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Biomedical subjects

D McCarthy

Publications and source records attributed to D McCarthy.

At least 127 records · Page 7Linked to original sources
PubMed1985

MRL mice show an age-related impairment of IgG aggregate removal from the circulation.

The fate of heat-aggregated human IgG (HAGG) was examined in young and old autoimmune MRL-lpr/lpr and MRL-+/+ mice and compared to BALB/c mice of different ages. Following iv injection of [125I] HAGG the older MRL-lpr/lpr and MRL-+/+ mice showed impaired hepatic and splenic uptake of this material. In addition the clearance rate of HAGG was significantly slower in the older MRL-lpr/lpr mice (t1/2 = 50 min) when compared to younger controls (t1/2 = 13 min) although this age-related retardation of clearance was not observed in the MRL-+/+ mice. No difference was seen in the clearance rate or organ uptake studies of the two age groups of BALB/c mice. Catabolic studies using trichloracetic acid suggested that the HAGG was catabolized to smaller fragments with time but not to such a great extent in the older diseased animals, again no age-related difference was seen in the BALB/c mice. Our studies suggest that with age both autoimmune strains of MRL mice show some saturation of the mononuclear phagocytic system (MPS) and that this process is more obvious in the MRL-lpr/lpr mice. MPS saturation may play a role in the pathogenesis of autoimmune disease in these mice.

Aging↗
PubMed1984

The effect of vitamin D3 metabolites on normal and leukemic bone marrow cells in vitro.

We studied the effects of 1,25-dihydroxyvitamin D3 and other metabolites of vitamin D3 on the maturation in liquid culture and on colony formation in semisolid media of marrow and buffy coat cells from patients with myeloid leukemias and from normal individuals. After incubation with 1,25-dihydroxy-vitamin D3, a proportion of both normal and leukemic myeloid cells resembled cells of the monocyte-macrophage lineage; these cells expressed alpha-naphthylacetate esterase and were able to phagocytize and kill candida organisms. When granulocyte-macrophage progenitor cells (CFU-GM) were incubated with 1,25-dihydroxyvitamin D3, the number of monocyte-macrophage colonies was increased and the number of granulocyte colonies was reduced; megakaryocyte colony formation (CFU-Mk) was inhibited substantially; and there was no effect on erythroid (BFU-E) or multilineage (CFU-GEMM) progenitor cell colony formation. We propose that 1,25-dihydroxyvitamin D3 may induce cells that are normally committed to differentiate along the granulocytic pathways to differentiate instead along the monocyte-macrophage pathway. If these in vitro observations reflect the in vivo activity of 1,25-dihydroxyvitamin D3, it may be involved in the modulation of collagen deposits in the bone marrow.

24,25-Dihydroxyvitamin D 3↗
PubMed1984

Plasmid containing a DNA ligase gene from Haemophilus influenzae.

A ligase gene from Haemophilus influenzae was cloned into the shuttle vector pDM2 . Although the plasmid did not affect X-ray sensitivity, it caused an increase in UV sensitivity of the wild-type but not excision-defective H. influenzae and a decrease in UV sensitivity of the rec-1 mutant.

Cloning, Molecular↗
PubMed1984

Changes in normal polymorphonuclear leucocyte motility after ingestion of IgG aggregates.

Changes in normal polymorphonuclear leucocyte (PMN) motility after membrane-binding and internalisation of IgG aggregates (a model of soluble immune complexes) have been studied by the micropore filter assay. The results have confirmed that IgG aggregates stimulate as well as inhibit PMN chemotaxis. These effects are dependent on the size and concentration of the IgG aggregates in solution as well as the length of time of incubation. Stimulated chemotaxis was observed in a small subset of the whole PMN population which was apparent only when cell distribution through the filters was analysed. These results indicate the need for caution when drawing conclusions about PMN function from results obtained by these assay techniques.

Antigen-Antibody Complex↗
PubMed1984

Delayed signal detection, differential reinforcement, and short-term memory in the pigeon.

In two discrete-trial delayed-detection experiments, six pigeons were trained on dependent concurrent variable-interval schedules. Pecking a red side key was reinforced when the brighter of two white lights (S1) had been presented on the center key, and pecking a green side key was reinforced when the duller of two white lights (S2) had been presented on the center key. Incorrect responses were red side-key pecks following S2 presentations and green side-key pecks following S1 presentations; these resulted in three-second blackouts. In Experiment 1, the time between presentation of S1 or S2 on the center key and the onset of the red and green side keys was varied nonsystematically from 0.06 seconds to 19.69 seconds across experimental conditions. Stimulus discriminability decreased as the stimulus-choice delay increased. A rectangular-hyperbolic function better described this decrease in discriminability over time than did a negative-exponential function. In Experiment 2, at each of three stimulus-choice delays (0.06, 3.85, and 10.36 seconds), relative reinforcer frequency for correct responses to the red and green side keys was varied by changing the values of the dependent concurrent variable-interval schedules. The sensitivity of choice to relative reinforcer frequency was independent of the decrease in stimulus discriminability with increasing stimulus-choice delay.

Animals↗
PubMed1984

Isobias and alloiobias functions in animal psycophysics.

An analogue of the human yes-no detection task was used to train six pigeons to discriminate luminance differences under two different reinforcer-scheduling procedures. When a controlled reinforce-ratio procedure was used, relative stimulus frequency was constant at .5, and relative reinforcer frequency for correct detections was held constant at three different values for each of five luminance differences. When an uncontrolled reinforcer-ratio procedure (the typical detection paradigm) was used, relative reinforcer frequency for correct detections was allowed to covary with changes in relative stimulus frequency for each of five luminance differences. Two measures of bias, response bias (Davison & Tustin, 1978) and the detection-theory likelihood-ratio measure (beta obt), were compared. The controlled reinforcer-ratio procedure generated equal- or iso-response-bias functions, and the uncontrolled reinforcer-ratio procedure gave changing or alloio-response-bias functions. The Davison-Tustin model accounted for 88% and 93% of the data variance in the controlled and uncontrolled reinforcer-ratio procedures, respectively. The best-fitting equal-beta functions accounted for an average of 53% and 69%, respectively, in the two procedures. In addition, neither procedure gave constant measures of beta obt for constant bias manipulations across different discriminability measures.

Animals↗
PubMed1983

Localization of enzymes and alkaloidal metabolites in Papaver latex.

In continuing studies on the metabolic activity of Papaver somniferum, latex has been examined for its enzyme and alkaloidal metabolite content. After an initial centrifugation of latex at 1000g, the pellet which contained a heterogeneous population of dense organelles was further resolved on sucrose gradients. Of the enzymes monitored, acid phosphatase and L-3,4-dihydroxyphenylalanine decarboxylase were found to be in the latex 1000g supernatant, whereas catecholase (polyphenolase) was localized in two distinct organelles within the 1000g sediment. The lighter organelles, sedimenting at 30% sucrose, contained a soluble enzyme which was readily released on organelle plasmolysis, whereas the catecholase found within the heavier organelles, sedimenting at 55-60% sucrose, was membrane bound and showed significant activity only in the presence of Triton X-100. These latter organelles also contained the alkaloids, including morphine and thebaine, and were observed to readily accumulate [14CH3]morphine. The alkaloid precursor, dopamine, was localized in the same dense vesicle fraction as the alkaloids. The rate of uptake of [7-14C]dopamine into these fractions at room temperature, however, was markedly lower than that of morphine. Electron microscopic examination of the organelles of various densities revealed that they possessed different morphology. The results are consistent with the concept that both the 1000g and supernatant fractions of the latex are required for alkaloid biosynthesis and that a subpopulation of dense organelles found in the 1000g sediment have at least a function as a storage compartment for both alkaloids and their catecholamine precursor.

Alkaloids↗
PubMed1983

The effects of lowered temperature on spontaneous eye movements in a teleost fish.

A new opto-electronic method has been used to measure spontaneous eye movements in a lightly restrained unanaesthetized marine teleost fish (Parore). The normal scanning pattern of eye movement is similar to that previously described in goldfish. The effects of cooling on eye movements were investigated by 2 degrees C step changes down from ambient temperature (13-14 degrees C). Lowered temperature altered the scanning pattern, decreased saccade velocity, increased mean saccade amplitude and impaired the ability of the fish to hold the eye stationary between saccades. All eye movements stopped at temperatures around 6 degrees C, but could be restored by subsequent warming.

Animals↗
PubMed1983

Respiratory illness and hypophosphatemia.

We retrospectively reviewed the charts of 308 admissions to a pulmonary disease ward and 100 admissions to the general medical service over one year to find the prevalence, sequelae, and etiology of hypophosphatemia. The overall prevalence of low serum phosphate levels (less than 2.4 mg/dl) occurring at least once during hospitalization in chest patients was 17 percent, but was higher in patients with respiratory infections (28 percent). Moreover, the prevalence of hypophosphatemia on admission (before institution of intravenous fluid or drug therapy) was ten times higher in patients with respiratory infections than in patients with noninfectious respiratory illness or general medical patients (21 vs 2 percent, p less than 0.001). Serum phosphate less than 2.0 mg/dl occurred in 4 percent of patients. Twenty-seven percent of the patients (including two with ventilatory failure) with abnormally low serum phosphate levels had symptoms or signs of uncertain etiology later explicable by the presence of hypophosphatemia. The most common additional laboratory finding associated with hypophosphatemia was elevation of muscle enzymes. Although mortality was no higher in hypophosphatemic patients, hospital stay was twice as long as that of patients with normal levels of serum phosphate. No correlation was found between simultaneous arterial blood gases and serum phosphate levels. Two patients given antacids had severe hypophosphatemia and worsened ventilatory function; phosphate-binding antacids should be used judiciously in patients with severe respiratory disease, since they may lead to the development or worsening of hypophosphatemia and diminished ventilatory function.

Female↗
PubMed1983

Measures of response bias at minimum-detectable luminance levels in the pigeon.

Using an operant analogue of the yes-no detection task, six pigeons were trained to detect luminance changes under two different reinforcement-scheduling procedures. In the first, an uncontrolled reinforcement-ratio procedure, the relative frequency of food reinforcers obtained for correct detections was free to vary with the birds' behavior as luminance levels were changed. In the second, a controlled reinforcement-ratio procedure, changes in preference could not alter the relative distribution of food reinforcers between the two response alternatives. Extreme response biases developed as luminance was decreased to threshold in the uncontrolled procedure. No progressive changes in response bias as a function of decreasing luminance were seen in the controlled procedure. Absolute thresholds for light intensity were lower in the controlled than in the uncontrolled procedure.

Animals↗
PubMed1982

The concentration and subcellular localisation of zinc, magnesium and calcium in human polymorphonuclear leukocytes.

The calcium, magnesium and zinc content of human polymorphonuclear leukocyte homogenates and their subcellular fractions has been determined by atomic absorption spectrophotometry. Neutrophils were homogenised in sucrose medium and subjected to analytical subcellular fractionation. The sucrose density gradient fractions were assayed for zinc, magnesium and the principal organelle marker enzymes. Zinc was found to be largely soluble, with small amounts in the alkaline phosphatase-containing granules (phosphasomes). Magnesium had a multimodal distribution with a soluble component, and peaks corresponding to plasma membrane, specific granules and azurophils. The level of calcium, expressed per mg DNA, was significantly decreased in both chronic granulocytic leukaemia (CGL) and pregnancy. Leucocyte zinc was only significantly reduced in CGL. Leukocyte magnesium showed no significant variation within the three groups of subjects. No significant correlation was noted between the zinc, calcium or magnesium content and leukocyte alkaline phosphatase activity in any of the three groups.

Alkaline Phosphatase↗
PubMed1982

Immunoglobulin inclusions in rheumatoid arthritis polymorphonuclear cells: lack of correlation with circulating immune complexes.

A discriminating direct immunofluorescent test has been used to identify immunoglobulin inclusions in polymorphonuclear leucocytes (PMNs) isolated from the blood of patients with rheumatoid arthritis. These inclusions are thought to represent phagocytosed immune complexes, since normal PMNs incubated in RA sera known to contain raised levels of immune complexes developed similar immunoglobulin inclusions. Inclusions did not develop in normal PMNs incubated in normal serum. No correlation was found between the percentage of either RA blood PMNs with immunoglobulin inclusions or normal PMNs developing inclusions after incubation in RA sera, and levels of immune complexes in the corresponding sera. Using heat-aggregated IgG as a laboratory model of immune complexes, a simple relationship has been demonstrated between the uptake of IgG aggregates by normal PMNs and the concentrations of IgG aggregates in the test solutions over a concentration range of 12.5-200 micrograms . ml-1. These results indicate that the C1q- PEG test gives no measure of the actual amounts of immune complexes available in serum for phagocytosis.

Antigen-Antibody Complex↗
PubMed1982

Novobiocin resistance marker in Haemophilus influenzae that is not expressed on a plasmid.

The plasmid pNov2, carrying a cloned chromosomal marker conferring resistance to at least 2.5 micrograms of novobiocin per ml, was constructed with a new Haemophilus influenzae cloning vehicle, pDM2. The novobiocin marker of pNov2 was not normally expressed, but in Rec+ cells approximately one in 10(4) cells in a culture of a transformant became novobiocin resistant, a frequency about four orders of magnitude higher than the spontaneous mutation frequency. Variants of such cells that had lost the plasmid were also novobiocin resistant. Since Rec- cultures bearing pNov2 showed novobiocin resistance only at the normal mutation frequency, we concluded that the Rec+ novobiocin-resistant transformants arose because of a rare recombination between plasmid and chromosome in which the chromosome acquired the novobiocin marker from the plasmid. Evidence is presented that novobiocin sensitivity is dominant over this particular novobiocin resistance marker.

Chloramphenicol↗
PubMed1982

A plasmid cloning vehicle for Haemophilus influenzae and Escherichia coli.

A new plasmid cloning vehicle (pDM2) was used to introduce a library of Haemophilus influenzae chromosomal fragments into H. influenzae. Transformants of the highly recombination-defective rec-1 mutant were more likely to contain exclusively recombinant plasmids after exposure to ligated DNA mixtures than was the wild type. pDM2 could replicate in Escherichia coli K-12.

Ampicillin↗
PubMed1982

Stimulus discriminability in free-operant and discrete-trial detection procedures.

Six pigeons were trained to discriminate different light intensities in four experimental procedures. Experiment 1 compared stimulus discriminability in a yes-no signal-detection task with discriminability measures obtained from two free-operant procedures. Discriminability estimates were significantly lower in the detection procedure. Experiment 2 showed this lowered discriminability to be a function of the delay between stimulus presentation and the availability of the choice-response keys in the standard detection task. In addition, reinforcement sensitivity was lowest when correct choice responses were intermittently, rather than continuously, reinforced.

Animals↗