Biomedical subjects
Publications and source records attributed to J F Soothill.
Passively transferred MOPC 315 IgA myeloma protein accelerated the elimination of DNP-ovalbumin, to which the myeloma protein bound with antibody-like affinity, from the circulation and increased the subsequent antibody response to hapten and to carrier, when injected with or without adjuvant.
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In six infants, from two families. the umbilical cords were still attached at 3 weeks of age. Five of these developed severe local and disseminated infections from which four died. Two of these children were tested, and both, including the survivor, had defective neutrophil mobility; in the survivor this was improved in vitro and in vivo by ascorbic acid. It is suggested that a primary genetic defect of a contractile protein could explain the association. The sixth child, with delayed cord separation but normal neutrophil mobility and no excess of infections, who has survived without special treatments, also has mastocytosis, apparently inherited independently.
Selected immunologic functions were assessed in 14 patients with the Shwachman syndrome. Nine patients were neutropenic and four had low levels of IgA or of IgM. Neutrophil mobility was significantly defective in the group of patients as a whole (in 12 it was below the lower limit of normal) and in their parents. No other consistent abnormality in immunity was found. These results suggest that the defective neutrophil mobility is a feature of Shwachman syndrome which may contribute to the vulnerability of these patients to frequent infections. The defect appears to be a primary genetic one, inherited as an autosomal recessive characteristic consistent with the assumed inheritance of Shwachman syndrome.
IgG-containing antigen-antibody complexes were detected in the sera of all of 7 patients with the systemic form of juvenile chronic arthritis, usually at high levels. Only 9 of 25 patients with the polyarticular form had such complexes, usually at low levels. Three patients had low levels of serum IgA which were probably drug induced; the one patient with low C2 and the 3 with low yeast opsonisation were probably not more than to be expected in a random population.
In a controlled trial, symptomatic treatment alone, or 12 weeks of cyclophosphamide or azathioprine were compared in Nigerian children with nephrotic syndrome (mainly quartan malarial nephropathy) and poorly selective proteinuria. Full remission in 2 patients in each of the two groups treated with drugs, and diminution of proteinuria in most patients in the cyclophosphamide group showed possible evidence of benefit. Infections during treatment were significantly more common in the drug-treated groups but were controllable. Mortality from renal failure in the 2nd year after treatment was significantly greater in the azathioprine-treated group than in the other two, suggesting that the drug may have exacerbated the nephritis. The 5-year survival rate was similar in the cyclophosphamide and the control group.
Six children, with severe deficiency of some or all of the immunoglobulins and minor somatic abnormalities, had chromosomal abnormalities: (1) 45,XY,t(13q/18q), (2) 46,XY,21ps +, (3) two brothers 46,XY (inv. 7) (4) 45,X,t(11p/10p)/46X,iXq,t(11p/10p) and, (5) in addendum, 45,XX,-18;46,XX, r18. The chromosome abnormalities were detected in B- as well as T-lymphocytes (as evidenced by using both PHA- and PWM-stimulated cultures) in all probands, but one was mosaic in PHA culture, although all his PWM-stimulated cells were abnormal. Chromosomal variants were also detected in relatives of three and immunodeficiency in relatives of two.
Antigenic proteins may be absorbed intact. We report here results from in vivo experiments in mice showing that the prior feeding of protein antigen may reduce the subsequent absorption of that antigen without altering its elimination from the circulation. This may be a function of local immunity. We have also shown that the same feeding regime can paradoxically induce a state of systemic tolerance and suggest that the two phenomena contribute to the safe handling of these antigens.
Thymidine uptake in PHA-stimulated culture of cord blood cells from smoking mothers is greater than that from non-smoking mothers. There was no such difference when separated lymphocytes were studied; this suggests that smoking suppresses a suppressor cell. No difference was detected in haemoglobin, immunoglobulins, transferrin, cell counts, E-rosette counts and leucocyte mobility.
Hyposensitisation with Dermatophagoides pteronyssinus tyrosine absorbate in asthmatic children with bronchial sensitivity to D. pteronyssinus was effective in a 12-month double-blind controlled clinical trial. Compared with controls, treated children used a smaller quantity of drugs while maintaining clinical and lung function improvements. In most children who improved there was no change in immediate response to D. pteronyssinus on bronchial provocation test, but the late reaction was lost in half the patients and these showed the greatest improvement in symptoms.
Macrophages and neutrophils from human milk phagocytose and kill Staphylococcus aureus and Escherichia coli in vitro after opsonisation by the aqueous phase of milk as effectively as blood leucocytes in serum. They also phagocytose Candida albicans. The overgrowth of E coli resulting from the addition of iron to cultures of the organism in the aqueous phase of milk is not influenced by the presence of cells. We conclude that the phagocytosis and killing of bacteria by milk cells may contribute to the lower incidence of infection among breast-fed than artificially fed babies.
20 out of 36 children (aged two to eight years) with atopic eczema completed a twelve-week, double-blind, controlled, crossover trial of an egg and cows' milk exclusion diet. During the first and third four-week periods, patients on an egg and cows' milk exclusion diet received a soya-based milk substitute (trial period) or an egg and cows' milk preparation (control period). Response was assessed in terms of eczema activity, number of areas affected, pruritus, sleeplessness, and antihistamine usage while on the two diets. During the middle period patients resumed their normal diet to minimise any carry-over effect. 14 patients responded more favourably to the antigen-avoidance diet than to the control diet, whereas only 1 responded more favourably to the control diet than the trial diet. Patients experienced more benefit during the first diet period than the second, whatever the nature of the diet. There was no correlation between a positive prick test to egg and cows' milk antigen and response to the trial diet.
We analyzed serums from 39 children with steroid-responsive nephrotic syndrome for the presence of circulating soluble immune complexes. Seventeen of 18 children in relapse had raised levels of IgG complexes: median titers were significantly higher in these patients than in control children (P less than 0.001) or in nephrotic children in sustained remission (P less than 0.001). Seven of nine children followed sequentially had raised complex levels in early remission but became normal after six weeks in remission. In contrast to patients with systemic lupus erythematosus these IgG complexes were not able to bind C1q. Serums from five patients in relapse contained complexes intermediate in size (2 to 2.5 X 10(6) daltons) as compared to those seen in systemic lupus erythematosus, and four of the five had small complexes as well (3 to 5 X 10(5) daltons). These findings suggest that immune complexes may have a pathologic role in steroid-responsive nephrotic syndrome, but the mechanism by which proteinuria is effected remains unclear.
A controlled trial of disodium cromoglycate treatment of steroid-responsive nephrotic syndrome failed to show a therapeutic effect on the tendency to relapse after withdrawal of corticosteroids.
Twenty-eight patients with defective neutrophil mobility were classified, largely on results of parent values, into primary (17)--mainly Shwachman's syndrome--and probable secondary (11). They presented with frequent infections and/or allergy and these symptoms were essentially similar in both groups. Neutropenia was virtually confined. to the patients with Shwachman's syndrome. Diagnoses associated with secondary neutrophil mobility defects included hydrocephalus with shunt, cystic fibrosis, and immunoglobulin deficiency. The neutrophil mobility of nearly nearly all the patients studied increased when levamisole was added in vitro, but there was no clear evidence of clinical benefit when patients were given the drug.
Diphenylhydantoin (DPH) depresses serum IgA and IgM concentrations and polyvinyl pyrrolidone (PVP) clearance in mice.
Twenty-seven per cent of atopic patients initially presenting with infantile eczema or hay fever were defective for yeast opsonization and 18% had low levels of C2; these deficiencies were mutually exclusive, suggesting that they are primary. Both defects were associated with each of four different atopic syndromes, some of which were related to certain HLA haplotypes.