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Biomedical subjects

C D Clark

Publications and source records attributed to C D Clark.

At least 19 recordsLinked to original sources

Effects of a red background on magnocellular functioning in average and specifically disabled readers.

Two experiments were conducted using metacontrast masking to examine responses in the magno system of adults, average reading adolescents and adolescents with specific reading disability. In Experiment 1 the effects of a red background field on the metacontrast functions of adult subjects were investigated. Results showed that a red, compared to a photometrically matched white background field, significantly attenuated metacontrast magnitude, supporting the interpretation of metacontrast as due to magno system suppression of parvo system responses. The finding of a red background effect was replicated in Experiment 2 with the two adolescent groups. The metacontrast functions of the adolescent groups also differed significantly, with those with specific reading disability exhibiting weaker metacontrast than the average readers. This result is consistent with a deficit in the magno system of individuals with specific reading disability and indicates the continuation of the deficit beyond childhood.

Adolescent

Blurring the image does not help disabled readers.

Previous research has found that poor readers performed a visual search task more slowly than good readers, but that this difference was virtually eliminated by blurring of the search array. Whereas blurring had little effect on the performance of the good readers, it led to a dramatic improvement in the search rate of the poor readers. The present study set out to replicate this research with groups of 10-12 yr old disabled and average readers but with methodological improvements in the procedure and the analysis. It was found that the disabled readers performed the search task as well as the average readers, and that blurring of the display conferred no advantage on either group. The results are discussed in relation to the transient deficit theory of reading disability.

Child

A comparison of temporal integration in children with a specific reading disability and normal readers.

Previous research has suggested that whereas some techniques show that subjects with a specific reading disability (SRD) have greater visible persistence than controls, a temporal integration of form technique does not. It has been suggested that the failure of the temporal integration task to show a difference results from the spatial separation between stimuli used in the technique. In this study SRD and control subjects were compared on a new version of a temporal integration task, under two conditions varying the spatial separation of elements in the display. It was predicted that there would be no difference between groups when spatial separation was large, but that the SRD subjects would show greater visible persistence at small separations. Neither prediction was confirmed, denying previous explanations of why the temporal integration task does not discriminate between groups. Analysis of errors showed that the result was not due to inattention nor to a general deficit on the part of the SRD subjects.

Afterimage

Factors influencing dairy calcium intake in women.

OBJECTIVES: Most national dietary studies have reported inadequate calcium (Ca) intake by women, indicating that marketing and educational efforts have not effected dietary behavior changes. The purpose of this study was to identify knowledge, attitudes, and behaviors which influence dairy Ca intake. METHODS: A questionnaire was developed to accomplish these objectives, and piloted for clarity and content validity. Dietary Ca intake was assessed using a food frequency questionnaire. After revisions, women were sampled from four sources: a health spa, elderhostel classes, through a Cooperative Extension Service program, and from the Illinois Older Women's League. The response rate was 66.5%. RESULTS: Mean total reported Ca intake (n = 351) was 591 +/- 355 mg/day. Over 40% of the women reported Ca intakes below 60% of the RDA and could therefore be considered to have deficient intake. Unfortunately, 27.1% of these with deficient intake believed they were meeting the Ca RDA. Significant differences (p < or = 0.01) were found in attitudes and beliefs about dairy Ca when comparing women whose intake was below 60% of the RDA with those whose intake was above 60%. The most commonly mentioned beliefs of the entire sample concerned cholesterol (16.5%), high calories (13.7%) and gastrointestinal discomfort (12.8%). CONCLUSIONS: These findings suggest an important discrepancy between perceived and actual Ca intake which could influence receptiveness to education. Non-dairy Ca rich food sources need to be clarified as does the caloric and cholesterol content of dairy foods.

Adult

Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect.

A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sibpair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = 0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; phi = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study..

Adolescent

Systematic mutagenesis of the yeast mating pheromone receptor third intracellular loop.

Signal transduction in the mating pathway of the yeast Saccharomyces cerevisiae is initiated by binding of a peptide pheromone to a G protein-coupled receptor (Ste2). We systematically have mutated the third intracellular loop of the Ste2 receptor to investigate its functional significance. We substituted each of the 13 amino acids in the loop with alanine individually or together with one other residue. In addition, we used a site-directed random replacement mutagenesis technique to replace a region encoding three amino acids in the loop with random sequence. Over 80 such Ste2 mutants have been analyzed by several functional and biochemical criteria in a yeast strain that carries a genomic deletion of the STE2 gene. The mutant phenotypes range from fully functional to severely compromised in signaling. The observation that amino acid substitutions in the third intracellular loop of the Ste2 receptor can affect activation of the yeast mating response implicates the loop in this signal transduction pathway. The types of mutations that compromise the function of the receptor may provide clues to the physical interaction between the receptor and the G protein.

Amino Acid Sequence

Bloodstream infections after interventional procedures in the biliary tract.

PURPOSE: To assess the adequacy of prophylaxis for interventional radiologic biliary procedures and the etiologic organisms of subsequent bloodstream infections. MATERIALS AND METHODS: Data from 148 patients who underwent 480 interventional radiologic biliary procedures were evaluated for evidence of bloodstream infection. Data analyzed included type of procedure performed, whether an antibiotic was used, and evidence of infectious complications occurring during and within 72 hours after the procedure. All culture data obtained before and after the procedure were recorded. RESULTS: Seven cases of new bloodstream infection were identified, five of which were caused by Enterococcus species. No substantial risk factors for bloodstream infection were identified, although it occurred only in patients who had recently undergone biliary surgery or underwent manipulations other than simple cholangiography. Microbial colonization of the bile was associated with older age. Evidence of possible or proved infection after the first interventional procedure was more common in patients with positive bile cultures. CONCLUSION: Although the importance of enterococcal bacteremia is uncertain, current recommendations for cephalosporin prophylaxis for interventional radiologic biliary procedures should be reevaluated.

Bacteremia

Anion and cation modulation of the guinea-pig ventricular action potential during beta-adrenoceptor stimulation.

Modulation of the ventricular action potential by beta-adrenergic activation of Ca2+, K+ and cyclic adenosine monophosphate (cAMP)-dependent Cl- channels was assessed in enzymatically isolated guinea-pig ventricular myocytes. The effectiveness and relative selectivity of 9-anthracene carboxylic acid (9-AC), as an antagonist of cAMP-dependent Cl- channels was also tested. Membrane currents and action potentials were recorded using the conventional whole-cell variant of the patch-clamp technique or with the amphotericin B perforated-patch technique. The beta-adrenergic agonist isoproterenol either increased or decreased action potential duration depending on whether the dominant effect was on inward Ca2+ currents or on outward K+ or Cl- currents. When Ca2+ and K+ channel modulation was prevented by nisoldipine and low temperature respectively, beta-adrenergic activation of Cl- channels caused a significant reduction in action potential duration and a slight depolarization of the membrane potential. The beta-adrenergic-mediated effects were reversed by the Cl- channel blocker, 9-AC. In the absence of beta-adrenergic stimulation, 9-AC had no detectable effects on action potentials or Ca2+ currents. These results suggest that beta-adrenergic activation of Cl- channels is a potent mechanism for regulation of action potential duration and that 9-AC may be a useful, relatively specific, pharmacological tool for evaluating the physiological role of cAMP-activated Cl- channels in heart. 9-AC also reversed the ability of isoproterenol to antagonize prolongation of action potential duration by the class III antiarrhythmic agent E-4031.

Action Potentials

Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure.

Changes in chromatin structure have frequently been correlated with changes in transcription. However, the cause-and-effect relationship between chromatin structure and transcription has been hard to determine. In addition, identifying the proteins that regulate chromatin structure has been difficult. Recent evidence suggests that a functionally related set of yeast transcriptional activators (SNF2/SWI2, SNF5, SNF6, SWI1, and SWI3), required for transcription of a diverse set of genes, may affect chromatin structure. We now present genetic and molecular evidence that at least two of these transcriptional activators, SNF2/SWI2 and SNF5, function by antagonizing repression mediated by nucleosomes. First, the transcriptional defects in strains lacking these SNF genes are suppressed by a deletion of one of the two sets of genes encoding histones H2A and H2B, (hta1-htb1) delta. Second, at one affected promoter (SUC2), chromatin structure is altered in snf2/swi2 and snf5 mutants, and this chromatin defect is suppressed by (hta1-htb1) delta. Finally, analysis of chromatin structure at a mutant SUC2 promoter, in which the TATA box has been destroyed, demonstrates that the differences in SUC2 chromatin structure between SNF5+ and snf5 mutant strains are not simply an effect of different levels of SUC2 transcription. Thus, these results strongly suggest that SNF2/SWI2 and SNF5 cause changes in chromatin structure and that these changes allow transcriptional activation.

Adenosine Triphosphatases

Mutations in SPT16/CDC68 suppress cis- and trans-acting mutations that affect promoter function in Saccharomyces cerevisiae.

SPT16 was previously identified as a high-copy-number suppressor of delta insertion mutations in the 5' regions of the HIS4 and LYS2 genes of Saccharomyces cerevisiae. We have constructed null mutations in the SPT16 gene and have demonstrated that it is essential for growth. Temperature-sensitive-lethality spt16 alleles have been isolated and shown to be pleiotropic; at a temperature permissive for growth, spt16 mutations suppress delta insertion mutations, a deletion of the SUC2 upstream activating sequence, and mutations in trans-acting genes required for both SUC2 and Ty expression. In addition, SPT16 is identical to CDC68, a gene previously shown to be required for passage through the cell cycle control point START. However, at least some transcriptional effects caused by spt16 mutations are independent of arrest at START. These results and those in the accompanying paper (A. Rowley, R. A. Singer, and G. C. Johnston, Mol. Cell. Biol. 11:5718-5726, 1991) indicate that SPT16/CDC68 is required for normal transcription of many loci in S. cerevisiae.

DNA, Fungal

Visible persistence following a brief increment in stimulus luminance.

In previous studies, it has been demonstrated that visible persistence--the period for which the perceived duration of a stimulus exceeds its physical duration--can be extended by briefly incrementing the luminance of the stimulus immediately prior to offset. Using a two-component pattern integration task, we show that this effect is not an artifact of change in the total luminous flux within the stimulus. Visible persistence was unaffected by overall luminance of the stimulus. It was also time-locked to the luminance increment. Visible persistence is seen to result from a process that is initiated by stimulus onset and that can be either wholly or partially reinitiated by the onset of the luminance increment. The duration of this process (which determines the duration of stimulus visibility) can be modified in a graded fashion by stimulus events that occur after its initiation. We outline a single-process inhibitory feedback model of the persistence mechanism that accounts for the present findings.

Afterimage

Chloride current in mammalian cardiac myocytes. Novel mechanism for autonomic regulation of action potential duration and resting membrane potential.

The properties of the autonomically regulated chloride current (ICl) were studied in isolated guinea pig ventricular myocytes. This current was elicited upon exposure to isoproterenol (ISO) and reversed upon concurrent exposure to acetylcholine (ACh). ICl was time independent and exhibited outward rectification. The responses to ISO and ACh could be blocked by propranolol and atropine, respectively, and ICl was also elicited by forskolin, 8-bromoadenosine 3',5'-cyclic monophosphate, and 3-isobutyl-l-methylxanthine, indicating that the current is regulated through a cAMP-dependent pathway. The reversal potential of the ISO-induced current followed the predicted chloride equilibrium potential, consistent with it being carried predominantly by Cl-. Activation of ICl produced changes in the resting membrane potential and action potential duration, which were Cl- gradient dependent. These results indicate that under physiological conditions ICl may play an important role in regulating action potential duration and resting membrane potential in mammalian cardiac myocytes.

Acetylcholine

Subcellular localization of yeast CDC46 varies with the cell cycle.

The Saccharomyces cerevisiae CDC46 protein accumulates in the nucleus of nondividing interphase cells. Soon after the cell has become committed to division, there is a rapid disappearance of CDC46 protein from the nucleus. This shift is not a consequence of variation in total CDC46 protein levels and is associated with DNA replication at the G1-S boundary. We propose that the CDC46 protein, which is required for DNA replication, becomes mobilized quickly from the cytoplasm into the nucleus as mitosis is completed and persists there until the next round of division is initiated. This partitioning of proteins in a cell cycle-dependent manner illustrates a general means of regulating events that must occur only once in each cycle, such as DNA initiation.

Cell Cycle

A chicken repetitive DNA sequence that is highly sensitive to single-strand specific endonucleases.

A DNA sequence consisting of the 5-mer AGAGG repeated tandemly 32 times has been detected in a chicken genomic clone and found to be present in about 2000 copies per chicken genome. This sequence was highly susceptible to single-strand specific endonucleases isolated from Aspergillus oryzae (S1) and mung bean, but cleavage by a single-strand specific endonuclease isolated from Neurospora crassa occurred only at a pH below 5.5. Endonucleolytic cutting of the AGAGG sequence by the single-strand specific enzymes required a supercoiled substrate and was independent of ionic strength.

Animals