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Biomedical subjects

D McCarthy

Publications and source records attributed to D McCarthy.

At least 55 records · Page 3Linked to original sources
PubMed1995

Delayed matching-to-sample performance: Effects of relative reinforcer frequency and of signaled versus unsignaled reinforcer magnitudes.

Six pigeons were trained on a delayed red-green matching-to-sample task that arranged four delays within sessions. Matching responses intermittently produced either 1.5-s access to food or 4.5-s access to food, and nonmatching responses produced either 1.5-s or 4.5-s blackout. Two phases were conducted: a signaled phase in which the reinforcer magnitudes (small and large) were signaled by houselights (positioned either on the left or right of the chamber), and an unsignaled phase in which there was no correlation between reinforcer magnitude and houselight position. In both phases, the relative frequency with which red and green matching responses produced food was varied across five values. Both matching accuracy and the sensitivity of performance to the distribution of reinforcers for matching responses decreased with increasing delays in both phases. In addition, accuracy and reinforcer sensitivity were significantly lower on signaled small-reinforcer trials compared with accuracy and sensitivity values on signaled large-reinforcer trials and on both types of unsignaled trials. These results are discussed in the context of research on both nonhuman animal and human memory.

Journal Article↗
PubMed1995

Effects of mild hypoxia on perceptual-motor performance: a signal-detection approach.

Twelve healthy male subjects were required to make speeded judgements concerning the orientation of visual stimuli while breathing air at reduced partial pressure in a hypobaric chamber at altitudes of 7000 and 12,000 ft. A control condition was also conducted at sea level, and subjects received practice on the task at sea level prior to the commencement of the experiment. Significantly slower response times were obtained at 7000 and 12,000 ft relative to sea level. A signal-detection analysis showed that accuracy of judgement was significantly poorer at 12,000 ft, but oxygen deprivation has no systematic effect on response criterion.

Adult↗
PubMed1994

Sequence of the rec-2 locus of Haemophilus influenzae: homologies to comE-ORF3 of Bacillus subtilis and msbA of Escherichia coli.

The nucleotide sequence of a 4243-bp PstI fragment containing the rec-2 gene of Haemophilus influenzae was determined. The amino acid (aa) sequences of four putative proteins were deduced from the corresponding open reading frames (ORFs). The 2400-bp ORF2 accounted for rec-2, based on the sequences of DNA fragments that contained rec-2::mini-Tn10 mutations. The rec-2 gene encoded a putative 800-aa protein with a M(r) of 90,561. Sequence analysis suggested that the rec-2 product contained nine highly probable integral membrane-spanning segments. Database searches showed that rec-2 was homologous to the comE-ORF3 gene of Bacillus subtilis. This hypothesis is consistent with the known involvement of both of these genes in the passage of transforming DNA through the competent-cell envelope. Although the sequences of the other three ORFs were incomplete, sufficient data were available to allow inferences about their homologies to other genes. ORF4, which overlapped ORF1, was homologous to the Escherichia coli dnaK suppressor gene, dksA, and therefore was named dsh-1 (dnaK suppressor homolog). Mutations in dsh-1 and its putative promoter region caused a mild sensitivity to UV light, but did not affect DNA recombination. ORF3, located downstream from rec-2, was homologous to msbA, an essential gene of E. coli with extensive similarity to the ATP-dependent translocators. ORF3 was named msh-1 (msbA homolog). Mutations in msh-1 had no effects on genetic transformation. The close juxtaposition of rec-2 and msh-1 implied that the expression of msh-1 could be linked to the translation of the rec-2 ORF.

ATP-Binding Cassette Transporters↗
PubMed1994

An activity gel assay for the detection of DNA helicases and nucleases from cell-free extracts.

An activity gel assay was developed for the detection of DNA helicases in crude extracts. The assay was based on the ability of DNA helicases to unwind radioactive fragments from single-stranded M13 circles that were immobilized in an SDS polyacrylamide gel. The displaced radioactive strands were detected by blotting them to a filter and visualizing the resulting bands by autoradiography. Experiments with purified proteins demonstrated that DNA helicases, endonucleases and exonucleases could produce activity bands. A one-dimensional gel assay was sufficiently sensitive to allow detection of DNA helicase I, DNA helicase II, DNA helicase IV, the RecQ helicase as well as 3 unidentified putative DNA helicases in crude extracts of Escherichia coli. Exonuclease and endonuclease activities from crude extracts could be distinguished from DNA helicase activities by their ATP-independence and from each other by their band morphologies.

Base Sequence↗
PubMed1994

Effects of the discriminability of alternatives in three-alternative concurrent-schedule performance.

Six pigeons were trained on two- and three-alternative concurrent schedules in which the alternatives were signaled by different wavelengths of light on the main pecking key. The schedules were arranged according to a switching-key procedure in which pecks on a white side key produced a 3-s blackout and, intermittently, a change in the variable-interval schedule of food programmed on the main (center) key after the blackout. In Part 1, a two-alternative concurrent variable-interval schedule was arranged in which the alternatives were signaled by 560 nm and 630 nm. Parts 2 and 3 arranged three-alternative concurrent variable-interval schedules with the alternatives signaled by 560 nm, 600 nm, and 630 nm (Part 2) and 560 nm, 623 nm, and 630 nm (Part 3). Within each part, the relative rate of food reinforcers available on the alternatives was varied across a wide range. In all parts of the experiment, the ratios of responses emitted between pairs of alternatives were more extreme than the ratios of reinforcers obtained on the pairs of alternatives, a result termed overmatching. In Parts 2 and 3, generalized matching sensitivities between pairs of alternatives were found to be higher when the reinforcer rate on the third alternative was low than when it was high-an apparent failure of the constant-ratio rule. The data were well described by an extension of the Davison and Jenkins (1985) model, which assumes differing discriminabilities between concurrent-schedule alternatives in combination with a punishing effect of blackout following changeovers.

Journal Article↗
PubMed1994

Leaving patches: Effects of travel requirements.

Five pigeons were trained in an analogue foraging procedure in which, by completing a travel requirement, they entered a "patch" in which a reinforcer might be available after an unpredictable time. They also had the opportunity, by emitting a defined response, to exit the patch and travel to another patch. Prey availability in a patch was not signaled. Data were collected on the length of time that subjects stayed in patches before exiting (residence times) as a function of various travel requirements: travel for a fixed time in blackout, fixed-interval schedule traveling, fixed-time traveling with an added response required to terminate traveling, and fixed-ratio traveling. For each of these conditions, the required amount of travel (time or responses) was varied over a wide range. As previously reported, residence times increased with increases in fixed-time traveling, as they did with increasing fixed-interval or fixed-ratio traveling. There was no evidence that adding response or work requirements systematically affected residence time except via increased travel time, although 3 of the 5 birds stayed longer in a patch under higher fixed-ratio values. A "threshold-maximization" model described the data well with a single parameter that was consistent across subjects, procedures, and experiments.

Journal Article↗
PubMed1994

Leaving patches: An investigation of a laboratory analogue.

Five pigeons were trained on a procedure that has been used as a laboratory analogue to natural patch residence. Trials commenced with two responses available. One of these might provide a reinforcer if the patch was a prey patch; the other ended the residence time in the patch and, after a fixed travel time in blackout, produced another patch that might or might not provide a reinforcer. Patch residence also ended, and was followed by the same travel time, after a reinforcer was obtained or after a fixed maximum time was spent in the patch. The dependent variable was patch residence time, from the commencement of the patch to the time at which the subject emitted a response to exit from the patch or until the maximum patch residence time had elapsed. In Parts 1 to 3, the duration of the imposed travel time was varied from 0.25 to 16 s at three different probabilities (.05, .1, and .2) of food per second (lambda) in prey patches. As reported in previous research, both increasing travel time and decreasing probabilities of reinforcers per second increased patch residence time. In Parts 4 to 7, the probability of prey trials (rho) was varied in an irregular order from .1, through .2, .5, and .7, to .9 for different combinations of lambda and travel time. Respectively, these were in Part 4, .05 per second and 0.25 s; in Part 5, .05 per second and 16 s; in Part 6, .2 per second and 0.25 s; and in Part 7, .2 per second and 16 s. A previously offered model, based on optimization assumptions, substantially and consistently underpredicted patch residence time. However, a modification of that model, which assumes that the subjects could not accurately discriminate the residence time that provided the minimum interreinforcer interval, described the data well. The same model also described previously reported residence times in a different species with a uniform distribution of prey-arrival times.

Journal Article↗
PubMed1994

The effect of pre-fitting counselling on the outcome of hearing aid fittings.

The effect of pre-fitting counselling on the outcome of fittings of NHS behind-the-ear hearing aids to adult first-time users was investigated. Questionnaires and diaries were sent both before and after fitting to 48 subjects who were given pre-fitting counselling and 47 control subjects, all of whom were fitted with standard NHS hearing aids in Southampton or Bath between September 1989 and July 1991. The test and control groups had similar distributions of age, sex and hearing loss. Analysis of the data showed that the counselling had no significant effect on levels of satisfaction, aid usage or benefit; these outcome measures also showed no significant correlation with any of the personal characteristics or attitude factors which were studied.

Aged↗
PubMed1994

A survey of methods of processing and storage of bone marrow and blood stem cells in the EBMT.

We conducted a survey to identify current practices in bone marrow processing, preservation and storage by mailing a questionnaire to 155 bone marrow transplant centres listed in the EBMT records. Approximately 57% of centres replied. There were wide variations in methodology which reflected the different types of disease being treated, local conditions and personal preferences. A number of areas where more caution could be exercised were identified: possible reinfusion of excessive quantities of heparin, possible misuse of disposable needles and lack of awareness of the implications of product liability rules relating to cooling rate, storage and viability data.

Anticoagulants↗
PubMed1993

Picosecond neodymium:yttrium lithium fluoride laser sclerectomy.

The picosecond neodymium:yttrium lithium fluoride laser, a high-power, short-pulse laser that uses low energy per pulse and has a high repetition rate and a highly coherent energy source of 1,053 nm, was used to perform sclerectomies by an ab externo approach in human cadaver eyes. We evaluated laser settings with regard to full-thickness scleral perforation and thermal damage to surrounding tissue. We studied energy per pulse, depth per burst (a present number of spots), spot and line separation of the pattern (spacing between spots of the laser in length [spot separation] and width [line separation]), and total energy required to perforate the sclera. Efficiency was determined by evaluating which settings required the fewest spots and least total energy to perforate the sclera. We studied histologic sections of the sclerectomy sites to determine thermal damage to the surrounding sclera. The picosecond neodymium:yttrium lithium fluoride laser is effective in performing full-thickness sclerectomy with minimal thermal damage to the surrounding tissue. The anterior chamber could be penetrated with an average total energy of 13.3 +/- 0.4 (SEM) J. The sclerectomy size was 545 +/- 11 microns externally and 163 +/- 4 microns internally. Successful sclerectomies were performed with as little as 3 to 5 microns of thermal damage to the surrounding scleral tissue with 250 microJ per pulse.

Cadaver↗
PubMed1993

The Lens Opacities Classification System III. The Longitudinal Study of Cataract Study Group.

OBJECTIVE: To develop the Lens Opacities Classification System III (LOCS III) to overcome the limitations inherent in lens classification using LOCS II. These limitations include unequal intervals between standards, only one standard for color grading, use of integer grading, and wide 95% tolerance limits. DESIGN AND RESULTS: The LOCS III contains an expanded set of standards that were selected from the Longitudinal Study of Cataract slide library at the Center for Clinical Cataract Research, Boston, Mass. It consists of six slit-lamp images for grading nuclear color (NC) and nuclear opalescence (NO), five retroillumination images for grading cortical cataract (C), and five retroillumination images for grading posterior subcapsular (P) cataract. Cataract severity is graded on a decimal scale, and the standards have regularly spaced intervals on a decimal scale. The 95% tolerance limits are reduced from 2.0 for each class with LOCS II to 0.7 for nuclear opalescence, 0.7 for nuclear color, 0.5 for cortical cataract, and 1.0 for posterior subcapsular cataract with the LOCS III, with excellent interobserver agreement. CONCLUSION: The LOCS III is an improved LOCS system for grading slit-lamp and retroillumination images of age-related cataract.

Aging↗
PubMed1993

Apoptosis as a mechanism of tributyltin cytotoxicity to thymocytes: relationship of apoptotic markers to biochemical and cellular effects.

Recent in vitro studies have suggested that activation of apoptosis could account for the profound depletion of cortical thymocytes, which characterizes tributyltin (TBT) immunotoxicity. However, it has also been shown that TBT disrupts macromolecular synthesis and cellular energetics to an extent that might be expected to interfere with the initiation of apoptosis. The purpose of these studies was to further evaluate the morphological and biochemical characteristics of thymocyte killing by TBT and to relate this to key cellular processes. Ex vivo thymocyte cultures from immature rats were treated with bis(tri-n-butyltin) oxide (TBTO) at concentrations ranging from those which rapidly produced necrosis (5-10 microM), down to cytotoxic but subnecrotic concentrations (0.1-2 microM). In cells exposed to TBTO concentrations that caused a rapid and near maximal inhibition of protein synthesis, it remained possible to demonstrate the stereotypic internucleosomal DNA cleavage and morphological changes indicative of apoptosis. Further confirmation that apoptosis was occurring independently from protein synthesis was provided by the absence of a protective effect following cycloheximide pretreatment. Apoptosis still occurred in TBTO-treated thymocytes although intracellular ATP levels were depressed to 20% or less of control values. Cytoprotective effects were noted with the intracellular Ca2+ chelators BAPTA-AM and Quin-2 AM, and also with zinc. Cell killing by TBTO occurred without overt disturbance of thymocyte cell cycle parameters. These results indicate that thymocyte apoptosis stimulated by TBT exposure occurs independently of a requirement for protein synthesis and does not require fully conserved cellular energetics.

Adenosine Triphosphate↗
PubMed1993

Leukocyte activation and function-associated antigens in inflammatory disease.

Expression of adhesion molecules, CD11a, CD11b and CD18, and of the function-associated molecules CD3, CD4, CD8, CD16, CD19, CD56 and CD57 was assayed on peripheral blood leukocytes from normal control subjects (n = 10), and from patients with adult periodontitis PD (n = 9), ankylosing spondylitis AS (n = 11) and rheumatoid arthritis RA (n = 14). A novel rapid fixation leukocyte preparation technique was used which prevents artefactual up-regulation of surface antigens. In RA patients, the percentage of CD18+ lymphocytes was decreased and that of CD11b+ neutrophils was increased. On lymphocytes the mean fluorescence intensity (MFI) of both CD11b and CD18 was decreased whereas that of CD57 was increased. In AS patients the percentages of CD11b+ lymphocytes and neutrophils were increased and CD18+ lymphocytes and neutrophils were decreased. On lymphocytes the MFIs of CD11b and CD18 were decreased, whilst that of CD16 was increased. On neutrophils the MFI for CD18 was increased. No significant differences (p < 0.01) were seen for the periodontitis patients. It is suggested that the antigen expression on peripheral blood cells from RA and AS patients is consistent with leukocyte activation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1993

Abnormal binding properties of blood monocytes in rheumatoid arthritis.

Blood monocytes from patients with RA exhibited a greater binding to monolayers of umbilical cord vein endothelium than monocytes from control subjects (mean 42% increase; p < 0.01). When control monocytes were added to TNF or IL-1 treated endothelium their adhesion was enhanced (mean 24% increase; p < 0.05), whereas the number of monocytes from RA patients binding to TNF or IL-1 treated monolayers was less than that adhering to untreated endothelial cells (mean 22% inhibition; p < 0.02). The surface expression of CD11b/CD18 on RA monocytes was increased and pretreatment of normal and RA cells with an anti-CD18 monoclonal antibody inhibited their attachment to untreated and cytokine-treated endothelial cells. Normal blood monocytes activated with LPS demonstrated an enhanced binding to untreated cultures (mean 23% increase; p < 0.05) and an inhibited attachment to cytokine-treated endothelial cells. This study suggests that blood monocytes in RA may be activated and that this property modifies the attachment of these cells to normal and "inflammatory" endothelium.

Arthritis, Rheumatoid↗
PubMed1993

Quantitating cataract and nuclear brunescence, the Harvard and LOCS systems.

Subjective and objective systems are used to quantify cataract at The Center for Clinical Cataract Research. We have described each system and its use, presented data on reproducibility and validity, and for objective systems, demonstrated the correlation to the subjective grade of the cataract as defined by the Lens Opacities Classification Systems, Versions II and III (LOCS II and III). The subjective systems are used to classify nuclear color, nuclear opalescence, cortical cataract, and posterior subcapsular cataract. Reported kappa scores for LOCS II range from 0.85 to 1.0. Intraclass correlation coefficients for LOCS III (r1) range from 0.67 to 0.94. The computerized objective system are: (1) fast spectral scanning colorimetry (FSSC) for assessment of nuclear color (r1 = 0.96 to 0.98); (2) nuclear mean density (NMD) for assessment of nuclear opalescence (r1 = 0.97); and (3) percent area opacity (anterior = a; posterior = p) (OPAC-a and OPAC-p) for assessment of cortical and posterior subcapsular cataract (r1 = 0.92 to 0.96).

Adult↗
PubMed1993

Association of mononuclear cells and eosinophils with airway resistance and responsiveness in rat pulmonary inflammatory responses.

To evaluate the association of various leukocytes with pulmonary resistance and methacholine responsiveness, we induced pulmonary eosinophil-rich inflammation in IgE-sensitized (ovalbumin) Sprague Dawley rats. Sensitized rats were challenged with either relevant (OA) or irrelevant antigen by tracheal insufflation a) with no other treatment, b) in conjunction with intravenous Sephadex beads pretreatment, or c) with antigen coupled covalently to Sepharose beads. About 24 h after antigen challenge, respiratory system resistance (Rrs), response to aerosolized methacholine, and pulmonary histopathology were evaluated. Challenge with OA, insufflation with Sepharose, and treatment with i.v. Sephadex all independently increased inflammatory cell infiltrates, but the combination of OA with the other agents did not significantly enhance the inflammatory response over OA alone. Interactive stepwise regression techniques were utilized to identify correlates for Rrs and methacholine responsiveness. Mononuclear cell score was a significant predictor (p < .01) for Rrs, and insufflation of Sepharose had a significant independent effect on Rrs (p = .01) above that predicted by mononuclear cell infiltrates. Conversely, eosinophil score and neutrophil score were not significant predictors for Rrs, and challenges with antigen or Sephadex had no significant independent effect on Rrs beyond that predicted from mononuclear cell infiltrates. Eosinophil score was the only significant histological predictor for methacholine responsiveness (p < .0001). Challenges with Sephadex, antigen and Sepharose did not significantly change methacholine responsiveness independently of the changes associated with eosinophil infiltrates. These findings suggest that mononuclear cells and eosinophils contribute to increases in airway resistance and responsiveness, respectively, following the induction of pulmonary inflammation by both allergic and non-allergic stimuli.

Airway Resistance↗
PubMed1993

Loss of contrast sensitivity in diabetic patients with LOCS II classified cataracts.

Contrast sensitivity function (CSF) was assessed in a population of diabetics with moderate cataracts to determine if CSF testing provides more information about visual dysfunction than Snellen or Lotmar interferometric visual acuity. With the Lens Opacities Classification Systems Version II (LOCS II) of cataract classification it was possible to grade accurately the type and severity of cataract and nuclear brunescence. The presence of statistically significant relationships between increasing LOCS II classification (worsening cataract) and diminished function, even when the regression model was controlled for Snellen visual acuity, supports the thesis that CSF measurements do provide more information about cataract related visual loss than Snellen acuity alone. Statistically significant (p < or = 0.05) relationships existed between different morphological types of cataract, nuclear colour, and CSF at specific frequencies. The frequencies affected differed with cataract type or nuclear colour, and with distance and near CSF.

Adult↗