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Biomedical subjects

D A Dean

Publications and source records attributed to D A Dean.

At least 73 records · Page 4Linked to original sources
PubMed1986

Attrition and temporal distribution of Schistosoma mansoni and S. haematobium schistosomula in laboratory mice.

The total number and distribution of schistosomula of Schistosoma mansoni and S. haematobium in all tissues and organs of mice from infection to 14-27 days was determined by compressed tissue autoradiography. Attrition of schistosomula, manifested as a decrease in the number of autoradiographic foci, was observed in organs other than the liver. Attrition commenced about 2 days after cercariae entered the skin, and conformed to a single exponential function with a rate constant (+/- standard error) of 7.0 +/- 0.5%/day for S. mansoni and 3.2 +/- 0.7%/day for S. haematobium. The temporal distribution of schistosomula of S. mansoni and S. haematobium differed quantitatively. In the case of S. mansoni, concomitant with a decrease in skin counts, the lung curve rose rapidly to a peak centred on day 6 and thereafter decreased more or less parallel to the total body curve. Significant accumulation in the liver was not observed until day 7, whereupon liver counts rose steadily to a plateau that extended from about day 14 to the end of the experiment and approximated the number of adult worms recovered from the hepatic portal vessels on day 42. A maximum of 26% and mean of 12% of all foci in the body were counted on autoradiograms of tissues other than the skin, lung and liver. The pelt averaged 14% of the body weight yet schistosomula were detected only in the area initially exposed to cercariae. The eviscerated carcass averaged 54% of the body weight yet contained only 0.8%-3.4% of the schistosomula during the period of accumulation in the liver. Between day 6 and day 14, the ratio of schistosomula in the pulmonary circulation to schistosomula in the systemic circulation did not remain constant, as would be the case if schistosomula circulated passively and randomly, but instead displayed a statistically significant decrease from 0.92 and 0.85. For these reasons, it was considered unlikely that schistosomula had circulated randomly and repeatedly through the pulmonary and systemic circulations and entered the hepatic portal system by chance as hypothesized by Miller & Wilson (1980). Instead it was considered more probable that schistosomula migrating from lungs to liver had followed a directed path through intervening vessels (Kruger, Heitman, van Wyk & McCully, 1969) or tissues (Wilks, 1967).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Migration of Schistosoma mansoni in normal and passively immunized laboratory rats.

Normal and passively immunized Fischer rats were infected with 75Se-selenomethionine-labeled cercariae of Schistosoma mansoni. Migration of the parasites from skin to lungs to liver was monitored by autoradiographic analyses of these sites. Labeled parasites migrated from skin to lungs with high efficiency in normal and immune rats; disappearance of labeled parasites from the lungs was slower in immune rats. Labeled parasites accumulated in the liver, reaching maximal values by 11 days post-infection in both groups and remaining constant through day 21. Half the number of labeled parasites were detected in the liver of immune rats. The total number of labeled parasites detected in the skin, lungs, and liver was constant through day 5, then declined to about 60% of this value by day 11 in both groups. Over the next 10 days, the rate of decline decreased significantly in normal rats but did not change in immune rats. By day 21 post-infection, nearly 50% fewer labeled parasites were detectable in immune rats. We conclude that a subpopulation of parasites in the lungs is the target of protective antibody in the serum used for passive immunization. Target parasites, retained longer in the lungs, were probably prevented from migrating successfully to the liver. Another parasite subpopulation migrated to the liver with normal kinetics. Lung schistosomula isolated from normal and passively immunized rats were transferred by intravenous injection into recipient rats and their continued migration from lungs to liver compared. No differences in portal perfusion worm yields were detected in normal recipients; equally reduced yields were detected in passively immunized recipients. We conclude that the effects of antibodies during week 1 post-infection were insignificant or reversible.

Autoradiography↗
PubMed1986

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↗
PubMed1984

The cellular IgE response of rodents to infection with Nippostrongylus brasiliensis, Trichinella spiralis and Schistosoma mansoni.

The IgE response at the cellular level to helminthic infection was studied in BALB/c mice inoculated with the infective larvae of the nematodes Nippostrongylus brasiliensis (Nb) or Trichinella spiralis (Ts) or with the cercariae of the trematode Schistosoma mansoni (Sm). Changes in mesenteric lymph node (MLN) cell number, cell surface(s) IgD, IgM, IgE and Thy-1.2 and intracytoplasmic (c) IgE were recorded. In addition, a comparable study was conducted in rats infected with Nb. At 11 days after infection (DAI) of mice with Nb or Ts, or rats with Nb, there was a 3-fold increase in cell number in the MNL. There was a marked increase in cell number in the MLN of mice infected with Sm at 7 weeks after infection (WAI) and in the spleens of Sm-infected mice at 4 WAI. The percentage of cIgE+ cells increased from undetectable levels in uninfected mice and rats to as high as 0.5-1.3% in the MLN of helminth-infected mice and rats. Analysis of cell surface molecules with a fluorescence activated cell sorter (FACS) showed that Nb and Ts infection induced slight increases in the percentages of B cells and slight decreases in the percentage of T cells. More remarkably, the percentage of sIgE+ cells in the MLN of both Nb- and Ts-infected mice rose from undetectable levels in uninfected mice to 33 and 27%, respectively, at 15 DAI. This rise was stimulated in Ts-infected mice predominantly by adult Ts. In the MLN of Nb-infected rats, the percentage of cells that were sIgE+ was greater than 50% at 15 DAI. However, there was no detectable increase in sIgE+ cells in the spleen and MLN of Sm-infected mice until 5 WAI; peak levels of approximately 20% sIgE+ cells were reached at 8 WAI. Treatment of MLN cells from mice infected with Nb, Ts or Sm and rats infected with Nb, with pH 4.0 acetate buffer for 1 min (acid treatment) removed all detectable sIgE from greater than 90% of the sIgE+ cells, but did not remove sIgD or sIgM from cells with these surface isotypes. The effect of acid treatment on sIgE was similar even after a secondary infection of mice or rats with nematode larvae. These data show that helminthic infection, in general, is a potent stimulator of the IgE system at the cellular level and that almost all of the sIgE+ cells that arise have acquired cytophilic sIgE.

Animals↗
PubMed1984

Comparison of Schistosoma mansoni migration patterns in normal and irradiated cercaria-immunized mice by means of autoradiographic analysis. Evidence that worm elimination occurs after the skin phase in immunized mice.

Migration and elimination of radiolabeled Schistosoma mansoni were compared in naive and irradiated cercaria-immunized mice by autoradiography of compressed host tissues. The results indicated that 1) most of the normal elimination of schistosomula in unimmunized mice and the additional elimination in immunized mice occur at some point(s) after arrival of schistosomula in the lungs and before their development into adult worms, 2) migration of schistosomula from skin to lungs is delayed for several days but not reduced in immunized mice, 3) migration of schistosomula from lungs to liver is delayed for several days in immunized mice, and 4) schistosomula reach the liver in reduced numbers or are killed and cleared in the liver in greater numbers in immunized mice. The lung chop procedure was shown to recover schistosomula from control and irradiated cercaria-immunized mice with equal efficiency. Autoradiography of all tissues of the body demonstrated that, in both control and immunized mice, at least 20-25% of the schistosomula detectable 2 and 3 weeks after infection were present in tissues other than the skin, lungs and liver.

Animals↗
PubMed1984

Autoradiographic analysis of resistance to reinfection with Schistosoma mansoni in mice. Evidence that the liver is a major site of worm elimination.

Migration and elimination of 75Se-labeled Schistosoma mansoni were studied in previously infected mice by means of autoradiography and worm recovery. As in control mice, there appeared to be little if any worm elimination in the skin of previously infected mice. In previously infected mice, there appeared to be some worm elimination in the lungs and in migration sites between the lungs and liver, though much less than would have been expected from previous studies. In two of three experiments most of the challenge worm elimination in previously infected mice, above the normal attrition level occurring in the controls, appeared to take place in the liver. In the third experiment, it appeared that all of the challenge worm elimination occurred after migration to the lungs, and at least one-third of it in the liver. It was also observed that the lung chop procedure recovered viable schistosomula much less efficiently from previously infected mice than from controls indicating that the reduction in lung schistosomulum recovery overestimates the amount of lung and prelung killing that occurs in reinfected mice.

Animals↗
PubMed1984

The migration and survival of gamma-irradiated Schistosoma mansoni larvae and the duration of host-parasite contact in relation to the induction of resistance in mice.

The migration in mice of 20, 50 and 90 krad. 60Co-irradiated Schistosoma mansoni larvae, biosynthetically radio-isotope labelled with [75Se]-selenomethionine, was evaluated by autoradiography of compressed tissues and compared to the migration of non-irradiated 75Se-labelled larvae. The migration of 20 krad.-irradiated schistosomula between skin and lungs was slightly delayed but otherwise paralleled the migration of normal, non-irradiated schistosomula during the first 8 days following exposure. By day 8 over 90% of both non-irradiated and 20 krad.-irradiated organisms were located in the lungs. In contrast to non-irradiated organisms, however, only a small proportion of 20 krad. organisms migrated to the liver. The delay in migration between skin and lungs was more pronounced with 50 krad.-irradiated schistosomula. Nevertheless, 45-93% of 50 krad.-irradiated organisms migrated to the lungs by 8 days post-exposure. Over 90% of the 50 krad. larvae detected in the mouse on day 21 were in the lungs; no more than an occasional 50 krad.-irradiated organism was ever detected in the liver. In three experiments, over 85% of the 90 krad.-irradiated organisms were retained in the skin; in a fourth experiment about half of the 90 krad.-irradiated organisms migrated as far as the lungs. As with 50 krad. organisms, only an occasional 90 krad. organism was ever detected in the liver. Removal of the skin exposure site within the first 4 days of immunization with either 50 or 90 krad.-irradiated cercariae completely blocked the induction of resistance. Removal between the 4th and 6th days gave variable results. Mice had to be in contact with the irradiated larvae for a minimum of 8-11 days to stimulate a level of resistance comparable to that of mice whose immunization site was not removed.

Animals↗
PubMed1983

Schistosoma mansoni: temporal distribution of radioselenium-labelled schistosomula in lungs of mice during the first two weeks of infection.

The number of schistosomula in lungs was determined by compressed organ autoradiography at intervals up to 14 days after exposure of mice to 75Se-labelled cercariae by tail immersion. Probit analysis of compressed lung autoradiogram focus counts, expressed as percentages of initial infection level, yielded estimates of the average time of arrival, peak accumulation in the lungs and average time of departure of schistosomula: 4.5 +/- 0.87, 6.3 +/- 0.45 and 11 +/- 0.58 days, respectively. At peak accumulation 92 +/- 3.5% of the initial number of schistosomula were found in the lungs. It thus appears that little or no significant attrition of schistosomula occurred in the skin and, instead, that most of the 50-70% of penetrant cercariae that fail to reach adulthood are lost somewhere between the pulmonary and hepatic phases of development. Loss of 75Se label from schistosomula during the first 14 days was exponential, with an average half-life of 4.5 +/- 0.81 days. However, the high sensitivity of autoradiography tended to compensate for this rather rapid rate of label loss. It was pointed out that autoradiographic detection of schistosomula as discrete loci of radioactivity can also be expected to overcome the problem posed by the accumulation in such tissues as liver and kidney of 75Se label that has become separated from larvae.

Animals↗
PubMed1983

Differences in hepatic fibrosis in ICR, C3H, and C57BL/6 mice infected with Schistosoma mansoni.

The collagen content of the liver, measured as hepatic hydroxyproline, was examined for a period of up to 52 weeks following Schistosoma mansoni infection. Hepatic fibrosis was much more marked in S. mansoni-infected mice of an outbred ICR strain than in C57BL/6J mice, while C3H/HeN mice occupied an intermediate position. The marked difference in hepatic fibrosis in ICR and C57BL/6J mice correlated with more rapid in vitro synthesis of collagen by the livers of infected ICR mice. Strains of mice exhibiting high and low levels of fibrosis provide an excellent tool for examining mechanisms of murine schistosomal hepatic fibrosis and its genetic regulation.

Animals↗
PubMed1983

Autoradiographic analysis of Schistosoma mansoni migration from skin to lungs in naive mice. Evidence that most attrition occurs after the skin phase.

A study was performed to determine the extent of attrition of Schistosoma mansoni in naive mice (innate resistance) during the 1st week of infection. Each mouse was exposed to exactly 50 cercariae radiolabeled with [75Se] selenomethionine. On 1, 4, and 7 days postexposure, skin, lungs and liver were analyzed by compressed organ autoradiography for the presence of labeled larvae. Using this technique it was determined that no more than one-third of the 59% attrition that occurred between the cercarial and adult worm stages could be attributed to losses during the skin phase; most of the attrition in naive mice occurred after the migration of larvae to the lungs.

Animals↗
PubMed1983

Immunization of mice with ultraviolet-irradiated Schistosoma mansoni cercariae: a re-evaluation.

Mice immunized by percutaneous exposure to ultraviolet-irradiated Schistosoma mansoni cercariae developed levels of resistance to subsequent S. mansoni infection comparable to those induced by gamma-irradiated cercariae (50-70% reduction in adult worm burden). Cercariae treated with ultraviolet doses ranging from one to three times the minimum dose required to prevent long-term survival induced the highest levels of resistance.

Animals↗
PubMed1982

Quantification of Schistosoma mansoni in mouse lungs by radioassay and autoradiography of 75Se-labeled schistosomula.

Lung radioassay and compressed lung autoradiography of 75Se-labeled schistosomula were used to quantify lung schistosomula. Recovery of schistosomula from minced lung tissue after a 4-hr incubation yielded 69.4 +/- 6.3% of the total number present as demonstrated by subsequent autoradiography of these tissues. Radioassay of lung tissue was considered a valid alternative to autoradiography only for parallel comparisons and those not requiring estimation of the actual number of schistosomula. The number of schistosomula in the lungs on day 6 was significantly correlated with radioactivity in the tail on day 1 (r2 = 91.8%). It was concluded that compressed lung autoradiography provides both an alternative to and an adjunct to standard schistosomulum recovery techniques in the assay of early S. mansoni infections.

Animals↗
PubMed1981

Immunization of Baboons with Schistosoma mansoni Cercariae attenuated by gamma irradiation.

Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70 percent) and egg excretion rates (82 percent). These results support immunization as a potential method for schistosomiasis control.

Animals↗
PubMed1981

Resistance induced by normal and irradiated Schistosoma mansoni: ability of various worm stages to serve as inducers and targets in mice.

Lung stage schistosomula exposed to 50 kilorads of gamma irradiation induced significant resistance to challenge infection with Schistosoma mansoni following intravenous (tail or mesenteric vein), intramuscular, or intraperitoneal injection into mice. Similar or higher levels were induced with irradiated cercariae, while irradiated 3- or 4-week-old worms induced little resistance. Non-irradiated day 6 and day 12 lung schistosomula injected into mice immunized with irradiated cercariae were susceptible to elimination, though to a lesser extent than a challenge infection administered at the cercarial stage. Day 20 liver worms injected into a mesenteric vein were not susceptible to irradiated cercaria-induced resistance. In contrast, cercariae, day 6 lung schistosomula, day 12 lung schistosomula and day 20 liver worms were all susceptible to the resistance induced by a chronic (non-irradiated) infection.

Animals↗
PubMed1981

Attrition of schistosomes in an irradiation-attenuated cercarial immunization model of Schistosoma mansoni.

The attrition of Schistosoma mansoni challenge worms was studied in irradiation-attenuated cercaria-immunized mice as a function of site and time. The peak recovery of schistosomula from the lungs of immunized mice was delayed 2 days in comparison with non-immunized controls. The difference between the peak recoveries of control and immunized mice accounted for about half of the final attrition observed at the 7-week adult worm stge. Hepatic-mesenteric vein worm recoveries obtained 10 to 42 days after challenge were reduced in most cases at least as much as the 49-day counts. Somewhat higher reductions were observed at 14 to 28 days than at 49 days, confirming the evidence of delayed migration obtained at the lung phase. These findings, coupled with histologic observations, indicate that at least half of the worm elimination attributable to immunization occurs 8 or more days after the challenge infection.

Animals↗
PubMed1981

Attempts to transfer the resistance of Schistosoma mansoni-infected and irradiated cercaria-immunized mice by means of parabiosis.

Acquired resistance to Schistosoma mansoni infection was measured in S. mansoni-infected or irradiated cercaria-immunized mice, and in normal mice to which the former had been surgically joined. Such parabiotic partners were shown to freely exchange humoral and cellular blood constituents. There was no detectable transfer of resistance from mice infected for 8, 12, or 28 weeks to their uninfected partners, even if parabiosis was established before the initial infection and maintained to autopsy. In comparison with parabiosed controls, the number of adult worms surviving from a challenge infection was reduced by 51-96% in the previously infected mice but was not significantly reduced in their uninfected partners. In contrast, mice immunized with irradiated cercariae and their nonimmunized parabiotic partners showed similar levels of resistance. These data indicate that the resistance induced in mice by irradiated cercariae can be transferred, confirm that at least under some experimental conditions the resistance induced in mice by a previous S. mansoni infection is not readily transferred, and provide additional evidence that the resistance induced by normal infection and irradiated cercarial immunization differ in some fundamental way.

Animals↗