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Biomedical subjects

R A Thompson

Publications and source records attributed to R A Thompson.

At least 91 records · Page 5Linked to original sources

Cellular immunity in congestive cardiomyopathy. The normal cellular immune response.

In vivo and in vitro tests of cellular immunity were studied in patients with congestive cardiomyopathy to determine whether these patients have normal or depressed cell mediated immunity to common environmental antigens and mitogens. No abnormality was found, but this does not exclude the possibility that transient depression of cell mediated mechanisms occurs early in the illness before clinical presentation.

Cardiomyopathy, Dilated↗

Cellular immunity in congestive cardiomyopathy. Hypersensitivity to cardiac antigens.

The presence of type IV hypersensitivity to cardiac antigens in 26 patients with congestive cardiomyopathy was sought by two in vitro techniques. Neither test showed a significant group abnormality, but 10 patients did have hypersensitivity to heart antigen, in particular to congestive cardiomyopathic heart antigen. These patients were characterised by worse haemodynamic data and a more rapid and malignant course of the disease than in the rest of the group.

Antigens↗

Characterization of patients with an increased susceptibility to bacterial infections and a genetic deficiency of leukocyte membrane complement receptor type 3 and the related membrane antigen LFA-1.

Three children from two unrelated families had a history of recurrent bacterial infections, and their neutrophils were shown to have deficient phagocytic and respiratory responses and possible deficiencies in chemotaxis or adherence. Their neutrophils were strikingly deficient in the ability to ingest or give a respiratory burst in response to unopsonized bakers' yeast or zymosan (Z). Tests for neutrophil and monocyte CR1 (C3b/iC3b receptor) and CR3 (iC3b receptor) demonstrated rosettes with both EC3b and EC3bi. However, EC3bi were bound only to CR1, and not to CR3, because EC3bi rosettes were inhibited completely by anti-CR1. Neutrophils, monocytes, and natural killer (NK) cells also did not fluorescence stain with monoclonal antibodies specific for the alpha-chain of CR3 (anti-Mac-1, anti-Mol, OKM1, and MN-41). Quantitation of C receptors with 125I monoclonal anti-CR1 and anti-CR3 indicated that neutrophils from each patient expressed normal amounts of CR1 per cell but less than 10% of the normal amount of CR3. Examination of neutrophils by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that a normal glycoprotein of approximately 165,000 daltons was missing. Immunoblotting of these gels indicated that the missing band was the alpha-chain of CR3. Subsequent analysis of all three patients' cells also demonstrated a deficiency of LFA-1 alpha-chain and the common beta-chain that is shared by the CR3/LFA-1/p150,95 membrane antigen family. The deficiency of LFA-1 probably explained the absent NK cell function, as normal NK cell activity is inhibited by anti-LFA-1 but not by anti-CR3. The reduced phagocytic and respiratory responses to Z were probably due to CR3 deficiency, because treatment of normal neutrophils with anti-CR3, but not anti-FLA-1, inhibits responses to Z by 80% to 90%. Ingestion of Staphylococcus epidermidis by normal neutrophils was shown to be partially inhibited by monoclonal antibodies to the alpha-chain of either CR3 or LFA-1, and monoclonal antibody to the common beta-chain inhibited ingestion by 75%. Thus, both CR3 and LFA-1 may have previously unrecognized functions as phagocyte receptors for bacteria. The absence of this type of nonimmune recognition of bacteria by these children's neutrophils may be one of the reasons for their increased susceptibility to bacterial infections.

Antigens, Surface↗

Inappropriate responses to Mycobacterium leprae infections--C reactive protein in man and serum amyloid P in mice.

In a study of C-reactive protein (CRP) levels in the sera of 77 patients with leprosy, it was found that in the majority of newly diagnosed patients, the level was within the normal range for a healthy Malaysian population. Elevated levels did occur, but were usually found in patients with complications, and were more likely to occur in patients who had been receiving drug treatment for some time. This suggested that Mycobacterium leprae infection by itself does not stimulate CRP synthesis and could reflect a failure of synthesis by macrophages of interleukin-1, or related molecules. This was supported by the study of an analogous acute phase protein, serum amyloid P (SAP) in mice bearing M. leprae from human sources in their hind footpads. Such mice showed no significant difference in SAP levels from control mice.

Amyloid↗

Tuberculin response two years after BCG vaccination at birth.

One hundred and forty nine Asian children who received BCG vaccine shortly after birth were reviewed at the age of 22 months. Many of them had an apparently inadequate response to the vaccine. A quarter had no scar, and half of the children with a scar had a negative response to 10 TU (Mantoux 1/1000) and these children showed only limited lymphocyte transformation in vitro in response to tuberculin. Various measurements of health at age 22 months suggested the Mantoux negative children were less privileged than the Mantoux positive ones, but the differences were not striking and most were not significant. It seemed more likely that the high incidence of poor response was due to some factor operating in the perinatal period. There was circumstantial evidence implicating perinatal nutrition, and there is a theoretical possibility of interference with vaccination by maternal antibody.

BCG Vaccine↗

Postcoronary pain and the postmyocardial infarction syndrome.

Since non-specific chest pain, which is a common feature after myocardial infarction, may be due to a mild form of Dressler's (postmyocardial infarction) syndrome 80 patients were studied after confirmed myocardial infarction. Two patients had clinical features of classical Dressler's syndrome with high erythrocyte sedimentation rates and strongly positive results for antimyocardial antibodies. Twenty three patients had non-specific chest pain; none had clinical features of Dressler's syndrome. There was no difference in the erythrocyte sedimentation rate between this group and the remainder who had no pain. Equal numbers in each group had weakly positive test results for antimyocardial antibodies; none had a strongly positive result. Thus there appears to be no evidence for a mild form of Dressler's syndrome, and the erythrocyte sedimentation rate and weakly positive results for antimyocardial antibodies are of no diagnostic value in Dressler's syndrome.

Antibodies↗

Severe acute polyarthropathy associated with levamisole therapy in a patient with Crohn's disease.

A 17 year old Caucasian youth with intractable Crohn's disease developed a severe, acute polyarthropathy during a second course of levamisole therapy. Rapid resolution of systemic symptoms occurred on stopping the drug but full joint recovery was not achieved until five months had elapsed. The relationship of levamisole to Crohn's disease and the underlying mechanisms of the polyarthropathy are discussed.

Acute Disease↗

Familial defect of polymorph neutrophil phagocytosis associated with absence of a surface glycoprotein antigen (OKMI).

Two siblings with delayed separation of the umbilical cord, recurrent skin ulceration and dental sepsis were shown to have defective neutrophil phagocytosis of opsonized yeast (S. cerevisiae) and respiratory burst to opsonized and unopsonized zymosan. Increased activity in the NBT reduction test, normal ingestion and killing of S. aureus, and normal spontaneous and directional motility were also demonstrated. These abnormalities of neutrophil phagocytosis were confined to the affected siblings; their healthy parents and brother showed normal neutrophil function. Both children had a polymorph neutrophil leucocytosis, and had normal humoral and cell-mediated immunity. SDS electrophoresis of neutrophil cell membrane preparations showed absence of a glycoprotein band of 175,000 daltons, which was present in the parents' neutrophils in reduced amounts. OKMI monoclonal antibody, which recognized the C3bi receptor (CR3) failed to bind to the affected siblings neutrophils. The findings in these children emphasize the importance of this receptor in phagocytosis, and possibly other neutrophil functions.

Antigens, Surface↗

How necessary are specific IgE antibody tests in allergy diagnosis?

In a 12-month study 301 patients referred to hospital consultants with putative allergic symptoms were tested for specific IgE antibodies to a panel of allergens and for total serum IgE levels. Examination of the data in relation to clinical information and the results of skin prick tests showed that the specific IgE antibody test has a limited role in the investigation of such patients.

Adolescent↗

Characterization of a non-functional form of C1q found in patients with a genetically linked deficiency of C1q activity.

A genetically defective form of C1q was purified from the sera of patients suffering from an immune complex related disease and who were homozygous for the defect. The defective C1q was haemolytically inactive and did not bind to immune aggregates or IgG-Sepharose. It showed the following similarities to the normal C1q molecule: a high glycine content and the presence of hydroxyproline and hydroxylysine; subunits with apparent mol. wts of 70,000 and 56,000, when examined by SDS-polyacrylamide gel electrophoresis under non-reducing conditions; preferential incorporation of 125I-label into only one of the types of chain present in the molecule, in a manner similar to that found for the C-chain of normal C1q. However, the defective molecule had an apparent mol. wt of approximately 155,000 in non-dissociating conditions, which is approximately one-third of the mol. wt of the normal molecule. Also, the material in the defective molecule preparation which corresponded, on the basis of mol. wt, to the disulphide-linked A-chain-B-chain dimer of normal C1q differed from that found in the normal molecule in that it did not appear to be sensitive to reducing agents. Collagenase and pepsin treatment of specific immunoprecipitates containing the radiolabelled defective molecule indicated that it is, like the normal molecule, composed of collagenous and non-collagenous domains.

Amino Acids↗

Humoral immunity in cardiomyopathy.

Sera from patients with heart disease were examined by single sandwich indirect immunofluorescence for the presence of antibodies to human heart muscle. Endocardial biopsy specimens were also examined by direct immunofluorescence for deposition of antibodies in vivo. No consistent or specific abnormality was found in the biopsy specimens or sera of patients with congestive cardiomyopathy. The presence of anti-heart antibodies in cardiac disease appears to reflect damage to cardiac muscle whatever the cause. Immunofluorescence is an insensitive test for anti-heart antibodies.

Antibody Formation↗