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Biomedical subjects

E R Smith

Publications and source records attributed to E R Smith.

At least 73 records · Page 4Linked to original sources
PubMed1998

ESA1 is a histone acetyltransferase that is essential for growth in yeast.

Posttranslational acetylation of core histone amino termini has long been associated with transcriptionally active chromatin. Recent reports have demonstrated histone acetyltransferase activity in a small group of conserved transcriptional regulators directly linked to gene activation. In addition, the presence of a putative acetyltransferase domain has been discovered in a group of proteins known as the MYST family (for its founding members MOZ, YBF2/SAS3, SAS2, and Tip60). Members of this family are implicated in acute myeloid leukemia (MOZ), transcriptional silencing in yeast (SAS2 and YBF2/SAS3), HIV Tat interaction in humans (Tip60), and dosage compensation in Drosophila (MOF). In this report, we express a yeast ORF with homology to MYST family members and show it possesses histone acetyltransferase activity. Unlike the other MYST family members in Saccharomyces cerevisiae this gene is essential for growth.

Acetyltransferases↗
PubMed1998

Knowledge acquisition, accessibility, and use in person perception and stereotyping: simulation with a recurrent connectionist network.

Connectionist models contrast in many ways with the symbolic models that have traditionally been applied within social psychology. In this article the authors apply an autoassociative connectionist model originally developed by J. L. McClelland and D. E. Rumelhart (1986) to reproduce several well-replicated and theoretically important phenomena related to person perception and stereotyping. These phenomena are exemplar-based inference, group-based stereotyping, the simultaneous application of several stereotypes to generate emergent characteristics, and the effects of recency and frequency of prior exposures on accessibility (the probability of a representation's use). Though many of these phenomena are explained by current theories in social psychology, the simulation contributes to parsimony and theoretical integration by showing that a single, very simple mechanism can generate them all. The model also predicts a new phenomenon--rapid recovery of accessibility after it has declined to zero.

Computer Simulation↗
PubMed1998

The actor as context for social judgments: effects of prior impressions and stereotypes.

Three experiments identified conditions under which trait judgments made about a behavior were more likely to influence later judgments of the behavior. In Experiment 1, participants made trait judgments about numerous behaviors presented with photos of actors. Some behaviors were repeated, paired with the same or a different actor. All repeated behaviors were judged faster than new behaviors. Facilitation was greatest when repeated behaviors were paired with the same actor, suggesting greater influence of prior judgments in this condition. Experiments 2 and 3 replicated this effect, and the pattern of response times (RTs) suggested a stronger association between the actor and behavior when a prior impression of the actor had been formed (Experiment 2) and when the behavior was stereotypic of the actor's group (Experiment 3). Level of prejudice moderated RT patterns in Experiment 3. Implications for context effects, the nature of trait inferences, and stereotype change are discussed.

Adult↗
PubMed1998

Intergroup relations: insights from a theoretically integrative approach.

In social psychology, specific research traditions, which often spring up in response to external events or social problems, tend to perpetuate the theoretical assumptions and methodological approaches with which they began. As a result, theories and methods that have proven powerful in 1 topic area are often not applied in other areas, even to conceptually similar issues. The authors adopt a theoretically integrative approach to the topic of intergroup relations. Theories and empirical approaches from the domains of attitudes, impression formation, the self, personal relationships, and norms offer many new insights into problematic issues, such as repeated findings of dissociations among stereotyping, prejudice, and discrimination. This integrative approach not only promises new theoretical advances, but also suggests numerous potential practical approaches to limiting or reducing destructive patterns of intergroup relations.

Humans↗
PubMed1998

Further studies on the influence of genotype and dietary protein on the performance of broilers.

An experiment was conducted to quantify genetic differences in response to dietary protein level of male vs female broilers. Broilers (1 d old) from a "high-yield" strain cross (Ross x Ross 208) and a "fast-growing" strain cross (Peterson x Arbor Acres) were placed on fresh pine shavings in floor pens. From Day 0 to 18, all birds were fed a 23% CP starter diet. During Days 18 to 53 male birds were fed either a 16, 18, 20, 22, 24, or 26% CP diet (3,200 kcal ME/kg) and female birds were fed the 16, 20, or 24% CP diet. Significant differences (P < 0.05) were noted in the performance of the different strains. Ross x Ross 208 male birds had a higher body weight (3.37 vs 3.16 kg), higher feed intake (7.08 vs 6.78 kg), higher breast yield (31.76 vs 29.25%), higher carcass yield (73.90 vs 71.85%), and a lower adjusted feed conversion ratio (FCR; 2.10 vs 2.16 g:g) than Peterson x Arbor Acres males at 53 d of age. As compared to Peterson x Arbor Acres females, Ross x Ross 208 female broilers also had a higher body weight (2.68 vs 2.55 kg), higher breast meat yield (33.61 vs 30.80%), higher carcass yield (75.31 vs 73.91%), and lower adjusted FCR (1.97 vs 2.04 g:g). Qualitative differences in the response of these strains were confirmed and better qualitative data is presented that can be used to predict the important output parameters from the import inputs in broiler production.

Aging↗
PubMed1998

Influence of broiler strain cross and dietary protein on the performance of broilers.

The purpose of this experiment was to quantify the responses of two broiler strain crosses to different dietary protein levels on performance and carcass yields. Day-old broiler chicks from a high-yield strain cross (Ross x Ross 208) and a fast-growing strain cross (Peterson x Arbor Acres) were placed in floor pens on fresh pine shavings. All birds were fed a 23% CP starter for the first 18 d. During Days 18 to 53, birds were fed either 16, 20, or 24% CP diets (3,200 kcal ME/kg). At 53 d of age, significant differences (P < 0.05) were noted in the performance of the strains. Overall, Ross x Ross birds had higher body weights (3.29 vs 3.10 kg), higher feed intakes (6.40 vs 6.11 kg), and higher carcass yields (72.51 vs 71.17%), although the differences were dependent on dietary protein levels. Strain cross had no significant effect on feed conversion (1.95 g feed: g gain vs 1.97 g:g). Results indicated that both strain cross and protein level had effects on body weight and feed intake, and there were significant strain cross by protein level interactions for body weight and carcass weight. Increasing dietary protein level increased body weights more for the Ross x Ross 208 than for the Peterson x Arbor Acres broilers. Feed conversion was indirectly proportional to dietary protein level, but was not affected by strain cross. Percentage carcass yield was greatly affected by strain (P < 0.0001), but protein level had no significant effect (P = 0.68). The significant interactions indicate that different strain crosses should have different feeding programs to maximize profitability.

Age Factors↗
PubMed1998

Quantitative assessment of independent contributions of pericardium and septum to direct ventricular interaction.

In the intact animal, it is difficult to discriminate between the independent effects of series and direct ventricular interaction (DI) or the individual contributions of the pericardium and septum to DI. Left ventricular (LV) venous return (LVVR) and right ventricular (RV) end-diastolic pressure (RVEDP) were varied independently in a right-heart bypass model. LV minor-axis diameters were measured, and the product of the two diameters was used as an index of LV volume (LVVI). At each RVEDP (0, 5, 10, and 15 mmHg), increased LVVR caused an increased LVVI. When RVEDP was increased, increased pump output was required to maintain a given LVVI. RV-to-LV pressure gain (DeltaLVEDP/DeltaRVEDP) reflects coupling and DI. With the pericardium closed, the gain was dependent on RVEDP; when RVEDP was increased from 0 to 5 mmHg, the gain was not statistically different from zero, indicating little or no DI. When RVEDP was increased from 10 to 15 mmHg, the gain was not statistically different from 1.0, indicating approximately 1:1 coupling of the ventricles. Opening the pericardium reduced the gain, but significant interaction remained. When the septal contribution was accounted for, the remaining interaction was eliminated. In conclusion, DI substantially affects LVEDP-volume relations. Considerable increases in RV output may be required to counterbalance increased constraint to LV filling. With the pericardium closed, RV-to-LV coupling is minimal when RVEDP is low and increases to 1:1 coupling when RVEDP is high. Opening the pericardium reduces DI, but significant septum-mediated interaction remains.

Animals↗
PubMed1998

Effects of short-term altitude training and tapering on left ventricular morphology in elite swimmers.

Short or long-term athletic training has been associated with left ventricular (LV) morphological adaptations, including increases in wall thickness, cavity dimension and estimated LV mass. A limitation of previous studies assessing the 'athlete heart' was that exercise training was performed at sea level. Since the 1968 Olympic summer games a popular method of maximizing athletic performance has been to use altitude training (AT) as a means of improving sea level performance. However, the effects of short term AT and taper training on LV morphology have not been well studied. Based on this limitation, the effects of three weeks of intense AT (1848 m) or low level control training (CT) (1050 m) followed by two weeks of taper training were investigated in 15 elite swimmers between 16 and 21 years of age. Short term AT or CT training followed by two weeks of taper training was not associated with alterations in LV diastolic cavity dimension (AT pre 53.3 +/- 2.8 mm versus post 52.6 +/- 4.3 mm; CT pre 52.9 +/- 3.7 mm versus post 51.2 +/- 4.0 mm), ventricular septal wall thickness (AT pre 9.6 +/- 1.0 mm versus post 9.4 +/- 1.1 mm; CT pre 8.4 +/- 1.2 mm versus post 8.6 +/- 1.1 mm), estimated LV mass (AT pre 186.4 +/- 45.8 g versus post 190.0 +/- 48.2 g; CT pre 159.1 +/- 35.8 g versus post 160.1 +/- 40.8 g) or fractional shortening (AT pre 36.8 +/- 3.5% versus post 34.8 +/- 2.7%; CT pre 32.6 +/- 5.0% versus post 32.8 +/- 4.7%). However, a main time effect, independent of training intervention, was observed for posterior wall thickness (pre 8.7 +/- 1.4 mm versus post 9.3 +/- 1.1 mm, P < 0.05). Therefore, with the exception of posterior wall thickness, short term AT followed by two weeks of taper training appears not to be associated with alterations in LV morphology or systolic function.

Adaptation, Physiological↗
PubMed1998

Comparison of the antimuscarinic and antispasmodic actions of racemic oxybutynin and desethyloxybutynin and their enantiomers with those of racemic terodiline.

Racemic oxybutynin (CAS 1508-65-2) is used clinically to treat urinary incontinence and reportedly undergoes N-deethylation to metabolites R- and/or S-desethyloxybutynin. To assess the role of these metabolites in the therapeutic effects of oxybutynin, the antimuscarinic and antispasmodic effects of RS-, R- and S-oxybutynin, RS-, R- and S-desethyloxybutynin and, for comparative purposes, RS-terodiline (CAS 7082-21-5) on isolated strips of guinea pig bladder, were examined. All of these compounds exhibited antimuscarinic activity: they competitively antagonized carbachol-induced contractions, with mean pA2 values (+/- S.E.) of 8.91 +/- 0.20, 8.80 +/- 0.27, 7.09 +/- 0.13, 8.55 +/- 0.32, 9.04 +/- 0.32, 7.31 +/- 0.35 and 6.77 +/- 0.22, respectively. Consistent with an antispasmodic action, all of the compounds produced similar inhibition of potassium-induced contraction; the mean IC50 values for reducing responses to 137.7 mmol/l potassium were between 2.22 and 5.68 mumol/l. Thus, RS- and R-oxybutynin and RS- and R-desethyloxybutynin exhibited high antimuscarinic activity relative to their antispasmodic activity, while S-oxybutynin, S-desethyloxybutynin and RS-terodiline exhibited relatively weak antimuscarinic activity. It is concluded that deethylation of oxybutynin to desethyloxybutynin does not appreciably alter its antimuscarinic or antispasmodic activity and that R- and/or S-desethyloxybutynin probably contribute significantly to the pharmacological properties of oxybutynin in humans. In addition, since the relative potency of the antimuscarinic-to-antispasmodic actions of S-oxybutynin was equivalent to that of RS-terodiline, S-oxybutynin deserves consideration for development as a single-enantiomer drug for the treatment of urinary incontinence. It may produce the same beneficial therapeutic effects as both RS-terodiline and RS-oxybutynin but, like RS-terodiline, produce a lower incidence of antimuscarinic side-effects than seen with RS-oxybutynin.

Animals↗
PubMed1997

Adipocyte fatty acid-binding protein: interaction with phospholipid membranes and thermal stability studied by FTIR spectroscopy.

Fatty acid-binding proteins (FABPs) found in many tissues constitute a family of low molecular weight proteins that are suggested to function as intracellular transporters of fatty acids. Studies of the transfer kinetics of fluorescent anthroyloxy-labeled long-chain fatty acids from FABP to model membranes led to the suggestion that the FABPs, typically considered to be cytosolic proteins, could nevertheless interact directly with membranes [Wootan, M. G., et al. (1993) Biochemistry 32, 8622-8627]. In the current study, the interaction of the adipocyte FABP (A-FABP) with vesicles of various phospholipids has been directly measured and confirmed with FTIR spectroscopy. The strength of this interaction was inferred from the lowering of the gel-liquid-crystal phase transition temperature as monitored from temperature-induced variations in the acyl chain CH2 stretching frequencies and from the intensities of the components of the CH2 wagging progressions. A-FABP interacts more strongly with anionic phospholipids (phosphatidylserine and cardiolipin) than with zwitterionic phosphatidylcholine. Unsaturation in the acyl chains leads to a greater reduction in Tm (stronger lipid-protein interaction). In contrast, neutralization of A-FABP surface charges by acetylation considerably weakens the interaction. Comparison of the shifts in lipid melting temperatures with those induced by other proteins suggests that A-FABP behaves like a typical peripheral membrane protein. The degree of membrane interaction correlates directly with the rate of fatty acid transfer, suggesting that contact between A-FABP and membranes is functionally related to its fatty acid transport properties. As expected, the protein exhibits a predominantly beta-sheet structure. It was found to aggregate with increasing temperature. With the exception of minor differences between the pure and lipid-associated A-FABP in the 1640-1660 cm-1 region, both the protein structure and thermal stability appeared essentially unchanged upon interaction with the lipid.

Acetylation↗
PubMed1997

Changing J774A.1 cells to new medium perturbs multiple signaling pathways, including the modulation of protein kinase C by endogenous sphingoid bases.

Sphingosine, sphinganine, and other long-chain (sphingoid) bases are highly bioactive intermediates of sphingolipid metabolism that have diverse effects when added to cells, including the inhibition of protein kinase C (PKC) as evaluated by both enzymatic activity and [3H]phorbol dibutyrate ([3H]PDBu) binding. Nonetheless, changes in endogenous sphingoid bases have not been proven to affect PKC or other signal transduction pathways. We have discovered recently that changing J774A.1 cells to new medium results in up to 10-fold increases in sphingoid bases (Smith, E. R., and Merrill, A. H., Jr. (1995) J. Biol. Chem. 270, 18749-18758); therefore, this system was used to elevate sphingosine and sphinganine and determine if PKC was affected. Incubation of J774A.1 cells in new medium for 30 min increased the levels of these endogenous sphingoid bases to approximately 0.5 nmol/mg of protein and decreased [3H]PDBu binding by 40-60%. Addition of NH4Cl, which suppresses the change in sphingosine, restored [3H]PDBu binding. Elevation of endogenous sphinganine by a second method (addition of fumonisin B1, an inhibitor of ceramide synthase) also reduced [3H]PDBu binding; therefore, elevations in sphingosine and sphinganine can both affect PKC. The elevation in sphingoid bases was also associated with an increase in the amount of PKC-delta (the major PKC isozyme in J774A. 1 cells) in the cytosol, as determined by activity assays and immunoblot analyses. Changing the culture medium affected other PKC isozymes, increased cellular levels of diacylglycerol, dihydroceramide, and ceramide, and altered the expression of two genes (the expression of JE was increased, and the induction of MnSOD by TNF-alpha was potentiated). Thus, changing the culture medium has numerous effects on J774A.1 cells, including the modulation of PKC by endogenous sphingoid bases.

Ammonium Chloride↗
PubMed1997

Postchemotherapy retroperitoneal lymph node dissection is effective therapy in selected patients with elevated tumor markers after primary chemotherapy alone.

OBJECTIVES: Elevated tumor markers after primary chemotherapy for metastatic testis cancer are usually an indication of persistent cancer. Subsequent treatment has usually been salvage chemotherapy. This article examines the possibility that selected patients can achieve long-term disease-free survival with surgery alone. METHODS: Using a computerized data base of 627 postinduction chemotherapy retroperitoneal lymph node dissections (PC-RPLND), 23 patients with elevated tumor markers who have undergone PC-RPLND after induction chemotherapy alone were identified. Of the 23 patients, 15 were considered candidates for salvage chemotherapy, but instead underwent salvage surgery. Case histories were reviewed to establish selection criteria for PC-RPLND. RESULTS: Eight patients originally presented as clinical Stage C, 6 as clinical Stage B-3, and 1 as clinical Stage B-2. All patients initially received cisplatin combination chemotherapy. Twelve patients had an elevated alpha-fetoprotein level and 3 patients had an elevated beta human chorionic gonadotropin level prior to PC-RPLND. Seven patients had rising markers at the time of PC-RPLND. Seven patients had teratoma only in their resected specimen and all have no evidence of disease (NED) at a median of 35 months. Two patients had necrosis only in their RPLND specimen and both are NED at 10 and 42 months. Six patients had cancer in their resected specimen and 2 are NED, 1 is alive with disease, and 3 are dead of disease. Five of the 6 patients with cancer in their resected specimen were the only patients who received postoperative chemotherapy. CONCLUSIONS: Some patients with modest elevations of tumor markers after induction chemotherapy may only have teratoma or necrosis in the postchemotherapy resected specimen. These patients (n = 9) remain continuously NED. Patients who undergo salvage surgery and have cancer in the resected specimen do less well, but selected patients can be cured with this modality and thus avoid the morbidity of salvage chemotherapy.

Adolescent↗