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Biomedical subjects

W J Jones

Publications and source records attributed to W J Jones.

At least 19 recordsLinked to original sources

Gene-gene concordance and the phylogenetic relationships among rare and widespread pygmy sunfishes (genus Elassoma).

Pygmy sunfishes (Elassoma) are primarily lowland species with an interesting biogeographic dichotomy: three species have broad geographic distributions, and three are narrowly distributed (and have been recommended for threatened or endangered status). To test phylogenetic predictions derived from the geographic distributions of pygmy sunfishes and possible historical factors contributing to the threatened/endangered status of the rare species, we reconstructed trees for two mitochondrial genes and introns of three nuclear genes. The pattern and rate of nuclear and mitochondrial sequence evolution were heterogeneous within Elassoma, but relationships were generally concordant across gene trees. Elassoma is monophyletic and, as predicted by geographic distributions, E. evergladei, E. okefenokee, and E. zonatum consistently branch from deeper nodes. Phylogeographic structure in mitochondrial and nuclear genes also supports an early origin of E. zonatum. Phylogenetic analyses of the five loci support widely divergent positions for the rare species E. alabamae. Two rare species, E. boehlkei and E. okatie, are sister taxa and are related to a widespread species, E. evergladei.

Animals↗

Mass spectrometric determination of a novel modification of the N-terminus of histidine-tagged proteins expressed in bacteria.

Two proteins, FKBP, and Spo0F, were expressed in bacteria as histidine-tagged fusion proteins and isolated under native conditions. MALDI-TOF-MS analysis revealed that each protein preparation contained two components, neither of which corresponded to the molecular weights predicted from DNA sequences. The difference in molecular weight between the two FKBP components and two Spo0F components was approximately 178 +/- 14 Da. Site-specific proteolytic cleavage resulted in the release of histidine-tagged peptide from the recombinant proteins. MALDI mass spectra of the cleaved proteins showed a single molecular ion peak for each species with the predicted molecular weights. The histidine-tagged peptide released from both fusion proteins displayed two distinct peaks by MALDI-FT-MS corresponding to monoisotopic molecular weights of 2269. 027 Da and 2447.087 Da, respectively, which were both inconsistent with the predicted peptide sequence M-G-H-H-H-H-H-H-H-H-H-H-S-S-G-H-I-E-G-R of 2400.055 Da. The peptide at 2269.027 Da was sequenced by ESI-MS-MS and found to be a truncated histidine tag resulting from an initiator methionine deletion. ESI-MS-MS analysis of the peptide at 2447.087 Da indicated a moiety of 178.0 Da attached to the second residue glycine of the histidine tag. This alteration of the N-terminus does not fit any known modifications. A synthetic peptide with the identical sequence of the isolated his-tag M-G-H-H-H-H-H-H-H-H-H-H remained unmodified during the protein purification process, suggesting that modification of the initiator methionine was carried out in vivo, rather than the result of a chemical reaction from the isolation procedure.

Amino Acid Sequence↗

Oxygen starvation induces cell death in Candida shehatae fermentations of D-xylose, but not D-glucose.

Candida shehatae cells, cultivated on D-glucose and D-xylose, were subjected to a shift from fully aerobic to anaerobic fermentative conditions. After anaerobic conditions were imposed, growth was limited to approximately one doubling or less as C. shehatae rapidly entered a stationary phase of growth. Following the shift to anoxia, cell viability rapidly declined and the total cell volume declined in the D-xylose fermentations. Moreover, the cell volume distribution shifted to smaller volumes. Cell viability, measured by plate counts, declined nine times faster for D-xylose fermentations than for D-glucose fermentations. Anaerobic growth did not occur on either D-glucose or D-xylose. Selected vitamins and amino acids did not stimulate anaerobic growth in C. shehatae, but did enhance anaerobic growth on D-glucose in S. cerevisiae. The decline in cell viability and lack of anaerobic growth by C. shehatae were attributed to oxygen deficiency and not to ethanol inhibition. The results shed light on why C. shehatae anaerobic fermentations are not currently practical and suggest that research directed towards a biochemical understanding of why C. shehatae can not grow anaerobically will yield significant improvements in ethanol fermentations from D-xylose.

Aerobiosis↗

Biotransformation of the antipsychotic agent, mazapertine, in dog--mass spectral characterization and identification of metabolites.

1. Biotransformation of the antipsychotic agent, mazapertine, was studied after a single oral administration of 14C-mazapertine succinate (10 mg/kg, free base) to six beagle dogs (three male, three female). 2. Following oral administration of 14C-mazapertine, plasma (0-48 h), urine (0-7 days), and faeces (0-7 days) were collected. Recoveries of total radioactivity in urine and faeces were 26.9 and 62.0% of the dose, respectively. 3. Unchanged mazapertine plus 14 metabolites were isolated and identified, which accounted for > 60% of the sample radioactivity in the plasma, 17% of the dose in urine and 28% of the dose in faecal extract. 4. Unchanged mazapertine accounted for < 4% of the radioactive dose in excreta samples and < 21% of the sample radioactivity present in plasma samples. 5. Seven metabolic pathways for the formation of metabolites were identified including: (1) phenyl hydroxylation, (2) piperidyl oxidation, (3) O-dealkylation, (4) N-dephenylation, (5) oxidative N-debenzylation, (6) depiperidylation and (7) conjugation. 6. Pathways 1, 2, 5 and 6 produced 4-OH-piperidyl, OH-phenyl-OH-piperidyl, carboxybenzoyl piperidine and depiperidyl analogues of mazapertine as major metabolites.

Administration, Oral↗

Public and private perspectives on hospital conversions: proposed MUSC-Columbia/HCA "partnership".

Conversion has been defined as "any type of transaction that results in the shift of all or a substantial portion of the assets of nonprofit health care organizations to for-profit use" (Claxton and Colleagues, 1997:10-11). Not surprisingly, efforts at such conversion create political conflict and opposition within communities with some groups supporting and others opposing the intended conversion. This study looks at a particular effort at conversion: the proposed "partnership" between three hospitals of the Medical University of South Carolina (MUSC) and Columbia/HCA, the largest for-profit health services network in the U.S. Beginning in 1995, the three-year effort (now at an impasse) has drawn local and state policy-markers into increasing controversy and acrimony. Beyond the details, the episode also raises fundamental issues about the nature of public health care and the extent to which we can convert public health facilities to private control while preserving their essential public missions.

Capital Financing↗

In vivo microdialysis and liquid chromatography/thermospray mass spectrometry of the novel anticonvulsant 2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate (topiramate) in rat brain fluid.

The concentration of a novel anticonvulsant, 2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate (topiramate), was determined in the extracellular fluid of rat brain by in vivo microdialysis combined off-line with liquid chromatography/thermospray mass spectrometry. A microdialysis probe was stereotaxically implanted in the nucleus accumbens region of the rat brain. The maximum concentration of topiramate in the brain dialysate for a dose of 50 mg kg-1 i.v. was approximately 10 microM and occurred 45 min post-injection. The detection limit of topiramate in the extracellular fluid of rat brain was in the 0.1 microM range using selected ion monitoring techniques. The base peak, which was the ammonium adduct ion [M + NH4]+, was used for detection. An internal standard of d12-labeled topiramate was utilized for quantitation by isotope dilution analysis.

Animals↗

Thermococcus guaymasensis sp. nov. and Thermococcus aggregans sp. nov., two novel thermophilic archaea isolated from the Guaymas Basin hydrothermal vent site.

Thermococcus strains TYST and TYT isolated from the Guaymas Basin hydrothermal vent site and previously described were compared by DNA-DNA hybridization analysis with the closest Thermococcus species in terms of physiology and nutritional aspects. On the basis of the new data and taking into consideration the molecular, physiological and morphological traits published previously, it is proposed that strains TYT and TYST should be classified as new species named Thermococcus aggregans sp. nov. and Thermococcus guaymasensis sp. nov., respectively. The type strain of T. aggregans is strain TYT (= DSM 10597T) and the type strain of T. guaymasensis is strain TYST (= DSM 11113T).

DNA, Archaeal↗

Clinical integration in a population-based planning framework.

Population-based planning provides context and scope to the goal of clinical integration. It also is a transforming process for organizations and programs devoted to a hospital-centric care system, as well as source of language that can support collaboration among buyers, payers, providers, and community groups. At the clinical care level, population-based planning recognizes the differences in how people perceive health and use health care services, as an important corollary to understanding specific diseases and clinical service needs.

Community Health Planning↗

Biochemical and phylogenetic characterization of two novel deep-sea Thermococcus isolates with potentially biotechnological applications.

The partial 16S rDNA gene sequences of two thermophilic archaeal strains, TY and TYS, previously isolated from the Guaymas Basin hydrothermal vent site were determined. Lipid analyses and a comparative analysis performed with 16S rDNA sequences of similar thermophilic species showed that the strains isolated from deep-sea vents were not identical to the other species belonging to the genus Thermococcus. On the basis of the results of the phylogenetic analyses, lipid analyses, and previously reported physiological data, we believe that strains TY and TYS are significantly different from the previously described Thermococcus species. According to specific physiological and molecular features, we propose the use of these isolates as potential tools for the development of biotechnological applications in the field of starch processing and DNA technology.

Archaea↗

A cost-effectiveness analysis of anemia screening before erythropoietin in patients with end-stage renal disease.

The treatment efficacy of erythropoietin (EPO) in end-stage renal disease (ESRD) can be limited by deficiencies of iron, folate, or vitamin B12, by hyperparathyroidism, or by aluminum intoxication. Since EPO costs are significant, this study attempted to determine the cost-effectiveness of performing a panel of screening tests for anemia before starting EPO. Anemia screening was performed prospectively in 48 new-onset ESRD patients at the Ralph H. Johnson Veterans Affairs Medical Center before EPO treatment was started. Serum iron, transferrin, folate, vitamin B12, parathyroid hormone, and aluminum levels were determined, and transferrin saturation (Tfsat) was calculated at the first dialysis session. At presentation for dialysis, the mean hematocrit was 0.264 +/- 0.036 and the mean blood urea nitrogen was 32 +/- 2 mmol/L. Eighteen patients (37.5%) had a serum iron level lower than 7 micromol/L, suggesting iron deficiency. Twenty-five patients (52%) had Tfsat less than 0.20, consistent with overt iron deficiency. No patient was found to be vitamin B12 deficient, to be aluminum intoxicated, or to have significant hyperparathyroidism. One patient had folate deficiency. A cost-effectiveness analysis was performed assuming that (1) EPO would be given at an average starting dose of 6,000 U/wk at a cost of $14/2,000 U of EPO; (2) that without screening 1 month would elapse before a poor response was identified; and (3) that the failure to treat aluminum intoxication and hyperparathyroidism or to replete iron, vitamin B12, or folate deficiency would significantly impair the response to EPO. The Tfsat screen had a cost-effectiveness ratio of 0.2019, saving approximately $5.00 in EPO use for each dollar of test administration. All other screens had cost-effectiveness ratios greater than 1.0, indicating that their testing costs exceeded dollar savings in EPO use. In conclusion, iron deficiency is common in anemic patients starting dialysis, but other causes of anemia are not. It is imperative that current clinical practices be influenced by cost-effectiveness considerations. Given the cost of laboratory screens, and the relative ineffectiveness of the other screens examined here to identify factors known to impair the response to EPO, anemia screening before initiating EPO therapy should be limited to tests to identify iron deficiency.

Adult↗

Genomic organization of the mouse double minute 2 gene.

Transfection of the mouse double minute 2 (Mdm2) oncogene has been found to induce immortalization of primary cells and to transform cultured cells. Amplification and/or overexpression of human MDM2 has been documented in a large percentage of human cancers. Mouse and human Mdm2 cDNA have been cloned from transformed cells and the cDNA sequence of both genes have been reported previously. In this report, we present the gene structure of mouse Mdm2. Comparison of the coding sequences of the Mdm2 gene with the previously reported cDNA sequence and with Mdm2 sequences obtained from an Mdm2-bearing cosmid clone capable of inducing transformation revealed that the reported cDNA sequence was in error, and that Mdm2-induced transformation of cells does not require an activating mutation in Mdm2. Ligation-anchor PCR analysis of transcripts produced from the P1 and P2 promoters indicates that transcription initiates at sites upstream of those reported previously for both promoters.

Amino Acid Sequence↗

Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways.

Mutants of the Saccharomyces cerevisiae ataxia telangiectasia mutated (ATM) homolog MEC1/SAD3/ESR1 were identified that could live only if the RAD53/SAD1 checkpoint kinase was overproduced. MEC1 and a structurally related gene, TEL1, have overlapping functions in response to DNA damage and replication blocks that in mutants can be provided by overproduction of RAD53. Both MEC1 and TEL1 were found to control phosphorylation of Rad53p in response to DNA damage. These results indicate that RAD53 is a signal transducer in the DNA damage and replication checkpoint pathways and functions downstream of two members of the ATM lipid kinase family. Because several members of this pathway are conserved among eukaryotes, it is likely that a RAD53-related kinase will function downstream of the human ATM gene product and play an important role in the mammalian response to DNA damage.

Ataxia Telangiectasia Mutated Proteins↗

Trauma management therapy: a preliminary evaluation of a multicomponent behavioral treatment for chronic combat-related PTSD.

The development and initial evaluation of a new, comprehensive and multicomponent behavioral treatment (Trauma Management Therapy, or TMT) for chronic combat-related Post-Traumatic Stress Disorder (PTSD) is described. The program utilizes elements of intensive exposure therapy, programmed practice, and structured social and emotional skills training to target the multiple aspects of chronic combat-related PTSD. The treatment was found to be effective in alleviating a broad spectrum of difficulties in combat veterans with chronic PTSD, most of whom had co-occurring Axis I and/or Axis II disorders. The results are discussed with respect to the implementation of the new treatment and the general need for a comprehensive approach to treating combat-related PTSD. Implications for the potential cost-effectiveness of the treatment program also are discussed.

Adult↗

A priority queuing model to reduce waiting times in emergency care.

Investigates the increased waiting time costs imposed on society due to inappropriate use of the emergency department by patients, seeking non-emergency or primary care. Proposes a simple economic model to illustrate the effect of this misuse at a public or not-for-profit hospital. Provides evidence that non-emergency patients contribute to lengthy delays in the ER for all classes of patients. Proposes a priority queuing model to reduce average waiting times.

Appointments and Schedules↗