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Biomedical subjects

R E Davis

Publications and source records attributed to R E Davis.

At least 37 records · Page 2Linked to original sources

Relocation of the institutionalized aged.

The effects of relocation and institutionalization upon frail older people have been studied extensively for the past several decades and have been a topic of some controversy. Because of varying methodologies, differing populations, overlooked variables, and mistakes in interpretation, this area of epidemiological research has resulted in debate among scholars in the field. It may be helpful to review some of the research that has been done, examine a theory of why mortality seems to increase when older people are involuntarily relocated, speculate upon how this effect might be minimized, and introduce some data that seemingly would confirm that careful planning for relocation might, in fact, reduce subsequent morbidity and mortality.

Adaptation, Psychological↗

Abnormal mitochondrial morphology in sporadic Parkinson's and Alzheimer's disease cybrid cell lines.

Diseases linked to defective mitochondrial function are characterized by morphologically abnormal, swollen mitochondria with distorted cristae. Several lines of evidence now suggest that sporadic forms of Parkinson's disease (PD) and Alzheimer's disease (AD) are linked to mitochondrial dysfunction arising from defects in mitochondrial DNA (mtDNA). Human neuroblastoma (SH-SY5Y) cells that are deficient in mtDNA (Rho(0)) were repopulated with mitochondria from AD or PD patients or age-matched controls. These cytoplasmic hybrid (cybrid) cell lines differ only in the source of their mtDNA. Differences between cybrid cell lines therefore arise from differences in mtDNA and provide a model for the study of how impaired mitochondrial function alters the mitochondria themselves and how these changes adversely affect the neuronal cells they occupy. Cybrid cell mitochondria were labeled with the mitochondrial membrane potential-sensitive dye, JC-1. Analysis of these JC-1 labeled mitochondria by confocal microscopy revealed that mitochondrial membrane potential was significantly reduced in both PD and AD cybrid cells when compared with controls. Ultrastructural examination showed that control cybrid cells contained small, morphologically normal, round or oval mitochondria with a dark matrix and regular distribution of cristae. PD cybrid cells contained a significant and increased percentage of mitochondria that were enlarged or swollen and had a pale matrix with few remaining cristae (0.26-0.65 microm(2)). AD cybrid cells also contained a significantly increased percentage of enlarged or swollen mitochondria (0.25-5.0 microm(2)) that had a pale matrix and few remaining cristae. Other pathological features such as crystal-like intramitochondrial inclusions and cytoplasmic inclusion bodies were also found in PD and AD cybrids. These observations suggest that transfer of PD or AD mtDNA into Rho(0) cells was sufficient to produce pathological changes in mitochondrial ultrastructure that are similar to those seen in other mitochondrial disorders. These data were reported in abstract form (Trimmer et al., 1998, Soc. Neurosci. Abstr. 24: 476).

Aged↗

CI-1017, a functionally M1-selective muscarinic agonist: design, synthesis, and preclinical pharmacology.

The five muscarinic receptor subtypes (M1-M5) are characterized by seven helices that define a transmembrane cavity which serves as the binding pocket for agonists and antagonists. The five cavities appear to be topographically different enough to permit subtype selectivity among antagonists but not among classical agonists which tend to be smaller in size than antagonists. It was reasoned that synthesis of muscarinic agonists longer/larger than their classical counterparts might result in subtype selectivity. M1 subtype selectivity was found in a class of 1-azabicyclo[2.2.1]heptan-3-one, O-(3-aryl-2-propynyl) oximes. One of these, CI-1017, improved spatial memory of hippocampally deficient mice and nbM-lesioned rats at doses of 1.0-3.2 and 0.1-0.3 mg/kg, respectively, while producing parasympathetic side effects only at very high doses (100-178 mg/kg). Additionally, CI-1017 inhibited production of amyloidogenic A beta and increased secretion of soluble APP. Thus, CI-1017, besides treating AD symptomatically, may also retard its progression. CI-1017 has recently completed phase I clinical trials.

Animals↗

Common elements of spiroplasma plectroviruses revealed by nucleotide sequence of SVTS2.

DNA of SpV1-like spiroplasma plectroviruses (rods with single-stranded circular DNA) is scattered in the genome of the phytopathogen Spiroplasma citri and has significant consequences for evolution of the S. citri genome. We determined the complete nucleotide sequence of SVTS2, a SpV1-like virus of S. melliferum, a honeybee pathogen, to ascertain, by comparison with S. citri SpV1 viruses (GenBank U28974 and X51344), the defining features of this important group. The 6,824 nt DNA contains nine ORFs homologous to ORFs of S. citri SpV1 viruses and five ORFs unique to SVTS2. The predicted amino acid sequences of the homologous ORFs were 17-38% identical to those of their S. citri counterparts. The SVTS2 predicted ORF 1 product (Mr 47,031) was considerably smaller than those of known S. citri SpV1 viruses. Also, in contrast to those viruses, SVTS2 lacked an ORF with recognizable similarity to a transposase. ORF 2 of all three viruses had a homologue among the products of genes of MVL-1, a virus of Acholeplasma laidlawii, another plectrovirus. The results suggest that, at most, only slightly more than half of SpV1 genomes consists of genes shared by all spiroplasma viruses of the group.

Amino Acid Sequence↗

Endoscopic valvuloplasty for GERD.

BACKGROUND: The transoral, endoscopic route has been suggested as a possible approach for the correction of severe gastroesophageal reflux. Such a procedure would involve no mobilization of the cardia or other structures. The optimal placement, number, and configuration of sutures remains undefined. METHODS: With the use of a previously developed endoscopic sewing machine, this study was undertaken in baboons with two suture arrangements immediately below the lower esophageal sphincter. A linear arrangement (group I) and a circular arrangement (group II) were compared. During the 6 months after the procedure, the animals were evaluated using manometry, fluoroscopic barium swallow, upper gastrointestinal endoscopy, and a pressure volume test. RESULTS: A significant increase in lower esophageal sphincter length was demonstrated only in group II (p = 0. 010). A significant increase in lower esophageal sphincter pressure was demonstrated only in group I animals (p = 0.008). The abdominal length increased in group I (p = 0.004) and group II (p = 0.004). The yield pressure and yield volume did not differ significantly from those measured previously in control animals. No evidence of reflux, stricture formation, esophagitis, or other pathology was noted. CONCLUSIONS: Some manometric parameters associated with gastroesophageal reflux are altered by the endoscopic placement of sutures below the gastroesophageal junction, with no associated serious complications.

Animals↗

Hyperoxic reperfusion exacerbates postischemic renal dysfunction.

BACKGROUND: Hyperoxic reperfusion from global ischemia worsens functional outcome because of oxygen radical-mediated injury. This study tested the hypothesis that hyperoxic reperfusion would exacerbate postischemic renal dysfunction. METHODS: Twenty-nine healthy, uninephrectomized, male mongrel rabbits (Oryctolagus cuniculus) in 3 groups were subjected to 30 minutes of complete normothermic renal ischemia followed by reperfusion under hyperoxic or normoxic conditions. The groups were: hyperoxically reperfused (n = 8), normoxically reperfused (n = 8), hyperoxic sham (no ischemia, n = 5), and allopurinol-pretreated (50 mg/kg, intravenously), hyperoxically reperfused animals (n = 8). Plasma concentrations of creatinine, urea nitrogen and electrolytes were measured at 0, 24, 48, and 72 hours after ischemia and served as functional outcome markers. Histopathologic analysis of kidneys for injury was performed by an expert who was blinded to the procedures. RESULTS: Plasma creatinine in hyperoxically reperfused rabbits was significantly elevated above normoxic (P =.02) and sham (P =.003) animals by 48 hours and remained elevated to 72 hours. Plasma urea nitrogen in hyperoxically reperfused rabbits was significantly elevated above the normoxic group (P = .01), the sham group (P = .02), and the allopurinol group (P = .04) by 72 hours. These coincided with a significantly elevated histopathologic injury score in hyperoxically reperfused rabbits compared with sham (P = .019), normoxic (P = .035), and allopurinol-pretreated hyperoxically reperfused animals (P = .037). CONCLUSIONS: Hyperoxic reperfusion exacerbates renal dysfunction after 30 minutes of complete normothermic ischemia. This dysfunction may be mediated by oxygen radical-related injury.

Allopurinol↗

Classification of aster yellows-group phytoplasmas based on combined analyses of rRNA and tuf gene sequences.

Seventy phytoplasma isolates, including 10 previously characterized reference strains, of the aster yellows group were examined by RFLP analysis of PCR-amplified rDNA and RFLP and sequence analysis of the tuf gene. On the basis of rDNA restriction profiles, seven previously proposed 16S rDNA subgroups (16SrI-A, -B, -C, -D, -E, -F and -K) were recognized in the material examined. In addition, three new subgroups that differ in the RFLP profiles were identified and designated 16SrI-L, 16SrI-M and 16SrI-N. Of the two types of rDNA sequences used, an 1800 bp fragment comprising the entire 16S rRNA gene and the 16S-23S rDNA spacer region proved more suitable for AY-group phytoplasma differentiation than a 1240 bp fragment of the 16S rRNA gene. Many differences in the rDNA profiles between the subgroups could be explained by sequence heterogeneity of the two phytoplasmal rRNA operons. The subgroups delineated by RFLP analysis of a 940 bp tuf gene fragment are consistent with subgroups defined on the basis of rDNA sequences. However, subgroups 16SrI-D, -L and -M showed the same tuf gene restriction profiles as subgroup 16SrI-B. This result was confirmed by sequence analysis in which these subgroups differed slightly in their tuf gene sequence, when compared with members of subgroup 16SrI-B. On the basis of combined analyses of rDNA and tuf gene sequences and in view of pathological aspects, the taxonomic distinction of AY-subgroups 16SrI-A, -B, -C, -D, -E, -F, -K and -N appears to be substantial.

Acholeplasmataceae↗

Cultural health care or child abuse? The Southeast Asian practice of cao gio.

Although the immigration of Southeast Asians more than doubled over the past 20 years, much misunderstanding still persists regarding traditional, culture-bound health practices used by Vietnamese, Cambodian and Laotian families. The research presented in this paper explains one such traditional practice, that of cao gio. Cao gio, a dermabrasion therapy, is used extensively by many Southeast Asian women to treat a variety of illnesses. Health care providers do not appreciate this practice, however, to the extent that it is claimed to be a form of child abuse in some of the literature reviewed. A better understanding of the practice by those involved in the primary care of Southeast Asian families is not only necessary, but essential to avoid the mislabeling and misinterpretation of cultural, traditional health practices as child abuse. Lack of awareness of Southeast Asian cultural practices is quite significant, even though the United States experienced three major waves of Southeast Asian immigration during the past 20 years (Takeuchi, & Young, 1994). Over the past decade, the number of Southeast Asian immigrants and refugees to the United States has increased 108% or by more than 1 million individuals (Fong, & Mokuau, 1994; Frank-Stromborg, 1991; Ja, & Aoki, 1993; Tran, 1991; U.S. Census Bureau, 1998). Yet, despite this, Southeast Asian individuals are poorly understood, and the literature reveals little about what health, illness and treatment constitute for these different cultures (Boston, 1992; Buchwald, Panwala, & Hooton, 1992). The ethnic groups that comprise Southeast Asians, formerly known as the Indochinese, include individuals from Vietnam, Cambodia and Laos (Catanzaro, & Moser, 1982; Chung, & Kagawa-Singer, 1993). The majority of these individuals are refugees who fled their countries due to political persecution (Toole, & Waldman, 1993). This paper describes the findings of a phenomenological research study completed among 19 Southeast Asian women regarding beliefs about health and health practices. The women discussed the practice of cao gio (phonetically pronounced as gow yaw) and its importance, effectiveness and significance to their cultures. The discussion relates the study findings to the debate and issues surrounding child abuse, the consequences of misreporting, as well as the consequences of cultural ignorance in the provision of health care to those of different cultural practices and beliefs, particularly those of Southeast Asian ethnicity.

Adult↗

Phytoplasma: phytopathogenic mollicutes.

During the past decade, research has yielded new knowledge about the plant and insect host ranges, geographical distribution, and phylogenetic relationships of phytoplasmas, and a taxonomic system has emerged in which distinct phytoplasmas are named as separate "Candidatus phytoplasma species." In large part, this progress has resulted from the development and use of molecular methods to detect, identify, and classify phytoplasmas. While these advances continue, research has recently begun on the phytoplasma genome, how phytoplasmas cause disease, the role of mixed phytoplasmal infections in plant diseases, and molecular/genetic phenomena that underlie symptom development in plants. These and other recent advances are laying the foundation for future progress in understanding the mechanisms of phytoplasma pathogenicity, organization of the phytoplasma genome, evolution of new phytoplasma strains and emergence of new diseases, bases of insect transmissibility and specificity of transmission, and plant gene expression in response to phytoplasmal infection, as well as the design of novel approaches to achieve effective control of phytoplasmal diseases.

Ecology↗

Refugee experiences and Southeast Asian women's mental health.

The wars in Southeast Asia displaced thousands of families from Cambodia, Laos, and Vietnam. The upheavals led to a number of waves of immigration to the United States. Current research supports hypotheses of post-traumatic stress disorder diagnoses in refugees from the wars in Vietnam but omits pertinent cultural factors. This phenomenological study of 19 women from Southeast Asia examines the meanings of their refugee experiences. Open-ended interviews with these women reveal themes of survival, despair, and isolation. Health care providers may notice cultural bereavement as opposed to post-traumatic stress disorder, reflecting a psychological resilience not extensively explored previously. Developing empathetic interactions and including important ethnic identity factors in caring for refugee women appear essential in providing appropriate health care.

Adult↗

A novel mitochondrial DNA-like sequence in the human nuclear genome.

We describe here a nuclear mitochondrial DNA-like sequence (numtDNA) that is nearly identical in sequence to a continuous 5842 bp segment of human mitochondrial DNA (mtDNA) that spans nucleotide positions 3914 to 9755. On the basis of evolutionary divergence among modern primates, this numtDNA molecule appears to represent mtDNA from a hominid ancestor that has been translocated to the nuclear genome during the recent evolution of humans. This numtDNA sequence harbors synonymous and nonsynonymous nucleotide substitutions relative to the authentic human mtDNA sequence, including an array of substitutions that was previously found in the cytochrome c oxidase subunit 1 and 2 genes. These substitutions were previously reported to occur in human mtDNA, but subsequently contended to be present in a nuclear pseudogene sequence. We now demonstrate their exclusive association with this 5842-bp numtDNA, which we have characterized in its entirety. This numtDNA does not appear to be expressed as a mtDNA-encoded mRNA. It is present in nuclear DNA from human blood donors, in human SH-SY5Y and A431 cell lines, and in rho(0) SH-SY5Y and rho(0) A431 cell lines that were depleted of mtDNA. The existence of human numtDNA sequences with great similarities to human mtDNA renders the amplification of pure mtDNA from cellular DNA very difficult, thereby creating the potential for confounding studies of mitochondrial diseases and population genetics.

Cell Nucleus↗

Rapid activation of heat shock factor-1 DNA binding by H2O2 and modulation by glutathione in human neuroblastoma and Alzheimer's disease cybrid cells.

Because cellular signaling systems are critical mediators of responses to oxidative stress, a condition associated with neurodegenerative disorders, the redox-dependent regulation of heat shock factor-1 (HSF-1) was investigated in human neuroblastoma SH-SY5Y cells. Exposure of cells to 200 microM H2O2 caused a rapid increase in HSF-1 DNA binding that was evident within 10 min, and caused a robust increase that reached levels 8-fold the basal activity. In comparison, the transcription factors, activator protein-1 (AP-1) and early growth response-1 (EGR-1), were activated more slowly and to a lesser extent. Activation of HSF-1 DNA binding activity was associated with a cytosolic to nuclear translocation of HSF-1 protein, and was detected with concentrations of H2O2 of 100 microM and greater. Intracellular glutathione modulated H2O2-induced HSF-1 DNA binding activity, as depletion of glutathione caused HSF-1 to be activated with lower concentrations of H2O2 (25 microM) and supplementation of glutathione blocked HSF-1 activation by 100 to 400 microM H2O2. Alzheimer's disease (AD) and control cybrid cells (SH-SY5Y cells in which the mitochondria were replaced with platelet mitochondria from AD or matched control subjects) were used to test the effects of the chronic oxidative stress caused by the excessive production of reactive oxygen intermediates (ROIs) in AD cybrids on HSF-1 activity. Basal and maximal (induced by H2O2 in glutathione-depleted cells) HSF-1 DNA binding activity were lower in AD than control cybrids, suggesting that the cells had compensated for excessive ROIs. These results indicate that the activation of HSF-1 is highly sensitive to oxidative stress and is regulated by endogenous antioxidant mechanisms.

Alzheimer Disease↗

Transient expression of DNA and RNA in parasitic helminths by using particle bombardment.

Parasitic helminths (worms belonging to several metazoan phyla) cause considerable morbidity and mortality in humans. They are an important veterinary problem, and they result in significant economic losses in animal grazing and agriculture. Experimental studies on parasitic helminths have been limited by a lack of parasite cell lines and methods for molecular genetic analyses. We evaluated particle bombardment (biolistics) as a strategy to introduce and express nucleic acids in these multicellular parasites. By using embryos of the parasitic nematode Ascaris as a model, we developed methods to introduce and express both DNA and RNA during several stages of Ascaris embryogenesis. Biolistic transfection will facilitate experimental strategies in Ascaris embryos complementing other biochemical tools available (e.g., in vitro whole-cell embryo extracts for transcription, RNA processing, and translation). Transfection experiments with adult schistosomes further suggest that the biolistic strategy should be applicable to a variety of other parasitic helminths. The development of these methods provides molecular genetic tools to study gene expression and the biology of a variety of types and developmental stages of important helminth parasites.

Animals↗

MPP+ inhibits proliferation of PC12 cells by a p21(WAF1/Cip1)-dependent pathway and induces cell death in cells lacking p21(WAF1/Cip1).

The molecular and biochemical mode of cell death of dopaminergic neurons in Parkinson's disease (PD) is uncertain. In an attempt at further clarification we studied the effects of 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on dopaminergic PC12 cells. In humans and nonhuman primates MPTP/MPP+ causes a syndrome closely resembling PD. MPP+ toxicity is thought to be mediated by the block of complex I of the mitochondrial electron transport chain. Treatment of undifferentiated PC12 cells with MPP+ primarily inhibited proliferation of PC12 cells and secondarily led to cell death after the depletion of all energy substrates by glycolysis. This cell death showed no morphological characteristics of apoptosis and was not blocked by treatment with caspase inhibitors. The inhibition of cell growth was not dependent on an inhibition of complex I activity since MPP+ also inhibited cell proliferation in SH-SY5Y cells lacking mitochondrial DNA and complex I activity (p0 cells). As shown by flow cytometric analysis, MPP+ induced a block in the G0/G1 to S phase transition that correlated with increased expression of the cyclin-dependent kinase inhibitor p21(WAF1/Cip1) and growth arrest. Since treatment with 1 microM MPP+ caused apoptotic cell death in p21(WAF1/Cip1)-deficient (p21(-/-)) but not in parental (p21(+/+)) mouse embryo fibroblasts, our data suggest that in an early phase MPP+-induced p21(WAF1/Cip1) expression leads to growth arrest and prevents apoptosis until energy depletion finally leads to a nonapoptotic cell death.

1-Methyl-4-phenylpyridinium↗

The phytoplasma associated with ash yellows and lilac witches'-broom: 'Candidatus phytoplasma fraxini'.

Phytoplasmas associated with the plant diseases ash yellows (AshY, occurring in Fraxinus) and lilac witches'-broom (LWB, occurring in Syringa) represent a putative species-level taxon. Phytoplasmal DNA from 19 ash or lilac sources across the known geographic range of AshY (71-113 degrees W) was examined to determine if AshY and LWB phytoplasmas are a coherent group, if variability exists in both conserved and anonymous DNA, and if variability in 16S rDNA is related to host or geographic origin. The 16S rRNA gene and the 16S-23S spacer were amplified using primer pair P1/P7 and analysed using 15 restriction enzymes. RFLPs were detected in digests obtained with Alul, Hhal or Taql, for a total of four RFLP profile types. Sequencing of the amplimers from strains AshY1T, AshY3, AshY5 and LWB3 (which represent the four 16S rDNA RFLP profile types) revealed only three positions in the 16S rRNA gene and one position in the 16S-23S spacer at which differences occurred; these were single nucleotide substitutions. Sequence homology between any two strains was > 99.8%. A portion of a ribosomal protein operon, amplified with primer pair rpF1/R1 from each of the four strains noted above, was analysed with six restriction enzymes, resulting in the detection of two RFLP profiles with Msel. Southern analysis, utilizing two non-specific probes from other phytoplasma groups, revealed three RFLP profile types in anonymous chromosomal DNA of strains representing the four 16S rDNA genotypes. Two strains, AshY3 and LWB3, had unique combinations of characters in the various assays. On the basis of RFLP profiles, the strains from the other plants sampled comprised two groups. The grouping was not clearly related to host or geographic origin. The genome size of strain AshY3 was estimated from PFGE data to be 645 kbp. Phylogenetic analysis of a 1423 bp 16S rDNA sequence from strains AshY1T, AshY3, AshY5 and LWB3, together with sequences from 14 other mollicutes archived in GenBank, produced a tree on which the AshY and LWB strains clustered as a discrete group, consistent with previous analyses utilizing only type strain AshY1T. Thus, the AshY phytoplasma group is coherent but heterogeneous. The name 'Candidatus Phytoplasma fraxini' is proposed for this group.

Acholeplasmataceae↗