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Biomedical subjects

I R Mackay

Publications and source records attributed to I R Mackay.

At least 271 records · Page 15Linked to original sources
PubMed1981

Delayed recovery of peripheral blood cell numbers after adjuvant cytotoxic chemotherapy for stage II breast cancer.

A study was made on the recovery of the bone marrow after adjuvant chemotherapy given to 30 post-mastectomy patients with stage II breast cancer treated with either melphalan or melphalan and methotrexate at 6-weekly intervals for 1 year. Counts of peripheral blood cells were made serially during treatment and then for a further 2 years after stopping chemotherapy. Mean counts for all cell types fell during chemotherapy and recovery was long-delayed. Thus 24 months after chemotherapy, mean counts for total leucocytes and platelets were significantly lower than mean pretreatment counts and counts for a normal female population, and the count for neutrophils was significantly lower than the count before treatment; after 24 months mean counts for lymphocytes were not significantly depressed. Melphalan was assumed to be the agent responsible. Slow haematological recovery after cessation of adjuvant chemotherapy with one particular regimen points to the need for including long-term post-chemotherapy observation of the bone marrow in the assessment of adjuvant chemotherapy programmes.

Antineoplastic Agents↗
PubMed1981

Antibody to myelin basic protein in extracts of multiple sclerosis brain.

Autoimmunity to a neural antigen is a suspected cause of multiple sclerosis (MS), and a candidate autoantigen is myelin basic protein (MBP). Accordingly, saline extracts of brain from patients with MS and other diseases were prepared and the content of immunoglobulin (Ig) determined. Antibody to MBP was measured with a highly-sensitive solid-phase radioimmunoassay using 125I-staphylococcal Protein A. Anti-MBP activity was detected in brain extracts of all eleven MS patients, and in seven out of the eight brain extracts from the patients with other diseases; however the level of anti-MBP activity was significantly higher in the MS extracts (P less than 0.01). Analysis of the MS brain extracts after purification by affinity chromatography columns revealed that the anti-MBP activity was specifically mediated by IgG and resided in the IgG1, IgG2, and/or IgG4 subclasses.

Adult↗
PubMed1981

Autoantibody to a novel neuronal antigen in systemic lupus erythematosus and in normal human sera.

A non-Fc receptor-bearing mouse neuroblastoma cell line, Neuro-2a, was used in indirect immunofluorescence tests to characterize the pattern of anti-neuronal activity of human sera in 41 cases of systemic lupus erythematosus (SLE), including seven cases of cerebral lupus, 30 "disease controls" (rheumatoid arthritis and chronic active hepatitis) and 30 healthy subjects. The immunofluorescence reaction with Neuro-2a gave a uniform ring fluorescence of the cell surface of cultured cells at 4 and at 37 degrees C, clusters were seen at 5 to 10 min and surface globules at 20 to 120 min. Titres of antibody to Neuro-2a in SLE ranged from less than 5 (seven cases), 5 to 20 (23 cases) and greater than or equal to 40 (11 cases). Titres of 80 to 160 were given by five of seven cases of cerebral lupus and two of 34 cases without cerebral lupus. Antibody to Neuro-2a was demonstrable in subjects without SLE, but to lower titres (less than 5-20). Of 11 SLE sera with antibody titres greater than or equal to 1:40, the antibody class was IgM in eight, IgG in two and both IgM and IgG in one. Absorption studies indicated that serum reactivity against Neuro-2a cells could be removed from some SLE sera with the cultured human neuroblastoma cell line, SK-N-SH, but not with mouse fibroblasts, mouse 3T3 cells, rat C6 glioma cells, rat transformed mesenchymal cells, nor by homogenates of mouse brain, heart, liver of kidney. Detection of antibody to Neuro-2a cell may be helpful in identifying patients with cerebral disease due to SLE.

Animals↗
PubMed1981

Interaction of HLA and Gm in autoimmune chronic active hepatitis.

An immunogenetic study of autoimmune chronic active hepatitis (CAH) showed the relative risk (RR) for this disease was 11.6 for patients who were HLA-B8, 11.7 for patients who were DR3 and 2.3 for patients who were Gma+x+. Moreover, the Gm haplotype Gma+x+ was present in 18 of 40 (45%) patients with HLA-B8, but in none of 10 patients negative for HLA-B8, whereas in 180 healthy controls Gma+x+ was evenly distributed among those positive (24%) and negative (18%) for HLA-B8. The RR was lowest in patients lacking HLA-B8 but positive for Gma+x+. Relative to this low-risk group, the risk was increased 39 times in subjects with both HLA-B8 and Gma+x+, 15 times in subjects with HLA-B8 who were not Gma+x+ and twice in subjects who were neither HLA-B8 nor Gma+x+. Statistical analysis indicated that the three-factor effect (disease risk affected by non-additive effects of HLA-B8 and Gma+x+) was significant (P less than 0.01), as were the main effects of HLA-B8 (P less than 0.001) and Gma+x+ (P less than 0.02). Thus in the presence of HLA-B8, genes linked to Gma+x+, an immunoglobulin CH allotype, may contribute to the development of autoimmune chronic active hepatitis; in the absence of HLA-B8 these same genes appear to be inactive. This may indicate interactions between MHC gene products and VH gene products in the presentation and recognition of autoantigen(s) in autoimmune hepatitis.

Autoimmune Diseases↗
PubMed1980

Diagnostic significance of thyroid microsomal antibodies in randomly selected population.

A longitudinal study among the population of Busselton, Western Australia, has identified individuals with persistent and transient thyroid microsomal antibodies (TMA). 59 (72%) of 82 subjects with persistent TMA, 18 (72%) of 25 with recently developed TMA, and 12 (23%) of 53 with transient antibody were found to have subclinical hypothyroidism, as indicated by high serum thyroid stimulating hormone concentrations. This study reveals the high specificity, sensitivity, and predictive value of persistent or recently required TMA.

Adult↗
PubMed1980

Utility analysis of a computer stored diagnosis index and other medical record data.

A computer-based system for storing items of medical record data including a complete coded list of diagnoses was established in 1971 for all patients admitted to a research-oriented medical ward. An analysis was made to assess the usefulness of such an electronically-stored data base from the stand-point of Unit activity, disease correlations, stability of diagnostic criteria, completeness of diagnosis lists and accuracy of coding. Over six years, 1972-77, there were 3569 admissions of which 1679 were first admissions. The most frequently made principal diagnoses were cerebrovascular accident (8%), myocardial infarction (5.4%), ischaemic heart disease (2.9%), rheumatoid arthritis (2%), duodenal ulcer (2%) and systemic lupus erythematosus (1.9%); the 33 most frequent principal diagnoses accounted for only 45% of all principal diagnoses made. The duration of stay (mean 16 days) was shown to depend on principal diagnosis but not significantly on age. Variability in annual incidence was significant for 24% of diagnoses; for some diagnoses this was readily explainable by extraneous causes, but for others it suggested an "instability" of criteria for that diagnosis. The probability of a minor diagnosis being "overlooked", using Dupuytren's contracture as an example, was shown to be high (50%). The rate of miscoding a diagnosis was 5%. This study, despite its illustration of the "softness' of diagnosis making in routine hospital ward practice, illustrates the potential or processing hospital diagnosis data by computer.

Computers↗
PubMed1980

Effect of multiple sclerosis materials on polymorphonuclear neutrophils of mice.

An assessment was made of a bioassay for a multiple sclerosis (MS)-associated agent claimed to cause a depression in the proportion of circulating polymorphonuclear neutrophils (PMN) in mice. Serum (1 sample), supernate from brain homogenates (four samples) and cerebrospinal fluid (four samples), and corresponding control materials, were tested under code by intraperitoneal injection into BALB/c mice. Results were plotted of proportions and absolute numbers of PMN over observation periods up to 2 weeks. Handling, injection and bleeding of mice did not significantly influence "baseline" counts of PMN. However, all samples from MS patients and controls caused an initial increase in PMN over 1--4 days, and then a later fall towards baseline. The claimed effect of MS materials in depressing counts of PMN in mice was not observed in these experiments, and variations in counts of PMN did not discriminate between samples from MS patients and controls.

Animals↗
PubMed1980

NK and K cell activity of human blood: differences according to sex, age, and disease.

We report a study on the activity of NK cells ('natural' killer cells) and K cells (antibody-dependent killer cells) in human peripheral blood in health and disease. The 'targets' used were cells of the Chang cell-line, sensitised with rabbit anti-Chang cell antibody for K cell activity, and killing was assessed by release of radiochromium at effector: target ratios of 50:1 and 100:1. The positive findings were that NK cell activity, but not K cell activity, was greater in males and in youth, that NK cell activity was reduced in systemic lupus erythematosus, that neither NK nor K cell activity was altered in rheumatoid arthritis, and that K cell activity was reduced in chronic active hepatitis.

Adult↗
PubMed1980

Interactive effect of Gm allotypes and HLA-B locus antigens on the human antibody response to a bacterial antigen.

Two hundred healthy adults were immunized with 1 microgram of the bacterial antigen monomeric flagellin from Salmonella adelaide, and grouped as responders and non-responders on the basis of a rise in titre of antibody 2 weeks after immunization. Immunoglobulin allotypes G1m(a), G1m(z) and G3m(g) were more frequent among responders who made immunoglobulin (Ig)G antibody (P less than 0.02), and HLA-B12 was more frequent among responders who made IgM antibody (P less than 0.05). The mean log titre of IgG antibody was higher in females (P less than 0.001), in subjects with T1m(a), G1m(z) and G3m(g) allotypes (P less than 0.05), and in Gm heterozygotes (P less than 0.01). The mean log titre of the IgG antibody response in subjects with particular Gm phenotypes was also dependent on the HLA-B locus phenotypes HLA-B7, B8 and B12 (P less than 0.005); for example, among those with the phenotype Gm(a-x-b) subjects with HLA-B7 were low responders and those with HLA-B8 were high responders. These findings are consistent with the hypothesis that there are immune response genes within the major histocompatibility complex (MHC) which interact with Gm-linked genes in determining levels of serum antibodies of different isotypes and specificities.

Adolescent↗
PubMed1980

Immunology of chronic hepatitis.

Of the two major types of chronic active hepatitis, that associated with autoimmunity, CAH-Type A, has been the more extensively studied and is better recognised. On the other hand, the type associated with the HBV carrier state, CAH-Type B, is the more prevalent, particularly so in South East Asia, and the time is ripe for the immunology of this type to be clarified. Whilst most encounters between host and HBV will result in an acute hepatitis with lasting immunity, a non-sterilizing outcome with a persisting carrier state may ensue. The reasons for persistent infection with HBV are still not elucidated, but may include: (i) incorporation of viral DNA into the host genome, (ii) a carrier state in which there is full T cell tolerance to the virus and its surface antigen, or (iii) an unstable tolerance marked by a persisting damaging immune response to viral antigens expressed on the liver cell membrane, with associated CAH. Whether an autoimmune-type CAH can be included as one possible outcome of HBV infection is uncertain; whilst the association of an HB viral antigen with a liver cell membrane component is one theoretical way by which an autoimmune response could be generated, most cases of autoimmune hepatitis, at least in Caucasian areas, show no evidence of current or past infection with HBV or indeed with any other virus. Thus, pending further knowledge, CAH-Type A must be regarded as a primary autoimmune disease of the liver, and CAH-type B as resulting from an ineffective host response to a chronic virus infection of the liver.

Antibodies, Antinuclear↗
PubMed1980

HLA associations with autoimmune-type chronic active hepatitis: identification of B8-DRw3 haplotype by family studies.

In 43 cases of chronic active hepatitis of autoimmune-type, HLA-D locus-related antigens (HLA-DR) as well as A and B locus antigens were typed serologically. For 14 patients carrying HLA-B8 and DRw3 family members were typed to establish haplotypes. Control groups consisted of healthy persons and patients with chronic liver disease unrelated to autoimmune CAH (alcoholic cirrhosis and cryptogenic cirrhosis). In autoimmune CAH, DRw3 was significantly increased, 74%, compared with healthy controls, 32%, and liver controls, 31%, this increase being similar to the increase of HLA-B8. There was marked co-occurrence of HLA-B8 and DRw3 in 31 of 33 individuals positive for either antigen. DRw3 was present in 23 of the 24 cases with disease-onset before age 30 hr. HLA typing on the 14 families showed that a haplotype including B8 and DRw3 was present in all index patients; this haplotype also included A1 in 10 cases, A9 in 2 cases, and A2 and A28 in 1 case. The results indicate that in the autoimmune type of chronic active hepatitis occurring characteristically in young females, there exists a disease susceptibility gene strongly associated with the B and D locus of the major histocompatibility complex (MHC), and acting in concert with other non-MHC gene loci and/or environmental factors.

Adult↗
PubMed1980

Occurrence of tumors and effects on longevity after limited x-irradiation in man.

An analysis was made of survival times and causes of death of patients given local irradiation in small dosage during 1948--1960. The study involved 61 patients with peptic ulcers in whom hyperacidity was treated by partial gastrectomy and gastric irradiation, and their mortality was compared with that of 61 age- and sex-matched gastrectomized but nonirradiated control patients. For both groups the survival rates were related to "normal population" survival rates calculated from age-, sex- and year-specific mortality rates for the population of Victoria. Ten years after irradiation the relative survival rates of the irradiated and control groups began to diverge, due to more deaths than expected in the irradiated group. The irradiated group had a significantly increased number of deaths due to cancer, particularly carcinoma of the stomach, as well as an increase in deaths not caused by cancer. The mortality of the nonirradiated control patients was not significantly greater than that of the normal population.

Adult↗
PubMed1980

Multiple myeloma and gastric carcinoma. Possible late effects of limited abdominal X-irradiation.

A man, aged 34, was treated in 1954 for duodenal ulcer by antroduodenectomy followed by X-irradiation to the stomach in a dose of 2,000 rads. Over two decades, he developed several conditions attributable to the previous irradiation, including the physical appearances of premature ageing, shrinkage of the left kidney due to irradiation nephritis, immune deficiency, multiple myeloma of IgA type, and lastly, carcinoma of the stomach. The kidneys, especially the left, the bone marrow and stomach would have been in the field of X-irradiation. These effects of local X-irradiation are discussed in relation to the known effects of total body irradiation in causing decreased longevity in animals and inducing cancer in man.

Aging↗
PubMed1979

Autoimmune disease and the theory of clonal abortion. Is it still relevant?

Explanations for self-tolerance and its failure in autoimmune disease remain conjectural. Earlier deletional theories and the later clonal abortion theory as a basis for central B-cell (and possibly T-cell) tolerance seemed to conflict with various experimental and clinical observations, including those relating to the ability to induce autoimmune reactivity in normal adult animals. Accordingly, immunoregulatory controls have dominated discussions. However, there is recent compelling experimental evidence in favour of clonal abortion of B lymphocytes in the absence of T-cell help. It is proposed that two sets of regulatory systems operate at different stages in life to establish and maintain self-recognition: a central tolerance operates through clonal abortion during embryonic and early postnatal life and during childhood and beyond, ancillary regulatory systems deal with the self-reactive cells which emerge in a milieu in which helper influences interfere with clonal abortion.

Adult↗