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Biomedical subjects

B D Smith

Publications and source records attributed to B D Smith.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Stimulation of collagen formation by insulin and insulin-like growth factor I in cultures of human lung fibroblasts.

We examined the effects of insulin and insulin-like growth factor I (IGF-I) on the production of collagen by cultures of human embryonic lung fibroblasts. Insulin at 20 ng/ml increased collagen accumulation by 58% and total protein formation by 18%. At 2 micrograms/ml, insulin increased collagen production by 2- to 3-fold and total protein production by 2-fold. The mRNA levels for alpha 1(I) and alpha 1(III) collagen chains were elevated by insulin compared with untreated control values. IGF-I at 10 ng/ml increased collagen production 2-fold. IGF-I at 100 ng/ml maximally increased collagen production 3-fold. A specific antibody to the IGF-I receptor (alpha IR-3) caused a concentration-related decline in insulin-induced collagen formation. The addition of antibody at 1 micrograms/ml, resulted in 80% inhibition of insulin-induced collagen accumulation. Higher levels of antibody were required to inhibit IGF-I mediated collagen formation. The presence of antibody (alpha IR-3) also blocked fibroblast proliferation stimulated by epidermal growth factor plus insulin. These data show that insulin-induced collagen formation is mediated primarily through an interaction with the IGF-I receptor. The modulation of extracellular matrix production by insulin may influence the repair of tissue injury and the development of the accelerated atherosclerosis that accompanies the diabetic state in humans.

Blotting, Northern↗

Undifferentiated F9 embryonal carcinoma cells produce a short-chain collagen molecule.

The undifferentiated F9 embryonal carcinoma cells produce a unique collagen that decreases in amount during retinoic acid-induced differentiation of F9 cells into basement-membrane parietal endoderm. A bacterial-collagenase-sensitive protein of approx. 60,000 Da was resolved on polyacrylamide-gel electrophoresis. After pepsin digestion, two pepsin-resistant fragments containing hydroxyproline were demonstrated, suggesting that a portion of the molecule has a stable triple helix. The mRNA from the undifferentiated F9 cells translates a collagenase-sensitive protein with a molecular mass consistent with the 60,000 Da collagenous protein produced by undifferentiated F8 cells.

Animals↗

Construction of a full-length cDNA encoding human pro-alpha 2(I) collagen and its expression in pro-alpha 2(I)-deficient W8 rat cells.

We have constructed a cDNA encoding the entire human pro-alpha 2(I) collagen molecule. Sequence determination for 2196 base pairs at the 5' end of the cDNA clone, and comparison with previously characterized human alpha 2(I) sequences, identified a number of nucleotide and amino acid polymorphisms. Functionality of the cDNA clone, under control of the long terminal repeat of Rous sarcoma virus, was demonstrated by its introduction into the W8 cell line. The W8 line, a chemically transformed variant of K16 rat liver epithelial cells, has been previously shown to lack detectable levels of alpha 2(I) RNA, but to secrete alpha 1(I) homotrimers. Introduction of the human cDNA into W8 cells, resulted in secretion of chimeric type I collagen comprised of rat alpha 1(I) and human alpha 2(I) chains. Availability of a functional full-length clone of human alpha 2(I) cDNA, combined with the W8 cell line as expression system, will allow detailed analysis, through site-directed mutagenesis, of domains on the pro-alpha 2(I) molecule involved in assembly, transport, secretion, and fibrillogenesis.

Amino Acid Sequence↗

Methylation of the alpha 2(I) collagen gene in chemically transformed rat liver epithelial cells.

W8 cells, 2-N-(acetoxyacetyl)aminofluorene-transformed rat liver epithelial-like cells, secrete no alpha 2(I) collagen chains. This paper reports the first demonstration of DNA methylation in the promoter-5' region of an alpha 2(I) collagen gene which occurs in W8 cells. Since inhibition of methylation by azacytidine induces transcription of the alpha 2(I) gene, DNA methylation of W8 alpha 2(I) promoter-5' region could contribute to altered collagen production in these cells.

Acetoxyacetylaminofluorene↗

Acquired Pelger-Huet anomaly in a case of non-Hodgkin's lymphoma.

Acquired Pelger-Huet anomaly has been found in association with both hematologic and nonhematologic diseases. While its association with myeloid hematologic disorders is well known, this granulocytic anomaly has also been found in chronic lymphocytic leukemia, multiple myeloma and Hodgkin's disease. This report describes a case of acquired Pelger-Huet anomaly in non-Hodgkin's lymphoma and reviews the association of this anomaly with both lymphoid and myeloid hematologic disorders.

Aged↗

Hemispheric asymmetry and emotion: lateralized parietal processing of affect and cognition.

The differential cerebral processing of affect and cognition may have important implications for a more general understanding of how these two complex sets of functions differ and how they interact. Building upon recent studies of hemispheric asymmetry in emotion, the present study focused on the differential parietal processing of emotional stimuli under affective and cognitive conditions. Subjects were exposed to neutral and emotional stimuli presented under cognitive and affective instructional sets. Bilateral electroencephalographic (EEG) data showed that the principal differentiation between affective and cognitive conditions occurred in the right hemisphere, whereas the highest overall level of activation during emotional stimulation was in the left hemisphere. It was also found that affective conditions produced higher of levels of both EEG and electrodermal activity than either cognitive or neutral conditions. Finally, significant patterns of gender differentiation suggested greater focal organization for affective arousal in females than males.

Affect↗

Cerebral processing of nonverbal affective stimuli: differential effects of cognitive and affective sets on hemispheric asymmetry.

The cerebral processing of emotion has been the subject of a number of recent studies, but results relating to hemispheric asymmetry have been quite mixed. The present study attempted to clarify and extend findings in this area by examining the differential effects of cognitive and affective sets on hemisphere asymmetry under conditions of nonverbal emotional stimulation. Electroencephalographic (EEG) data, recorded bilaterally, showed that differential hemispheric processing interacted with emotion (positive or negative), condition (cognitive or affective), and sex. In those emotion/condition combinations where hemispheric asymmetry was observed, there was greater activity in the left hemisphere than in the right. In addition, positive affect produced greater asymmetry than negative, and females showed greater activity in response to positive emotional stimuli than did males. Further, affective conditions yielded higher levels of activity than did cognitive. Finally, electrodermal activity showed lateralization effects as a differential function of cognitive and affective conditions.

Affect↗

Subjective concomitants of motion sickness: quantifying rotation-induced illness in squirrel monkeys.

It has been suggested by numerous researchers that the development of conditioned food aversion (CFA) in experimental animals represents the presence of a subjective state of illness. Squirrel monkeys with proven susceptibility to rotation-induced vomiting were given surgical bilateral labyrinthectomies, a procedure known to abolish signs and symptoms of motion sickness in human beings. Postoperatively, labyrinthectomized monkeys neither vomited nor revealed any reduction in food consumption when exposed to provocative rotation. Other samples of monkeys known to be refractory to horizontal rotation and to sinusoidal vertical motion also exhibited little tendency to acquire a conditioned aversion to banana. But monkeys who had sham operations and those who revealed weak-to-strong signs of motion sickness exhibited a marked CFA (significant reduction in food intake). The strength of CFA was much greater when elicited in the test vehicle when compared with response in the home cage. The findings are interpreted as support for a limited application of CFA procedures for inferring the presence of motion-induced nausea and malaise.

Animals↗

Erythrocyte-endothelial cell adherence in senescence and in hemolytic disorders.

Adherence of normal human erythrocytes to cultured endothelial cells when exposed to in vitro fluid shear forces typical of venules, capillaries and arterioles is very low, less than 0.03 percent, in the presence of an albumin-buffer but increases five fold by the effects of autologous plasma. Senescent erythrocytes obtained by density separation had an adherence frequency in the normal cell range, suggesting that predisposition to endothelial adherence is not a key factor in regulation of life span by the sequestration, identification and phagocytosis modulated by immune recognition. Sickle cells' frequency of adherence exceeds that of normal cells particularly at low shear forces calculated to resemble those of veins and sinuses, and increases five to ten fold when autologous plasma obtained during sickle crisis is present; these findings add support to the hypothesis that excessive tendency for sickle cell adherence may contribute to the vascular obstructive phenomena of the disorder. The behavior of hereditary spherocytes and thalassemic erythrocytes resembles normal cells, suggesting that hemolytic mechanisms are not significantly dependent on erythrocyte-endothelial cell interaction. Erythrocytes from patients having diabetes exhibit the characteristics of control cells, suggesting that their membrane adhesion to endothelium may not be critical to initiation of vessel wall pathophysiological processes; however, the behavior in relation to damaged endothelial cells may differ importantly.

Anemia, Sickle Cell↗

Adaptation and habituation of motion-induced vomiting in squirrel monkeys.

Nonrestrained adult squirrel monkeys were found to be prolific vomiters when rotated in the horizontal plane for at least 1 h with visual cues available. When multiple daily spins were given, monkeys who vomited early during the first session tended to habituate during subsequent rotations. Subjects who vomited late during the first spin tended to vomit increasingly earlier for several days before the trend reverted to habituation. When a single rotation was continued for up to 8 h, emetic waves occurred with a high probability density for about 2 h, then ceased for many hours with an occasional animal exhibiting isolated emetic episodes. Adaptation effects were transient; when retested beyond a week, most subjects vomited in less time than did inexperienced monkeys on their first exposure to rotation. Attempts to confirm the findings using sinusoidal vertical acceleration were unsuccessful because of failure to induce vomiting using this type of motion.

Adaptation, Physiological↗