Hybridomas expressing murine gamma delta T-cell receptors were found to produce cytokines in response to cardiolipin (CL) and structurally related anionic phospholipids. This response required serum ...at concentrations related to the amount of CL in cultures. The purified serum factor, beta sub(2)-glycoprotein 1 ( beta sub(2)-GP1) (apolipoprotein H), supported the CL response alone, whereas several other serum proteins and ovalbumin did not. beta sub(2)-GP1 is known to form complexes with anionic phospholipids, particularly CL, which are often recognized by pathological autoantibodies. We speculate that gamma delta T cells also recognize such complexes and that the hybridoma response reported here reflects this specificity.
Hybridomas expressing murine gammadelta T-cell receptors were found to produce cytokines in response to cardiolipin (CL) and structurally related anionic phospholipids. This response required serum ...at concentrations related to the amount of CL in cultures. The purified serum factor, beta2-glycoprotein 1 (beta2-GP1) (apolipoprotein H), supported the CL response alone, whereas several other serum proteins and ovalbumin did not. beta2-GP1 is known to form complexes with anionic phospholipids, particularly CL, which are often recognized by pathological autoantibodies. We speculate that gammadelta T cells also recognize such complexes and that the hybridoma response reported here reflects this specificity.
The updated second edition of the "Curriculum cardiology", first edition 2013, aims to show which competences a cardiologist should nowadays master. It is very pleasing that in this second edition ...representatives of the Young German Cardiac Society (Young DGK) have contributed as authors. The increasing specialization within cardiology should, however, only represent one side of the coin: there must also still be a common foundation of cardiology, embedded in the discipline "internal medicine". This foundation includes the basis of theoretical knowledge, practical skills (competence levels I-III) and an occupational and professional attitude of the (prospective) cardiologist. New additions to the advanced training since the first edition of the curriculum in 2013 are, for example a chapter on digital cardiology, the further training in psychocardiology, which was newly introduced into the model further training regulations and finally also the explicit formulation of shared decision making in the interests of cardiac patients. The curriculum should give the prospective cardiologist the possibility to structure the further training as efficiently as possible and ultimately to retain and expand that which has been learned in the sense of a "professional lifelong" qualification. The curriculum also aims to reach the trainers and the Medical Councils and demonstrate which contents and skills should be mediated in the further training to become a cardiologist from the perspective of the German Cardiac Society (DGK).
There is growing evidence that exhaustive exercise can induce a suppression of the innate immune functions. Most studies so far describe exercise induced changes in cell counts or functional ...responses while information regarding intracellular signal transduction parameters is lacking. Therefore in the present study we investigated in granulocytes the regulation of intracellular calcium (Ca2+i) which is an important intracellular second messenger. Healthy volunteers underwent a treadmill exercise test at 80% of their maximal oxygen uptake until exhaustion. Granulocytes were separated before and 1 hour after the test. Ca2+i was analyzed spectrophotometrically using the Ca2+ sensitive fluorescent dye Fura-2, while the oxidative burst and phagocytosis were measured by flow cytometry. While resting Ca2+i levels were unchanged, the Ca2+ transient induced N-formyl-methionyl-leucyl phenylalanine (fMLP) and platelet activating factor (PAF) were enhanced 1 hour after the test compared to pre-exercise values although fMLP receptor density did not change. In contrast, oxidative burst and phagocytosis evoked by fMLP and phorbol-myristate-acetate (PMA) were decreased after exercise. Together, our data support the view that exhaustive exercise affects regulation of Ca2+ signaling in granulocytes. The potentiation of Ca2+ signals is not accompanied by an enhancement of cellular functional parameters suggesting a blockade in intracellular signalling pathways.
Rat pulmonary surfactant protein A is an oligomer of 18 polypeptide chains which are associated by triple helix formation in the collagen-like domain and interchain disulfide bridges at the NH2 ...terminus. The roles of the intermolecular bond at Cys6 and the collagen-like domain (Gly8-Pro80) in the interactions of SP-A with phospholipids and alveolar type II cells were investigated using mutant forms of the protein. Wild type SP-A (SP-Ahyp), SP-A with the substitution Cys6 → Ser to prevent disulfide formation (SP-Ahyp,C6S), and SP-A with the collagen-domain deleted (SP-AΔG8-P80) were synthesized in insect cells using recombinant baculoviruses. The SP-As were glycosylated and secreted from the invertebrate cells and the binding affinities of the wild type and mutant proteins for the mannose-Sepharose matrix used for purification were nearly identical. The SP-Ahyp and SP-AΔG8-P80 were at least nonameric in solution based on gel exclusion chromatography, and demonstrated extensive sulfhydryl-dependent oligomerization under nonreducing conditions. The SP-Ahyp,C6S was also oligomeric in solution and formed disulfide-dependent dimers, indicating the presence of at least one additional interchain disulfide bond. The SPAΔG8-P80 but not the SP-Ahyp,C6S aggregated lipid vesicles at 20 °C and augmented the surface tension lowering effect of extracts of natural surfactant. The SP-AΔG8-P80 competed poorly with native SP-A for receptor occupancy on isolated alveolar type II cells and was a potent but nonspecific (concanavalin A-like) inhibitor of surfactant secretion. In contrast, the SP-Ahyp,C6S partially competed for receptor occupancy and weakly inhibited surfactant secretion in a specific manner. Neither the SP-AΔG8-P80 nor the SP-Ahyp,C6S supported the association of phospholipid liposomes with type II cells. We conclude that: 1) the Cys6interchain disulfide bond of SP-A is required for aggregation of liposomes and for potent inhibition of surfactant secretion. 2) The collagen-like region is required for competition with125I-SP-A for receptor occupancy and specific inhibition of surfactant secretion in the presence of competing sugars. 3) Both the NH2-terminal disulfide and the collagen-like region are required to enhance the association of phospholipid vesicles with type II cells.
Objectives. This exercise study assessed the relation between valvular resistance and flow in patients with mitral stenosis.
Background. Valvular resistance has been proposed as an alternative measue ...of stenotic valvular lesions, which is speculated to remain stable under changing hemodynamic conditions.
Methods. In 35 of 40 patients with pure or predominant mitral stenosis, continuous wave Doppler measurements of the mitral stenotic jet were possible at rest and during supine bicycle ergometry. Simultaneously, transvalvular flow was assessed by thermodilution technique. For calculation of valvular resistance, the mean mitral valve pressure gradient was determined according to the simplified Bernoulli equation and divided by transvalvular flow. Additionally, effective mitral valve area was calculated according to the continuity equation method, dividing flow by the mean diastolic low velocity.
Results. Valvular resistance was 65 ± 32 dynes · s · cm−5at rest and increased to 82 ± 43 dynes · s · cm−5at 25 W (p < 0.001). The most prominent increase in valvular resistance (rest to 25 W 63 ±28 to 95 ± 48 dynes · s · cm−5, p < 0.001) was found in those patients who had no or only a moderate (< 20%) change in effective mitral valve area. In contrast, valvular resistance remained constant (67 ± 36 vs. 70 ± 32 dynes · s · cm−5) in patients with significant (≥ 20%) increase in mitral valve area with exercise.
Conclusions. In patients with mitral stenosis, the exercise induced change in valvular resistance are heterogeneous. This is the result of the variable response of mitral valve area to an increase in flow. In the individual patient, mital valve area can significantly increase, a factor that has to be taken into account when interpreting the hemodynamic relevance of the obstruction. Calculated valvular resistance is flew dependent and has no advantage over valve area calculation for quantifying stenosis.
In this work, we demonstrate how constrained Moving Horizon Estimation (MHE) and Model Predictive Control (MPC) can be simultaneously addressed via multi-parametric programming. First, we present a ...method for obtaining the error dynamics of constrained MHE for linear, time-invariant systems by solving the constrained optimization problem of the MHE by multi-parametric programming methods. Set-theoretical methods are then used to derive bounds on the estimation error - it is shown that the estimation error is bounded in an invariant set for the error dynamics described by a set of linear inequalities. The error dynamics and the error bounds can then be used for the design of a robust output feedback explicit/multi-parametric MPC yielding a simultaneous estimation and control design which is illustrated with an example of robust tube-based MPC.
Recessive mutations at the suppressor of sable su(s) locus in Drosophila melanogaster result in suppression of second site mutations caused by insertions of the mobile element 412. In order to ...determine whether su(s) mutations might have other phenotypes, a saturation mapping of the su(s) region was carried out. The screen yielded 76 mutations that comprise ten genetic complementation groups ordered distal to proximal as follows: l(1)1Bh, l(1)1Bi, M(1)1B, su(s), l(1)1Bk, l(1)1Ca, mul, tw, l(1)lDa and brc. Twenty-three of the mutations are su(s) alleles, and all are suppressors of the 412-insertion-caused v1 allele. Although the screen could have detected su(s) mutations causing sex-specific dominant lethality or sterility as well as all types of recessive lethality or sterility, the only other phenotype observed was male sterility that is enhanced by cold temperature. This type of sterility is exhibited only by alleles induced by base-substitution-causing mutagens. Genetic functions of the poly(A+) messages transcribed from the su(s) microregion were identified by the reintroduction of cloned sequences into embryos by P element transformation. su(s) function has been attributed to a 5-kb message. The segment of DNA encoding only this 5-kb message rescues both the suppression and cold-sensitive male sterility phenotypes of su(s). Minute (1)1B has been provisionally identified as encoding a 3.5-kb message; lethal (1)1Bi encodes a 1-kb message; and lethal (1)1Bk encodes a 4-kb message. The possible functions of su(s) and M(1)1B are discussed
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