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Biomedical subjects

S Whittingham

Publications and source records attributed to S Whittingham.

At least 73 records · Page 4Linked to original sources
PubMed1978

Levamisole: lack of immunopotentiation in a controlled trial.

The immunopotentiating effect of levamisole was assessed in a double-blind trial in two comparable groups of patients with Down's syndrome, with which the immunodeficiency and susceptibility to infection are known to be associated. One group was given levamisole continuously and at the same dose for 16 weeks, and the other group was given placebo tablets. A checklist was designed to record the type, frequency, and duration of all infections which occurred in the patients, and delayed type hypersensitivity responses to various antigens were measured. There were no differences between the two groups in body weight, number of intercurrent infections, duration of illness, nor was there any change in degree of depression or cutaneous delayed-type hypersensitivity. These findings, taken with claims of success in some patients and failure in others, suggest that levamisole is not a general immunopotentiating agent, although it may have a specific site (or sites) of action on the immune system. If levamisole is to be used more selectively, this action needs to be characterized.

Adult↗
PubMed1978

Localization of genetic control in mice over response to liver-specific F antigen.

Antibody production to the liver-specific F antigen was tested in recombinant strains of mice of different H-2 types to determine whether a histocompatibility-linked immune response (Ir) gene controlled responsiveness to this antigen. Responseiveness was found to be controlled by an Ir gene located in the K end (K and/or I-A subregions) of the H-2 complex.

Animals↗
PubMed1978

A 'profile' of immune responsiveness in multiple sclerosis.

An 'immunological profile' of various indices of B-cell function and T-cell function was developed for the 'early' case of multiple sclerosis (MS). This was compared against two groups of controls comprising age and sex-matched healthy subjects, and patients with other disabling neurological diseases (CNS controls) who were matched for age, sex, and type and duration of disability. Some indices of humoral immune responsiveness, such as the induced primary response to monomeric flagellin and the 'resting' levels of antibody to measles and rubella viruses, showed significant augmentation. Cellular immune deficits were attributed to an illness effect per se because (a) cell-mediated immunity was depressed, but only when compared with that of healthy subjects and not when compared with that of the CNS controls, and (b) transformation responses of lymphocytes to viral antigens were inversely related to disability status. The abnormalities in humoral immune responses demonstrable in this study do not provide an explanation for this disease; if there is a relevant 'immunological fault', the nature of this needs to be sought from within the neuraxis rather than from the systemic circulation.

Adult↗
PubMed1978

Werner's syndrome: a model of premature aging?

A 34 year-old woman with Werner's syndrome has been studied in the light of the current concept that this disorder is a model of premature aging. Endocrine function assays revealed an abnormal glucose tolerance and in vivo insulin insensitivity after prednisolone, and ovarian failure. Immune function assays revealed hypo-responsiveness in skin tests for delayed hypersensitivity, a poorly sustained IgG anti-body response after immunization with flagellin, and a low count of colony-forming T lymphocytes in blood. Cultured fibroblasts had a very limited capacity to replicate in vitro, in comparison with donors of similar age and, moreover, 85% of glucose-6-phosphate dehydrogenase in the patient's cultured fibroblasts was heat-stable at 60 degrees C compared with 100% for a healthy control. Cell receptors (for insulin) were examined by insulin binding to isolated fat-cells, with the finding that fat-cells were abnormally large for the patient's size, and their receptor density was low. The findings from the study point to a genetic defect in Werner's syndrome which, in its effect on particular tissues, may simulate features of aging, but the disease is not a true model of premature aging.

Adult↗
PubMed1978

Cloning of T-lymphocytes in systemic lupus erythematosus.

Colony-forming T-lymphocytes were studied in the blood of twenty-two patients with systemic lupus erythematosus (SLE) by the technique of plating phytohaemagglutinin (PHA) stimulated lymphocytes in soft agar. The mean count of T-lymphocyte colonies in SLE of 70+/-64 (1 s.d.)/mm3 of blood was considerably less than the count of 218+/-102/mm3 for healthy young adults and of 139+/-99/mm3 for aged persons. In SLE, counts of T-lymphocyte colonies correlated with low counts of T-lymphocytes in blood and with other indices of T-lymphocyte impairment. The data point to derangement of factors which influence the capacity of T-lymphocytes to proliferate, but it cannot be stated to what degree this is a cause and/or result of the autoimmune disease process associated with SLE. Cloning of peripheral blood T-cells could help determine whether the essential defect in SLE is in the T-lymphocyte or one of its sub-sets, or in factors produced by adherent cells which are essential for growth in vitro of T-lymphocyte colonies.

Adolescent↗
PubMed1978

Factors influencing the secondary antibody response to flagellin in man.

The secondary antibody response to 5.0 microgram flagellin was studied by haemagglutination in 132 healthy or convalescent subjects given a primary challenge with 5.0 microgram flagellin from 1 to 44 months previously. The peak titre, expressed as total antibody, occurred at 2 weeks and was mainly immunoglobulin (Ig)G. The magnitude of the titre of total antibody was influenced predominantly by that of total antibody in the primary response (P less than 0.001), the interval between primary and secondary responses (P less than 0.005) and the subjects' age (P less than 0.05) and sex (P less than 0.08). Together these accounted for 23% of the variability observed in the secondary response, with total antibody titre in the primary response accounting for 11% of the variability. The titre of IgG antibody was likewise influenced by these four variables, but the influence of age or sex on IgG antibody was not statistically significant. In human vaccination programmes, choice of the appropriate interval between primary and booster inoculations could increase prophylactic effectiveness and, if two inoculations were to prove as effective as three, there would be reduced work and increased public acceptance. Moreover, the demonstrable capacity for responsiveness of aged and debilitated persons should encourage the wider use of appropriate prophylactic immunization in these groups.

Adolescent↗
PubMed1977

Stress deficiency of the T-lymphocyte system exemplified by Down syndrome.

A comparison of immune competence in 26 patients with Down syndrome in an institution and 26 matched healthy controls revealed an atypical pattern of T-cell immunodeficiency in the Down-syndrome patients. The patients with Down syndrome had a lymphocytosis in blood with high counts of T (and B) cells, but with impaired effector function of T cells as judged by anergy to dinitrochlorobenzene, low responsiveness to ubiquitous antigens which elicit delayed-type hypersensitivity reactions, and low mitogenic activity of non-stimulated and phytohaemagglutinin-stimulated lymphocytes in culture. Helper-T-cell function measured by the humoral immune response to flagellin was intact, and there were minor abnormalities of the B-cell system. Attempted restoration of T-cell function with levamisole was unsuccessful. This pattern of T-lymphocytosis with impaired effector function could be explained by "stress-deficiency" of the immune system consequent upon a heavy load of infection in early life.

Adolescent↗
PubMed1977

Tissue antigens: autoantigens, alloantigens, xenoantigens and neoantigens.

The subject of Clinical Immunology is developing hand in hand with a wide and rapidly moving area of laboratory technology. The result is a better understanding of autoimmune disease, tissue transplantation rejection, foetal-maternal incompatibility, allergic disease, immunodeficiency disorders, adverse reactions to drugs, aberrant responses to bacterial and viral infections, and growth and spread of malignant cells. Basic to this understanding is the need to appreciate the character and composition of natural substances which act as immunogens and elicit antibodies. These substances have, according to their origin, been classified as autoantigens, alloantigens, xenoantigens and neoantigens. This review summarizes our knowledge relating to such antigens, emphasizing those aspects relevant to human disease and pointing to the major gaps that future research must bridge.

Animals↗
PubMed1977

Colony formation by human T lymphocytes in agar medium.

An improved method is described for growing human T-lymphocyte colonies in agar medium containing phytohaemagglutinin (PHA) and sheep red blood cells (SRBC). Cluster and colony growth was obtained when blood mononuclear cells were plated directly in the agar-medium (one-step procedure) or after incubation of cells in liquid medium with PHA (two-step procedure). In the one-step procedure approximately 1 per 100 cells plated formed a cluster containing four to fifty cells. In the two-step procedure 1 per 20 cells plated formed a cluster or a colony (more than fifty cells). The proliferating cells were shown to be sheep-erythrocyte rosette-forming cells (E-RFC). Optimal proliferation was dependent on the presence of phagocytic cells in the cell suspensions cultured. No growth occurred in cultures depleted of E-RFC. Detailed studies of the cycle, velocity sedimentation, and density of the cells plated showed that the majority of cluster- and colony-forming cells were small non-cycline lymphocytes with a sedimentation velocity of 4 mm/hr, and a density between 1-069 and 1-077 g/cm3.

Agar↗
PubMed1976

Adverse reactions to drugs: relationship to immunopathic disease.

Immunopathic disease resulting from drug treatment occurs when drugs interact with lymphoid cells and induce an immunological reaction. Drugs, being foreign to the body, are immunogenic, either as such or as haptens bound to carrier proteins. The immune response is usually innocuous or unnoticed but occasionally becomes pathogenic. The impact is especially obvious when the immunopathic response affects blood, skin, liver or kidney. Immunopathic responses and effector mechanisms of injury, whether to drugs or other antigens, are considered in terms of four types: Type I--anaphylactic and mediated by immunoglobulin (Ig) E antibody, and exemplified by immediate penicillin reactions; Type II--cytolytic and complement-associated, mediated by IgG antibody, and exemplified by haemolytic reactions; Type III--vasculonecrotic (Arthus reaction), mediated by immune complexes, and exemplified by serum sickness-like reaction; Type IV--delayed hypersensitivity involving T lymphocytes but no antibody, and exemplified by contact dermatitis. In addition, certain drugs induce true autoimmune reactions exemplified by reactions to procaine amide (lupus erythematosus) and alpha methyldopa (positive Coombs test result). Drug reactions must be interpreted in terms of modern immunology, with involvement of both the B and T lymphocyte systems. Inherited predisposition exists, probably dependent both on immune response genes and on the rate of enzymatic handling of drugs. Diagnosis depends on a carefully taken history of drug administration, recognition of clinical manifestations, and results of tests now available in departments of clinical immunology.

Aged↗
PubMed1976

Experimental autoimmune myasthenia gravis and myasthenia gravis: biochemical and immunochemical aspects.

Stucture of acetylcholine receptor protein (AChR) purified from Electrophorus electricus (eel) by affinity chromatography is described. AChR is detected in extracts from human muscle, rat muscle, and rat thymus. Rats immunized with eel AChR develop humoral antibodies, a small fraction of which recognize AChR from rat muscle. Rats immunized with AChR exhibit myasthenia, but those immunized with denatured AChR do not. Immunoglobulin fraction of antisera to eel AChR can block the activity of AChR in electroplaques. Sera from patients with myasthenia gravis contain antibodies to AChR from human muscle detectabe at an average value 300-fold the background level in sera from nonmyasthenics. Relationship of thymoma and disease intensity to antibody titer is examined. The chronic phase of EAMG appears a good model of MG, since in both cases similar concentrations of 7-S immunoglobulin against determinants on muscle AChR other than the toxin binding site are found. Assay of anti-AChR antibody in sera from MG patients using AChR from rat muscle gives titers 10%-15% of those obtained using AChR from human muscle, and using AChR from eel gives negligible titers. The assay method described for assaying antibodies against AChR from human muscle is suggested as a diagnostic test for MG.

Acetylcholine↗
PubMed1976

Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value.

Elevated amounts of antibodies specific for acetylcholine receptors were detected in 87 percent of sera from 71 patients with myasthenia gravis but not in 175 sera from individuals without myasthenia gravis, including those with other neurologic or autoimmune diseases. Antireceptor antibodies were not directed at the acetylcholine binding site of the receptor. Presence or titer of antibody did not appear to correlate with age, sex, steroid therapy, or duration of symptoms. Myasthenia gravis patients with only ocular symptoms had lower antibody titers, while the majority of titers in myasthenia gravis patients with thymoma exceeded the median titer of the myasthenia gravis group as a whole. Assay of antireceptor antibody should prove a useful test in the diagnosis of myasthenia gravis.

Acetylcholine↗
PubMed1975

Quantitation of cell-mediated immunity: responses to dinitrochlorobenzene and ubiquitous antigens.

T-lymphocyte immune capacity in man was assessed semiquantitatively by two in vivo procedures: the primary type of response to dinitrochlorobenzene and the secondary type of response, representing memory, to a group of five uniquitous antigens. Controlling for degree of illness proved important in assessing immune capacity in specific diseases; thus, the number of responders and mean score of semiquantitated responses was significantly lower in groups of patients with cancer and multisystem autoimmune disease when comparisons were made with healthy persons, but less so when comparisons were made with a group of subjects with other incapacitating diseases. A notable finding was the lack of correlation in the results of tests of cell-mediated immunity between the two procedures described. Depressed cell-mediated immunity shown in multisystem autoimmune disease is relevant to both predisposition to infection and the postulated role of thymic dysfunction in the pathogenesis of autoimmunity.

Adolescent↗
PubMed1975

Influence of immunosuppression on antinuclear antibody and survival of wehi mice.

The effect of immunosuppression with cyclophosphamide was assessed in 200 male and female Walter and Eliza Hall Institute outbred mice which are known to develop antinuclear antibody (ANA). Their longevity and the incidence of ANA were studied in comparison with controls. In females, life-span was longer despite a higher age-related incidence of ANA. Cyclophosphamide significantly delayed the development of ANA in both sexes; despite this, life-span was decreased. This is in contrast to what occurs in the highly autoimmune NZB/NZW F1 hybrid mouse. Thus, in weakly autoimmune mice the toxic effects of cyclophosphamide outweighed any benefit resulting from suppression of antinuclear autoantibodies.

Animals↗