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Biomedical subjects

D C Wallace

Publications and source records attributed to D C Wallace.

At least 55 records · Page 3Linked to original sources
PubMed2000

Exploring parish nursing from an ethnographic perspective.

PURPOSE: This study examined a parish program as an evolving nursing specialty. DESIGN: This is an ethnographic study of a parish nursing program in a southeastern U.S. city that included interviews with key informants, participant observations, and document analysis. Data were content analyzed. FINDINGS AND RESULTS: Findings indicate positive perceptions of the parish nursing program. Cultural themes include the process of discovery, commitment to the parish nurse and program, and fit with values and missions. Taxonomies of parish nurse attributes, actions, offerings, roles, and entrance requirements were derived. DISCUSSION AND CONCLUSION: Parish nursing offers nurses the opportunity to bridge physical, social, emotional, and spiritual lives into one caregiving experience. IMPLICATIONS FOR PRACTICE: Findings provide clinical guidance for parish nurses.

Adult↗
PubMed1999

Cytochrome c-mediated apoptosis in cells lacking mitochondrial DNA. Signaling pathway involving release and caspase 3 activation is conserved.

Mitochondria serve as a pivotal component of the apoptotic cell death machinery. However, cells that lack mitochondrial DNA (rho(0) cells) retain apparently normal apoptotic signaling. In the present study, we examined mitochondrial mechanisms of apoptosis in rho(0) osteosarcoma cells treated with staurosporine. Immunohistochemistry revealed that rho(0) cells maintained a normal cytochrome c distribution in mitochondria even though these cells were deficient in respiration. Upon staurosporine treatment, cytochrome c was released concomitantly with activation of caspase 3 and loss of mitochondrial membrane potential (Deltapsi(m)). After mitochondrial loss of cytochrome c, rho(0) cells underwent little change in glutathione (GSH) redox potential whereas a dramatic oxidation in GSH/glutathione disulfide (GSSG) pool occurred in parental rho(+) cells. These results show that mitochondrial signaling of apoptosis via cytochrome c release was preserved in cells lacking mtDNA. However, intracellular oxidation that normally accompanies apoptosis was lost, indicating that the mitochondrial respiratory chain provides the major source of redox signaling in apoptosis.

Apoptosis↗
PubMed1999

Mitochondrial DNA variation in human evolution and disease.

Analysis of mitochondrial DNA (mtDNA) variation has permitted the reconstruction of the ancient migrations of women. This has provided evidence that our species arose in Africa about 150000 years before present (YBP), migrated out of Africa into Asia about 60000 to 70000 YBP and into Europe about 40000 to 50000 YBP, and migrated from Asia and possibly Europe to the Americas about 20000 to 30000 YBP. Although much of the mtDNA variation that exists in modern populations may be selectively neutral, studies of the mildly deleterious mtDNA mutations causing Leber's hereditary optic neuropathy (LHON) have demonstrated that some continent-specific mtDNA lineages are more prone to manifest the clinical symptoms of LHON than others. Hence, all mtDNA lineages are not equal, which may provide insights into the extreme environments that were encountered by our ancient ancestor, and which may be of great importance in understanding the pathophysiology of mitochondrial disease.

Biological Evolution↗
PubMed1999

Coordinate induction of energy gene expression in tissues of mitochondrial disease patients.

We have examined the transcript levels of a variety of oxidative phosphorylation (OXPHOS) and associated bioenergetic genes in tissues of a patient carrying the myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) A3243G mitochondrial DNA (mtDNA) mutation and the skeletal muscles of 14 patients harboring other pathogenic mtDNA mutations. The patients' tissues, which harbored 88% or more mutant mtDNA, had increased levels of mtDNA transcripts, increased nuclear OXPHOS gene transcripts including the ATP synthase beta subunit and the heart-muscle isoform of the adenine nucleotide translocator, and increased ancillary gene transcripts including muscle mitochondrial creatine phosphokinase, muscle glycogen phosphorylase, hexokinase I, muscle phosphofructokinase, the E1alpha subunit of pyruvate dehydrogenase, and the ubiquinone oxidoreductase. A similar coordinate induction of bioenergetic genes was observed in the muscle biopsies of severe pathologic mtDNA mutations. The more significant coordinated expression was found in muscle from patients with the MELAS, myoclonic epilepsy with ragged red fibers, and chronic progressive external ophthalmoplegia deletion syndromes, with ragged red muscle fibers and mitochondrial paracrystalline inclusions. High levels of mutant mtDNAs were linked to a high induction of the mtDNA and nuclear OXPHOS genes and of several associated bioenergetic genes. These observations suggest that human tissues attempt to compensate for OXPHOS defects associated with mtDNA mutations by stimulating mitochondrial biogenesis, possibly mediated through redox-sensitive transcription factors.

Adolescent↗
PubMed1999

Mouse models of mitochondrial disease, oxidative stress, and senescence.

During the course of normal respiration, reactive oxygen species are produced which are particularly detrimental to mitochondrial function. This is shown by recent studies with a mouse that lacks the mitochondrial form of superoxide dismutase (Sod2). Tissues that are heavily dependent on mitochondrial function such as the brain and heart are most severely affected in the Sod2 mutant mouse. Recent work with a mouse mutant for the heart/muscle specific isoform of the mitochondrial adenine nuclear translocator (Ant1) demonstrates a potential link between mitochondrial oxidative stress and mitochondrial DNA mutations. These mutations can be detected by Long-extension PCR, a method for detecting a wide variety of mutations of the mitochondrial genome. Such mutations have also been observed in the mitochondrial genome with senescence regardless of the mean or maximal lifespan of the organism being studied. Mutations have been detected with age in Caenorhabditis elegans, mice, chimpanzees, and humans. This implies that a causal relationship may exist between mitochondrial reactive oxygen species production, and the senescence specific occurrence of mitochondrial DNA mutations.

Aging↗
PubMed1999

Up-regulation of nuclear and mitochondrial genes in the skeletal muscle of mice lacking the heart/muscle isoform of the adenine nucleotide translocator.

Mice deficient in the heart/muscle specific isoform of the adenine nucleotide translocator (ANT1) exhibit many of the hallmarks of human oxidative phosphorylation (OXPHOS) disease, including a dramatic proliferation of skeletal muscle mitochondria. Because many of the genes necessary for mitochondrial biosynthesis, OXPHOS function, and response to OXPHOS disease might be expected to be up-regulated in the Ant1(-/-) mouse, we used differential display reverse transcription-polymerase chain reaction techniques in an effort to identify these genes. 17 genes were identified as up-regulated in Ant1-deficient mice, and they fall into four categories: 1) nuclear and mitochondrial genes encoding OXPHOS components, 2) mitochondrial tRNA and rRNA genes, 3) genes involved in intermediary metabolism, and 4) an eclectic group of other genes. Among the latter genes, we identified the gene encoding anti-apoptotic Mcl-1, the Skd3 gene, and the WS-3 gene, which were previously unknown to be related to mitochondrial function. These results indicate that identification of genes up-regulated in the skeletal muscle of the Ant1-deficient mouse provides a novel method for identifying mammalian genes required for mitochondrial biogenesis.

Adenosine Triphosphatases↗
PubMed1999

Mitochondrial disease in mouse results in increased oxidative stress.

It has been hypothesized that a major factor in the progression of mitochondrial disease resulting from defects in oxidative phosphorylation (OXPHOS) is the stimulation of the mitochondrial production of reactive oxygen species (ROS) and the resulting damage to the mtDNA. To test this hypothesis, we examined the mitochondria from mice lacking the heart/muscle isoform of the adenine nucleotide translocator (Ant1), designated Ant1(tm2Mgr) (-/-) mice. The absence of Ant1 blocks the exchange of ADP and ATP across the mitochondrial inner membrane, thus inhibiting OXPHOS. Consistent with Ant1 expression, mitochondria isolated from skeletal muscle, heart, and brain of the Ant1-deficient mice produced markedly increased amounts of the ROS hydrogen peroxide, whereas liver mitochondria, which express a different Ant isoform, produced normally low levels of hydrogen peroxide. The increased production of ROS by the skeletal muscle and heart was associated with a dramatic increase in the ROS detoxification enzyme manganese superoxide dismutase (Sod2, also known as MnSod) in muscle tissue and muscle mitochondria, a modest increase in Sod2 in heart tissue, and no increase in heart mitochondria. The level of glutathione peroxidase-1 (Gpx1), a second ROS detoxifying enzyme, was increased moderately in the mitochondria of both tissues. Consistent with the lower antioxidant defenses in heart, the heart mtDNAs of the Ant1-deficient mice showed a striking increase in the accumulation of mtDNA rearrangements, whereas skeletal muscle, with higher antioxidant defenses, had fewer mtDNA rearrangements. Hence, inhibition of OXPHOS does increase mitochondrial ROS production, eliciting antioxidant defenses. If the antioxidant defenses are insufficient to detoxify the ROS, then an increased mtDNA mutation rate can result.

Animals↗
PubMed1999

Mitochondrial diseases in man and mouse.

Over the past 10 years, mitochondrial defects have been implicated in a wide variety of degenerative diseases, aging, and cancer. Studies on patients with these diseases have revealed much about the complexities of mitochondrial genetics, which involves an interplay between mutations in the mitochondrial and nuclear genomes. However, the pathophysiology of mitochondrial diseases has remained perplexing. The essential role of mitochondrial oxidative phosphorylation in cellular energy production, the generation of reactive oxygen species, and the initiation of apoptosis has suggested a number of novel mechanisms for mitochondrial pathology. The importance and interrelationship of these functions are now being studied in mouse models of mitochondrial disease.

Aging↗
PubMed1999

Mitochondrial disease in superoxide dismutase 2 mutant mice.

Oxidative stress has been implicated in many diseases. The chief source of reactive oxygen species within the cell is the mitochondrion. We have characterized a variety of the biochemical and metabolic effects of inactivation of the mouse gene for the mitochondrial superoxide dismutase (CD1-Sod2(tm1Cje)). The Sod2 mutant mice exhibit a tissue-specific inhibition of the respiratory chain enzymes NADH-dehydrogenase (complex I) and succinate dehydrogenase (complex II), inactivation of the tricarboxylic acid cycle enzyme aconitase, development of a urine organic aciduria in conjunction with a partial defect in 3-hydroxy-3-methylglutaryl-CoA lyase, and accumulation of oxidative DNA damage. These results indicate that the increase in mitochondrial reactive oxygen species can result in biochemical aberrations with features reminiscent of mitochondrial myopathy, Friedreich ataxia, and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

Aconitate Hydratase↗
PubMed1999

Mitochondrial DNA variation in Koryaks and Itel'men: population replacement in the Okhotsk Sea-Bering Sea region during the Neolithic.

In this study, we analyzed the mitochondrial DNA (mtDNA) variation in 202 individuals representing one Itel'men and three Koryak populations from different parts of the Kamchatka peninsula. All mtDNAs were subjected to high resolution restriction (RFLP) analysis and control region (CR) sequencing, and the resulting data were combined with those available for other Siberian and east Asian populations and subjected to statistical and phylogenetic analysis. Together, the Koryaks and Itel'men were found to have mtDNAs belonging to three (A, C, and D) of the four major haplotype groups (haplogroups) observed in Siberian and Native American populations (A-D). In addition, they exhibited mtDNAs belonging to haplogroups G, Y, and Z, which were formerly called "Other" mtDNAs. While Kamchatka harbored the highest frequencies of haplogroup G mtDNAs, which were widely distributed in eastern Siberian and adjacent east Asian populations, the distribution of haplogroup Y was restricted within a relatively small area and pointed to the lower Amur River-Sakhalin Island region as its place of origin. In contrast, the pattern of distribution and the origin of haplogroup Z mtDNAs remained unclear. Furthermore, phylogenetic and statistical analyses showed that Koryaks and Itel'men had stronger genetic affinities with eastern Siberian/east Asian populations than to those of the north Pacific Rim. These results were consistent with colonization events associated with the relatively recent immigration to Kamchatka of new tribes from the Siberian mainland region, although remnants of ancient Beringian populations were still evident in the Koryak and Itel'men gene pools.

Alaska↗
PubMed1999

Traumatic aortic rupture: recent outcome with regard to neurologic deficit.

BACKGROUND: Traumatic aortic rupture is highly lethal, and its surgical treatment is complicated by a high rate of paraplegia. METHODS: The charts of 263 patients with traumatic aortic rupture from vehicular accidents treated between 1971 and 1998 were reviewed. Patients were grouped according to four periods: group 1, 1971 to 1975, (n = 31); group 2, 1976 to 1985, (n = 83); group 3, 1986 to 1994, (n = 82); and group 4, 1994 to 1998 (n = 67). Seventy-one patients died of exsanguination before definitive care. One hundred-ninety two patients had surgical repair with the following techniques: clamp and sew, 6 in group 1, 22 in group 2, 54 in group 3, none in group 4; shunt, 23 in group 1, 39 in group 2, 2 in group 3; cardiopulmonary bypass, 2 in group 1, 1 in group 3. Forty-three patients had partial bypass with the centrifugal pump and heparin-coated circuits in group 4. RESULTS: Operative mortality was 6 of 31 (19%) in group 1, 22 of 61 (36%) in group 2, 15 of 57 (26%) in group 3, and 7 of 43 (16%) in group 4. There was one case of paraplegia in group 1 (4%), ten in group 2 (18%), 11 in group 3 (26%), and none in group 4. This difference of paraplegia between the groups was significant (p<0.002). Significant factors for paraplegia were intraoperative hypotension (p<0.000002), cross-clamp time longer than 30 minutes (p<0.008), pump versus no pump (p<0.008), and younger age group (28+/-11 versus 39+/-17 years) (p<0.03). CONCLUSIONS: There were no statistically significant improvements in mortality rate over the four periods, although, the mortality rate was lowest in the last period when partial bypass with the centrifugal pump was used exclusively. Further, the use of the centrifugal pump with heparin-coated circuits, with femoral vein cannulation into the right atrium and distal aortic perfusion, reduced paraplegia significantly.

Accidents, Traffic↗
PubMed1999

Transfer of chloramphenicol-resistant mitochondrial DNA into the chimeric mouse.

The mitochondrial DNA (mtDNA) chloramphenicol (CAP)-resistance (CAPR) mutation has been introduced into the tissues of adult mice via female embryonic stem (ES) cells. The endogenous CAP-sensitive (CAPS) mtDNAs were eliminated by treatment of the ES cells with the lipophilic dye Rhodamine-6-G (R-6-G). The ES cells were then fused to enucleated cell cytoplasts prepared from the CAPR mouse cell line 501-1. This procedure converted the ES cell mtDNA from 100% wild-type to 100% mutant. The CAPR ES cells were then injected into blastocysts and viable chimeric mice were isolated. Molecular testing for the CAPR mutant mtDNAs revealed that the percentage of mutant mtDNAs varied from zero to approximately 50% in the tissues analyzed. The highest percentage of mutant mtDNA was found in the kidney in three of the chimeric animals tested. These data suggest that, with improved efficiency, it may be possible to transmit exogenous mtDNA mutants through the mouse germ-line.

Animals↗
PubMed1999

Combined use of biallelic and microsatellite Y-chromosome polymorphisms to infer affinities among African populations.

To define Y-chromosome haplotypes, we studied seven biallelic polymorphic sites. We combined data with those from four dinucleotide-repeat polymorphisms, to establish Y-chromosome compound superhaplotypes. Eight biallelic haplotypes that matched the dendrogram proposed by other investigators were identified in 762 Y chromosomes from 25 African populations. For each biallelic site, coalescence time of lineages carrying the derived allele was estimated and compared with previous estimates. The "ancestral" haplotype (haplotype 1A) was observed among Ethiopians, "Khoisan" (!Kung and Khwe), and populations from northern Cameroon. Microsatellite distributions within this haplotype showed that the Khoisan haplotypes 1A are widely divergent from those of the other two groups. Populations from northern Africa and northern Cameroon share a haplotype (i.e., 1C), which is not observed in other African populations but represents a major Eurasian cluster. Haplotypes 1C of northern Cameroon are clearly distinct from those of Europe, whereas haplotypes 1C of northern African are well intermingled with those of the other two groups. Apportionment of diversity for the Y-chromosomal biallelic haplotypes was calculated after populations were clustered into different configurations. Despite some correspondence between language affiliation and genetic similarity, geographic proximity seems to be a better predictor of genetic affinity.

Africa↗
PubMed1999

Application of liquid dynamics theory to the glass transition.

In monatomic liquid dynamics theory, the system moves among a large number of intersecting nearly harmonic valleys in the many-particle potential energy surface. The same potential surface underlies the motion of atoms in the supercooled liquid. As temperature is decreased below the melting temperature, the motion among the potential valleys will begin to freeze out, and the system will pass out of equilibrium. It is therefore necessary to develop a nonequilibrium theory, based on the Hamiltonian motion. The motion is separated into two distinct parts, and idealized as follows: (a) the vibrational motion within a single valley is assumed to be purely harmonic, and remaining in equilibrium; and (b) the transit motion, which carries the system from one valley to another, is assumed to be instantaneous, and energy and momentum conserving. This idealized system is capable of exhibiting a glass transition behavior. An elementary model, incorporating the idealized motion, is the independent atom model, originally developed to treat self diffusion in monatomic liquids. For supercooled liquids, in the independent atom model, the vanishing of self diffusion at a finite temperature implies the same property for the transit probability. The vanishing of the transit probability at a finite temperature supports the view that transits are not merely thermally activated, but are controlled by phase-space correlations. For supercooled liquid sodium, the transit probability has Vogel-Tamann-Fulcher temperature dependence. The independent atom model is shown to be capable of exhibiting all the essential glass transition properties, including rate dependence of the glass transition temperature, and both exponential and nonexponential relaxation.

Journal Article↗
PubMed1999

Use of home and community-based services by elderly black and white females.

The study purpose was to determine the impact of demographic, social, environmental, and health indicators on utilization of community-based services among black and white female elders. Existing data from a regional Area Agency on Aging was used and the sample (N = 1816) included low income and rural females. Races differed in use and services most frequently used were case management, outreach, congregate meal, and home delivered meals. Multiple linear and logistic regression indicated that age, payment source, income adequacy, residence, health conditions, sensory impairment, and function were associated with the number and types of services used, but these differed by race. Study findings have implications for health care providers, educators, policy makers, and planners.

Activities of Daily Living↗
PubMed1998

MITOMAP: a human mitochondrial genome database--1998 update.

We have continued to develop MITOMAP (http://www.gen.emory. edu/MITOMAP ), a comprehensive database for the human mitochondrial DNA (mtDNA). MITOMAP uses the mtDNA sequence as the unifying element for bringing together information on mitochondrial genome structure and function, pathogenic mutations and their clinical characteristics, population associated variation, and gene-gene interactions. Over the past year we have increased the degree of interlinking of MITOMAP information available on the web page, by using our generalized information management system, GENOME. As increasingly larger regions of the human genome are sequenced and characterized, the need for integrating such information is growing. Consequently, MITOMAP and GENOME provide a valuable reference for the mitochondrial biologist, in addition to being a model for the development of comprehensive, information storage and retrieval systems for other components of the human genome. This paper documents the changes to MITOMAP which have been implemented over the past year.

Computer Communication Networks↗