polypeptides arranged in the region of beta 11 and beta 12 dimers. All the collagen I preparation, extracted from skin of the patient 1.I.K., contained molecules with unstabilized N-terminal sites. These results suggest that mutation occurred in the N-terminal region of alpha 1(I) chain. Analysis of collagen from the patient 1.I.K. rib cartilage demonstrated a slight decrease in total stability of collagen II as well as elevated concentration of collagen II molecules containing unstabilized N-terminals. Mechanisms responsible for formation of cross-links between polypeptide chains of collagens I and III detected in human skin are discussed.