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Biomedical subjects

R A Wilson

Publications and source records attributed to R A Wilson.

At least 217 records · Page 12Linked to original sources

Schistosoma mansoni: dynamics of migration through the vascular system of the mouse.

Autoradiography of compressed mouse tissues has been used to estimate the numbers of 75Se-labelled schistosomula present in different mouse organs. Day 7 parasites extracted from the lungs of donor mice were delivered by injection to the lungs, systemic organs and liver of recipient mice as a discrete pulse. The numbers detected in various locations with time post-injection were then used to analyse the dynamics of intravascular migration. Approximately 98% of cercaria-associated label was lost during the first 14 days of parasite life, two-thirds of this in the first 7 h post-infection. Nevertheless, 99-113% of schistosomula could be detected 30 min post-injection into the locations chosen. The efficiency of the parasite delivery system was 95%. The time required for the number of foci in the lungs to decline to 50%, after injection of parasites via the femoral vein, was 55 h. Adjustment of this data to allow for parasites returning to the lungs after passage round the systemic vasculature gave a value of 30-35 h for the true mean time of lung transit. The distribution of parasites to systemic organs after their exit from the lungs was proportional to the fractional distribution of cardiac output. The probability (P) of a schistosomulum being distributed to splanchnic beds was estimated at 0.32 and its P of being trapped in the hepatic portal distributaries within the liver as 0.72-0.86. On this basis, the entire hepatic portal population of adult schistosomes would be recruited during 2-3 circuits of parasites around the pulmonary--systemic vasculature. The mean transit time of schistosomula through intestinal capillaries was 6.5 h whilst that through other systemic organs combined (muscles, kidneys, brain, etc) was 16 h, considerably more rapid than lung transit. The time taken for schistosomula to pass between organs, in arterial and venous blood, was shown to be less than 30 min in both cases (probably much less).

Animals↗

Migration of the schistosomula of Schistosoma mansoni in mice vaccinated with radiation-attenuated cercariae, and normal mice: an attempt to identify the timing and site of parasite death.

The migration of the schistosomula of Schistosoma mansoni labelled with [75Se]methionine, has been followed from the skin to the hepatic portal system. Parasites were detected in all mouse tissues by compressed organ autoradiography. Two separate experiments were performed to track parasites in normal mice, and in mice previously vaccinated with irradiated cercariae. In normal mice, the profile of numbers of autoradiographic foci detected in the skin, lungs, systemic and splanchnic organs was described with time post-infection. The distribution of parasites to systemic organs, following exit from the lungs, paralleled the fractional distribution of cardiac output. Accumulation of schistosomula in the hepatic portal system was complete by day 21 post-infection. Only 2-3 passes of parasites around the vascular system would be required to produce the hepatic portal population. No significant decline in total foci was detected in the first 12 days post-infection. The majority of parasite elimination appeared to occur in the lungs as late as day 21, with lesser proportions in the systemic organs and skin infection site. The pattern of migration in vaccinated mice was similar to that in normal animals. One difference observed was the longer duration of stay in the skin; however, the majority of parasites eventually reached the lungs. The systemic phase of migration occurred on a reduced scale, as did accumulation of parasites in the hepatic portal system. The decline in total foci in vaccinated mice commenced approximately 7 days earlier than in normal mice and proceeded to a lower end-point. Again the majority of parasite elimination appeared to occur in the lungs with lesser proportions in the systemic organs and skin infection site. It is suggested that resistance to reinfection in vaccinated mice has two additive components which combine to retard the migration of schistosomula within the vasculature, preventing them from reaching the hepatic protal system.

Animals↗

Schistosoma mansoni: an ultrastructural examination of pulmonary migration.

The migration of schistosomula through the lungs of mice has been investigated at the ultrastructural level. On Days 4 and 7 post-infection schistosomula were located only within the vasculature. Newly arrived Day 4 schistosomula were highly convoluted and completely occluded vessels measuring approximately 15-25 micron in diameter. By Day 7 parasites were located in pulmonary capillaries, often causing considerable distension. The subtegumentary fibrous interstitial layer was absent in elongated lung schistosomula. The minimum diameter of such parasites was 8 micron, and their tegument was usually unridged and flattened against the vascular endothelium, thus resulting in close apposition of endothelial and tegumental membranes. The tight fit of schistosomula in the pulmonary capillaries implies that migration through them is both a strenuous and slow process. The migratory delay in the lungs after arrival from the skin occurs because dimensional changes are necessary for successful capillary migration.

Animals↗

The role of pulmonary cellular reactions in the resistance of vaccinated mice to Schistosoma mansoni.

A histopathological and ultrastructural study was made of schistosomula and associated inflammatory reactions in the lungs of normal mice, and mice previously vaccinated with irradiated cercariae. In normal mice at day 7 post-infection all schistosomula were located in blood vessels. From day 11 onwards an increasing proportion of schistosomula were intra-alveolar (80% from day 20). No cellular reactions were evident around intravascular parasites in normal mice but at later sampling times large compact foci were associated with alveolar parasites. Initial reactions, probably in response to non-specific tissue damage, were approximately 50% polymorphonuclear, and 50% mononuclear. Mononuclear cells predominated at later times. In spite of inflammation, no damage to the schistosomula was observed. There was no evidence for re-entry of schistosomula into blood vessels, and it was assumed entry into alveoli occurred accidentally as parasites attempted to traverse pulmonary blood vessels. The pattern of localization of schistosomula in vaccinated mice was similar to that in normal mice, the proportion in alveoli increasing with time (64% from day 20). The most significant difference was that intravascular schistosomula attracted foci of host leucocytes which were always 85% or more mononuclear, containing both lymphocytes and macrophages. The infiltrating cells enlarged the intersititium, separating the vascular endothelium from the alveolar epithelium. Fibrous protein was also deposited in the interstitial region. In some instances the complete blood-air barrier was destroyed by the infiltrates. Unusual paracrystalline inclusions were observed in alveolar macrophages and giant cells. The differences in cellular responses in vaccinated and normal mice suggest that challenge schistosomula stimulated an anamnestic immune response. The resulting inflammation, by impeding movement through the vasculature, terminated migration in the lungs, and accounted for the observed resistance to reinfection. The reactions in vaccinated mice have many of the features of a delayed hypersensitivity response implying that lung phase resistance in vaccinated mice may be T-cell rather than antibody-mediated.

Animals↗

The effect of eating on thallium myocardial imaging.

To determine if eating between initial and delayed thallium images alters the appearance of the delayed thallium scan, a prospective study was performed; 184 subjects sent for routine thallium imaging were randomized into two groups, those who ate a meal high in carbohydrates between initial and delayed thallium myocardial images (n = 106), and those who fasted (n = 78). The 201Tl images were interpreted in blinded fashion for global myocardial and pulmonary clearance of 201Tl myocardial defects. The eating group had a significantly lower incidence of transient myocardial defects compared to the noneating group (7 percent vs 18 percent, respectively; p less than 0.05). The time between initial and delayed images and the incidence of exercise-induced ischemic ST-segment depression or pathologic Q waves on the electrocardiogram were not significantly different between the two groups. These data suggest that eating a high-carbohydrate meal between initial and delayed 201Tl images causes increased 201Tl myocardial clearance rates and may alter 201Tl myocardial redistribution over time.

Adult↗

In vitro growth of mastitis pathogens in mammary secretions of the dry and peripartum periods.

In vitro growth of Escherichia coli, Streptococcus uberis, and Staphylococcus aureus was measured in skimmed, cell-free secretions of bovine mammary glands collected on d 0, 7, 14, and 28 of the dry period; 12, 8, and 4 d before expected calving; and on d 0 and 14 postpartum. There were marked and nearly inverse changes in growth of Escherichia coli and Streptococcus uberis over the experimental period. Escherichia coli grew well in secretions of d 0 of the dry period and d 0 and 14 postcalving but poorly or not at all in secretions of the mid-dry period. In contrast, Streptococcus uberis grew well in secretions of the involuted gland and poorly in samples from day of dry off and day of calving. Growth of Staphylococcus aureus changed relatively little over the dry period, but there was reduction in growth at d 7 of the dry period. Changing ability of the secretion to support bacterial growth may influence changing susceptibility to infection, but for Streptococcus uberis, poor correspondence between changes in growth supported by the secretion and changes in the incidence of naturally occurring infection over the dry period indicates that other factors may be more important.

Animals↗

Site requirements and kinetics of immune-dependent elimination of intravascularly administered lung stage schistosomula in mice immunized with highly irradiated cercariae of Schistosoma mansoni.

Experiments were performed to compare the migration and survival of 75Se-labeled schistosomes, introduced by percutaneous cercarial exposure or by intravascular administration of 7-day-old lung stage schistosomula, in control and irradiated cercaria-immunized mice. Schistosomula were intravascularly introduced into the lungs, systemic organs and liver by injection via the femoral vein (FV), left ventricle (LV), and superior mesenteric vein (SMV), respectively. The fate of challenge larvae was examined by autoradiography of host tissues and by recovery of adult worms. It was found that both normal and immune elimination were site-dependent. In control mice 45%-60% of cercarial penetrants and lung schistosomula injected into the FV and LV were recoverable as adult worms, while a significantly greater number (70%-85%) were recoverable when lung schistosomula were injected into the SMV. In immunized mice, parasites introduced as either cercariae or FV-injected schistosomula were both highly sensitive to immune elimination. LV-injected schistosomula were also sensitive but to a slightly lesser degree. In contrast, schistosomula placed directly in the liver by SMV injection were totally insensitive to immune elimination. It was concluded that elimination of schistosomula in irradiated cercaria-immunized mice occurs in the lungs and/or in the systemic organs, but not in the liver. Also, it was concluded that immune elimination is not a rapid process, since more than 7 days were required after intravascular challenge for the development of demonstrable differences between control and immunized mice.

Animals↗

Fimbriae and enterotoxins associated with Escherichia coli serogroups isolated from pigs with colibacillosis.

A comprehensive study of 223 Escherichia coli isolates from pigs with colibacillosis included determination of O serogroups, detection of heat-labile enterotoxin, heat-stable enterotoxin (STa and STb), and identification of K88, K99, 987-P, F-41, and type 1 fimbriae. The incidence of the various E coli types among isolates of pigs of different ages was also determined. Escherichia coli bearing K88 fimbriae accounted for 48% of all isolates studied, were most often of serogroup O157, O149, or O8, and usually produced labile toxin alone or in combination with STa or STb. These E coli were commonly isolated from pigs in each age group studied (0 to 5 days, 6 to 10 days, 11 to 24 days, and greater than 24 days). Escherichia coli bearing 987-P accounted for 30% of the isolates, were most often of serogroup O141 or O20, and usually produced STa. Escherichia coli bearing K99 accounted for 13% of the isolates, usually were of serogroup O101 or O8, and almost always produced STa. Escherichia coli bearing 987-P or K99 were most often isolated from pigs less than 6 days of age. Fimbriae F-41, when identified, were usually on E coli of serotype O101:K99. Although infrequently found, type 1 fimbriae were on E coli of most of the serogroups identified in this study.

Animals↗

Clinical problems in coronary disease are caused by wide variety of ischemic episodes that affect patients out of hospital.

Transient ischemia arising from proximal events in epicardial coronary arteries causes important symptoms, such as angina pectoris, and is usually studied in the hospital with provocative tests. However, Holter monitoring of ST-segment disturbances in patients out of the hospital has shown frequent asymptomatic evidence of ischemia that is surprisingly prolonged and that is not associated with the obvious tachycardia of exercise or stress. Positron emission tomography has been developed to measure the regional myocardial uptake of a cation (rubidium-82) in order to assess repeatedly the directional changes in regional coronary blood flow during these events. This method has been used to show that both symptomatic and asymptomatic episodes of ST depression are reliably associated with disturbances in regional myocardial perfusion. The daily activities of patients have been analyzed and reproduced in the hospital to assess the effects of cold stimulation, mental arithmetic, cigarette smoking, and exercise. Physical exercise was associated with angina, ST-segment change, and regional abnormalities of myocardial perfusion, including decreased perfusion in poststenotic segments. The other tests caused the same disturbances in myocardial perfusion; these perfusion disturbances were mostly asymptomatic and surprisingly prolonged, with periods of recovery that were two to five times longer than the ST-segment disturbance and the pain. Current studies using a structured diary indicate that the episodes of transient ischemia occurring out of the hospital are more frequently associated with different levels of mental arousal than with any other activity. Physical exercise is a relatively infrequent cause of transient ischemia. The examination of coronary blood flow using provocative tests derived from the patients' own activities out of the hospital have confirmed that, irrespective of the pattern of angina, patients have frequent episodes of asymptomatic transient ischemia that are surprisingly prolonged and that these episodes occur in response to previously unsuspected ordinary daily activities. The disturbances in coronary blood flow usually include a regional decrease in myocardial perfusion that can only be explained by pathophysiologic events in the proximal epicardial coronary arteries.

Activities of Daily Living↗

The effect of glucose-insulin-potassium on thallium-201 myocardial redistribution.

Intravenous infusion of glucose-insulin-potassium (GIK) has been shown to alter the net rate of clearance of 201Tl from transiently ischemic and normally perfused canine myocardium. This study was performed to determine if GIK would also decrease the extent of thallium redistribution after transient myocardial ischemia. Six anesthetized, open-chest dogs underwent two studies, one with GIK and another with saline infusion. The left anterior descending coronary artery was occluded, 201Tl injected, and the occlusion released 5-min later. An i.v. infusion of either GIK (4 dogs) or saline (2 dogs) was then begun and continued for the 120-min duration of serial myocardial imaging using a standard scintillation camera. The experiment was then repeated with an infusion of saline (4 dogs) or GIK (2 dogs). The dose of 201Tl for the second study was at least 5 times more than was used for the first study. The serial 2-min images were then displayed on computer and regions of interest were drawn over the areas of transient ischemia (TI) and normal perfusion (NP). The ratio of average counts per picture element for the area of TI compared to NP was calculated. One hundred and twenty minutes after 201Tl administration, the change in the TI/NP ratio (% fill-in) was significantly less for the GIK infusion compared to saline infusion (control) 15.4 +/- 4.0% vs 26.2 +/- 6.0% (mean +/- SE) (P less than 0.01), respectively. Therefore, GIK infusion appeared to decrease the extent of thallium redistribution compared to saline control.

Animals↗

The next logical step in the emergency radiographic evaluation of cervical spine trauma: the five-view trauma series.

The five-view standard series is considered the golden standard in the radiographic evaluation of the cervical spine. Although the three-view trauma series has proved significantly more accurate than the cross-table lateral view in the emergency evaluation of patients with cervical spine trauma, this series does not deal with questionable findings. The introduction of a five-view trauma series, with the inclusion of supine oblique views, is the next logical step in the emergency evaluation of these patients. An algorithm for the emergency radiographic evaluation of patients with suspected cervical spine trauma is proposed.

Cervical Vertebrae↗

Induction of resistance to Schistosoma mansoni in mice by chemotherapy: migration of schistosomula in primary and challenge infections.

The fate of 75Se-labelled schistosomula in mice treated at 24 h post-infection with either Ro 11-3128 or oxamniquine, compared to untreated controls, was followed by compressed organ autoradiography. No difference in the total percentage of schistosomula detected as foci was found between the three groups at each sampling time. However, the distribution of schistosomula was altered. In oxamniquine-treated mice there was a delayed migration from the skin relative to controls and fewer parasites in total appeared to reach the lungs. In Ro 11-3128 treated mice very few parasites left the skin. Ro 11-3128 treatment induces resistance to challenge whereas oxamniquine does not. The fate of challenge schistosomula in previously infected Ro 11-3128 treated mice was also compared to that in control mice. There was evidence for delayed or reduced migration from the skin of Ro 11-3128 treated mice. Significant death of challenge parasites occurred in the lungs, or post-lung sites in both control and treated mice. It was not possible to conclude that any of the late attrition was immune-dependent in the treated mice and the results appeared to indicate that a significant fraction of parasite death occurred at the skin stage.

Animals↗

An ultrastructural examination of irradiated, immunizing schistosomula of Schistosoma mansoni during their extended stay in the lungs.

An ultrastructural study has been performed on radiation-attenuated parasites fixed in situ during their extended stay in the lungs. At day 7 post-infection all parasites were located within blood vessels. In contrast to normally migrating parasites, at days 13 and 21 post-infection the majority of radiation-attenuated parasites were lying free within alveoli. As far as could be seen, radiation-attenuated parasites had undergone the normal developmental changes associated with the lung stage of migration. These included elongation of the body and loss of mid-body spines and the fibrous layer beneath the tegument. No ultrastructural evidence was found to suggest why schistosomula failed to migrate further and instead burst into alveoli. No parasites observed on day 7 post-infection were associated with a host inflammatory reaction. At day 13, inflammation was noticeable but could have been a response as much to pulmonary tissue damage as to the presence of parasites. At day 21 post-infection some parasites were internally disrupted but were not associated with host inflammatory reactions and had intact tegumental surfaces - all facts consistent with death by autophagy. One parasite was observed at day 21 with an adherent neutrophil infiltrate and extensive tegumental damage. The relevance of persisting lung-stage parasites to the induction of resistance to challenge is discussed.

Animals↗

Schistosoma mansoni: an ultrastructural examination of skin migration in the hamster cheek pouch.

The hamster cheek pouch has been used to investigate the skin migration of schistosomula at the ultrastructural level. Parasites have been observed up to 72 h post-infection. Despite rapidly reaching the epidermal basement membrane schistosomula remain in an epidermal location for at least 40 h post-infection, by which time the acetabular glands and their ducts have been lost and the transformation from cercaria to schistosomulum completed. Entry into the dermis and exit from the skin via the blood vessels is therefore by mechanical means or by lytic secretions emanating from a source other than the acetabular glands. The head gland which persists in the dermal schistosomula is a probable source of such secretions. The observations suggest that the apical area and musculature of the head capsule are important in gaining access to the lumen of blood vessels.

Animals↗

Evaluation of a monoclonal antibody to the K99 fimbrial adhesin produced by Escherichia coli enterotoxigenic for calves, lambs and piglets.

All the K99+ Escherichia coli grown at 37 degrees C stained strongly with a peroxidase labelled K99 monoclonal antibody using a direct immunoperoxidase staining procedure. There was no reaction when these bacteria were cultured at 18 degrees C or when K99- E coli were grown at either temperature. The binding of the monoclonal antibody to K99 antigen was inhibited by OK antisera to heterologous K99+ E coli but OK antisera to E coli producing adhesins other than K99 were without effect. Using the slide agglutination test the reactions of the monoclonal antibody were identical to those of a polyclonal antiserum to K99 when both were used in parallel to examine 100 K99+ E coli from at least 10 somatic O groups and 1308 K99+ E coli from at least 82 different somatic O groups submitted for routine serological typing in England or the, USA. The monoclonal antibody reacted with K99+ E coli in cryostat sections of the ileum from a piglet infected with E coli strain B44 (O9: K30, K99, F41) but there was no reaction with similar material from piglets infected by E coli strains 1751 (O101: F41), X177/81 (O9: K103, 987P) or Abbotstown (O149: K91, K88ac).

Adhesins, Escherichia coli↗