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Biomedical subjects

I McKenzie

Publications and source records attributed to I McKenzie.

At least 19 recordsLinked to original sources
PubMed1998

Affinity of antibodies to MUC1 antigens.

The binding affinity of a monoclonal antibody to its ligand has been often used as a qualitative and quantitative measure for the specificity of the antibody. The aim of this paper was to assess the affinity of binding to recombinant and synthetic MUC1 peptides of 52 monoclonal antibodies as part of the ISOBM TD-4 Workshop. Affinity of binding was assessed using a surface plasmon resonance biosensor (BIAcore). The monoclonal antibodies exhibited variable affinity to MUC1 peptides, and overall 25/52 antibodies showed significant binding to the test peptides with affinities ranging from 2.4 x 10(6) to 3.1 x 10(8) M-1. Affinities calculated by analysis of kinetic biosensor data agreed well with affinities determined by equilibrium binding analysis of radiolabelled antibodies. The affinity measurements may provide help when determining the use of various monoclonals in tumour biology research.

Amino Acid Sequence↗
PubMed1994

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↗
PubMed1993

Heart rate and blood pressure variability in subjects exposed to simulated increases in gravity.

The effect of simulated increases in gravity (G) force on blood pressure and heart rate variability was investigated in seven normal healthy subjects using a man-carrying centrifuge. Subjects were exposed to G forces up to 3.6 times the gravity at the earth's surface (3.6 G). Blood pressure was measured non-invasively using a finger cuff (Finapres), while the subjects breathed at a fixed rate and depth. The blood pressure waveform was digitized and systolic blood pressure, diastolic blood pressure and beat-to-beat intervals were extracted from these data. Power spectra were produced from these values. Increases in G force produced increases in spectral power of systolic blood pressure and diastolic blood pressure at the respiratory frequency (0.2 Hz) and less conspicuous but significant increases in spectral power at lower frequencies (0.045-0.15 Hz). The spectral power of beat-to-beat interval did not change. It is postulated that the reduction in central blood volume produced by increased gravity is affecting blood pressure control in a similar way to that seen in hypovolaemic animals. The marked increase in blood pressure fluctuations induced by respiration at the higher G levels may be a result of the alteration in venous return to the right atrium, ultimately reflected as fluctuating left ventricular output and pressure.

Acceleration↗
PubMed1993

Incidence of cardiac dysrhythmias occurring during centrifuge training.

High-G training has been reported to provoke dysrhythmias in many subjects. These reports have been based on small subject groups. Students attending aeromedical professional courses at the USAF School of Aerospace Medicine are offered the opportunity to participate in high-G centrifuge training on the Armstrong Laboratory centrifuge, during which ECG monitoring is routinely performed. This study documents the incidence of dysrhythmias in this large group of subjects. The pertinent information from the records of 1,180 training sessions from 1984-91 were transcribed to a database on a personal computer. Dysrhythmias were recorded in 552 (47%) of the training sessions. Ventricular ectopy occurred in 480 (41%) of the sessions, and supraventricular dysrhythmias appeared in 127 (11%). In 53 (4.5%) of the sessions, training either was or would have been terminated because of the dysrhythmia. Session-terminating dysrhythmias included: 26 ventricular tachycardias (2.2%), including 18 triplets (1.5%); 9 ventricular couplets (0.8%); 8 episodes of too-frequent ventricular premature beats (0.7%); 4 of supraventricular tachycardia (0.3%), including 2 with aberrant conduction (0.2%); 2 of aberrantly conducted beats (0.2%); and 4 of anomalous bradycardia (0.3%). Centrifuge training can provoke serious dysrhythmias in ostensibly healthy individuals, and ECG monitoring of aircrew undergoing such training is recommended for their safety. Because some of these dysrhythmias are disqualifying for aircrew duties, the need for a more lenient aeromedical disposition policy must be considered.

Adult↗
PubMed1991

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↗
PubMed1987

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↗
PubMed1981

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↗
PubMed1980

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↗
PubMed1980

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↗