Biomedical subjects
Publications and source records attributed to David Farrell.
Recent outbreaks of human tuberculosis in the United States caused by Mycobacterium bovis have implicated cheese originating in Mexico as a source of these infections. A total of 203 samples of cheese originating in Mexico were cultured, and M. bovis was recovered from one specimen. Therefore, M. bovis can be recovered from cheese and may be a source of human infections.
Treatment of N-methyl substituted aminocryptand hosts with copper(II) generates monocopper(II) cryptates where copper(II) coordinates an oxygen-centered species, formally H3O+, which is also strongly hydrogen bonded to three aminocryptand N-methyl atoms via bonds which may best be viewed as NH(delta+)...O(delta-) in consequence of charge transfer. The strength of this hydrogen bonding precludes successful competition of another copper ion for the second coordination site thus suppressing formation of any Cu-Cu bonded average-valent system.
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Antibiotic combinations are used to enhance antibacterial efficacy and to prevent the development of resistance. We have tested a possible synergistic effect of several antibacterial combinations on Bacillus anthracis. The in vitro activities of antibiotic combinations against two strains of B. anthracis, strain Sterne and the Russian anthrax vaccine strain STi, were tested by the fractional inhibitory concentration (FIC) method, derived from the MICs of the agents in combination, and by measuring the rate of bacterial killing over time by several antibiotic combinations. The FIC results showed that synergism against both B. anthracis strains was observed only with the combination of rifampin and clindamycin. The telithromycin-amoxicillin combination showed synergism against strain Sterne only. All other combinations were either indifferent or antagonistic. The results of the bacterial time-kill study demonstrated indifferent effects for all combinations. These in vitro results demonstrate the difficulties in obtaining synergistic combinations of antibiotics against B. anthracis.
OBJECTIVES: To identify and characterize the mechanisms of high-level fluoroquinolone resistance in two strains of Bacillus anthracis following serial passage in increasing concentrations of fluoroquinolones. METHODS: Fluoroquinolone-resistant isolates of the Sterne and Russian Anthrax Vaccine STi strains were obtained following serial passage in the presence of increasing concentrations of four different fluoroquinolones. The quinolone-resistance-determining regions of the type II topoisomerase genes from the resistant strains were amplified by PCR and characterized by DNA sequence analysis. The MICs in the presence and absence of reserpine were determined using broth microdilution as a means of detecting active efflux. RESULTS: Single and double amino acid substitutions in the GyrA (Ser-85-Leu; Glu-89-Arg/Gly/Lys) and GrlA (Ser-81-Tyr; Val-96-Ala; Asn-70-Lys) were most common. A single amino acid substitution in GyrB (Asp-430-Asn) was also identified. Efflux only applied to isolates selected for by either levofloxacin or ofloxacin. CONCLUSIONS: Specific amino acid substitutions in the type II topoisomerase enzymes significantly contributed to the development of high-level fluoroquinolone resistance in B. anthracis. However, notable differences between the strains and the drugs tested were identified including the role of efflux and the numbers and types of mutations identified.
The WATCH (Wellness for African Americans Through Churches) Project was a randomized trial comparing the effectiveness of 2 strategies to promote colorectal cancer preventive behaviors among 587 African American members of 12 rural North Carolina churches. Using a 2 X 2 factorial research design, the authors compared a tailored print and video (TPV) intervention, consisting of 4 individually tailored newsletters and targeted videotapes, with a lay health advisor (LHA) intervention. Results showed that the TPV intervention significantly improved (p <.05) fruit and vegetable consumption (0.6 servings) and recreational physical activity (2.5 metabolic task equivalents per hour) and, among those 50 and older (n = 287), achieved a 15% increase in fecal occult blood testing screening (p =.08). The LHA intervention did not prove effective, possibly because of suboptimal reach and diffusion.
Screening of newly synthesized organic peroxides for tumor initiating/promoting activity would be greatly facilitated if predictive methodologies could be developed using topical exposures shorter than those required for definitive tumor assessment in mouse skin models. Nine organic peroxides [benzoyl peroxide (BZP), di-t-butyl peroxide (DTBP), t-butyl peroxybenzoate (TBPB), p-t-butyl isopropylbenzene hydroperoxide (TBIBHP), cumene hydroperoxide (CHP), dicetyl peroxydicarbonate (DPD), dicumyl peroxide (DCP), methyl ethyl ketone peroxide (MEKP) and O,O-t-butyl-O-(2-ethylhexyl) monoperoxycarbonate (TBEC)] were evaluated for their ability to increase biomarkers of tumor promotion in mouse skin, i.e. sustained epidermal hyperplasia, dermal inflammation and oxidative DNA damage. Evaluations were performed using SENCAR mice exposed topically for 4 weeks. The organic peroxides varied in their effects on these biomarkers. BZP, TBPB and TBIBHP exhibited significant increases in all three biomarkers associated with tumor promoting activity, CHP produced increases only in sustained epidermal hyperplasia and dermal inflammation, MEKP and DCP produced increases only in sustained epidermal hyperplasia and TBEC produced an increase only in dermal inflammation. DTBP and DPD had no effect on the three parameters studied. TBPB and TBIBHP were selected for further examination of their ability to produce mutations in codons 12, 13 and 61 of the c-Ha-ras protooncogene, i.e. those mutations known to be involved in the initiation of mouse skin tumors, because they were the only peroxides to exhibit significant positive results in all assays except the Ha-ras mutation following 4 weeks of exposure. Evaluations were performed using SENCAR mice dosed topically for 8 or 12 weeks in a complete carcinogenesis protocol or 16 weeks in an initiation/promotion protocol using 7,12-dimethylbenz[a]anthracene, urethane, benzo[a]pyrene and N-methyl-N'-nitro-N-nitrosoguanidine as positive controls. Neither TBPB nor TBIBHP produced detectable mutations in the c-Ha-ras protooncogene, indicating that they are not likely to possess tumor initiating or complete carcinogenic activity.
The virulence plasmid pJM1 enables the fish pathogen Vibrio anguillarum, a gram-negative polarly flagellated comma-shaped rod bacterium, to cause a highly fatal hemorrhagic septicemic disease in salmonids and other fishes, leading to epizootics throughout the world. The pJM1 plasmid 65,009-nucleotide sequence, with an overall G+C content of 42.6%, revealed genes and open reading frames (ORFs) encoding iron transporters, nonribosomal peptide enzymes, and other proteins essential for the biosynthesis of the siderophore anguibactin. Of the 59 ORFs, approximately 32% were related to iron metabolic functions. The plasmid pJM1 confers on V. anguillarum the ability to take up ferric iron as a complex with anguibactin from a medium in which iron is chelated by transferrin, ethylenediamine-di(o-hydroxyphenyl-acetic acid), or other iron-chelating compounds. The fatDCBA-angRT operon as well as other downstream biosynthetic genes is bracketed by the homologous ISV-A1 and ISV-A2 insertion sequences. Other clusters on the plasmid also show an insertion element-flanked organization, including ORFs homologous to genes involved in the biosynthesis of 2,3-dihydroxybenzoic acid. Homologues of replication and partition genes are also identified on pJM1 adjacent to this region. ORFs with no known function represent approximately 30% of the pJM1 sequence. The insertion sequence elements in the composite transposon-like structures, corroborated by the G+C content of the pJM1 sequence, suggest a modular composition of plasmid pJM1, biased towards acquisition of modules containing genes related to iron metabolic functions. We also show that there is considerable microheterogeneity in pJM1-like plasmids from virulent strains of V. anguillarum isolated from different geographical sources.
BACKGROUND: Associations between optimal use of a tailored decision-aid and levels of accuracy of perceived breast cancer risk, confidence in decision-making, and satisfaction with decisions about HRT were evaluated in a randomized intervention trial with a community sample of women aged 45-54. METHODS: Data are from 289 women randomized to receive a computer-tailored three-step decision-aid. RESULTS: Forty-seven percent of participants reported optimal use of the intervention materials. African American women and those with low confidence in decision-making were less likely to use the intervention optimally than white women and those with higher confidence (P<0.05). Optimal use of the decision-aid was associated with increased accuracy of perceived risk and confidence to make a decision. DISCUSSION: When used optimally, self-directed decision-aids can improve women's ability to make decisions about HRT. Additional refinement of these aids is needed. For some subgroups of women, adjuncts such as telephone counseling also might be considered.
OBJECTIVE: This article describes the development and randomized evaluation of a tailored nutrition education CD-ROM program for participants in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) in North Carolina. DESIGN: After randomization to intervention or control groups, participants completed a baseline survey and were resurveyed immediately after program use and 1 to 2 months postintervention. SETTING: Two WIC clinics in central North Carolina. PARTICIPANTS: A total of 307 respondents to the follow-up survey (response rate 74.8%) comprised the study sample. Participants were female (96%), 20% were pregnant, and 50% were minorities (African American and other). INTERVENTION: The interactive CD-ROM consisted of a targeted video soap opera, dietary assessment, and individually tailored dietary feedback and strategies for change. MAIN OUTCOME MEASURES: Measures included total fat and fruit and vegetable intake, knowledge of low-fat and infant feeding choices, self-efficacy, and stages of change. ANALYSIS: Descriptive statistics assessed baseline comparability of study groups; analysis of covariance and F tests were used to assess program effects at follow-up. RESULTS: INTERVENTION group members increased self-efficacy (P <.01) and scored significantly higher (P <.05) on both low-fat and infant feeding knowledge compared with controls. No differential effect was observed for dietary intake variables. CONCLUSIONS AND IMPLICATIONS: The findings suggest that one dose of an interactive CD-ROM program can impact mediators of dietary change but may be insufficient to change behavior.