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Biomedical subjects

W Johnson

Publications and source records attributed to W Johnson.

At least 55 records · Page 3Linked to original sources

The 6-min walk and peak oxygen consumption in advanced heart failure: aerobic capacity and survival.

BACKGROUND: This study sought to determine to what extent the 6-min walk (6MW) distance in advanced heart failure predicts aerobic capacity and provides comparable information regarding survival. Peak oxygen uptake ( VO(2)) and the 6MW both describe function and predict outcome over a wide range of heart failure, but their determinants and implications may differ within a narrower clinical spectrum. This study compared 6MW with aerobic capacity both at peak exercise and during low-level cycling. METHODS AND RESULTS: Both the 6MW and symptom-limited cycle ergometry were performed by 307 patients of whom 264 patients additionally performed 6 min of 20-W cycling to estimate aerobic capacity during sustained low-level activity. In the first 198 patients, multivariate analysis of survival was performed with the 6MW and peak VO (2). Patients achieved the 6MW of 393 +/- 104 m and peak VO (2) of 14 +/- 5 mL/kg per minute. Although low peak VO (2) was more likely with the shorter 6MW, the relation was weak within peak VO (2) range of 10 to 20 mL/kg per minute (n = 213, 69% of patients, r = 0.28). During 20-W exercise, VO (2) was 9.2 +/- 2.0 mL/kg per minute, with respiratory exchange ratio poorly correlated with the 6MW. In contrast to peak VO (2), the 6MW in meters did not predict survival. Division into short, medium, and long walks, however, supplemented simple clinical description. CONCLUSIONS: Although helpful in broader populations for identification of patients with obvious clinical compromise, the 6MW distance is not a surrogate for peak VO (2) in assessing aerobic capacity or prognosis for individuals with advanced heart failure.

Exercise Test↗

Effect of intensive therapy for heart failure on the vasodilator response to exercise.

OBJECTIVES: The purpose of the study was to evaluate the lower extremity vascular responsiveness to metabolic stimuli in patients with heart failure and to determine whether these responses improve acutely after intensive medical therapy. BACKGROUND: Metabolic regulation of vascular tone is an important determinant of blood flow, and may be abnormal in heart failure. METHODS: The leg blood flow responses were measured in 11 patients with nonedematous class III-IV heart failure before and after inpatient medical therapy and in 10 normal subjects. Venous occlusion plethysmography was used to measure peak blood flow and total hyperemia in the calf after arterial occlusion and also after isotonic ankle exercise. Measurements were repeated following short-term inpatient treatment with vasodilators and diuretics administered to decrease right atrial pressure (18+/-2 to 7+/-1 mm Hg), pulmonary wedge pressure (32+/-3 to 15+/-2 mm Hg), and systemic vascular resistance (1581+/-200 to 938+/-63 dynes.s.cm(-5), all p < 0.02). RESULTS: Leg blood flow at rest, after exercise, and during reactive hyperemia was less in heart failure patients than in control subjects. Resting leg blood flow did not increase significantly after medical therapy, but peak flow after the high level of exercise increased by 59% (p = 0.009). Total hyperemic volume in the recovery period increased by 73% (p = 0.03). Similarly, the peak leg blood flow response to ischemia increased by 88% (p = 0.04), whereas hyperemic volume rose by 98% (p = 0.1). CONCLUSIONS: The calf blood flow responses to metabolic stimuli are blunted in patients with severe heart failure, and improve rapidly with intensive medical therapy.

Blood Flow Velocity↗

Genetic characterization of antimicrobial resistance in Canadian isolates of Salmonella serovar Typhimurium DT104.

PCR was used to identify antibiotic resistance determinants in 31 Canadian Salmonella serovar Typhimurium DT104 isolates. Genes encoding resistance to ampicillin (pse1 or blaP1), chloramphenicol (pasppflo-like), streptomycin-spectinomycin (aadA2), sulfonamide (sulI), and tetracycline [tet(G)] were mapped to a 13-kb region of DNA of one isolate. Two copies of sulI were identified and mapped to the 3' end of either pse1 or aadA2 integrons. The two integrons were separated by the pasppflo-like gene and the tet(G) gene. The kanamycin resistance determinant (aphA-1) was present on a 2.0-MDa plasmid (five isolates) or on the chromosome (three isolates).

Canada↗

Virulence of Mycobacterium tuberculosis CDC1551 and H37Rv in rabbits evaluated by Lurie's pulmonary tubercle count method.

The virulence of the CDC1551 strain of Mycobacterium tuberculosis was compared to that of H37Rv in a rabbit inhalation model. While rabbits that inhaled the two strains produced equal numbers of grossly visible primary tubercles, CDC1551 tubercles were smaller and contained fewer bacilli than H37Rv tubercles. These findings suggest that a miniepidemic near the Kentucky-Tennessee border caused by CDC1551 was due not to increased virulence but to increased transmissibility.

Animals↗

Analysis of Legionella pneumophila serogroup 1 isolates by pulsed-field gel electrophoresis.

At a hospital in Halifax, Nova Scotia, Canada, three strains of Legionella pneumophila were detectable based on plasmid content, while the isolates collected at another hospital in Halifax had no plasmids. Genomic DNA was digested with BssHII, SalI, and SpeI and subjected to pulsed-field gel electrophoresis (PFGE). We found no relationship between plasmid profile and PFGE pattern.

Bacterial Typing Techniques↗

Bovine colostrum is a health food supplement which prevents NSAID induced gut damage.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for arthritis but cause gastrointestinal injury. Bovine colostrum is a rich source of growth factors and is marketed as a health food supplement. AIMS: To examine whether spray dried, defatted colostrum or milk preparations could reduce gastrointestinal injury caused by indomethacin. METHODS: Effects of test solutions, administered orally, were examined using an indomethacin restraint rat model of gastric damage and an indomethacin mouse model of small intestinal injury. Effects on migration of the human colonic carcinoma cell line HT-29 and rat small intestinal cell line RIE-1 were assessed using a wounded monolayer assay system (used as an in vitro model of wound repair) and effects on proliferation determined using [3H]thymidine incorporation. RESULTS: Pretreatment with 0.5 or 1 ml colostral preparation reduced gastric injury by 30% and 60% respectively in rats. A milk preparation was much less efficacious. Recombinant transforming growth factor beta added at a dose similar to that found in the colostrum preparation (12.5 ng/rat), reduced injury by about 60%. Addition of colostrum to drinking water (10% vol/vol) prevented villus shortening in the mouse model of small intestinal injury. Addition of milk preparation was ineffective. Colostrum increased proliferation and cell migration of RIE-1 and HT-29 cells. These effects were mainly due to constituents of the colostrum with molecular weights greater than 30 kDa. CONCLUSIONS: Bovine colostrum could provide a novel, inexpensive approach for the prevention and treatment of the injurious effects of NSAIDs on the gut and may also be of value for the treatment of other ulcerative conditions of the bowel.

Animals↗

Repeat tear of postoperative meniscus: potential MR imaging signs.

PURPOSE: To determine the usefulness of five magnetic resonance (MR) signs of repeat tears of the postoperative meniscus. MATERIALS AND METHODS: Fat-saturated proton-density-weighted and T2-weighted MR images in 20 patients who had undergone at least two knee surgeries were reviewed. Second-look arthroscopic confirmation of meniscal status was available in all patients. MR images of 39 menisci (10 repeat tears, 11 postoperative menisci without repeat tears, three tears in previously normal menisci, and 15 normal menisci) were evaluated for (a) a linear area of abnormal signal intensity extending to an articular surface on intermediate-weighted images, (b) abnormal meniscal morphology, (c) likelihood of a typical postoperative appearance, (d) fluid extending into the linear area on T2-weighted images, and (e) cartilage defects. Two radiologists rated their confidence on a five-point scale for the presence of these signs and were compared for level of agreement. RESULTS: The intraclass correlation coefficient (range, 0.75-0.91) indicated a high level of agreement. Areas under the receiver operating characteristic curves were large (range, 0.70-0.87) for all five signs, with a line (grade 3 signal intensity) and fluid within a line having the highest areas. These two signs also had the highest statistical scores (chi 2 = 14.12 and 13.30; P < .002; odds ratio, 1.588 and 1.599 for the line and the fluid within the line, respectively). CONCLUSION: The two best MR signs of repeat tear of the postoperative meniscus were the presence of a line and fluid within the line extending to an articular surface.

Adult↗

AP-2 (activating protein 2) and Sp1 (selective promoter factor 1) regulatory elements play distinct roles in the control of basal activity and cyclic adenosine 3',5'-monophosphate responsiveness of the human chorionic gonadotropin-beta promoter.

The CG beta-subunit gene (CGbeta) arose evolutionarily from the LH beta-subunit gene (LHbeta) through gene duplication. Although the promoter sequences of the CGbeta and human (h) hLHbeta genes are greater than 90% homologous, their expression patterns are distinct. LHbeta is expressed in pituitary gonadotrope cells and CGbeta is expressed in placental trophoblast cells. The placental specific and cAMP-inducible region within the CGbeta promoter has been mapped to a complex enhancer element spanning 118 bp (-318 to -200). Transcription factor-binding sites within this enhancer have been partially characterized and include multiple binding sites for AP-2 (activating protein 2) and Sp1 (selective promoter factor 1), which activate basal and cAMP-induced expression. In this study, we performed a detailed analysis of the recognition sites for these transcription factors and examined the functional roles of these elements in the control of CGbeta expression. An upstream Sp1/AP-2 binding site (-318 to -279) preferentially binds Sp1, which occludes AP-2 binding to an adjacent site. In contrast, both Sp1 and AP-2 bind concurrently to a downstream composite Sp1/AP-2 element (-220 to -188). Functionally, mutations in any of the Sp1 or AP-2 binding sites cause a progressive decrease in basal CGbeta expression. However, cAMP stimulation of the CGbeta promoter is reduced by AP-2 mutations, whereas Sp1 mutations enhance cAMP activation. We conclude that multiple AP-2 and Sp1 elements are required to maintain basal CGbeta promoter activity, but these factors have opposing effects on cAMP regulation, which is mediated primarily by AP-2.

Base Sequence↗

Targeting bacteriophage to mammalian cell surface receptors for gene delivery.

Filamentous bacteriophages represent one of nature's most elegant ways of packaging and delivering DNA. In an effort to develop novel methods for ligand discovery via phage gene delivery, we conferred mammalian cell tropism to filamentous bacteriophages by attaching basic fibroblast growth factor (FGF2), transferrin, or epidermal growth factor (EGF) to their coat proteins and measuring CMV promoter-driven reporter gene expression in target cells. In this system, FGF2 was a more effective targeting agent than transferrin or EGF. The detection of green fluorescent protein (GFP) or beta-galactosidase (beta-Gal) activity in cells required FGF2 targeting and was phage concentration dependent. Specificity of the targeting for high-affinity FGF receptors was demonstrated by competing the targeted phage with FGF2, by the failure of FGF2-targeted bacteriophage to transduce high-affinity FGF receptor-negative cells, and by their ability to transduce these same cells when stably transfected with FGFR1, a high-affinity FGF receptor. Long-term transgene expression was established by selecting colonies for G418 resistance, suggesting that with the appropriate targeted tropism, filamentous bacteriophage can serve as a vehicle for targeted gene delivery to mammalian cells.

Animals↗

Establishing the level of digitization for wrist and hand radiographs for the third National Health and Nutrition Examination Survey.

In the third National Health and Nutrition Examination Survey (NHANES III) conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention, radiographs of the hands and knees were taken of participants 60 years and older as part of the study of arthritis and musculoskeletal conditions. The purpose of the study was to decide the digitizing resolution to be used for these radiographs. A set of wrist and hand radiographs (N = 49) was graded by two radiologists for degree of bone erosions and served as a "gold standard." The radiographs were then digitized at three resolution levels; low-resolution 150 microns (2001 x 1634 x 12 bit matrix); intermediate-resolution 100 microns (3000 x 2400 x 12 bit matrix); and high-resolution 50 microns (4900 x 3000 x 12 bit matrix). A comparison of the digital images versus the gold standard reading was made at the three resolutions by two radiologists. Kappa statistics suggested fair (K > .4) to excellent (K > .75) agreement between the gold standard and the images at all levels. Intraclass correlation coefficient suggested high agreement between readers (ICC > .5), with minimal individual reader effect. Variance component estimates showed that the major contribution (78-83%) to scoring came from variability in the images themselves, not from the readers. The 100 microns resolution was selected over the 150 and 50 microns on the basis of practical considerations such as storage requirements, display time, and easier manipulation of the digital images by the readers.

Arizona↗

Sensitivities and specificities of premier E. coli O157 and premier EHEC enzyme immunoassays for diagnosis of infection with verotxin (Shiga-like toxin)-producing Escherichia coli. The SYNSORB Pk Study investigators.

This study describes the performance of two rapid enzyme immunoassays, Premier E. coli O157 and Premier EHEC (Meridian Diagnostics Inc., Cincinnati, Ohio) for the detection in stools of Escherichia coli O157 and verotoxins (Shiga-like toxins), respectively. Both tests were performed on stools from 876 children presenting to eight emergency departments with diarrhea. Standard culture, including E. coli O157:H7 isolation, was performed, and paired sera were taken for anti-O157-lipopolysaccharide antibody determination. Stools from patients enrolled in the study, and those yielding discordant results, were sent to a reference laboratory for repeat testing and further investigation, including cytotoxicity and non-O157 verotoxin-producing E. coli culture. Results were classified as field results (obtained in the eight site laboratories) and resolved results (obtained after repeat testing in the central laboratory). The "gold standard" for sensitivity of both tests and for specificity of Premier E. coli O157 was isolation of E. coli O157:H7 or a fourfold anti-O157 antibody rise. Specimens positive by the Premier EHEC test and negative for E. coli O157 culture were examined for non-O157 verotoxin-producing E. coli. The field sensitivity of Premier E. coli O157 was 86%, that of Premier EHEC was 89%, and the specificity of Premier E. coli O157 was 98%. Ten of 13 discordant Premier E. coli O157 results were reassigned as true results after repeat testing. Ten non-O157 verotoxin-producing E. coli isolates were recovered from Premier EHEC-positive, E. coli O157 culture-negative stools. Only one specimen gave an unequivocally false-positive Premier EHEC result. Both tests are highly sensitive and are specific if correctly performed. The Premier EHEC test will be particularly valuable as a practical routine test for the detection of non-O157 verotoxin-producing E. coli.

Antibodies, Bacterial↗

The effects of noncontingent and contingent attention for self-injury, manding, and collateral responses.

To date, most functional analysis studies have focused on the effects of treatment contingencies on specific targeted aberrant and alternative responses. In the current investigation, the main and collateral effects of the assessment and treatment of attention-maintained self-injury were assessed. Specifically, we evaluated the effects of noncontingent and contingent social attention on four categories of behavior: self-injury, a novel mand, preexisting prosocial responses (e.g., babbling and reaching out), and other aberrant responses (i.e., aggression and destruction). Results suggested that self-injury, prosocial responses, and other aberrant behaviors were within the same functional response class. Possible impact of these results when selecting mands for functional communication training is discussed.

Attention↗

The thyroid hormone receptor variant alpha2 is a weak antagonist because it is deficient in interactions with nuclear receptor corepressors.

The thyroid hormone receptor splice variant, alpha2, is unable to bind thyroid hormone (T3) and has been proposed to function as an endogenous inhibitor of T3 action. In this report, we examined further the DNA sequence requirements for alpha2 binding to thyroid hormone response elements (TREs) in an attempt to identify response elements that mediate potent inhibition by alpha2. Heterodimers of alpha2 and retinoid X receptor were found to bind to a subset of TREs (DR4, direct repeats spaced by 4 bp) in which selected flanking and spacer sequences enhanced interactions with the AGGTCA core binding sequence. Despite the optimization of the TRE-binding sites, alpha2 remained a weak dominant negative inhibitor of TRE-driven transcription. A promoter interference assay was also developed for testing inhibition by alpha2. In these studies, alpha2 blocked gene transcription, but it required cotransfected retinoid X receptor, and it was not as potent as unliganded thyroid hormone receptors. These results led to the hypothesis that alpha2 might be deficient in interactions with nuclear receptor corepressors. Consistent with this view, alpha2 did not silence basal transcription in its native form or when linked to Gal4. Alpha2 also failed to interact with corepressors (NCoR and SMRT) in both gel shift assays and mammalian two-hybrid assays. We conclude that alpha2 is a weak antagonist of thyroid hormone action because it binds weakly to a limited repertoire of response elements, and it does not interact with corepressors. Thus, alpha2 may be able to compete with thyroid hormone receptors for binding to a limited group of target sites, but it is not able to actively inhibit transcription.

Binding Sites↗

Salmonella typhimurium DT104: a virulent and drug-resistant pathogen.

Salmonella typhimurium phage type (PT) or definitive type (DT) 104 is a virulent pathogen for humans and animals, particularly cattle. It has been isolated increasingly from humans and animals in the United Kingdom and several other European countries and, more recently, in the United States and Canada. Humans may acquire the infection from foods of animal origin contaminated with the infective organism. Farm families are particularly at risk of acquiring the infection by contact with infected animals or by drinking unpasteurized milk. The symptoms in cattle are watery to bloody diarrhea, a drop in milk production, pyrexia, anorexia, dehydration and depression. Infection may result in septicemic salmonellosis and, upon necropsy, a fibrinonecrotic enterocolitis may be observed. The infection occurs more commonly in the calving season than at other times. Feedlot cattle and pigs may also be affected. Prolonged carriage and shedding of the pathogen may occur. Symptoms in humans consist of diarrhea, fever, headache, nausea, abdominal pain, vomiting, and, less frequently, blood in the stool. Salmonella typhimurium DT104 strains are commonly resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline.

Agricultural Workers' Diseases↗