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Biomedical subjects

M J Gallimore

Publications and source records attributed to M J Gallimore.

At least 19 recordsLinked to original sources
PubMed1992

Aprotinin in cardiopulmonary bypass--effects on the Hageman factor (FXII)--Kallikrein system and blood loss.

Aprotinin has been used in our hospital in open heart surgery for almost 20 years and recently published studies have revealed a reduction in postoperative blood loss under this therapy. In the present study patients undergoing aorto-coronary bypass operations received either 20,000 KIU aprotinin/kg body weight (group 2) or 60,000 KIU aprotinin/kg body weight (group 3). Another group of patients without aprotinin served as a control (group 1) and postoperative bleeding was more pronounced in these patients compared with the other groups. In parallel, slight reductions in kallikrein-like activity were observed in patients treated with aprotinin. Furthermore, we have shown that the main inhibitor of the contact phase, C1-esterase-inhibitor, loses some of its activity against beta-FXIIa in the presence of heparin. Aprotinin was able to partly antagonize this phenomenon. All studies dealing with the effect of aprotinin in extracorporeal circulation demonstrate hyperfibrinolysis in untreated patients. Aprotinin is known to inhibit plasmin at low concentrations and thus reduced the postoperative bleeding tendency (group 2). In addition, plasma kallikrein is inhibited by high aprotinin concentrations and is responsible for a reduced activation of the contact phase system. This effect led to a further reduction in blood loss (group 3).

Aprotinin↗
PubMed1992

The effects of fractionated and unfractionated heparins with and without aprotinin on plasma inhibition of alpha and beta FX11a.

Chromogenic peptide substrate assays were used to compare the effects of fractionated and unfractionated heparins on plasma inhibition of alpha and beta FX11a, with and without various concentrations of aprotinin. All of the heparins reduced beta FX11a inhibition at 1 or 2U/ml. Four heparins increased alpha FX11a inhibition. Aprotinin counteracted the reduction in beta FX11a inhibition and augmented the heparin potentiation of alpha FX11a inhibition.

Aprotinin↗
PubMed1992

Studies on components of the plasma kallikrein system as a risk factor in diabetics undergoing cardiopulmonary bypass.

Components of the FX11-kallikrein systems were determined in blood samples from non diabetics and diabetics undergoing cardiopulmonary bypass (CPB). FX11 and prekallikrein levels fell in both groups with the largest falls in the diabetic group. Kallikrein inhibition was also lower in the diabetic group. Alpha-2-macroglobulin levels were lower in the diabetic group before operation and were markedly lower throughout CPB. Kallikrein like activities were also lower in the diabetic group. Beta FX11a inhibition values were higher in the diabetic group and fell in both groups during CPB. From the results obtained we concluded that the lower levels of FX11, prekallikrein, kallikrein inhibition and alpha-2-macroglobulin in the diabetic patients during CPB reflect enhanced activation of the FX11-plasma kallikrein systems. Blood loss in the diabetic group was higher than the for non diabetic group.

Biomarkers↗
PubMed1991

Chromogenic peptide substrate assays and their clinical applications.

Chromogenic peptide substrates were first introduced into research laboratories in the early 1970s and were quickly utilised to develop assays for the determination of enzymes, proenzymes and inhibitors of the coagulation system. These assays were gradually introduced into coagulation and clinical chemistry laboratories as laboratory tools in the diagnosis and treatment of coagulation disorders. From the knowledge of the structures of the natural substrates attacked by enzymes other than those of the coagulation system or by synthesis and random screening, substrates for enzymes of the fibrinolytic, plasma and glandular kallikrein and complement systems were produced. These allowed various research groups to develop assays for components of these systems and subsequently led to the use of these assays in studies on various clinical conditions. Substrates for activated protein C ensured that assays for this enzyme and its inhibitors could be developed and introduced into the haematological routine. With the introduction of substrates for limulus lysate not only were assays for endotoxins in clinical samples produced but the control of all disposable products and injectables for endotoxin contamination can now be effected. Initially high costs and time-consuming manual assays were a hinderence to the general acceptance of the use of chromogenic peptide substrate assays and they were only used routinely in a few specialised laboratories. With the introduction of automated and microtitre plate methods however, these assays are are now available in most hospital laboratories. Since the first chromogenic peptide substrate was described thousands of articles have been published on the use of chromogenic substrate assays to measure proenzymes, enzyme activators, enzyme cofactors and inhibitors in blood and other body fluids in normal subjects and clinical material. We have endeavoured to cover as many of these as possible in this review.

Blood Chemical Analysis↗
PubMed1990

FXII.

The plasma protein FXII (Hageman factor) has been shown to be linked with the plasma defence systems of coagulation, fibrinolysis, kallikrein-kinin and complement. It can be activated by surface contact activation and in solution. Surface contact activation is a complex phenomenon involving negatively charged surfaces, FXII, high molecular weight kininogen and plasma kallikrein. Fluid-phase activation can be effected by a variety of serine proteases. In both types of activation the FXII zymogen is converted to active enzymes. FXII levels in plasma are low or undetectable in both inherited deficiencies and in a variety of clinical conditions. FXII levels can also be elevated in some clinical conditions. Although discovered as a clotting protein FXII appears to play an important role in the kallikrein-kinin and fibrinolytic systems and also has effects on cells. Recent studies suggest that therapeutic blockade of activation of FXII can be of benefit in certain clinical conditions.

Animals↗
PubMed1989

Modulation of morphological differentiation of human neuroepithelial cells by serine proteases: independence from blood coagulation.

We have previously shown that a serum protein, termed differentiation reversal factor (DRF), is responsible for neurite retraction in differentiated cultures of an adenovirus 12 (Ad12) transformed human retinoblast cell line. Data is presented here to show that DRF is identical to the serine protease prothrombin. Both proteins have been immunoprecipitated using an antibody raised against purified prothrombin and have been shown to hydrolyse a specific thrombin substrate only after activation by the snake venom ecarin. Following addition to Ad12 HER 10 cells, which had previously been differentiated by culture in the presence of 2 mM dibutyryl cAMP in serum-free medium, thrombin and prothrombin caused half-maximal retraction of neurites at concentrations of 0.5 ng/ml and 20 ng/ml respectively. Interestingly, activation of prothrombin was shown to be unnecessary for biological activity. Using the inhibitor di-isopropylfluorophosphate (DIP), we have shown that abrogation of the proteolytic activity of thrombin also results in a loss (greater than 2000 fold) of differentiation reversal activity. Thrombin and its zymogen both stimulated the mitosis of differentiated Ad12 HER 10 cells to a similar extent. In addition, differentiation reversal was highly specific since, at physiologically significant concentrations, closely related serine proteases did not cause neurite retraction. Prothrombin and thrombin also reversed morphological differentiation in the SK-N-SH neuroblastoma cell line and in heterogeneous cultures of cells from various regions in the human foetal brain.

Axons↗
PubMed1988

Parameters of the kallikrein-kinin, coagulation and fibrinolytic systems as early indicators of kidney transplant rejection.

In order to find early indicators of kidney transplant rejection before clinical symptoms were noticed, parameters of the coagulation, fibrinolytic and kallikrein-kinin systems were measured. Nineteen patients were followed before and daily after kidney transplantation during the first week and every second day in the following weeks. All patients received immunosuppressive therapy with cyclosporin and corticoids. Ten patients suffered from transplant rejection. The first rejection occurred on the 7th day after transplantation. Of all the parameters measured, kallikrein inhibition, beta-FXIIa inhibition, plasminogen and antithrombin III were early indicators of kidney transplant rejections. A rise in these parameters could be demonstrated 2-3 days before clinical signs were noticed. In the other 9 patients no significant rises in antithrombin III, plasminogen, kallikrein inhibition and beta-FXIIa inhibition could be found.

Adrenal Cortex Hormones↗