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Biomedical subjects

I McKenzie

Publications and source records attributed to I McKenzie.

At least 19 recordsLinked to original sources

Recombinant MUC 1 vaccinia virus: a potential vector for immunotherapy of breast cancer.

Breast cancer is considered as the major cause of mortality by cancer for women. Even if chemotherapy, radiotherapy and surgery have improved the life expectancy of patients bearing tumours, breast cancer is responsible for the death of 42,000 women per year in USA and 25,000 women in France. In this context, cancer vaccines may add an attractive alternative therapeutic strategy to the current existing treatments. We describe here the construction of recombinant vaccinia viruses co-expressing a tumour associated antigen (MUC 1) and an "adjuvant" cytokine, which have potential applications in the active immunotherapy of breast cancer. Indeed, recombinant vaccinia viruses have been extensively used during the past decade to induce a protective response against a whole variety of pathogens, and has proven to be of great value in the elicitation of a cellular immune response leading to the rejection of tumour grafts in mouse models.

Animals

Isoelectric heterogeneity of human prorenin (inactive renin) in body fluids.

Using flat bed isoelectric focusing, inactive renins from various body fluids were compared. Normal plasma inactive renin demonstrated six consistent peaks at pH 4.98, 5.14, 5.29, 5.47, 5.63 and 5.91, the largest being 5.29, 5.47 and 5.63. The isoelectric pattern of ovarian follicular fluid inactive renin was similar, with slight shifts at major peaks to a higher pH. Pregnancy plasma had inactive renin patterns like normal human plasma as did pleural fluid, lymphocoele fluid and plasma from anephric humans. Amniotic fluid inactive renin showed a markedly different pattern with major peaks at pH 5.00, 5.16 and 5.30. Fetal plasma (cord blood) also showed differences with only four peaks at 5.24, 5.40, 5.58 and 5.83. We conclude that human prorenin isoelectric patterns are similar for plasma, ovarian and most tissue fluid prorenins, but different for fetal plasma and amniotic fluid suggesting that these forms of renin do not cross the placental barrier.

Amniotic Fluid

A monoclonal antibody to the surface membrane of human platelets which inhibits ristocetin- and collagen-induced platelet aggregation reacts with H1 histones of cell nuclei.

A murine monoclonal antibody HuPIA3, produced by immunization with human platelet membranes, reacted by radioimmunoassay with platelets, and inhibited ristocetin- and collagen-induced platelet aggregation and release of 14C-serotonin. The antibody also inhibited ristocetin-induced aggregation of washed, formaldehyde-fixed platelets by von Willebrand factor. On cultures of human and rodent fibroblasts, and on frozen sections of rabbit liver and rat kidney, the antibody gave a diffuse, homogenous immunofluorescence staining of cell nuclei which could be abolished by treatment with 0.1 M HC1 or 2 M NaCl and restored by reconstitution with histones, suggesting a reaction with nuclear histones. Absorption of the antibody with histones abolished nuclear staining and abrogated the inhibitory effect of the antibody on ristocetin- and collagen-induced platelet aggregation and 14C-serotonin release. Conversely, absorption with platelets removed antibody reactivity for platelets and for cell nuclei. In addition, the antibody reacted with H1 histones by radioimmunoassay, and immunoblotting studies showed that the antibody reacted with a protein of 199,000 daltons on platelets and with H1 histones (31,000 dalton and 32,000 dalton). These observations suggest that the antibody recognizes epitopes found on surface molecules of platelets as well as on H1 histones of cell nuclei.

Antibodies, Antinuclear

Protamine sulphate hypersensitivity.

Protamine hypersensitivity has been documented by intra-dermal skin testing in three patients who demonstrated sudden cardiovascular collapse and bronchospasm following the use of intravenous protamine sulphate. All patients had been given protamine previously. The effects of the anaphylactic response were terminated quickly by the administration of intravenous adrenaline associated with plasma volume expansion. Intra-dermal skin testing against all anaesthetic agents is recommended so that the specific allergen can be identified. In patients who are shown to be allergic to protamine sulphate and who require cardiac or vascular surgery careful monitoring of heparin dosage and neutralisation with hexadimethrine (Polybrene) intravenously appears to be a safe alternative.

Anaphylaxis

Variance function estimation for immunoassays.

A computer program is described which implements a recently described [1], modified likelihood method of determining an appropriate weighting function to use when fitting immunoassay dose-response curves. The relationship between the variance of the response and its mean value is assumed to have an exponential form, and the best fit to this model is determined from the within-set variability of many small sets of repeated measurements. The program estimates the parameter of the exponential function with its estimated standard error, and tets the fit of the experimental data to the proposed model. Output options include a list of the actual and fitted standard deviation of the set of responses, a plot of actual and fitted standard deviation against the mean response, and an ordered list of the 10 sets of data with the largests ratios of actual to fitted standard deviation. The program has been designed for a laboratory user without computing or statistical expertise. The test-of-fit has proved valuable for identifying outlying responses, which may be excluded from further analysis by being set to negative values in the input file.

Analysis of Variance

An evaluation of the 14C-glycocholic acid breath test in the diagnosis of bacterial colonisation of the jejunum.

In order to assess the performance of the 14C-glycocholic acid breath test as an indicator of bacterial colonisation of the jejunum, 145 combined breath tests and jejunal aspirate cultures were carried out on a total of 50 subjects who had an increased probability of being colonised. Ninety-one of the 145 cultures were positive while only 31 of the breath tests were positive. This poor performance of the breath test relative to the aspirate culture can be predicted with reasonable accuracy from known bile deconjugating capabilities of bacteria found in the small intestine.

Bacterial Infections

Quality control of radioimmunoassays for proteins: the first two and a half years of a national scheme for serum growth hormone measurements.

The philosophy and achievements of the first two and a half years of a national quality control scheme for serum growth hormone assays are described. Three serum samples were distributed to participating laboratories every two weeks. A computer-produced summary of the quality control results, which contained scattergrams and a statistical analysis, was returned to participants four weeks after despatch. The performance of 11 experienced (SAS) laboratories was found to fulfil the necessary accuracy criteria, and their results provided the 'reference group mean', which served as the target value. Gross positive bias exhibited by several laboratories was due to the use of assays with inadequate sensitivity, and this practice was eliminated during the first six months. During the course of the Scheme the average bias fell from 30 to 14%. With assays of adequate sensitivity, bias was almost invariably due to the misuse of standards. Median within-laboratory, between-batch precision (CV) improved from 23 to 15%. The best performers achieved between-batch CV of 7% which was 1.5 x their within-batch CV: the worst had three- to four-fold differences between within- and between-batch CV. Rudimentary quality control of interpretation was found to result in improvements in interpretation per se and also served to reinforce the desire to improve numerical agreement. A 'recommended procedure' based upon supplied first and second antibody, and a communal 'reference range' from 280 untreated acromegalics, both proved valuable.

Growth Hormone

Hereditary C2 deficiency associated with immune complex disease.

A patient presenting with a syndrome probably due to immune complex deposition was investigated and found to possess an inherited C2 complement deficiency. Family studies indicated that the deficiency was transmitted as an autosomal recessive trait. HLA typing for the HLA-A and HLA-B specificities and HLA-D specificities indicated a close linkage between the HLA and C2 genes, as has been described elsewhere. The HLA-A and B locus specificities HLA-AW25 and HLA-B18 were coded for by each of the two chromosomes carrying the C2(0) gene. However, the two chromosomes differed at the HLA-D locus, as one coded for HLA-DW2 whilst the other did not. This case, therefore, provides a unique haplotype and may be of importance in mapping the C2(0) locus, as it suggests that the gene order on chromosome 6 is HLA-D, C2(0), HLA-B, HLA-A. Extensive complement component assays indicated that utilization of complement in the patient was occurring via the alternate complement pathway. It is suggested that, as a result of the C2 deficiency, infections with viruses and other agents could lead to an immune complex disease due to an impaired capacity to effectively eliminate circulating complexes.

Adult

Microvascular transplantation of the human fallopian tube.

An unsuccessful human fallopian tube transplant is reported. A microsurgical technique is described which initially secured a viable transplant. However, the allograft subsequently died, probably as a result of rejection. Immunosuppression of the patient caused no complications or difficulties, the donor sharing one HL-A haplotype with the patient. The operative procedure, the risks of immunosuppression, and the ethical aspects of the case are discussed in order to present the problems associated with fallopian tube transplantation.

Fallopian Tubes