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Eric Anderson

Publications and source records attributed to Eric Anderson.

17 recordsLinked to original sources
PubMed2006

Combating the stress of residency: one school's approach.

Residency is a time of stress and turmoil for many residents. The stresses are varied and great, often involving both personal and professional issues. One institutional mechanism that has been shown to help residents cope with stress is the use of residents' wellness, or assistance, programs. The University of South Florida (USF) College of Medicine developed the USF Residency Assistance Program (RAP) in 1997, modeled after business employee assistance programs but tailored to enhance the well-being of residents. The program was developed in an organized, thoughtful manner starting with a Request for Proposals to all local employee assistance programs and the selection of one of these to run the program. The RAP is broad-based, readily available, easily accessible, totally voluntary and confidential, and not reportable to the state board of medicine. It is well integrated into all residency programs and has had excellent acceptance from the administration; information about access to the RAP is available to all residents through multiple venues. The cost is minimal, at only seven cents a day per resident. The authors present data from the eight years the RAP has been operating, including information on program use, referral rates, acceptance, and types of problems encountered. One suicide occurred during this time period, and the RAP provided a significant role in grief counseling. Assistance programs are critical to the well-being of residents. The USF program presents a model that can be used by other programs around the country.

Academic Medical Centers↗
PubMed2005

Electrostatic interactions govern both nucleation and elongation during phage P22 procapsid assembly.

Icosahedral capsid assembly is an example of a reaction controlled solely by the interactions of the proteins involved. Bacteriophage P22 procapsids can be assembled in vitro by mixing coat and scaffolding proteins in a nucleation-limited reaction, where scaffolding protein directs the proper assembly of coat protein. Here, we investigated the effect of the buffer composition on the interactions necessary for capsid assembly. Different concentrations of various salts, chosen to follow the electroselectivity series for anions, were added to the assembly reaction. The concentration and type of salt was found to be crucial for proper nucleation of procapsids. Nucleation in low salt concentrations readily occurred but led to bowl-like partial procapsids, as visualized by negative stain electron microscopy. The edge of the partial capsids remained assembly-competent since coat protein addition triggered procapsid completion. The addition of salt to the partial capsids also caused procapsid completion. In addition, each salt affected both assembly rates and the extent of procapsid formation. We hypothesize that low salt conditions increase the coat protein:scaffolding protein affinity, causing excessive nuclei to form, which decreases coat protein levels leading to incomplete assembly.

Bacteriophage P22↗
PubMed2005

Transcytosis of NgCAM in epithelial cells reflects differential signal recognition on the endocytic and secretory pathways.

NgCAM is a cell adhesion molecule that is largely axonal in neurons and apical in epithelia. In Madin-Darby canine kidney cells, NgCAM is targeted to the apical surface by transcytosis, being first inserted into the basolateral domain from which it is internalized and transported to the apical domain. Initial basolateral transport is mediated by a sequence motif (Y(33)RSL) decoded by the AP-1B clathrin adaptor complex. This motif is a substrate in vitro for tyrosine phosphorylation by p60src, a modification that disrupts NgCAM's ability to interact with clathrin adaptors. Based on the behavior of various NgCAM mutants, it appears that after arrival at the basolateral surface, the AP-1B interaction site is silenced by phosphorylation of Tyr(33). This slows endocytosis and inhibits basolateral recycling from endosomes, resulting in NgCAM transcytosis due to a cryptic apical targeting signal in its extracellular domain. Thus, transcytosis of NgCAM and perhaps other membrane proteins may reflect the spatial regulation of recognition by adaptors such as AP-1B.

Adaptor Protein Complex 1↗
PubMed2005

An investigation of moral judgement in frontotemporal dementia.

OBJECTIVE: To investigate the basis of disturbed moral judgment in patients with frontotemporal dementia (FTD). BACKGROUND: FTD is characterized by difficulty in modulating social behavior. Patients lack social propriety and may perform sociopathic acts. In addition, FTD patients often lack empathy for others. These findings suggest alterations in the nature of morality in patients with FTD. METHOD: We administered an inventory of moral knowledge and two moral dilemmas to 26 patients with the frontal variant of FTD, 26 patients with Alzheimer disease (AD), and 26 normal control subjects. The FTD patients met Consensus Criteria for FTD and had corroborative frontal abnormalities on functional neuroimaging. The FTD and AD patients were comparably impaired on dementia measures. RESULTS: All these groups showed the retention of knowledge for moral behavior and the ability to make "impersonal" moral judgments. In contrast, the FTD patients were impaired in their ability to make immediate, emotionally based moral judgments compared with the patients with AD and the normal control subjects. CONCLUSIONS: These findings are consistent with an attenuation of the automatic emotional identification with others that is part of the innate moral sense. Such a disturbance may result from neurodegenerative disease affecting the ventromedial frontal cortex.

Aged↗
PubMed2004

A concerted mechanism for the suppression of a folding defect through interactions with chaperones.

Specific amino acid substitutions confer a temperature-sensitive-folding (tsf) phenotype to bacteriophage P22 coat protein. Additional amino acid substitutions, called suppressor substitutions (su), relieve the tsf phenotype. These su substitutions are proposed to increase the efficiency of procapsid assembly, favoring correct folding over improper aggregation. Our recent studies indicate that the molecular chaperones GroEL/ES are more effectively recruited in vivo for the folding of tsf:su coat proteins than their tsf parents. Here, the tsf:su coat proteins are studied with in vitro equilibrium and kinetic techniques to establish a molecular basis for suppression. The tsf:su coat proteins were monomeric, as determined by velocity sedimentation analytical ultracentrifugation. The stability of the tsf:su coat proteins was ascertained by equilibrium urea titrations, which were best described by a three-state folding model, N <--> I <--> U. The tsf:su coat proteins either had stabilized native or intermediate states as compared with their tsf coat protein parents. The kinetics of the I <--> U transition showed a decrease in the rate of unfolding and a small increase in the rate of refolding, thereby increasing the population of the intermediate state. The increased intermediate population may be the reason the tsf:su coat proteins are aggregation-prone and likely enhances GroEL-ES interactions. The N --> I unfolding rate was slower for the tsf:su proteins than their tsf coat parents, resulting in an increase in the native state population, which may allow more competent interactions with scaffolding protein, an assembly chaperone. Thus, the suppressor substitution likely improves folding in vivo through increased efficiency of coat protein-chaperone interactions.

Bacteriophage P22↗
PubMed2004

Activation of NR1a/NR2B receptors by soluble factors from APP-stimulated monocyte-derived macrophages: implications for the pathogenesis of Alzheimer's disease.

Amyloid-beta peptide (Abeta), the major component of amyloid plaques, can activate brain mononuclear phagocytes (MP; macrophages and microglia), leading to their secretion of neurotoxins. Recent studies strongly suggest that MP-mediated neurotoxicity plays an important role in the pathogenesis of Alzheimer's disease (AD). To further explore this notion, human monocyte-derived macrophages (MDM) were stimulated with naturally secreted alpha-processing soluble amyloid precursor protein/p3 (alphaAPPs/p3) or beta-processing APP/Abeta (betaAPPs/Abeta). MDM conditioned media (MCM) was recovered and tested for its ability to activate recombinant N-methyl-d-aspartate (NMDA) receptor subtype NR1a/NR2B expressed in Xenopus oocytes. Pressure ejection of alphaAPPs/p3- and betaAPPs/Abeta-stimulated MCM produced inward currents of 59.5 +/- 8.9 nA (mean +/- S.E.M., n = 31) and 111.1 +/- 21.0 nA (n = 42) in NR1a/NR2B-expressing oocytes, respectively. The MCM-induced currents were concentration dependent and blocked by 50 microM of the NMDA receptor antagonist 2-amino-5-phosphnovalerate, but not by a non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM). The alphaAPPs/p3- and betaAPPs/Abeta-stimulated MCM placed in non-injected oocytes failed to generate inward current. These results demonstrate that APPs/Abeta-stimulated MCM directly activate NMDA receptor subtypes relevant in the pathogenesis of AD.

Alzheimer Disease↗
PubMed2004

Assessing progress in analysis interminable.

A case study is provided of a schizoid patient in her mid-sixties who in a lengthy analysis had made significant clinical improvement. The treating analyst's impression of clinical improvement was independently verified through systematic analysis of transcripts of audiotapes of thirty-six sessions over a four-year period of treatment. The patient showed significant improvement on measures of character pathology, object relations, mentalization, and superego anxiety. The results suggest that some patients with entrenched character pathology who seem to be in analysis interminable may still make clinically significant improvement. It is suggested that the scientific status of psychoanalysis would be greatly enhanced if the anecdotal evidence generated in private practice were supported by independent verification. The current study illustrates one methodology, "case study plus," for providing independent verification while retaining the richness of the traditional case study.

Female↗
PubMed2003

Rapid unfolding of a domain populates an aggregation-prone intermediate that can be recognized by GroEL.

Some amino acid substitutions in phage P22 coat protein cause a temperature-sensitive folding (tsf) phenotype. In vivo, these tsf amino acid substitutions cause coat protein to aggregate and form intracellular inclusion bodies when folded at high temperatures, but at low temperatures the proteins fold properly. Here the effects of tsf amino acid substitutions on folding and unfolding kinetics and the stability of coat protein in vitro have been investigated to determine how the substitutions change the ability of coat protein to fold properly. The equilibrium unfolding transitions of the tsf variants were best fit to a three-state model, N if I if U, where all species concerned were monomeric, a result confirmed by velocity sedimentation analytical ultracentrifugation. The primary effect of the tsf amino acid substitutions on the equilibrium unfolding pathway was to decrease the stability (DeltaG) and the solvent accessibility (m-value) of the N if I transition. The kinetics of folding and unfolding of the tsf coat proteins were investigated using tryptophan fluorescence and circular dichroism (CD) at 222 nm. The tsf amino acid substitutions increased the rate of unfolding by 8-14-fold, with little effect on the rate of folding, when monitored by tryptophan fluorescence. In contrast, when folding or unfolding reactions were monitored by CD, the reactions were too fast to be observed. The tsf coat proteins are natural substrates for the molecular chaperones, GroEL/S. When native tsf coat protein monomers were incubated with GroEL, they bound efficiently, indicating that a folding intermediate was significantly populated even without denaturant. Thus, the tsf coat proteins aggregate in vivo because of an increased propensity to populate this unfolding intermediate.

Amino Acid Substitution↗
PubMed2003

Folding of phage P22 coat protein monomers: kinetic and thermodynamic properties.

To assemble into a virus with icosahedral symmetry, capsid proteins must be able to attain multiple conformations. Whether this conformational diversity is achieved during folding of the subunit, or subsequently during assembly, is not clear. Phage P22 coat protein offers an ideal model to investigate the folding of a monomeric capsid subunit since its folding is independent of assembly. Our early studies indicated that P22 coat protein monomers could be folded into an assembly-competent state in vitro, with evidence of a kinetic intermediate. Using urea denaturation, coat protein monomers are shown to be marginally stable. The reversible folding of coat protein follows a three-state model, N if I if U, with an intermediate exhibiting most of the tryptophan fluorescence of the folded state, but little secondary structure. Folding and unfolding kinetics monitored by circular dichroism, tryptophan fluorescence, and bisANS fluorescence indicate that several kinetic intermediates are populated sequentially through parallel channels en route to the native state. Additionally, two native states were identified, suggesting that the several conformers required to assemble an icosahedral capsid may be found in solution before assembly ensues.

Bacteriophage P22↗
PubMed2003

Mind your pricing cues.

For most of the items they buy, consumers don't have an accurate sense of what the price should be. Ask them to guess how much a four-pack of 35-mm film costs, and you'll get a variety of wrong answers: Most people will underestimate; many will only shrug. Research shows that consumers' knowledge of the market is so far from perfect that it hardly deserves to be called knowledge at all. Yet people happily buy film and other products every day. Is this because they don't care what kind of deal they're getting? No. Remarkably, it's because they rely on retailers to tell them whether they're getting a good price. In subtle and not-so-subtle ways, retailers send signals to customers, telling them whether a given price is relatively high or low. In this article, the authors review several common pricing cues retailers use--"sale" signs, prices that end in 9, signpost items, and price-matching guarantees. They also offer some surprising facts about how--and how well--those cues work. For instance, the authors' tests with several mail-order catalogs reveal that including the word "sale" beside a price can increase demand by more than 50%. The practice of using a 9 at the end of a price to denote a bargain is so common, you'd think customers would be numb to it. Yet in a study the authors did involving a women's clothing catalog, they increased demand by a third just by changing the price of a dress from $34 to $39. Pricing cues are powerful tools for guiding customers' purchasing decisions, but they must be applied judiciously. Used inappropriately, the cues may breach customers' trust, reduce brand equity, and give rise to lawsuits.

Attitude↗
PubMed2002

HIV-1-associated dementia: a metabolic encephalopathy perpetrated by virus-infected and immune-competent mononuclear phagocytes.

Infection of the nervous system by HIV-1 commonly causes a broad range of cognitive, behavioral, and motor abnormalities called, in its most severe form, HIV-1-associated dementia (HAD). HAD is a metabolic encephalopathy caused by productive viral infection of brain mononuclear phagocytes (MPs) (perivascular and parenchymal brain macrophages and microglia) and sustained by paracrine-amplified, inflammatory, neurotoxic responses. MP neurotoxins are, in large measure, homeostatic secretory products that can have a negative effect on neuronal cell function when produced in abundance. Proinflammatory cytokines, chemokines, platelet-activating factor, arachidonic acid and its metabolites, nitric oxide, quinolinic acid, progeny virions, and viral structural and regulatory proteins are all included as part of these cellular and viral toxic elements. In addition, neuronal damage can occur directly by engaging specific receptors or through inducing widespread inflammatory activities in brain tissue that ultimately induce neuronal demise. The mechanisms for immune-and viral-mediated neural injury in HAD are made more striking by the effects of abused drugs on cognitive function. Ultimately, linkages between neuronal function and disordered MP immunity will provide insights into how HIV-1 infection of the brain leads to compromised mental function as well as providing clues into the pathogenesis of other neurodegenerative disorders.

AIDS Dementia Complex↗
PubMed2002

Impaired spatial cognition and synaptic potentiation in a murine model of human immunodeficiency virus type 1 encephalitis.

Injection of human immunodeficiency virus type 1 (HIV-1)-infected human monocyte-derived macrophages (MDMs) into the basal ganglia of severe combined immunodeficient mice recapitulates histopathologic features of HIV-1 encephalitis (HIVE). Here, we show that the neural damage in HIVE mice extends beyond the basal ganglia and is associated with cognitive impairment. Morris water maze tests showed impaired spatial learning 8 d after MDM injection. Moreover, impaired synaptic potentiation in the hippocampal CA1 subregion was demonstrated at 8 and 15 d. By day 15, post-tetanic, short-term, and long-term potentiation were reduced by 14.1, 29.5, and 45.3% in HIVE mice compared with sham-injected or control animals. Neurofilament (NF) and synaptophysin (SP) antigens were decreased significantly in the CA2 hippocampal subregion of HIVE mice with limited neuronal apoptosis. By day 15, the CA2 region of HIVE mice expressed 3.8- and 2.6-fold less NF and SP than shams. These findings support the notion that HIV-1-infected and immune-competent brain macrophages can cause neuronal damage at distant anatomic sites. Importantly, the findings demonstrate the value of the model in exploring the physiological basis and therapeutic potential for HIV-1-associated dementia.

AIDS Dementia Complex↗
PubMed2002

Childhood trauma associated with smaller hippocampal volume in women with major depression.

OBJECTIVE: Smaller hippocampal volume has been reported only in some but not all studies of unipolar major depressive disorder. Severe stress early in life has also been associated with smaller hippocampal volume and with persistent changes in the hypothalamic-pituitary-adrenal axis. However, prior hippocampal morphometric studies in depressed patients have neither reported nor controlled for a history of early childhood trauma. In this study, the volumes of the hippocampus and of control brain regions were measured in depressed women with and without childhood abuse and in healthy nonabused comparison subjects. METHOD: Study participants were 32 women with current unipolar major depressive disorder-21 with a history of prepubertal physical and/or sexual abuse and 11 without a history of prepubertal abuse-and 14 healthy nonabused female volunteers. The volumes of the whole hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans by a single rater who was blind to the subjects' diagnoses. RESULTS: The depressed subjects with childhood abuse had an 18% smaller mean left hippocampal volume than the nonabused depressed subjects and a 15% smaller mean left hippocampal volume than the healthy subjects. Right hippocampal volume was similar across the three groups. The right and left hippocampal volumes in the depressed women without abuse were similar to those in the healthy subjects. CONCLUSIONS: A smaller hippocampal volume in adult women with major depressive disorder was observed exclusively in those who had a history of severe and prolonged physical and/or sexual abuse in childhood. An unreported history of childhood abuse in depressed subjects could in part explain the inconsistencies in hippocampal volume findings in prior studies in major depressive disorder.

Adult↗
PubMedDate not supplied

Human endothelial cell interaction with biomimetic surfactant polymers containing Peptide ligands from the heparin binding domain of fibronectin.

Biomimetic materials that mimic the extracellular matrix (ECM) provide a means to control cellular functions such as adhesion and growth, which are vital to successful engineering of tissue-incorporated biomaterials. Novel "ECM-like" biomimetic surfactant polymers consisting of a poly(vinyl amine) backbone with pendant cell-adhesive peptides derived from one of the heparin-binding domains of fibronectin were developed to improve endothelial cell adhesion and growth on vascular biomaterials. Heparin-binding peptide (HBP) sequences, alone and in combination with RGD peptides, were examined for their ability to promote human pulmonary artery endothelial cell (HPAEC) adhesion and growth (HBP1, WQPPRARI; HBP2, SPPRRARVT; HBP1:RGD; and HBP2:RGD) and compared with cell adhesion and growth on fibronectin and on negative control polymer surfaces in which alanines were substituted for the positively charged arginine residues in the two peptides. The results showed that HPAECs adhered and spread equally well on all HBP-containing polymers and the positive fibronectin control, showing similar stress fiber and focal adhesion formation. However, the HBP alone was unable to support long-term HPAEC growth and survival, showing a loss of focal adhesions and cytoskeletal disorganization by 24 h after seeding. With the addition of RGD, the surfaces behaved similarly or better than fibronectin. The negative control polymers showed little to no initial cell attachment, and the addition of soluble heparin to the medium reduced initial cell adhesion on both the HBP2 and HBP2:RGD surfaces. These results indicate that the HBP surfaces promote initial HPAEC adhesion and spreading, but not long-term survival.

Biocompatible Materials↗