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R Altman

Publications and source records attributed to R Altman.

136 records · Page 8Linked to original sources
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Efficacy of unfractionated heparin, low molecular weight heparin and both combined for releasing total and free tissue factor pathway inhibitor.

Unfractionated heparin (UFH) exerts its anticoagulant properties by increasing the inactivation of thrombin and activated factor X by antithrombin III. Apart from this main action release of tissue factor pathway inhibitor (TFPI) from endothelial cells could also be important for the antithrombotic activity of heparins. Four different heparin preparations were injected subcutaneously into 5 healthy volunteers 1 week apart: (1) UFH 2,500 IU fix dose (FixUFH), (2) 1 mg/kg body weight of low molecular weight heparin (LMWH), (3) the combined LMWH-adjusted dose plus UFH 2,500 IU fix dose (ComHep) and (4) UFH 2,500 IU/10 kg body weight (UFHvar). Plasma samples were drawn before and 1, 2, 4, 6, 12 and 24 h afterwards. FixUFH did not affect the concentration of total and free TFPI. Total TFPI increased in the 1st hour after LMWH injection from 74 to 124 ng/ml (p < 0.01), after ComHep from 82 to 144 ng/ml (p < 0.01), and after UFHvar from 91 to 113 ng/ml (p < 0.05). All observed elevations were significant at the peak value (+/- 2 h, p < 0.01 compared with baselines). The increase of free TFPI produced by UFHvar (74.5 and 70.5 ng/ml) was significantly higher than with LMWH (42.8 and 38.0 ng/ml) at 2 and 4 h (p < 0.001 and p < 0.01, respectively). UFHvar and ComHep but not LMWH produced a statistically significant increase of free TFPI compared with FixUFH at 2, 4 and 6 h (p < 0. 01). We concluded that at comparable therapeutic doses, subcutaneous UFHvar released more free TFPI than LMWH and ComHep. A synergism between LMWH and low dose of UFH was found in 4-, 6- and 12-hour blood samples.

Adult↗
PubMedDate not supplied

[Nuclear magnetic resonance and protein structure].

NMR provides a wealth of structural information about proteins in solution, but does not, by itself, permit an unambiguous determination of a unique structure. A rigorous interpretation of NMR data to obtain the entire family of structures compatible with a given data set requires extensive, systematic and unbiased sampling of the conformational space of the polypeptide chain. Methods of sampling based on the exclusion paradigm--i. e. those that generate structures, check constraints and accept or reject members of the family on that basis, avoid the problem of generating erroneous structures by converging on local minima, which is a common pitfall of methods based on the optimization paradigm. Their much higher computational cost can be reduced by solving the structure in stages, using abstract representations of partial structures, and guiding the computation by control heuristics. The heuristic refinement method developed at Stanford and encoded in the expert system PROTEAN yields more or less extensive families of structures, depending on the size of the NMR data set, and defines the "allowed volume" in which each atom (or other substructure) may lie, with all experimental constraints satisfied. The allowed volume is a measure of the uncertainty of our knowledge of the structure, to which both the limitations of the data and the uncertainty of position resulting from molecular motion may contribute. Prediction of the experimental NMR spectra by solving the generalized Bloch equations (or the Redfield density matrix) for the protein, using atomic coordinates that lie within the allowed atomic volume, provides the final test for the correctness of the proposed structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic Resonance Spectroscopy↗