Woman & the Midwives Chronicle.
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Biomedical subjects
Publications and source records attributed to G Inglis.
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Eleven patients were reviewed an average of 23 years after they had been treated by excision of a symptomatic calcaneonavicular bar in 16 of their feet. Of these feet 69% (11 feet) had a good or excellent result. Of the five failures, three feet had good results after subsequent triple arthrodesis, but two treated by repeated excision of the bar were still unsatisfactory. Beaking of the talus seen before operation correlated with poor results.
The inhibitor of human renin, H142, was studied in nine male volunteers. On three occasions, in random order, volunteers were infused with 5% dextrose or with H142 at 1.0 or 2.5 mg/kg per h for 30 min while supine and thereafter with dextrose for 1 1/2 h. There was a marked reduction in plasma active renin concentration as assayed by an enzyme-kinetic method, with parallel falls in the circulating concentrations of angiotensins (ANG) I and II, all of which rebounded transiently to values above basal after the H142 infusion was stopped. In contrast, total renin concentration as measured by radio-immunoassay rose while ANG I and II fell, subsiding when H142 was discontinued. There was a slight but significant increase in plasma noradrenaline as renin became inhibited; plasma adrenaline was unchanged. H142 produced a slight fall in systolic blood pressure (SBP) and a clearer, highly significant, dose-related fall in diastolic blood pressure (DBP). There was a modest but significant increase in the heart rate. These studies confirm H142 as an effective inhibitor of human renin in vivo.
Two mouse monoclonal antibodies with specificity for the Lea blood group determinant of human red cells have been produced by immunising mice with soluble Lewis substance. Both antibodies were of the IgM class and agglutinated only trypsinised or papainised Lea-positive red cells. The precise antigenic conformations recognised by these antibodies have been defined by inhibition studies with monosaccharides, disaccharides and synthetic blood group oligosaccharides. These studies have suggested that the alpha-side of a 1-substituted D-galactosyl residue is a central part of the determinants recognised by the antibodies. Preliminary studies have shown these antibodies to be superior to many of the presently available human and animal polyclonal reagents for routine Lea typing of red cells.
In order to get more standardized reagents for blood group typing and to get more information on the chemical nature of blood group antigens we have immunized Balb/c mice with whole red blood cells and with sialoglycoprotein fraction from group OMMss cells. As fusion partners mouse myeloma cell lines P3-NS1/1-Ag 4-1 and X63-Ag8.653 were used. Several monoclonal antibodies were obtained, which showed specificity for the M/N antigens. Because of the relationship between M and N antigens this system is a very good example for studying the influence of different parameters on the reactivity of monoclonal antibodies. Each monoclonal antibody behaves like an individuum and for each antibody the dependence of the agglutination reaction of temperature, pH, buffer for dilution and medium, in which the reaction takes place, has to be investigated. Otherwise the results are not comparable and unspecific reactions might occur. By standardizing these parameters specific reactions were obtained and the antibodies might be used as routine reagents.
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The incidence and characteristics of P1-antibodies in Scottish pigeon fanciers has been assessed. Of 223 individuals participating in the study, 23.3% were P1-negative and of these, 53.9% had detectable P1-antibodies. These antibodies were shown to belong to the IgM class and the highest serum levels were found in those pigeon fanciers with symptoms of respiratory disease who were sensitized to pigeon antigens. Of pigeon fanciers' sera, 10.3% gave false positive reactions for the Hepatitis B surface antigen in a reversed passive haemagglutination test. The reactions were most prevalent in sensitized fanciers and were shown to be directed not against the absorbed HBsAg antibody, but against the turkey red cells used as carriers in the test. No relationship was observed between the existence of P1-antibodies and false-positive hepatitis reactions. It was concluded that the inhalation of avian antigens by pigeon fanciers can induce the production of at least three distinct populations of antibodies. No evidence was obtained to imply any special role for P1-antibodies in the aetiology of pigeon fanciers' disease.
An investigation of the serological and biochemical properties of red cells in two unrelated British families revealed the probable presence of examples of the rare genotype EnaEn. In one family the En-modified red cells carried N-like determinants associated with s. In the other family M-like determinants associated with S were found.
Tk polyagglutinable erythrocytes are described in which A and H activities were reduced. It is suggested that Bacteroides fragilis isolated from cultures of the patient's blood was responsible for each of these membrane modifications.
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A new type of polyagglutination is described in which the T and Tk receptors are both exposed on the erythrocyte membrane. It is suggested that there may be an association between this type of polyagglutination and infection by Bacteroides fragilis.
Incubation of normal human erythrocytes with the supernatant of centrifuged culture of some strains of Bacteroides fragilis results in the exposure of Tk polyagglutination determinants on the erythrocyte membrane. These determinants are present on non papain-labile structures and are probably exposed by an enzyme mechanism. Other strains of B. fragilis were found to produce neuraminidase, haemolysins, and protease. It is suggested that early recognition of Tk determinants may be an aid to the diagnosis of B. fragilis infection.
By observing the aggregation of erythrocytes in protamine sulphate or Polybrene it is possible to predict MN phenotypes with 97 per cent accuracy. It is probable that one factor influencing aggregation is the relative site density of a receptor common to both M and N antigen structures although other nondiscriminating receptor sites on a lower layer of sialic acid are possible also involved.
Four mouse monoclonal antibodies were produced with specificities related to human blood group M antigen. The antibodies react in direct hemagglutination systems, and their specificities were investigated by their reactions with variant and enzyme-modified red cells. The effects of temperature and pH on their hemagglutination reactions also were investigated, and all four were murine IgG antibodies. Physicochemical and serologic investigations showed them to be four distinct antibodies, and each one could be used for M blood grouping under appropriate conditions.
Mouse monoclonal anti-Lea produced in this center was found to agglutinate only Le(a+) red cells which had been modified with proteases. In order to provide a stable medium in which the monoclonal anti-Lea would directly agglutinate unmodified red cells, the potentiating effect of a variety of colloids was assessed. Satisfactory results were obtained when 10 percent (wt/vol) dextran and 2 percent (wt/vol) bovine serum albumin were added to the culture supernatant containing anti-Lea. It is suggested that direct hemagglutination mediated by these colloids resulted from a combination of increased antibody uptake by Le(a+) red cells and change in the shape of these red cells induced by dextran.
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A directly agglutinating murine monoclonal antibody of the IgG3 isotype has been produced after mice were immunized with papain-treated Bombay phenotype, e-positive red cells (RBCs). The antibody strongly agglutinated all e-positive RBCs and gave negative reactions with RBCs from Rhnull persons and those homozygous for Rh deletion genes. Variable reactivity was found with e-negative RBCs, ranging from weak to negative with R2R2, slightly stronger with r"r", and stronger still with RzRz. These reactions, together with results from tests with a large panel of Rh-variant RBCs, suggested a specificity for an epitope that is part of the e mosaic but is also expressed at least partially on e-negative RBCs and is influenced by the presence of C. This antibody has been standardized for use as a screening reagent for R2R2 cells by a microplate technique, and over 6000 donations have been screened in this way. No discrepancies have been found in confirmatory tests for e-negative status using human anti-e.