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Biomedical subjects

R A Wilson

Publications and source records attributed to R A Wilson.

At least 163 records · Page 9Linked to original sources

Cryoablation of medically refractory nodoventricular tachycardia.

Paroxysmal wide QRS tachycardia, based on a nodoventricular accessory connection, is an uncommon arrhythmia. In this report, the endocardial and epicardial mapping and cryoablation of a nodoventricular fiber, documented to participate in medically refractory tachycardia in an 11-year-old boy, are described. Epicardial cryothermia, applied at the earliest site of right ventricular activation, resulted in the abrupt termination of tachycardia. Endocardial cryothermia was subsequently applied in the perinodal region, the presumed site of origin of the nodoventricular fiber. No tachyarrhythmias were inducible postoperatively, and no antiarrhythmic treatment has been required during 18 months of follow-up. Based on precise anatomic localization of the nodoventricular connection, a definitive cure of associated tachyarrhythmias may be possible utilizing cryothermia, without the requirement for extensive intraoperative dissection.

Bundle of His↗

Inverse relationship between total glutathione S-transferase content and bile acid release in isolated hepatocytes from untreated, phenobarbital pretreated and hypothyroid rats.

The role of cytosolic anion binding proteins (glutathione S-transferases) in the hepatic transport of bile acids remains controversial. To investigate whether increased levels of the hepatocyte total glutathione S-transferase content were associated with changes in the release of bile acids from the hepatocyte, we measured the rate of release of radioactive bile acids in isolated hepatocytes from thyroidectomized, phenobarbital pretreated and untreated rats. The isolated hepatocytes were preincubated with either 14C-cholic acid or 14C-taurocholic acid, and the release rate of radiolabeled bile acids was determined. Hepatocyte total glutathione S-transferase content was measured by rocket immunoelectrophoresis. The release rate of the radiolabeled bile acids was significantly (P less than 0.005) decreased in both hypothyroid and phenobarbital pretreated hepatocytes. The levels of total glutathione S-transferase content were significantly (P less than 0.001) increased in the hepatocytes from both hypothyroid and phenobarbital pretreated animals. Our findings reveal a striking inverse relationship between the total glutathione S-transferase content of the hepatocyte and the release rate of radiolabeled bile acids in isolated hepatocytes from two independent animal models. These observations support the hypothesis that cytosolic anion binding proteins (glutathione S-transferases) may influence the net flux across the hepatocyte plasma membrane largely by limiting efflux.

Animals↗

Genetic relationships among strains of avian Escherichia coli associated with swollen-head syndrome.

Genetic diversity among 22 Escherichia coli strains isolated from chickens with swollen-head syndrome (SHS), an acute respiratory disease of domestic poultry, and 93 strains isolated from birds with colibacillosis was assessed on the basis of allelic variation at 20 enzyme-encoding loci detected by multilocus enzyme electrophoresis. SHS isolates from Spain and Canada were polymorphic at 14 loci and were classified into 19 multilocus genotypes, defining clones that differed on average at 34% of the loci. In most cases, SHS isolates of different clonal genotypes were distinct in O:H serotype and expressed different fimbrial antigens. Comparisons with 93 isolates obtained from birds with colibacillosis revealed enzyme polymorphisms at 17 of 20 loci, with an average of 3.5 alleles per locus. In the total sample, 56 clonal genotypes were distinguished, with 27 (23%) of the isolates belonging to one of three common clones. Both SHS and colibacillosis isolates were genetically diverse, with an average single-locus diversity of 0.36, indicating that a wide variety of naturally occurring bacterial clones is associated with these acute avian infections. Six previously defined groups of clones identified in diseased birds from the United States were represented in isolates from Spain, indicating that similar clones occur in widely separated geographic areas. In addition, one group of SHS isolates was closely related to a recognized widespread clone complex incriminated in human septicemia and meningitis. The results suggest that certain strains implicated in SHS infections belong to a clone complex whose members have special attributes that promote involvement in invasive diseases in humans and animals.

Alleles↗

Restriction fragment length polymorphisms among uropathogenic Escherichia coli isolates: pap-related sequences compared with rrn operons.

Among the adhesin-encoding virulence operons associated with uropathogenic Escherichia coli, only pap (pyelonephritis-associated pilus)-related gene clusters typically exhibit variation in their structure and chromosomal copy number. To access further such variability, we compared pap restriction fragment length polymorphisms (RFLPs) with those detected among rRNA (rrn) operons, which encode an essential host function unrelated to virulence. To place such findings in a phylogenetic perspective, the E. coli isolates were also characterized by using multilocus enzyme electrophoresis. Variation in the rrn RFLP profiles correlated with evolutionary divergence resolved by multilocus enzyme electrophoresis; isolates with identical rrn profiles represented the same or closely related electrophoretic types. In contrast, such isolates frequently had different pap-related RFLPs, indicating that these genetic variations have developed recently relative to the changes associated with essential rrn operons or metabolic enzymes. Despite such fluctuations, two lines of evidence indicate conditions under which the pap-related RFLPs can be stably maintained. First, for each of 20 patients with urosepsis, both the primary urinary tract isolate and the concurrent blood isolate were identical. Second, although obtained from different patients, some isolates representing the same electrophoretic type also had identical pap-related RFLPs. Thus, the genotypic diversity of this virulence adhesin operon was not generated during the course of acute infection or during laboratory manipulations. Since fecal E. coli isolates frequently carry chromosomally encoded pap-related gene clusters, these findings suggest that the intra- and interchromosomal recombination events generating the polymorphisms associated with the pap-related sequences likely occur among the E. coli of the commensal reservoir.

Base Sequence↗

Vasodilatory effects of lidocaine on epicardial porcine coronary arteries.

To investigate the mechanism of lidocaine's effect to cause vasorelaxation, swine epicardial mid-right coronary arterial rings were placed under constant (5 g) tension in a muscle bath, precontracted with 35 mmol/l KCl and exposed to increasing concentrations of lidocaine (3-2,000 micrograms/ml). At a concentration of 10 micrograms/ml, mild vasoconstriction occurred, increasing tension 1.9 +/- 0.1% above baseline. Vasodilation began to occur at 30 micrograms/ml and was maximal at 2,000 micrograms/ml, reducing tension 97.5 +/- 0.2% below baseline. Vasodilation was not altered significantly by removal of endothelium or by pretreatment with propranolol or indometacin.

Animals↗

In situ pulmonary responses of T cell and macrophage subpopulations to a challenge infection in mice vaccinated with irradiated cercariae of Schistosoma mansoni.

Cellular events related to the resistance induced by radiation-attenuated cercariae of Schistosoma mansoni were determined immunocytochemically in the lung tissues of mice. Thy-1, CD4, CD8, Mac-1 MOMA-1, MOMA-2, and Ia antigens were identified on cryostat sections by the immunogold-silver staining technique with specific monoclonal antibodies. In mice vaccinated with irradiated cercariae and challenged with normal cercariae, the number of Thy-1+ and CD4+ lymphocytes was increased dramatically relative to the normal numbers both in perivascular tissues and in focal cellular aggregates in the parenchyma of the lungs. A high ratio of CD4+/CD8+ T cells was noted in the aggregates, both in perivascular tissues and in the foci. Macrophages showing positive reactions for Mac-1, MOMA-1, MOMA-2, and Ia also infiltrated the foci. In control mice that were unvaccinated and challenged, foci showing positive reactions for the lymphocyte subpopulations barely were detectable in the lungs by day 14. The numbers of Thy-1+, CD4+, and CD8+ cells and the CD4+/CD8+ ratio in controls were considerably less than those in vaccinated/challenged mice over the period of observation. In conclusion, pulmonary cellular aggregates in vaccinated and challenged mice were composed mainly of Thy-1+ and CD4+ cell populations characteristic of delayed-type hypersensitivity (DTH) reactions. Thus, Thy-1+ and CD4+ cells in the lungs of vaccinated mice may be involved in the elimination of challenge parasites through DTH reactions.

Animals↗

Lung-phase immunity to Schistosoma mansoni. Flow cytometric analysis of macrophage activation states in vaccinated mice.

A delayed-type hypersensitivity response has been postulated as the effector mechanism of lung-phase immunity to Schistosoma mansoni. We have sought evidence for this response by examining the state of alveolar macrophage activation in C57BL/6 mice vaccinated with radiation-attenuated cercariae, and challenged with normal parasites. As an index of activation, the capacity of macrophages to produce an oxidative burst upon stimulation with PMA, was measured at the single cell level by a flow cytometric method. Fourteen to 28 days after vaccination with 20-kr parasites, highly activated macrophages were recovered from the airways by bronchoalveolar lavage. Their probable role in resistance is to recruit T lymphocytes and macrophages to "arm" the lungs against subsequent challenge. The level of macrophage activation had declined to near background by the time challenge parasites arrived, although pulmonary leucocyte numbers remained elevated. Activated alveolar macrophages were not detected after vaccination with 80-kr parasites, which fail to reach the lungs or induce resistance. Challenge parasites, arriving in the lungs of 20-kr vaccinated mice, stimulated a rapid increase in the activation state of recruited macrophages, coincident with their retention in the pulmonary vasculature. These events occurred later in challenge control mice, with peak activation at day 21, when migration of parasites to the liver is complete. Mice vaccinated with 80-kr parasites lacked the accelerated response to challenge, behaving like the control group. The absence of activated peritoneal macrophages suggests a response restricted to organs such as the lungs, through which both vaccinating and challenge parasites migrate. We suggest that the role of activated alveolar macrophages in lung-phase immunity is to initiate and maintain the focal inflammatory responses which block onward migration of parasites and lead to their demise.

Animals↗

Characteristics of protective immunity in mice induced by drug-attenuated larvae of Schistosoma mansoni. Antigen localization and antibody responses.

Partial resistance to reinfection developed in mice with immature infections of Schistosoma mansoni treated with the drug Ro11-3128, whereas mice vaccinated with irradiated cercariae and treated in a similar way did not become immune. Persistence of drug-treated parasites in the skin and draining lymph nodes, which prolonged the opportunity for efficient Ag presentation, was necessary for the development of protective immunity. Death and clearance of parasites solely in the skin, was not sufficient to induce protection. The expansion in the number of lymphocytes in the skin-draining nodes after vaccination, was reflected in the contrasting levels of resistance induced by the different drug-treatment regimes. Challenge parasites were eliminated predominantly after they reached the lungs. An investigation of antibody reactivity revealed an immunodominant response against a doublet of Ag of Mr 97 to 99 kDa. Recognition of this complex by antisera from different groups of mice was not related to their immune status. Western blots and inhibition analysis showed that this doublet has epitopes in common with the Sm97/paramyosin protective Ag, originally identified by antisera reactivity from mice immunized with a nonliving vaccine.

Animals↗

Chronic aortic insufficiency: factors associated with progression to aortic valve replacement.

STUDY OBJECTIVE: To determine whether the initial measurement of clinical variables in patients with chronic stable aortic insufficiency is helpful in identifying patients at risk for earlier progression to aortic valve replacement. DESIGN: Prospective analysis of a cohort of patients for a median follow-up time of 44 months (range, 8 to 57). SETTING: Referral-based cardiology clinics at two university hospitals and their affiliated Veterans Administration medical centers. PATIENTS: Cohort of 50 asymptomatic or minimally symptomatic patients with chronic aortic insufficiency and left ventricular enlargement. Patients had preserved left ventricular ejection fraction at rest and no evidence of coronary artery disease or significant noncardiac illness. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Baseline evaluation included a history and physical examination, chest roentgenogram. M-mode echocardiogram, treadmill test, and radionuclide angiogram done at rest and during supine bicycle exercise. Ten patients progressed to surgery because of the onset of limiting symptoms or objective evidence of left ventricular dysfunction, or both; the overall rate was 4% +/- 3% per year. The Breslow and Mantel-Cox statistics were used to compute survival (surgery-free) dichotomized by prognostic variables. The progression to surgery was earlier in patients with left ventricular end-diastolic volume indices of 150 cc/m2 or more, end-systolic volume indices of 60 cc/m2 or more, a left ventricular ejection fraction at maximal exercise of less than 0.50, or an end-systolic wall stress of 86 dynes/cm2 or more. CONCLUSIONS: Patients at higher and lower risk for early progression to aortic valve replacement can be identified through the measurement of left ventricular size and function. This information can be used to decide the frequency and intensity of follow-up evaluation in these patients.

Actuarial Analysis↗

Portal shunting and resistance to Schistosoma mansoni in 129 strain mice.

The integrity of the hepatic portal vasculature was examined, relative to the resistance to Schistosoma mansoni observed in 68% of 129/Ola mice. The passage of microspheres to the lungs, following their injection via the superior mesenteric vein, indicated the presence of shunts in the majority of both naive and infected mice. There was a negative association between shunting of microspheres to the lungs and paucity of liver worms at 28/35 days post-infection. Schistosomula accumulated in the livers of resistant mice at a slower rate than in susceptible animals, and after day 21 relocated to the lungs. Many lung schistosomula injected via the superior mesenteric passed immediately to the lungs; the shunts thus greatly reduce the probability of trapping in the liver. Some parasites migrated back from the lungs, successfully lodged in the liver and began to feed on blood. Latex infusion demonstrated the location of large intrahepatic connections between the portal and hepatic veins. We suggest that as these liver worms grow, migrating upstream into progressively larger vessels, they reach the connections, pass out of the hepatic portal system, and relocate to the lungs. The presence of the natural shunts thus accounts for the resistant status of the mice.

Animals↗

Schistosoma mansoni: circulating and pulmonary leucocyte responses related to the induction of protective immunity in mice by irradiated parasites.

The leucocyte responses in peripheral blood and pulmonary airways are described following vaccination of mice with radiation-attenuated parasites, and subsequent challenge with normal parasites. Percutaneous vaccination stimulated a large and sustained expansion of the circulating lymphocyte pool, more marked than after intradermal vaccination with lung schistosomula which induced comparable levels of resistance. Macrophages and lymphocytes infiltrated the pulmonary airways in response to vaccination by both routes, the lymphocytes being particularly abundant after intradermal vaccination. Exposure of mice to an equivalent number of normal cercariae induced an earlier lymphocytosis of short duration; far fewer macrophages and lymphocytes infiltrated the lungs than after vaccination. An intense but transient pulmonary eosinophilia peaked at 3 weeks after primary exposure to either normal or attenuated parasites. Percutaneous challenge of vaccinated mice elicited higher levels of circulating lymphocytes than challenge of unsensitized controls. However, whilst leucocyte numbers of all cell types were still elevated in the airways at challenge as a consequence of vaccination, no further cellular recruitment was observed coincident with parasite elimination. Our data are compatible with the hypothesis that the mechanism of immunity in once-vaccinated mice involves a T lymphocyte-macrophage interaction triggered by antigen release from lung schistosomula.

Administration, Cutaneous↗

Reactivity of anti-tegument monoclonal antibodies with target epitopes in different worm tissues and developmental stages of Schistosoma mansoni.

Sixteen monoclonal antibodies (MABs) were selected for their reactivity with adult schistosome tegument. The distribution of target epitopes in different tissues of the adult and in various developmental stages was investigated by indirect immunofluorescence. The distinct patterns of reactivity of the MABs permitted their classification into 9 groups. The distribution of epitopes in larvae, particularly 3 h schistosomula, generally mirrored that in adults. A change in distribution of epitopes coincided with transformation from cercaria to schistosomulum providing a marker for this process. Two MABs reacted with surface membranes of intact cercariae, and 5 with the surfaces of intact 3 h schistosomula. The target epitopes of these 5 MABs were present in the tegument of adults, but not accessible externally. These observations suggest masking of antigens, not shedding, in the course of development. Indeed, no MAB reacted with intact lung or liver worms unless they were damaged. Three MABs reacted with membranes of the tegument and most other tissues, implying properties in common. Evidence for shared functions between epithelia was provided by the reactivity of 2 MABs with the tegument and protonephridia. Eight MABs bound both to the tegument and its cell bodies. Since the latter contains the machinery for protein synthesis, it is difficult to explain why 5 MABs bound to the tegument alone. Little cross-reactivity was found with the tissues of the tapeworm Hymenolepis, rather more with the closely related Schistosoma japonicum. It was concluded that tegument antigens are to a degree tissue specific but definitely not stage specific.

Animals↗

Genetic relationships among Escherichia coli isolates causing urinary tract infections in humans and animals.

Genetic variation in isolates of Escherichia coli obtained mostly from urinary tract infections in humans and domesticated animals (dogs and cats) was assessed for 16 enzymes using multilocus enzyme electrophoresis to characterize chromosomal genotypes. A total of 148 isolates comprised 63 distinct electrophoretic types (ETs) and about half of the isolates belonged to one of 9 common ETs. A bootstrap analysis of genetic distance between ETs revealed three significant groups of strains. Variation in allele frequencies among groups accounted for 40% of the total genetic diversity. The majority of the common ETs fell into a major cluster of closely related strains. The recovery of multiple isolates of the same electrophoretic types and serotypes from unassociated hosts suggests that these bacteria represent uropathogenic clones that are widely disseminated in humans and animals.

Animals↗

Abnormal exercise hemodynamics in cardiac allograft recipients 1 year after cardiac transplantation. Relation to preload reserve.

The well-established elevation in left ventricular filling pressures during exercise in patients after transplantation may contribute to decreased exercise tolerance. A proposed mechanism for this increase in filling pressures is an abnormal pressure-volume homeostasis of the transplanted heart. Twenty-three patients undergoing routine 1-year evaluations performed supine bicycle exercise during right heart catheterization. Within 24 hours, these patients underwent supine bicycle exercise to the identical work load during radionuclide ventriculography. For the group, resting hemodynamics and resting left and right ventricular ejection fractions were normal. With exercise, right atrial and pulmonary wedge pressure rose markedly (from 6 +/- 2 to 14 +/- 7 mm Hg, p less than 0.0001, and from 10 +/- 3 to 20 +/- 6 mm Hg, p less than 0.0001, respectively). Left ventricular ejection fraction increased appropriately with exercise (from 0.58 +/- 0.08 to 0.63 +/- 0.07, p = 0.004). End-diastolic volume also increased mildly (from 100 +/- 31 to 117 +/- 39 ml, p = 0.001), but change in end-diastolic volume was highly variable. Patients with little or no change in end-diastolic volume with exercise had the greatest resting and exercise left ventricular filling pressures resulting in significant negative correlations between filling pressures and change in end-diastolic volume (r = -0.64, p = 0.002 and r = -0.50, p = 0.025, respectively). Negative linear relations between exercise left ventricular filling pressures or resting heart rates and donor to recipient body weight ratio (r = -0.35, p = 0.10, and r = -0.37, p = 0.06, respectively) suggested that initial donor heart size influenced subsequent cardiac function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The growth and development of Schistosoma mansoni in mice exposed to sublethal doses of radiation.

The maturation of Schistosoma mansoni was studied in mice exposed to various sublethal doses of radiation. Although the treatment of mice with 500 rads of radiation prior to infection did not alter parasite maturation, doses in excess of 500 rads led to a reduction in worm burden. This could not be attributed to a delay in the arrival of parasites in the hepatic portal system. Worms developing in mice treated with 800 rads commenced egg-laying about 1 wk later than worms in intact mice, and the rate of egg deposition appeared to be lower in irradiated hosts. The data demonstrate that exposure of C57BL/6 mice to doses of radiation in excess of 500 rads impairs their ability to carry infections of S. mansoni. The findings do not support the hypothesis that primary worm burdens in the mouse are controlled by a host immune response.

Animals↗

Effect of thallium-201 blood levels on reversible myocardial defects.

To determine if 201Tl plasma blood levels correlate with the presence of reversible myocardial defects during exercise testing, 14 patients with stable coronary artery disease underwent two separate exercise 201Tl stress tests. Between initial and delayed imaging, on one test the patients drank an instant breakfast drink (eating) and on the other they drank an equivalent volume of water as a control (H2O). Thallium-201 imaging was performed immediately postexercise, immediately after eating/H2O and 210 min after eating/H2O. Between initial and immediate post eating/H2O images 201Tl reversible defects occurred in 27/38 regions in the H2O test versus 15/38 regions in the eating test (p = 0.02). Over this early time period, plasma 201Tl activity was significantly higher in the H2O test than eating test (p less than 0.05). In conclusion, early reversal of 201Tl defects may, in part, be the result of higher plasma 201Tl activity early after initial postexercise 201Tl imaging.

Angina Pectoris↗

Left ventricular response to submaximal and maximal exercise in asymptomatic aortic regurgitation.

In patients with chronic aortic regurgitation the quantitative changes in loading conditions and left ventricular performance from rest to submaximal exercise have not been related to the magnitude of change observed from rest to maximal exercise. Changes in end-diastolic volume index, as a measure of preload, and measures of contractile performance (ejection fraction and the systolic blood pressure/end-systolic volume index ratio) were assessed at rest, submaximal and maximal supine bicycle exercise using radionuclide angiography in 74 patients with chronic moderate to severe aortic regurgitation. With exercise, end-diastolic volume index decreased in a stepwise manner from 166 +/- 47 to 152 +/- 41 to 143 +/- 41 ml/m2 at rest, submaximal and maximal exercise, respectively. For the entire group, these changes were not associated with a significant change in ejection fraction but were associated with stepwise increases in systolic blood pressure to end-systolic volume index ratio. However, when patients were divided into 3 subgroups based on an increase (group I), minimal change (group II) or a decrease (group III) in ejection fraction from rest to maximal exercise, stepwise increases in systolic blood pressure to end-systolic volume index were again observed in groups I and II but not in group III. These changes were significantly greater in group I than in group II at submaximal and maximal exercise levels. Differences in ejection fraction response and end-diastolic and end-systolic volumes with exercise in the 3 groups were evident at the submaximal exercise level.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Insufficiency↗