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Biomedical subjects

I R Mackay

Publications and source records attributed to I R Mackay.

At least 307 records · Page 17Linked to original sources
PubMed1977

Experimental autoimmune encephalomyelitis in mice: antigen binding lymphocytes to basic protein of myelin in susceptible and resistant strains.

Antigen-binding lymphocytes (ABL) to basic protein of myelin (BPM) were demonstrable in the thymus and spleen of various strains of mice. Counts of ABL did not differ in strains resistant and susceptible to EAE, and did not differ when human or murine 125I-labelled BPM was used as a labelled antigen to detect ABL. After injection with mouse spinal cord and adjuvants, under conditions known to be immunogenic and encephalitogenic for susceptible strains of mice, counts of ABL increased two- to four-fold in suceptible strains but did not icnrease in resistant strains. Antigen binding could not be accounted for by the attachment to cells of cytophilic antibody with specificity for BPM, because such antibody was seldom demonstrable even after immunization. Inferences from the study were: (i) that tolerate (non-responsiveness) to certain autoantigens at least must depend on control over continually present antigen-reactive lymphocytes rather than on any lack of capacity to recognize antigen; (ii) differences in susceptible and resistant strains are evident after, rather than before, immunization.

Animals↗
PubMed1977

HLA and chronic active hepatitis (CAH).

A family study of 2 parents and 5 SD identical (HLA-A1, A3, B7, B8) siblings, one of whom has 'classic CAH' has been used to demonstrate that in this family the maternally ingerited HLA-B8 antigen is not solely serving to mark genetic predisposition to this disease. The patient's lymphocytes both responded to, and stimulated those of her 4 siblings in MLR indicating the possible involvement of an HLA-D antigen in CAH. This HLA-D antigen could have been of paternal orgin, or could have been a result of a recombination event involving an HLA-D antigen liked to the maternal HLA-A2, B12 haplotype. The lymphocytes of the four helthy siblings were mutually unresponsive in MLR.

Chronic Disease↗
PubMed1977

Anti-T cell activity of niridazole in experimental autoimmune encephalomyelitis.

The antischistosomal drug niridazole, known to selectively depress cell-mediated immune function, was assessed in experimental autoimmune encephalomyelitis (EAE) in mice. EAE results from an immune attack by activated T lymphocytes on the central nervous system. Niridazole given orally at a dose of 100 mg/kg body weight three times a week and starting either before or after immunization caused a significant suppression of signs and histological lesions of EAE, lasting up to ten weeks after cessation of treatment. There was no effect of niridazole on either release of macrophage migration inhibition factor in response to specific neural antigen, production of antibody, or on the nonspecific inflammatory reaction to adjuvant. Niridazole presumably acts by preventing release of lymphokines by activated T cells after contact with antigens.

Animals↗
PubMed1977

Improvement in multiple sclerosis during prolonged induced hypothermia.

Moderate hypothermia (33 degrees C) was induced for 7 and 3 days, respectively, in two patients with multiple sclerosis. In both patients, striking improvement of clinical signs persisted throughout the period of cooling, indicating the potential for sustained reversal of the neurologic deficit. Hypothermia may aid management of severe acute exacerbations of multiple sclerosis.

Acute Disease↗
PubMed1977

What happens when hospitalized patients see their own records.

The effect of giving hospitalized medical patients access to their problem-oriented hospital records was investigated. Twenty-five subjects were given free access to their records while 25 other subjects served as controls. Few of the open record group actively sought and studied their records; most elected to see them only as part of routine ward rounds; and one objected to seeing the record at all. Taking the experimental group as a whole, there was no measurable effect of seeing the record on the subjects' ability to list their diagnoses or medications, their self-assessment of depression, anxiety or contentment, or their attitudes toward selected components of the health care system. On the other hand, in individual instances access to the hospital record seemed to facilitate communication and provide an opportunity for hospital inpatients to monitor objectively their hospital course.

Australia↗
PubMed1977

Studies on antigen-induced arthritis in mice. II. Immunologic correlates of arthritis susceptibility in mice.

Antigen-induced arthritis was developed in mice as a model of human rheumatoid arthritis by using methylated bovine serum albumin (mBSA) as antigen. It was found that most strains were susceptible, whereas CBA mice were resistant. We therefore investigated the humoral and cell-mediated immune responses to mBSA in resistant mice (CBA) and susceptible mice (exemplified by C57BL) to determine whether these were associated with susceptibility to arthritis. The resistant strain (CBA) differed from the suceptible strains in the following respects. First, there was a lower humoral immune response to mBSA as measured by passive hemagglutination, but this could be overcome by a larger immunogenic dose. Secondly, there were differences in response to low doses of DNP-mBSA after mBSA carrier preimmunization. Thirdly, there were striking differences in delayed-type hypersensitivity (DTH) to mBSA as determined by a radioisotopic assay in vivo; the response of CBA mice occurred early, at 5 days, declined quickly, and was weaker, whereas that of C57BL mice developed later and was long sustained. Genetic studies of the DTH response with hybrids and backcrosses showed an oligogenic control of immune responsiveness, with one gene being linked to the H-2b allele of the susceptible C57BL mice, and another being independent of the H-2 complex. Our findings indicate that in mice, susceptibility to antigen-induced arthritis with mBSA correlates with a higher responder state to this antigen, and that T cells are the major if not the only determinant of the high responder state.

Animals↗
PubMed1977

Studies on antigen-induced arthritis in mice. III. Cell and serum transfer experiments.

Antigen-induced arthritis in mice occurs after immunization and subsequent intraarticular challenge with methylated bovine serum albumin (mBSA). In adoptive transfer experiments, susceptible C57BL mice and resistant CBA mice were compared in their capacity to express delayed-type hypersensitivity (DTH) by ear assay, and to express arthritis. The expression of DTH could be transferred incrementally by lymphoid cells in C57BL mice, but not in CBA mice. Both immune lymphoid cells and, to a much lesser extent, serum transferred the capacity to develop arthritis in C57BL mice. The reactivity of transferred cells was abolished by anti-Thy-1 but enhanced by enrichment for T cells with anti-immunoglobulin columns. If this model disease can be equated with human rheumatoid synovitis, the lesions in the human disease would be an expression of a T cell-dependent activity.

Animals↗
PubMed1976

A problem-orientated outpatient record.

A problem-orientated record for use in outpatient clinics has been in operation over a period of 2 1/2 years. Its special features include: (i) preprinted stationery bound in appropriate sequence in the conventional hospital record; (ii) clear presentation of an up-to-date list of each patient's past and present diagnoses; (iii) problem-orientated progress notes. This study considers the definition of an illness problem, recording of progress information, adjustments to a problem list in the outpatient setting and recording of minor "noise" problems. Experience with the system consisted of 5,000 patient attendances. A sampling of these indicated that there were 3-1 +/- SD 1-5 concurrently treated problems per patient, and there were 9-3 +/- SD 6-6 clinic visits per patient. The system was subjectively assessed by 18 doctors, using a semantic differential technique, with a high frequency of "yes" responses to "saves time", "benefits the patient" and "benefits the doctor". This and similar systems may help to resolve the present paradox of the clinical chart becoming decreasingly useful with increasing complexity of illness.

Attitude of Health Personnel↗
PubMed1976

Medical decision profiles derived from a symptom questionnaire.

The introduction of formalized systems for data acquisition provide a basis for the investigation of medical decision making. Patients admitted to a general medical ward completed a comprehensive, medical history. Decisions relating to their subsequent diagnosis, investigation and management were made after complete investigation and were recorded with their questionnaire responses. A computer programme was developed to compare questionnaire responses from patients who did, and patients who did not have each particular decision made, and to assign a value to each question depending on the significance of its association with the decision. The set of values, one for each question, was termed a decision profile and was characteristic of that decision.

Barium Sulfate↗
PubMed1976

T cell necessity in the pathogenesis of experimental autoimmune encephalomyelitis in mice.

Cellular transfer of experimental autoimmune encephalomyelitis (EAE) was effected in mice with lymph node and spleen cells from appropriately immunized donors. In contrast to lymphoid cells, immune serum did not transfer this autoimmune disease nor did serum have any facilitating or inhibitory effect on the capacity of lymphoid cells to transfer EAE. Transfer of EAE was effected in normal mice, lightly irradiated (350 rad) and lethally irradiated (850 rad) and bone marrow-protected mice, but not in mice which had been given 850 rad total-body irradiation. There was a striking augmentation of severity of transferred EAE in the lightly irradiated recipients, possibly attributable to selective radiosensitivity of suppressor T cells. Cell-mediated immunity but not circulating antibody to basic protein of myelin was demonstrated in recipients with transferred EAE. The immune lymphoid cells responsible for transfer of EAE were T lymphocytes. Thus transfer was successful after passage of sensitized cells through anti-immunoglobulin columns and was abrogated following treatment with anti-Thy-1 serum and complement. Neonatally thymectomized mice failed to develop either EAE, cell mediated immunity or humoral antibody against myelin basic protein (BPM). Inhibition of EAE and immune responsiveness was solely due to the removal of the source of thymus lymphocytes, because reconstitution of neonatally thymectomized mice with T lymphocytes completely restored these functions. It is concluded that T lymphocytes are required for the production and adoptive transfer of EAE, for the development of cell-mediated immunity to BPM and for the production of antibody to BPM.

Animals↗
PubMed1976

Carcinoembryonic antigen (CEA), smoking, and cancer in a longitudinal population study.

In 1969, the prevalence of raised levels (5 ng/ml of serum) of carcinoembryonic antigen (CEA) was estimated in 2372 persons aged 40 years and over in Busselton, Western Australia. There were raised levels of CEA in 73 subjects (3%). The prevalence increased progressively with age in both non-smokers and smokers with a higher rate of prevalence at all ages in smokers, and a peak of 11% in smokers aged 65--74 years. Among non-smokers, the prevalence was similar in both men and women (1%), in smokers there was a stepwise rise in prevalence with increasing tobacco consumption. Subsequently, levels of CEA of 5 ng/ml or over tended to disappear from the sera in a greater proportion of the non/exsmokers than of smokers. In the following five years, "CEA-associated" cancer occurred in nine of 73 subjects (13%) with raised levels of CEA compared with 25 in 2299 (1%) in those with normal CEA levels. This association was independent of the confounding effects of age, sex, and smoking habit. The five year data on 2372 subjects have confirmed that CEA screening of healthy Busselton subjects has identified a group at future risk of developing "CEA-associated" cancers, in addition to drawing attention to the presence of existing cancers.

Adult↗
PubMed1975

Vulnerability of cell-surface receptors to autoimmune reactions.

A previous hypothesis in which myasthenia gravis was explained by an immune response to acetylcholine receptors has been validated, and is here extended to cell receptors in general. Receptors on target cells, being accessible to circulating trophic hormones or transmitters, must also be accessible to antibodies which compete with the natural mediator for access to the site. To detect anti-receptor antibodies, physiological assay systems would be more sensitive than conventional immunological assays. Autoimmune responses to receptor sites would require a genetic predisposition to failure of immunological tolerance such as occurs in various autoimmune diseases. This hypothesis is supported by recent findings in hyperthyroidism and a type of insulin-resistant diabetes mellitus, and is applicable to other endocrinopathies, diseases in which dysfunction at receptor sites can be postulated, and regulatory functions within the immune system itself.

Animals↗
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

Hepatitis B antigen and antibody in active chronic hepatitis and other liver diseases in Australia. A multicenter collaborative study.

In a multicenter cooperative study, sera from 85 patients with active chronic hepatitis (ACH) were examined for the presence of hepatitis B (Australia) antigen (HBAg) by radioimmunoassay (RIA) and antibody to HBAg (anti-HBAg) by RIA and passive hemagglutination (PHA), the most sensitive currently available techniques. In addition, sera from 83 patients with other liver diseases 98 other hospital patients, and 67 healthy controls were tested. HBAg was detected in 3 of the 85 patients (four percent) with ACH. In a further 3 patients (four percent) anti-HBAg was detected. Thus, 6 patients with ACH (seven percent) had evidence of present or prior infection with the hepatitis B virus (HBV). HBAg was also detected in 7 of the patients with other liver diseases, 2 of the other hospital patients, and none of the healthy controls. Anti-HBAg was detected in 17 of the non-ACH subjects. These results indicate that neither persistent nor prior self-limited infection with HBV is a major factor in the pathogenesis of ACH in Australia.

Acute Disease↗
PubMed1975

Carcinoembryonic antigen in an unselected elderly population: a four year follow up.

Sera obtained in 1969 from 956 unselected elderly persons in Busselton, Western Australia were tested for carcinoembryonic antigen (CEA) by a "double antibody" microradioimmunoassay. Forty-four (4-5%) were positive for CEA (5 ng/ml or greater). Review of health records for the 4-year period subsequent to accession of sera showed that 6 (14%) of the 44 persons positive for CEA died of CEA associated cancers, 15 were heavy smokers, 2 had colonic diverticula and 1 a peptic ulcer. On the other hand, 18 (2%) of the 912 persons negative for CEA developed CEA associated cancers. Thus, a significantly greater proportion of cancers (P = 0-01) was found in the persons positive for CEA. Furthermore, when 21 persons who were positive for CEA in 1969, but clinically well 4 years later, were examined 2 had occult cancer of lung and colon respectively. However, the relatively low yield of diagnosis of cancer from our present population survey led to the conclusion that, if screening for cancer were to be solely dependent on testing for CEA, increased specificity and sensitivity of test systems should be awaited.

Adenocarcinoma↗