Experimental constraints on left-right symmetric models from muon decay.

The TWIST Collaboration has completed a new measurement of the energy-angle spectrum of positrons from the decay of highly polarized muons. A simultaneous measurement of the muon decay parameters ρ, δ, and P(µ)(π)ξ tests the standard model in a purely leptonic process and provides improved limits for relevant extensions to the standard model. Specifically, for the generalized left-right symmetric model |(g(R)/g(L))ζ|<0.020 and (g(L)/g(R))m(2)>578 GeV/c(2), both 90% C.L.

Cooperative binding of substrates to transketolase from Saccharomyces cerevisiae.

Catalytic activity of two active sites of transketolase and their affinity towards the substrates (xylulose-5-phosphate and ribose-5-phosphate) has been studied in the presence of Ca2+ and Mg2+. In the presence of Ca2+, the active sites exhibit negative cooperativity in binding both xylulose-5-phosphate (donor substrate) and ribose-5-phosphate (acceptor substrate) and positive cooperativity in the catalytic transformation of the substrates. In the presence of Mg2+, nonequivalence of the active sites is not observed.

The changes in the energy metabolism of human muscle induced by training.

The biochemical effects of training programmes have been studied with a kinetic model of central metabolism, using enzyme activities and metabolite concentrations measured at rest and after 30 s maximum-intensity exercise, collected before and after long and short periods of training, which differed only by the duration of the rest intervals. After short periods of training the glycolytic flux at rest was three times higher than it had been before training, whereas during exercise the flux and energy consumption remained the same as before training. Long periods of training had less effect on the glycolytic flux at rest, but increased it in response to exercise, increasing the contribution of oxidative phosphorylation.

Unusual kinetic behavior predicted for alpha-keto acid dehydrogenase complexes.

A novel regulation type, which may be observed as an unusual kinetic 'cooperativity', is predicted for the alpha-keto acid dehydrogenase complexes. The inter-relationship of this regulation with the well-known regulatory effect of enzyme phosphorylation is discussed.

Activity oscillations predicted for pyruvate dehydrogenase complexes.

A kinetic model for the pyruvate dehydrogenase complex is analyzed. The model takes into account intermediate channeling through the lipoyl network attached to the complex core, as well as inter-related regulatory effects of protein X acetylation and enzyme phosphorylation. The model predicts undamped oscillations of enzyme activity.

Kinetic mechanism of active site non-equivalence in transketolase.

The two-step mechanism of coenzyme (TDP) binding to apotransketolase has been examined by kinetic modeling, and the rate and equilibrium constants for each binding step for two active sites have been determined. The dissociation constants for the primary fast binding step and the forward rate constants for the secondary slow binding step have been shown to be similar for two active sites. The backward rate constants for the secondary binding step are different for two active sites, providing the kinetic mechanism of their non-equivalence in TDP binding.

Effect of abdominal operations on survival after septic challenge in normal rats.

We evaluated the effect of 60% small-bowel enterectomy that removed 75% of Peyer's patches, and the effects of lesser abdominal operations, on the survival of rats following inducement of peritonitis. We divided 286 female Fischer rats weighing 140 to 200 g into four experimental and two control groups. Following enterectomy, rats recovered for ten to 14 days before peritonitis was induced by intraperitoneal injection of 0.7 mL/100 g of body weight of a solution of 4% hemoglobin and Escherichia coli (10(9)/mL). At 48 hours after enterectomy, the survival rate was better than that in rats not operated on or anesthetized. Survival rates for rats having lesser intra-abdominal operations were significantly greater after peritonitis than the rates for controls, but were similar to rates for rats having enterectomies. Our results suggest that intra-abdominal operation of minimal or large magnitude is associated with improved survival from hemoglobin-E coli adjuvant peritonitis.

A model of mitochondrial Ca(2+)-induced Ca2+ release simulating the Ca2+ oscillations and spikes generated by mitochondria.

Recent evidence underlines a key role of mitochondrial Ca2+ fluxes in cell Ca2+ signalling. We present here a kinetic model simulating the Ca2+ fluxes generated by mitochondria during mitochondrial Ca(2+)-induced Ca2+ release (mCICR) resulting from the operation of the permeability transition pore (PTP). Our model connects the Ca2+ fluxes through the ruthenium redsensitive Ca2+ uniporter, the respiration-dependent and passive H+ fluxes, the rate of oxygen consumption, the movements of weak acids across the mitochondrial membrane, the electrical transmembrane potential (delta psi), and operation of the PTP. We find that two factors are crucial to account for the various mCICR profiles that can be observed experimentally: (i) the dependence of PTP opening and closure on matrix pH (pHi), and (ii) the relative inhibition of the respiratory rate consecutive to PTP opening. The resulting model can simulate irreversible Ca2+ efflux from mitochondria, as well as the genesis of damped or sustained Ca2+ oscillations, and of single Ca2+ spikes. The model also simulates the main features of mCICR, i.e. the threshold-dependence of mCICR triggering, and the all-or-nothing nature of mCICR operation. Our model should appear useful to further mathematically address the consequences of mCICR on the spatiotemporal organisation of Ca2+ signals, as a 'plug-in' module for the existing models of cell Ca2+ signalling.

The accuracy of computed tomography in the diagnosis of blunt small-bowel perforation.

BACKGROUND: Computed tomography (CT) is commonly used to evaluate patients with possible blunt intra-abdominal injury. One of its reported weaknesses is failure to demonstrate intestinal trauma. However, CT accuracy in identifying blunt small-bowel perforation has not been adequately assessed. PATIENTS AND METHODS: We tracked 883 consecutive stable trauma victims who had abdominal CT because of equivocal physical findings. Initial "wet reading" results were compared with laparotomy findings and patient outcome. RESULTS: Small-bowel perforation occurred in 26 patients (3%). Twenty-four had CT abnormalities suggesting the injury. Twelve had CT findings considered diagnostic: contrast extravasation (n = 5) and/or extraluminal air (n = 11). One additional patient was thought to have free air on CT, but had no intestinal injury at laparotomy. Another 12 patients had CT scans that were non-diagnostic but suggestive: free fluid without solid organ injury (n = 10), or small-bowel thickening (n = 4) or dilatation (n = 3). Two patients with small-bowel injuries had normal CT scans. Of 857 patients without small-bowel disruption, 802 had normal abdominal CT scans, and 55 had 67 CT findings suggesting intestinal injury. Thus, CT diagnosed small-bowel perforation with a sensitivity of 92%, a specificity of 94%, and negative and positive predictive accuracies of 100% and 30%, respectively. The test had an overall accuracy (validity) of 94%. CONCLUSIONS: Blunt small-bowel injury is uncommon. When it is present, abdominal CT is usually abnormal. CT findings in intestinal perforation can be subtle and nonspecific. Any unexplained abnormality on CT after blunt abdominal trauma may signal the presence of intestinal perforation and warrants close clinical observation or further diagnostic tests.

[Analysis and interaction of myosin active centers during a mechanochemical cycle]. / Analiz vzaimodeistviia aktivnykh tsentrov miozina v protsesse mekhanokhimicheskogo tsikla.

A model of myosin complex with two active sites is considered. Each of the sites is supposed to pass through four states during a cycle of ATP hydrolysis. The model describes the distribution of the complex between states and the ATP hydrolysis rate as dependent on ATP concentration and reaction constants. Some of the constants were determined experimentally [6], but these values reproduce experimental curves [5] only with the assumption of cooperativity. If the first site is bind to actin, the rate of binding for the second one is shown to increase tenfold. If one of the sites is bind to actin by a "pulling" bridge, and the second site is in "rigor" state, then the ATP binding for the second site is about ten times faster. The transition into the rigor state proceeds much faster if both sites form pulling bridges. The rate of binding to actin is the same for one and for two sites.

[Light-induced changes in pH and buffer capacity in reaction center preparations of Rhodopseudomonas spheroides]. / Indutsirovannye svetom izmenenniia pH i bufernoi emkosti v suspenzii fotosinteticheskikh reaktsionnykh tsentrov iz Rhodopseudomonas sphaeroides.

In experiments with reaction centers (RC) preparations of Rps. sphaeroides, strain 1760-1, pH of the suspension medium was found to change under continuous light excitation. The concentration of hydrogen ions starts to decrease fastly (t1/2 = 2--4 s) after the light is on, whereupon it increases slowly, to a steady-state level, within t1/2 = 5--7 min. During the fast phase 0.3 microM H+/1 microM of RC are absorbed and 7--8 microM H+/1 microM of RC are released under the slow phase. The fast phase is suppressed by ortho-phenantroline (10 mM)--an inhibitor of electron transfer from the primary (Fe-quinone complex) to the secondary (quinone) electron acceptors. Glutaraldehyde which is known to modify a protein structure of the RC inhibits the slow phase. The obtained data suggest that fast light-induced pH changes are due to a H+ uptake by the secondary quinoid anion-radical products; slow pH changes are ascribed to structural changes within the RC complex, which lead to a pK shift and/or changes in the amount of dissociating groups on the protein interfacial surface. The conclusion was supported by an observation of light-induced changes in buffer capacity of an RC suspension and by a light-induced increase in the amount of SH-groups titrated by 5.5-dithio-bis(2 nitro)-benzoic acid. The role of conformational dynamics of photoactive pigment--protein complexes in the functions of the RC is discussed.

[Capacity of bone marrow cells to restore thrombocytopoiesis in lethally irradiated animals]. / Izuchenie sposobnosti kletok kostnogo mozga vosstanavlivat' trombotsitopoéz u lethal'no obluchennykh zhivotnykh.

A study was made of the kinetics of thrombocytopoiesis restoration in lethally irradiated mice after transplantation to them of the donor marrow cells. In the initial period, the thrombocytopoiesis restoration is provided by transite cells-precursors of megakaryocytes present in the transplanted bone marrow; the subsequent restoration is due to cells of the self-maintaining population. The level of restoration does not correlate with the number of polypotent cells that form macrocolonies in the spleen of irradiated recipients.

[Patterns of thrombocytopoiesis regulation]. / Zakonomernosti reguliatsii trombotsitopoéza.

Based on literature data, the main kinds of thrombocytopoiesis regulation are analyzed. It is shown that humoral factors regulate the intensity of proliferation of committed precursors and the mean sizes of mature megakaryocytes. The activity of these factors depends on the numbers of thrombocytes in blood and of megakaryocytes in bone marrow. The evidence presented in the review enables one to give a quantitative description of the relationship between the rate of thrombocytopoiesis and the content of thrombocytes in blood. The fact that the alteration of the time of megakaryocyte maturation does not depend on the duration and strength of the influences points to a non-specificity of this reaction. A scheme for the thrombopoiesis regulation is proposed which can serve as a basis for its mathematic description.

[Regulation of thrombocytopoiesis studied by a mathematical model]. / Izuchenie reguliatsii trombotsitopoéza s ispol'zovaniem matematicheskoi modeli.

A mathematical model of thrombocytopoiesis is proposed which accounts for the recent data on its regulation. It is shown that the compensatory response of the system to a decrease in the level of thrombocytes in the blood is controlled by the total amount of thrombocytes and megakaryocytes. The proliferation intensity of megakaryocytes and the total number of thrombocytes reveal, respectively, a lineary and a logarithmical dependence on the total number of thrombocytes and megakaryocytes. The limits of the post-transfusion level of thrombocytes are defined, within which the thrombocytopoiesis is controlled only by the number of thrombocytes. The values of parameters characterizing the behaviour of the thrombocytopoiesis system are calculated.

[Comparison of 2 methods of studying polypotent hematopoietic cells]. / Sravnenie dvukh metodov izucheniia polipotentnykh krovetvornykh kletok.

The cells giving rise to colonies in the spleen of a lethally irradiated recipient after their transplantation (exogenous CFUs) have a higher self-maintaining ability than those that repopulate their own hemopoietic territory after irradiation, due to the migration of these cells from screened territories (endogenous CFUs). The number of exogenous CFUs and their self-maintaining ability do not change with animals ageing.

[Mathematical model of oscillations in mammalian erythrocytes. The role of calmodulin-dependent Ca-activated Ca-pump]. / Matematicheskaia model' kolebanii v éritrotsitakh mlekopitaiushchikh.Rol' kal'modulinzavisimogo Ca-aktiviruemogo Ca-nasosa.

A kinetic model of ionophore-induced oscillation of ion fluxes in mammalian erythrocytes is proposed. The model is based on the regulation by Ca2(+)-ions and calmodulin of (Ca2(+) + Mg2+)-dependent ATPase of erythrocytes. The results obtained are in a good agreement with the experimental data available.

[Mechanism of low intensity ultrasound effect on mitochondria]. / O mekhanizme deistviia ul'trazvuka nizkikh intensivnostei na mitokhondrii.

Ultrasound of 0,2 Wt/cm2 intensity affects the ionic transport across the mitochondrial membrane in vitro. In the presence of 1 mM EGTA in the incubation medium ultrasound slows down K+ exit into the external medium after the addition of an uncoupling agent (2,4-dinitrophenol). With the addition of 100 divided by 400 mM Ca2+ to the starting medium ultrasound makes the amount of Ca2+ absorbed by mitochondrial decrease and the rate of Ca2+/H+ electroneutral exchange increase. Without Ca2+ ultrasound does not influence the rate of coupled and 2,4-dinitrophenol uncoupled respiration and oxidative phosphorylation, i.e. does not produce strong functional changes.

[Megakaryocytopoiesis studied in a mathematical model. 3. Regulation of cell differentiation in immune thrombocytopenia]. / Izuchenie megakariotsitopoéza s pomoshch'iu matematicheskoi modeli. 3. Reguliatsiia differentsirovki kletok pri immunnoi trombotsitopenii.

Simulation experiments have shown that just after antiplatelet serum of rabbit blood is introduced into mice the transit time of early proliferating precursors of the megakaryocytes is reduced by about 17 h, the transit time for megakaryoblasts increases, and within 24 h after the treatment the transit time for mature megakaryocytes is reduced b about 17 h. The data obtained confirmed our earlier hypothesis on correlation between the duration of proliferative period and the mean size of megakaryocytes.

[Mathematical model study of megakaryocytopoiesis. 1. The simulation model, cell steady-state distribution and the number of divisions in a proliferating population]. / Izuchenie megakariotsitopoéza s pomoshch'iu matematicheskoi modeli. 1. Imitatsionnaia model', statisionarnoe raspredelenie kletok, chislo delenii v proliferiruiushchei populiatsii.

A method of simulation has been proposed for studying megakaryocytopoiesis. A model has been developed which takes into account the age structure of cell population, the stochasticity of their maturation, and the principles of megakaryocytopoiesis regulation (known from the experiments). The mean number of divisions in a proliferating pool has been determined, as well as the duration of development of the cells with a positive acetylcholine esterase reaction.

[Megakaryocytopoiesis studied in a mathematical model. 2. Regulation of cell differentiation following damage to part of the proliferating bone marrow pool by hydroxyurea]. / Izuchenie megakariotsitopoéza s pomoshch'iu matematicheskoi modeli. 2. Reguliatsiia differentsirovki kletok posle porazheniia chasti proliferiruiushchego pula kostnogo mozga oksimochevinoi.

Analysis of the earlier obtained data on the effect of hydroxyurea on megakaryocytopoiesis by a simulation model has shown that differentiation of proliferating precursors of the megakaryocytes depends on their amount in bone marrow; the time of their involvement in the proliferating pool increases if the number of proliferating cells decreases. Within 24 h after the treatment with hydroxyurea (900 mg/kg), the transit time for the mouse megakaryocytes is reduced by about 14 h due to acceleration of the latest developmental stages. A hypothesis is put forward which accounts for correlation between the duration of proliferative period and the volume and maturation time of megakaryocytes.