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Biomedical subjects

M J Doenhoff

Publications and source records attributed to M J Doenhoff.

At least 109 records · Page 6Linked to original sources
PubMed1983

Retarded development of Schistosoma mansoni in immunosuppressed mice.

Previous observations, which showed that treatment of mice with hydrocortisone acetate around the time of their infection with Schistosoma mansoni reduced the mature worm burden, have been confirmed. The number of eggs produced by the surviving worms during early patency was also significantly reduced. Cyclophosphamide and another steroid immunosuppressant, betamethasone, also caused a reduction in fecundity of S. mansoni when given at the time of infection, as did T-cell deprivation of the mice by adult thymectomy and injection of anti-thymocyte serum 1 month before infection. There was no effect of these three treatments on worm numbers. In contrast, injection of mice with anti-thymocyte serum at the time of infection marginally increased the size of the mature worm burden. The deleterious effects of hydrocortisone acetate on S. mansoni worm numbers and fecundity were only apparent if the steroid was given within 1 week of infection. Indomethacin, a compound which inhibits tissue inflammatory reactions by inhibiting prostaglandin synthesis, and which therefore mimics one of the actions of corticosteroids, had no effect on S. mansoni worm maturation and fecundity.

Adrenal Cortex Hormones↗
PubMed1982

Studies on the host-parasite relationship of Schistosoma japonicum in normal and immunosuppressed mice.

Infections of Schistosoma japonicum were studied in mice which were immunosuppressed either by thymectomy and administration of antithymocyte serum or by treatment with hydrocortisone acetate. The relation of S. japonicum with the immunosuppressed host differed with that reported for Schistosoma mansoni. The pathogenesis of the S. japonicum infection in the immunosuppressed host was less severe than that caused by S. mansoni, with respect to survival of, and hepatocellular damage to, the host. In contrast with S. mansoni, S. japonicum did not have a reduced fecundity in immunosuppressed mice and there was no significant reduction in the numbers of faecal eggs excreted by these hosts.

Animals↗
PubMed1981

Immunological control of hepatotoxicity and parasite egg excretion in Schistosoma mansoni infections: stage specificity of the reactivity of immune serum in T-cell deprived mice.

Within seven weeks of infection with 200 Schistosoma mansoni cercariae, T-cell deprived mice have been shown to suffer from extensive microvesicular damage to hepatocytes, and an inability to excrete parasite eggs at the same rate as comparably infected, immunologically intact controls. Administration of serum (CIS) from chronically infected, immunologically intact donors prevented the development of microvesicular cell damage and partially restored egg excretion rates in infected deprived mice. Serum pools obtained from mice injected either with intact S. mansoni eggs or with a homogenate of eggs emulsified in Freund's complete adjuvant (FCA) were as effective as CIS in preventing hepatotoxicity and restoring the rate of egg excretion in infected deprived recipients. The degree of protection of liver tissue afforded by immune sera could be monitored either by histopathological examination of liver sections or by estimation of serum transaminase concentrations, the results from both assays being generally in agreement. Sera from donor mice injected with cercarial or worm antigens in FCA were relatively inactive either in protecting against S. mansoni-induced liver damage or in reconstituting egg excretion rates in infected deprived mice. Serum from donor mice infected with 25 cercariae became hepato-protective between 49 and 53 days after infection of the donors, and the degree of hepatoprotective activity and egg excretion reconstituting capacity in the serum of 25 cercariae-infected donors was shown to increase between 8 and 16 weeks after infection. Increasing the size of infection of the serum donors to 100 cercariae gave only a marginal increase of hepatoprotective activity at 7 weeks when compared with serum donors infected with 25 cercariae for 7 weeks. Liver parenchymal cells of very heavily infected, immunologically intact mice were found to show microvesicular damage similar to that in livers of infected deprived mice, and administration of CIS to these normal mice was histopathologically protective. However, the elevated serum transaminase concentrations obtaining in the infected normal mice were not reduced to any extent by CIS. The results obtained from serum-reconstituted deprived mice are discussed in terms of the contribution they may make to a better understanding of the host-parasite relationship in immunologically intact mice.

Animals↗
PubMed1981

Identification and partial purification of an antigen (omega 1) from Schistosoma mansoni eggs which is putatively hepatotoxic in T-cell deprived mice.

T-cell deprived mice heavily infected with Schistosoma mansoni suffer from severe microvesicular damage to hepatocytes within seven weeks of infection. The damage can be prevented by administration of serum (CIS) obtained from mice chronically infected with S. mansoni or from mice immunized with intact or homogenized S. mansoni eggs. Reaction of serum samples from individual chronically infected mice in immunoelectrophoresis with S. mansoni egg homogenate has enabled the identification of at least 12 distinct immuno precipitation reactions. Precipitating antibody against one S. mansoni egg antigen, omega 1, has been detected in all mice with patent chronic infections, and anti-omega 1 antibody is the most concentrated of the precipitating anti-egg antibody species in pooled CIS. Pooled serum obtained from infected intact mice reacting predominantly against omega 1 was found partially to prevent the hepatotoxicity reaction on transfer to infected deprived mice. Serum samples from mice injected with egg homogenate fractionated either by preparative electrophoresis or by cation exchange chromatography, and containing antibodies reactive with antigen omega 1 in immunoprecipitation, were fully protective against liver cell damage induced by S. mansoni in deprived mice. Sera from mice immunized with other S. mansoni egg fractions, and which did not contain antibodies reactive with omega 1, were not hepatoprotective. Antigen omega 1 is compared and contrasted with other S. mansoni egg antigens that have been described.

Animals↗
PubMed1981

Serodiagnosis of human Schistosoma mansoni infections: enhanced sensitivity and specificity in ELISA using a fraction containing S. mansoni egg antigens omega 1 and alpha 1.

Six fractions of Schistosoma mansoni egg homogenate obtained by cation exchange chromatography were tested in an enzyme-linked immunosorbent assay (ELISA) for their efficacy in serodiagnosis of human S. mansoni infections. One cationic fraction (CEF6) containing egg antigens omega 1 and alpha 1, was found to be highly reactive with a S. mansoni positive reference serum pool. 94 of 95 sera from individuals infected with S. mansoni gave a positive reaction with CEF6, and no cross reactivity was obtained with this antigenic fraction and sera from donors infected with heterologous non-schistosome parasites and cases of avian cercarial dermatitis. Only 10 of 165 sera from patients with S. haematobium and three of 10 sera from patients with S. japonicum were positive with S. mansoni egg CEF6. In one group of patients from West Africa, examined both serologically and parasitologically at a six-monthly interval, the measurement of antibody to CEF6 provided a more sensitive diagnostic aid than stool examination.

Animals↗
PubMed1981

Successful development of Brugia pahangi in T-cell deprived CBA mice.

CBA mice were thymectomized and treated with anti-thymocyte serum. Seven such mice were given 90--100 infective larvae of Brugia pahangi each by intraperitoneal (ip) injection and 5 given 99-100 larvae each by subcutaneous (sc) injection. From 62 days after infection 6 of 7 mice infected ip had microfilariae in their peritoneal cavities. Only one mouse infected by sc injection showed microfilariae in peripheral blood and this not until 98 days. At autopsy 5-45 adult worms were recovered from the ip infected mice. Only 2 od the 5 sc infected mice had adults and these only 3 each. No microfilariae or adult worms were detected in similarly infected unthymectomized CBA mice.

Animals↗
PubMed1980

Abnormal development of Hymenolepis nana larvae in immunosuppressed mice.

Observations on the course of Hymenolepis nana infection in immunosuppressed mice are presented. Treatment of the host with hydrocortisone acetate caused superinfection of the bowel with worms and the development of normal cysticercoids in the mesenteric lymph node and liver. Natural infection of mice deprived of their T-cells by pre-adult thymectomy and administration of antithymocyte serum resulted in superinfection and widespread metastasis of aberrant cysticercoids that were greatly enlarged and without scolices, causing death after about five months. The significance of these findings and their possible relevance to human infection with H. nana are discussed.

Animals↗
PubMed1980

Serum protein concentrations during Schistosoma mansoni infection in intact and T-cell deprived mice. I. The acute phase proteins, C3 and serum amyloid P-component (SAP).

Normal mice developed marked elevation of two acute phase plasma proteins, C3 and serum amyloid P-component (SAP), between 40 and 50 days after percutaneous infection with cercariae of Schistosoma mansoni. The high levels persisted until the end of the experiment (day 106). The onset of this acute phase response corresponds with the reported time at which granulomata develop in the liver. In mice deprived of T cells by thymectomy and anti-thymocyte serum, the granulomata were significantly smaller and all the animals died between days 70 and 80. These mice had normal C3 levels throughout although there was a rise in SAP concentration. C3 and SAP levels in infected control mice, which had been thymectomized but not deprived of T cells with anti-thymocyte serum, were the same as in intact infected animals. The different behaviour of C3 and SAP in infected T-cell deprived mice may reflect the alteration in specific schistosomal pathology and/or a role for T cells in mediation of the acute phase production of some proteins.

Amyloid↗
PubMed1979

Immunization of mice with gamma-irradiated intramuscularly injected schistosomula of Schistosoma mansoni.

The parameters involved in the induction of resistance against Schistosoma mansoni by injection of irradiated, artificially transformed schistosomula were studied in mice. Single intramuscular injections of 500 schistosomula exposed to radiation doses in the range 2.3 to 160 krad. resulted in significant protection (in the range 20 to 50% as assessed by reduced worm burdens) against a challenge infection administered at intervals from 3 to 24 weeks post-vaccination. However, schistosomula irradiated with 20 krad. consistently resulted in better protection than those exposed to either higher or lower radiation doses despite the persistence of stunted adults from the infections irradiated with 2.3 krad. Vaccination with 40 krad. schistosomula resulted in significant protection in terms of reduced worm and tissue egg burdens and increased survival following lethal challenge. Varying the number of irradiated schistosomula, the frequency and route of their administration, the site of challenge and the strain of host all failed to enhance the level of resistance. However, percutaneously applied, irradiated cercariae were found to be more effective in stimulating resistance (60%) than intramuscularly injected, irradiated schistosomula (40%).

Animals↗
PubMed1979

Increased hepatotoxicity of bacterial lipopolysaccharide in mice infected with Schistosoma mansoni.

Mice infected with Schistosoma mansoni were highly sensitive to the lethal effects of bacterial lipopolysaccharide (LPS). The hyper-reactive state of LPS coincided with the development around the parasite eggs of multiple granulomas in the liver. Elevated aspartate transaminase levels in blood and severe hypoglycaemia in LPS-challenged animals indicated extensive liver parenchymal cell damage. There was also a complete depletion of glycogen in hepatocytes of these animals. From this work and studies on other hepatitis models, it is suggested that individuals affected with granulomatous disorders may be at risk because of everyday exposure to LPS from the gut.

Animals↗
PubMed1979

Schistosoma mansoni infections in T-cell deprived mice, and the ameliorating effect of administering homologous chronic infection serum. II. Pathology.

Liver changes occurring in mice deprived of their T-cells by a combination of thymectomy and anti-mouse thymocyte serum, and in immunologically intact control mice, were followed during the early stages of heavy Schistosoma mansoni infections. Lesions in both groups began developing by day 38 and were maximal by day 48. Hepatic changes in control mice culminated in large hypersensitivity granulomas, tissue eosinophilia, portal periphlebitis, fibrosis, vascular obstruction, and infarction leading to arterialization and preferential sinusoidal channeling. Deprived mice showed greatly reduced egg reactions composed principally of macrophages, monocytes, and occasional neutrophils, and only minimal alteration of liver architecture; however, focal and disseminated hepatocellular lesions became prominent as the infections progressed, and by day 48 virtually every hepatocyte was affected. Typically, hepatocytes showed microvesicular cytoplasmic damage (steatosis) or ballooning degeneration with accompanying nuclear pyknosis or karyorrhexis. This cellular pathology may be attributed to the direct or indirect effect of eggs or egg products on liver cells. The administration of chronic infection serum obtained from immunocompetent mice to T-cell deprived mice dramatically eliminated the hepatocellular lesions. It also increased eosinophil participation and fibrosis in the egg reactions but did not restore the size and other cellular features typical of egg hypersensitivity granulomas. Serum from uninfected normal mice was found to lack these effects.

Animals↗
PubMed1979

Restricted heterogeneity of antibody synthesized by T-cell deprived mice.

Mice which had been thymectomized and injected with anti-thymocyte serum to remove long-lived recirculating T cells, initially failed to produce haemagglutinating and haemolysing antibody after injection of sheep erythrocytes. After six fortnightly injections of heterologous erythrocytes, however, haemolysin titres in the T-cell deprived mice were comparable to those in similarly challenged but immunologically intact animals. Isoelectric focusing of these sera indicated that the anti-sheep erythrocyte antibody eventually synthesized by the T-cell deprived mice was less heterogeneous than antibodies found in the sera of control mice.

Animals↗
PubMed1979

Adult and pre-adult thymectomy of mice: contrasting effects on immune responsiveness, and on numbers of mitogen-responsive and Thy-1+ lymphocytes.

Peripheral lymphoid tissues of mice which have been thymectomized at 2 or 4 weeks of age, that is, before they achieve adult body weight, have been shown to be lacking in cells responsive to the T-cell mitogen, phytohaemagglutinin, when the animals became adult, and these mice have also been shown to have a deficient immune response against sheep erythrocytes. It is suggested these effects of pre-adult thymectomy are consequent upon removal of the prime source of T cells prior to the animal having acquired complete T-cell populations of the adult. Spleens and lymph nodes of mice thymectomized at 8 weeks of age were found to have reduced numbers of cells susceptible to the cytotoxic effects of anti-Thy-1 serum as early as 4 weeks after the operation, whereas the number of lymphocytes responsive to T-cell mitogens in these lymphoid tissues was not reduced at this time. The number of spleen-borne antibody-producing cells in a primary or secondary response was not affected by 8-week thymectomy, either when the response was tested in the operated animal, or after transfer of cells from such an animal to an irradiated recipient. The results are discussed with respect to other work on the effects of thymectomy of mice during the post-neonatal and pre-adult period.

Age Factors↗
PubMed1978

The immune-dependence of schistosomicidal chemotherapy: relative lack of efficacy of an antimonial in Schistosoma mansoni-infected mice deprived of their T-cells and the demonstration of drug-antiserum synergy.

When T-cell deprived CBA mice, infected with Schistosoma mansoni, were treated orally with potassium antimony tartrate, the reduction in size of their worm burdens was less than in similarly treated, immunologically-intact animals. The defect in deprived mice could be restored by the administration of serum obtained from S. mansoni-infected normal mice simultaneously with the drug, but by a different route. A serum component, probably immunoglobulin, obtained from rabbits which had been injected with an extract from S. mansoni adult worms was also found to act synergystically with the antimonial in the chemotherapeutic eradication of S. mansoni worms from immunologically intact mice.

Animals↗
PubMed1978

Studies of hyperthymic mice. I. The influence of multiple thymus grafts on the size of the peripheral T cell pool and immunological performance.

Following the implantation of syngeneic chromosomally marked thymuses under the kidney capsule of normal adult mice, donor T cells were found in the blood and other lymphoid organs. The mice were found to have increased numbers of Thy.1-positive cells in spleen and lymph nodes, increased peripheral blood lymphocyte levels and also augmented immune responses to sheep erythrocytes. The contribution made by an individual graft to the donor T cell pool was independent of the number of thymuses grafted as was the growth of the grafts themselves. The results reaffirm that there is no homeostatic feedback control of thymus growth in adult mice.

Animals↗