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Biomedical subjects

A Girolami

Publications and source records attributed to A Girolami.

At least 271 records · Page 15Linked to original sources
PubMed1993

A family with an abnormal protein C and a thrombotic tendency.

An Italian family with a dysfunctional protein C (type II deficiency) tentatively designated Protein C Padua has been investigated. Five family members had this defect. Thrombotic manifestations occurred in the propositus, his sister, and his 87-year-old mother, who suffered from a transitory ischemic attack (TIA). All other deficient patients were asymptomatic. The abnormality was consistent with normal protein C (PC) antigen level but reduced both anticoagulant and amidolytic activities after PC activation by Protac. When thrombin was used as activator, PC activity level was also reduced. The abnormal PC molecule seemed to have a defect involving the activation region or the active site mechanism (reduced activity level regardless of the PC activators and the methods used in the functional assays). The electrophoretic mobility of the dysfunctional protein, assayed by crossed-immunoelectrophoresis (CIE), was normal in presence of both Na citrate and calcium lactate. The kinetics of antigen-antibody complex formation between the abnormal PC and anti-PC polyclonal antibody was investigated by means of a laser nephelometer and a peculiar pattern was found in the affected patients suggesting a possible anomalous interaction between the antibody and the abnormal protein.

Aged↗
PubMed1993

Combined haemophilia A and type I von Willebrand's disease: a family study including an evaluation of the effects of DDAVP infusion.

A family with concurrent haemophilia A and type I von Willebrand's disease (vWd) is described. The propositus was affected by both disorders. The propositus' mother was an obligate carrier of haemophilia A being the daughter of a haemophilic. The father and sister were affected by vWd. The sister was also a possible carrier of haemophilia A. This is the first report of both disorders occurring simultaneously. The infusion of 1-desamino-8-d-arginine vasopressin (DDAVP) induced, in the propositus, a normalization of circulating levels of vWf, with a less pronounced enhancement of factor VIII:C. In the father, the response to DDAVP infusion of factor VIII/vWf complex was normal. In the mother, the time-course of factor VIII:C was characterized, after a peak at 30 min, by a progressive decrease until 2 hours after infusion, in contrast to vWf which appeared further increased at the same times. Therefore, the low factor VII:C/vWf:Ag ratio, already present before infusion, became significantly more pronounced 2 hours after DDAVP. Similar findings were observed in another obligate carrier of the family, in the propositus' sister and in 10 other haemophilia A carriers, belonging to different kindreds. In all patients, even when the basal factor VIII:C/vWf:Ag ratio was normal, two hours after DDAVP it decreased in agreement with the haemophilia A carrier state.

Adult↗
PubMed1993

Effect of recombinant-tissue plasminogen activator, low molecular weight urokinase and unfractionated heparin on platelet aggregation.

We studied the interaction of two thrombolytic agents, recombinant-tissue plasminogen activator (r-TPA) and low molecular weight urokinase (UK), with platelet aggregation in the absence or presence of unfractionated heparin (UH). With platelet rich plasma (PRP), a dose dependent inhibition was seen for both r-TPA and UK. However, this effect was more evident in the presence of r-TPA. UH did not modify this effect. However, it enhanced platelet aggregation induced by ADP and decreased the aggregation induced by collagen (COL) as already shown by us. With washed platelets, only r-TPA decreased platelet aggregation in a dose dependent manner in the presence of COL and only at the highest dose (100 micrograms) in the presence of TH. The presence of ten units of plasminogen (PLG) together with 10 micrograms of r-TPA or 1250 units of UK totally inhibited TH-induced platelet aggregation. UH reversed this effect. In contrast, when COL was the aggregating agent, the inhibition of platelet aggregation in presence of PLG, seems to be further increased by UH. Since UH is an adjunct of thrombolytic therapy to prevent rethrombosis, this double edged sword could partially explain the lack of therapeutic effect in some patients.

Adenosine Diphosphate↗
PubMed1993

First report of combined factor VII Padua defect and von Willebrand's disease due to casual association of the two defects.

We report a family with a combined factor VII Padua defect and von Willebrand's disease (vWd). The propositus is a 9-year-old child with a moderate bleeding tendency who appeared to be heterozygous for both factor VII Padua and type I vWd. The diagnosis of factor VII Padua was based on a normal factor VII antigen and factor VII activity which was low with rabbit brain thromboplastin but normal with ox brain thromboplastin. Type I vWd was diagnosed because of a concomitant decrease of von Willebrand factor antigen (vWf:Ag) and vWf ristocetin-cofactor activity (vWf:RCoF), associated with the presence of vWf multimers of all sizes in plasma and platelets. The parents were not consanguineous but came from the same isolated river Piave valley in North Eastern Italy where the factor VII Padua defect was first described. The father had the factor VII Padua defect but was clinically asymptomatic in accordance with the heterozygous state. The propositus's mother had type I vWd and was mildly symptomatic. The propositus' sisters, who were clinically asymptomatic, were both heterozygotes for factor VII Padua. The infusion of DDAVP normalized the factor VIII/vWf pattern in all patients. In the propositus, in contrast to the mother and normal subjects, showed a more rapid clearance both of vWf and factor VIII. The same pattern, albeit to a lesser degree, was also observed in the father.

Child↗
PubMed1992

Combined inherited protein S and heparin co-factor II deficiency in a patient with upper limb thrombosis: a family study.

A 42-year-old Italian woman presenting with spontaneous deep vein thrombosis of the right arm, was found to have inherited a deficiency of both protein S (PS) and heparin co-factor II (HC II). The two defects seemed to segregate independently, since her son exhibited only a HC II deficiency while one of her sisters manifested only the PS defect. All affected patients appeared heterozygous for one or other or both deficiency states. The proposita and her sister exhibited a congenital PS deficiency consisting of normal or near normal levels of total PS antigen and C4b-binding protein (C4b-BP) but a moderate reduction both of free PS antigen and of PS functional activity. In addition, the proposita and her son had half normal levels of HC II antigen and activity. Except for the proposita, all were asymptomatic. Inherited deficiencies either of PS or of HC II have been associated with thrombotic manifestations. Since the proposita had an inherited combined defect of the two proteins, severe thrombotic events might be expected. However, this was not found to be the case. The role of HC II deficiency in the pathogenesis of thrombosis whether alone or combined remains to be fully investigated.

Adolescent↗
PubMed1992

Urokinase-type plasminogen activator release after DDAVP in von Willebrand disease: different behaviour of plasminogen activators according to the synthesis of von Willebrand factor.

Nine healthy volunteers and 23 patients with various types of von Willebrand disease were studied before and after DDAVP infusion. We investigated the behaviour of factor VIII/von Willebrand factor measurements, and of tissue plasminogen activator and urokinase-type plasminogen activator. In mild von Willebrand disease the increase of both plasminogen activators was similar to that seen in normal controls. A different fibrinolytic behaviour was found in the type I platelet low and in the type III von Willebrand disease patients. An impaired and absent fibrinolytic response to DDAVP was seen in the former and in the latter von Willebrand disease, respectively. A close relation between either u-PA and t-PA or von Willebrand factor was observed. The possibility of a linkage among these three proteins was discussed.

Adolescent↗
PubMed1992

Labeling of platelet surface glycoproteins with biotin derivatives.

We describe a non-radioactive method for the labeling of platelet surface proteins, consisting of platelet protein biotinylation by means of N-hydroxysuccinimido-biotin (NHS-B) and biotin-hydrazide (H-B); NHS-B labels proteins amino residues while H-B binds to periodate-modified sialoglycoproteins. Washed platelets were biotinylated and protein bands were detected after SDS-electrophoresis and western-blot using avidin-peroxidase and luminol as substrate to enhance the signal which was then detected by X-ray film. Biotin-labeled platelet proteins were also immunoprecipitated with monoclonal antibodies against glycoproteins Ib and the IIb-IIIa complex. The use of periodate induced biotinylation is the method of choice for labeling platelet surface glycoproteins while NHS-B also labels internal proteins. The sensitivity of this new procedure is similar to that obtained with radiolabeling techniques; biotinylation does not interfere with the antigenic properties of Ib and IIb-IIIa glycoproteins.

Antibodies, Monoclonal↗
PubMed1992

Detection of two missense mutations and characterization of a repeat polymorphism in the factor VII gene (F7).

The 3' portion of the coagulation factor VII gene, containing the activation and serine protease domains, was investigated in four subjects with factor VII deficiency by temperature gradient gel electrophoresis and sequencing of polymerase chain reaction (PCR) products. Molecules displaying an altered melting behaviour were detected in three subjects, and direct sequencing showed two mutations. A G-to-T transversion causing a missense mutation, Cys-310 to Phe, suppresses a disulphide bond conserved in the catalytic domain of all serine proteases. This mutation, which in the homozygous form causes a severe reduction in protease activity (4%), was found in two patients from different Italian regions. A G-to-A transition, which gives rise to a missense mutation, Arg-304 to Gln, and is associated with the factor VII padua variant, was found in the heterozygous form in a subject also affected by von Willebrand disease. Two polymorphic alleles, which differ in one repeat monomer element, were precisely mapped in a region spanning the exon-intron 7 border of the factor VII gene and studied in families with factor VII or X deficiency.

Base Sequence↗
PubMed1992

Impaired release of tissue plasminogen activator (t-PA) following DDAVP infusion in von Willebrand's disease with low platelet von Willebrand factor content.

Tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) are both released by vascular endothelial cells after the infusion of DDAVP. Such release has not been observed in patients with severe von Willebrand's disease (vWD). In the present work we demonstrate that the degree of simultaneous DDAVP-induced release of t-PA and vWF, in patients with vWD, is strictly related to the platelet vWF content. Twelve patients with type I, and three patients with type III vWD were studied. The type I vWD group included three patients with reduced platelet vWF content (platelet-low) and nine patients with normal levels (platelet-normal). In all patients studied the plasma t-PA levels were within the normal range. No significant change in either t-PA or vWF was observed after DDAVP in the patients with undetectable levels of platelet vWF (type III vWD). A mild increase was found in those patients with type I platelet-low, while in type I platelet-normal vWD the response was similar to that observed in normal subjects. The release of the two molecules appeared, therefore, to be linked to platelet vWF content and the rates of increase in both t-PA and vWF were similar in each group of patients studied. Since platelets are regarded as a tissue compartment of vWF our findings seem to suggest that the presence of vWF and its release from endothelial cells is required for a normal concomitant release of t-PA. In contrast, post-DDAVP release of vWF seems to be independent from that of t-PA since it was normal in a patient with congenital deficiency of t-PA release.

Adolescent↗
PubMed1992

The fibrinolytic potential in patients with Cushing's disease: a clue to their hypercoagulable state.

The aim of our study was to determine the fibrinolytic potential in a large group of patients with Cushing's disease. These patients had a significant shortening of the activated partial thromboplastin time and increase in factor VIII/von Willebrand factor complex compared to normal controls. The mean levels of plasminogen, tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity were significantly higher than in normal subjects, whereas the basal fibrinolytic activity was similar to that seen in the control group. In 17 out of 30 Cushing patients and in 17 normal subjects the fibrinolytic potential was determined with the venous occlusion test. In the Cushing group, the release of t-PA antigen after 20 min of venous occlusion was comparable to that observed in the control group. However, Cushing patients showed a lower fibrinolytic activity than normal subjects, since a lesser shortening of the euglobulin lysis time and a non-significant rise of plasminogen activator activity levels were found. Moreover, in these patients the PAI activity values remained unchanged and significantly increased after venous occlusion test also. In conclusion, the impaired fibrinolytic activation seen in Cushing patients after venous occlusion can be explained by the inhibitory effect of the high PAI levels on plasminogen activators. The defective fibrinolytic potential could further contribute to the hypercoagulable state in Cushing's disease. High PAI levels before surgery may represent an additional risk factor for post-surgical thromboembolic complications in Cushing patients.

Adult↗
PubMed1992

Incidence of thrombocytosis in lymphomas.

Reactive thrombocytosis due to malignancies and in particular those related to lymphomas have not yet been extensively evaluated. We report data on thrombocytosis recognized in 18 out of 101 patients with lymphomas diagnosed in our department over the last 3 years. All showed high platelet counts at the time of diagnosis. The incidence of thrombocytosis seems to be more frequent in males (21.2%) than in females (14.8%) and a slightly higher frequency was found in Hodgkin's disease (21.4%) than in non Hodgkin's lymphomas (16.4%). The incidence of thrombocytosis in lymphomas seems to be similar to that seen in other malignancies and because of this we conclude that a high platelet count cannot be used to distinguish malignancies.

Bone Marrow↗