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Biomedical subjects

D B McClelland

Publications and source records attributed to D B McClelland.

At least 55 records · Page 3Linked to original sources

Serum ALT levels in patients with primary hypogammaglobulinaemia receiving replacement therapy with intravenous immunoglobulin or fresh frozen plasma.

The intravenous immunoglobulin (IV. IgG) preparation used in this study is manufactured by the Scottish National Blood Transfusion Service (SNBTS) by the pH 4/mild pepsin method. Recent reports suggest that non-A, non-B hepatitis may be transmitted by certain intravenous immunoglobulin preparations. Serum ALT levels were therefore measured prospectively in 16 patients with primary hypogammaglobulinaemia who received an intravenous immunoglobulin replacement therapy (SNBTS IV IgG) over a period ranging from 6 to 25 months. Retrospective analysis of serum ALT levels was also carried out in 8 patients with primary hypogammaglobulinaemia who received fresh frozen plasma (FFP) for periods ranging from 8 months to 13 years. There was no evidence of non-A, non-B hepatitis transmission by either SNBTS IV IgG or by FFP in all the patients studied.

Adolescent↗

Enhancement of factor VIII-von Willebrand factor ristocetin cofactor activity by monoclonal antibodies.

Five monoclonal antibodies to human von Willebrand factor were selected for characterization from 18 produced in murine hybridomas. All showed a high and specific affinity for human von Willebrand factor (vWf) but exhibited little if any cross-reaction with sera from other species. The antibodies defined four epitopes on vWf, none of which were involved in platelet binding. Binding of two distinct antibodies at one of these epitopes was associated with enhancement of the rate of vWf-dependent platelet agglutination in the presence of ristocetin. This effect was more noticeable when cryosupernatant plasma was used in place of normal plasma as the source of vWf, and was not explicable simply in terms of antibody-induced cross-linking of vWf.

Animals↗

Human T-lymphotropic virus type III (HTLV-III) infection in seronegative haemophiliacs after transfusion of factor VIII.

Fifteen haemophiliac patients acquired antibodies to human T-lymphotropic virus type III during 1984. One batch of factor VIII concentrate given to all these patients is presumed to be the cause of the seroconversion. A further eighteen patients who received the same batch did not seroconvert and one other patient became seropositive but had not received this batch. Before transfusion of the implicated batch the patients had low T-helper-cell numbers and T-helper/suppressor ratios; neither changed in those who seroconverted. The probability of seroconversion was independently related to the pre-existing low T-helper/suppressor ratio, the number of vials of the implicated batch transfused, and the total annual factor VIII consumption. Ten other patients received a batch of factor IX concentrate from the same donor plasma; none of these patients seroconverted.

Acquired Immunodeficiency Syndrome↗

Immune hepatitis B plasma procurement.

The requirement for hepatitis B immunoglobulin for passive immunisation persists despite the availability of a safe hepatitis B vaccine, and there is therefore a need for immune plasma for immunoglobulin production. We have screened a large number of blood donors to identify potentially suitable hepatitis B immune plasma donors. The logistics of this have been examined, and the programme was found to be inefficient and labour-consuming. A suitably designed programme of active immunisation with hepatitis B vaccine should provide a more effective means of obtaining plasma.

Blood Donors↗

Macroaggregate formation in optimal additive red cells.

The formation of macroaggregates weighing up to 9 g was observed in optimal additive red cells. Such aggregates, with a mean wet weight of 3 g, formed progressively during storage and were present in up to 85% of units. They were composed of leucocyte and platelet debris, together with some fibrin. Macroaggregates formation was halved by less stringent centrifugation during preparation and was reduced by use of an optimal additive system in which the additive solution contained citrate. Extra mixing during transfer of the additive solution only delayed aggregate formation. Partial leucocyte depletion or addition of 200,000 KIU of the enzyme inhibitor aprotinin did not prevent macroaggregate formation.

Blood Preservation↗

A mouse monoclonal antibody with anti-A,(B) specificity which agglutinates Ax cells.

A hybridoma (ES-15) was obtained by fusing the NS-1 cell line with spleen cells from a mouse immunised with soluble blood group A2 substance. The cloned hybridoma culture supernatant was shown to contain an IgM class antibody which strongly agglutinates group A cells and weakly agglutinates group B cells. The serological specificity of this antibody is described as anti-A,(B) in this report. The abilities of unconcentrated monoclonal anti-A,(B), a commercial human polyclonal anti-A,B (group O serum) and a commercial monoclonal anti-A reagent to detect 15 examples of Ax cells were compared by both slide and tube techniques. Using a slide technique monoclonal anti-A,(B) agglutinated 14 examples of Ax cells, human anti-A,B 2 examples, while monoclonal anti-A failed to detect any of the Ax cells tested. Similar differences in the reactivity of the three antibodies were observed using a tube technique. Data are also presented which show that a 1:1 (v/v) mixture of monoclonal anti-A,(B) with a monoclonal anti-B reagent is an effective replacement for human anti-A,B in ABO grouping procedures.

ABO Blood-Group System↗

Clinical use of immunoglobulins.

The use of immunoglobulins for prophylaxis and therapy are reviewed. Normal and hyperimmune immunoglobulins have well established clinical applications. These are summarized in Table 14. This form of therapy has now entered a period of rapid change due to the availability of human immunoglobulins which are safe for intravenous use, permitting large doses to be given rapidly. This will permit reappraisal of many conventional applications and exploration of new possibilities for the use of these products. The approaching wide availability of monoclonal antibodies for clinical use will open up a further wide range of new therapeutic applications, providing that concerns over the products' safety are allayed .

Antibodies, Monoclonal↗

Experiences in the production of human monoclonal antibodies to tetanus toxoid.

The production of human monoclonal antibodies has been attempted using tetanus toxoid as a model antigen since a human antibody of this specificity could have clinical applications. Both mouse and human myeloma cell lines were used as fusion partners and the effects of in vivo and in vitro antigen boosting were also investigated. A cell line, ES12, which secreted specific tetanus toxoid antibody arose following fusion of lymphocytes from a donor who had been boosted three months earlier. Antibody was secreted by this cell line at a high titre (2.5 I.U/ml); it was of IgG isotype and it protected mice against challenge with tetanus toxin. This is, therefore, a first step in producing a therapeutically useful monoclonal antibody.

Animals↗

Protein concentrations in fluid from gross cystic disease of the breast.

Wide variations in the concentrations of IgA, IgG, lactoferrin, lysozyme and albumin were found in 96 cyst fluids obtained from 75 patients with gross cystic disease of the breast. Sedimentation coefficient determination were performed on 19 of the cyst fluids with the highest IgA concentrations in an attempt to discover the basis for the wide variation and two types of cyst fluids were found: cyst fluids that resembled external secretions such as colostrum of milk with the IgA wholly or predominantly in the 11S (secretory) form, and low concentrations of IgG and albumin, and cyst fluids that resembled serum with the IgA wholly or predominantly in the 7S (serum) form, and high concentrations of IgG and albumin. Some cyst fluids contained low concentrations of all proteins measured, and no relationship was observed between the concentrations of the proteins studied, and age, parity or menstrual status.

Adult↗

Humoral defence factors in the breast milk of Ethiopian women with leprosy and healthy controls.

Secretory IgA, lactoferrin, albumin, and total protein were quantitated in colostrum and milk samples obtained from 215 Ethiopian nursing mothers over a period ranging from 1 day to 2 yr postparturition. IgG, IgM, C3, and C4 complement components were quantitated in 11 day 1 samples. The subjects were classified into three groups: lepromatous leprosy, borderline lepromatous leprosy, and a nonlepromatous group consisting of women with tuberculoid leprosy and healthy controls. Results obtained from the above groups were also compared with a group from Edinburgh. No major variation in levels of secretory IgA, lactoferrin, albumin, and total protein was found between the three groups of Ethiopian women. Results from the Edinburgh group were significantly higher, mainly in the level of total protein. When the individual proteins were expressed as a percentage of the total protein, there was no difference between the milk samples from the Ethiopian and Edinburgh mothers.

Albumins↗

Hyperimmune immunoglobulin therapy for cytomegalovirus infections in renal transplant patients.

Eleven renal transplant patients with CMV infection have been treated by passive immunisation, one with high-titre anti-CMV plasma and 10 with fractionated hyperimmune anti-CMV immunoglobulin. All were pyrexial for at least seven days before treatment with typical clinical and laboratory features of CMV infection. Seven of the 11 patients treated showed a striking and sustained response within 24-48 hours of therapy, with lysis of fever, resolution of pneumonitis, a rise in white cell count and improvement in renal function and liver function tests.

Adolescent↗