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Biomedical subjects

B D Smith

Publications and source records attributed to B D Smith.

At least 19 recordsLinked to original sources
PubMed1992

DNA methylation inhibits transcription of procollagen alpha 2(I) promoters.

Our previous studies have demonstrated that a 2-[N-(acetoxyacetyl)amino]fluorene-transformed rat epithelial-like cell line, W8, contains a transcriptionally inactive alpha 2(I) gene with a hypermethylated promoter/first-exon region. We have cloned the rat promoter/first-exon region (-211 to +207) from W8 cells and their parent cell line, K16, which expresses alpha 2(I) collagen. There were no sequence differences between the clones from the two cell lines, indicating that a mutation was not responsible for transcriptional inhibition. The alpha 2(I) rat promoters were cloned upstream of the chloramphenicol acetyltransferase gene. Both constructs were equally active in both cell lines, suggesting that trans-activating factors for alpha 2(I) transcription are present in W8 cells. Finally, methylation of plasmids at all CpG sites with SssI methylase completely inhibited transcription using alpha 2(I) promoters, but methylation did not inhibit simian-virus-40 promoter-driven transcription. Certain methylation sites partially inhibit promoter activity. An HhaI methylation site inhibited transcriptional activity of the alpha 2(I) promoter 8-fold, whereas methylation at the HpaII site in the rat alpha 2(I) promoter did not decrease transcriptional activity. This provides further evidence that methylation at specific sites in the collagen alpha 2(I) promoter is responsible for the inactivation of transcription in W8 cells.

Animals↗
PubMed1992

Discordant regulation of human type I collagen genes by prostaglandin E2.

We examined the expression of type I collagen genes in prostaglandin E2 (PGE2)-treated human lung fibroblast cultures. Addition of PGE2 to fibroblast cultures inhibited alpha 1(I) mRNA levels by approx. 25% after 6 h and 60% after 24 h. Further studies showed that dibutyryl cAMP did not inhibit alpha 1(I) mRNA levels and that cycloheximide blocked the inhibitory effect of PGE2. In contrast, PGE2 treatment with or without cycloheximide did not affect alpha 2(I) mRNA levels. Moreover, in vitro translation of RNA derived from untreated and PGE2-treated cells yielded similar amounts of alpha 2(I) collagen peptides. Taken together, these results suggest that PGE2 induces a protein which inhibits alpha 1(I) transcription through distinct regulatory elements not under the control of cAMP and provide further evidence that the type I collagen genes can be discordantly regulated.

Blotting, Northern↗
PubMed1992

Lateralized mediation of arousal and habituation: differential bilateral electrodermal activity in unilateral temporal lobectomy patients.

The purpose of the present study was to increase our understanding of the differential hemispheric processing of arousal and habituation. Subjects were unilateral temporal lobectomy patients and controls. Each was exposed to an arousal/habituation task consisting of a series of tones and an auditory discrimination paradigm. Electrodermal activity was recorded from the left and right hands throughout. Results provide evidence for a state of hypoarousal in right temporal patients and some support for hyperarousability in lefts. This is consistent with data showing that right hemisphere damage is associated with inattention and denial and left hemisphere damage with hypervigilance and anxiety. The concept of laterally differentiated mediation of arousal and habituation was supported.

Adult↗
PubMed1992

Effects of habitual caffeine use and acute ingestion: testing a biobehavioral model.

A recently proposed model of the biobehavioral effects of caffeine suggests that acute ingestion impacts physiology and behavior differentially depending on the level of habitual usage of the drug. Acute ingestion and habitual usage are particularly expected to affect arousal and attentional processes. Subjects in the present study were preselected for high and low habitual caffeine use, given caffeine or a placebo, exposed to white noise or no white noise, and asked to perform on several tasks. Included were an arousal/habituation task (pure tones), reaction time, paired associates, anagrams, and vigilance. Electrodermal activity and performance were recorded. As predicted, virtually all effects were on the arousal/habituation and attentional (vigilance) tasks. Both acute ingestion and habitual use increased tonic EDA, and chronic use also reduced phasic responding, especially in the presence of a strong habituating stimulus. Both acute and habitual use also liberalized the vigilance response criterion, in that subjects risked more false alarms in order to attain more hits. In addition, habitual use increased sensitivity and reduced accuracy, and acute ingestion increased vigilance response time in the presence of white noise. Overall, the model was partially supported by these early results, though considerable further research is needed.

Adult↗
PubMed1992

The role of 99Tcm-HMPAO white cell imaging in suspected orthopaedic infection.

Accurate diagnosis is essential for the effective management of suspected bone infection. Current imaging techniques have had limited success and further work is required. Although white cell labelling techniques have been available for many years the radiopharmaceuticals employed have disadvantages, particularly in their availability and suitability for imaging. These problems have been overcome by the use of 99Tcm-HMPAO as an in vitro leukocyte labelling agent. The aims of this study were to assess retrospectively its role and accuracy in imaging orthopaedic infection and to compare the results with three-phase bone imaging. 30 patients with suspected bone infection underwent three-phase methylene diphosphonate (MDP) bone imaging and labelled leukocyte imaging on separate occasions. 16 bone scans were positive for infection, of which 14 were subsequently confirmed, and there were no false negatives. There were no false positive white cell studies and only one infection was not identified. 99Tcm-HMPAO white cell imaging has been shown to be an accurate technique for the diagnosis of bone infection but should be performed only following a positive finding on three-phase bone scanning, since the latter is highly sensitive but significantly less expensive, making it a more appropriate screening procedure.

Adolescent↗
PubMed1992

A comparison of two epidural alpha 2-agonists, guanfacine and clonidine, in regard to duration of antinociception, and ventilatory and hemodynamic effects in goats.

Epidural clonidine produces analgesia in humans with acute and chronic pain. Its use is limited because of short-lasting analgesia, hemodynamic depression, sedation, and respiratory depression. Intrathecal guanfacine has a longer duration of action than intrathecal clonidine. The present study compares these two drugs administered epidurally. Pulmonary artery, carotid artery, and epidural catheters were inserted into five goats. Each animal received guanfacine 5 mg/10 mL, clonidine 750 micrograms/10 mL, or a 10-mL saline control solution on separate occasions. Antinociception (tested via a point pressure stimulation device), arterial blood pressure, heart rate, cardiac output, pulmonary capillary wedge pressure, and arterial and mixed venous blood gases were measured every 30 min for 8 h. Guanfacine produced a longer duration of antinociception (guanfacine = 8 h vs clonidine = 5.5 h). Increases in PaCO2 were more pronounced in the clonidine group. There were no marked hemodynamic differences between the two drugs. Pretreatment with epidural idazoxan, an alpha 2-antagonist, blocked the antinociceptive effects of guanfacine. Because of a longer duration of action and less respiratory depression, epidural guanfacine may be superior for postoperative analgesia and chronic pain syndromes.

Animals↗
PubMed1991

Transforming-growth-factor-beta activation elements in the distal promoter regions of the rat alpha 1 type I collagen gene.

We have located a cis-acting element (alpha 1-TAE) within the promoter sequences of the rat collagen alpha 1(I) gene (COL1A1) 1600 bases upstream of the transcription start site which mediates transcriptional activation by transforming growth factor beta (TGF-beta). The functional significance of this region was established by (1) deletion analysis of the alpha 1(I) promoter cloned upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and (2) by co-transfection of promoter constructs with double-stranded oligonucleotides. DNA-mobility-shift assays with radiolabelled alpha 1-TAE demonstrated increased nuclear binding activity after TGF-beta stimulation. Oligonucleotides encoding the alpha 1-TAE, additional upstream regions within the alpha 1(I) promoter, as well as consensus nuclear-factor-1 (NF-1) sequences, competed with the alpha 1-TAE sequence. The two collagen type I genes are stimulated by TGF-beta through different regions of their promoters.

Animals↗
PubMed1991

Caffeine and novelty: effects on electrodermal activity and performance.

Caffeine has been shown to affect both physiological functioning and certain aspects of performance. These effects are typically attributed to a simple increase in general arousal. The present study was based on the theory that the effects of caffeine are actually multidimensional. Specifically, we hypothesized that the drug raises arousal, acts to maintain elevated arousal under conditions otherwise conductive to habituation, and enhances the impact of situational and psychological sources of arousal. Subjects were given caffeine (300 mg) or placebo and white noise or no noise and exposed to a series of pure tones and two Backwards Recall Tasks, one novel, the other repetitive. Electrodermal activity (EDA) and task performance were recorded. Caffeine increased arousal as measured by EDA. It also acted to slow habituation during repetitive stimulation, thus maintaining heightened arousal. Finally, it enhanced the effects of novel stimulation, which also independently raised arousal. These results support a multidimensional theory of caffeine effects and provide some understanding of the popularity of caffeine as a psychotropic agent.

Acoustic Stimulation↗
PubMed1990

Sensation-seeking: electrodermal and behavioral effects of stimulus content and intensity.

Although a number of studies support an arousal theory interpretation of differential sensation-seeking behavior, the conditions under which arousal correlates of this personality dimension are manifest is as yet unclear. Both theory and research suggest that among the external factors affecting the differential arousal response are stimulus relevance and stimulus intensity. The present study assessed the impact of these factors on both psychophysiological and behavioral responses. Subjects were preselected to represent the extremes of the sensation-seeking dimension, then exposed to auditory and visual presentations of a series of sexual and aggressive stimuli of systematically varied intensity. High sensation seekers gave larger amplitude SCRs to violent stimuli and larger initial responses to sexual stimuli presented visually, while verbal response intensities showed an opposite pattern. Overall, results provided support for an arousal theory interpretation of sensation-seeking, but suggested that the probability and magnitude of group differences is a somewhat complex function of stimulus intensity, stimulus modality, and perhaps other factors not yet assessed.

Adult↗
PubMed1990

The differential hemispheric processing of emotion: a comparative analysis in strongly-lateralized sinistrals and dextrals.

The neural processing of emotion and the differential processing of affect and cognition are thus far poorly understood. Complex results across studies suggest involvement of the left hemisphere, the right hemisphere, or both. Since handedness is related to cerebral dominance, the present study undertook a comparative analysis of neural processing in strongly lateralized left- and right-handed populations. Parietal EEG and bilateral electrodermal activity were recorded while carefully selected subjects were exposed to emotional stimuli under cognitive, affective, and neutral conditions. Results showed greater lateral differentiation and differentially greater left-hemisphere activation in dextrals but greater overall activation in sinistrals. These findings are consistent with the common observation that cerebral organization is more diffuse in left-handed populations. It seems clear that the comparative study of sinistrals and dextrals can help us to better understand how emotion is processed in the brain.

Brain↗
PubMed1990

The accumulation of type I collagen mRNAs in human embryonic lung fibroblasts stimulated by transforming growth factor-beta.

We examined the expression of type I collagen mRNAs (alpha 1(I) and alpha 2 (I)) by embryonic lung fibroblasts in cultures treated with transforming growth factor-beta (TGF-beta). TGF-beta caused a concentration dependent increase in the expression of alpha 1(I) mRNA for type I collagen. TGF-beta at low concentration (0.1 ng/ml) slightly increased the level of alpha 1(I) mRNA. Higher concentrations of TGF-beta (1.0 and 5.0 ng/ml) further increased the amount of alpha 1(I) mRNA. The increase in alpha 1(I) mRNA was associated with a marked increase in production of intact type I collagen molecules. TGF-beta did not increase expression of alpha 2(I) mRNA. The alpha 2(I) mRNA levels in human lung fibroblast cultures were not affected by varying the duration of exposure to TGF-beta nor the concentration of TGF-beta. In contrast, TGF-beta increased the amount of both alpha 1(I) and alpha 2(I) mRNA in NIH3T3 cells. These data suggest that the amount of alpha 2(I) mRNA is not rate limiting with respect to type I collagen production during TGF-beta stimulation in human lung fibroblast cultures.

Cells, Cultured↗
PubMed1989

The differential effect of prostaglandin E2 on transforming growth factor-beta and insulin-induced collagen formation in lung fibroblasts.

We examined the effect of prostaglandin (PG) E2 on transforming growth factor-beta (TGF-beta) and insulin-stimulated collagen formation in lung fibroblast cultures. TGF-beta increased type I collagen production 2-3-fold as determined by the densitometric analysis of autoradiograms from polyacrylamide gels and by measuring the amount of nondialyzable hydroxyproline. This was associated with a 5-6-fold increase in alpha 1(I) mRNA levels. PGE2 at 10(-7) M strongly inhibited type I collagen formation in TGF-beta-stimulated cultures by 60-70%. PGE2 blocked collagen formation in TGF-beta-stimulated cultures by decreasing levels of alpha 1(I) gene expression. PGE2 inhibited alpha 1(I) gene expression in part through inhibition of transcription. In contrast, insulin increased type I collagen production 2-fold and was associated with a 30-40% increase in alpha 1(I) mRNA. Although PGE2 also decreased alpha 1(I) mRNA levels in insulin-treated cultures, PGE2 had no effect on collagen formation. Taken together, these results demonstrate that collagen formation may proceed through two distinct pathways. These two pathways are distinguishable by their sensitivity to PGE2 treatment and their relationship to increases in collagen mRNAs.

Collagen↗
PubMed1989

Parietal processing of affect and cognition: cerebral organization in strongly lateralized left-handed subjects.

Cerebral organization for the processing of emotion and for the differential processing of affect and cognition have thus far been studied exclusively in right-handed subjects. Since handedness is related to cerebral dominance, our understanding of the neural processing of affect and cognition should be further enhanced by the study of sinistral subjects. The present study examined the differential parietal processing of emotional stimuli under affective and cognitive conditions in left-handed subjects. The subjects were exposed to emotional stimuli presented under affective and cognitive instructional sets and to neutral, control stimuli. Bilateral electroencephalographic and bilateral electrodermal activity data showed greater responsiveness to emotional than neutral stimuli but no differential lateralization of affect and cognition in left-handed subjects. Results also showed that female subjects were more responsive to emotional stimuli than male subjects. Results were interpreted as suggesting that left-handed individuals may be less strongly lateralized for the differential processing of affect and cognition than right-handed individuals and that females may have greater focal organization for the processing of emotion than males.

Adult↗
PubMed1989

Increased proteoglycan synthesis following the differentiation of F9 embryonal carcinoma cells: formation of a differentiation-specific proteoheparan sulfate.

We have examined changes in proteoglycan synthesis by F9 embryonal carcinoma cells after the cells have been treated with retinoic acid or retinoic acid plus cholera toxin. Retinoic acid is known to stimulate the differentiation of this cell type to a primitive endoderm-like cell characterized by the production of basement membrane components such as type IV collagen, laminin and proteoglycans. We have now demonstrated that proteoglycan synthesis and secretion were further stimulated when cholera toxin was added in addition to retinoic acid. Moreover, media of these fully differentiated cells was found to contain a different species of proteoheparan sulfate not produced by stem cells or retinoic acid-treated cells. This proteoheparan sulfate had a high density upon CsCl gradient centrifugation. The protein core of this proteoheparan sulfate was estimated by SDS gel electrophoresis to be approximately 15,000 daltons.

Animals↗
PubMed1989

For better or for worse: left-handedness, pathology, and talent.

Geschwind and his colleagues have hypothesized that left-handedness may be a marker for anomalous dominance and is associated with certain immune disorders, learning disorders, and special talents. The few relevant studies done to date have yielded somewhat mixed findings, and little had been done to study the relationship of relevant findings to the definition of handedness employed in a given study. The present study assessed the association between handedness and a variety of disorders, talents, and skills in subjects and their parents and siblings. Results showed that mathematical, artistic, and musical talents varied systematically as a function of handedness. Verbal skills, stuttering, and asthma were also significant discriminators in some discriminant function analyses, and certain variations in the definition of handedness produced systematic variations in results. Finally, certain disorders, particularly eczema, stuttering, and epilepsy, in the parents were related to handedness in their offspring.

Adult↗