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Biomedical subjects

B J McGuire

Publications and source records attributed to B J McGuire.

7 recordsLinked to original sources
PubMed2004

Theoretical predictions of maximal oxygen consumption in hypoxia: effects of transport limitations.

A Krogh-type model for oxygen transport is used to predict maximal oxygen consumption (V(.-) O(2max)) of human skeletal muscle under hypoxic conditions. Assumed values of capillary density, blood flow, and hemoglobin concentration are based on measurements under normoxic and hypoxic exercise conditions. Arterial partial pressure of oxygen is assumed to decrease with reductions in inspired partial pressure of oxygen (P(I)O(2)), as observed experimentally. As a result of limitations of convective and diffusive oxygen delivery, predicted V(.-) O(2max) values decline gradually as P(I)O(2) is reduced from 150 mmHg to about 80 mmHg, and more rapidly as P(I)O(2) is further reduced. At very low levels of P(I)O(2), V(.-) O(2max) is limited primarily by convective oxygen supply. Experimentally observed values of V(.-) O(2max) in hypoxia show significant dispersion, with some values close to predicted levels and others substantially lower. These results suggest that maximal oxygen consumption rates in hypoxia are not necessarily determined by oxygen transport limitations and may instead reflect reduced muscle oxygen demand.

Biological Transport↗
PubMed2003

Estimation of capillary density in human skeletal muscle based on maximal oxygen consumption rates.

A previously developed Krogh-type theoretical model was used to estimate capillary density in human skeletal muscle based on published measurements of oxygen consumption, arterial partial pressure of oxygen, and blood flow during maximal exercise. The model assumes that oxygen consumption in maximal exercise is limited by the ability of capillaries to deliver oxygen to tissue and is therefore strongly dependent on capillary density, defined as the number of capillaries per unit cross-sectional area of muscle. Based on an analysis of oxygen transport processes occurring at the microvascular level, the model allows estimation of the minimum number of straight, evenly spaced capillaries required to achieve a given oxygen consumption rate. Estimated capillary density values were determined from measurements of maximal oxygen consumption during knee extensor exercise and during whole body cycling, and they range from 459 to 1,468 capillaries/mm2. Measured capillary densities, obtained with either histochemical staining techniques or electron microscopy on quadriceps muscle biopsies from healthy subjects, are generally lower, ranging from 123 to 515 capillaries/mm2. This discrepancy is partly accounted for by the fact that capillary density decreases with muscle contraction and muscle biopsy samples typically are strongly contracted. The results imply that estimates of maximal oxygen transport rates based on capillary density values obtained from biopsy samples do not fully reflect the oxygen transport capacity of the capillaries in skeletal muscle.

Blood Flow Velocity↗
PubMed2001

A theoretical model for oxygen transport in skeletal muscle under conditions of high oxygen demand.

Oxygen transport from capillaries to exercising skeletal muscle is studied by use of a Krogh-type cylinder model. The goal is to predict oxygen consumption under conditions of high demand, on the basis of a consideration of transport processes occurring at the microvascular level. Effects of the decline in oxygen content of blood flowing along capillaries, intravascular resistance to oxygen diffusion, and myoglobin-facilitated diffusion are included. Parameter values are based on human skeletal muscle. The dependence of oxygen consumption on oxygen demand, perfusion, and capillary density are examined. When demand is moderate, the tissue is well oxygenated and consumption is slightly less than demand. When demand is high, capillary oxygen content declines rapidly with axial distance and radial oxygen transport is limited by diffusion resistance within the capillary and the tissue. Under these conditions, much of the tissue is hypoxic, consumption is substantially less than demand, and consumption is strongly dependent on capillary density. Predicted consumption rates are comparable with experimentally observed maximal rates of oxygen consumption.

Algorithms↗
PubMed1988

B-lymphocytes from melanoma patients and normal individuals react with melanoma cells but also with irrelevant antigens.

Peripheral B-lymphocytes of 13 patients with uveal melanoma and of 5 healthy individuals were transformed with Epstein-Barr virus (EBV). The reactivity of these transformed cells with autologous or allogeneic melanoma cells and lymphocytes was measured by the enzyme-linked immunosorbent assay (ELISA). Antigens which are neither self nor common environmental antigens (i.e., plant protoplasts, schistosome antigen and keyhole limpet haemocyanin) were used for controls. Lymphocyte reactivity with all types of antigen was apparent both in patients with uveal melanoma and in normal controls. The response detected by the techniques available is likely to reflect antibody multispecificity leading to mis-identification of irrelevant antigens.

Animals↗
PubMed1987

Monoclonal antibodies to uveal melanoma.

Rat monoclonal antibodies were prepared against antigens expressed by uveal melanomas. Uncultured cells from primary human uveal melanomas were used for the rat inoculations and for the screening of hybridomas by enzyme-linked immunosorbent assay (ELISA). One of the monoclonal antibodies, designated 4A3, recognised a cytoplasmic antigen which was relatively specific for melanoma cells and which could be detected by immunohistochemistry in formalin-fixed, paraffin embedded tumour tissue. Western blotting showed the antigen to have a molecular weight of approximately 55-60 kD, with a doublet configuration which showed inter-tumour variation. The antigen was also detected by Western Blotting in the subretinal fluid of patients with uveal melanoma.

Animals↗
PubMed1986

Monoclonal antibodies to human primary uveal melanomas demonstrate tumor heterogeneity.

Five rat monoclonal antibodies to human uveal melanoma were produced using primary tumor tissue for immunization and screening. These monoclonal antibodies were tested by enzyme-linked immunosorbent assay against 12 uveal melanomas, one breast carcinoma, and peripheral blood lymphocytes from five healthy volunteers. One monoclonal antibody, 4A3, reacted against all the melanomas and none of the controls. On immunoblotting, this monoclonal antibody identified a protein doublet in the molecular weight range 55,000. With these monoclonal antibodies, it was possible to demonstrate significant variation in the antigenic profiles of the uveal melanomas which was not present in the controls.

Animals↗