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Biomedical subjects

M Blumenstein

Publications and source records attributed to M Blumenstein.

At least 73 records · Page 4Linked to original sources
PubMed1982

Mass transfer in membrane plasma exchange.

In vitro and in vivo sieving coefficients (SC) have been determined for a spectrum of proteins ranging in molecular weight from 66,500 daltons (albumin) to 2.4 million (beta-lipoprotein) daltons for three commercially available membrane plasma separation devices: the Plasmaflo 0.1, Plasmaflo 02, and Plasmaflux. A model relating serum level of a protein to pretherapy level, plasma volume, plasma filtration rate, membrane SC, and duration of treatment has been used to investigate the influence of SC on exchange efficiency. Comparison of predicted and clinically obtained reductions in serum solute levels demonstrated the validity of the model. The results of the analysis suggest that all three plasma separators are capable of delivering equally acceptable therapy. The model further demonstrates the decreasing effectiveness, and increased cost in terms of replacement fluid per unit of solute removed, with prolonged treatment times.

Biological Transport↗
PubMed1982

[Treatment of emergency situations in autoimmune diseases with plasma exchange].

Plasma exchange has been applied successfully to treat severely ill patients with autoimmune diseases in recent years. We report on 12 patients with systemic lupus erythematosus (SLE), myasthenia gravis (MG), and Goodpasturés syndrome (GS), that have been treated with membrane plasma separation. Two to three liters of plasma were exchanged per session. Three to nine treatments were done within 1--4 weeks. Human albumin solution was used for replacement of the discarded plasma. Improvement was seen in 3 out of 5 SLE patients, in all 5 myasthenic patients and in one of the two patients with GS. Plasma exchange in combination with immunosuppressive therapy is indicated in states of active autoimmune diseases, not controllable by routine immunosuppression. For long-term treatment, however, immunosuppressive medication should be used.

Adolescent↗
PubMed1980

19F NMR studies of the binding of 5-fluoro-2'-deoxyuridylate to thymidylate synthase.

In the presence of thymidylate synthase, the 19F signal of 5-fluoro-2'-deoxyuridylate is shifted upfield 0.6 ppm or 4.5 ppm depending on the enzyme preparation used. The bands of these positions represent different species of binary complex. When either binary complex is reacted with methylenetetrahydrofolate a ternary complex is formed with a 19F signal shifted 12.5 ppm upfield and broadened to 120 Hz. Substitution of the hydrogen atoms of the methylene group of methylenetetrahydrofolate with deuterium atoms results in line-narrowing of the spectrum of the ternary complex from 120 to 80 Hz indicating the close proximity of the methylene group to the fluorine atom in the ternary complex. A model compound, 5-fluoro-6-hydroxy-5-methyl-5, 6-dihydrouracil, gives a chemical shift in the same direction and of similar magnitude to that seen with the ternary complex.

Deoxyuracil Nucleotides↗
PubMed1979

Metal binding sites of a gamma-carboxyglutamic acid-rich fragment of bovine prothrombin.

The metal binding sites of a gamma-carboxyglutamic acid-rich fragment derived from bovine prothrombin were examined using paramagnetic lanthanide ions to evaluate the role of gamma-carboxyglutamic acid resideus in metal binding. A gamma-carboxyglutamic acid-rich peptide, fragment 12-44, was isolated from a tryptic digest of prothrombin. Using 153Gd(III), fragment 12-44 was found to contain one high affinity metal binding site (KD = 0.55 microM) and four to six lower affinity metal binding sites (KD approximately 4 to 8 microM). The S-carboxymethyl derivative of fragment 12-44, in which the disulfide bond in fragment 12-44 was reduced and alkylated, contained no high affinity metal binding site and four or five lower affinity sites (KD = 8 microM). The effects of paramagnetic lanthanide ions on fragment 12-44 and its S-carboxymethyl derivative were studied by natural abundance 13C NMR spectroscopy. The 13C NMR spectrum of fragment 12-44 was recorded at 67.88 MHz and the resonances were assigned by comparison to the chemical shift of carbon resonances of amino acids and peptides previously studied. The proximity between bound metal ions and carbon atoms in fragment 12-44 was estimated using Gd(III), based upon the strategy that the magnitude of the change in the transverse relaxation rate of resonances of carbon nuclei induced by bound metal ions is related in part to the interatomic distances between bound metal and carbon nuclei. Titration of fragment 12-44 with Gd(III) resulted in the selective broadening of the gamma-carboxyl carbon, C gamma, C beta, and C alpha resonances of gamma-carboxyglutamic acid, and the C epsilon of the arginines. S-Carboxymethyl fragment 12-44, which lacked the high affinity metal binding site, showed markedly decreased perturbation of the C epsilon of the arginine residues upon titration with Gd(III). These studies indicate that gamma-carboxyglutamic acid residues in prothrombin fragment 12-44 participate in metal liganding. A high affinity metal binding site in fragment 12-44 is in close proximity of Arg 16 and Arg 25 and is stabilized by the disulfide bond. On the basis of these data, a model of the metal binding sites is proposed in which the high affinity site is composed of two gamma-carboxyglutamic acid residues which participate in intramolecular metal-dependent bridging of two regions of the polypeptide chain. The lower affinity metal binding sites, formed by single or paired adjacent gamma-carboxyglutamic acid residues, then may participate in intermolecular metal-dependent protein . protein or protein . membrane complex formation.

1-Carboxyglutamic Acid↗
PubMed1979

Nuclear magnetic resonance studies on the structure of the tetrapeptide tuftsin, L-threonyl-L-lysyl-L-prolyl-L-arginine, and its pentapeptide analogue L-threonyl-L-lysyl-L-prolyl-L-prolyl-L-arginine.

Nuclear magnetic resonance spectroscopy has been used to investigate the solution conformation of tuftsin, threonyllysylprolylarginine, as well as a pentapeptide inhibitor of tuftsin, threonyllysylprolylprolylarginine. Both proton and carbon-13 studies were performed. In water, neither peptide gives evidence of a preferred conformation. In dimethyl-d6 sulfoxide, tuftsin appears to prefer a particular conformation, but the inhibitor does not. The conformation of tuftsin is one in which the amide NH proton of arginine is solvent shielded. The conformation does not, however, appear to be such that a normal 4 leads to 1 beta turn exists.

Hydrogen-Ion Concentration↗
PubMed1979

31P NMR studies on the interaction of deoxyuridylate with thymidylate synthase.

The 31P nuclear magnetic resonance signal of deoxyuridylate was studied in the presence and absence of thymidlate synthase. In the absence of enzyme the chemical shift of deoxyuridylate is pH dependent with a pKa of 6.25. In the presence of enzyme, a peak corresponding to the dianioinc form of deoxyuridylate is observed which is independent of pH between pH 5.7 and pH 7.4. The pKa of the phosphate in the deoxyuridylate-thymidylate synthase complex is therefore less than 5. The release of inorganic phosphate from deoxyuridylate catalyzed by contaminating phosphatase was also observed.

Deoxyuracil Nucleotides↗
PubMed1979

Investigation of the interactions of oxytocin with neurophysins at low pH using carbon-13 nuclear magnetic resonance and carbon-13-labeled hormones.

The specifically 13C-labeled (90% 13C-enriched) peptide hormone derivatives [1-hem[2-13C]cystine]oxytocin, [1-hemi[1-13C]cystine]oxytocin, and [2-[-2-13C]tyrosine[-oxytocin and the analogue [3-[2-13C]leucine]oxytocin were prepared by total synthesis and used to study the interactions of the neurohypophyseal hormones with the bovine neurophysins as a function of pH and temperature. Under all conditions, whether high or low pH, the chemical shifts of the labeled carbon atoms of the bound hormones are the same, but they are shifted significantly from their positions in the free hormone. These results indicate that interactions of the side chain and disulfide moieties of the hormone with the neurophysins do not change as a function of pH. At neutral pH and 20--35 degrees C, the labeled atoms of the hormone are in slow exchange (1--5 s-1) with the neurophysins for the above hormone derivatives, but at low pH they are in intermediate or fast exchange depending upon the pH and temperature. At low pH, the dissociation rate constant (koff) is about 100-fold greater than the value at neutral pH, and this increase appears to be due exclusively to the breaking of the salt bridge involving the N-terminal amino group of oxytocin and a side-chain carboxyl group of neurophysin. Since the dissociation constant (Kd) also increases by about 100-fold in going from neutral to low pH, the association rate constant is deduced to be the same at neutral and low pH. In contrast to the low pH results, an increase in pH (from 6.6 to 10.5) leads to a continual decrease in the binding constant but to no apparent change in the dissociation rate constant. The bound hormone is always in slow exchange at high pH, even when the binding constant has been reduced by 2 or 3 orders of magnitude. At high pH, the decrease in binding affinity is due solely to the deprotonation of the alpha-amino group of the free hormone. Thus, at high pH the apparent association rate constant decreases, while the dissociation rate constant remains unchanged.

Animals↗