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Biomedical subjects

D McCarthy

Publications and source records attributed to D McCarthy.

At least 109 records · Page 6Linked to original sources

Effect of age and chronic obstructive pulmonary disease on the Breathalyzer estimation of blood alcohol level.

Twenty volunteers, 10 with chronic obstructive pulmonary disease (COPD) and 10 with no disease, ingested a vodka cocktail. Serial determinations of blood alcohol level (BAL) by gas-liquid chromatography and simultaneous Breathalyzer estimations of BAL were used to calculate blood:breath alcohol partition coefficients (PCs). Data from the present study were combined with data obtained in a previous study using identical methodology to examine the relationship between age and BAL estimation. It was found that the Breathalyzer significantly underestimated BAL as a function of age. It was hypothesized that the underestimation may be due to closing volume (CV) as the Breathalyzer samples end-expiratory breath.

Adult↗

Electron microscopy of single-stranded structures in the DNA of competent Haemophilus influenzae cells.

Chromosomal DNAs from exponential-phase and competent cells of Haemophilus influenzae were examined by electron microscopy to determine whether the chromosome undergoes structural changes during competence development. Single-stranded gaps and single-stranded tails formed in chromosomal DNA during competence development. The generation of gaps was dependent on the rec-2 function. Since the rec-2 mutant is defective in the translocation of donor DNA, it was inferred that the gaps were involved in the translocation step of transformation. The generation of single-stranded tails was independent of the rec-1 and rec-2 genes. Therefore, these structures were assumed to play no direct role in the interaction of donor and recipient DNAs during transformation. Gaps were preferentially associated with a readily denaturable, possibly A + T-rich fraction of the genome. This finding raised the possibility that hot spots for transformation might be associated with A + T-rich DNA.

Chromosomes, Bacterial↗

Isolation of Haemophilus influenzae genes that suppress Escherichia coli polA mutations.

Haemophilus influenzae was found to produce a DNA polymerase that was similar to polymerase I of Escherichia coli. E. coli polA mutants were used as backgrounds for the selection of H. influenzae polA suppressor genes. Six different H. influenzae fragments were isolated that could suppress E. coli polA mutations. None of the suppressors appeared to encode the H. influenzae equivalent of the E. coli polA gene. One type of clone, represented by pGW41, caused a polymerase I activity to appear in a suppressed polA1 mutant. Plasmids from the pGW41 class contained two genes (pol-2 and pol-3) that were both required for polA suppression. Mutated nonsuppressing derivatives of the pGW41 class were used to create H. influenzae mutants that were deficient in polymerase I.

DNA Polymerase I↗

Rheumatoid blood decreases the adherence of polymorphonuclear cells (PMNs) to cultured endothelium.

Rheumatoid sera and plasma inhibited the adherence of normal blood polymorphonuclear cells (PMNs) to cultured porcine endothelium. This inhibition of adhesion was not seen when PMNs were treated with the plasma or serum from normal subjects or patients with other inflammatory arthropathies. The abrogation of PMN adherence was directly related to the levels of circulating immune complexes and was not dependent upon the type of anti-inflammatory therapy that the patients were receiving nor on any of the recorded clinical parameters. A similar inhibition of adhesion was seen with heat induced aggregated human IgG (HAGG) provided that serum was present in the culture medium. In view of these results we propose that circulating immune complexes in RA may have a significant role in controlling the interaction of PMNs with vascular endothelium and in perpetuating the entry of these cells into the synovial fluid of the inflamed joints.

Antigen-Antibody Complex↗

Is the surface charge on granulocytes really decreased following their exposure to chemotactic factors?

The mean axial ratio of polarised granulocytes has been determined and interpolated with plots relating settling factors (the inverse of relative frictional coefficients) to the axial ratios of simple isotropic solids. The estimate for the relative frictional coefficient of polarised granulocytes obtained by this procedure (f/fo = 1.11) suggests that a change in cell shape can account largely for the previously observed decreases in granulocyte electrophoretic mobility that occur following exposure to chemotaxins. In consequence, the widely held view that chemotaxins induce an alteration in cell surface charge is open to re-appraisal.

Cell Movement↗

Progress toward developing a cataract classification system.

A cataract classification system is being developed based on a set of standard photographs. The system uses an ordinal scale ranging from 0 (no opacities) to 2 (definite opacities) to classify cataractous changes in the nuclear, cortical, and posterior subcapsular lens zones. The reproducibility of slitlamp-derived and photo-derived classifications using the system was evaluated. The reproducibility between 2 observers for slitlamp-derived classifications was very high (n = 60). The reproducibility within and among 4 photography readers was also good for photo-derived classifications (n = 100). Discrepancies were found between ratings derived from slitlamp examinations and from photographs; such discrepancies were most frequent for gradings of cortical opacities.

Cataract↗

The interaction of stimulus and reinforcer control in complex temporal discrimination.

Six pigeons were trained in a discrete-trials signal-detection procedure to discriminate between a fixed-duration stimulus (5 s or 20 s) and a set of variable durations ranging from 2.5 s to 57.5 s in steps of 5 s. For each fixed-duration stimulus, the ratio of reinforcer frequencies contingent upon reporting the fixed versus the variable stimulus was systematically manipulated. Detection performance was well controlled by both the stimulus value and the reinforcer ratio. Both the discriminability between the fixed duration and the set of variable durations, and the discriminability between the fixed duration and each of the variable durations, were independent of the reinforcer-frequency ratio when discriminability was measured as log d. The sensitivity of response bias to reinforcement-ratio changes was independent of the value of the fixed duration, but was not independent of the discriminability of the variable durations from the fixed durations. Under current models, discriminability measures in complex temporal discrimination may be independent of biasing manipulations, but bias measures are not independent of stimulus values.

Animals↗

Sources of variance in the objective documentation of human cataractous change with Topcon SL-45 and Neitz-CTR retroillumination photography and computerized image analysis.

In the application of Topcon SL-45 Scheimpflug slit and Neitz CTR retroillumination photography to in vivo documentation of cataractous change, several sources of variance affect the results of each technique. We have measured the between-person, between-photographer, between-focal plane (Neitz), between-photo session, replicate photograph (Topcon), between-image analyst and replicate image analysis variances encountered in in vivo documentation of human cataracts with the Topcon SL-45 and Neitz-CTR cameras and our system of computerized image analysis.

Adult↗

MRL-lpr/lpr mice show an impairment of IgG aggregate removal which relates to parameters of disease activity.

MRL-lpr/lpr mice show an age-related impairment in the removal of heat-aggregated IgG (HAGG) from the circulation. The female mice, which have an earlier mortality than their male counterparts, clear HAGG more slowly than the male animals. Delay in clearance of this probe of mononuclear phagocytic system (MPS) function relates directly to high levels of circulating immune complexes (CIC) and to significant renal damage. In addition it relates indirectly to hepatic and splenic uptake of HAGG. MPS saturation plays a significant role in the pathogenesis of the disease seen in MRL-lpr/lpr mice.

Aging↗

rpe, a cis-acting element from the strA region of the Haemophilus influenzae chromosome that makes plasmid establishment independent of recombination.

Plasmids that share homology with the Haemophilus influenzae chromosome transform wild-type cells more efficiently than they transform recombination-defective mutants. A 5.2-kilobase-pair chromosomal fragment containing the strA gene of H. influenzae was found to promote efficient plasmid establishment in recombination-defective mutants. A cis-acting element in the insert, called rpe for rec-less plasmid establishment, promoted plasmid transformation in rec-1 and rec-2 mutants without suppressing the recombination defects of these strains. The rpe locus increased plasmid transformation in wild-type cells without interfering with the pathway of plasmid establishment that is dependent on recombination functions.

Chromosome Mapping↗

Delayed reinforcement and delayed choice in symbolic matching to sample: Effects on stimulus discriminability.

Six pigeons were trained to peck a red side key when the brighter of two white lights (S(1)) had been presented on the center key, and to peck a green side key when the dimmer of two white lights (S(2)) had been presented on the center key. Equal frequencies of reinforcers were provided for the two types of correct choice. Incorrect choices, red side-key pecks following S(2) presentations and green side-key pecks following S(1) presentations, resulted in blackout. With 0-s delay between choice and reinforcement, the delay between sample presentation and choice was varied from 0 to 20 s. Then, with 0-s delay between sample presentation and choice, the delay between choice and reinforcement was varied from 0 to 20 s. Both types of delay resulted in decreased discriminability (defined in terms of a signal-detection analysis) of the center-key stimuli, but delayed choice had more effect on discriminability than did delayed reinforcement. These data are consistent with the view that the two kinds of delay operate differently. The effect of a sample-choice delay may result from a degradation of the conditional discriminative stimuli during the delay; the effect of a choice-reinforcer delay may result from a decrement in control by differential reinforcement.

Journal Article↗

Pepsinogen--an immunoglobulin binding artefact in 'collagen' preparations.

It has previously been shown that extracts of human articular cartilage, many many of which contain type II collagen, react with heat-aggregated immunoglobulin and artificially prepared immune complexes. Sera from patients with rheumatoid arthritis and psoriatic arthritis, but not from patients with inflammatory bowel disease, react with these extracts. There are two distinct patterns of binding, either as low molecular weight immune complexes or as free antibody directed against collagen. Aggregate-binding activity identified in extracts of human articular cartilage following pepsin digestion was found to be distinct from collagen in its salt solubility. Further purification of this aggregate-binding factor by SDS gel electrophoresis has shown it to be an artefact resulting from the binding of small immune complexes to pepsinogen present in the pepsin preparation used to digest the cartilage.

Antigen-Antibody Complex↗

Cellular processing of bovine factors X and Xa by cultured bovine aortic endothelial cells.

Previous studies have shown that Factor X and Factor Xa bind specifically to distinct sites on the endothelial cell surface. Since the coagulant activity of a cell-bound clotting protein is dependent on its remaining on the cell surface, endocytosis and degradation studies have been carried out. Cell-bound Factor X was internalized at 0.07 fmol/min/10(6) cells, a rate slower than its dissociation from the cell surface. Endocytosed Factor X was not degraded, but was returned to the cell surface. In contrast, Factor Xa was internalized at an initial rate of 0.38 fmol/min/10(6) cells and subsequently degraded at about the same rate. The degradation of Factor Xa was prevented by chloroquine. These results suggest that Factor Xa is internalized and degraded by a lysosomal-dependent pathway. Studies with Factor X- and Xa-colloidal gold conjugates showed endocytosis proceeding at coated pit regions, and accumulation of Factor Xa-gold particles in lysosome-like structures. Endocytosis was studied as a clearance pathway for cell-bound Factor Xa by activating Factor X with Factors IXa and VIII on the endothelial cell surface. Endocytosis of the Factor Xa formed was significant, as only 44% of the Factor Xa formed was released into the supernatant, whereas the remainder was internalized and degraded. Thus, endocytosis of Factor Xa bound to its specific endothelial cell sites may be an important factor in the balance of vessel wall hemostatic mechanisms.

Animals↗

Monocytic differentiation induced by 1,25 dihydroxyvitamin D3 in myeloid cells: an ultrastructural immunocytochemical study.

We have studied, by ultrastructural morphology and immunocytochemistry, the alterations that occur in cells from the HL60 leukaemia cell line and from patients with CGL following incubation in vitro with 1,25(OH)2D3 for 2-5 days. The main morphological changes observed were in the nuclear shape, the development of autophagic vacuoles and the appearance of a population of small granules in the cytoplasm. These changes were associated with a significant reduction in MPO activity and increased expression of membrane antigens detected by the monocyte-specific McAb FMC17 and FMC32, as shown by the IGM at EM level, and a decrease in granulocyte-specific antigens demonstrated by the McAb FMC10. These observations suggest that promyelocytes and myelocytes could transform into monocyte-like cells and that this remodelling of cells was associated with autophagic digestion of cellular structures.

Antibodies, Monoclonal↗

Studies on the significance of the R1 anti-reticulin antibody associated with gluten sensitivity.

The R1 type anti-reticulin antibody (ARA) is closely associated with gluten-sensitive enteropathy. It disappears from the circulation within a few weeks of starting on a gluten-free diet and often reappears following gluten challenge. It is not clear how gluten ingestion leads to the production of the ARA. We have investigated four possibilities. (1) The ARA is simply a food antibody generated against meats in the diet. (2) The ARA is an anti-gluten antibody which cross-reacts with reticulin. (3) Gluten binds to gut reticulin in vivo rendering reticulin autoimmunogenic. (4) Immune complexes of gluten and anti-gluten antibody bind to reticulin (by virtue of the affinity that gluten has for reticulin) to give the appearance of an ARA in immunofluorescence tests. Our results do not support any of these possible explanations, and the significance of the ARA remains obscure.

Antibodies↗

Component probability and component reinforcer rate as biasers of free-operant detection.

Six pigeons were trained on multiple schedules whose components were concurrent variable-interval extinction and concurrent extinction variable-interval schedules. In Experiments 1a and 1b the stimuli signaling the components were two different light intensities, and in Experiments 2a and 2b they were two identical intensities. The components of the multiple schedule changed probabilistically after each reinforcer. In Experiments 1a and 2a, the probability of presenting the components was varied over five conditions and a replication. In Experiments 1b and 2b, the component probability was .5 and the component reinforcer rates were varied systematically over five conditions and a replication. The data, analyzed according to the Davison-Tustin behavioral detection model, confirmed that the discriminability of the stimuli signaling the components was high when the stimuli were different, and low when the stimuli were the same. Discriminability, measured by log d, was unaffected by component probability variation and by component reinforcer-rate variation. When discriminability was high, bias, or the response allocation between the two keys, was more strongly affected by variation of reinforcer rate within components than by variation of component probability, but the reverse was found when discriminability was low. The results suggest that free-operant detection performance is controlled by the rates of reinforcers in periods of time in which stimuli signal differential contingencies. These periods comprise the components when the component stimuli are discriminable, and comprise the total session when the components are indiscriminable. An extension of the Davison-Tustin behavioral detection model that incorporates these results is presented.

Journal Article↗

Measurements of maximum respiratory pressures in polymyositis and dermatomyositis.

Measurements of maximum respiratory pressures and routine pulmonary function tests were performed in 8 patients with polymyositis (PM) and 2 patients with dermatomyositis (DM). Serial measurements of routine pulmonary function tests in 8 patients remained unchanged. Maximum respiratory pressures were decreased initially in 7 patients with proximal muscle weakness and clinically active muscle disease and improved with corticosteroid therapy in the 5 patients who were followed serially. In 3 patients with clinically stable disease the maximum respiratory muscle power was normal. Serial measurements of maximum respiratory pressures have been of value in monitoring patients with PM and DM.

Adult↗