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Biomedical subjects

R A Wilson

Publications and source records attributed to R A Wilson.

At least 199 records · Page 11Linked to original sources

Biodistribution of tantalum-178: a short-lived radiopharmaceutical for blood pool imaging.

178Ta is a short lived radionuclide (half life = 9.3 min), which results in favorable radiation exposure compared to 99mTc (half life 6 h). The energy spectrum of 178Ta consists of imageable photons in the 55-65 keV (61.2%) and 93 keV (33.7%) range but also 6% of disintegrations result in photons with energies greater than 500 keV. These high energy photons cause septal penetration in low energy collimators so that resolution is degraded. However, a medium energy collimator prevents the septal penetration of these higher energy photons. Serial blood samples obtained from dog and rabbit models indicate that 178Ta is retained in the blood pool for at least 20-30 min after intravenous injection. The 178Ta appears to be associated with the protein fraction of the plasma and not primarily with the red blood cell fraction as determined by centrifugation and column chromatography. Gated equilibrium blood pool images using 178Ta were comparable in quality to images using the 99mTc labelled red blood cell technique. Therefore, 178Ta may allow comparable equilibrium gated blood pool imaging with much more favorable radiation dosimetry. Thus, serial studies over prolonged periods of observation may be obtained.

Animals↗

Asymptomatic myocardial ischemia following cold provocation.

Cold is thought to provoke angina in patients with coronary disease either by an increase in myocardial demand or an increase in coronary vascular resistance. We investigated and compared the effects of cold pressor stimulation and symptom-limited supine bicycle exercise on regional myocardial perfusion in 35 patients with stable angina and coronary disease and in 10 normal subjects. Regional myocardial perfusion was assessed with positron emission tomography and rubidium-82. Following cold pressor stimulation 24 of 35 patients demonstrated significant abnormalities of regional myocardial perfusion with reduced cation uptake in affected regions of myocardium: 52 +/- 9 to 43 +/- 9 (p less than 0.001 vs normal subjects). Among these 24 patients only nine developed ST depression and only seven had angina. In contrast, 29 of 35 patients underwent supine exercise, and abnormal regional myocardial perfusion occurred in all 29, with a reduction in cation intake from 48 +/- 10 to 43 +/- 14 (p less than 0.001 vs normal subjects). Angina was present in 27 of 29 and ST depression in 25 of 29. Although the absolute decrease in cation uptake was somewhat greater following cold as opposed to exercise, the peak heart rate after cold was significantly lower than that after exercise (82 +/- 12 vs 108 +/- 16 bpm, p less than 0.05). Peak systolic blood pressures after cold and exercise were similar (159 +/- 24 vs 158 +/- 28). Thus, cold produces much more frequent asymptomatic disturbances of regional myocardial perfusion in patients with stable angina and coronary disease than is suggested by pain or ECG changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Silent myocardial ischemia during mastication.

Ambulatory outpatient monitoring of patients with angina suggests a different view of myocardial ischemia than is conventionally obtained from in-hospital tests. Multiple episodes of ST segment depression occur, and the majority of these disturbances are not associated with symptoms. Recently, studies of regional myocardial perfusion using the technique of positron emission tomography with rubidium 82 have confirmed the ischemic nature of these silent ST changes. Furthermore, activities of everyday life such as mental stress or cold exposure seem to provoke both symptomatic and asymptomatic ischemia, as judged by ST depression and reduced cation uptake. This report presents an unusual case of silent myocardial ischemia observed during the chewing of food.

Aged↗

Immunity after treatment of human schistosomiasis mansoni quantitative and qualitative antibody responses to tegumental membrane antigens prepared from adult worms.

Quantitative antibody responses of individual Kenyan children to a tegument membrane preparation from adult schistosomes have been studied by enzyme-linked immunosorbent assay. Qualitative differences between patients were examined by electrophoretic fractionation of the membrane preparation followed by Western blotting analysis. All individuals had antibodies to the preparation, the level increasing twofold shortly after chemotherapy and declining to pre-treatment levels by 6 months. Susceptible children had significantly higher levels of antibody than resistant individuals at 12 and 18 months after chemotherapy. Antibody levels were positively associated with patient age (particularly over the range 8-12 years at the first bleed after chemotherapy) and the logarithm of pre-treatment egg excretion. The strongest association was observed between initial antibody level and subsequent levels. A total of 47 distinct antigens was detected in the membrane preparation. The major antigens were detected equally strongly by sera from both susceptible and resistant groups of children. At the outset the resistant group responded more strongly to 35%, and more weakly to 15%, of the antigens than the susceptible group. At the end of the study the figures were reversed, being 21% and 38% respectively, probably reflecting the reflecting the reinfection of the susceptible group. 3 antigens of molecular mass 100, 50 and 27 kDa were exceptions to the trend, being detected more strongly by the resistant than the susceptible group at one or more later times. It was concluded that the differences in total antibody level to the tegument membrane preparation were insufficient to account for the resistant or susceptible status of the children.

Animals↗

The transport and metabolism of bovine IgM.

IgM is present in cows milk, is able to bind secretory component (SC), has a purported role as a secretory immunoglobulin in other species and has been identified with various antibody functions in cows milk. To determine the origin of cows milk IgM, we administered extrinsic 131I-IgM to lactating cows with cannulated bile and parotid ducts and studied the kinetics of its disappearance from serum and its appearance in milk, bile and parotid saliva for 60 hr post-injection. Pentameric IgM appeared to require a long equilibration time and disappeared from serum with a T1/2 of 40 hr. The transport of IgM into bile also appeared biphasic. Results showed that no 131I-IgM was transported intact into parotid saliva and that most radioactivity in milk and bile after 6 hr was in the form of low mol. wt, TCA-precipitable fragments rather than of the size of a pentamer. During the first 24 hr only 0.83% of the administered dose reached the milk in pentameric form, nevertheless, isotope dilution calculations indicated that nearly all milk IgM was derived from serum. During a 12 hr collection period, corresponding to one milking, greater than 200 mg of serum IgM is secreted in milk. During the first 24 hr, only 0.70% of the administered IgM reached the bile as a pentamer. It was calculated that 50% of the pentameric IgM in bile, 3 hr after administration, was serum-derived. Twenty-five per cent of the IgM appearing in bile and ca 10% of the IgM appearing milk, becomes associated with secretory component. A hypothesis to explain the degradation associated with this inefficient transport mechanism is presented.

Animals↗

The outer bilayer of the adult schistosome tegument surface has a low turnover rate in vitro and in vivo.

An immunoradiometric assay has been used to determine the rate of loss of host erythrocyte antigen from the tegumental surface of adult Schistosoma mansoni. Host antigens were lost from the parasite surface with a half-time of up to 45 h during chase incubation in vitro, and with a half-time of about 5 days during residence in vivo in naive recipient hamsters. Since the host antigens were associated intimately with the outer bilayer of the tegument surface, it is suggested that the rate of surface turnover may similarly be very low. The implications of these findings for immune evasion by the adult parasite are discussed.

Animals↗

Returns to entering the medical profession in the U.K.

This paper examines the idea that medical professions in the United Kingdom have, as a result of restrictive practices of various kinds, managed to obtain rates of return to their education and training well above those achieved in other professions. It concludes that after making various adjustments, in particular allowing for differences in hours worked, the returns obtained are in most cases not very different from those for other professions. With the exception of dentists there is therefore no clear-cut evidence from earnings data alone of restrictive practices in the medical professions.

Data Collection↗

Studies on heterologous resistance between Schistosoma mansoni and Fasciola hepatica in inbred rats.

Fischer rats infected with Fasciola hepatica showed significant resistance to Schistosoma mansoni challenge, and vice versa, whereas immunization with 20 Krad-irradiated S. mansoni cercariae failed to protect against F. hepatica challenge, but did protect against homologous challenge. When groups of rats received intraperitoneal implants of newly excysted juvenile flukes, 20- to 22-day-old juveniles, or 8- to 10-week-old flukes, none was significantly protected against S. mansoni challenge, whereas juvenile implants did protect against homologous F. hepatica challenge. In passive transfer experiments in rats, serum from F. hepatica-infected rats or rabbits protected recipients against homologous, but not heterologous challenge, and serum from rats vaccinated with 20 Krad-irradiated S. mansoni cercariae protected recipients against homologous, but not heterologous challenge. These experiments provide evidence that the mechanisms involved in homologous and heterologous resistance are different, the latter lacking immunological specificity. Microsphere injections in F. hepatica-infected rats demonstrated 'shunting' from the portal system to the systemic circulation. If migrating schistosomula are also 'shunted' in Fasciola-infected rats, this, rather than immunologically specific effector mechanisms, might explain their failure to establish in the portal system.

Animals↗

Pathologically induced alterations in the dimensions of the hepatic portal vasculature of mice infected with Schistosoma mansoni.

Alterations in the hepatic portal vasculature of NMRI mice infected with Schistosoma mansoni were assessed using a microsphere injection technique. The accumulation of eggs in the livers of infected mice and the development of portal hypertension were closely related to the worm pair burden during the first 15 weeks of infection. Individual variation between mice harbouring identical patent worm pair burdens was partially explained by the reduced fecundity of females from sexually biased infections. As eggs accumulated in the liver and portal hypertension increased, the number of injected microspheres escaping from the hepatic portal system rose in rank order of diameter from 9 microns through 15 microns and 25 microns to 50 microns. There was a strong correlation between the numbers of parasite eggs in the lungs and injected microspheres recovered from the lungs. The pattern of detection of microspheres in the lungs indicated a progressive increase in diameter of intra-hepatic porta-systemic connexions, followed by development of large-bore extra-hepatic collateral vessels. An accurate temporal profile of the pathological state of the host and the extent of collateral vessel formation was obtained. Injection of 141-Ce-labelled microspheres demonstrated that the arterial supply to all organs of the body was affected by alterations in the microvasculature of the liver and lungs.

Animals↗

The relationship between pathology and resistance to reinfection with Schistosoma mansoni in mice: a causal mechanism of resistance in chronic infections.

The development of resistance in mice to reinfection with Schistosoma mansoni was recorded during an early chronic infection, and compared with hepatic portal pathological and vascular changes. The latter were assessed using a microsphere injection technique. The degree of acquired resistance was directly dependent on the patent worm burden and the time post-infection. Strong correlations were noted between the development of resistance and the appearance of parasite eggs in the lungs and spleens of infected hosts. Weaker associations were present between resistance and other aspects of the disease pathology, such as portal hypertension and organ weights. The appearance of injected microspheres in the lungs and spleens correlated well with the appearance of eggs in those organs and with the development of resistance. The levels of resistance had risen and microspheres were detected in the lungs, before the development of major extra-hepatic, porta-systemic collateral vessels. It is concluded that intra-hepatic vascular alterations may be a causal factor in the development of resistance, preventing the sequestration of migrating schistosomula in the liver. It is estimated that as much as 70-75% of the recorded resistance can be attributed to this immunologically non-specific mechanism.

Animals↗

Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni.

Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni.

Animals↗

Use of short- and long-lived rubidium tracers for the study of transient ischemia.

Positron emission tomography (PET) with rubidium-82 (82Rb) has been developed to measure regional myocardial perfusion and to detect transient ischemia both in the experimental laboratory and in humans. There are known and separate contaminating effects of the 82Rb signal by disturbances in wall motion, wall thinning, and the partial volume effect that occur during transient ischemia. In nine anesthetized greyhounds, PET with 82Rb (T1/2 = 78 sec) was used to determine the regional myocardial uptake of this cation during a control period that consisted of a mild stenosis of the left anterior descending coronary artery in the absence of ischemia (to limit reactive hyperemia), during 10 min of total occlusion and, finally, at 30 and 60 min of recovery with release of the occlusion but not of the stenosis. Separately, rubidium-81 (81Rb); T1/2 = 4.58 hr) was given as a peripheral intravenous injection 2 hr before the study to allow this long-lived tracer to distribute in the potassium space of the myocardium. Observations during control and ischemia revealed marked decreases in 82Rb uptake (0.84 +/- 0.12 to 0.28 +/- 0.12, p = 0.001) in affected regions and were paralleled by similar decreases in microsphere blood flow (0.88 +/- 0.08 to 0.12 +/- 0.10 ml/min/g, p = 0.003), which gradually recovered by 60 min postischemia. Lesser decreases in 81Rb activity (0.84 +/- 0.11 to 0.76 +/- 0.17, p = 0.83) were observed in the same regions during ischemia, but these were immediately reversible. Separate in vitro postmortem experiments in eight rabbits confirmed a linear relationship between plasma and myocardial activities of stable potassium and 81Rb although there was a greater concentration of 81Rb in the myocardium that in the plasma relative to potassium (y = -3.29 +/- 0.79 x, s.e.e. 1.91, r = 0.95). These studies demonstrate that if 81Rb is given intravenously to distribute into the potassium pool, tomograms of the heart may be recorded to measure the potassium-rich mass of myocardium providing information about the acute effects of wall thinning during ischemia. Rubidium-81 used in this way may be helpful in assessing the effects of wall thinning and/or scar when other tracers are being used to assess perfusion or metabolism.

Animals↗

Direct effects of smoking on the heart: silent ischemic disturbances of coronary flow.

Cigarette smoking is strongly associated with ischemic heart disease and acute coronary events. The effect of smoking a single cigarette on regional myocardial perfusion was studied in 13 chronic smokers with typical stable angina pectoris using positron emission tomography and rubidium-82 (82Rb). Findings were compared with the effects of physical exercise. After exercise, 8 patients (61%) had angina, ST depression and abnormal regional myocardial perfusion. Uptake of 82Rb increased from 49 +/- 8 to 60 +/- 7 in remote myocardium, but decreased from 46 +/- 3 to 37 +/- 5 in an ischemic area. The remaining 5 patients (39%) had homogeneous increases in 82Rb uptake without angina or ST depression. After smoking, 6 of the 8 patients with positive exercise test responses had a decrease in 82Rb uptake, from 47 +/- 3 to 35 +/- 6 in the same segment of myocardium affected during exercise. However, in contrast to exercise, the events during smoking were largely silent. The absolute decreases in regional 82Rb uptake after smoking occurred at significantly lower levels of myocardial oxygen demand than after exercise. This suggests that an impairment of coronary blood supply is responsible. Thus, in smokers with coronary artery disease, each cigarette can cause profound silent disturbances of regional myocardial perfusion that are likely to occur frequently during daily life. Such repeated insults may represent an important mechanism linking smoking with coronary events.

Adult↗

High technology diagnostics: detection of enterotoxigenic Escherichia coli, using DNA probes.

A relatively new technique termed colony blot hybridization appears to be a reliable replacement for the ligated porcine gut loop assay previously used to detect stable toxin-B producing Escherichia coli. The highly reproducible blot assay enables screening of large numbers of isolants for the presence of E coli stable-B toxin genes, thus avoiding variations in phenotypic expression and poor repeatability inherent in the in vivo assays. Availability of this diagnostic test can aid practitioners in identifying enterotoxigenic E coli related disease in swine and in determining the benefits of vaccination programs.

Animals↗

A qualitative and quantitative analysis of proteins found in vespid venoms.

Diagnosis and immunotherapy with venom extracts of patients sensitive to Hymenoptera stings has led to the problem of improving the standardization of Hymenoptera venom products. Current methods of standardization use the Lowry protein determination and a radial-diffusion assay for hyaluronidase activity. This study demonstrates that the results of these analyses do not always correlate with the actual quantity of allergenic protein present in the extracts. A method of standardization is examined herein that uses polyacrylamide gel electrophoresis to quantitate phospholipase A, antigen 5, and hyaluronidase, the proteins that together comprise most allergenic protein present in the venoms. Also discussed in this study is the biochemical variability of phospholipase A and antigen 5 in the venoms of the different vespid species examined.

Bee Venoms↗

The metabolism and transport of bovine serum SIgA.

Experiments were undertaken in six Holstein-Friesian cattle to determine whether secretory IgA (SIgA) could be transported from serum into exocrine body fluids. Preliminary data indicated that when IgG1, IgG2, IgM and SIgA were administered i.v., only SIgA and IgG1 appeared in bile 90 min later at concentrations equal to or exceeding those in serum at the same time. Two hours post-injection, 70% of the SIgA recovered in bile was intact however only 30% co-precipitable with anti-secretory component (SC) while greater than 90% of the administered IgA was precipitated by this method. All recovered IgG1 was of low molecular weight. More detailed studies indicated that the IgA recovered in bile 7 h post-injection or in milk 3 h post-injection, was predominantly lower molecular weight than intact SIgA. Most of this low molecular weight radioactivity was TCA precipitable and ca 50% was dialyzable; these data indicate that TCA-precipitability is an inadequate criterion for determining whether intact SIgA is transported. The radioactivity recovered in parotid saliva was almost entirely non-TCA precipitable and dialyzable. Almost all SIgA recovered in bovine serum remained intact and had a t1/2 of 15.7 h. When transport into milk and bile was calculated from total, recovered radioactivity (i.e. 29% and 2.7, respectively), data compared favorably with those conducted in sheep in which dimeric IgA (without SC) was administered i.v. When we calculated transport on the basis of recovered intact IgA, only 1.47 and 0.54% of the injected dose had been transported into milk and bile, respectively, 24 h later. Most IgA in ruminant bile may be of serum origin although the same appears to be unlikely for the IgA in milk.

Animals↗

A study of bovine T-cell subsets in the blood and mammary gland secretions during the dry period.

Blood and mammary secretions were obtained from cows throughout the dry period. Quantitative and qualitative assays were performed to determine the cell types and cell distributions at weekly intervals from day of dry off until parturition. The total cell counts in secretions increased during involution and remained at high levels until a few weeks prepartum. The macrophages were the predominant cell type in mammary secretions whereas the numbers of lymphocytes were always less than neutrophils or macrophages. Enriched mononuclear cell populations derived from blood and mammary secretions were also evaluated using "T-cell rosette" assays. Changes observed in the relative distribution of three T-cell subsets in secretions did not reflect the dynamics of the cells in the peripheral blood. T-cell subsets that predominated in mammary secretions were the EN+ EAET+ and EN-EAET+ phenotypes. Distinct patterns of migration or differentiation of T-cell subsets were suggested by the changes of subsets observed in mammary secretions collected throughout the dry period.

Animals↗

Techniques for locating isotopically labelled schistosomula of Schistosoma mansoni in host tissues for ultrastructural investigations.

The use of 75 Selenomethionine labelled cercariae of Schistosoma mansoni for ultrastructural localization of parasites in host tissues has been evaluated. Both gamma counting of tissue, and autoradiography of resin-embedded tissue were successful. The autoradiographic technique was more sensitive and schistosomula were readily located in pulmonary tissue up to 24 days post-infection.

Animals↗