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K M Jurd

Publications and source records attributed to K M Jurd.

13 recordsLinked to original sources
PubMed1999

Markers of endothelial cell activation and injury in childhood haemolytic uraemic syndrome.

Diarrhoea-associated haemolytic uraemic syndrome (D+ HUS) is usually caused by verotoxin-producing Escherichia coli. Histology shows endothelial swelling with localised thrombus. Activation of coagulation and fibrinolysis also occurs. These facts, combined with the knowledge that recovery usually follows within weeks, led us to hypothesise that verotoxin causes localised endothelial cell activation but not injury. Markers of endothelial cell activation and injury were measured serially in 30 children with acute D+ HUS, healthy children, and children receiving chronic dialysis. Interpretation of markers was complicated by the renal dysfunction characteristic of D+ HUS. Nevertheless there was no evidence for endothelial cell injury, as soluble tissue factor levels were not increased and soluble thrombomodulin levels were lower than dialysed controls (P<0.001). In the acute phase, soluble vascular cell adhesion molecule levels were raised above normal (P<0.001), but were lower than dialysed controls (P<0.001), and soluble E-selectin levels were not significantly increased compared with normal controls (P=0.2). Hence, there was no evidence for endothelial cell damage or endothelial cell activation by the time children reached hospital; but this study did not exclude the possibility that endothelial cell activation occurred prior to hospital admission.

Adolescent↗
PubMed1997

Activation of coagulation and fibrinolysis in childhood diarrhoea-associated haemolytic uraemic syndrome.

Diarrhoea-associated haemolytic uraemic syndrome (D+ HUS) is usually caused by verotoxin producing Eschericia coli. We hypothesized that verotoxin binding to glomerular endothelial cells causes localised endothelial cell activation and thus activation of coagulation and reduction of fibrinolytic potential. We also proposed that treatment with fresh frozen plasma or dialysis would not affect these changes. Markers of activation of coagulation and fibrinolysis were measured in 30 children with acute D+ HUS serially, in healthy children and in children on dialysis. In acute D+ HUS, levels of thrombin-antithrombin III complex and prothrombin fragment 1+2 were significantly increased (p <0.001). The source of thrombin generation was unclear. Factor XIIa levels were increased in patients and controls with renal failure. Factor VIIa levels were not significantly raised in children with acute D+ HUS. D-dimers were increased, but fibrinolytic potential as measured by fibrin plate was reduced. Levels of plasminogen activator inhibitor antigen and activity and tissue plasminogen activator antigen were increased. Neither peritoneal dialysis nor administration of blood products, the most common treatments, altered parameters of coagulation or fibrinolysis.

Antithrombin III↗
PubMed1996

Activation of human prothrombin by porcine aortic endothelial cells--a potential barrier to pig to human xenotransplantation.

A potential solution to the shortage of human organs for transplantation lies in the use of animal organs with the pig as the most likely donor. Perfusion of porcine organs with human blood, however, results in hyperacute rejection (xenograft reaction) which occurs within minutes to hours and is characterised by intravascular thrombosis. The pathogenesis of this xenograft reaction is attributed to xenoreactive natural antibodies (XNA) binding to epitopes on porcine endothelium activating complement with subsequent haemostatic activation. We have investigated whether there is direct activation of human coagulation by porcine endothelium in the absence of XNA and complement. Previous experiments demonstrated possible pathological activation of the common pathway, thus human prothrombin and factor X were added separately to porcine endothelium and monitored for activation. Human prothrombin was activated by porcine but not human endothelium. There was no activation of factor X. Hirudin inhibited prothrombin activation suggesting that a conformational change may occur in prothrombin on binding to porcine endothelium, such that its catalytic centre is exposed with subsequent autocatalytic cleavages. If this in vitro observation of direct prothrombin activation is translated to the in vivo situation then this phenomenon may pose a non-immunological obstacle to pig to human xenotransplantation.

Animals↗
PubMed1996

Endothelial cell activation in cutaneous vasculitis.

Markers of endothelial cell activation were measured in 28 patients presenting with various forms of limited or focal type cutaneous vasculitis. Plasma levels of tissue plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) and PAI-1 activity, fibrin plate, von Willebrand factor antigen (vWF:Ag), tissue factor (TF) and soluble thrombomodulin (sTM) were measured. In comparison with the control group (n = 20) there was a significant increase in t-PA:Ag, vWF:Ag and TF (P < 0.05, Mann-Whitney U-test) in the cutaneous vasculitis group. This study confirms that measurable degrees of endothelial activation occur in cutaneous vasculitis. Cutaneous vasculitis includes a diverse group of clinical conditions, which are associated with inflammatory changes in cutaneous blood vessels with local fibrin deposition. The aetiology and pathogenesis of the majority of these entities remain unknown. Causative mediators are thought to include immune complexes, anti-endothelial cell antibodies, cytotoxic lymphocytes and viruses. Histologically, immune complexes and complement are frequently detected on the vessel wall, and serologically anti-endothelial antibodies are often detected in patients with vasculitis and in systemic lupus erythematosus (SLE) which correlate with the severity of cutaneous vasculitis, arthritis and nephritis. Lymphocyte-mediated toxicity to endothelial cells has been reported in a small number of patients with giant cell arteritis and Takayasu's arteritis. The vascular endothelium plays a central part in the control of haemostasis. Under physiological conditions endothelial cells present an anticoagulant surface to blood constituents, partially due to surface expression of heparan sulphate and thrombomodulin (TM). Heparan sulphate binds antithrombin III (ATIII), thereby accelerating inactivation of intrinsic coagulation enzymes. Thrombomodulin is an endothelial cell surface glycoprotein which promotes anticoagulation by forming a complex with thrombin which then activates protein C. Activated protein C together with a cofactor, protein S, inactivates FVa and FVIIIa. von Willebrand factor (vWF) is synthesized by endothelial cells, stored in Weibel-Palade bodies and released into the circulation upon endothelial stimulation. vWF mediates the binding of platelets to the subendothelium and is the carrier molecule for FVIIIC. The endothelium controls fibrinolysis by producing t-PA and its inhibitor PAI-1. Inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) activate endothelial cells, causing a shift from an antithrombotic to prothrombotic state, including expression of tissue factor, increased synthesis of PAI-1 and decreased expression of TM. Fibrin deposition and intravascular thrombosis are seen in cutaneous vasculitis syndromes, suggesting local endothelial cell activation. The aim of this pilot study was to assess whether perturbation of the endothelium in cutaneous vasculitis could be detected in the patients' plasma samples. If so, further studies to assess any correlation in levels of these markers with disease activity might prove useful in the future.

Adult↗
PubMed1995

Thrombophilic factors in ischaemic and non-ischaemic idiopathic retinal vasculitis.

Two common causes of visual loss in idiopathic retinal vasculitis (RV) are retinal ischaemia and cystoid macular oedema. This study investigated whether thrombophilic factors are more prevalent in patients with ischaemic RV than non-ischaemic RV. Twenty patients with RV (10 ischaemic, 10 non-ischaemic) were prospectively recruited before starting systemic immunosuppression. Twenty-one different haemostatic parameters were tested. Seventeen patients had at least one haemostatic abnormality. Three patients had low Protein S, one had low Protein C. Three patients had positive anticardiolipin antibody titres, 1 had poor fibrinolytic activity, 3 had raised fibrinogen levels. Ten patients had raised lipoprotein (a) levels. Fibrinogen levels were higher in the smokers (p = 0.02). Although all von Willebrand's factor levels were within the normal range, they were higher in the ischaemic group (p = 0.008), in which smoking was more prevalent. This study has shown a high prevalence of thrombophilic abnormalities in RV patients, and implicates smoking in the aetiology of ischaemic RV.

Adult↗
PubMed1992

Anticoagulants from marine algae.

Anticoagulant properties were first described in extracts from marine algae over 50 years ago. Currently over 60 species, representing the three major divisions of marine algae, have been reported to have such properties. The major active components are a variety of sulphated polysaccharides, some of which characterize as proteoglycans. These sulphated polysaccharides/proteoglycans exert antithrombin properties, primarily mediated by heparin cofactor II (HCII). However antithrombin III (ATIII) mediated anticoagulant activities, as well as an element of direct antithrombin activity, have also been observed.

Amino Acid Sequence↗
PubMed1987

Structural differentiation and fluid reabsorption in the ductuli efferentes testis of the rat.

The ductuli efferentes testis of the rat form a cord which is embedded in adipose tissue. The cord is anatomically differentiated into a proximal cylindrical region, the initial zone, and an ampulla, the coni vasculosi. The initial zone contains six or seven ductuli which leave the rete testis and run in a sinuous path, roughly parallel with one another. However, the ductuli in the coni vasculosi are more sinuous than in the initial zone and they anastomose; pairs join together to form ultimately a single, common ductulus efferens. Stereological studies of paraffin sections and electron micrographs showed that the differentiation of the ductuli into two parts can be recognized at tissue and cellular levels of organization. Stereological and micropuncture studies showed that the ductuli efferentes reabsorb most of the fluid leaving the testis and it was concluded that most reabsorption occurred in the initial zone. It was estimated that the rate of fluid absorption is greater in the ductuli efferentes than in the proximal convoluted tubules of the kidney. The mechanism of fluid transport across the mucosa of the ductuli is considered in the Discussion. It is concluded that transport in vesicles and vacuoles could not account for the rate of fluid reabsorption and that the main mechanism of transport probably involves the coupling of water and active salt transport.

Absorption↗