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Biomedical subjects

R E Smith

Publications and source records attributed to R E Smith.

At least 37 records · Page 2Linked to original sources
PubMed2001

Expression of excitatory amino acid transporter transcripts in the thalamus of subjects with schizophrenia.

OBJECTIVE: Recent investigations of schizophrenia have targeted glutamatergic neurotransmission, since phencyclidine, an N-methyl-D-aspartate (NMDA) receptor antagonist, can induce schizophreniform psychosis. The authors previously reported alterations in thalamic NMDA receptor subunit expression in schizophrenia, consistent with the hypothesis that thalamic glutamatergic hypofunction may contribute to the pathophysiology of this illness. In this study they generalized this hypothesis to include other molecules of the glutamate synapse, specifically excitatory amino acid transporters (EAATs), whose normal expression and regulation in the thalamus may also be disrupted in subjects with schizophrenia. METHOD: In situ hybridization with riboprobes specific for the human excitatory amino acid transporter transcripts EAAT1, EAAT2, and EAAT3 was performed in discrete thalamic nuclei in persons with schizophrenia and comparison subjects. RESULTS: Higher expressions of transcripts encoding EAAT1 and EAAT2, but not EAAT3, were detected in the thalamus of subjects with schizophrenia. CONCLUSIONS: These findings support the hypothesis of glutamatergic dysfunction in schizophrenia and suggest that molecules other than glutamate receptors are abnormally expressed in glutamatergic synapses in this illness.

ATP-Binding Cassette Transporters↗
PubMed2001

Aquatic reclamation in the Athabasca, Canada, oil sands: naphthenate and salt effects on phytoplankton communities.

Microcosm experiments with natural indigenous phytoplankton communities were conducted to assess the effects of waters from oil sands extraction processes, emphasizing the naphthenate and salt constituents. Process waters of varying ages (zero to eight years) remediation histories, and chemical composition were obtained from outdoor mesocosms and inoculated with phytoplankton assemblages from a reference lake in the study area. Community composition measures, including percentage model affinity (PMA) and canonical correspondence analysis (CCA), revealed significant community effects of water from systems less than five years old, with naphthenate concentrations greater than 20 mg/L, compared to water from the reference lake. Canonical correspondence analysis, PMA, and regression analyses further showed that naphthenate concentration was significantly correlated with community structure. Using CCA, groups of taxa characteristic of waters with > 20 mg/L naphthenates (including Botryococcus braunii, Gloeococcus schroeteri, Cosmarium depressum, Chrysococcus rufescens, Chromulina spp., Ochromonas spp., and Keratococcus spp.) were identified. Salinity, as reflected in conductivity, was positively correlated with naphthenate concentration and itself appeared to influence the community structure. The results confirmed an important role for naphthenates in ecological effects of process waters from oil sands mining, but the influence of covarying factors such as salinity requires further investigation.

Carboxylic Acids↗
PubMed2001

Role of p27(Kip1) in cAMP- and TGF-beta2-mediated antiproliferation in rabbit corneal endothelial cells.

PURPOSE: To determine whether p27(Kip1) plays a role in antiproliferation mediated by antimitogens (cAMP and TGF-beta2) in rabbit corneal endothelial cells (CECs). METHODS: Cell proliferation was assayed using a colorimetric method to determine the number of viable cells. Subcellular localization of cell cycle-regulatory proteins was determined by immunofluorescent staining, and expression of the proteins was analyzed by immunoblot analysis. RESULTS: When cells were treated with cAMP or TGF-beta2, serum-mediated cell proliferation was inhibited in a dose-dependent manner. Simultaneous treatment of the two antimitogens did not show a synergistic effect on inhibition of cell growth. Expression of cell cycle-regulatory proteins, such as cyclin-D1, cyclin-E, cdk2, cdk4, p21(Cip1), and p27(Kip1) was determined using immunofluorescent staining. A strong nuclear staining was observed for p27(Kip1). The other proteins were not stained or were only very faintly stained. Treatment of cells with either cAMP or TGF-beta2 did not change the staining potential of any proteins other than p27(Kip1), but all cells were positive for nuclear p27(Kip1) when treated with either TGF-beta2 or cAMP. In contrast, mitogen (FGF-2)-containing medium decreased the number of p27(Kip1)-positive cells. When the expression level of p27(Kip1) was determined using immunoblot analysis in the cells treated either with FGF-2 alone or with a concomitant treatment with FGF-2 and cAMP for 24 hours, FGF-2 markedly decreased the p27(Kip1) level, and cAMP prevented the decrease in p27(Kip1) level induced by FGF-2. No such phenomenon occurred during a short-term exposure of cells to either FGF-2 or cAMP or to a combination of the two. When cells were stained for phosphorylated p27(Kip1), FGF-2 markedly enhanced the staining of phosphorylated p27(Kip1) in nuclei, whereas both cAMP and TGF-beta2 prevented the phosphorylation of p27(Kip1). CONCLUSIONS: These findings suggest that both antimitogens upregulate the expression of p27(Kip1) as they prevent the decrease of the p27(Kip1) level mediated by mitogen. Furthermore, cAMP and TGF-beta2 may inhibit the G(1)-to-S transition by blocking phosphorylation of p27(Kip1), which is a prerequisite for nuclear export of the inhibitor molecule for degradation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Induction paclitaxel in previously untreated, resectable, advanced squamous cell carcinomas of head and neck.

BACKGROUND: Previous Phase II trials evaluating paclitaxel as a single agent have produced objective response rates of 38-40%. However, in these studies patients had recurrent disease and had received previous treatment with chemotherapy, radiation, surgery, or some combination of the same. To the authors' knowledge, the study reported here is the first to examine the role of paclitaxel in affecting objective antitumor response, as a single agent, in a previously untreated patient population. METHODS: Patients with untreated, resectable, advanced squamous cell carcinoma of the head and neck were eligible for this Phase II trial. The treatment plan included paclitaxel 250 mg/m(2) administered by 24-hour intravenous infusion every 21 days for a total of 3 courses and primary prophylaxis with colony stimulating factor during each course of chemotherapy. Surgical resection was performed after recovery from the final course of chemotherapy. After adequate wound healing, patients received external beam radiotherapy (median dose to primary site, 55.8 Gray [Gy]; median dose to neck sites, 50.4 Gy). RESULTS: Forty-five patients were registered. Thirty-eight patients completed the planned chemotherapy, 41 patients underwent surgical resection, and 37 patients completed the intended radiotherapy. The objective response rate was 50% (10% complete response; 40% partial response). Severe or life-threatening (Grade 3 or higher) granulocytopenia or thrombocytopenia occurred in 78% and 27% of patients, respectively. Two patients died of sepsis. Seventy-one percent, 67%, and 91% of patients were free of local, lymph node, and distant recurrence, respectively, with a median follow-up of 37 months. The 4-year overall survival and disease-related survival rates were 44.4% and 52.9%, respectively. CONCLUSION: The authors conclude that paclitaxel is an active agent in patients with advanced head and neck carcinoma. However, the overall disease control, achieved by using paclitaxel as induction therapy, did not appear to be better than that achieved with standard treatment methods. Combined modality regimens with concurrent chemotherapy and radiotherapy have demonstrated more promise.

Adult↗
PubMed2000

Extracellular matrix components in retrocorneal fibrous membrane in comparison to corneal endothelium and Descemet's membrane.

PURPOSE: To investigate the extracellular matrix macromolecules found in Descemet's membrane and in retrocorneal fibrous membrane (RCFM), and to examine whether the corneal endothelium has the capacity to produce both basement and non-basement membrane phenotypes. METHODS: Rabbit corneas with and without RCFM were analyzed by immunofluorescence using antibodies to 8 different collagens (basement membrane collagens: types IV and VIII; fibrillar collagens: types I and III; interfibrillar collagens: type VI and two spliced variant forms of type XII and one anchoring fiber: type VII), proteoglycans (perlecan and decorin), (beta)ig-h3 and laminin-1. RESULTS: Normal corneal endothelium stains positively for all of the tested collagen types except type VII collagen. On the other hand, Descemet's membrane reacts positively only to the type IV collagen antibody. When non-collagenous components in normal cornea were examined, corneal endothelium stained positively for perlecan, decorin, (beta)ig-h3 and laminin, whereas Descemet's membrane staining for these proteins was negative. When collagenous components of RCFM were examined, RCFM stained positively for all of the tested collagen types except type IV collagen. When non-collagenous components of RCFM were examined, RCFM demonstrated a strong positive staining with decorin, (beta)ig-h3 and laminin, while perlecan staining was weak. CONCLUSIONS: These observations suggest that corneal endothelium is able to produce both basement membrane phenotypes and non-basement membrane, fibrillar phenotypes. This in vivo study confirms our in vitro model of endothelial mesenchymal transformation, in which corneal endothelial cells are transformed to fibroblasts that are responsible for fibrosis.

Animals↗
PubMed2000

Synthesis and evaluation of hydroxylated polyamine analogues as antiproliferatives.

The synthesis of four hydroxylated polyamine analogues, (2R, 10R)-N(1),N(11)-diethyl-2,10-dihydroxynorspermine, (2S,10S)-N(1), N(11)-diethyl-2,10-dihydroxynorspermine, (3S,12S)-N(1), N(14)-diethyl-3,12-dihydroxyhomospermine, and (3R,12R)-N(1), N(14)-diethyl-3,12-dihydroxyhomospermine, is described along with their impact on the growth and polyamine metabolism of L1210 murine leukemia cells. Four different synthetic approaches are set forth, two each for the hydroxylated norspermines and for the hydroxylated homospermines. The key step in the assembly of the norspermines was the coupling of either N-[(2R)-2,3-epoxypropyl]-N-ethyl p-toluenesulfonamide or N-[(2S)-2,3-epoxypropyl]-N-ethyl trifluoromethanesulfonamide to N,N'-dibenzyl-1,3-diaminopropane. The key step with homospermines employed alkylation of putrescine with (3S)-N-(benzyloxycarbonyl)-N-ethyl-3,4-epoxybutylamine or of N, N'-bis(mesitylenesulfonyl)-1,4-butanediamine with (2R)-2-benzyloxy-4-[N-(mesitylenesulfonyl)ethylamino]-O-tosyl-1-++ +butan ol. All of the hydroxylated analogues were active against L1210 cells with 96-h IC(50) values of </=2 microM, and they also effectively reduced putrescine and spermidine, although the effect on spermine pools ranged from moderate to insignificant. Interestingly, the impact of the hydroxylated analogues on ornithine decarboxylase (ODC) was significantly less than that of unhydroxylated parent drug (e.g., N(1),N(11)-diethylnorspermine [DENSPM]) at 1 microM; however, S-adenosylmethionine decarboxylase (AdoMetDC) depletion was nearly identical to what was observed in cells treated with parent drug. The most notable difference between the parent and hydroxylated analogues was seen with spermidine/spermine N(1)-acetyltransferase (SSAT) upregulation in the DENSPM series. The hydroxylated analogues, especially (R, R)-(HO)(2)DENSPM, were much less effective at upregulation than the parent DENSPM. Finally, a comparison of the toxicity of (R, R)-(HO)(2)DENSPM with that of DENSPM at subchronic doses revealed that the neurological effects seen with DENSPM were now absent.

Animals↗
PubMed2000

Traumatic Acremonium atrogriseum keratitis following laser-assisted in situ keratomileusis.

A 52-year-old man underwent bilateral laser-assisted in situ keratomileusis. Eight months later, he sustained a penetrating corneal injury to the left eye. A dense white infiltrate, unresponsive to antimicrobial therapy, developed in the corneal stroma. Corneal biopsy and eventual penetrating keratoplasty were performed, and both specimens demonstrated fungal elements with branching, septate hyphae. Culture identified the organism as Acremonium atrogriseum. Histopathologic features of this organism and its differentiation from other, more common fungal organisms are discussed herein.

Acremonium↗
PubMed2000

Idiopathic polypoidal choroidal vasculopathy and sickle cell retinopathy.

PURPOSE: To report a patient who had concomitant idiopathic polypoidal choroidal vasculopathy and sickle cell retinopathy. METHOD: Case report. A 46-year-old black woman presented with sudden onset of "blurring" in the left eye. Her ocular history was unremarkable, and her medical history was relevant for sickle cell disease with yearly episodes of sickle cell crises. RESULTS: Both eyes had evidence of idiopathic polypoidal choroidal vasculopathy and peripheral retinal neovascularization secondary to sickle cell disease. The left eye had hemorrhagic retinal pigment epithelial detachments secondary to idiopathic polypoidal choroidal vasculopathy. CONCLUSION: We present this case as an example of concomitant sickle cell retinopathy and idiopathic polypoidal choroidal vasculopathy. We are unaware of previous reports with these findings.

Anemia, Sickle Cell↗
PubMed2000

Dimerization and domain swapping in G-protein-coupled receptors: a computational study.

In recent years there has been an increasing number of reports describing G protein-coupled receptor (GPCR) dimerization and heterodimerization. However, the evidence on the nature of the dimers and their role in GPCR activation is inconclusive. Consequently, we present here a review of our computational studies on G protein-coupled receptor dimerization and domain swapping. The studies described include molecular dynamics simulations on receptor monomers and dimers in the absence of ligand, in the presence of an agonist, and in the presence of an antagonist (or more precisely an inverse agonist). Two distinct sequence-based approaches to studying protein interfaces are also described, namely correlated mutation analysis and evolutionary trace analysis. All three approaches concur in supporting the proposal that the dimerization interface includes transmembrane helices 5 and 6. These studies cannot distinguish between domain swapped dimers and contact dimers as the models used were restricted to the helical part of the receptor. However, it is proposed that for the purpose of signalling, the domain swapped dimer and the corresponding contact dimer are equivalent. The evolutionary trace analysis suggests that every GPCR family and subfamily (for which sufficient sequence data is available) has the potential to dimerize through this common functional site on helices 5 and 6. The evolutionary trace results on the G protein are briefly described and these are consistent with GPCR dimerization. In addition to the functional site on helices 5 and 6, the evolutionary trace analysis identified a second functional site on helices 2 and 3. Possible roles for this site are suggested, including oligomerization.

Animals↗
PubMed2000

Stereolithographic models of biopolymers.

Stereolithography (STL) has been used to make plastic models of the solvent accessible surfaces of biopolymers. Models have been made of proteins and proteins bound to DNA and RNA. The STL process uses a laser to photopolymerize a liquid resin. Using the ACES (accurate, clear, epoxy, solid) building technique, parts are made with minimum postcure shrinkage. Protein Data Bank files are converted to STL files that represent the surface topology of the biopolymer as a series of triangles and an index that describes their orientation. The models are useful in teaching biomolecular structure and the principle of docking. They are especially useful to the visually impaired.

Acetylcholinesterase↗
PubMed2000

Masking effects of social desirability response set on relations between psychosocial factors and sport injuries: a methodological note.

Social desirability has long been viewed as a potential source of error variance in self-report measures. We suggest that social desirability (whether in the form of impression management or self-deception) has the capacity to mask relations between psychosocial variables and sport-related outcome or criterion measures that are not measured by selfreport. To illustrate what can occur, we present data from a longitudinal study in which life stress and psychological coping skills were studied as predictors of behaviorally-defined athletic injuries. When data from the entire sample of 352 athletes were analyzed, virtually no injury variance was accounted for by life stress, psychological coping skills, or their interaction. In contrast, deletion from the sample of athletes with high social desirability response set scores resulted in significant predictive relations involving both life stress and coping skills, as well as a significant moderator effect for coping skills. We propose that social desirability masking effects can significantly increase the likelihood of Type II errors in sports medicine research that involves self-report measures, and that social desirability responding needs to be controlled or minimized.

Adaptation, Psychological↗
PubMed2000

Bisphenol A and its biomaterial monomer derivatives alteration of in vitro cytochrome P450 metabolism in rat, minipig, and human.

Bisphenol A (BPA) is a common structural component in a wide variety of biomaterial monomers. The effects of BPA and the following derivatives: bisphenol A glycidyl methacrylate (BisGMA), bisphenol A glycidyl diacrylate (BAGDA), bisphenol A ethoxylate dimethacrylate (BAEDM), bisphenol A dimethacrylate (BADM), and bisphenol A diglycidyl ether (BADGE) on mixed function oxidases (MFOs) are reported in this study. The rate of formation of metabolites from isoform-specific substrates for the MFOs (or cytochromes) CYP 1A, 2A, 2C, 2E, 3A, and 4A in the absence (control) and presence of BPA and derivatives was used to assess inhibition or stimulation of human, rat (male and female) liver, and minipig liver microsomal MFO activity. For human preparations the strongest inhibition by BPA was observed for CYP 2C. The inhibition was most prominent when a lower dose of BPA was used on the complete post-mitochondrial fraction. BPA inhibited rat microsomal CYP 1A isoform-specific metabolite production to 29 +/- 3% of control levels (100%). Biomaterial monomers exhibited mixed effects. For example, BPA stimulated CYP 4A in pooled human S9 to 129 +/- 1% of control. Also, BADM and BAGDA stimulated CYP 4A to 141% and 142% of control values, respectively.

Animals↗
PubMed2000

Generalization effects of coping-skills training: influence of self-defense training on women's efficacy beliefs, assertiveness, and aggression.

Concern for personal safety is a pervasive stressor for many women. Developing competencies in physical self-defense may empower women to engage more freely in daily activities with less fear. This study assessed the effects of physical self-defense training on multiple aspects of women's perceived self-efficacy and other self-reported personality characteristics. Training powerfully increased task-specific (self-defense) efficacy beliefs as well as physical and global efficacy beliefs. Training increased self-reported assertiveness, and posttraining decreases in hostility and aggression were found on several of the subscales of The Aggression Questionnaire (A. H. Buss & M. Perry, 1992), indicating that training did not have an aggression-disinhibiting effect. In the experimental condition, most of the effects were maintained (and some delayed effects appeared at follow-up.

Adaptation, Psychological↗
PubMed2000

In vivo inhibition of cysteine proteinases delays the onset of growth of human pancreatic cancer explants.

An animal model was used to study the effects of oral treatment with a small molecular selective inhibitor of cysteine proteinases, Z-Phe-Arg-fluoromethylketone (Z-Phe-Arg-FMK) on primary tumour development. Poorly differentiated rapidly growing and moderately differentiated slowly growing human pancreatic tumours were implanted in the neck of nude mice that were orally treated or not with the inhibitor. Growth rates of the tumours were determined during 38 days after implantation. The poorly differentiated tumours were not affected by treatment with the inhibitor. Development of the moderately differentiated tumours was inhibited significantly by Z-Phe-Arg-FMK treatment. Moreover, the amount of stroma was increased and the volume of cancer cells was reduced in the moderately differentiated tumours that had grown in the treated animals. Reduction in size of the tumours was not achieved by reduction in growth rate but in a delay of the onset of growth. It is concluded that cysteine proteinases play a transient role at the start of tumour development only when cancer cells are surrounded by stroma as was the case in the moderately differentiated but not in the poorly differentiated pancreatic tumours. However, this role of cysteine proteinases can easily be taken over by other proteinases.

Animals↗
PubMed2000

Embodiment of evolutionary computation in general agents.

Holland's Adaptation in Natural and Artificial Systems largely dealt with how systems, comprised of many self-interested entities, can and should adapt as a whole. This seminal book led to the last 25 years of work in genetic algorithms (GAs) and related forms of evolutionary computation (EC). In recent years, the expansion of the Internet, other telecommunications technologies, and other large scale networks have led to a world where large numbers of semi-autonomous software entities (i.e., agents) will be interacting in an open, universal system. This development cast the importance of Holland's legacy in a new light. This paper argues that Holland's fundamental arguments, and the years of developments that have followed, have a direct impact on systems of general network agents, regardless of whether they explicitly exploit EC. However, it also argues that the techniques and theories of EC cannot be directly transferred to the world of general agents (rather than EC-specific) without examination of effects that are embodied in general software agents. This paper introduces a framework for EC interchanges between general-purpose software agents. Preliminary results are shown that illustrate the EC effects of asynchronous actions of agents within this framework. Building on this framework, coevolutionary agents that interact in a simulated producer/consumer economy are introduced. Using these preliminary results as illustrations, areas for future investigation of embodied EC software agents are discussed.

Algorithms↗
PubMed2000

The influence of distinctive processing on retrieval-induced forgetting.

Recall of a portion of a previously experienced list benefits subsequent recall of that portion of the list but leads to poorer recall of nonpracticed items from the same set (Anderson, Bjork, & Bjork, 1994). One explanation for this retrieval-induced forgetting is that during practice of part of a set, the non-practiced items compete for recall and are suppressed; this suppression process inhibits later recall of the nonpracticed items. Two experiments were conducted to investigate the relationship between distinctive processing of the original set and retrieval-induced forgetting, on the assumption that distinctive processing reduces response competition. In the first experiment, distinctive processing induced by difference judgments among the studied items did reduce forgetting relative to a standard encoding task and a similarity judgment task. In fact, the difference judgment task completely eliminated retrieval-induced forgetting. In the second experiment, the similarity judgment task was analyzed in relation to a task assumed to foster associative integration (Anderson & McCulloch, 1999). Even though the similarity judgment met the requirements for associative integration, retrieval-induced forgetting persisted following similarity judgment. The results are consistent with the view that distinctive processing benefits memory within an organizational context (Hunt & McDaniel, 1993; Smith & Hunt, in press).

Adult↗