PubMed Health⌕ Search

Biomedical subjects

A A Karelin

Publications and source records attributed to A A Karelin.

At least 19 recordsLinked to original sources

Study of total lipid peroxidation and antioxidant activity in pulmonary and mediastinal malignant and benign tumor tissue.

Total lipid peroxidation and antioxidant activity were studied in pulmonary and mediastinal malignant and benign neoplasms. In malignant tumors total lipid peroxidation increased and antioxidant activity decreased; the intensity of these shifts depended on histological characteristics and degree of malignancy: the most pronounced changes were observed in thymoma and adenocarcinoma tissues and minimum changes were found in bronchoalveolar carcinoma tissue.

Adenocarcinoma↗

Activity of glutathione-metabolizing and antioxidant enzymes in malignant and benign tumors of human lungs.

We measured the content of glutathione and activity of glutathione-metabolizing and antioxidant enzymes superoxide dismutase and catalase in samples obtained from 52 patients with malignant lung tumors and 20 patients with benign lung tumors. The content of glutathione and activity of glutathione-metabolizing enzymes underwent similar changes, but these changes were most pronounced in malignant tumors. Antioxidant enzyme activity changed insignificantly in benign tumors, but significantly decreased in malignant tumors (squamous cell carcinoma and adenocarcinoma). The severity of changes in malignant tumors depended on the degree of malignancy. Most pronounced changes were observed in adenocarcinoma, which often metastasizes and is resistant to chemotherapy. These changes were least pronounced in bronchoalveolar carcinoma sensitive to chemotherapy.

Adult↗

[Hypothermal perfusion: protection or damage?].

Ninety six patients were examined during operations on the open heart and great vessels: 25 perfusions were performed at a temperature of 30-32 degrees C; 41 perfusions at 26-29 degrees C; 10 at 23-26 degrees C; 20 at 12-14 degrees C. It was found that with superficial hypothermia and moderate PaO2, blood myoglobin (MG) release was minimal and the count and activity of platelets were optimal. The degree of myoglobinemia increased as PaO2 rose. As the body's temperature lowered, the blood concentrations of MG, its differences smoothed in the subgroups with different PaO2 values. Critical myoglobinemia (over 30 times higher than the baseline values) was noted in a group with superdeep cooling to a temperature of 14 degrees C. By taking into account the fact that the myocardium contains large quantities of MG, loss of this heme-containing protein involves myocardial blood supply disorders and hence decreased myocardial contractility. A considerable platelet loss entails higher postoperative hemorrhagic diathesis and requires efforts in correcting coagulopathies.

Body Temperature↗

[Neutrophilic respiratory response in surgical infection and an association with plasma membranous synthesis of ATP].

Early studies have demonstrated that the unique phenomenon ATP aerobic synthesis on neutrophilic plasma membranes is observed when neutrophils are activated with the chemoattractive peptide FMLP. This paper presents the results of the study of a possible association of ATP plasma membranous synthesis with priming, with the occurrence of respiratory explosion and apoptosis of the neutrophils isolated from the blood of donors and patients with surgical infection of different severity. The interaction of neutrophilic plasma membranes with FMLP and with hTNF (was attended by ATP synthesis. Examining the level of FMLP-stimulated production of superoxide in patients with surgical infection revealed that the amount of the superoxide produced by neutrophils noticeably decreased and droppped by more than 5 times in sepsis. The FMLP-stimulated plasma membranous synthesis of ATP was determined in the same patients. A decrease in the production of superoxide was simultaneously accompanied by a reduction in the plasma membranous synthesis of ATP. Both the plasma membranous synthesis of ATP and the production of superoxide declined in sepsis at the most. The neutrophils isolated from peripheral blood of the same patients showed DNA damage whose degree was directly related to the condition of a patient. The maximum DNA damages were observed in sepsis. The findings suggest that apoptosis is induced in surgical infection in the peripheral neutrophils. The DNA damage and the FMLP-stimulated plasma membranous synthesis of ATP was estimated in the neutrophils isolated from the inflammation focus. It turned out that in local surgical infection, there were the maximum DNA damages and the FMLP-stimulated plasma membranous synthesis of ATP was lower than that in the peripheral neutrophils. It can be suggested that the FMLP-stimulated plasma membranous synthesis of ATP may be a regulators of neutrophilic functional states in surgical infection and sepsis.

Adenosine Triphosphate↗

[Disorders of protein C anticoagulant system in various clinical conditions].

A study was carried out on activity of protein C4 in 73 surgical patients (coagulation test, reagents of company PEHAM). The reduction in activity of protein C was observed in patients with focal liver lesion related to disturbance of protein formation function. This percent of disturbances in protein C system is more often found in patients with vascular pathology. This is explained by the mechanism of its action and implication of vascular endothelium into the process. Disturbances in patients with injury infection are stipulated with activity of C and S proteins and availability of mutant factor V--factor Leiden in patients with diabetes. In the first days after surgical intervention the activity of C protein was much reduced. The obtained results emphasize the importance of research in the system of protein C in surgical patients.

Blood Coagulation Disorders↗

Endogenous fragment of hemoglobin, neokyotorphin, as cell growth factor.

It is shown that neokyotorphin (the alpha-globin fragment 137-141) stimulates proliferation of normal cells (murine embryonic fibroblasts, red bone marrow and spleen cells) and tumor cells (murine melanoma and transformed fibroblasts L929) in the absence or in the presence of fetal bovine serum. In contrast to serum deprivation conditions, the ability to potentiate L929 cell growth in the presence of fetal serum is strongly cell density dependent. The peptide also enhances the viability of L929 cells, murine embryonic fibroblasts and of the primary cultures of murine red bone marrow cells and splenocytes under serum-deprivation conditions for at least 72 h. The results of flow cytometry analysis suggest that the effect of neokyotorphin on survival of L929 cells in serum-free culture medium is due to maintenance of cell proliferation in the absence of growth factors. Along with cell cycle progression the peptide induces reversible reduction of L929 cell size.

Animals↗

GABA-induced changes of the tissue-specific peptide pool of white rat brain.

Internasal administration of gamma-aminobutyric acid (GABA) induced prolonged behaviour changes and the appearance of three new compounds absent in the brain extracts of control rats. Two peptides associated with GABA administration were isolated and sequenced: Thr-Tyr-Thr-Phe, which corresponds to a gamma-immunoglobulin segment, and Val-Leu, which is present in a great number of proteins, hence its precursor could not be established. The third compound was not amenable to the Edman degradation technique. The data obtained show that the introduction of a neurotransmitter could cause specific changes in the levels of tissue-specific peptide components.

Animals↗

Peptides comprising the bulk of rat brain extracts: isolation, amino acid sequences and biological activity.

Chromatographic separation of rat brain extracts followed by automatic Edman sequencing of the major individual components resulted in identification of 61 endogenous peptides derived from known functional proteins (hemoglobin, myelin basic protein, cytochrome-c oxidase, etc.) or unknown precursors. The results are compared with the data obtained earlier for bovine brain. Although the sequences of bovine and rat hemoglobin contain about 20% of amino acid substitutions, the families of structurally related peptides are very similar in both extracts. Several other proteins also give rise to identical or closely related peptide fragments in the two mammalian species. The outlined similarity extends almost exclusively to the most abundant peptides present in the extracts. The minor components show less overlap. Four hemoglobin-derived peptides isolated from rat brain were shown to be biologically active in tumor cells. Eleven are identical to bioactive peptides from other species. Ten structurally overlap with bioactive peptides from other sources. The data obtained show similar biosynthetic pathways of pool components in different species, the resultant peptides being aimed at fulfilling related functions.

Amino Acid Sequence↗

Platelet monoamine oxidase activity during surgical intervention under condition of hypothermic perfusion.

Platelet and plasma monoamine oxidase activity was determined at early stages of hypothermic perfusion and circulatory arrest. Monoamine oxidase activity decreased more drastically and restored more slowly against the background of deep (14 degrees C) compared to moderate hypothermia (26-29 degrees C). The decrease in platelet monoamine oxidase activity was accompanied by its increase in the plasma, which attests to mechanical (in tubes) and toxic damage to platelets. The latter is associated with increased partial O(2) pressure in the plasma during hypothermia, which promotes the formation of reactive oxygen species.

Adult↗

[Effects of some growth factors and cytokines on ATP synthesis by plasma-membrane-enriched particles isolated from different human tumors].

Plasma-membrane-enriched particles isolated from the tissues of malignant tumors of different sites are shown to accumulate ATP under the influence of polypeptide growth factors and cytokines whose receptors have a tyrosine kinase activity. Polypeptide growth factors, such as EGF, FGF, NGF, TNF, insulin, and the cytokine IL-2, were studied on the accumulation of adenosine-5'-triphosphate (ATP) by the preparations of plasma-membrane-enriched particles isolated from the target tissues of human malignant tumors. The tumor (transformed) cell plasma membranes of the lung, bowel, stomach, pancreas, as well as the cells of neurinoma and a retroperitoneal extra-organ malignant tumor (leiomyosarcoma) are demonstrated to be able to synthesize ATP from inorganic phosphate and ADP under aerobic conditions human with the participation of the cyanide-insensitive proton phoric NADH-bound transversely oriented chain. Signal-stimulated accumulation of plasma membranous ATP was found to increase in the tissues in malignant transformation as compared to that in normal tissues. Experiments using selective inhibitors of tyrosine kinases (tyrphostin-25, quercetin) indicated the involvement of plasma membranous signal-transducing ATP in the activation of receptor tyrosine kinase growth factors.

Adenosine Diphosphate↗

In vitro effects of folic acid on gamma-glutamyltransferase and glutathione reductase activities in malignant lung and thymus tumors.

In vitro effects of folic acid (10(-5), 10(-4), and 10(-3)M) on activities of gamma-glutamyltransferase and glutathione reductase, the enzymes involved in glutathione metabolism, were studied in tissue samples obtained after surgical treatment of the lungs and thymus. Folic acid did not change gamma-glutamyltransferase activity in lung cancer tissue, but in thymoma tissue this substance in a concentration of 10(-3)M inhibited it by 16%. Folic acid had no effects on glutathione reductase activity in benign tumors and normal lung and thymus tissues, but increased this activity in thymoma and lung cancer tissues. Activation of glutathione reductase was probably related to binding of folic acid in the allosteric center of the enzyme, which probably induced conformational changes in the catalytic center, acceleration of electron transport from NADPH(2) to oxidized glutathione via flavin adenine nucleotide, and intense production of reduced glutathione.

Dose-Response Relationship, Drug↗

Fragments of functional proteins: role in endocrine regulation.

Systematic analysis of structures, localization, formation and biological activities of endogenous peptides derived from functional proteins, such as hemoglobin, myelin basic protein, immunoglobulins, etc., allowed establishing the basic features of that group of compounds. The sets of these peptides in mammalian tissues, or "tissue-specific peptide pools" are: (i) tissue specific; (ii) stable at normal conditions; (iii) conservative in the same tissues of different mammalian species; (iv) dependent on the general state of homeostasis of tissue or the whole organism. Formation of such peptides has features of both conformation and site specificity and also involves the action of carboxy- and amino-peptidases. As a result, the families of structurally related families of peptides are generated. The fragments of functional proteins exhibit a wide range of the biological effects, characteristic both for hormones and parahormones, from hormone-releasing to growth-regulatory activity. At the same time, the molecular mechanisms of action of the majority of such peptides are unknown. On the basis of the data obtained the components of tissue-specific peptide pools are considered to form a novel regulatory system, complementary to other peptidergic systems such as hormonal, nervous, immune, etc. The biological role of the fragments of functional proteins in vivo and the patterns of interaction with other regulatory systems are suggested.

Animals↗

LVV- and VV-hemorphins: comparative levels in rat tissues.

Screening of hemorphins in extracts of rat lung, brain, heart and spleen was carried out. The threshold for detection of hemorphins was 0.01 nmol for spleen and 0.05 nmol for other tissues. Both the content and the composition of hemorphins differed significantly in the tissues analyzed. Heart and lung extracts were rich in these peptides, the content of the most abundant components reaching 16-44 nmol/g of tissue. In contrast, spleen and brain contained much lower amounts of hemorphins, i.e. about 0.3-2.6 nmol/g of tissue. The most represented hemorphin in lung, heart and brain was VV-hemorphin-5, while the content of other members of the hemorphin family depended significantly on the tissue analyzed: lung extract was also rich in LVV-hemorphin-5, heart contained similar amounts of LVV-hemorphin-7 and LVV-hemorphin-5 and brain of LVV-hemorphin-6. In contrast, the hemorphin family in spleen was represented mainly by C-terminally shortened VV-hemorphins, i.e. VV-hemorphin-4 and VV-hemorphin-3. The levels of hemorphins in all cases were sufficient to activate the opioid receptors of the respective tissues.

Amino Acid Sequence↗

A novel system of peptidergic regulation.

Systematic analysis of structure and biological activity of peptide components of tissue extracts and biological fluids allows us to formulate a novel concept of a peptidergic regulatory system, complementary to the conventional regulatory systems (i.e. nervous, endocrine and paracrine systems). According to that concept, the proteolytic degradation of tissue proteins carried out by a specific and regulated system of tissue-specific enzymes and protein substrates gives rise to a large group of peptides, which we define as tissue-specific peptide pool. As a result, functional proteins provide their proteolytically derived fragments for maintaining tissue homeostasis.

Amino Acid Sequence↗

Peptides from bovine brain: structure and biological role.

Fractionation of bovine brain extracts followed by automatic Edman sequencing of individual components resulted in identification of 107 endogenous peptides formed from functional proteins (haemoglobin, myelin basic protein, cytochrome c oxidase, etc) or unknown precursors. Several of the newly identified brain peptides demonstrate different types of biological activity; some of the substances show considerable overlap with the known biologically active peptides. It is suggested that these peptides should participate in regulation of extracellular and intracellular biochemical processes. A concept of 'tissue-specific peptide pool' is formulated describing a novel system of peptidergic regulation, complementary to the conventional hormonal and neuromodulatory systems. According to that description functional proteins provide their proteolytically derived fragments for maintaining the tissue homeostasis by modulating the availability of peptide receptors to respective 'true' ligands.

Amino Acid Sequence↗