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Biomedical subjects

D McCarthy

Publications and source records attributed to D McCarthy.

At least 91 records · Page 5Linked to original sources
PubMed1990

Interleukin-2 inhibits growth of fibroblasts derived from human bone marrow.

The adherent layer that forms in human bone marrow suspension cultures contains fibroblast colonies which arise from colony-forming cells (CFU-F). We have demonstrated that recombinant interleukin-2 (r-IL2) inhibits growth of CFU-F by preventing their entry into S phase. This inhibition is not mediated by gamma-interferon, nor by T lymphocytes, and can be abrogated by anti-IL2 receptor antibody. r-IL2 may influence haematopoiesis by its effect on bone marrow CFU-F.

Biological Factors↗
PubMed1989

Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma.

32 previously untreated patients with multiple myeloma received vincristine, doxorubicin ('Adriamycin'), and dexamethasone (VAD) as first-line therapy. The overall response rate was 84%, with 28% of all patients entering complete remission. Response was rapid, with near-maximum response occurring after two courses of treatment and rapid improvement in bone-marrow function. Median response duration was 18 months and this seemed to be unaffected by initial prognostic criteria or by degree of remission achieved. The projected median survival was 44 months, with 75% of all patients and 83% of responders being alive at 2 years. Side-effects due to steroids were common, but there was only 1 treatment-related death. The high response rate and lack of toxicity offer an advantage over other forms of initial treatment, although other strategies will be necessary to prolong the duration of response.

Administration, Oral↗
PubMed1989

Cloning of the rec-2 locus of Haemophilus influenzae.

A collection of transposon mutants of Haemophilus influenzae was constructed by additive transformation with mutagenized chromosomal DNA. A rec-2::miniTn10 km mutation was cloned from a transformation-defective member of the mutant collection, followed by the reconstruction of the wild-type rec-2 locus by recombination to create pDM62. Southern blots showed that the commonly studied Rec-2 mutant, Rd(DB117)rec-, contained either a large deletion or a substitution that removed part of rec-2 locus. A collection of transposon mutations in pDM62 was used to characterize the rec-2 locus by complementation. A corresponding collection of mutants was also constructed. A single segment was required to complement the transformation defect in Rd(DB117)rec-. All of the transformation-defective transposon mutants failed to translocate donor DNA into then cell, in agreement with previous studies of Rd(DB117)rec-.

Blotting, Southern↗
PubMed1989

Binding of monomeric and aggregated immunoglobulin to enzymes. A source of artefact in antibody assays.

Pepsinogen has previously been shown to bind non-specifically to immune complexes and aggregated immunoglobulins. We demonstrate here using a solid-phase immunoassay that immunoglobulins aggregated by heat or glutaraldehyde bind non-specifically to several different enzymes. Some of these, including pepsinogen (marketed as pepsin), hyaluronidase and trypsin, are used in the breakdown of tissues or biochemical preparations during the preparation of antigens. Contamination of impure antigens by enzyme is likely to lead to products which bind non-specifically to immune complexes. This can cause misidentification of complexes as antibodies. We recommend that all tests for specific antibody involving the use of antigens prepared by these or other enzymes should include a control with aggregated immunoglobulin substituted for the test serum.

Antibodies↗
PubMed1989

Lens opacities classification system II (LOCS II)

The Lens Opacities Classification System, version II (LOCS II), uses a set of colored slit-lamp and retroillumination transparencies to grade different degrees of nuclear, cortical, and subcapsular cataract. The system uses four nuclear standards for grading nuclear opalescence and color, five cortical standards, and four subcapsular standards. The LOCS II can be used to grade patients' cataracts at the slit lamp or to grade slit-lamp and retroillumination photographs; it is easy to learn and can be applied consistently by different observers. We obtained very good interobserver reproducibility of the clinical gradings at the slit lamp, excellent intraobserver reproducibility, very good to excellent interobserver reproducibility of photographic gradings, and good agreement between clinical and photographic gradings. The LOCS II is potentially useful for both cross-sectional and longitudinal studies of cataract.

Cataract↗
PubMed1989

The prevalence and management of pain in patients with AIDS: a review of 134 cases.

In light of the lack of any prior systematic evaluations of the prevalence and types of pain syndromes and treatments found in patients with AIDS, a chart review study was undertaken to evaluate this issue. Fifty-two of 96 charts reviewed (54%) had at least one note on nonprocedural pain or analgesic prescription. Although chest pain was the most prevalent pain location (22%), presumably because of the high incidence of Pneumocystis carinii pneumonia, other possible AIDS-related entities, such as peripheral neuropathy and thrombophlebitis, were also found. No specific AIDS syndromes could be identified that were related to a higher incidence of pain. Nearly one-third of patients with pain received codeine (31%), others received acetaminophen (27%), and 17% of patients received acetaminophen and oxycodone HCl. Specific pain management interventions must be evaluated and applied to control the nontrivial occurrence of pain in patients who have AIDS symptoms that may be overlooked by the physician given the overwhelming disease process.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Identification of Escherichia coli DNA helicase IV with the use of a DNA helicase activity gel.

A DNA helicase activity gel was developed based on the assumption that DNA helicases could unwind double-stranded DNA in a polyacrylamide matrix. The production of single-stranded DNA was detected by staining the activity gel with acridine orange and visualizing the gel under long-wave UV light. The products of DNA helicase activities appeared as red bands within a green fluorescent background. A novel DNA helicase, called helicase IV, was detected in crude extracts of Escherichia coli with the use of the helicases activity gel assay. The new DNA helicase was purified to near homogeneity. The chromatographic properties and the sequence of its 11 amino-terminal residues proved that helicase IV was distinct from all of the previously described DNA helicases from E. coli.

Amino Acid Sequence↗
PubMed1989

A quantitative analysis of chain-schedule performance.

Six pigeons were trained with a chain variable-interval variable-interval schedule on the left key and with reinforcers available on the right key on a single variable-interval schedule arranged concurrently with both links of the chain. All three schedules were separately and systematically varied over a wide range of mean intervals. During these manipulations, the obtained reinforcer rates on constant arranged schedules also frequently changed systematically. Increasing reinforcer rates in Link 2 of the chain increased response rates in both links and decreased response rates in the variable-interval schedule concurrently available with Link 2. Increasing Link-1 reinforcer rates increased Link-1 response rates and decreased Link-2 response rates. Increasing reinforcer rates on the right-key schedule decreased response rates in Link 1 of the chain but did not affect the rate in Link 2. The results extend and amplify previous analyses of chain-schedule performance and help define the effects that a quantitative model must describe. However, the complexity of the results, and the fact that constant arranged reinforcer schedules did not necessarily lead to constant obtained reinforcer rates, precluded a quantitative analysis.

Journal Article↗
PubMed1989

Effects of relative reinforcer frequency on complex color detection.

Pigeons were trained under a discrete-trials detection procedure in which one of a set of color stimuli was presented on the center key and a single response turned off the stimulus and illuminated two side keys. Single responses to one or the other side key produced occasional reinforcers depending on the value of the color stimulus. In Experiment 1, one color-stimulus set comprised 559, 564, 569, and 574 nm, and right-key pecks were occasionally reinforced following presentations of members of this set. The other stimulus set comprised 579, 584, 589, and 594 nm, and left-key pecks were occasionally reinforced following presentations of members of this set. Across seven experimental conditions, the left/(left + right) relative reinforcer frequency was varied from .1 to .9. In Experiment 2, one stimulus set contained only one member, 574 nm, and right-key responses were occasionally reinforced following its presentation. Over 12 experimental conditions, two manipulations were carried out. First, the number of stimuli comprising the other stimulus set was increased from one (579 nm) to two (579 and 584 nm) to three (579, 584, and 589 nm) and to four (579, 584, 589, and 594 nm), and left-key responses were reinforced occasionally following center-key presentations of members of this set. Second, for each stimulus combination, the left/(left + right) relative reinforcer frequency was varied from .1 to .5 to .9 across three experimental conditions. The principal finding of Experiments 1 and 2 was that reinforcers and stimuli interacted in their effects on behavior. In Experiment 3, pairs of adjacent stimuli (5 nm apart) in the range 559 to 594 nm were presented in each experimental condition, and the left/(left + right) relative reinforcer frequency was held constant at .5. The data from all three experiments were analyzed according to a detection model describing performance in multiple-stimulus two-response procedures. This model provided independent measures of stimulus discriminability, contingency discriminability, and bias. The analysis showed that (a) consistent with the color-naming function, pigeons were better able to discriminate between higher nanometer values than lower nanometer values; (b) their ability to discriminate between the stimuli was independent of the number of wavelengths comprising each stimulus set; (c) they allocated delivered reinforcers very accurately to the previously emitted response; and (d) no consistent biases emerged.

Journal Article↗
PubMed1989

Strategies for measuring the rate of age-related cataract formation in vivo.

The Lens Opacities Classification System (LOCS II) has been tested as a method for detecting and grading longitudinal changes in cataract severity. The LOCS I and II systems have already been tested and validated for cross-sectional classification of human cataracts in vivo. 130 eyes (of 68 patients) were photographed at baseline and follow-up visits with Neitz CTR and Zeiss slit photography. The mean length of follow-up was 14.7 +/- 4.4 months. The severity of nuclear opalescence (NO), cortical (C) and posterior subcapular cataract (P) was graded in a masked fashion using the LOCS II standards. Side-by-side comparisons of baseline and follow-up photos were also done in a masked fashion to detect more subtle changes than might be evident in the LOCS II gradings. The annual percent progression in cataracts graded by LOCS II standards are: (NO): 12.4%, (C): 17.9%, and (P): 6.5%. The LOCS II standards are offered as a promising subjective method for longitudinal grading of human cataractous change in vivo.

Aged↗
PubMed1989

Heat-induced aggregated human IgG modifies the adherence of human polymorphonuclear cells to cultured endothelium.

The adherence of human blood polymorphonuclear cells (PMNC) to cultured porcine aortic endothelium was enhanced by high concentrations of heat-stable IgG aggregates (HAGG) when sera was omitted from the culture media. With 20% human serum present in the media, HAGG induced a dose-related inhibition of PMNC adhesions with concentrations as low as 10 micrograms/ml producing a significant effect. This inhibitory action of HAGG, which was optimally expressed after 30 min of incubation, seemed to be directed at the PMNC rather than the endothelium. Heat-inactivation of the sera resulted in a marked decline of the inhibitory activity of HAGG. Aggregates of size 15-21 s were demonstrated to be most effective in inhibiting PMNC attachment and it is complexes of this size which are commonly found in the circulation of patients with chronic inflammatory diseases. Immune complex modification of PMNC adherence may control leucocyte extravasation during inflammation.

Antigen-Antibody Complex↗
PubMed1988

Evaluation of a Lens Opacities Classification System.

A simple system, based on standard photographs, has been developed to classify lens opacities. The system allows the definition of cataract cases and noncases according to the location of lens opacification (nuclear, cortical, posterior subcapsular) and its extent (early or more advanced). Evaluation of the system has shown good to excellent reproducibility for clinical and photographic classifications. Comparisons of clinical and photograph-derived gradings has shown generally good agreement in classifying the presence and type of cataract; this agreement is highest for nuclear cataract. Photographic gradings of posterior subcapsular and, to a lesser degree, cortical opacities tend to underestimate the extent of opacification found by clinical gradings. The Lens Opacities Case-Control Study system is simple, reproducible, and easy to implement; it is offered for use in case-control and other cross-sectional studies of cataract with compatible classification goals.

Aged↗
PubMed1988

Lens Opacities Classification System.

The Lens Opacities Classification System (LOCS) is a simple system for classifying age-related human lens opacities at the slit lamp or in retroilluminated and slit-lamp photographs. The system employs a set of standard Neitz CTR retroilluminated black-and-white photographs for classification of cortical and posterior subcapsular cataracts and a single color slit-lamp photograph for classification of nuclear color and opalescence. We present a detailed description of the system.

Cataract↗
PubMed1988

Genetic transformation system in the archaebacterium Methanobacterium thermoautotrophicum Marburg.

A wild-type strain of Methanobacterium thermoautotrophicum Marburg was transformed by DNA from strains resistant to 5-fluorouracil. Recipient cells were grown without selection on gellan gum (GELRITE) plates with DNA. Drug-resistant cells were recovered by replica plating the resulting colonies onto drug plates. Transformation required high-molecular-weight DNA with appropriate markers and was not observed on agar or in liquid media under a variety of conditions.

Culture Media↗
PubMed1988

Reduction of the surface charge of blood polymorphonuclear cells by rheumatoid sera and heat induced aggregated human IgG (HAGG).

Cell electrophoresis identifies two main subpopulations of blood polymorphonuclear cells (PMNs), which in terms of the speed of their anodic migration are referred to as the fast and slow population. When blood PMNs from normal healthy subjects were incubated in medium containing 20% RA serum there was a decrease in the percentage of fast cells with a corresponding increase in the slow population that was directly related to the levels of circulating immune complexes present in the sera. Similar results were obtained when using heat induced aggregated human IgG (HAGG) or Candida albicans instead of RA serum. The 'slowing' effect of HAGG, which was transient and time dependent, appeared to be due to its internalisation by the PMNs. These results suggest that in RA the large number of blood PMNs with a low surface charge (i.e., the slow population) may arise as a result of the constant interaction of these cells with circulating immune complexes.

Antigen-Antibody Complex↗
PubMed1987

The mechanism of action of capsaicin on sensory C-type neurons and their axons in vitro.

The selective excitant and neurotoxic action of capsaicin on vagal sensory neurons in the rat has been investigated in vitro using three techniques: extracellular recording of compound spike potentials from the whole nerve; intracellular recording from ganglion cells using single-electrode current and voltage clamp; and electron microscopy of the nerve and nodose ganglion. Capsaicin (0.1-10 microM) depolarized vagal sensory C fibres and cell bodies, and produced an increased conductance. The conductance increase appeared to be due to an increased permeability to sodium and calcium, plus a secondary increase in potassium (and perhaps chloride) conductance consequent upon calcium entry. The early entry of calcium seems to be a significant priming event in the neurotoxic process, since dramatic ultrastructural changes take place within a few minutes of capsaicin application, which are minimized by removing extracellular calcium ions. The observations indicate that in sensory C neurons capsaicin opens a conductance of limited specificity and that a resultant large calcium entry is closely involved in the rapid development of cell injury.

Animals↗