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M Gallimore

Publications and source records attributed to M Gallimore.

8 recordsLinked to original sources
PubMed1992

Contact factor proteases and the complexes formed with alpha 2-macroglobulin can interfere in protein C assays by cleaving amidolytic substrates.

Plasma from women taking combined oral contraceptives and cold-activated plasma contain proteases which cleave chromogenic substrates in protein C assays in the absence of protein C activators such as Protac. This spontaneous activity makes a background substraction necessary and makes protein C (PC) assays less accurate. We investigated two commonly used substrates < Glu-Pro-Arg-pNA (S-2366) and 2AcOH.H-D-Lys(Cbo)-Pro-Arg-pNA (PC substrate) and found that cold-activated normal and protein C-deficient plasmas gave absorbance values up to 300 times higher than buffer blanks. FXIa cleaves these substrates but activity was not blocked by corn or lima bean trypsin inhibitors, soy bean trypsin inhibitor (SBTI), hirudin or epsilon-amino-n-caproic acid (EACA). Kaolin activation of normal, FXI, FIX, FVIII, FVII and protein C-deficient, but not of FXII or prekallikrein (PKK)-deficient plasmas led to cleavage of chromogenic substrate for protein C. The protein C substrates were cleaved by purified kallikrein and alpha- and beta-FXIIa. Immunoabsorption with alpha 2-macroglobulin (alpha 2M) antibodies removed 60% of the alpha 2M and 70% of the activity on PC Substrate. Gel filtration of normal plasma on Sephadex G-150 gave a single peak of protein C activity and antigen in the included volume. After cold activation of the fractions, a second protein C-like peak appeared in the void volume, but with no detectable protein C antigen. This peak coincided with alpha 2M (chromogenic and ELISA) and plasma kallikrein (S-2302), but FXII (measured with a substrate insensitive to kallikrein) eluted separately.(ABSTRACT TRUNCATED AT 250 WORDS)

Amides↗
PubMed1992

Procoagulant changes induced by oral contraceptives are balanced by an increased fibrinolytic tendency.

Oral contraceptives caused increased fibrinogen, FVII, FX, and fibrinolysis. The latter was associated with elevated FXII and PKK, while C1-INH was decreased, ATIII and alpha 2M were unchanged; it could not be accounted for by changes in t-PA, u-PA, PAI, plasminogen, alpha 2-AP, proteins C or S. HCII and alpha 1-PI were increased and may regulate the availability of thrombin and FXIa. The increased FXII/PKK dependent fibrinolytic potential and HCII may offset any increase in thrombin generation, while alpha 1-PI limits intrinsic coagulation.

Adult↗
PubMed1991

Detection of protein C deficiency during oral anticoagulant therapy--use of the protein C:factor VII ratio.

Laboratory diagnosis of protein C deficiency is complicated by the fact that many patients referred for investigation are already being treated with oral anticoagulants. Protein C and factor VII have similar half lives and by using the protein C:factor VII ratio we hoped to be able to detect protein C deficiency in patients receiving oral anticoagulants. We have studied activity levels of protein C and factor VII to produce protein C:factor VII activity ratios in 105 patients receiving oral anticoagulants, 42 normal subjects, and nine patients with known inherited protein C deficiency. The mean ratios for these groups were 1.38, 1.12 and 0.63 respectively. In patients receiving oral anticoagulants, the protein C level showed a poor correlation with the international normalized ratio (INR) value. Reference ranges for protein C at different levels of anticoagulation were therefore considered unsuitable for the identification of inherited protein C deficiency. Five patients with inherited protein C deficiency were studied with and without oral anticoagulation; their protein C:factor VII ratios remained relatively unchanged, despite alterations in the level of the individual proteins. These results suggest that measurement of the protein C:factor VII ratio may help to identify patients with inherited protein C deficiency whilst on oral anticoagulants.

Adolescent↗
PubMed1990

Heparin cofactor II levels are increased by the use of combined oral contraceptives.

Heparin cofactor II (HCII) was assayed by a microtitre amidolytic substrate technique. A linear response was obtained up to 1.5 U/ml and HCII levels were not affected by freezing and thawing the plasma. The assay was validated by comparing HCII and antithrombin III (AT III) levels in AT-III-deficient plasmas and samples from critically ill patients. Higher HCII levels were found in healthy normal women than in healthy normal men (means 1.16 and 0.97 U/ml, respectively, P less than 0.01). A significant increase in HCII levels from 0.86 to 1.10 U/ml (mean values) was seen in healthy normal women starting on combined oral contraceptive (COC) preparations (P less than 0.001). Increased HCII levels were maintained over a 6-month period, but fell towards normal 14 days after stopping COC, although they were still significantly higher than before starting COCs. The discrepancy in HCII level between normal men and women may be due to COC use. In clinical studies, different reference ranges should be used for men and women, and the need for careful questioning about the use of COCs is emphasized.

Adolescent↗
PubMed1978

Effects of slow intravenous administration of endotoxin on blood cells and coagulation in dogs.

Endotoxin shock was induced in dogs by slow administration of a lethal dose of Escherichia coli endotoxin. During the 3-hour infusion period a state of disseminated intravascular coagulation (DIC) was noted. The drop in platelets and leukocytes was the most rapid and pronounced effect of the infusion, while consumption of coagulation factors occurred more slowly. Activation of the extrinsic and intrinsic pathways of coagulation appeared to be closely parallel. Concomitantly increasing amounts of fibrin(ogen) degradation products were detected, while soluble fibrin monomers were observed only inconstantly. Intravascular hemolysis was slight and occurred in the late stages of shock, and could not have influenced the development of DIC.

Animals↗
PubMed1978

Chromogenic substrate assay of plasma prekallikrein. With a note on its site of biosynthesis.

A method for assaying plasma prekallikrein has been developed applying the chromogenic substrate Chromozym PK. Different variables have been investigated, and the final assay system was found to give a reproducible and reliable assay procedure. A normal value of 99.0 +/- 18% was found, the coefficient of variation being 7.9. Studies on material from patients with various liver diseases indicated that the main site of prekallikrein biosynthesis is the liver.

Adult↗