Circadian optimization of treatment time using DNA replication-dependent cell-cycle-specific halogenated pyrimidines.
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Animals↗
Biomedical subjects
M Carroll
Publications and source records attributed to M Carroll.
Pieces in the puzzle: novel arachidonate metabolites.
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Animals↗
Erythropoietin receptor contains both growth-promoting activity and differentiation-promoting activity.
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Amino Acid Sequence↗
The effects of modality and elaboration on perceptual identification.
This paper describes two experiments on the effects of spoken and written priming on perceptual identification (visual word identification in Experiment 1 and auditory word identification in Experiment 2). Much previous work that has based the priming phase on the processing of word lists suggests that cross-modal priming (auditory-visual and visual-auditory) should be relatively weak. The present studies employed script- or story-based priming and represent a development on the earlier work by Carroll and Freebody (1987). In contrast to priming by list-processing, the reported findings show that homo-modal and cross-modal priming are indistinguishable, although only when the words are congruent with the story. Modality-shift effects are found when target words are incongruent with the stories in which they are found when target words are incongruent with the stories in which they are embedded at study. Results indicated that memory tests may be much more flexible with respect to the type of processing that can support performance than previous research suggests, and that the data-driven/conceptually driven distinction is not sufficient to account for the pattern of results obtained.
Adolescent↗
Autoimmune hemolytic anemia in chronic mucocutaneous candidiasis.
Chronic mucocutaneous candidiasis is an immunodeficiency disease characterized by T-cell dysregulation and chronic superficial candidal infections. We report on three patients with chronic mucocutaneous candidiasis who developed autoantibodies to erythrocytes. Our first patient, a 19-year-old female, developed autoimmune hemolytic anemia (AIHA) that required multiple courses of treatment, including corticosteroids, intravenous immunoglobulin, and danazol. During the last exacerbation of AIHA, intensive treatment with corticosteroids and intravenous immunoglobulin failed and yet the patient responded to plasmapheresis. Our second patient, a 21-year-old male, developed AIHA which responded to oral corticosteroid therapy. Our third patient, a 6-year-old female without evidence of hemolysis, was found to have erythrocyte autoantibodies on routine screening. These three patients had positive direct antiglobulin tests, and the first patient had both immunoglobulin G (IgG) and IgM erythrocyte autoantibodies, while the remaining two patients had only IgG autoantibody. This is the first report of the association of AIHA with chronic mucocutaneous candidiasis. We suggest that all patients with chronic mucocutaneous candidiasis be screened periodically for erythrocyte autoantibodies. Plasmapheresis, a safe ancillary procedure in the management of AIHA, may be life-saving in some cases. The occurrence of erythrocyte autoantibodies in mucocutaneous candidiasis may be related to immunoregulatory disorders in this disease.
Adolescent↗
Airway effects of local challenge with hypertonic saline in exercise-induced asthma.
Hypertonicity of airway lining fluid has been suggested as the stimulus for bronchoconstriction in exercise-induced asthma. We explored the airway effects of delivering a direct hypertonic stimulus to asthmatic airways via a fiberoptic bronchoscope, comparing hypertonic saline challenge by direct instillation with local aerosol delivery. A group of 18 asthmatic subjects responsive to inhaled hypertonic saline with a history of EIA were studied; the first 9 subjects received local challenge with hypertonic saline by direct instillation, and the next 9 subjects were challenged by local aerosol delivery. A control challenge with isotonic saline by either instillation or aerosol was performed at a same bronchoscopy. Local challenge with hypertonic saline by aerosol delivery was found to be more effective in inducing local bronchoconstriction (8 of 9 subjects) than instillation (2 of 6 subjects). Paired BAL fluid samples and bronchial biopsies were obtained in total of 11 and 9 subjects, respectively. Local challenge with hypertonic saline either by instillation or aerosol produced no significant change in histamine, tryptase, or PGD2 levels in BAL fluid or mast cell numbers and degranulation in bronchial biopsies. A significant correlation was observed between histamine levels in BAL fluid and airway responsiveness to inhaled hypertonic saline (rs = -0.59, p < 0.05). Bronchial biopsies showed evidence of extensive epithelial damage; however, this was not related to airway responsiveness to inhaled hypertonic saline.
Adolescent↗
Differentiation domains of the erythropoietin receptor.
Ectopic expression of the erythropoietin receptor (Epo-R) in Ba/F3, an interleukin-3 (IL-3)-dependent progenitor cell line, confers both Epo-dependent cell growth and Epo-dependent induction of beta-globin mRNA. We have used this system of limited erythroid differentiation to characterize the role of the Epo-R in differentiation. In particular, we have been interested in identifying a differentiation domain of the Epo-R. We have studied three chimeras encoding regions of the extracellular region of the Epo-R and the intracellular region of the IL-3R beta IL-3. After transfection into Ba/F3 cells, all three chimeras conferred Epo-dependent growth and induced the expression of beta-globin, suggesting that the extracellular region of the Epo-R plays a critical role in differentiation. However, a truncated Epo-R containing only the extracellular region of the Epo-R and a 15 amino acid cytoplasmic tail does not induced beta-globin expression, although it is processed to the cell surface and binds Epo. These experiments show that the extracytoplasmic region of the Epo-R is necessary but not sufficient to induce erythroid-specific differentiation in this system.
Cell Differentiation↗
Erythropoietin receptor signals both proliferation and erythroid-specific differentiation.
Ectopic expression of the erythropoietin receptor (EPO-R) in Ba/F3, an interleukin 3-dependent progenitor cell line, confers EPO-dependent cell growth. To examine whether the introduced EPO-R could affect differentiation, we isolated Ba/F3-EPO-R subclones in interleukin 3 and assayed for the induction of beta-globin mRNA synthesis after exposure to EPO. Detection of beta-globin mRNA was observed within 3 days of EPO treatment, with peak levels accumulating after 10 days. When EPO was withdrawn, expression of beta-globin mRNA persisted in most clones, suggesting that commitment to erythroid differentiation had occurred. Although EPO-R expression also supports EPO-dependent proliferation of CTLL-2, a mature T-cell line, those cells did not produce globin transcripts, presumably because they lack requisite cellular factors involved in erythrocyte differentiation. We conclude that the EPO-R transmits signals important for both proliferation and differentiation along the erythroid lineage.
Animals↗
Antibody to an abnormal protein in amyotrophic lateral sclerosis identifies Lewy body-like inclusions in ALS and Lewy bodies in Parkinson's disease.
Ubiquitinated cytoplasmic inclusions are a characteristic feature of the neuronal pathology of neurodegenerative diseases. Immunocytochemical techniques have identified intermediate filaments associated with ubiquitin-immunoreactive inclusions in Alzheimer's disease (AD), Parkinson's disease (PD), and Pick's disease; however, no core protein has been detected in the ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS). The pathogenesis of these inclusions is not known, but the inclusion may result from an accumulation of an abnormal proteins. Here we report a novel protein of 32.5 kDa detected by polyacrylamide gel electrophoresis, in the spinal cord in ALS patients. A polyclonal antibody raised against this protein and used for Western blotting, suggests that the novel protein is related to actin. Immunocytochemical studies using this antibody indicate that the protein is found in Lewy body-like inclusions in anterior horn cells of ALS, and in Lewy bodies in the substantia nigra in PD.
Actins↗
Effect of a series of 1-alkyl ether lipids on inhibition of phospholipase A2 activity and PAF responses.
Several 1-alkyl ether lipids were studied for their ability to inhibit PLA2 and antagonize PAF responses. Studies with synthetic micellar substrate (1-stearyl-2-arachidonyl phosphocholine), at concentrations ranging from 0.02 to 1000 microM, demonstrate that CL 118326 inhibits porcine pancreatic PLA2 in vitro. As the substrate concentration increases, there is a dose-dependent increase in the IC50 value (IC50 ranges: 1.6-84.6 micrograms/ml or 2.6-137 microM). CL 118326 inhibits mammalian pancreatic PLA2, but not snake or bee venom PLA2. CL 118326 inhibits thrombin (IC50 = 7.9 microM), but not Na arachidonate- (IC50 > 100 microM) induced platelet aggregation, indicative of inhibition of cellular PLA2. CL 118326 inhibits other PLA2-dependent processes such as antigen-induced leukotriene (LTC4) release (IC50 = 2.3 micrograms/ml or 3.8 microM) and histamine release (IC50 = 1.4 micrograms/ml or 2.2 microM) in basophil-enriched WBCs. Intradermal coinjection of CL 118326 (10 micrograms) with PLA2 into guinea pig skin inhibits pancreatic PLA2-induced increase in vascular permeability and leakage, but not snake or bee venom PLA2-induced leakage. CL 118326 shows no PAF-like agonist activity in stimulating rabbit platelet-rich plasma. It inhibits PAF-induced aggregation (IC50 = 5.8 microM), but not ADP-induced aggregation. CL 118326 has greater efficacy as a PLA2 inhibitor than as a PAF antagonist since the IC50-substrate concentration ratio for PLA2 inhibition is < or = 1.0 at substrate concentrations of 10-1000 microM while the IC50-agonist ratio for PAF antagonism is > 100. Results for four other compounds related to CL 118326 are also presented.
Animals↗
High-density lipoprotein cholesterol and alcohol consumption in US white and black adults: data from NHANES II.
OBJECTIVES: High-density lipoprotein (HDL) cholesterol is known to be positively related to moderate alcohol consumption from studies in selected populations. This study describes the association in a representative sample of the US adult population. METHODS: Stratification and multivariate regression analyses were used to examine HDL cholesterol levels and alcohol consumption. RESULTS: Fewer women than men reported consumption of alcohol at any frequency. Similar percentages of Whites and Blacks reported alcohol consumption. Age-adjusted mean HDL cholesterol levels were higher among alcohol drinkers than among nondrinkers in all sex-race strata. Mean HDL cholesterol levels of Whites and Blacks of both sexes increased consistently with increased frequency of consumption of beer, wine, and liquor. With age, education, body mass index, smoking, and physical activity controlled for, there were higher age-adjusted HDL cholesterol levels with increasing reported quantities of alcohol consumed. Daily or weekly use of alcohol led to an increase of 5.1 mg/dL in mean HDL cholesterol level, whereas consumption of 1 g of alcohol led to an increase of 0.87 mg/dL. CONCLUSION: Even if there is a causal association between alcohol consumption and higher HDL cholesterol levels, it is suggested that efforts to reduce coronary heart disease risks concentrate on the cessation of smoking and weight control.
Adult↗
Failure to obtain a generation effect during naturalistic learning.
Many experiments have obtained a generation effect (GE) with various kinds of laboratory items. Six of the present seven experiments failed to find a GE when the responses were answers to general information questions that had been learned by college undergraduates who had either read or generated the answers during learning several days before the retention test. A GE also did not occur when those same answers were used as responses in paired-associate learning and were tested 20 min after learning. The GE appeared only when subjects learned lists of answers in the absence of the question context, followed by recognition testing. Implications of these findings are drawn both for the generality of the GE, especially to the kind of items and naturalistic situations in which learning occurs outside the laboratory, and for the theoretical mechanisms that may underlie the GE in traditional laboratory situations.
Adult↗
Serum lipids of adults 20-74 years: United States, 1976-80.
This report presents descriptive and analytic data for serum total cholesterol, cholesterol lipoproteins, and triglycerides for adults 20-74 years of age by age, sex, and selected subgroups of the population at risk of developing coronary heart disease. This information is from the second National Health and Nutrition Examination Survey, which was conducted during the years 1976-80.
Adult↗
Apparent reversal of early gastric mucosal atrophy after triple therapy for Helicobacter pylori.
Helicobacter pylori may be difficult to detect in individuals with intestinal metaplasia or atrophic gastritis, even though bacteria may persist in the mucosa in low numbers, maintaining elevated serum H. pylori antibody levels. We report a patient with marked, endoscopically visible gastric mucosal changes and focal changes of histological atrophic gastritis, who was negative for H. pylori on urease test, culture, and histology, but had positive H. pylori serology. When treated with triple therapy and reassessed at 6 months, his H. pylori antibody titer fell to low/negative levels, abnormal mucosa was replaced by a velvety, normal lining, and the previous evidence of histological atrophic gastritis was no longer detectable.
Anti-Bacterial Agents↗
Effect of overlearning on the feeling of knowing is more detectable in within-subject than in between-subject designs.
Conflicting results in the literature concerning the influence of overlearning on subsequent feeling of knowing (FOK) judgments for unrecallable items were resolved in an experiment that contrasted within-subject and between-subject designs. In the between-subject design, participants gave FOK judgments about items all of which had been learned to a criterion of either one or six correct recalls 4 weeks earlier. In the within-subject design, these judgments were made about the same items, half of which had been correct once and half six times. Results showed that the effect of overlearning on FOK ratings was more detectable in the within-subject design than in the between-subject design. It is suggested that future experiments on metacognition should use within-subject designs for maximal detectability of the effect of an independent variable on metacognitive judgments.
Female↗
Induction of markers of normal differentiation in human colon carcinoma cells by the v-rasH oncogene.
The molecular events that regulate differentiation of human colon mucosal cells are not known. Although a number of in vitro models to study this question exist, none have identified a gene product which could function as a mediator of cell differentiation. Although the Ki-ras gene is frequently mutated in human colon cancer, the Ha-ras protooncogene is maximally expressed in the most differentiated cells of intestinal mucosa. In order to study the effects of Ha-ras gene overexpression on the differentiation phenotype in human colon cancer cells, we have expressed the v-rasH oncogene in CaCO2 cells. This maneuver resulted in a marked induction of gene expression of multiple markers characteristic of intestinal brush border differentiation. These include a > or = 30-fold induction of sucrase, a 10-fold increase in intestinal alkaline phosphatase, a 20-fold induction of transforming growth factor alpha, and a 5-fold increase in transforming growth factor beta 1 steady-state mRNA levels. Finally, the CaCO2-ras cells undergo a > or = 95% reduction in DNA synthesis under serum-deficient conditions and cannot be restimulated after such treatment, suggesting terminal differentiation, whereas the same treatment has no effect on the proliferative capacity of the parent CaCO2 cell line. These studies with CaCO2 human colon cancer cells provide a model to study the role of v-rasH and related genes in colon epithelial differentiation.
Antigens, Differentiation↗
Isolation of anonymous DNA markers for human chromosome 22q11 from a flow-sorted library, and mapping using hybrids from patients with DiGeorge syndrome.
DiGeorge syndrome (DGS) is a human developmental defect of the structures derived from the third and fourth pharyngeal pouches. It apparently arises due to deletion of 22q11. We describe a strategy for the isolation of DNA probes for this region. A deleted chromosome 22, which includes 22q11, was flow-sorted from a lymphoblastoid cell line of a patient with cat eye syndrome and used as the source of DNA. A DNA library was constructed from this chromosome by cloning into the EcoR1 site of the vector Lambda gt10. Inserts were amplified by PCR and mapped using a somatic cell hybrid panel of this region. Out of 32 probes, 14 were mapped to 22q11. These probes were further sublocalised within the region by dosage analysis of DGS patients, and by the use of two new hybrid cell lines which we have produced from DGS patients. One of these lines (7939B662) contains the altered human chromosome segregated from its normal homologue. This chromosome 22 contains an interstitial deletion in 22q11, and will be useful for localising further probes to the DGS region.
Base Sequence↗