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Biomedical subjects

C L Thompson

Publications and source records attributed to C L Thompson.

At least 55 records · Page 3Linked to original sources

Modulation of ppp(A2'p)nA-dependent RNase by a temperature-sensitive mutant of vaccinia virus.

Activation of the ppp(A2'p)nA (2-5A)-dependent RNase was investigated during the abortive infection of BSC40 cells by a temperature-sensitive mutant of vaccinia virus, ts22. At the nonpermissive temperature, ts22 has an abortive late phenotype. At the onset of late-viral-gene expression, viral mRNA is degraded and rRNA is cleaved into discrete fragments in the absence of prior interferon treatment (R. F. Pacha and R. C. Condit, J. Virol. 56:395-403, 1985). Concomitant with rRNA cleavage, an increase in 2-5A occurred late during infection. Discrete 18S- and 28S-rRNA degradation products from BSC40 cells infected with ts22 at the nonpermissive temperature comigrated in denaturing agarose gels with rRNA cleaved fragments produced by the activation of 2-5A-dependent RNase in uninfected cells transfected with exogenous 2-5A. An increase in 2-5A levels and a similar discrete and characteristic degradation of rRNA were observed in BSC40 cells infected with wild-type vaccinia virus in the presence of isatin-beta-thiosemicarbazone. The results show that the ts22 lesion and the action of isatin-beta-thiosemicarbazone may affect the same pathway, leading to the activation of latent 2-5A-dependent RNase and resulting in indiscriminate RNA degradation and inhibition of viral replication.

Adenine Nucleotides↗

Distribution and lateral mobility of GABA/benzodiazepine receptors on nerve cells.

The distribution and mobility of GABA/benzodiazepine receptors has been examined on living nerve cells by fluorescence digital imaging and fluorescence photobleach recovery with 2 novel fluorescent derivatives of the benzodiazepines Ro7-1986 and 1012S. These fluorescent derivatives retain their high affinity for the GABA/benzodiazepine receptor complex with Ks of 79 and 85 nM, respectively. Digital fluorescence imaging of GABA/benzodiazepine receptors on rat spinal cord neurons maintained in culture reveal that, even in the absence of observable synaptic contact, GABA/benzodiazepine receptors are localized on the cell body in clusters of very high density. Receptor density on processes is lower than on cell bodies, although occasional areas of intense fluorescence were observed. Fluorescence photobleach recovery measurements show that 70% of the GABA/benzodiazepine receptors on the cell body and greater than 85% on the processes of rat spinal cord neurons are immobile. In comparison, voltage-gated sodium channels are diffusely distributed and very mobile on the cell body (D = 10(-9) cm2/sec). The results suggest that even in the absence of nerve-nerve cell contact, there are specific mechanisms that segregate GABA/benzodiazepine receptors to the neuronal cell body and control their lateral mobility.

4-Chloro-7-nitrobenzofurazan↗

Cytogenetic and chemical detection of human exposure to polyhalogenated aromatic hydrocarbons.

Peripheral lymphocytes from Taiwanese women (n = 35) exposed to polychlorinated aromatic hydrocarbons and from matched controls (n = 24) were assessed for the levels of sister chromatid exchanges (SCEs) after a 72-hour incubation of whole blood in the presence or absence of alpha-naphthoflavone (ANF) and for chromosome aberrations after 48 hours of incubation. Serum levels of polychlorinated biphenyl (PCB) congeners were measured for all individuals, and serum levels of several polychlorinated dibenzofurans (PCDFs) were measured for 12 exposed individuals by gas chromatography-mass spectometry. Blood concentrations of total PCBs in the exposed population averaged approximately 15 ppb, whereas mean PCDF values were 14 ppt. Major PCB congeners detected were 2,2' 4,4', 5,5'-hexa CB and 2,2'3,4,4',5-hexa CB. PCDFs detected were primarily 1,2,3,4,7,8,-hexachlorodibenzofuran (10.8 ppt) and 2,3,4,7,8-pentachlorodibenzofuran (2.7 ppt). Average SCE frequencies were 7.61 for controls and 7.30 for exposed individuals when assays were conducted in the absence of ANF, whereas respective values were 8.85 and 10.75 in the presence of ANF. Differences in the level of ANF-induced SCEs between the two populations were highly significant (P less than .001). Moreover, the ANF-induced SCEs were highly correlated with the serum concentrations of total PCBs and of several PCB congeners (P less than .001). Increases in ANF-induced SCEs appeared to be linear up to a PCB concentration of approximately 30 ppb. Chromosome aberration frequencies were similar in control and exposed populations. These studies demonstrate that in vivo exposure to PCBs and PCDFs result in an enhanced sensitivity of lymphocytes to the SCE-causing actions of ANF.

Benzoflavones↗

Metabolic activation of alpha-naphthoflavone by 2,3,7,8-tetrachlorodibenzodioxin-induced rat liver microsomes.

Previous studies in our laboratory had demonstrated that addition of alpha-naphthoflavone (ANF) to lymphocytes from smokers or polychlorinated biphenyls (PCB)s-exposed individuals caused an increase in sister chromatid exchange (SCE) frequency whereas lymphocytes from controls were relatively unaffected. In order to investigate the mechanism responsible, metabolism of ANF by uninduced and 2,3,7,8-tetrachlorodibenzodioxin (TCDD)-induced microsomes was studied as a function of microsomal protein concentration and incubation time. Nonpolar metabolites were analyzed and the amount of conjugated (polar) and protein-bound metabolites determined. The initial ANF-metabolism rate was 10-fold higher in TCDD-induced microsomes (4.9 +/- 0.6 nmol/min per mg TCDD-induced microsomal protein vs. 0.5 +/- 0.2 nmol/min per mg uninduced microsomal protein) than in uninduced microsomes. Moreover, uninduced microsomes no longer metabolize ANF after 30-40 min while TCDD-induced microsomes metabolize ANF for longer than 2 h or until all the ANF is gone. In addition to the metabolites formed by uninduced microsomes [7,8-dihydro-7,8-dihydroxy-ANF (7,8-dihydrodiol); 5,6-dihydro-5,6-dihydroxy-ANF (5,6-dihydrodiol); 5,6-oxide-ANF and 6-hydroxy-ANF], TCDD-induced microsomes from unidentified metabolites. When TCDD-induced microsomes and 40 microM ANF were added to Chinese hamster ovary (CHO) cells, we found a correlation between the concentration of 5,6-oxide-ANF and clastogenicity to CHO cells. However, purified 5,6-oxide-ANF did not induce SCEs in CHO cells in the absence or presence of TCDD-induced microsomes. However, a minor metabolite (identified as the 9,10-dihydro-9,10-dihydroxy-ANF by acid dehydration) formed with TCDD-induced microsomes produces clastogenicity in CHO cells. These data indicate that a minor metabolite of ANF is a potent clastogen which suggests that this metabolite may be responsible for the ANF-mediated increases in SCE frequency in lymphocytes from smokers or PCB-exposed individuals.

Animals↗

Marker rescue mapping of vaccinia virus temperature-sensitive mutants using overlapping cosmid clones representing the entire virus genome.

A set of 11 overlapping cosmid clones of wild type (wt) vaccinia virus DNA was constructed. The clones together span almost the entire vaccinia virus genome. The clones were used to map temperature-sensitive (ts) mutants of vaccinia virus by marker rescue. Map positions were obtained for mutants representing 29 of 32 complementation groups tested.

Chromosome Mapping↗

Effects of alpha-naphthoflavone on levels of sister chromatid exchanges in lymphocytes from active and passive cigarette smokers: dose-response relationships.

The frequency of sister chromatid exchanges (SCE) were determined in lymphocytes of nonsmokers, passive smokers, and active smokers in the presence and absence of alpha-naphthoflavone (ANF). Higher levels of SCEs were detected for all smoking groups after in vitro addition of ANF when compared with an assay without ANF. There was a highly statistically significant difference between heavy smokers and nonsmokers (9.25 versus 7.43 SCE/cell) for the assay without ANF and for the ANF assay (14.2 versus 8.8). When considering the numerical difference in SCEs between the assays with and without ANF (delta SCE), higher values were noted for moderate smokers (2.7) and heavy smokers (4.9) compared to nonsmokers (1.4). Significant dose-response relationships were found between the frequency of SCEs and factors related to smoking, such as duration and frequency of cigarette use, tar, nicotine, carbon monoxide content of brand, and urinary measures of nicotine metabolites (cotinine and thiocyanate). No elevation of SCEs in passive smokers was found when compared to nonsmokers using either assay. The mechanism for SCE enhancement by ANF is unclear, but may be related to metabolic activation of the ANF by the cytochrome P-450 system in lymphocytes. The dosimetry relationships between cigarette smoke exposure and SCE frequency indicate that culture of human lymphocytes via ANF may provide a sensitive tool to detect exposure to cigarette smoke.

Adolescent↗

Cytosolic and nuclear estrogen receptors in the isolated perfused rat liver.

The isolated perfused rat liver was investigated as a potential model to analyze binding of 17 beta-[3H]estradiol (E2) to cytosolic and nuclear estrogen receptors. Viability of the isolated perfused liver was monitored by measuring leakage of cytosolic enzymes into the perfusate. These studies indicated that the liver remained viable for at least a 90-min perfusion period although significant decreases in cytosolic estrogen receptor concentrations occurred during this perfusion period. Estrogen receptor loss was minimized by supplementing the red blood cell-free perfusion medium with 5 micrograms of insulin per ml. Uptake of [3H]E2 by hepatic cytosolic estrogen receptors of the isolated perfused liver was rapid as measured by partial purification of radiolabeled ligand receptor complexes after varying times of perfusion. Peak liver concentrations of receptor-bound E2 were achieved 15 min after the onset of perfusion when using livers from either male or female rats. After 15 min, radiolabeled cytosolic ligand receptor complexes decreased rapidly, reaching lowest concentrations at 60 min. Radiolabeled salt-extractable nuclear-binding sites increased up to 30 min and then decreased slightly between 30 and 90 min. Both 4S and 5S forms of nuclear binding sites were detected in the isolated perfused livers as evaluated by sedimentation analysis on 5 to 20% sucrose density gradients. Concentrations of radiolabeled cytosolic and nuclear receptors were greater in females than males at all perfusion periods examined when the initial concentration of [3H]E2 was 4 nm. Sex differences in receptor uptake were not as great when higher concentrations of [3H]E2 were added to the perfusion medium. These studies suggest that the isolated perfused liver is a suitable model to investigate short-term uptake of estrogens by cytosolic and nuclear receptors.

Animals↗

Masked discrimination of interaural time delays with narrow-band signal.

Interaural time just-noticeable-difference (jnd) of a narrow-band noise masked by a wideband noise was measured for nine different interaural configurations of the masking noise at a fixed signal-to-noise ratio. The narrow-band noise was 1/3 octave wide centered about 500 Hz, and the wideband masker was bandpass filtered between 250 and 1500 Hz. Our results are in agreement with earlier results with tones [M. F. Cohen, J. Acoust. Soc. Am. Suppl. 1 64, S35 (1978); J. Acoust. Soc. Am. 70, 1289-1293 (1981); J. E. Slocum and R. M. Stern, J. Acoust. Soc. Am. Suppl. 1 68, S60 (1980)] and are the opposite of what may be expected from the results of binaural detection experiments: the jnd is largest for the interaurally phase reversed masker and smallest for the diotic masker. In addition, no consistent relation was observed between the size of the jnd and the perceptual location of the masker. Predicted jnds were calculated from a model based on the interaural phase difference of the stimuli in the two ears and were in rough agreement with the experimental results.

Auditory Perception↗

Autonomic effects of dextroamphetamine in normal men: implications for hyperactivity and schizophrenia.

This study test the effects on autonomic nervous system (ANS) activity of two doses (0.25 mg/kg and 0.50 mg/kg) of dextroamphetamine in normal men. Skin conductance and heart rate were recorded during rest, tone presentation, and a reaction time task. Compared to placebo, dextroamphetamine increased both skin conductance and heart rate indices of arousal, slowed habituation, and reduced ANS responsivity selectively to more important vs. less important stimuli. The last result differs from previous findings on hyperactive and normal boys. The pattern of ANS effects closely resembles findings on drug-free schizophrenics, suggesting that it may be a matter for biologic changes occurring in amphetamine psychosis and spontaneous psychotic episodes.

Adult↗

Binaural interaction of impaired listeners. A review of past research.

This paper reviews past studies of binaural interaction in impaired listeners. The topics covered include localization and lateralization; equal loudness, centering and lateralization adaptation; detection of signals in noise; and discrimination of interaural time delay and interaural amplitude ratio. Comments concerning experimental design and procedures, as well as interpretation of results, are often included with descriptions of the studies.

Auditory Perception↗

Autonomic and behavioral effects of dextroamphetamine and placebo in normal and hyperactive prepubertal boys.

The hypothesis is tested that the response to dextroamphetamine in terms of activity, attention, impulsivity, and autonomic activity is similar in normal (N) and hyperactive (H) children. Fourteen N and 15 H boys had skin conductance (SC), heart rate (HR), and finger temperature (ST) recorded during rest, presentation of eight 75-dB tones, and a reaction time (RT) procedure on three occasions: off drug (Day 1) and after ingestion (double-blind) of placebo and of .5 mg/kg dextroamphetamine. Both N and H groups showed drug effects, compared to placebo, of reduced motor activity and impulsivity, improved attention (RT), increased HR and HR slowing during RT foreperiods, and decreased ST. Both groups also had decreases in SC responsivity but in different parts of the test. Placebo compared to Day 1 produced increased activity and autonomic "arousal" but no change in Rt. Stimulant drugs thus have similar behavioral and autonomic effects in both N and H boys, but the beneficial effects on behavior do not depend critically on increases in arousal.

Arousal↗

Masking level differences: auditory evoked responses with homophasic and antiphasic signal and noise.

Two studies were devised to determine if objective quantification of the masking level difference is possible using the auditory evoked response (AER). In the first study, click stimuli were presented under three conditions: both the stimulus and masker in phase (SoNo); stimulus in phase, masker antiphasic (SoN pi); and stimulus antiphasic with masker in phase (S pi No). In the second study 1000 Hz puretone stimuli were presented under SoNo and S pi No phasic conditions. AER's were obtained at various intensity levels for each condition. The AER demonstrated differences in N1-P2 amplitudes evoked by the homophasic and antiphasic conditions for threshold and suprathreshold levels.

Adolescent↗

RAPORT system.

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Computers↗