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Biomedical subjects

S Kozlowski

Publications and source records attributed to S Kozlowski.

At least 37 records · Page 2Linked to original sources
PubMed1992

Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules.

T cell stimulation by the human immunodeficiency virus 1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules in a cell-free system was found to require proteolytic cleavage. This extracellular processing was mediated by peptidases present in fetal calf serum. In vitro processing of p18 resulted in a distinct reverse phase high performance liquid chromatography profile, from which a biologically active product was isolated and sequenced. This peptide processing can be specifically blocked by the angiotensin-1 converting enzyme (ACE) inhibitor captopril, and can occur by exposing p18 to purified ACE. The ability of naturally occurring extracellular proteases to convert inactive peptides to T cell antigens has important implications for understanding cytotoxic T lymphocyte responses in vivo, and for rational peptide vaccine design.

Amino Acid Sequence↗
PubMed1992

Solution binding of an antigenic peptide to a major histocompatibility complex class I molecule and the role of beta 2-microglobulin.

The major histocompatibility complex-encoded class I molecule, a noncovalent dimer of a polymorphic 45-kDa heavy chain and a nonpolymorphic 12-kDa beta 2-microglobulin (beta 2m) light chain, binds peptide antigen prior to its interaction with T-cell antigen receptors. We report here that the binding in aqueous solution at 37 degrees C of a soluble purified murine major histocompatibility complex class I protein, H-2Lds (a soluble analogue of H-2Ld consisting of the alpha 1 and alpha 2 domains of H-2Ld, the alpha 3 domain and the C terminus of Q10b), to an antigenic peptide is controlled by the light-chain subunit beta 2m. Analysis of the equilibrium binding data favors a model in which two classes of peptide binding sites exist, the high-affinity class having an equilibrium constant for dissociation, KH, of 3.7 x 10(-7) M and accounting for 12% of the theoretically available sites. Studies of binding in the presence of excess beta 2m indicate that this increases the concentration of available high-affinity sites. These data are consistent with a ternary model in which high-affinity sites are generated by the interaction of beta 2m with the peptide-binding class I heavy chain.

Amino Acid Sequence↗
PubMed1992

Exercise performance, core temperature, and metabolism after prolonged restricted activity and retraining in dogs.

To study physiological effects of restricted activity (RA) and subsequent retraining, 10 male mongrel dogs (1-5 years) performed a submaximal exercise endurance test on a treadmill (12 degrees slope, 1.6 m.s-1) during kennel control, after 8 weeks of cage (40 cm-w x 80 cm-h x 110 cm-l) confinement, and after 8 weeks of retraining using the same treadmill protocol 1 h/d for 6 d/week. Compared with control endurance (172 +/- 19 min), endurance decreased to 102 +/- 15 min (delta = -41%, p less than 0.05) after RA and increased to 223 +/- 24 min (delta = +30%, p less than 0.05) after training: the respective final levels and changes in rectal temperature were 41.25 and +2.15 degrees C, 41.60 and +2.70 degrees C (NS), and 41.35 and +2.40 degrees C (NS), respectively. Resting and post-exercise blood glucose and lactate concentrations were unchanged in the three experiments. After RA, resting muscle glycogen was reduced from a control level of 49.9 +/- 4.3 to 34.1 +/- 4.5 mmol.kg-1 (delta = 32%, p less than 0.05) which returned to the control level of 58.4 +/- 3.5 mmol.kg-1 after retraining. Resting plasma FFA levels were unchanged, but the RA post-exercise change was decreased from a control level of +0.400 +/- 0.099 to +0.226 +/- 0.039 mmol.L-1 (p less than 0.05). Neither restricted activity nor training affected glucose tolerance significantly. The results indicated that RA reduces exercise endurance, the effectiveness of exercise thermoregulation, muscle glycogen stores, and the lipolytic response to exercise and to noradrenaline stimulation. All these changes were reversed following 8 weeks of retraining.

Animals↗
PubMed1991

Excess beta 2 microglobulin promoting functional peptide association with purified soluble class I MHC molecules.

T lymphocytes expressing alpha beta receptors recognize antigenic peptide fragments bound to major histocompatibility complex class I or class II molecules present on the surface membranes of other cells. Peptide fragments are present in the two available HLA crystal structures and recent data indicate that peptide is required for the stable folding of the class I heavy chain and maintenance of its association with the class I light chain, beta 2-microglobulin (beta 2m), at physiological temperature. To explain how the exogenous peptide used to create targets for cytotoxic cells bearing CD8 antigen could associate with apparently peptide-filled extracellular class I molecules, we hypothesized that stable binding of exogenous peptide to mature class I molecules reflects either the replacement of previously bound peptide during the well documented beta 2m exchange process or the loading of 'empty' class I heavy chains dependent on the availability of excess beta 2m. In either case, free beta 2m should enhance peptide/class I binding. Using either isolated soluble class I molecules or living cells, we show here that free purified beta 2m markedly augments the generation of antigenic complexes capable of T-cell stimulation.

Cell-Free System↗
PubMed1989

Effect of endurance training on cardiovascular response to static exercise performed with untrained muscles.

Eighteen male volunteers (20-23 years) were submitted to 13 weeks of training consisting of 30 min of exercise (at 50%-75% VO2max) on a bicycle ergometer, performed three times a week. Every 4 weeks the heart rate (HR), blood pressure (BP), and systolic time interval (STI) responses to the static handgrip (at 30% MVC) were examined. Before and after 13 weeks of training echocardiograms were recorded in seven subjects at rest and during the handgrip. Significant decreases in HR and BP responses to static exercise were found already after 4 weeks of training. Resting STI and left ventricular dimensions were not affected by training, but during the static exercise the pre-ejection period (PEP) and isovolumic contraction time interval (ICT) at the corresponding HR were significantly shortened after 8 weeks of training. The values of echocardiographic indices of left ventricular function obtained during exercise after training did not differ significantly from those found before training. It is concluded that endurance training of moderate intensity improves cardiac function during static exercise performed with untrained muscles.

Adult↗
PubMed1985

Plasma testosterone and catecholamine responses to physical exercise of different intensities in men.

Plasma testosterone, noradrenaline, and adrenaline concentrations during three bicycle ergometer tests of the same total work output (2160 J X kg-1) but different intensity and duration were measured in healthy male subjects. Tests A and B consisted of three consecutive exercise bouts, lasting 6 min each, of either increasing (1.5, 2.0, 2.5 W X kg-1) or constant (2.0, 2.0, 2.0 W X kg-1) work loads, respectively. In test C the subjects performed two exercise bouts each lasting 4.5 min, with work loads of 4.0 W X kg-1. All the exercise bouts were separated by 1-min periods of rest. Exercise B of constant low intensity resulted only in a small increase in plasma noradrenaline concentration. Exercise A of graded intensity caused an increase in both catecholamine levels, whereas, during the most intensive exercise C, significant elevations in plasma noradrenaline, adrenaline and testosterone concentrations occurred. A significant positive correlation was obtained between the mean value of plasma testosterone and that of adrenaline as well as noradrenaline during exercise. It is concluded that both plasma testosterone and catecholamine responses to physical effort depend more on work intensity than on work duration or total work output.

Adult↗
PubMed1984

Endocrine response to physical efforts with equivalent total work loads but different intensities in man.

The purpose of this study was to determine relationships between some exercise-induced neurohormonal changes and either exercise intensity, or its duration, or the total work output. Plasma catecholamine, cortisol, growth hormone and insulin concentrations were measured in healthy male subjects having performed three bicycle-ergometer exercise tests of the same total work output (2160 J kg-1) but differing in intensity and duration. The results showed that during the relatively short exercise plasma noradrenaline, adrenaline and cortisol responses depend more on work intensity than on the total work output. No relationship was demonstrated between the exercise-induced increases in plasma growth hormone concentration and work intensity or its duration, while the plasma insulin concentration was more decreased during the effort of lower intensity, but longer duration than during a short exercise of high intensity.

Adult↗
PubMed1983

Mechanism of sympathetic activation during prolonged physical exercise in dogs. The role of hepatic glucoreceptors.

It seems likely that depletion of body carbohydrates may account for the rise in the sympathetic activity during prolonged exercise, since glucose given during or before exercise reduces the increase in plasma catecholamines. The aim of the present study was to find out whether the increase in plasma noradrenaline (NA) in response to exercise can be reduced by 1. increasing of the amount of carbohydrate available for metabolism without producing hyperinsulinemia and 2. by inhibition of afferent activity from hepatic glucoreceptors. The study was performed on dogs which exercised whilst receiving either the intravenous fructose infusion (2.2 mmol/min) or a slow glucose infusion (0.25 mmol/min) which was given either via the portal or a peripheral vein. Fructose infusion reduced the muscle glycogen depletion during exercise and reduced the increase in plasma NA and glycerol concentrations without altering the blood glucose or insulin levels. The exercise-induced increases in plasma NA and glycerol concentrations were significantly smaller with intraportal than with peripheral glucose infusion but there were no differences between these two cases in the concentration of glucose in the systemic circulation. These findings indicate that the reduction of the plasma NA response to physical effort under conditions of increased carbohydrate availability cannot be attributed to the inhibitory effect of insulin on sympathetic activity and provide evidence for the participation of hepatic glucoreceptors in the control of the sympathetic activity during exercise.

Animals↗
PubMed1983

Sequence dependence of hydrogen exchange kinetics in DNA duplexes at the individual base pair level in solution.

The kinetics for hydrogen exchange at individual base pairs in self-complementary deoxydodecanucleotide duplexes have been estimated from NMR saturation recovery measurements on the resolved imino protons as a function of temperature. The imino protons of dA . dT base pairs in the center of the fully alternating d(C-G-C-G-T-A-T-A-C-G-C-G) duplex exchange a factor of 2- to 3-fold faster than the corresponding protons at the same positions in the partially alternating d(C-G-C-G-A-A-T-T-C-G-C-G) duplex. These exchange parameters are a direct measure of the rate constants for transient opening of individual dA . dT base pairs in the dodecanucleotide duplexes and demonstrate faster opening kinetics for the "TATA" box region compared to the related "AATT" segment.

Base Sequence↗
PubMed1982

Reduction in peak oxygen uptake after prolonged bed rest.

The purpose was to test the hypothesis that the magnitude of the reduction in peak oxygen uptake (VO2) after bed rest is directly proportional to the level of pre-bed rest peak VO2. Complete pre- and post-bed rest working capacity and body weight data were available from three studies involving 24 men (19-24 yr; peak VO2, 2.39-4.80 l . min-1) and 8 women (23-34 yr; peak VO2 1.47-2.58 l . min-1), who underwent bed rest for 14-20 d with no remedial treatments. Regression analysis of percent change in post-bed rest peak VO2 on pre-bed rest peak VO2 with 32 subjects resulted in correlation coefficients (r) of--0.03 (NS) for data expressed in l . min-1 and -0.17 (NS) for data expressed in ml . min-1 . kg-1. Significant correlations were found that supported the hypothesis only when peak VO2 data were analyzed separately from studies that utilized the cycle ergometer, particularly with subjects in the supine position, as opposed to data obtained from treadmill peak VO2 tests. We conclude that orthostatic factors, associated with the upright body position and relatively high levels of physical fitness from endurance training, appear to increase variability of pre- and particularly post-bed rest peak VO2 data, which would lead to rejection of the hypothesis.

Adult↗
PubMed1981

Suppression of thirst in dogs with arteriovenous fistula.

The aim of the present study was to investigate the effect of moderate continuous overloading of the heart on 24-h water intake (WI), urine (Vu), sodium (UNaV), potassium (UKV), solute (Cosm) and free water (CH20) excretion. The overloading of heart was produced by construction of the fistula (AVF) between the femoral artery and the vena cava inferior. Twenty four hours WI, Vu, UNaV, UKV, Cosm, CH20, as well as central venous (CVP), arterial (MABP) and interstitial (IP) pressure and volume of the extracellular fluid (ECW) were examined before and 1, 2 or 3 months after production of AVF. Daily water intake, and water/food ratio decreased, whereas CVP, MABP and IP increased significantly after production of the fistula. A significant increase in ECW was found 1 month after production of AVF. It is suggested that a moderate overloading of the heart may cause a prolonged decrease in water intake, possibly due to augmentation of the inhibitory input from the cardiovascular receptors.

Animals↗
PubMed1980

Plasma catecholamines during exercise-induced bronchoconstriction in bronchial asthma.

Plasma levels of adrenaline and noradrenaline during and after submaximal exercise in patients with bronchial asthma were investigated. Three groups were studied comprising 10 patients with exercise-induced bronchoconstriction (EIB), 10 asthmatic patients without EIB and four normal control subjects. Plasma catecholamines were measured at rest, at the end of exercise, and five and 15 minutes after exercise. Changes in airway resistance were assessed by measuring peak expiratory flow rate. Significant differences in catecholamine levels between reacting and non-reacting patients were found. In 10 patients developing EIB adrenaline and noradrenaline levels had risen significantly by the end of exercise and remained elevated up to the fifth minute of recovery. The rise in catecholamine levels in non-reacting asthmatics was insignificant. In control subjects noradrenaline had increased significantly by the end of exercise.

Adult↗