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Biomedical subjects

C F Scott

Publications and source records attributed to C F Scott.

80 records · Page 5Linked to original sources
PubMed1979

Prekallikrein activation by Hageman factor: potentiation by proteins in the absence of high molecular weight kininogen.

Proteins which potentiate the conversion of prekallikrein to kallikrein by Hageman factor fragments are present in cryoprecipitate prepared from the plasma of an individual lacking HMW kininogen as well as in purified von Willebrand's factor preparations. However, the potentiator activity could be separated from the von Willebrand's antigen and ristocetin cofactor activity by chromatography on QAE-Sephadex. Moreover, it was present in plasma from an individual lacking von Willebrand's factor. These observations indicate that von Willebrand's factor is not responsible for the potentiator activity in cryoprecipitate.

Blood Coagulation↗
PubMed1978

Plasma kallikrein activation and inhibition during typhoid fever.

As an ancillary part of a typhoid fever vaccine study, 10 healthy adult male volunteers (nonimmunized controls) were serially bled 6 days before to 30 days after ingesting 10(5)Salmonella typhi organisms. Five persons developed typhoid fever 6-10 days after challenge, while five remained well. During the febrile illness, significant changes (P < 0.05) in the following hematological parameters were measured: a rise in alpha(1)-antitrypsin antigen concentration and high molecular weight kininogen clotting activity; a progressive decrease of platelet count (to 60% of the predisease state), functional prekallikrein (55%) and kallikrein inhibitor (47%) with a nadir reached on day 5 of the fever and a subsequent overshoot during convalescence. Despite the drop in functional prekallikrein and kallikrein inhibitor, there was no change in factor XII clotting activity or antigenic concentrations of prekallikrein and the kallikrein inhibitors, C1 esterase inhibitor (C1-INH) and alpha(2)-macroglobulin. Plasma from febrile patients subjected to immunoelectrophoresis and crossed immunoelectrophoresis contained a new complex displaying antigenic characteristics of both prekallikrein and C1-INH; the alpha(2)-macroglobulin, antithrombin III, and alpha(1)-antitrypsin immunoprecipitates were unchanged. Plasma drawn from infected-well subjects showed no significant change in these components of the kinin generating system. The finding of a reduction in functional prekallikrein and kallikrein inhibitor (C1-INH) and the formation of a kallikrein C1-INH complex is consistent with prekallikrein activation in typhoid fever. The correlation of these changes with the drop in platelet count suggests that a common mechanism may be responsible.

Adult↗
PubMed1977

Potentiation of the function of Hageman factor fragments by high molecular weight kininogen.

Patients lacking high molecular weight (HMW) kininogen have profound abnormalities of the Hageman factor-dependent pathways of coagulation, kinin formation, and fibrinolysis. The ability of HMW kininogen to potentiate the Hageman factor fragments (HFf) activation of prekallikrein and Factor XI in plasma was studied. HFf only partially converted Factor XI to XIa and prekallikrein to kallikrein in plasma deficient in HMW kininogen (Williams trait), while enhanced activation of Factor XI and prekallikrein by HFf resulted after reconstitution with HMW kininogen. In a system using highly purified components, HMW kininogen increased the initial rate of prekallikrein activation whether the kallikrein formed was assayed by arginine esterase activity or kininforming ability. The potentiation of prekallikrein activation occurred over a 12-fold range of enzyme (HFf) concentration and was nonhyperbolic with respect to substrate (prekallikrein). HMW kininogen exerted its effect even in the absence of prekallikrein since the hydrolysis of acetylglycyl-lysine methyl ester by HFf was increased by HMW kininogen. These results suggest that one of the functions of HMW kininogen is to augment the catalytic action of HFf.

Blood Coagulation Disorders↗
PubMed1975

Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways.

An asymptomatic woman (Ms. Williams) was found to have a severe abnormality in the surface-activated intrinsic coagulation, fibrinolytic, and kinin-generating pathways. Assays for known coagulation factors were nromal while Fletcher factor (pre-kallikrein) was 45%, insufficient to account for the observed markedly prolonged partial thromboplastin time. Plasminogen proactivator was present at 20% of normal levels and addition of highly purified plasminogen proactivator containing 10% plasminogen activator partially corrected the coagulation and fibrinolytic abnormalities but not the kinin-generating defect. This effect was due to its plasminogen activator content. In addition, Williams trait plasma failed to convert prekallilrein to lakkilrein or release kinin upon incubation with kaolin. Kininogen antigen was undetectable. When normal plasma was fractionated to identify the factor that corrects all the abnormalities in Williams trait plasma, the Williams factor was identified as a form of kininogen by its behavior on ion exchange chromatography, gel filtration, disc gel electrophoresis, and elution from an anti-low molecular weight kininogen immunoadsorbent. High molecular weight kininogen as well as a subfraction of low molecular weight kininogen, possessed this corrective activity while the bulk of low molecular weight kininogen functioned only as a kallikrein substrate. Kininogen therefore is a critical factor required for the functioning of Hageman factor-dependent coagulation and fibrinolysis and for the activation of prekallikrein.

Adsorption↗
PubMedDate not supplied

Preparation and characterization of interleukin-2-gelonin conjugates made using different cross-linking reagents.

Conjugates of IL-2 with the ribosome-inactivating protein gelonin were prepared using heterobifunctional reagents to link the proteins via disulfide, acid-labile, and noncleavable linkers. In each case, one protein was modified using 2-iminothiolane. The sulfhydryl groups so introduced were then reacted either with 2-nitro-5-dithiobenzoate groups or with iodoacetamido groups which had been introduced into the second protein. In the case of the acid-labile linkage, a reagent which forms a labile bond upon reaction with amino groups, 4-(iodoacetamido)-1-cyclohexene-1,2-dicarboxylic acid anhydride (its synthesis is described in this paper) was used to modify the toxin. The conjugates were separated from nonconjugated proteins by gel filtration on Sephadex G100 (SF). Each was analyzed with respect to its ribosome-inactivating activity, its ability to bind to the IL-2 receptor, and its in vitro cytotoxicity. The ribosome-inactivating activity of gelonin was unaffected by modification with 2-iminothiolane and was retained in conjugates prepared using this reagent. Modification of the toxin with 4-(iodoacetamido)-1-cyclohexene-1,2-dicarboxylic acid anhydride to form the acid-labile link drastically reduced the activity of the toxin. However, the activity of the toxin was recovered following acid treatment to release the native protein. Conjugates containing each type of linkage exhibited both specific binding and selective cytotoxicity toward cells expressing the IL-2 receptor. The most potent of these toxins, that containing the disulfide linkage, exhibited a cytotoxicity which was 2 orders of magnitude greater than that of unconjugated gelonin.

Animals↗
PubMedDate not supplied

Experimental allergic encephalitis; treatment with drugs which alter CNS serotonin levels.

Lennon and Carnegie have proposed that the clinical symptomatology of experimental allergic encephalitis (EAE), an acute autoimmune demyelinating disease, may be due, at least in part, to an immune response directed against CNS serotonin receptors. To test this hypothesis we treated strain 13 guinea pigs, which had been immunized with guinea pig basic protein (GPBP) in complete Freund's adjuvant (CFA), with drugs known to affect central nervous system (CNS) serotonin levels. These drugs included imipramine hydrochloride, tryptophan and carbidopa which increase CNS serotonin and reserpine which decreases it. Five experiments were conducted in which all immunized animals treated with saline only died, as expected, as did all animals treated with reserpine which died even more quickly. A significant proportion of animals treated with the other three drugs, alone or in combination, survived or lived longer than controls. We conclude that survival of animals with EAE is enhanced by treatment with these drugs. We suggest that further evaluation of a possible blockade in serotonin transmission in EAE and multiple sclerosis (MS) is warrented, since, if such a blockade were demonstrated, it is possible that these drugs may have potential for therapeutic efficacy in patients with MS.

Animals↗