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Biomedical subjects

D A Lane

Publications and source records attributed to D A Lane.

At least 127 records · Page 7Linked to original sources
PubMed1990

The elderly on dialysis: some considerations in compliance.

Compliance with scheduled treatments, dietary and fluid restrictions, and multiple medications is an important component in the care and well-being of end-stage renal disease (ESRD) patients. Given the rigorus and complex demands of dialysis, it is important to examine the issue of compliance, focusing on a large and ever-increasing segment of our patient population, the elderly. The ESRD literature reflects efforts to define and measure levels of compliance, identify factors that influence and predict compliance, and develop intervention strategies to improve adherence to treatment regimens. While limited attention has been focused specifically on the elderly, there are studies suggesting that age may be a factor associated with improved adherence and that social support may be a significant contributor to compliance in this patient group. In an effort to examine the current status and needs of the dialysis elderly, research is in progress at Chromalloy American Kidney Center, Washington University, which replicates a study of 5 years ago. Eighty-four patients age 60 and over, on dialysis for a minimum of 6 months, were identified. Sociodemographic, treatment, compliance, and functional capacity data were collected; additional mental and psychological testing was completed on patients willing and able to participate. Preliminary data suggest the current elderly population is larger and significantly older than that of 5 years ago. Other sociodemographic data indicate the population is increasingly female, black, and more socioeconomically disadvantaged. In regard to compliance, the vast majority of elderly demonstrate good compliance as measured by serum potassium, fair to good compliance with phosphorus, and fair to poor compliance with fluid restrictions.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1990

A low-molecular-weight heparin (Kabi 2165, 'Fragmin') in repeated use for haemodialysis: prevention of clotting and prolongation of the venous compression time in comparison with commercial unfractionated heparin.

We have compared a low-molecular-weight heparin (LMWH), Kabi 2165, with commercial unfractionated heparin (UFH) in 21 patients undergoing haemodialysis (1 month with each heparin). The UFH dose regimen comprised a UFH-saline prime of the extracorporeal circuit, an initial bolus of 5000 international units (IU) and an infusion of 1500 IU/h. The LMWH dose regimen comprised a LMWH-saline prime, a bolus of 3000-4000 anti-factor Xa units (aXa U) and an infusion of 750 aXa U/h. Plasma concentrations of the LMWH were slightly less than those of UFH for the first hour of dialysis (0.87 aXa U/ml vs 0.99 IU/ml) but were very similar by the end of the infusion (0.96 vs 1.00) and slightly greater at the end of dialysis, an hour later (0.85 vs 0.69). All haemodialysis sessions were completed uneventfully, with infrequent wispy clot deposits in the drip chamber. The mean frequency of clot deposition was slightly higher with the LMWH (0.20 vs 0.15). Fibrin generation was almost fully suppressed: plasma concentrations of fibrinopeptide A were slightly greater during dialysis with the LMWH (3.31-3.98 vs 2.29-2.75 pmol/ml) but were almost identical by the end of dialysis (5.62 vs 5.49 pmol/ml). The mean 'venous' compression time at the end of dialysis was significantly shorter with the LMWH than with UFH (8.45 min vs 11.12 min). We conclude that the LMWH is effective and safe in repeated use for haemodialysis. It prevents fibrin generation and clot formation to a similar degree as UFH. The shorter venous compression time of the LMWH may reflect a reduced haemorrhagic risk.

Bleeding Time↗
PubMed1990

A comparative evaluation of assays for markers of activated coagulation and/or fibrinolysis: thrombin-antithrombin complex, D-dimer and fibrinogen/fibrin fragment E antigen.

Measurements were made of levels of D-dimer in plasma and serum, thrombin-antithrombin complex (TAT) in plasma and fibrinogen/fibrin fragment E antigen (FgE) in serum in a normal healthy control group and in patients with a range of disorders associated with hypercoagulability. Levels were determined in 31 normal healthy controls, 30 patients with disseminated intravascular coagulation (DIC), 21 patients with deep venous thrombosis (DVT), 27 patients with myocardial infarction (MI), 26 patients with acute leukaemia and 56 patients with liver disease. Considering all subjects, significant correlations were established between the results of all assays. Notably high correlations (r greater than 0.9) were established between plasma and serum levels of D-dimer, between plasma levels of D-dimer and serum levels of FgE, and between serum levels of D-dimer and FgE. All assays showed very high discrimination (sensitivity) between the normal control group and patients with DIC (97-100%), but there were marked differences between the assays in sensitivity for DVT and MI. In general, the FgE assay was more sensitive than the D-dimer assay, whilst both the FgE and D-dimer assays were more sensitive than the TAT assay. The same trends were apparent in the capability of the assays to discriminate between the normal control group and patients with acute leukaemia and liver disease: disorders with an unknown prevalence of activation of coagulation/fibrinolysis. Our results indicated that measurements of fibrinogen/fibrin degradation products (FDPs) in serum were almost unaffected by artefacts. The data further suggested that the broad-spectrum FgE assay was better than the more specific D-dimer assay in detecting clinical hypercoagulability. Our study showed that, in the clinical conditions examined, FDPs were more effective markers of hypercoagulability than TAT.

Acute Disease↗
PubMed1989

Anti-thrombin activities of heparin. Effect of saccharide chain length on thrombin inhibition by heparin cofactor II and by antithrombin.

The interactions of two proteinase inhibitors, heparin cofactor II and antithrombin, with thrombin are potentiated by heparin. Using two methods, we have studied the potentiating effects of a series of heparin (poly)saccharides with high affinity for antithrombin and mean Mr ranging from approx. 1700 to 18,800. First, catalytic amounts of heparin (poly)saccharide were added to purified systems containing thrombin and either heparin cofactor II or antithrombin. Residual thrombin activity was determined with a chromogenic substrate. It was found that only the higher-Mr polysaccharides (Mr greater than 8000) efficiently catalysed thrombin inhibition by heparin cofactor II, there being a progressive catalytic effect with increasing Mr of the polysaccharide. Weak accelerating effects were noted with low-Mr saccharides (Mr less than 8000). This contrasted with the well-characterized interaction of heparin with antithrombin and thrombin, where heparin oligosaccharides of Mr less than 5400 had absolutely no ability to accelerate the reaction, while (poly)saccharides of Mr exceeding 5400 showed rapidly increasing catalytic activity with increasing Mr. Secondly, these and other heparin preparations were added in a wide concentration range to plasma with which 125I-labelled thrombin was then incubated for 30 s. Inhibited thrombin was determined from the distribution of labelled thrombin amongst inhibitor-thrombin complexes, predominantly antithrombin-thrombin and heparin cofactor II-thrombin complexes. In this situation, where the inhibitors competed for thrombin and for the (poly)saccharides, it was found that, provided the latter were of high affinity for antithrombin and exceeded a Mr of 5400, thrombin inhibition in plasma was mediated largely through antithrombin. Polysaccharides of Mr exceeding 8000 that were of low affinity for antithrombin accelerated thrombin inhibition in plasma through their interaction with heparin cofactor II. High concentrations of saccharides of Mr 1700-5400 exhibited a size-dependent acceleration of thrombin inhibition, not through their interaction with antithrombin, but through their interaction with heparin cofactor II.

Antithrombins↗
PubMed1989

The effect of heparin on the inositol 1,4,5-trisphosphate receptor in rat liver microsomes. Dependence on sulphate content and chain length.

Heparin is known to inhibit the binding of inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) to high-affinity binding sites and to inhibit Ins 1,4,5-P3-induced Ca2+ release from intracellular membrane-bound stores [(1987) J. Biol. Chem. 262, 12132-12136; (1987) FEBS Lett. 228, 57-59]. We have performed studies to clarify the structural requirements for this action of heparin in rat liver microsomes. Both N- and O-linked sulphate groups contribute to binding activity, since de-N-sulphated heparin was without effect on the Ins 1,4,5-P3 receptor whereas a polyxylan bearing only O-linked sulphates (pentosan polysulphate) was as active as heparin. Therefore, the density of negative charge contributed by sulphate groups is important for the binding of heparin. Heparins with high and low affinity for antithrombin III both inhibited Ins 1,4,5-P3 binding. There was a strong dependence on chain length, since binding activity decreased dramatically as the size of the heparin chain was reduced below that of 18-24 monosaccharide units.

Animals↗
PubMed1989

Plasma D dimer: a useful marker of fibrin breakdown in renal failure.

D dimer and other large fragments produced during the breakdown of crosslinked fibrin may be measured by enzyme immunoassay using monoclonal antibodies. In 91 patients with renal disease and varying degrees of renal dysfunction, plasma D dimer showed no correlation with renal function, whereas FgE antigen, a fibrinogen derivative which is known to be cleared in part by the kidney, showed a significant negative correlation with creatinine clearance. Plasma concentrations of D dimer were, however, increased in patients with chronic renal failure (244 +/- 31 ng/ml) (mean +/- SEM) and diabetic nephropathy (308 +/- 74 ng/ml), when compared with healthy controls (96 +/- 13 ng/ml), and grossly elevated in patients with acute renal failure (2,451 +/- 1,007 ng/ml). The results indicate an increase in fibrin formation and lysis, and not simply reduced elimination of D dimer by the kidneys, and are further evidence of activated coagulation in renal disease. D dimer appears to be a useful marker of fibrin breakdown in renal failure.

Biomarkers↗
PubMed1989

Antithrombin Chicago, amino acid substitution of arginine 393 to histidine.

Antithrombin Chicago is a functionally inactive antithrombin variant whose inheritance is associated with thrombotic disease. The variant antithrombin was isolated from plasma of the propositus by chromatography on heparin-Sepharose, followed by passage through thrombin-Sepharose to remove the normal antithrombin component that is present. A pool of fragments ("CNBr pool 4") containing the reactive site region was prepared from the reduced and S-carboxymethylated variant by cleavage with cyanogen bromide followed by reverse-phase HPLC. Sequential treatment of CNBr pool 4 with trypsin and V8 protease produced peptides whose molecular masses were then determined by fast atom bombardment mass spectrometry. The variant protein digests were characterised by a reduction of a peptide of mass 1086, corresponding to the normal antithrombin sequence Ala382-Arg393. However, they contained a peptide of mass 1748, which arises when Arg393 is replaced by His in the sequence Ala382-Arg399. It is concluded that the functional and clinical abnormalities of antithrombin Chicago are all probably caused by a single amino acid substitution, Arg393 to His.

Amino Acid Sequence↗
PubMed1989

A novel amino acid substitution in the reactive site of a congenital variant antithrombin. Antithrombin pescara, ARG393 to pro, caused by a CGT to CCT mutation.

Antithrombin is a plasma protein inhibitor that can be grouped within a serine proteinase inhibitor superfamily. Antithrombin Pescara is a functional variant of antithrombin found in a family with a high incidence of thrombosis. Preliminary functional analysis has suggested that the abnormality resides in the reactive site rather than in the heparin binding domain of the molecule. Accordingly, we have isolated the variant from plasma using heparin-Sepharose chromatography, followed by chromatography upon thrombin-Sepharose to remove the normal antithrombin that is present (the propositus is heterozygous for the variant). The variant protein was reduced, S-carboxy-methylated, and fragmented with CNBr. A pool ("CNBr pool 4") containing the reactive site region was isolated by reverse-phase high performance liquid chromatography and sequentially treated with trypsin and V8 protease. Fast atom bombardment-mass spectrometric analysis of this subdigest identified a novel peptide of mass 1708. Four steps of Edman degradation together with further analysis by fast atom bombardment-mass spectroscopy identified the NH2-terminal sequence of this peptide as Ala-Ala-Ala-Ser. The mass of the novel peptide and its changing mass in response to Edman degradation are only compatible with its identity as Ala382-Arg399, with the reactive site Arg393 replaced by Pro. Using specific oligonucleotide hybridization, we demonstrated that the molecular defect of antithrombin Pescara is caused by a CGT to CCT mutation in codon 393. These findings may be of broad interest, as other members of the serine protease inhibitor superfamily contain arginine at their reactive sites and may be expected to undergo a similar mutation.

Amino Acid Sequence↗
PubMed1989

On the cytotoxicity of chrysotile asbestos fibers toward pulmonary alveolar macrophages. II. Effects of nicotinamide on the cell metabolism.

Since it was recently shown that the addition of nicotinamide (NAM) to pulmonary alveolar macrophages (PAM) cell monolayers significantly altered their ATP pools (Nadeau and Lane, 1988), the effects of the vitamin on the metabolism of the cells, exposed or not to very short chrysotile asbestos fibers (VSF), were evaluated. First, it was found that the addition of NAM to the culture medium caused a dose-dependent (5-30 mM) decrease in the extracellular liberation of lactate and pyruvate by PAM. This is suggestive of a direct effect of NAM on the metabolism of glucose. A decrease in extracellular lactate was also observed when control PAM were exposed to 50 micrograms of VSF asbestos. This latter effect was however progressively abolished when the NAM was added to the asbestos-exposed cell monolayers. Second, contrary to the lactic acid production, the exposure to chrysotile caused an increase in the extracellular liberation of pyruvate by PAM. This cell response to the asbestos fibers could represent an antioxidative defense mechanism. Yet, interestingly enough, this effect of the VSF on PAM was not suppressed by the presence of the vitamin. The NAM also induced a dose-dependent decrease in the total lactate dehydrogenase content of PAM monolayers. By comparison, 3-aminobenzamide (up to 5 mM) did not appreciably modify these parameters. After an 18-hr incubation period with 20 mM NAM, the NAD+ pools of control PAM increased by approximately 300% comparatively to a approximately 40% increase for the NADP+ content. The exposure to the VSF asbestos caused a dose-dependent depletion of the cellular NAD+ and NADH pools. However, for the latter, the vitamin prevented the depletion effect of the asbestos fibers. Comparatively, the NADP(H) pools increased. This shift toward the phosphorylated pyridine nucleotide forms could also represent a defense of the cell against the oxygen radicals produced during the ingestion of the fibers. Overall, it is shown that changes in the energy metabolism could be implicated in the toxicity of chrysotile asbestos fibers toward PAM, and that the cells seem to be able to respond to an oxidant stress. Although not fully elucidated at the present time, these data tend nonetheless to point out that the protective effect of NAM could involve some modifications of the host defenses against prooxidants.

Animals↗
PubMed1989

Assessing methods for causality assessment of suspected adverse drug reactions.

Reproducibility and validity as currently defined are inappropriate criteria for the evaluation of methods for causality assessment. Reproducibility leads to suppression rather than resolution of real disagreements and the method used to establish validity relies on the tarnished gold standard of expert opinion. We describe six alternative criteria that attempt to address a potential user's main concerns--the need to know whether to believe the results in general and in a particular case. These criteria focus on the internal structure of a method rather than its output. When we assessed the published methods by these criteria most of the methods failed most of the criteria. We believe that the problem and its solution lie at a fundamental level--real understanding of the true nature of causality assessment, which we suggest is an inherently subjective evaluation based on the multiple uncertainties that an assessor has about a case and not an objective attribute of the drug-event connection that can be determined from unambiguous evidence elicited in response to "operational questions".

Drug-Related Side Effects and Adverse Reactions↗
PubMed1989

Antithrombin: structure, genomic organization, function and inherited deficiency.

Antithrombin is a major plasma protein inhibitor of proteinases generated during blood coagulation; it plays an important role in the regulation of thrombin in blood. The anticoagulant heparin greatly accelerates the rate of inactivation of proteinases by antithrombin, predominantly through its well defined, highly specific binding reaction with the inhibitor, but also through a less strictly defined interaction with some of the proteinases (such as thrombin). There is evidence for an analogous acceleratory mechanism in vivo, that functions by the binding of antithrombin to a subpopulation of heparan sulphate proteoglycans intercalated in the surface of endothelial cells. The location and structure of the gene for antithrombin are known. Both its overall organization and the structure of the subdomains of the expressed protein can be considered in terms of their relationships to a serine proteinase inhibitor superfamily, which is believed to have evolved from a common ancestor. The region of the antithrombin gene 5' to the coding region has been characterized. Unlike other members of the serpin family, there is no TATA-like promoter sequence. Two enhancer sequences have been identified that are homologous to enhancer regions of other genes. There are two polymorphisms: an intragenic polymorphism arising from a translationally silent A to G transition in codon 305, and a length polymorphism arising from the presence of 32 bp or 108 bp non-homologous sequences 345 bp upstream from the translation initiation codon. Inherited deficiency of antithrombin is associated with familial thromboembolism. The molecular genetic basis of some subtypes of deficiency is increasingly yielding to investigation. It is interesting to note that a number of mutations have been identified in CpG dinucleotides, supporting the suggestion that this dinucleotide sequence may represent a mutation hotspot in the human genome.

Amino Acid Sequence↗
PubMed1989

Antithrombin Sheffield: amino acid substitution at the reactive site (Arg393 to His) causing thrombosis.

A Sheffield family with a predisposition towards thrombosis has been shown to have a functional abnormality of antithrombin. The abnormality was detected as reduced heparin cofactor activity, with normal antigenic levels of antithrombin. Crossed immunoelectrophoresis performed in the absence and presence of heparin was normal. The antithrombin was isolated by heparin Sepharose affinity chromatography. It had normal mobility on SDS polyacrylamide gel electrophoresis. However, the second order rate constant of inhibition of thrombin was about half that of normal, and this was compatible with a heterozygous abnormality involving the reactive site. The antithrombin was further purified by chromatography on thrombin-Sepharose (to remove the normal component), reduced, S-carboxymethylated and fragmented with cyanogen bromide. A pool containing the reactive site region was digested with trypsin and the molecular size of peptides generated determined by fast atom bombardment mass spectrometry. The two peptides adjacent to the Arg393-Ser394 bond of mass 2290 and 700 were almost absent from the mass spectrum, but an additional peptide of mass 2952 was present. Subdigestion with V8 protease reduced the mass of this peptide to 1748. These peptides generated by trypsin and V8 protease were almost identical to those obtained when another variant, antithrombin Glasgow, was treated in the same way (Erdjument et al, 1988). It is concluded that the molecular abnormality of antithrombin Sheffield is identical to that of antithrombin Glasgow, Arg393 to His.

Adult↗
PubMed1989

A low molecular weight heparin ("fragmin") for routine hemodialysis: a crossover trial comparing three dose regimens with a standard regimen of commercial unfractionated heparin.

In 20 hemodialysis patients using mainly flat plate dialyzers, we have conducted a controlled randomized crossover trial of three dose regimens of a low molecular weight heparin (LMWH), "Fragmin" (Kabi 2165), in comparison with a standard dose regimen of commercial unfractionated heparin (UFH) that had previously been shown to provide effective anticoagulation. The aim of the present study was to find the lowest dosage regimen of the LMWH which would be as effective as the standard UFH regimen. The UFH regimen comprised a prime with heparinized saline, an initial intravenous bolus of 5,000 international units (IU) and an infusion of 1,500 IU/h. The three LMWH regimens comprised a LMWH-saline prime, an infusion of 750 anti-factor Xa (aXa) U/h and three different bolus doses: 1) LMWH-low: 3,000 aXa U. 2) LMWH-medium: 4,000 aXa U. 3) LMWH-high: 5,000 aXa U. With the UFH regimen, plasma heparin levels of around 1.0 IU/ml were maintained during the heparin infusion, declining to 0.71 IU/ml an hour after the infusion was terminated. The LMWH-medium regimen produced very similar plasma aXa levels. The LMWH-high regimen also produced similar plasma aXa levels: therefore, it had no advantage over the LMWH-medium regimen. The LMWH-low regimen produced significantly lower levels than the other regimens during the heparin infusion (0.81-0.85 aXa U/ml, p less than 0.025). Dialysis proceeded uneventfully at all times and plasma levels of fibrinopeptide A (FPA) were suppressed well with all 4 regimens (2.77-5.74 pmol/ml) but tended to rise after the infusion was switched off (5.52-8.45 pmol/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Protocols↗
PubMed1989

Should blood cultures be obtained in the evaluation of young febrile children without evident focus of bacterial infection? A decision analysis of diagnostic management strategies.

The technique of decision analysis was used to compare the benefits (prevention of major infectious sequelae of bacteremia) and risks (unnecessary hospitalization and intravenous antibiotic treatment of children whose bacteremia would have resolved spontaneously, discomfort of venipuncture) of alternative diagnostic management strategies in the evaluation of children 3 to 24 months of age with fever (rectal temperature greater than or equal to 39 degrees C) of acute (less than or equal to 4 days) onset and without evident focus of bacterial infection. The diagnostic strategies compared at the initial visit were blood culture in all, blood culture in none, and selective blood culture (restricted to children judged to be at high risk). Probability estimates were based on published epidemiologic studies and case series, and utilities were elicited from mothers of 3- to 24-month-old children and from pediatricians. Based on initial probabilities and utilities, the "no blood culture" strategy had the highest expected utility, followed closely by the "selective blood culture" strategy, with the "blood culture all" strategy a distant third. Sensitivity analyses based on increased risk of major infectious sequelae or of bacteremia had no effect on the ranking of the three initial management options. Eliminating the "disutility" of venipuncture or augmenting the disutility of major infectious sequelae also failed to alter the ranking. Even when an extreme relative disutility for major sequelae was assumed, the "blood culture all" strategy was not favored. Thus, the risk of unnecessary hospitalization and intravenous antibiotic treatment of the relatively large number of children whose bacteremia spontaneously resolves appears to outweigh the benefit of preventing serious infectious sequelae in the few children in whom positive blood culture results permit timely intervention. The explicitness and coherence of the decision analysis approach should help in developing a rational diagnostic approach to the young febrile child.

Blood↗
PubMed1988

Antithrombin Milano, single amino acid substitution at the reactive site, Arg393 to Cys.

Antithrombin Milano is an unusual antithrombin variant, exhibiting an abnormal, fast moving component on crossed immunoelectrophoresis (in the absence of heparin). Antithrombin isolated from the propositus could be resolved into two peaks on anion-exchange chromatography; antithrombin Milano peak 1 of Mr approximately 60,000 which could inhibit thrombin, and antithrombin Milano peak 2 of Mr approximately 120,000 which was inactive. The latter component also reacted with antisera to both antithrombin and albumin on immunoblotting. Under reducing conditions, the approximately 120,000 Mr component migrated on SDS-PAGE as two distinct bands with Mr approximately 60,000, one of which reacted with antiserum to antithrombin and the other (of slower mobility) of which reacted with antiserum to albumin only. These and other results established the approximately 120,000 Mr component to be an inactive, disulphide-linked variant antithrombin and albumin complex. The variant antithrombin was isolated, following reduction and S-carboxymethylation, by reverse-phase HPLC and then it was fragmented with CNBr. A major CNBr pool containing the sequence Gly339-Met423 was treated with trypsin, followed by V8 protease. The resulting peptides were analysed by fast atom bombardment mass spectrometry (Fab-MS) mapping. A peptide of molecular mass 1086, corresponding to the normal sequence Ala382-Arg393, was almost absent from the mass spectrum, but an additional peptide of mass number 1772 was present. These results are almost identical to those found in another variant antithrombin, Northwick Park (Erdjument et al., J Biol Chem, 262: 13381, 1987; Erdjument et al., J. Biol Chem, 263: 5589-5593, 1988), indicating the same single amino acid substitution of Arg393 to Cys.

Amino Acid Sequence↗
PubMed1988

Relationship between anticoagulant activities and polyanionic properties of rabbit thrombomodulin.

Rabbit thrombomodulin displays three distinct blood anticoagulant activities: it promotes the activation of protein C by thrombin (protein C activation cofactor activity); it promotes the inactivation of thrombin by thrombin (direct anticoagulant activity). The effects on these activities of mouse anti-thrombomodulin monoclonal antibodies and of the heparin-neutralizing proteins, platelet factor 4, histidine-rich glycoprotein, and S-protein, were investigated. One of the antibodies, which did not influence the functional properties of thrombomodulin, was used as an immunoaffinity ligand for purification of the protein. Two other antibodies, which were found to abrogate the protein C activation cofactor activity of the purified thrombomodulin, also abolished the antithrombin-dependent and the direct anticoagulant activities. The heparin-neutralizing proteins all inhibited the two latter activities, albeit to a varying extent, but did not appreciably affect the activation of protein C. These results are interpreted in relation to our previous finding that rabbit thrombomodulin contains an acidic domain, tentatively identified as a sulfated glycosaminoglycan (Bourin, M.-C., Boffa, M.-C., Björk, I., and Lindahl, U. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 5924-5928). It is proposed that the acidic domain interacts with thrombin at the protein C activation site and that this interaction is a prerequisite to the expression of direct as well as antithrombin-dependent anticoagulant activity. The interaction is not essential to, but compatible with, the activation of protein C. Experiments involving treatment of thrombomodulin with various glycanases or with nitrous acid, followed by measurement of anticoagulant activities, indicated that the acidic domain is constituted by a sulfated galactosaminoglycan and not by a heparin-related polysaccharide as previously suggested.

Animals↗