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Biomedical subjects

A Wallmark

Publications and source records attributed to A Wallmark.

24 records · Page 2Linked to original sources

Two allotypes of factor IX present in haemophilia B.

Factor IX antigen (IX:Ag) was measured with three different immunoradiometric assays (IRMAs) in 30 healthy people and 43 patients with haemophilia B of varying severity. Two of the IRMAs were based on monoclonal antibodies capable of differentiating between two genetically determined molecular variants of normal factor IX. Most patients with severe hemophilia B lacked demonstrable IX:Ag. The factor IX variant that is undetectable with one of the monoclonal antibodies used was present in 2 out of 6 families with moderate haemophilia B and in 1 out of 6 families with mild haemophilia B. The existence of allotypes of factor IX in hemophilia B may have practical implications for carrier detection and prenatal diagnosis.

Alleles↗

Polymorphism of normal factor IX detected by mouse monoclonal antibodies.

Hemophilia B is an X-chromosomal recessive disease due to deficiency of coagulation factor IX. Three monoclonal antibodies against factor IX were prepared and used to develop immunoradiometric assays (IRMAs) of factor IX antigen (IX-Ag). IX-Ag was measured in 65 normal individuals with one IRMA based on polyclonal anti-IX antibodies and two IRMAs based on three monoclonal anti-IX antibodies. One of the monoclonal antibodies differed in specificity since it neutralized less than 50% of the clotting activity of factor IX (IX-C), whereas the other two monoclonal antibodies neutralized 80-95%. When the former antibody was used as the solid phase in IRMA, two groups of normal individuals were distinguished: group A with measurable IX-Ag, and group B without demonstrable IX-Ag. There were no differences between the groups either in IX-C or in IX-Ag measured with polyclonal antibodies. A subgroup comprising only women could be distinguished in group A, in whom intermediate IX-Ag concentrations were found. Family studies showed the group B variant of normal factor IX to be transmitted according to the pattern of X-linked recessive inheritance. The allelic frequency of group A was 0.66, and that of group B was 0.34.

Adolescent↗

The use of monoclonal antibodies in measuring factor VIII/von Willebrand factor.

Here we report the production of four different monoclonal antibodies against factor VIII/von Willebrand factor (F VIII/vWF) and the use of these antibodies in immunoradiometric assay (IRMA), crossed immunoelectrophoresis (CIE) and multimeric sizing (MS) for analysing the various types of von Willebrand's disease. None of the antibodies inactivated factor VIII coagulant activity and one (R1) of them partly inhibited the ristocetin co-factor activity. One monoclonal antibody (R2) was radiolabelled and compared with 125I rabbit affinity purified antibody against F VIII/vWF. The two IRMA techniques gave similar results in 26 normals and 22 samples representing all variants of von Willebrand's disease. This monoclonal antibody could also be used in multimeric sizing and not only produced patterns identical to those obtained with the rabbit affinity purified antibody, but also gave better resolution. Further advantages of using monoclonal antibodies in these tests are: practically unlimited access to the same specific antibody, time-consuming affinity purification of the rabbit antibody can be avoided and the overall use of radioactivity reduced. This study demonstrates that one (R2) of the four monoclonal antibodies is suitable for routine analysis of F VIII/vWF and the use of this antibody simplifies the laboratory work in classifying von Willebrand's disease.

Animals↗

Monoclonal antibody specific for the mutant PiZ alpha 1-antitrypsin and its application in an ELISA procedure for identification of PiZ gene carriers.

The PiZ genetic variant of alpha 1-antitrypsin in its homozygous form is associated with an increased risk for chronic lung and liver disease. About 5% of the population are carriers of one PiZ deficiency gene resulting in intermediate levels of plasma alpha 1-antitrypsin (PiMZ, PiSZ, PiPZ). We report the preparation of a hybridoma cell line, ATZ 11, produced by fusion of spleen cells from BALB/c mice immunized with a purified liver PiZ alpha 1-antitrypsin and Sp 2/0 Ag 14 mouse myeloma cells. ATZ 11 produces monoclonal antibodies (IgG1 kappa) specifically interacting with PiZ alpha 1-antitrypsin. These antibodies were used in an ELISA procedure permitting easy and accurate identification of PiZ gene carriers. The method is especially well-suited for studying large population samples concerning the putative relationship between intermediate alpha 1-antitrypsin deficiency and disease.

Animals↗

Feasibility of extracorporeal on-line large-scale plasma adsorptions on protein A-sepharose columns in cancer patients.

The feasibility of extracorporeal adsorption of 1.5-3 L plasma on protein A-Sepharose was investigated in six patients with advanced cancer. Anticoagulation with heparin was associated with respiratory distress syndrome in two patients, most likely caused by complement activation as indicated by a transient leukopenia during plasma reinfusion and appearance of C3 degradation products in the extracorporeal circulation. Addition of citrate abolished the respiratory symptoms, C3 degradation, and leukopenia, and no adverse reactions were observed. No objective tumor regression was observed in any of the patients. Three patients progressed during therapy. In one of these, multifocal central tumor necrosis was observed as a possible, although unproven, therapeutic effect. Increased natural killer and/or killer cell activities were recorded in three patients and increased complement-dependent serum cytotoxicity in one patient. The level of circulating immune complexes decreased significantly (18-28%) in three patients studied. It is concluded that extracorporeal plasma adsorption on protein A-Sepharose is feasible when citrate is added to the extracorporeal system, but its therapeutic efficacy is uncertain.

Adsorption↗

Renal revascularization after intrarenal implantation of the splenic artery with a distal arteriovenous fistula.

Renal revascularization by splenic artery implantation was performed in 5 dogs using a temporary arteriovenous fistula in the distal end of the implanted artery for the purpose of increasing the blood flow and counteracting the thrombus formation in the artery. Following creation of renal artery stenosis, the revascularization process was evaluated by serial consecutive splenic arteriographies and by estimation of blood flow through the implanted arteries. The experimental animals survived occlusion of the ipsilateral renal artery and contralateral nephrectomy with maintenance of a reasonably good renal function. The present study also indicates a facilitation of a vascularization from the implanted artery when the initial thrombus formation within the artery was prevented by creation of such a fistula.

Angiography↗