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Biomedical subjects

B D Smith

Publications and source records attributed to B D Smith.

At least 73 records · Page 4Linked to original sources
PubMed1995

The lateralized processing of affect in emotionally labile extraverts and introverts: central and autonomic effects.

The purpose of the present study was to better understand both the lateralized hemispheric processing of emotion and the differential neural processing of arousal in extraverts and introverts. We preselected right-handed male and female extraverts and introverts who were high in emotional lability. Each subject was exposed to two positive and two negative emotional stimuli under each of three counterbalanced conditions, including affective, cognitive, and neutral, while EEG and electrodermal activity (EDA) were recorded. Results showed that introverts are more aroused and that extraversion interacts with gender to produce differentiated patterns of lateralized neural activity. In addition, affective conditions produced higher levels of arousal than did cognitive or neutral conditions, particularly in the left hemisphere and under negative as opposed to positive stimuli. Finally, the hemispherically differentiated processing of positive and negative stimuli was affected by the contextual conditions under which they were experienced.

Adolescent↗
PubMed1994

Expression of alpha 2 type I collagen in W8 cells increases cell adhesion and decreases colony formation in soft agar.

A chemically transformed cell line, W8, produces alpha 1(I) homotrimers with no alpha 2(I) chains whereas the parent cell line, K16, produces heterotrimers. When W8 cells were transfected with plasmid constructs containing the full length human alpha 2(I) cDNA driven by viral promoters, the cells expressed alpha 2(I) collagen chains forming varying amounts of heterotrimers. Previously, we have shown that K16 and W8 cells have different growth characteristics (Smith, B.D. et al., Cancer Research 43: 4275-4282, 1983) including population doubling, saturation density, cell adhesion and colony formation in soft agar. These parameters were tested for each transfected cell line in order to determine if the alpha 2(I) expression and heterotrimer formation alters cell characteristics. The cells expressing alpha 2(I) forming heterotrimers needed higher concentrations of trypsin or longer time periods to lift from the plate suggesting a role for alpha 2(I) in cell adhesion. The W8 cells formed colonies in soft agar exhibiting anchorage independent growth. However, W8 cells expressing alpha 2(I) chains formed less colonies in soft agar than W8 cells or W8 cells transfected with a neomycin resistant gene indicating that the alpha 2(I) producing cells were less anchorage independent than W8 cells. Population doubling time, morphology and saturation densities were similar to W8 cells with small alterations towards an epithelial morphology. These results demonstrated that alpha 2(I) within heterotrimer is important for cell adhesion and anchorage independent growth.

Animals↗
PubMed1993

Regulation of the alpha 1(I) collagen promoter via a transforming growth factor-beta activation element.

A transforming growth factor-beta (TGF-beta) activating element (TAE), with a nuclear factor-1 (NF-1)-like sequence, was previously located 1.6 kilobases upstream from the transcription start site in the alpha 1(I) collagen promoter (Ritzenthaler, J. D., Goldstein, R. H., Fine, A., Lichtler, A., Rowe, D. W., and Smith, B. D. (1991) Biochem. J. 280, 157-162). Double-stranded TAE, but not NF-1 consensus sequences, abrogated TGF-beta stimulation of co-transfected collagen promoter-chloramphenicol acetyltransferase constructs. Mutations in non-NF-1 binding sites, located by methylation interference, eliminated activity of the TAE oligonucleotide. However, TAE sequences failed to bind in vitro expressed NF-1 protein, to compete for NF-1-binding proteins, and to bind with protein which reacts with antibodies to NF-1 family of proteins. Within the TAE there was an activator protein 2 (AP-2) binding site. Although AP-2 protein bound to TAE, antibodies to AP-2 did not react with nuclear protein-TAE complexes. TAE bound to a 34,000-Da protein on Southwestern analysis. However, the UV-cross-linked TAE-nuclear protein complex was 82,000 Da. Finally, a dose-response study demonstrated that TGF-beta increased TAE nuclear binding proteins at lower doses with a different response curve than NF-1 nuclear binding proteins. Taken together these data demonstrated that TGF-beta functions in human lung fibroblasts to activate collagen transcription through TAE sites by protein complexes independent of NF-1 or AP-2 protein.

Base Sequence↗
PubMed1993

Symptomatic renal metastasis from testicular cancer.

The clinical course of a patient who presented with a massive left renal metastasis from testicular carcinoma is described. Treatment with cisplatin-based chemotherapy produced a dramatic response. Symptomatic renal metastases from testicular cancer are rare and may be reflective of a high tumor burden or refractory disease.

Adult↗
PubMed1993

Cost accounting in radiation oncology: a computer-based model for reimbursement.

PURPOSE: The skyrocketing cost of medical care in the United States has resulted in multiple efforts in cost containment. The present work offers a rational computer-based cost accounting approach to determine the actual use of resources in providing a specific service in a radiation oncology center. METHODS AND MATERIALS: A procedure-level cost accounting system was developed by using recorded information on actual time and effort spent by individual staff members performing various radiation oncology procedures, and analyzing direct and indirect costs related to staffing (labor), facilities and equipment, supplies, etc. Expenditures were classified as direct or indirect and fixed or variable. A relative value unit was generated to allocate specific cost factors to each procedure. RESULTS: Different costs per procedure were identified according to complexity. Whereas there was no significant difference in the treatment time between low-energy (4 and 6 MV) or high-energy (18 MV) accelerators, there were significantly higher costs identified in the operation of a high-energy linear accelerator, a reflection of initial equipment investment, quality assurance and calibration procedures, maintenance costs, service contract, and replacement parts. Utilization of resources was related to the complexity of the procedures performed and whether the treatments were delivered to inpatients or outpatients. In analyzing time motion for physicians and other staff, it was apparent that a greater effort must be made to train the staff to accurately record all times involved in a given procedure, and it is strongly recommended that each institution perform its own time motion studies to more accurately determine operating costs. Sixty-six percent of our facility's global costs were for labor, 20% for other operating expenses, 10% for space, and 4% for equipment. Significant differences were noted in the cost allocation for professional or technical functions, as labor, space, and equipment costs are higher in the latter. External beam treatment-related procedures accounted for more than 50% of all technical and professional revenues, simulation for 8% to 10%, and other physics/dosimetry procedures for 11% to 14% of revenues. Some discrepancies were identified between the actual cost and level of reimbursement of various procedures. Details are described in the manuscript. CONCLUSION: It is imperative to develop an equitable reimbursement system for radiation oncology services, based on cost accounting and other measures that may enhance productivity and reduce the cost per procedure unit, while at the same time preserving the highest quality of service provided to patients.

Accounting↗
PubMed1993

Effects of caffeine and gender on physiology and performance: further tests of a biobehavioral model.

The present study extended testing of our biobehavioral model describing the effects of arousal and caffeine to include an examination of gender differences and their interactions with habitual and acute caffeine ingestion. Males and females selected as high or low habitual caffeine users were randomly assigned to receive either caffeine or a placebo and exposed to novel and repetitive recall tasks and to simple auditory stimuli. Electrodermal activity and recall task performance were recorded. The four major factors examined, including habitual caffeine use, acute ingestion, gender, and stimulus novelty, affected behavior, physiology, or both. Results showed that habitual caffeine usage systematically affected tonic arousal (skin conductance level) and improved recall task performance. Acute caffeine ingestion increased phasic arousal (skin conductance response amplitude) and reduced habituation rates. Gender interacted with other factors to significantly affect both tonic and phasic arousal, and females performed better than males on the recall tasks. These results were partially supportive of the theoretical model, and further work is needed to examine the interactions of acute and chronic caffeine intake with gender and novelty.

Adult↗
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↗