Search PubMed⌕ Search

Biomedical subjects

R Wallin

Publications and source records attributed to R Wallin.

At least 91 records · Page 5Linked to original sources
PubMed1986

Effect of N-acetylcysteine on fibrin deposition in the rat lung due to intravascular coagulation.

Intravascular coagulation was induced in rats by i.p. injection of a fibrinolysis inhibitor, tranexamic acid (AMCA, 200 mg/kg B.W.), and i.v. injection of bovine thrombin (500 NIH units/kg B.W.) and the fibrin deposition in the lungs was assessed with 125I-labelled fibrinogen. Treatment with N-acetylcysteine (NAC) partly prevented the deposition of fibrin in the lungs, and the disappearance of fibrinogen from the blood, but did not seem to influence the elimination of fibrin in the lungs. The results indicate that NAC may counteract pulmonary damage in this experimental model, by inhibiting intravascular fibrin formation.

Acetylcysteine↗
PubMed1985

Fibrin(ogen)-derived peptide B beta 30-43 increases coronary blood flow in the anesthetized dog.

The hemodynamic effects of intracoronary administration of a fibrin (ogen)-derived peptide B beta 30-43 (Arg-Pro-Ala-Pro-Pro-Pro-Ile-Ser-Gly-Gly-Gly-Tyr-Arg-Ala) were evaluated in open-chest anesthetized dogs. Coronary blood flow (CBF) increased and coronary vascular resistance (CVR) decreased with intracoronary administration of peptide B beta 30-43. These changes were dependent on the amount of the peptide B beta 30-43 administered. There were no significant effects of peptide B beta 30-43 on aortic & left ventricular end-diastolic pressures. Plasma 6-keto-PGF1 alpha (stable hydrolysis product of PGI2) concentrations increased in coronary sinus blood samples in conjunction with increase in CBF. Intravenous administration of indomethacin (5 mg/kg) inhibited the release of PGI2 and almost completely abolished the effects of the fibrin(ogen)-derived peptide on CBF. This study suggests that this fibrin (ogen)-derived peptide has potent effects on the coronary vascular bed of the dog, and that these effects are in large part mediated through PGI2 release. These coronary hemodynamic effects of fibrin(ogen)-derived products may have important autoregulatory effects in atheromatous coronary circulation, wherein thrombi may form spontaneously.

Animals↗
PubMed1985

Peptide 6A, a fibrin(ogen) degradation product, increases coronary blood flow.

The coronary hemodynamic effects of intracoronary administration of a fibrin(ogen)-derived pentapeptide, Ala-Arg-Pro-Ala-Lys (peptide 6A), were evaluated in open-chest anesthetized dogs. With administration of peptide 6A (2.5-30 mumol), coronary blood flow increased and coronary vascular resistance decreased promptly in a dose-related manner. Increase in coronary blood flow was independent of any change in indexes of myocardial O2 demand, indicating the peptide 6A exerts direct effects on coronary arterial tone. Systemic arterial and left ventricular end-diastolic pressures remained unchanged with smaller doses but decreased when higher doses of peptide 6A (greater than or equal to 20 mumol) were administered. Plasma concentrations of 6-ketoprostaglandin F1 alpha, stable hydrolysis product of prostacyclin, increased in coronary sinus blood samples in conjunction with increase in coronary blood flow. Administration of indomethacin (5 mg/kg iv) inhibited peptide 6A-induced release of prostacyclin and significantly attenuated the effects of peptide 6A on coronary hemodynamics. Pretreatment of animals with H2-receptor blocker cimetidine (500 mg iv) or with H1-and H2-receptor blocker diphenhydramine (50 mg iv) had no significant effects on peptide 6A-induced increase in coronary blood flow. This study suggests that this fibrin(ogen)-derived peptide has potent vasodilator effects on the coronary vascular bed of the dog, and these effects are in part mediated by stimulation of prostacyclin release.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Vitamin K-dependent carboxylation and vitamin K metabolism in liver. Effects of warfarin.

The systems involved in vitamin K-dependent carboxylation and vitamin K metabolism have been extensively studied in rat liver. To determine how clinically applicable this information is, similar in vitro studies were completed using human liver. One major difference exists in the pathways that provide reduced vitamin K1 cofactor for the carboxylation reaction. The coumarin-sensitive DT-diaphorase (EC.1.6.99.2) in human liver appears to play a relatively minor role in the dehydrogenase pathway. However, similar to rat liver, the human liver contains a warfarin-insensitive enzyme in this dehydrogenase pathway. The data suggest that this enzyme is responsible for the antidotic effect of vitamin K1 in cases of coumarin intoxication. Human vitamin K epoxide reductase, which constitutes the other pathway for vitamin K1 reduction, has kinetic and enzymological characteristics that are very similar to the rat enzyme. This enzyme exhibited similar activity in rat and human microsomes. Initial velocities for vitamin K1 epoxide reduction in rat and human microsomes were 20 and 32 pmol/mg X min, respectively. The human enzyme is highly sensitive to warfarin inhibition. The mechanism for this inhibition appears to be similar to what has been proposed for the rat enzyme. Also, a vitamin K-dependent carboxylation system is described that allows both pathways to support the carboxylation reaction with reduced vitamin K1 cofactor. The effect of warfarin on this in vitro system is consistent with the current model for the mechanism of action of coumarin anticoagulant drugs in the rat.

Animals↗
PubMed1984

Two forms of alpha 2-antiplasmin: differences in KAV and isoelectric point.

The plasminogen-binding (PB-AP) and the non-plasminogen-binding (NPB-AP) forms of alpha 2-antiplasmin were assayed by a modified rocket electroimmunoassay technique using an intermediary gel containing kringles 1-3 from plasminogen. Gel chromatography of normal human plasma (HNP) showed differences in KAV between PB-AP and NPB-AP. PB-AP had a KAV of 0.33 and NPB-AP a KAV of 0.39. Isoelectric focusing of HNP showed pI differences between PB-AP and NPB-AP. PB-AP was heterogeneous, with a main peak at pI = 4.69 and a minor peak at pI = 4.92, while NPB-AP had only one peak, at pI = 4.59.

Chromatography, Gel↗
PubMed1984

NAD(P)H dehydrogenase from rabbit and rat liver: purification and some properties.

NAD(P)H dehydrogenase from rabbit liver was purified to electrophoretic homogeneity using a procedure also found applicable for the rat liver enzyme. Rabbit and rat liver enzymes showed different behaviour in isoelectric focusing and different Km values and turnover numbers. Both enzymes were inhibited to similar extents by warfarin. The rabbit enzyme is composed of two subunits of mol. wt 27,000 and contained 1 FAD group per subunit. Some absorption and circular dichroism properties of the rat enzyme are shown.

Animals↗
PubMed1984

A structural model of human erythrocyte band 2.1: alignment of chemical and functional domains.

Protein 2.1 is a 210-kilodalton protein that connects erythrocyte spectrin to the NH2-terminal cytoplasmic domain of band 3 and thereby functions as the essential linkage between the membrane skeleton and the bilayer. We cleaved this protein into specific chemical domains by limited digestion with trypsin and alpha-chymotrypsin at 0 degrees C. Intermediate-sized peptides were separated by two-dimensional isoelectric focusing/NaDodSO4/polyacrylamide gel electrophoresis and characterized by high resolution peptide mapping. We have established a provisional structural model of protein 2.1 by comparing the peptide maps of these chemical domains to maps obtained from larger overlapping chymotryptic fragments as well as fragments obtained from 2-nitro-5-thiocyanobenzoic acid cleavage. In addition to providing a provisional structural map of protein 2.1, we have identified two functional domains of protein 2.1, an 83-kilodalton tryptic peptide (T-83) which binds band 3 and a 65-kilodalton tryptic peptide (T-65) which binds spectrin. We have therefore localized the functional domains along our linear map of protein 2.1.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1983

Structural requirements for microvascular permeability-increasing ability of peptides. Studies on analogues of a fibrinogen pentapeptide fragment.

A pentapeptide, Ala-Arg-Pro-Ala-Lys, liberated from fibrinogen during plasmin-mediated fibrinolysis, was shown earlier to increase microvascular permeability in rat and human skin. Eighteen new analogues have now been synthesized in addition to the 15 previously prepared and examined for their effect on permeability. The old concept that a tetrapeptide with basic amino acids at both ends and a proline residue adjacent to the N-terminal amino acid is essential for high activity on permeability, has now been challenged. The results obtained with several of the new analogues strengthen this concept. More interestingly, however, the third amino acid, which was found in earlier studies to be less sensitive to exchange, has now been deleted as well as duplicated with only a modest loss of activity of the peptide. The chirality of the C-terminal amino acid, most surprisingly, does not seem to be crucial for peptide activity. Slightly superpotent analogues were obtained on amidation of the C-terminus. In addition, a few naturally occurring peptides, namely tuftsin, substance P, neurotensin and bradykinin, the amino acid sequences of which all exhibit characteristic features of some of our active peptide analogues were investigated in the same test system. Tuftsin displayed a potency equal to that of the pentapeptide. The other three peptides were all highly superpotent in this assay system.

Animals↗
PubMed1983

Fibrin-derived vasoactive peptides release histamine.

Two fibrin-derived peptides. Ala-Arg-Pro-Ala-Lys and Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys, increase microvascular permeability in rat skin. In the present investigation it is shown that they release histamine from rat mast cells and that their effect on microvascular permeability can be inhibited by previous histamine depletion of the skin or treatment with an antihistamine, the H1-blocker mepyramine maleate. It is concluded that histamine release contributes to the permeability-increasing effect of these peptides as well as of the structurally similar peptides bradykinin, substance P and neurotensin.

Animals↗
PubMed1982

Vitamin K-dependent carboxylation. Evidence that at least two microsomal dehydrogenases reduce vitamin K1 to support carboxylation.

It has been shown that NAD(P)H dehydrogenase (EC 1.6.99.2) reduces vitamin K1 and can support the [vitamin K1 + NADH]-dependent carboxylation reaction in rat liver microsomes (Wallin, R., Gebhardt, O., and Prydz, H. (1978) Biochem. J. 169, 95-101). Antibodies were raised in rabbits against the purified enzyme from liver cytosol and used to study the importance of NAD(P)H dehydrogenase in the vitamin K-dependent carboxylation reaction. The antibodies neutralized the warfarin-sensitive NAD(P)H dehydrogenase activity in Triton X-100-solubilized microsomes; however, they neutralized only 45% of the total [vitamin K1 + NADH]-dependent carboxylation activity. Chromatography on protein A-sepharose showed that the remaining carboxylase activity was not the result of soluble antigen-antibody complexes. The data presented support the conclusion that the microsomal preparation also contains a non-warfarin-sensitive dehydrogenase(s) that, in addition to NAD(P)H dehydrogenase, can reduce vitamin K1 to support the carboxylation reaction.

Animals↗
PubMed1980

Structure-activity studies on synthetic analogs to vasoactive peptides derived from human fibrinogen.

Counterparts to two vasoactive peptides previously isolated from fibrin(ogen) degraded by plasmin (EC 3.4.21.7) were synthesized by the solid phase procedure. The synthetic undecapeptide (Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys) was isolated in a homogeneous state by chromatography on Sephadex G-25 and DEAE-Sepharose CL-6B and the pentapeptide (Ala-Arg-Pro-Ala-Lys) by chromatography on BioGel P-6 and column zone electrophoresis. The effect of these two peptides and of fifteen analogs to the pentapeptide on microvascular permeability in rat skin was investigated. The two synthetic counterparts were as potent as the natural peptides. With respect to the analogs, the influence of different functional groups was first studied. This was followed by attempts to minimize the active structure, induce or relieve rigidity of the peptide back-bone or otherwise accomplish modifications by a change in chirality at critical positions. Our results show that the tetrapeptide Arg-Pro-Ala-Lys has the same effect on microvascular permeability as the pentapeptide in the assay system used. Basic amino acids at both ends, as well as a proline residue adjacent to the N-terminal amino acid appear important for full or essentially full activity. On the other hand, substitution of the Ala at position 4 with several other amino acids did not result in a significant loss in biological potency.

Capillary Permeability↗
PubMed1979

Some molecular properties of NAD(P)H dehydrogenase from rat liver.

NAD(P)H dehydrogenase (EC 1.6.99.2) purified from rat liver cytosol revealed three discrete bands, of mol.wts. about 27000, 18000 and 9000, when subjected to polyacrylamidegel electrophoresis in the presence of sodium dodecyl sulphate. Elution of the bands from the gel and individual re-electrophoresis on separate gels showed that the 27000-mol.wt. band yielded three bands similar to those obtained with the intact enzyme, whereas the 18000-mol.wt. band retained its characteristic mobility. Amino acid analysis of native enzyme and protein extracted from each of the three bands from sodium dodecyl sulphate/polyacrylamide gels suggests that the native enzyme is composed of two subunits and that each subunit consists of two dissimilar non-covalently bound polypeptides, so that altogether the enzyme is composed of four polypeptides, two of mol.wt. 18000 and two of mol.wt. 9000. NAD(P)H dehydrogenase was active over a wide pH range with no sharp optimum. The same K(m) value for NADH but different values for V(max.) were obtained for the enzyme purified from Sprague-Dawley and Wistar rats. In immunodiffusion, however, the enzymes from the two rat strains showed a reaction of complete identity. NAD(P)H dehydrogenase was effectively inhibited by thiol-blocking reagents, indicating that the activity is dependent on free thiol group(s). By amino acid analysis six cysteine residues were found per mol of enzyme. Guanidino-group- and amino-group-selective reagents had only moderate inactivating effects on the enzyme activity.

Amino Acids↗