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Biomedical subjects

A V Kuznetsov

Publications and source records attributed to A V Kuznetsov.

At least 19 recordsLinked to original sources
PubMed2006

Numerical modeling of in vivo plate electroporation thermal dose assessment.

Electroporation is an approach used to enhance the transport of large molecules to the cell cytosol in which a targeted tissue region is exposed to a series of electric pulses. The cell membrane, which normally acts as a barrier to large molecule transport into the cell interior, is temporarily destabilized due to the development of pores in the cell membrane. Consequently, agents that are ordinarily unable enter the cell are able to pass through the cell membrane. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with joule heating. This paper explores the thermal effects of various geometric, biological, and electroporation pulse parameters including the blood vessel presence and size, plate electrode configuration, and pulse duration and frequency. A three-dimensional transient finite volume model of in vivo parallel plate electroporation of liver tissue is used to develop a better understanding of the underlying relationships between the physical parameters involved with tissue electroporation and resulting thermal damage potential.

Cell Membrane↗
PubMed2004

Detection of buried explosives using portable neutron sources with nanosecond timing.

Significant reduction of time needed to identify hidden explosives and other hazardous materials by the "neutron in, gamma out" method has been achieved by introducing timed (nanosecond) neutron sources-the so-called nanosecond neutron analysis technique. Prototype mobile device for explosives' detection based on a timed (nanosecond) isotopic (252)Cf neutron source has been created. The prototype is capable of identifying 400 g of hidden explosives in 10 min. Tests have been also made with a prototype device using timed (nanosecond) neutron source based on a portable D-T neutron generator with built-in segmented detector of accompanying alpha-particles. The presently achieved intensity of the neutron generator is 5x10(7)n/s into 4pi, with over 10(6) of these neutrons being correlated with alpha-particles detected by the built-in alpha-particle detector. Results of measurements with an anti-personnel landmine imitator are presented.

Blast Injuries↗
PubMed2004

Effect of the arginine-containing mu,delta-opiate receptor agonist sedatin on DNA synthesis in the epithelium of the gastric fundus in albino rats.

We studied the effect of arginine-containing mu,delta-opiate receptor agonist sedatin on DNA synthesis in the epithelium of the gastric fundus in albino rats. Fivefold intraperitoneal injection of sedatin in various doses increased the index of labeled nuclei. Similar changes were observed after intranasal and intraperitoneal treatment with sedatin in a dose of 10 microg/kg for 21 days. Administration of sedatin for 21 days prevented the decrease in weight gain induced by experimental stress. Our results suggest that arginine entering the composition of sedatin plays a role in its biological effects.

Administration, Intranasal↗
PubMed2003

Metabolic consequences of functional complexes of mitochondria, myofibrils and sarcoplasmic reticulum in muscle cells.

Regulation of mitochondrial respiration both by endogenous and exogenous ADP in the cells in situ was studied in isolated and permeabilized cardiomyocytes, permeabilized cardiac fibers and 'ghost' fibers (all with a diameter of 10-20 micro m) at different (0-3 micro moll(-1)) free Ca(2+) concentrations in the medium. In all these preparations, the apparent K(m) of mitochondrial respiration for exogenous ADP at free Ca(2+) concentrations of 0-0.1 micro moll(-1) was very high, in the range of 250-350 micro moll(-1), in contrast to isolated mitochondria in vitro (apparent K(m) for ADP is approximately 20 micro moll(-1)). An increase in the free Ca(2+) concentration (up to 3 micro moll(-1), which is within physiological range), resulted in a very significant decrease of the apparent K(m) value to 20-30 micro moll(-1), a decrease of V(max) of respiration in permeabilized intact fibers and a strong contraction of sarcomeres. In ghost cardiac fibers, from which myosin was extracted but mitochondria were intact, neither the high apparent K(m) for ADP (300-350 micro moll(-1)) nor V(max) of respiration changed in the range of free Ca(2+) concentration studied, and no sarcomere contraction was observed. The exogenous-ADP-trapping system (pyruvate kinase + phosphoenolpyruvate) inhibited endogenous-ADP-supported respiration in permeabilized cells by no more than 40%, and this inhibition was reversed by creatine due to activation of mitochondrial creatine kinase. These results are taken to show strong structural associations (functional complexes) among mitochondria, sarcomeres and sarcoplasmic reticulum. Inside these complexes, mitochondrial functional state is controlled by channeling of ADP, mostly via energy- and phosphoryl-transfer networks, and apparently depends on the state of sarcomere structures.

Adenosine Diphosphate↗
PubMed2002

Electron mass operator in a strong magnetic field and dynamical chiral symmetry breaking.

The electron mass operator in a strong magnetic field is calculated. The contribution of higher Landau levels of virtual electrons, along with the ground Landau level, is shown to be essential in the leading log approximation. The effect of the electron dynamical mass generation by a magnetic field is investigated. In a model with N charged fermions, it is shown that some critical number N(cr) exists for any value of the electromagnetic coupling constant alpha, such that the fermion dynamical mass is generated with a doublet splitting for N N(cr), thus leaving the chiral symmetry unbroken.

Journal Article↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2001

Increased number and size of atypical reticular cells in the palatine tonsil of patients with remote cancer.

Atypical cells have been consistently found in the palatine tonsil (PT) in patients with breast, stomach, and rectal cancer, and less often with gastric polyposis, mastopathy, and soft tissue papilloma. The vast majority of the atypical cells is represented by reticular cells, which are found in smears irrespective of the tumor stage. The number and size of PT atypical reticular cells in patients with remote cancer is higher than in those with non-malignant conditions and have brightly expressed dysplasia. No atypical reticular cells were found in cytologic smears in normals or in patients with similar demographics and with oral, local, or systemic infection.

Adult↗
PubMed2000

DNA interaction with rabbit sperm cells and its transfer into ova in vitro and in vivo.

Exogenous DNA interaction with rabbit sperm cells and its transfer into ova has been studied. It was shown that rabbit sperm cells are able to capture, hold, and transfer exogenous DNA to ova during fertilization. Sperm/DNA transfer leads to genetically transformed offspring. Transfection efficiency varied within a large range. Low expression and rearrangements of the transgene were observed.

Animals↗
PubMed2000

Mitochondrial defects by intracellular calcium overload versus endothelial cold ischemia/reperfusion injury.

Questions as to the critical stress factor and primary targets of cold ischemia/reperfusion (CIR) injury were addressed by comparing mitochondrial defects caused by (1) CIR injury and (2) intracellular Ca2+ overload. CIR was simulated in transformed human umbilical vein endothelial cell cultures (tEC) by 8 h cold anoxia in University of Wisconsin solution and reoxygenation at 37 degrees C. Intracellular Ca2+ concentrations were changed by permeabilization of suspended cells with digitonin in culture medium (RPMI, 0.4 mM Ca2+). Binding of free Ca2+ by ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid in RPMI or mitochondrial incubation medium served as controls. Extracellular Ca2+ protected the cell membrane against permeabilization. Mitochondrial functions were determined before and after permeabilization of the cell membrane. After CIR, mitochondrial respiratory capacity declined, but oxygen consumption remained coupled to adenosine triphosphate (ATP) production. In contrast, Ca2+ overload caused uncoupling of mitochondrial respiration. High intracellular Ca2+ overload, therefore, does not reproduce cold ischemia/reperfusion injury in endothelial cells.

Adenosine↗
PubMed2000

Effect of mu-opiate receptor agonist tetrapeptide A10 on DNA synthesis and protein content in the myocardium of albino rats.

Effect of intraperitoneal injection of tetrapeptide A10 (H-Tyr-D-Orn-Phe-Gly-OH), selective mu-opiate receptor agonist, synthetic analog of dermorphine, in a dose of 100 microg/kg on DNA synthesis and protein content in the myocardium was studied in albino rats. Five injections of tetrapeptide on days 2-6 after birth caused no changes in DNA synthesis 17 days after the last injection, i. e. in 24-day rats. The number of nucleoli and their area increased. In adult males long-term (3-week) treatment with tetrapeptide A10 increased the number of nucleoli and the mean and integral optical density of isolated cardiomyocytes stained with amido black B, which probably attested to activation of protein synthesis in the myocardium. Simultaneously, the content of catecholamines in the heart increased. These data are comparable with delayed effects of kappa-opiate receptor agonist dinorphine A1-13 and indicate that morphogenetic properties of opioid peptides in rat myocardium are realized via the same routes.

Animals↗
PubMed1999

Metabolic consequences of the cytochrome c oxidase deficiency in brain of copper-deficient Mo(vbr) mice.

Biochemical micromethods were used for the investigation of changes in mitochondrial oxidative phosphorylation associated with cytochrome c oxidase deficiency in brain cortex from Mo(vbr) (mottled viable brindled) mice, an animal model of Menkes' copper deficiency syndrome. Enzymatic analysis of cortex homogenates from Mo(vbr) mice showed an approximately twofold decrease in cytochrome c oxidase and a 1.4-fold decrease in NADH:cytochrome c reductase activities as compared with controls. Assessment of mitochondrial respiratory function was performed using digitonin-treated homogenates of the cortex, which exhibited the main characteristics of isolated brain mitochondria. Despite the substantial changes in respiratory chain enzyme activities, no significant differences were found in maximal pyruvate or succinate oxidation rates of brain cortex homogenates from Mo(vbr) and control mice. Inhibitor titrations were used to determine flux control coefficients of NADH:CoQ oxidoreductase and cytochrome c oxidase on the rate of mitochondrial respiration. Application of amobarbital to titrate the activity of NADH:CoQ oxidoreductase showed very similar flux control coefficients for control and mutant animals. Alternately, titration of respiration with azide revealed for Mo(vbr) mice significantly sharper inhibition curves than for controls, indicating a more than twofold elevated flux control coefficient of cytochrome c oxidase. Owing to the reserve capacity of respiratory chain enzymes, the reported changes in activities do not seem to affect whole-brain high-energy phosphates, as observed in a previous study using 31P NMR.

Animals↗
PubMed1998

Mitochondrial respiration in the low oxygen environment of the cell. Effect of ADP on oxygen kinetics.

Oxygen levels in the intracellular microenvironment of tissues such as heart are extremely low, at 1-2% of standard atmospheric oxygen pressure. Kinetic studies with isolated mitochondria suggest a regulatory role of oxygen under these conditions, particularly in active states at high ADP concentration, when oxygen affinity was lower than in the resting state at ADP limitation. The oxygen pressure at 50% of maximum flux, p50, was 0.035 and 0.057 kPa in heart and liver mitochondria, respiring in state 3 on substrates for complex I or II and II, respectively. p50 in the resting state 4 was 0.02 kPa. The apparent kinetic efficiency, Jmax/p50, increased from the resting to the active state, despite the decrease of oxygen affinity, 1/p50. Consequently, the relative increase of respiratory flux by ADP activation, expressed as the adenylate control ratio, declined under hypoxia, but not to the extreme of a complete loss of the scope for activation, which would occur at constant Jmax/p50. High oxygen affinity is achieved by an excess capacity of cytochrome c oxidase relative to the respiratory chain and a correspondingly low turnover rate of this enzyme, consistent with the concept of kinetic trapping of oxygen [1].

Adenosine Diphosphate↗
PubMed1998

Functional imaging of mitochondria in saponin-permeabilized mice muscle fibers.

Confocal laser-scanning and digital fluorescence imaging microscopy were used to quantify the mitochondrial autofluorescence changes of NAD(P)H and flavoproteins in unfixed saponin-permeabilized myofibers from mice quadriceps muscle tissue. Addition of mitochondrial substrates, ADP, or cyanide led to redox state changes of the mitochondrial NAD system. These changes were detected by ratio imaging of the autofluorescence intensities of fluorescent flavoproteins and NAD(P)H, showing inverse fluorescence behavior. The flavoprotein signal was colocalized with the potentiometric mitochondria-specific dye dimethylaminostyryl pyridyl methyl iodide (DASPMI), or with MitoTrackerTM Green FM, a constitutive marker for mitochondria. Within individual myofibers we detected topological mitochondrial subsets with distinct flavoprotein autofluorescence levels, equally responding to induced rate changes of the oxidative phosphorylation. The flavoprotein autofluorescence levels of these subsets differed by a factor of four. This heterogeneity was substantiated by flow-cytometric analysis of flavoprotein and DASPMI fluorescence changes of individual mitochondria isolated from mice skeletal muscle. Our data provide direct evidence that mitochondria in single myofibers are distinct subsets at the level of an intrinsic fluorescent marker of the mitochondrial NAD-redox system. Under the present experimental conditions these subsets show similar functional responses.

Animals↗