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Biomedical subjects

B D Smith

Publications and source records attributed to B D Smith.

At least 109 records · Page 6Linked to original sources

Hemispheric asymmetry and emotion: effects of nonverbal affective stimuli.

The purpose of the present study was to investigate the cerebral processing of affect by measuring the electroencephalographic activity of the frontal lobes and electrodermal activity in response to a series of nonverbal affective stimuli. Cognitive and sensorimotor processes were minimized by employing a design that did not require subjects to perform any task other than attending to the stimuli. Summated frontal alpha activity was determined during nonemotional, positive, and negative stimuli. Changes in bilateral skin conductance were also measured during the presentation of the stimuli. Results demonstrated that there was bilateral activation of the frontal lobes in response to the positive affective stimuli. The level of activation of the frontal lobes was the same in response to both negative and nonemotional stimuli. There was no evidence of hemispheric asymmetry or gender-related differences in patterns of activation. Furthermore, there was no evidence of lateralization in the skin conductance response magnitude.

Acoustic Stimulation↗

pH-induced modification of BCNU toxicity on glial cells.

A dose-response relationship for the dependence of the cytotoxic activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on extracellular pH has been established. The hypothesis, that the integral dose of the rapidly degrading BCNU determines cytotoxicity, has been examined. Human glial cells exhibited lower survival rates for BCNU exposure at pH 6.5 and pH 6.7, compared to pH 7.4. This effect can be explained by the more rapid decay of BCNU at pH 7.4, leading to a lower integral dose. However, the determination of BCNU decay constants for different pH values and calculation of the integral exposure dose reveal that tolerance to BCNU is increased with decreasing pH.

Astrocytoma↗

Erythrocyte-endothelial cell adherence in sickle cell disorders.

Detachment of individual sickle erythrocytes from cultured endothelial cell monolayers has been evaluated by a fluid-shearing technique in an effort to quantitate adherence at shear forces that would be anticipated in the in vivo circulation. Nonirreversibly sickled cells (non-ISC) were more adherent at normal oxygen tensions than control cells. More than 1% non-ISC remained attached to the monolayer at forces greater than physiologic shear stresses in capillary and venous circulations, and many of the most avidly attached cells, once separated, immediately reattached to adjacent endothelial cells. These data suggest that hemoglobin S-containing erythrocytes may have a higher frequency of adherence in vivo in regions of low shear stress where prolonged erythrocyte-endothelial cell contact could occur. Some of these cells detached by shear force would subsequently reattach in in vivo conditions. Plasma-enhanced attachment frequency and plasma from blood in a case of sickle crisis caused further increase. These observations further support the concept that sickle erythrocyte-endothelial cell interaction may be a significant factor in initiation of vascular occlusive events in sickle cell disease.

Anemia, Sickle Cell↗

Abnormal erythrocyte fragmentation and membrane deformability in paroxysmal nocturnal hemoglobinuria.

Hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) is considered to be a result of an intrinsic membrane defect. This defect may result in abnormal material properties of PNH erythrocytes. To examine this hypothesis, fragmentation failure, and membrane deformability were assessed in the absence of complement by micropipette techniques. Membrane viscosity was determined by observing relaxation of deformed cells. Results show a bimodal distribution of force for membrane failure, membrane viscoelasticity, and elastic shear modulus. One population requires significantly less force for fragmentation, mean 0.56 X 10(-6) dyne; has increased membrane viscosity, mean 0.205 X 10(-2) dyne sec/cm; and has decreased elastic shear modulus, mean 0.56 X 10(-2) dyne/cm. A second population resembles control with fragmentation force, mean 1.19 X 10(-6) dyne, control 1.05 X 10(-6) dyne; membrane viscosity, mean 0.112 X 10(-2) dyne/cm, control 0.102 X 10(-2) dyne sec/cm; elastic shear modulus, mean 0.70 X 10(-2) dyne/cm, control 0.78 X 10(-2) dyne/cm. The percent of cells with abnormal material properties corresponds to the percent of PNH III cells determined by complement lysis. Thus, the hemolysis attributed to an abnormal clone of erythrocytes in PNH is associated with an intrinsic membrane abnormality which predisposes to lysis.

Blood Viscosity↗

Comparison of follicular response in patients with one or two ovaries in a program of in vitro fertilization.

Some patients undergoing in vitro fertilization have had a previous oophorectomy. The purpose of this study was to provide a preliminary comparison of the follicular response to ovulation induction with sequential clomiphene citrate and human menopausal gonadotropin (hMG) in patients with one (n = 14) or two (n = 14) ovaries. No statistically significant differences were detectable in the following parameters: mean number of ampules of hMG required, mean number of days of hMG therapy, mean number of follicles greater than 15 mm on ultrasound, mean number of mature or number of immature oocytes, mean number of embryos transferred, and number of pregnancies. Patients with both ovaries in situ demonstrated a trend for greater numbers of follicles greater than 15 mm aspirated at laparoscopy (5.9 versus 3.4, P = 0.03). We conclude that the presence of a single ovary does not appear to influence the outcome of in vitro fertilization.

Clomiphene↗

Binding of lysyl oxidase to fibrils of type I collagen.

The binding of highly purified bovine aortic lysyl oxidase to native fibrils of type I collagen has been measured by assay of unbound lysyl oxidase activity in the supernatants of enzyme-collagen mixtures after centrifugation. The apparent binding affinity of lysyl oxidase for native fibrils is quite similar to that for fibrils prepared from pepsin- or chymotrypsin-digested type I collagen, demonstrating that the enzyme binds to the triple-helical portion of collagen molecules. The data also indicate that the enzyme binds predominantly to the fibrillar surface. The results suggest that lysyl oxidase initiates crosslink formation at an early stage in collagen fibrillogenesis.

Amino Acid Oxidoreductases↗

Cardiac electrophysiologic effects of pancuronium.

A microelectrode examination of guinea pig left ventricular papillary muscle was performed to determine whether there was a direct effect of pancuronium on cardiac cells and, if so, to attempt to ascertain the mechanism of this effect. Electrical events were measured before and during superfusion with pancuronium, epinephrine, propranolol, and verapamil; alone and in various combinations. Pancuronium prolonged the duration of the action potential (AP); increased resting potential (Em), AP magnitude, and rate of rise of the AP (dV/dt); and resulted in spontaneity in 12% of the muscles. Epinephrine and pancuronium combined caused spontaneity in 80% of the muscles and oscillatory behavior. Additionally, this combination decreased AP magnitude, Em, and dV/dt in several preparations--a pattern of response similar to that seen in ouabain-treated myocardial cells under the influence of catecholamines. These changes were always reversed by verapamil or by perfusion with a drug-free medium, and were usually reversed by propranolol. The data suggest a combined pancuronium/epinephrine induced increase in cardiac membrane permeability to Ca2+.

Action Potentials↗

Absence of procollagen alpha 2(I) mRNA in chemically transformed rat liver epithelial cells.

The W8 cell line, a chemically transformed variant of K16 rat liver epithelial cells, does not produce a normal type I collagen but instead secretes alpha 1(I) trimer and no alpha 2(I) chains (Smith, B.D., and Niles, R. (1980) Biochemistry 19, 1820-1825). Analysis of total cellular RNA from the K16 and W8 cells by cell-free translation in a rabbit reticulocyte lysate demonstrates the specific absence of translatable pro-alpha 2(I) collagen mRNA. No alpha 2(I) collagen mRNA sequences were detected by Northern hybridization analysis using cloned rat alpha 2(I) cDNAs as a probe. The total amount of alpha 1(I) collagen mRNAs, however, was the same in both cell types, suggesting a lack of coordinate control of alpha 1(I) and alpha 2(I) mRNAs in the transformed cells.

Acetoxyacetylaminofluorene↗

Pathogenesis of tumor desmoplasia. II. Collagens synthesized by line 1 and line 10 guinea pig carcinoma cells and by syngeneic fibroblasts in vitro.

For the investigation of the pathogenesis of desmoplasia, the capacities to synthesize collagen in vitro of 2 bile duct carcinomas (lines 1 and 10) of Sewall-Wright inbred strain 2 guinea pigs and of syngeneic dermal fibroblasts were studied. Line 10 cells synthesized collagen type IV as judged by sensitivity to bacterial collagenase, by immunoprecipitation, by migration of pro alpha (IV) chains and pepsin-resistant fragments on sodium dodecyl sulfate-polyacrylamide gels, and by immunofluorescence. Line 1 cells also synthesized small amounts of collagenase-sensitive protein. Neither line 1 nor line 10 cells synthesized detectable collagen type I, III, or V. Only about 1% of [14C]proline incorporated by tumor cells was found in collagenase-sensitive protein. In contrast, dermal fibroblasts synthesized 4 and 128 times as much collagenase-sensitive protein as line 10 and line 1 cells, respectively, amounting to 20% of total protein synthesized. Fibroblasts produced mostly collagen types I and III, in a ratio of 7:1, and smaller amounts of collagen type V. Thus lines 1 and 10 carcinoma cells produce primarily basement membrane collagen, whereas interstitial collagens, abundant in desmoplastic tumor stroma, are fibroblast products.

Animals↗

Pathogenesis of desmoplasia. I. Immunofluorescence identification and localization of some structural proteins of line 1 and line 10 guinea pig tumors and of healing wounds.

The structural proteins of the scirrhous line 1 and the medullary line 10 bile duct carcinomas, both syngeneic in strain 2 Sewall-Wright inbred guinea pigs, were studied. Tumor structural proteins were compared with those of healing wounds. A provisional stromal matrix of cross-linked fibrin and fibronectin was initially deposited in both tumors and wounds and was subsequently replaced by granulation tissue containing collagen types I and III. The amounts of stromal fibrin-fibronectin and collagen were characteristic of each tumor: Line 1 contained significantly greater amounts than line 10. These differences were augmented when line 1 tumor rejection was prevented with cyclosporine, permitting time for stromal maturation. In tumors and wounds laminin and collagen type IV were found only in basement membranes. The findings suggest that 1) tumor desmoplasia is analogous to wound healing, 2) both processes involve replacement of an antecedent fibrin-fibronectin provisional matrix, 3) the extent of fibrin-fibronectin is characteristic of each tumor, and 4) tumor desmoplasia correlates with the amount of fibrin-fibronectin matrix deposited.

Animals↗

A secreted phosphoprotein marker for neoplastic transformation of both epithelial and fibroblastic cells.

A wide variety of virally and spontaneously transformed fibroblasts secrete a major transformation-related phosphoprotein with a molecular weight (MW), depending on the species of origin, of about 62,000 (62K). Markedly elevated extracellular levels of this major 32P-labelled protein are not simply linked to exponential growth but instead are associated directly with transformation. The phosphoprotein is not antigenically related to p60src, p60c-src or simian virus 40 (SV40) non-viral T antigen, and it is further distinguishable from SV40 non-viral T antigen (pp 53) on the basis of its electrophoretic mobility. In this study we have compared a variety of normal and transformed epithelial cells for secretion of this 32P-labelled protein and have found that this marker distinguishes neoplastic from preneoplastic and normal mouse mammary epithelium and also identifies highly tumorigenic cells derived from guinea pig bile duct epithelium and rat liver epithelium. Because the classical phenotypic properties commonly associated with transformation of fibroblasts cannot be generally used to discriminate tumorigenic from non-tumorigenic epithelial cells, this phosphoprotein, which identifies tumorigenic cells of both fibroblastic and epithelial origin, is likely to be of particular importance.

Acetoxyacetylaminofluorene↗

Identification of collagens synthesized by cultures of normal human corneal and keratoconus stromal cells.

We have examined the collagens synthesized by cultures of normal human corneal stromal cells. Radioactively labeled products, accumulated in the culture medium during a 24-h labeling period, were treated with pepsin and analyzed by SDS-polyacrylamide gel electrophoresis. The cell layer collagen was characterized by 2.6 M and 4.4 M salt fractionation at neutral pH. CM-cellulose column chromatography, SDS-gel electrophoresis, and cyanogen bromide peptide mapping. Type I alpha 1 and alpha 2 chains were the predominant components in both the cell layer and the medium fractions of normal human stromal cultures; type III collagen was found mostly in the culture medium; and type V collagen was associated with the cell layer. Immunofluorescent techniques used to visualize collagen deposition in the cell layer confirmed the presence of these collagen types. Keratoconus is a disease characterized by thinning and scarring of the central cornea. Stromal cells grown from keratoconus corneas produced similar types of collagen (types I, III, and V) as normal human controls. Cells from keratoconus patients, however, contained more type V collagen in the cell layer than did normal cells. The difference was seen only in the 4.4 M salt precipitates. Since type V collagen is one component of cell surfaces, the primary defect in cultures from keratoconus corneas could involve cell membrane and cell surface components.

Adult↗

The depressed mother as a source of stimulation for her infant.

Compared a group of 25 postpartum depressed mothers and 25 control mothers with respect to the level and quality of stimulation they provided for their newborn infants during a feeding session. Observer measures of maternal behavior included visual, auditory and kinesthetic stimulation and levels of unconditional positive regard. Results did not indicate any differences between the two groups in levels of stimulation. However, depressed mothers provided significantly lower levels of unconditional positive regard and exhibited less continuity of rocking behavior with their infants. A post hoc analysis that compared the extremes of the two S groups (N = 22) revealed significant differences in gazing behavior, with more depressed mothers gazing less at their infant's faces. Depressed mothers exhibited significantly lower levels of marital adjustment and had more extensive postpartum concerns. Contrary to expectations, no relationship was demonstrated between level of marital adjustment and maternal behavior toward the infant.

Adaptation, Psychological↗

Cone beam convolution formula.

This paper presents a three-dimensional convolution formula for a general set of cone beam data. This formula is illustrated by examining at length the formula for a particular set of cone beam data--the set of cone beam data from source points which are located along a straight line. How the three-dimensional formula could be implemented for a general set of cone data is discussed.

Mathematics↗

Job enrichment.

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Humans↗

Inverse correlation of collagen production to anchorage independence and tumorigenicity in W8- and M-cell lines.

Collagen production by fibroblasts has been shown to be transformation sensitive and to correlate inversely with tumorigenicity. Therefore, it is of interest to determine if carcinoma cell collagen production is similar to fibroblast collagen production. Since there are few carcinoma model systems available for this study that have cultured cells with increasing tumorigenic potential, a new series of cell lines, referred to as M-cells, were developed from the well-described rat liver epithelial cell line W8, originally established by I. B. Weinstein. The W8 cell line is a N-acetoxy-2-acetylaminofluorene-treated, weakly tumorigenic rat liver cell derived from the parent K16 cell line. The M-cells were serially selected by isolating cell lines from tumors and reinjecting them into animals. Although these M-cells maintain their epithelial characteristics, their overall protein production, their type of collagen, and their ability to form undifferentiated carcinomas in vivo, they progressively exhibit increasing tumorigenic potential, increasing anchorage independence, and decreasing collagen production. The W8 and M-cells maintain decreasing amounts of collagen type I trimer production, which most likely contributes to the decreasing connective tissue stroma observed in their carcinomas. This cell system provides a new model to examine epithelial cell surface and extracellular substrate attachment interactions.

Acetoxyacetylaminofluorene↗