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Biomedical subjects

W Johnson

Publications and source records attributed to W Johnson.

At least 37 records · Page 2Linked to original sources

Efficacies of BCG and vole bacillus (Mycobacterium microti) vaccines in preventing clinically apparent pulmonary tuberculosis in rabbits: a preliminary report.

Tuberculosis (TB) kills more people in the world today than any other infectious disease, and the number of drug-resistant Mycobacterium tuberculosis isolates is increasing. Vaccines, better than most of the currently available strains of bacille Calmette-Guérin (BCG), are urgently needed to control this disease. TB in rabbits resembles human TB more closely than TB in any other common laboratory animal and a most pertinent method of assessing vaccine efficacy is Lurie's tubercle count method in this species. Vaccinated and control rabbits were infected by aerosol with virulent human-type tubercle bacilli (H37Rv). At necropsy 5 weeks thereafter, the grossly visible primary tubercles in the entire lung were counted. A decrease in the number of such tubercles is a quantitative measure of vaccine efficacy: An effective vaccine prevents microscopic tubercles from growing to grossly visible (clinically apparent) size. The Pasteur substrain of BCG and two substrains of Mycobacterium microti (the vole bacillus) reduced the number of visible primary tubercles an average of 75%, whereas three other substrains of BCG and three other substrains of vole bacilli only reduced the number an average of 40%. These initial studies indicate that Lurie's tubercle-count method in rabbits is a precise way to choose the best available tuberculosis vaccines.

Animals↗

Role of Ets2 in cyclic AMP regulation of the human chorionic gonadotropin beta promoter.

Activation of the human chorionic gonadotropin beta (hCGbeta) by the protein kinase A (PKA) pathway has been shown to occur through an activating protein-2 (AP-2)-dependent mechanism. However, in HepG2 cells, which are deficient in AP-2, the PKA catalytic subunit is still able to stimulate the hCGbeta promoter. Ets2 plays a critical role in placental development as revealed by placental abnormalities in Ets2 knockout mice. Transfection of Ets2 into JEG-3 placental cells causes a slight, but reproducible, increase in hCGbeta promoter basal activity. However, cotransfection with the PKA catalytic subunit causes a strong synergistic increase in hCGbeta promoter activity. Ets2 synergistic activation of the hCGbeta promoter is specific for the PKA pathway, as activation of the ras pathway, which also acts through Ets2, does not activate the hCGbeta promoter. c-Jun-mediated repression of hCGbeta is inhibited by Ets2 cotransfection, indicating that protein-protein interactions may be responsible for Ets2 activation of the hCGbeta promoter.

Animals↗

Effects of the seafood toxin domoic acid on glutamate uptake by rat astrocytes.

Pronounced glutamic acid uptake was observed after only 15 min with glutamate concentrations of 60 nmol/mg protein when astrocytes were incubated with 1 mM glutamic acid. The uptake increased with time to a steady-state glutamate level of above 160 nmol/mg protein by 45 min. The uptake was energy dependent. Reduced temperature (0 degrees C) and ouabain (100 microM) inhibited uptake by 86.7% (P<0.001; n=18) and 84.4% (P<0.001; n=18), respectively, when compared with controls. After exposure of astrocytes to glutamate (1 mM) in the incubation medium, in the presence of domoic acid (10 and 100 microM) at 5 and 60 min, domoic acid (10 microM) elevated glutamate uptake by 64.0% (P<0.05; n=34) at 5 min but decreased glutamate uptake by 47.8% (P<0.01; n=19) at 60 min compared with controls. A higher dose of domoic acid (100 microM) decreased glutamate uptake by 49.6% (P<0.01; n=20) and 61.3% (P<0.001; n=20) at 5 and 60 min, respectively, compared with controls. This study suggests that domoic acid may induce neurotoxicity because of the failure of astrocytes to remove extracellular glutamate. This may contribute to excitotoxic injury.

Animals↗

Multiresistant Salmonella Typhimurium DT104 infections of humans and domestic animals in the Pacific Northwest of the United States.

Salmonella Typhimurium definitive type 104 with chromosomally encoded resistance to five or more antimicrobial drugs (R-type ACSSuT+) has been reported increasingly frequently as the cause of human and animal salmonellosis since 1990. Among animal isolates from the northwestern United States (NWUS), R-type ACSSuT+ Typhimurium isolates increased through the early 1990s to comprise 73% of Typhimurium isolates by 1995, but subsequently decreased to comprise only 30% of isolates during 1998. NWUS S. Typhimurium R-type ACSSuT+ were consistently (99%) phage typed as DT104 or the closely related DTu302. S. Typhimurium isolates from cattle with primary salmonellosis, randomly selected from a national repository, from NWUS were more likely to exhibit R-type ACSSuT+ (19/24, 79%) compared to isolates from other quadrants (17/71, 24%; P < 0.01). Human patients infected with R-type ACSSuT+ resided in postal zip code polygons of above average cattle farm density (P < 0.05), while patients infected with other R-types showed no similar tendency. Furthermore, humans infected with R-type ACSSuT+ Typhimurium were more likely to report direct contact with livestock (P < 0.01) than humans infected with other R-types.

Animals↗

Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure.

BACKGROUND: This study determined whether evidence of congestion after 4 to 6 weeks of heart failure management predicted outcome for patients hospitalized with chronic New York Heart Association class IV symptoms. Class IV symptoms predict high mortality rates, but outcome is not known for patients who improve to establish freedom from congestion. Revised estimates at 1 month could facilitate decisions regarding transplantation and other high-risk interventions. METHODS: At 4 to 6 weeks after hospital discharge, 146 patients were evaluated for congestion by 5 criteria (orthopnea, jugular venous distention, edema, weight gain, and new increase in baseline diuretics). Heart failure management included inpatient therapy tailored to relieve congestion, followed by adjustments to maintain fluid balance during the next 4 weeks. RESULTS: Freedom from congestion was demonstrated at 4 to 6 weeks in 80 (54%) patients, who had 87% subsequent 2-year survival compared with 67% in 40 patients with 1 or 2 criteria of congestion and 41% in 26 patients with 3 to 5 criteria. The Cox proportional hazards model identified left ventricular dimension, pulmonary wedge pressure on therapy, and freedom from congestion as independent predictors of survival. Persistence of orthopnea itself predicted 38% 2-year survival (without urgent transplantation) versus 77% in 113 without orthopnea. Serum sodium was lower and blood urea nitrogen and heart rate higher when orthopnea persisted. CONCLUSIONS: The ability to maintain freedom from congestion identifies a population with good survival despite previous class IV symptoms. At 4 to 6 weeks, patients with persistent congestion may be considered for high-risk intervention.

Disease Progression↗

Identification of Campylobacter jejuni, C. coli, C. lari, C. upsaliensis, arcobacter butzleri, and A. butzleri-like species based on the glyA gene.

Currently, the detection and identification of Campylobacter and Arcobacter species remains arduous, largely due to cross-species phenotypic similarities and a relatively narrow spectrum of biochemical reactivity. We have developed a PCR-hybridization strategy, wherein degenerate primers are used to amplify glyA fragments from samples, which are then subjected to species-specific oligodeoxyribonucleotide probe hybridizations, to identify and distinguish between Campylobacter jejuni, C. coli, C. lari, C. upsaliensis, Arcobacter butzleri, and an A. butzleri-like species. Evaluation of this strategy with genomic DNA from different type strains suggests that this approach is both specific and sensitive and thus may be applicable in a diagnostic assay to identify and differentiate these highly related species.

Arcobacter↗

Epidemiologic subtyping of Escherichia coli serogroup O157 strains isolated in Ontario by phage typing and pulsed-field gel electrophoresis.

Phage typing and DNA macrorestriction fragment analysis by pulsed-field gel electrophoresis (PFGE) were evaluated for use in the epidemiological subtyping of Escherichia coli serogroup O157 strains isolated in Ontario, Canada. Among 30 strains isolated from patients with sporadic cases of infection, 22 distinct XbaI macrorestriction patterns were identified and 17 strains exhibited unique PFGE patterns. In contrast, phage typing identified only seven different phage types and 17 strains belonged to the same phage type. A total of 25 phage type-macrorestriction pattern combinations were identified among the strains from patients with sporadic cases of infection. PFGE subtyping differentiated between unrelated strains that exhibited the same phage type, and in one group of strains, phage typing differentiated between strains of the same PFGE subtype. Both typing procedures correctly identified outbreak-related isolates as belonging to the same type in four separate outbreaks. Each outbreak strain was characterized by a distinct macrorestriction pattern, while phage typing subdivided the outbreak strains into only three different types. A small percentage of outbreak-related isolates had PFGE patterns that differed slightly (one or two DNA fragment differences) from that of the outbreak strain. On the other hand, each isolate from the same outbreak belonged to the same phage type as that of the outbreak strain. We conclude that phage typing and PFGE fingerprinting represent complementary procedures for the subtyping of E. coli serogroup O157 and that the combined use of these procedures provides optimal discrimination.

Bacterial Typing Techniques↗

Self-confidence, self-esteem, and assumption of sex role in young men and women.

This study investigated the use of the English translation of a paper-and-pencil self-confidence scale developed in French by Garant, Charest, Alain, and Thomassin in 1995. The translated self-confidence scale measured self-confidence, or the belief that one will succeed at whatever one undertakes, as distinct from self-esteem or the feeling that one is a worthwhile person. Unlike a number of previous studies. there was no sex difference in self-confidence favoring men: however, scores on the masculinity portion of Bem's Sex role Inventory (1974) were highly correlated with self-confidence for both men (r=.59) and women (r=.69).

Adult↗

Overall self-confidence, self-confidence in mathematics, and sex-role stereotyping in relation to salivary free testosterone in university women.

This study investigated in 40 young university women the possible relationships between levels of testosterone and specific measures of overall self-confidence and self-confidence in approaching mathematics. Correlations of -.43 and -.49 with each measure of self-confidence, respectively, and level of testosterone were found in the portion of the sample displaying normal ovulatory function. There was no correlation (r=.02) between the measures of mathematics and overall self-confidence. 19 women did not display normal ovulatory function. The only significant result for the full sample was a significant correlation of -.73 between scores on the Bem Sex Role Inventory Masculinity and overall self-confidence. The reasons for the high anovulatory percentage are not clear, nor are the associations which anovulation might have with either hormonal levels or the personality characteristics in question.

Adolescent↗

Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.

BACKGROUND: Inherited mutations cause approximately 35 percent of cases of dilated cardiomyopathy; however, few genes associated with this disease have been identified. Previously, we located a gene defect that was responsible for autosomal dominant dilated cardiomyopathy and conduction-system disease on chromosome 1p1-q21, where nuclear-envelope proteins lamin A and lamin C are encoded by the LMNA (lamin A/C) gene. Mutations in the head or tail domain of this gene cause Emery-Dreifuss muscular dystrophy, a childhood-onset disease characterized by joint contractures and in some cases by abnormalities of cardiac conduction during adulthood. METHODS: We evaluated 11 families with autosomal dominant dilated cardiomyopathy and conduction-system disease. Sequences of the lamin A/C exons were determined in probands from each family, and variants were confirmed by restriction-enzyme digestion. The genotypes of the family members were ascertained. RESULTS: Five novel missense mutations were identified: four in the alpha-helical-rod domain of the lamin A/C gene, and one in the lamin C tail domain. Each mutation caused heritable, progressive conduction-system disease (sinus bradycardia, atrioventricular conduction block, or atrial arrhythmias) and dilated cardiomyopathy. Heart failure and sudden death occurred frequently within these families. No family members with mutations had either joint contractures or skeletal myopathy. Serum creatine kinase levels were normal in family members with mutations of the lamin rod but mildly elevated in some family members with a defect in the tail domain of lamin C. CONCLUSIONS: Genetic defects in distinct domains of the nuclear-envelope proteins lamin A and lamin C selectively cause dilated cardiomyopathy with conduction-system disease or autosomal dominant Emery-Dreifuss muscular dystrophy. Missense mutations in the rod domain of the lamin A/C gene provide a genetic cause for dilated cardiomyopathy and indicate that this intermediate filament protein has an important role in cardiac conduction and contractility.

Adolescent↗

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↗