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Biomedical subjects

B A Brown

Publications and source records attributed to B A Brown.

At least 37 records · Page 2Linked to original sources
PubMed2001

Lack of transmission of mycobacterium abscessus among patients with cystic fibrosis attending a single clinic.

We retrospectively analyzed 1062 respiratory specimens from 214 patients with cystic fibrosis, of whom 5 patients had 36 cultures positive for M. abscessus. Results of molecular typing demonstrated that each of these 5 patients carried a single unique strain (genotype), which suggests that it may not be necessary to segregate patients with CF who are colonized or infected with M. abscessus from those who are not.

Bacterial Typing Techniques↗
PubMed2001

MRI artifact masquerading as orbital disease.

OBJECTIVES: To describe the diagnostic challenge associated with magnetic resonance imaging (MRI) artifact and to describe methods of minimizing this artifact. METHODS: Gadolinium enhancement was demonstrated to be artifact by using an inversion recovery pulse sequence technique. RESULTS: A patient with complaints of painless loss of vision also had radiologic abnormalities that led to subsequent referral to a tertiary care facility. Increased signals on the fat-suppressed contrast enhanced MRI was demonstrated to be artifact by using an inversion recovery technique which produced a normal MRI of the orbit. CONCLUSIONS: Clinical confusion leading to unnecessary and costly evaluation may be avoided if one considers the possibility of artifact when reviewing magnetic resonance studies. When magnetic susceptibility is suspected, the use of an inversion recovery sequence can better delineate the true nature of the abnormality.

Adult↗
PubMed2001

Effective steroid-sparing treatment for peripheral ulcerative keratitis and pyoderma gangrenosum.

OBJECTIVE: To report a patient with a rare clinical presentation of marginal keratitis and pyoderma gangrenosum (PG) that responded to the steroid-sparing agent azathioprine. DESIGN: Interventional case report. METHODS: Case report and MEDLINE review of the medical literature on PG-associated peripheral ulcerative keratitis (PUK) and its treatment. RESULTS: A patient with a biopsy-proven history of PG developed an explosive episode of PUK. The ocular inflammation was minimally responsive to topical therapy and required significant long-term oral steroids for control. The patient's active skin lesions and marginal keratitis responded dramatically to systemic oral azathioprine. Since the initiation of treatment with azathioprine, there have been no subsequent recurrences of PG or marginal keratitis. CONCLUSIONS: PUK may be associated with other inflammatory conditions, such as PG and arthritis. Systemic azathioprine may successfully control ocular and extraocular conditions and should be considered in the clinical setting of topical therapy failure and/or extraocular inflammatory conditions.

Administration, Oral↗
PubMed2001

North Carolina law.

Explore the source record for details and available documents.

Child, Preschool↗
PubMed2001

The left-handed double helical nucleic acids.

The conversion of right-handed dsDNA and dsRNA to the left-handed Z-conformation involves a reorganization of the nucleotides relative to each other. This conversion can be facilitated by the tight binding of a Z-conformation-specific protein domain from the editing enzyme dsRNA adenosine deaminase. This may influence the modification of both pre-mRNAs as well as some replicating RNA viruses.

Adenosine Deaminase↗
PubMed2000

Neutron radii in nuclei and the neutron equation of state.

The root-mean-square radius for neutrons in nuclei is investigated in the Skyrme Hartree-Fock model. The main source of theoretical variation comes from the exchange part of the density-dependent interaction which can be related to a basic property of the neutron equation of state. A precise measurement of the neutron radius in 208Pb would place an important new constraint on the equation of state for neutron matter. The Friedman-Pandharipande neutron equation of state would lead to a very precise value of 0.16+/-0.02 fm for the difference between the neutron and the proton root-mean-square radius in 208Pb.

Journal Article↗
PubMed2000

Double-octupole states in 208Pb.

The states of 208Pb are calculated in a 24 orbit model space which includes all excitations up to two particles and two holes beyond the closed shell. All of the known low-lying states are reproduced by this model. The observed distributions of electromagnetic excitation strength from the ground state to low-lying excited states are well described by the model. The double-octupole excitation strength is calculated and found to be concentrated in 0+, 2+, and 4+ states around 5.2 MeV, but it is fragmented over many 6+ states, in agreement with recent experiments.

Journal Article↗
PubMed2000

The zalpha domain of the editing enzyme dsRNA adenosine deaminase binds left-handed Z-RNA as well as Z-DNA.

The Zalpha domain of human double-stranded RNA adenosine deaminase 1 binds specifically to left-handed Z-DNA and stabilizes the Z-conformation. Here we report spectroscopic and analytical results that demonstrate that Zalpha can also stabilize the left-handed Z-conformation in double-stranded RNA. Zalpha induces a slow transition from the right-handed A-conformation to the Z-form in duplex r(CG)(6), with an activation energy of 38 kcal mol(-1). We conclude that Z-RNA as well as Z-DNA can be accommodated in the tailored binding site of Zalpha. The specific binding of Z-RNA by Zalpha may be involved in targeting double-stranded RNA adenosine deaminase 1 for a role in hypermutation of RNA viruses.

Adenosine Deaminase↗
PubMed2000

Serotype-specific identification of enterovirus 71 by PCR.

BACKGROUND: Enterovirus 71 and coxsackievirus A16 are closely related genetically and are causative agents of hand foot and mouth disease. Because enterovirus 71 is more often associated with severe neurological disease, there is a need to rapidly discriminate between enterovirus 71 and coxsackievirus A16 during hand, foot, and mouth disease outbreaks. OBJECTIVES: Our goal was to develop and evaluate a serotype-specific reverse transcription-polymerase chain reaction (RT/PCR)-based typing method for enterovirus 71. STUDY DESIGN: Two sets of PCR primers were designed to match conserved amino acid intervals of enterovirus 71. One diagnostic primer pair contains deoxyinosine at sites of 4-fold codon degeneracy. A second primer pair was designed for use in sequencing and molecular epidemiology studies. Primer pairs were tested on strains encountered in routine diagnostic samples. RESULTS: Using both sets of primers on a panel of 61 prototype enteroviral strains, both primer pairs gave strong positive signals for only enterovirus 71. These primers amplified all enterovirus 71 isolates tested and discriminated between enterovirus 71 and the most closely related enterovirus, coxsackievirus A16. CONCLUSIONS: Our RT-PCR assay can be used for specific identification of enterovirus 71 clinical isolates. Furthermore, the 484-bp product of one primer pair has proven useful in sequencing studies to identify distinct genotypes of enterovirus 71.

Amino Acid Sequence↗
PubMed2000

Early results (at 6 months) with intermittent clarithromycin-including regimens for lung disease due to Mycobacterium avium complex.

We initiated a prospective noncomparative trial of treatment for lung disease due to Mycobacterium avium complex (MAC) in human immunodeficiency virus-negative patients, with a regimen of clarithromycin (1000 mg), rifabutin (300-600 mg), and ethambutol (25 mg/kg) administered 3 times per week. Fifty-nine patients were enrolled. Twelve (20%) were lost to follow-up, and 6 (10%) developed clarithromycin intolerance. The remaining 41 patients (69%) completed the initial 6 months of therapy. The sputum of 32 of these patients (78%) converted to negative. When results were compared with the sputum response rates at 6 months in previous studies with a regimen including daily clarithromycin and regimens including intermittent (3 times per week) azithromycin with the same companion drugs, no differences in treatment responses were evident. Adverse reactions related to rifabutin were a major problem, and for 24 (41%) of 59 patients the dosage was decreased or the drug was withdrawn. Intermittent (3 times per week) administration of clarithromycin appears to be as effective as daily administration in effecting sputum conversion in pulmonary MAC disease.

Adult↗
PubMed2000

Multisite reproducibility of Etest for susceptibility testing of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum.

A multicenter study was conducted to assess the inter- and intralaboratory reproducibility of the Etest for susceptibility testing of the rapidly growing mycobacteria. The accuracy also was evaluated by comparing Etest results to those obtained by broth microdilution. Ten isolates (four of the Mycobacterium fortuitum group, three of Mycobacterium abscessus, and three of Mycobacterium chelonae) were tested against amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem, and trimethoprim-sulfamethoxazole in each of four laboratories. At each site, isolates were tested three times on each of three separate days (nine testing events per isolate) using common lots of media and Etest strips. Interlaboratory agreement among MICs (i.e., mode +/- 1 twofold dilution) varied for the different drug-isolate combinations and overall was best for trimethoprim-sulfamethoxazole (75% for one isolate and 100% for all others), followed by doxycycline and ciprofloxacin. Interlaboratory agreement based on interpretive category also varied and overall was best for doxycycline (100% for all isolates), followed by trimethoprim-sulfamethoxazole and ciprofloxacin. Interlaboratory reproducibility among MICs was most variable for imipenem, and agreement by interpretive category was lowest for imipenem and amikacin. Modal Etest MICs agreed with those by broth microdilution only for doxycycline and the sulfonamides. For all other drugs, the modal MICs by the two methods differed by more than +/- 1 twofold dilution for one or more isolates. In all cases, the Etest MIC was higher and would have caused reports of false resistance. In summary, the Etest in this evaluation did not perform as well as broth microdilution for susceptibility testing of the rapidly growing mycobacteria. It was problematic for most species and drugs, primarily because of a trailing endpoint and/or high MICs compared to broth. Its use will necessitate further investigation, including determination of the optimal medium and incubation conditions and clarification of endpoint interpretation.

Anti-Bacterial Agents↗
PubMed2000

Challenges of recruitment: focus groups with research study recruiters.

To rectify the historic lack of research on women's health and the exclusion of women from many significant clinical trials, regulations have been promulgated requiring the inclusion of women and minorities in research studies. Acknowledging that the National Institutes of Health (NIH) mandate has resulted in more inclusive research, the unintended consequences associated with implementation of these regulations must also be explored. While the requirements preclude the use of cost as a reason for excluding women and/or minorities, the additional funding necessary to recruit adequate numbers of study participants has not been provided. Consequently, study recruiters often face unacknowledged expectations and job pressures as they attempt to meet recruitment goals. While it is important to support the NIH mandate, the additional stress imposed upon research study recruiters must also be recognized. Focus groups with study recruiters from various backgrounds and types of research provide an understanding of the challenges recruiters face when attempting to recruit diverse populations of women into research, and provide an understanding of the impact of recruitment goals on study recruiters' job satisfaction.

Academic Medical Centers↗
PubMed2000

Disease attributed to Mycobacterium chelonae in South African clawed frogs (Xenopus laevis).

The fast-growing nontuberculous mycobacterial species Mycobacterium chelonae was isolated from six captive South African clawed frogs (Xenopus laevis) with chronic weight loss and nonhealing ulcerative skin lesions. Three of the M. chelonae isolates were evaluated to confirm the species identification using polymerase chain reaction restriction analysis. Disease associated with M. chelonae is reported mainly in people and in fish. To our knowledge, this is the first report of disease associated with M. chelonae in a colony of captive Xenopus sp.

Animals↗
PubMed1999

Proteolytic dissection of Zab, the Z-DNA-binding domain of human ADAR1.

Zalpha is a peptide motif that binds to Z-DNA with high affinity. This motif binds to alternating dC-dG sequences stabilized in the Z-conformation by means of bromination or supercoiling, but not to B-DNA. Zalpha is part of the N-terminal region of double-stranded RNA adenosine deaminase (ADAR1), a candidate enzyme for nuclear pre-mRNA editing in mammals. Zalpha is conserved in ADAR1 from many species; in each case, there is a second similar motif, Zbeta, separated from Zalpha by a more divergent linker. To investigate the structure-function relationship of Zalpha, its domain structure was studied by limited proteolysis. Proteolytic profiles indicated that Zalpha is part of a domain, Zab, of 229 amino acids (residues 133-361 in human ADAR1). This domain contains both Zalpha and Zbeta as well as a tandem repeat of a 49-amino acid linker module. Prolonged proteolysis revealed a minimal core domain of 77 amino acids (positions 133-209), containing only Zalpha, which is sufficient to bind left-handed Z-DNA; however, the substrate binding is strikingly different from that of Zab. The second motif, Zbeta, retains its structural integrity only in the context of Zab and does not bind Z-DNA as a separate entity. These results suggest that Zalpha and Zbeta act as a single bipartite domain. In the presence of substrate DNA, Zab becomes more resistant to proteases, suggesting that it adopts a more rigid structure when bound to its substrate, possibly with conformational changes in parts of the protein.

Adenosine Deaminase↗
PubMed1999

Folding of pyrimidine-enriched RNA fragments from the vicinity of the internal ribosomal entry site of hepatitis A virus.

Two RNA fragments from the region just upstream of the internal ribosome entry site of Hepatitis A virus (HAV) were studied, a 35mer (HAV-35), 5'U4C3U3C3U4C3U3C2UAU2C3U33(4), and a 23mer (HAV-23), 5(4)U4C3U3C3U4C3U33(4). Secondary structural predictions and nuclease digestion patterns obtained with genomic RNAs suggested that they link two stable Watson-Crick (WC) hairpins in the genomic RNA and do not form conventional WC secondary structure, but do fold to form a condensed, stacked 'domain'. To obtain more information, folding of HAV-23 and -35 RNA fragments was characterized using 1H nuclear magnetic resonance, in H2O as a function of pH and temperature, circular dichroism as a function of NaCl concentration, pH and temperature, and square-wave voltammetry as a function of pH. The results indicate that these oligo-nucleotides form intramolecular structures that contain transient U*U base pairs at pH 7 and moderate ionic strength (100 mM NaCl). This folded structure becomes destabilized and loses the U*U base pairs above and below neutral pH, especially at ionic strengths above 0.1. All of the cytidine protons exchange relatively rapidly with solvent protons (exchange lifetimes shorter than 1 ms), so the structure contains few if any C*CH+base pairs at neutral pH, but can apparently form them at pH values below 6. We present a series of possible models in which chain folding draws the strand termini closer together, possibly serving to pull the attached WC hairpin domains together and providing a functional advantage by nucleating reversible formation of a more viable RNA substrate.

Base Pairing↗
PubMed1999

Mycobacterium wolinskyi sp. nov. and Mycobacterium goodii sp. nov., two new rapidly growing species related to Mycobacterium smegmatis and associated with human wound infections: a cooperative study from the International Working Group on Mycobacterial Taxonomy.

Previous investigations demonstrated three taxonomic groups among 22 clinical isolates of Mycobacterium smegmatis. These studies were expanded to 71 clinical isolates, of which 35 (49%) (group 1) were identical to five ATCC reference strains including the type strain ATCC 19420T. Twenty-eight isolates (39%) were group 2, and eight isolates (11%) were group 3. Isolates of groups 2 and 3 were most often associated with post-traumatic or post-surgical wound infections including osteomyelitis, were susceptible to sulfamethoxazole, amikacin, imipenem and the tetracyclines, variably resistant to clarithromycin, and susceptible (group 1), intermediately resistant (group 2) or resistant (group 3) to tobramycin. The three groups were similar by routine biochemical and growth characteristics, but had different mycolic acid dimethoxy-4-coumarinylmethyl ester elution patterns by HPLC and different PCR-restriction enzyme patterns of a 439 bp fragment of the hsp-65 gene. Group 3 isolates differed from group 1 by 18 bp by 16S rRNA sequencing and exhibited < 25% homology by DNA-DNA hybridization, being most closely related to Mycobacterium mageritense. The 16S rRNA of group 1 and group 2 isolates differed by only 3 bp, but by DNA-DNA hybridization they exhibited only 40% homology. The following names are proposed: Mycobacterium goodii sp. nov. for group 2 isolates (type strain ATCC 700504T = MO69T), Mycobacterium wolinskyi sp. nov. for group 3 isolates (type strain ATCC 700010T = MO739T) and Mycobacterium smegmatis sensu stricto for group 1 isolates.

Adolescent↗
PubMed1999

Typing of human enteroviruses by partial sequencing of VP1.

Human enteroviruses (family Picornaviridae) are the major cause of aseptic meningitis and also cause a wide range of other acute illnesses, including neonatal sepsis-like disease, acute flaccid paralysis, and acute hemorrhagic conjunctivitis. The neutralization assay is usually used for enterovirus typing, but it is labor-intensive and time-consuming and standardized antisera are in limited supply. We have developed a molecular typing system based on reverse transcription-PCR and nucleotide sequencing of the 3' half of the genomic region encoding VP1. The standard PCR primers amplify approximately 450 bp of VP1 for most known human enterovirus serotypes. The serotype of an "unknown" may be inferred by comparison of the partial VP1 sequence to those in a database containing VP1 sequences for the prototype strains of all 66 human enterovirus serotypes. Fifty-one clinical isolates of known serotypes from the years 1991 to 1998 were amplified and sequenced, and the antigenic and molecular typing results agreed for all isolates. With one exception, the nucleotide sequences of homologous strains were at least 75% identical to one another (>88% amino acid identity). Strains with homologous serotypes were easily discriminated from those with heterologous serotypes by using these criteria for identification. This method can greatly reduce the time required to type an enterovirus isolate and can be used to type isolates that are difficult or impossible to type with standard immunological reagents. The technique may also be useful for the rapid determination of whether viruses isolated during an outbreak are epidemiologically related.

5' Untranslated Regions↗