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Biomedical subjects

W Nelson

Publications and source records attributed to W Nelson.

At least 19 recordsLinked to original sources

Genome of Geobacter sulfurreducens: metal reduction in subsurface environments.

The complete genome sequence of Geobacter sulfurreducens, a delta-proteobacterium, reveals unsuspected capabilities, including evidence of aerobic metabolism, one-carbon and complex carbon metabolism, motility, and chemotactic behavior. These characteristics, coupled with the possession of many two-component sensors and many c-type cytochromes, reveal an ability to create alternative, redundant, electron transport networks and offer insights into the process of metal ion reduction in subsurface environments. As well as playing roles in the global cycling of metals and carbon, this organism clearly has the potential for use in bioremediation of radioactive metals and in the generation of electricity.

Acetates↗

Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis.

The complete genome sequence of Enterococcus faecalis V583, a vancomycin-resistant clinical isolate, revealed that more than a quarter of the genome consists of probable mobile or foreign DNA. One of the predicted mobile elements is a previously unknown vanB vancomycin-resistance conjugative transposon. Three plasmids were identified, including two pheromone-sensing conjugative plasmids, one encoding a previously undescribed pheromone inhibitor. The apparent propensity for the incorporation of mobile elements probably contributed to the rapid acquisition and dissemination of drug resistance in the enterococci.

Adhesins, Bacterial↗

Complete genome sequence and comparative analysis of the metabolically versatile Pseudomonas putida KT2440.

Pseudomonas putida is a metabolically versatile saprophytic soil bacterium that has been certified as a biosafety host for the cloning of foreign genes. The bacterium also has considerable potential for biotechnological applications. Sequence analysis of the 6.18 Mb genome of strain KT2440 reveals diverse transport and metabolic systems. Although there is a high level of genome conservation with the pathogenic Pseudomonad Pseudomonas aeruginosa (85% of the predicted coding regions are shared), key virulence factors including exotoxin A and type III secretion systems are absent. Analysis of the genome gives insight into the non-pathogenic nature of P. putida and points to potential new applications in agriculture, biocatalysis, bioremediation and bioplastic production.

Bacterial Proteins↗

Risk-reduction mastectomy: clinical issues and research needs.

Risk-reduction mastectomy (RRM), also known as bilateral prophylactic mastectomy, is a controversial clinical option for women who are at increased risk of breast cancer. High-risk women, including women with a strong family history of breast cancer and BRCA1/2 mutation carriers, have several clinical options: risk-reduction surgery (bilateral mastectomy and bilateral oophorectomy), surveillance (mammography, clinical breast examination, and breast self-examination), and chemoprevention (tamoxifen). We review research in a number of areas central to our understanding of RRM, including recent data on 1) the effectiveness of RRM in reducing breast cancer risk, 2) the perception of RRM among women at increased risk and health-care providers, 3) the decision-making process for follow-up care of women at high risk, and 4) satisfaction and psychological status after surgery. We suggest areas of future research to better guide high-risk women and their health-care providers in the decision-making process.

Anticarcinogenic Agents↗

Using action research in paediatric oncology to develop an oral care algorithm.

The concurrent use of an oral assessment guide and oral care algorithm proved valuable in providing a more consistent approach to the oral care of children on a particular paediatric oncology ward (Gibson et al. 1997). However, as action research was chosen to develop practice, the diagnosis of new problems was anticipated. The identification of problem areas arose from two sources-informal feedback from the practice setting and via a formal audit using a tripartite approach consisting of a structured interview, vignettes and an analysis of existing documentation. The findings firstly demonstrated that practitioners experienced problems associated with the interpretation of the information contained within the existing algorithm. Secondly, there was also strong evidence to show that the production of a second 'therapeutic' algorithm would be beneficial to patient care. Finally, to ensure clarity, minor changes were required to the oral assessment guide. By using a collaborative approach between researchers and practitioners a positive resolution to a commonly identified clinical problem was expedited.

Journal Article↗

How is the liver primed or sensitized for alcoholic liver disease?

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hidekazu Tsukamoto and Yoshiyuki Takei. The presentations were (1) Tribute to Professor Rajendar K. Chawla, by Craig J. McClain; (2) Dysregulated TNF signaling in alcoholic liver disease, by Craig J. McClain, S. Joshi-Barve, D. Hill, J Schmidt, I. Deaciuc, and S. Barve; (3) The role of mitochondria in ethanol-mediated sensitization of the liver, by Anna Colell, Carmen Garcia-Ruiz, Neil Kaplowitz, and Jose C. Fernandez-Checa; (4) A peroxisome proliferator (bezafibrate) can prevent superoxide anion release into hepatic sinusoid after acute ethanol administration, by Hirokazu Yokoyama, Yukishige Okamura, Yuji Nakamura, and Hiromasa Ishii; (5) S-adenosylmethionine affects tumor necrosis factor-alpha gene expression in macrophages, by Rajendar K. Chawla, S. Barve, S. Joshi-Barve, W. Watson, W. Nelson, and C. McClain; (6) Iron, retinoic acid and hepatic macrophage TNFalpha gene expression in ALD, by Hidekazu Tsukamoto, Min Lin, Mitsuru Ohata, and Kenta Motomura; and (7) Role of Kupffer cells and gut-derived endotoxin in alcoholic liver injury, by N. Enomoto, K. Ikejima, T. Kitamura, H. Oide, Y. Takei, M. Hirose, B. U. Bradford, C. A. Rivera, H. Kono, S. Peter, S. Yamashina, A. Konno, M. Ishikawa, H. Shimizu, N. Sato, and R. Thurman.

Animals↗

Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39.

The genome sequences of Chlamydia trachomatis mouse pneumonitis (MoPn) strain Nigg (1 069 412 nt) and Chlamydia pneumoniae strain AR39 (1 229 853 nt) were determined using a random shotgun strategy. The MoPn genome exhibited a general conservation of gene order and content with the previously sequenced C.trachomatis serovar D. Differences between C.trachomatis strains were focused on an approximately 50 kb 'plasticity zone' near the termination origins. In this region MoPn contained three copies of a novel gene encoding a >3000 amino acid toxin homologous to a predicted toxin from Escherichia coli O157:H7 but had apparently lost the tryptophan biosyntheis genes found in serovar D in this region. The C. pneumoniae AR39 chromosome was >99.9% identical to the previously sequenced C.pneumoniae CWL029 genome, however, comparative analysis identified an invertible DNA segment upstream of the uridine kinase gene which was in different orientations in the two genomes. AR39 also contained a novel 4524 nt circular single-stranded (ss)DNA bacteriophage, the first time a virus has been reported infecting C. pneumoniae. Although the chlamydial genomes were highly conserved, there were intriguing differences in key nucleotide salvage pathways: C.pneumoniae has a uridine kinase gene for dUTP production, MoPn has a uracil phosphororibosyl transferase, while C.trachomatis serovar D contains neither gene. Chromosomal comparison revealed that there had been multiple large inversion events since the species divergence of C.trachomatis and C.pneumoniae, apparently oriented around the axis of the origin of replication and the termination region. The striking synteny of the Chlamydia genomes and prevalence of tandemly duplicated genes are evidence of minimal chromosome rearrangement and foreign gene uptake, presumably owing to the ecological isolation of the obligate intracellular parasites. In the absence of genetic analysis, comparative genomics will continue to provide insight into the virulence mechanisms of these important human pathogens.

Animals↗

Ligand-dependent regulation of vascular endothelial growth factor and erythropoietin expression by a plasmid-based autoinducible GeneSwitch system.

We investigated the ability of an improved mifepristone-dependent GeneSwitch system to regulate the expression of genes for two therapeutic proteins: vascular endothelial growth factor (VEGF) and erythropoietin. The GeneSwitch system consisted of two plasmids, one encoding the chimeric GeneSwitch protein, the other an inducible transgene. When the constitutive CMV promoter of the GeneSwitch plasmid was replaced by an autoinducible promoter consisting of four copies of GAL4 DNA binding sites linked to a minimal thymidine kinase promoter, the tightness of transgene regulation was improved by an order of magnitude. Quantitative RT-PCR analysis of GeneSwitch mRNA confirmed that the autoinducible promoter was responsive to mifepristone. We demonstrated the ability of the improved GeneSwitch system to regulate the expression of VEGF or erythropoietin in a biologically relevant manner after delivery of plasmids to the hind-limb muscle of adult mice. This ability of the autoinducible GeneSwitch system to regulate the expression of therapeutic proteins in mice indicates its potential for use in human gene therapy applications.

Animals↗

Goals and strategies for teaching death and dying in medical schools.

Teaching medical students to respond to needs of the dying represents an important challenge for medical educators. This article describes the goals and objectives that should be identified before medical schools can meet this challenge, as well as strategies that, when implemented, will provide students with the necessary knowledge, skills, and attitudes to meet the needs of the dying patients. The goals and objectives were identified through a modified group consensus process developed during Choice In Dying's 5-year project "Integrating Education on Care of the Dying into Medical Schools." The authors have diverse experiences and backgrounds and are actively involved in death and dying teaching at 11 medical schools. They conclude that after accepting the goals and objectives, key medical school faculty can work cooperatively to develop strategies to integrate them into the school's curriculum. Without first establishing a set of goals and objectives and developing evaluation methods, medical schools could miss their mark in fostering the student's ability to care for the dying.

Journal Article↗

Mood states and disease activity in patients with systemic lupus erythematosus treated with bromocriptine.

We tested mood states in patients with systemic lupus erythematosus (SLE) treated with the prolactin-lowering drug, bromocriptine. Bromocriptine was given to seven patients in an open-label study to test its effects on active SLE. Two independent measures of SLE activity, the SLE Activity Measure (SLAM) and the SLE Disease Activity Index (SLEDAI), were scored and the Symptom Questionnaire (SQ) mood survey was administered at entry and at 6 monthly follow-up visits. The SLAM and SLEDAI scores improved significantly during treatment. Two of the four mood scales in the SQ (Anxiety Scale and Anger-Hostility Scale) showed significant improvement compared to the entry value at least once during treatment. Significant improvement was also observed in the Total Distress Score, which is the sum of the four scales and is a more sensitive measure of distress than the score of an individual scale. Depression, anxiety, somatic complaints, and total distress correlated positively with SLAM and/or SLEDAI scores. The Anxiety Scale and the Total Distress Score improved with treatment and did correlate positively with SLE activity. In contrast, the Anger-Hostility Scale improved with treatment but did not correlate with SLE activity.

Affect↗

Evaluation of conflict of interest in economic analyses of new drugs used in oncology.

CONTEXT: Recent studies have found that when investigators have financial relationships with pharmaceutical or product manufacturers, they are less likely to criticize the safety or efficacy of these agents. The effects of health economics research on pharmaceutical company revenue make drug investigations potentially vulnerable to this bias. OBJECTIVE: To determine whether there is an association between pharmaceutical industry sponsorship and economic assessment of oncology drugs. DESIGN: MEDLINE and HealthSTAR databases (1988-1998) were searched for original English-language research articles of cost or cost-effectiveness analyses of 6 oncology drugs in 3 new drug categories (hematopoietic colony-stimulating factors, serotonin antagonist antiemetics, and taxanes), yielding 44 eligible articles. Two investigators independently abstracted each article based on specific criteria. MAIN OUTCOME MEASURE: Relationships between funding source and (1) qualitative cost assessment (favorable, neutral, or unfavorable) and (2) qualitative conclusions that overstated quantitative results. RESULTS: Pharmaceutical company-sponsored studies were less likely than nonprofit-sponsored studies to report unfavorable qualitative conclusions (1/20 [5%] vs 9/24 [38%]; P = .04), whereas overstatements of quantitative results were not significantly different in pharmaceutical company-sponsored (6/20 [30%]) vs nonprofit-sponsored (3/24 [13%]) studies (P = .26). CONCLUSIONS: Although we did not identify bias in individual studies, these findings indicate that pharmaceutical company sponsorship of economic analyses is associated with reduced likelihood of reporting unfavorable results.

Biomedical Research↗

Complete nucleotide sequence analysis of a Western Pacific dengue-1 virus strain.

We have determined the complete nucleotide sequence and the deduced amino acid polypeptide sequence of the genome of a dengue-1 (DEN-1) virus strain isolated from a patient on Nauru in the Western Pacific in 1974 (West Pac 74). The complete genome is 10,735 nucleotides in length and contains a single long open reading frame of 10,176 nucleotides encoding a polyprotein of 3392 amino acids. When compared to DEN-1 Singapore S275/90, the nucleotide and amino acid sequence homology are 94% and 97.8%, respectively.

Amino Acid Sequence↗

A method to compare two samples of recurrence data.

This paper presents a nonparametric comparison of two samples of units subject to recurrent events. The method is illustrated with applications to the repair of locomotive braking grids and to recurrent bladder tumors in patients.

Data Interpretation, Statistical↗

Incorporating palliative care into primary care education. National Consensus Conference on Medical Education for Care Near the End of Life.

The confluence of enhanced attention to primary care and palliative care education presents educators with an opportunity to improve both (as well as patient care) through integrated teaching. Improvements in palliative care education will have benefits for dying patients and their families, but will also extend to the care of many other primary care patients, including geriatric patients and those with chronic illnesses, who make up a large proportion of the adult primary care population. In addition, caring for the dying, and teaching others to carry out this task, can be an important vehicle for personal and professional growth and development for both students and their teachers.

Curriculum↗

Rapid pathogen detection using a microchip PCR array instrument.

An array of PCR microchips for rapid, parallel testing of samples for pathogenic microbes is described. The instrument, called the Advanced Nucleic Acid Analyzer (ANAA), utilizes 10 silicon reaction chambers with thin-film resistive heaters and solid-state optics. Features of the system include efficient heating and real-time monitoring, low power requirements for battery operation, and no moving parts for reliability and ruggedness. We analyzed cultures of Erwinia herbicola vegetative cells, Bacillus subtilis spores, and MS2 virions, which simulated pathogenic microbes such as Yersinia pestis, Bacillus anthracis spores, and Venezuelan equine encephalitis, respectively. Detection of microbes was achieved in as little as 16 min with detection limits of 10(5)-10(7) organisms/L (10(2)-10(4) organisms/mL).

Bacillus subtilis↗

Outbreak of Salmonella infantis infection in a large animal veterinary teaching hospital.

During the past 11 years, there have been numerous reports of outbreaks of salmonellosis involving horses in veterinary teaching hospitals. Some of these outbreaks have been associated with Salmonella serotypes not commonly associated with infection of horses. Salmonella infantis is among the more common Salmonella serotypes isolated from human beings, and is an important pathogen in the broiler chicken industry. However, it was not commonly isolated from horses or cattle on a national basis between 1993 and 1995. In this report, we describe an outbreak of S infantis infection among large animals, primarily horses, in a veterinary teaching hospital and the control measures that were implemented. Factors that appeared to be key in control of this outbreak in this hospital included providing biosecurity training sessions for hospital personnel, adopting a standard operating procedure manual for biosecurity procedures, installing additional handwashing sinks throughout the facility, painting the interior of the facility with a nontoxic readily cleanable paint, replacing the dirt flooring in 4 stalls with concrete flooring, and removing noncleanable surfaces such as rubber stall mats, wooden hay storage bins, and open grain bins. Our experience with this outbreak suggests that although it is virtually impossible to eliminate Salmonella organisms from the environment, minimizing contamination is possible. Prevention of nosocomial infection must be approached in a multifaceted manner and care must be taken to search out covert sources of contamination, especially if standard intervention procedures do not prevent spread of the disease.

Animals↗