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Biomedical subjects

D G Anderson

Publications and source records attributed to D G Anderson.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal.

Recent evidence indicates a role for oxidative stress and resulting products, e.g. 4-hydroxy-2-nonenal (4HNE) in the pathogenesis of Parkinson's disease (PD). 4HNE is a known inhibitor of mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme very important to the dopamine (DA) metabolic pathway. DA undergoes monoamine oxidase-catalyzed oxidative deamination to 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is metabolized primarily to 3,4-dihydroxyphenylacetic acid (DOPAC) via ALDH2. The biotransformation of DOPAL is critical as previous studies have demonstrated this DA-derived aldehyde to be a reactive electrophile and toxic to dopaminergic cells. Therefore, 4HNE produced via oxidative stress may inhibit ALDH2-mediated oxidation of the endogenous neurotoxin DOPAL. To test this hypothesis, ALDH2 in various model systems was treated with 4HNE and activity toward DOPAL measured. Incubation of human recombinant ALDH2 with 4HNE (1.5-30 microM) yielded inhibition of activity toward DOPAL. Furthermore, ALDH2 in rat brain mitochondrial lysate as well as isolated rat brain mitochondria was also sensitive to the lipid peroxidation product at low micromolar, as evident by a decrease in the rate of DOPAL to DOPAC conversion measured using HPLC. Taken together, these data indicate that 4HNE at low micromolar inhibits mitochondrial biotransformation of DOPAL to DOPAC, and generation of the lipid peroxidation product may represent a mechanism yielding aberrant levels of DOPAL, thus linking oxidative stress to the uncontrolled production of an endogenous neurotoxin relevant to PD.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Noncontact dipole effects on channel permeation. V. Computed potentials for fluorinated gramicidin.

Experimental and theoretical calculations indicate that the dipole moment of the four Trp side chains in gramicidin A (gA) channels modify channel conductance through long-range electrostatic interactions. Electrostatic ion/side-chain interaction energies along the channel were computed with CHARMM using ab initio atom charges for native and 4-, 5-, or 6-fluorinated Trp side chains. The bulk water reaction to the polar side chains was included using the method of images as implemented by, and channel waters in idealized structures were included. Ion/Trp interaction energies were approximately -0.6 kcal/mol throughout the channel for all four of the native Trp pairs. Channel waters produced a modest reduction in the magnitude of interactions, essentially offsetting images representing the bulk water outside the channel. The effects of side-chain fluorination depended on ring position and, to a lesser extent, residue number. Compared with native Trp, 5-fluorination reduces the translocation barrier with minor effects on the exit barrier. In contrast, 6-fluorination primarily reduces exit barrier. 4-Fluorination produces a more complex double-well energy profile. Effects of measured side-chain movements resulting from fluorination or change in lipid bilayer were negligible whereas thermal side chain librations cause large effects, especially in the region of the ion-binding sites.

Binding Sites↗
PubMed2001

Internet patient care applications in ambulatory care.

Over the next decade, the Internet and related technologies will revolutionize the administrative and clinical practices of ambulatory care, enhancing the ability of physicians to provide quality care, enabling "virtual care teams" to help patients deal effectively with acute episodes and chronic conditions, and reducing the cost of care. Like any major paradigm shift, this change will not happen overnight. Nor will it be without cost. The explosion of venture capital and meteoric rise of the Nasdaq in 1999 reflected the promise of the Internet to revolutionize many aspects of American business. The Nasdaq's equally rapid descent in 2000 reflected a growing realization that this change will not be free--that "creative destruction," to use Schumpeter's term, will inevitably require significant investment and produce substantial losses. This article takes a longer term view than the ups and downs in the stock market. We believe the forces unleashed by the Internet are inexorable and that 10 years from now we will look back at the millennium's first decade as a period when the practice of ambulatory medicine was transformed by communication technology.

Ambulatory Care↗
PubMed2001

Families of origin of homeless and never-homeless women.

Naturalistic inquiry was used to compare the characteristics of families of origin of homeless women with never-homeless women. The women's experiences in their families of origin were explored during in-depth interviews using Lofland and Lofland's conceptions of meanings, practices, episodes, roles, and relationships to guide the analysis. The two groups were similar with respect to family abuse history, transience, and loss. The never-homeless women had support from an extended family member who provided unconditional love, protection, a sense of connection, and age-appropriate expectations, as contrasted with homeless women who described themselves as being without, disconnected, and having to be little adults in their families of origin. The experience of family love and connection seemed to protect never-homeless women from the effects of traumatic life events in childhood. These findings provide support for the influence of a woman's family of origin as a precursor to homelessness.

Adaptation, Psychological↗
PubMed2000

Coping strategies and burnout among veteran child protection workers.

OBJECTIVES: First, to learn how veteran (2 years or more) child protective service (CPS) investigations workers cope with job stress; and secondly, to examine the relationship between coping strategies and levels of emotional exhaustion, depersonalization, and sense of reduced personal accomplishment (burnout syndrome). METHOD: Cross-sectional, self-report methodology was used to measure coping strategies and the burnout syndrome. The voluntary subjects were 151 front-line CPS workers with at least 2 years experience in a southeastern Department of Social Services. They attended one of nine stress management workshops provided in various locations around the state. Quantitative analyses were run on the data. RESULTS: These workers perceived themselves to use Engaged (active) coping strategies more than Disengaged (avoidant) strategies. Sixty-two percent of participants scored in the high range on Emotional Exhaustion, the aspect some researchers consider to be the heart of Burnout. Those who used Engaged coping were less likely to feel depersonalized and more likely to feel a sense of personal accomplishment. Those who used Disengaged coping were more likely to feel emotionally exhausted, depersonalized, and to have a sense of reduced personal accomplishment. CONCLUSION: Neither the use of active nor avoidant coping strategies saved these workers from Emotional Exhaustion. The problem-focused strategies they are taught and use most do not help deal with the emotional content and context of their work, suggesting the use of emotion-focused coping to prevent and remediate burnout.

Adaptation, Psychological↗
PubMed1999

A single mutation, RecB(D1080A,) eliminates RecA protein loading but not Chi recognition by RecBCD enzyme.

Homologous recombination and double-stranded DNA break repair in Escherichia coli are initiated by the multifunctional RecBCD enzyme. After binding to a double-stranded DNA end, the RecBCD enzyme unwinds and degrades the DNA processively. This processing is regulated by the recombination hot spot, Chi (chi: 5'-GCTGGTGG-3'), which induces a switch in the polarity of DNA degradation and activates RecBCD enzyme to coordinate the loading of the DNA strand exchange protein, RecA, onto the single-stranded DNA products of unwinding. Recently, a single mutation in RecB, Asp-1080 --> Ala, was shown to create an enzyme (RecB(D1080A)CD) that is a processive helicase but not a nuclease. Here we show that the RecB(D1080A)CD enzyme is also unable to coordinate the loading of the RecA protein, regardless of whether chi sites are present in the DNA. However, the RecB(D1080A)CD enzyme does respond to chi sites by inactivating in a chi-dependent manner. These data define a locus of the RecBCD enzyme that is essential not only for nuclease function but also for the coordination of RecA protein loading.

DNA Helicases↗
PubMed1999

Coatings.

Explore the source record for details and available documents.

Chemistry Techniques, Analytical↗
PubMed1999

The RecBC enzyme loads RecA protein onto ssDNA asymmetrically and independently of chi, resulting in constitutive recombination activation.

Double-strand DNA break repair and homologous recombination in Escherichia coli proceed by the RecBCD pathway, which is regulated by cis-acting elements known as chi sites. A crucial feature of this regulation is the RecBCD enzyme-directed loading of RecA protein specifically onto the 3'-terminal, chi-containing DNA strand. Here we show that RecBC enzyme (lacking the RecD subunit) loads RecA protein constitutively onto the 3'-terminal DNA strand, with no requirement for chi. This strand is preferentially utilized in homologous pairing reactions. We propose that RecA protein loading is a latent property of the RecBCD holoenzyme, which is normally blocked by the RecD subunit and is revealed following interaction with chi.

Blotting, Southern↗
PubMed1999

Noncontact dipole effects on channel permeation. II. Trp conformations and dipole potentials in gramicidin A.

The four Trp dipoles in the gramicidin A (gA) channel modulate channel conductance, and their side chain conformations should therefore be important, but the energies of different conformations are unknown. A conformational search for the right-handed helix based on molecular mechanics in vacuo yielded 46 conformations within 20 kcal/mol of the lowest energy conformation. The two lowest energy conformations correspond to the solid-state and solution-state NMR conformations, suggesting that interactions within the peptide determine the conformation. For representative conformations, the electrostatic potential of the Trp side chains on the channel axis was computed. A novel application of the image-series method of. Biophys. J. 9:1160-1170) was introduced to simulate the polarization of bulk water by the Trp side chains. For the experimentally observed structures, the CHARm toph19 potential energy (PE) of a cation in the channel center is -1.65 kcal/mol without images. With images, the PE is -1.9 kcal/mol, demonstrating that the images further enhance the direct dipole effect. Nonstandard conformations yielded less favorable PEs by 0.4-1.1 kcal/mol.

Amino Acid Sequence↗
PubMed1999

A clinical assessment of the effects of 10% carbamide peroxide gel on human pulp tissue.

Bleaching vital teeth with 10% carbamide peroxide gel is a routine procedure in which there has been no evidence of associated permanent pulpal damage. Synthesis of the enzyme heme oxygenase-1 (HO-1) is increased after exposure of eukaryotic cells to conditions of oxidative stress (including H2O2) as a defense against the damaging effects of free radicals. Dental pulps were evaluated for HO-1 (aka Heat Shock Protein 32) presence in teeth treated with 10% carbamide peroxide. Seventeen intact first premolars scheduled for orthodontic extraction were bleached for 4 h immediately preceding extraction. Fourteen additional premolars from the same individuals were not bleached. All 31 teeth were extracted, fixed, demineralized, frozen, sectioned, and immunostained with anti-HO-1 antibody using a standard ABC protocol. There was no significant difference in the presence of HO-1 between total bleached versus total unbleached teeth using the Fisher's Exact Test (p < or = 0.05). However, the histological findings could be interpreted to suggest that coronal odontoblasts and endothelial cells in the underlying pulp proper may have the potential to respond to oxidative stress by increasing the synthesis of HO-1 (HSP32). This could represent a component of an initial defensive response by specific cells in strategic locations in the pulp that precedes classical inflammatory pathways.

Adolescent↗
PubMed1998

Reconstitution of an SOS response pathway: derepression of transcription in response to DNA breaks.

E. coli responds to DNA damage by derepressing the transcription of about 20 genes that make up the SOS pathway. Genetic analyses have shown that SOS induction in response to double-stranded DNA (dsDNA) breaks requires LexA repressor, and the RecA and RecBCD enzymes--proteins best known for their role as initiators of dsDNA break repair and homologous recombination. Here we demonstrate that purified RecA protein, RecBCD enzyme, single-stranded DNA-binding (SSB) protein, and LexA repressor respond to dsDNA breaks in vitro by derepressing transcription from an SOS promoter. Interestingly, derepression is more rapid if the DNA containing the dsDNA break has a chi recombination hot spot (5'-GCTGGTGG-3'), suggesting a novel regulatory role for one of the most overrepresented octamers in the E. coli genome.

Bacterial Proteins↗
PubMed1998

SSB protein controls RecBCD enzyme nuclease activity during unwinding: a new role for looped intermediates.

The RecBCD enzyme of Escherichia coli initiates homologous recombination by unwinding and simultaneously degrading DNA from a double-stranded DNA end. Single-stranded DNA loops are intermediates of this unwinding process. Here we show that SSB protein reduces the level of DNA degradation by RecBCD enzyme during unwinding, by binding to these ssDNA intermediates. Prior to interaction with the recombination hot spot chi, RecBCD enzyme has both 3'-->5' exonuclease and a weaker 5'-->3' exonuclease activity. We show that degradation of the 5'-terminal strand at the entry site is much more extensive in the absence of SSB protein. After interaction with chi, the level of 5'-->3' exonuclease activity is increased; as expected, degradation of the 5'-strand is also elevated in the absence of SSB protein. Furthermore, we show that, in the absence of SSB protein, the RecBCD enzyme is inhibited by the ssDNA products of unwinding; SSB protein alleviates this inhibition. These results provide insight into the organization of helicase and nuclease domains within the RecBCD enzyme, and also suggest a new level at which the nuclease activity of RecBCD enzyme is controlled. Hence, they offer new insight into the role of SSB protein in the initiation phase of recombination.

DNA Helicases↗
PubMed1998

Environmental endocrine disruption: an effects assessment and analysis.

This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter.

Animals↗
PubMed1997

The translocating RecBCD enzyme stimulates recombination by directing RecA protein onto ssDNA in a chi-regulated manner.

Double-stranded DNA break repair and homologous recombination in E. coli are initiated by the RecBCD enzyme, which unwinds and simultaneously degrades DNA from a double-stranded DNA end. This process is stimulated by cis-acting DNA elements, known as chi sites. Using both in vitro pairing and nuclease protection assays, we demonstrate that the translocating RecBCD enzyme, which has been activated by chi, coordinates the preferential loading of the homologous pairing protein, RecA, onto the resultant single-stranded DNA downstream of chi. This facilitated loading of RecA protein results in a substantial increase in both the efficiency and rate of in vitro recombination reactions and offers an explanation for stimulation of recombination and repair in vivo by chi.

Base Sequence↗
PubMed1997

The recombination hot spot chi is a regulatory element that switches the polarity of DNA degradation by the RecBCD enzyme.

Homologous recombination in Escherichia coli is stimulated at DNA sequences known as chi sites. Stimulation requires the multifunctional RecBCD enzyme, which is both a helicase and a 3' --> 5' exonuclease. Upon recognition of a properly oriented chi site, the 3' --> 5' exonuclease activity is attenuated. Here we show that in addition to attenuation of the 3' --> 5' exonuclease activity, recognition of chi by the RecBCD enzyme also up-regulates a nuclease activity of the opposite polarity, resulting in an enzyme that now preferentially degrades 5' --> 3'. These results demonstrate that chi is a unique regulatory element that converts the antirecombinogenic form of the RecBCD enzyme into a recombinogenic form by causing two distinct enzymatic changes: attenuation of the 3' --> 5' nuclease activity, and up-regulation of the 5' --> 3' nuclease activity. The consequence of chi recognition is the production of a recombination intermediate possessing a 3'-ssDNA overhang terminating at the chi sequence. This processing of a dsDNA end to a 3'-ssDNA overhang parallels that which occurs during the initation of homologous recombination in other pathways in E. coli, and in other organisms such as the yeast Saccharomyces cerevisiae.

Binding Sites↗