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M J Doenhoff

Publications and source records attributed to M J Doenhoff.

At least 91 records · Page 5Linked to original sources
PubMed1988

Anti-schistosome chemotherapy enhanced by antibodies specific for a parasite esterase.

The immune-dependent action of praziquantel has been investigated in Schistosoma mansoni-infected mice by passive transfer of rabbit antisera simultaneously with drug treatment. Significant synergistic activity was obtained with polyspecific sera against culture medium extracts of adult worms, but not with sera against detergent extracts or whole worm homogenates. Serum from a rabbit 'infected' with unattenuated S. mansoni cercariae was also synergistically active with praziquantel, and from this serum were derived two further active and monospecific sera which immunoprecipitated a 27,000 MW antigen with non-specific esterolytic enzyme activity. The antigen against which the monospecific sera reacted was detected by indirect immunofluorescence on the tubercles of drug-treated worms, but not on control worms. The immune-dependence of praziquantel thus appears related to drug-induced damage on the surface on the worm, which results in exposure of antigens sensitive to damage by antibody.

Animals↗
PubMed1987

Parasitological evaluation of curative and subcurative doses of 9-acridanone-hydrazone drugs against Schistosoma mansoni in baboons, and observations on changes in serum levels of anti-egg antibodies detected by ELISA.

Derivatives in the class of 9-acridanone-hydrazones were found to be highly active against Schistosoma mansoni in baboons. Single doses of 25 mg/kg were fully effective. Data are presented showing changes detected by ELISA in antibody levels against schistosome eggs which correlated positively with the effect of chemotherapy. This approach may help to evaluate the effects of treatment of human schistosomiasis where the detection of low egg counts is problematic.

Acridines↗
PubMed1987

Reduced efficacy of chemotherapy of Plasmodium chabaudi in T cell-deprived mice.

Immunologically intact and T cell-deprived CBA mice were infected with Plasmodium chabaudi and treated with chloroquine, pyrimethamine or quinine. Chloroquine and pyrimethamine rapidly reduced the levels of parasitaemia in both types of host, but whereas the normal mice remained free of blood parasites thereafter, the deprived mice suffered recrudescences of the infection. Quinine was therapeutically more effective in the intact mice than in the deprived mice early after initiation of treatment and, while the normal mice suffered a transient recrudescence after quinine, the deprived mice retained a high parasitaemia during and after treatment. The results indicate that the immune response may contribute to effective chemotherapy of malaria.

Animals↗
PubMed1987

Evidence for an immune-dependent action of praziquantel on Schistosoma mansoni in mice.

Effective schistosomicidal action of praziquantel against Schistosoma mansoni infections in mice appears to be dependent to some extent on appropriate immunological stimulation. Indirect evidence consistent with this hypothesis was obtained by demonstrating a positive relationship between drug efficacy and both the intensity and the age of the parasitic infection. More directly, it has previously been shown that praziquantel kills fewer S. mansoni worms in immunosuppressed T cell-deprived mice than in immunologically intact controls; and we show here that infections 5 weeks old, against which the drug alone is sub-optimally active, are more effectively killed by a combination of drug and a rabbit antiserum raised against adult worm antigens.

Animals↗
PubMed1987

Comparison of the live vaccine potential of different geographic isolates of Schistosoma mansoni.

We have investigated the capacity of irradiated larvae of each of six different isolates of Schistosoma mansoni to protect mice against challenge infections from the homologous or a different isolate. The isolates differed in respect of their geographic origins, and in the lengths of time they had been maintained in the laboratory. All isolates induced significant protection against unattenuated challenge infections, and neither the degree of geographic disimilarity between vaccinating and challenge parasites, nor the numbers of laboratory cycles, appeared to influence the degree of protection induced by irradiation-attenuated larvae.

Animals↗
PubMed1987

Parasitological observations of Schistosoma bovis in normal and T-cell deprived mice.

A laboratory life-cycle of Schistosoma bovis was established in order to study the host-parasite relationship in immunologically intact and T-cell deprived mice. Normal mice were found to have 'self-cured' their S. bovis infections almost completely by 10 weeks after cercarial administration, and there was no evidence of self-cure by day 79 in T-cell deprived animals. Thus, groups of deprived mice autopsied between 9 and 11 weeks after infection were invariably found to have greater worm burdens and a greater total number of eggs in the liver than comparably-infected normal mice. However, liver egg counts/worm pair were similar in the two types of host, and differences between normal and deprived mice with respect to total S. bovis egg counts in the intestine were also not consistently in the same direction in all experiments. Faecal egg counts were always less in deprived mice than in normal mice, even in an experiment in which the deprived mice had a significantly higher intestinal tissue egg count than the normal control group. The results are discussed in relation to the better known S. mansoni/mouse host-parasite relationship.

Animals↗
PubMed1987

The response to Schistosoma bovis in normal and T-cell deprived mice.

Normal and T-cell deprived mice have been compared in their response to infection with Schistosoma bovis. The deprived mice survived longer than comparably infected, immunologically intact controls, despite an increased longevity of the adult S. bovis worms in the former animals giving rise to higher tissue egg densities. The reduced pathology in deprived mice was due to inhibition of T-cell dependent granuloma formation around tissue-bound schistosome eggs, with concomitantly decreased tissue disruption as evidenced by smaller spleens and lower circulating transaminase concentrations. These observations on S. bovis contrast with the greater morbidity and earlier mortality induced by S. mansoni in T-cell deprived mice, the latter due to an hepatotoxic potential of S. mansoni eggs that is expressed in the absence of the host immune response. The absence of hepatocyte damage around S. bovis eggs in deprived mice indicates that this schistosome lacks such a toxin, and this could explain why during S. bovis infection synthesis of the two acute-phase proteins, complement C3 and serum amyloid P-component (SAP) here seemed less T-dependent than has previously been found during S. mansoni infection of mice. In a time-course experiment the hypergammaglobulinaemia induced by S. bovis, and the specific IgG antibody response against egg antigens were significantly T-cell dependent during the early stages of patency. Similarly, in most experiments assayed once between 9 and 11 weeks after S. bovis infection, deprived mice had significantly reduced hypergammaglobulinaemias, and reduced specific IgM and IgG antibody responses against both worm and egg antigens.

Acute-Phase Proteins↗
PubMed1986

Schistosoma mansoni: chemotherapy of infections of different ages.

Mice were treated with potassium antimony tartrate, hycanthone, oxamniquine, niridazole, or praziquantel at different times after infection with Schistosoma mansoni. The rate of cure was assessed by perfusion of surviving worms approximately 4 weeks after treatment, and the percentage reduction in worm burden was estimated relative to the number of adult worms perfused from control mice, comparably infected but untreated. All six drugs were relatively inactive against S. mansoni between 3 and 4 weeks after infection when compared with treatment at 5 to 6 weeks. However, the drugs differed in the patterns of cure they achieved in the 2-week period after administration of cercariae and in the period around the onset of patency. Worms that had been subjected to amoscanate or hycanthone in the third week after infection showed evidence of this as adults in having a reduced fecundity. Factors such as worm or host physiology, or host immune status may have had roles in the outcome of chemotherapy at different stages of maturation of S. mansoni.

Animals↗
PubMed1986

The schistosome egg granuloma: immunopathology in the cause of host protection or parasite survival?

The granulomatous inflammatory response induced by schistosome eggs entrapped in the microvasculature of host tissues is considered responsible for much of the symptomatology of schistosomiasis. However, the evolutionary role of the egg granuloma in the host-parasite relationship is not yet well defined. Some evidence indicates that the lesion may protect the host, either by shielding tissues against toxic egg products, or by interfering with the migration patterns of secondary infections, and thereby non-specifically contributing to the host's acquired "immunity". We here review earlier work concerned with the role of the egg granuloma in the host-parasite relationship in schistosomiasis, and we present new experimental evidence to suggest that the function of this cell-mediated immune response might, in addition to its putative host protective function, facilitate the extravasation of parasite eggs in the mesenteries, and thereby contribute directly to the continuation of the schistosome life-cycle.

Animals↗
PubMed1986

Schistosoma mansoni egg antigens: preparation of rabbit antisera with monospecific immunoprecipitating activity, and their use in antigen characterization.

A simple method for producing monospecific rabbit antisera, applied originally to the constituents of human serum (Goudie et al. 1966), has been adapted for use with Schistosoma mansoni egg antigens. Replicate isolated immunoprecipitin arcs resulting from the immunoelectrophoretic reaction between an egg antigen and a polyspecific antiserum were excised, washed extensively to remove non-precipitated contaminants, homogenized, and emulsified with complete Freund's adjuvant. Rabbits were given weekly subcutaneous injections of the emulsion in multiple sites, and a monospecific precipitating antibody against the respective immunizing antigen generally resulted within 6 weeks of the commencement of immunization. Antisera raised in this manner against S. mansoni egg antigens omega 1, alpha 1 and kappa 5 have been used to characterize the antigen with respect to their stage- and species-specificity. After immunoabsorption to remove background activity, the sera could be used to detect unequivocally the respective antigens in crude egg homogenate that had been subjected to SDS-PAGE and electrotransfer to nitrocellulose paper.

Animals↗
PubMed1986

Evaluation of drugs against Onchocerca microfiliariae in an inbred mouse model.

The model of Onchocerca lienalis microfilariae (mf) injected into CBA mice has been examined for its application to chemotherapy studies in onchocerciasis. Parasite recoveries following treatment relative to the levels obtained from controls were not significantly affected by suramin, whereas they were reduced by up to 56% with amoscanate, 71% with levamisole, 82% with mebendazole, 82% with diethylcarbamazine (DEC) and 100% with ivermectin. More detailed evaluation of the latter two compounds demonstrated that far greater intrinsic microfilaricidal activity was possessed by ivermectin compared with DEC. Single doses of ivermectin down to 0.2 mg/kg destroyed 83% of the mf within 12 hours and 100% within 5 days. The same dose administered at various times prior to mf injection reduced parasite recoveries by 92% after four days and by 35-40% for up to one month. In contrast, DEC was only effective at doses of 5 X 50 mg/kg or higher, reducing mf levels by an equivalent amount following subcutaneous or intraperitoneal routes of administration. However, it was of limited efficacy when given to mice during the first week after mf injection compared with the third week, when parasite levels in untreated rodents start to decline under a host immune response. DEC treatment during the third week after mf injection resulted in a smaller depression in parasite recoveries from T-cell deprived mice compared with intact animals, but in similar levels of reduction in CBA/H (normal) and CBA/N (B-cell deficient) mice. Depletion of C3 complement levels in mice with cobra venom factor had a negligible effect on drug efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Schistosoma mansoni: reduced efficacy of chemotherapy in infected T-cell-deprived mice.

The effect of host immunosuppression on the efficacy of schistosomicidal chemotherapy has been tested in T-cell-deprived CBA mice infected with Schistosoma mansoni. The drugs hycanthone, oxamniquine, and praziquantel were found to kill fewer adult S. mansoni worms in deprived mice than in comparably infected strain-, age-, and sex-matched, immunologically intact controls. Inconsistent results were obtained with niridazole, and amoscanate was as effective in deprived mice as in controls. The possibility that hycanthone, oxamniquine, praziquantel, and previously studied antimony act synergistically with immune effector mechanisms in killing adult schistosomes is discussed.

Animals↗
PubMed1985

Basement membrane proteins and type III procollagen in murine schistosomiasis.

The livers of female CBA mice were examined 9 to 10 weeks after subcutaneous infection with Schistosoma mansoni. Cryostat liver sections and isolated liver cells were examined by indirect immunofluorescence using specific antibodies against basement membrane proteins (laminin, fibronectin and type IV collagen and type III collagen precursor. Liver cells were isolated by collagenase digestion, purification on Percoll density gradients and centrifugal elutriation to yield enriched fractions of hepatocytes, endothelial and Kupffer cells (Fractions I, II, III respectively). Infected animals yielded more than three times the control number of non-parenchymal cells; electron microscopy revealed that the increase in Fraction II was due mainly to eosinophilic leucocytes and in Fraction III due to Kupffer cells and macrophages from the schistosomal granulomata. Studies of cryostat liver sections showed that the schistosomal granulomata contained dense deposits of type III collagen precursor and fibronectin in the distribution of the reticulin fibres but laminin and type IV collagen were conspicuous only in new vessels in the periphery of the granuloma. Isolated liver cells showed fibronectin on their surface. Immunofluorescence studies could not be performed on Kupffer and endothelial cell fractions because of marked non-specific fluorescence. These experiments indicate that centrifugal elutriation is a useful method for isolating the constituent cells of murine schistosomal granulomata.

Animals↗
PubMed1985

Resistance against Schistosoma mansoni induced by highly irradiated infections: studies on species specificity of immunization and attempts to transfer resistance.

Significant levels of resistance against Schistosoma mansoni challenge were developed by mice exposed to highly irradiated (20 krad.) cercariae of the homologous species (53-67%), whereas vaccination with S. bovis, S. haematobium or S. japonicum failed to confer significant levels of resistance (-5-12%), thus confirming the specificity of the immunizing procedure. Attempts to transfer resistance to naive recipients by injection of serum and of spleen or lymph node cells from donor mice vaccinated with highly irradiated cercariae were largely unsuccessful. However, significant levels of resistance could be transferred to mice by injection of serum from rabbits exposed to irradiated cercariae. Comparable levels of resistance were conferred by injection of serum at the time of challenge (34-69%) or 5-6 days later (31-56%). In contrast, sera from rabbits injected with soluble egg antigen or homogenized cercariae failed to confer protection upon recipient mice. Sera from vaccinated mice, vaccinated rabbits and antigen-injected rabbits all caused cell adherence to skin-transformed schistosomula but neither the level of adherence nor the serum titre correlated with the ability to confer protection to mice.

Animals↗
PubMed1985

Serodiagnosis of mansonian schistosomiasis with CEF6, a cationic antigen fraction of Schistosoma mansoni eggs.

Studies of the host-parasite relationship of Schistosoma mansoni in mice revealed that the parasite's eggs were toxic to liver cells of immunosuppressed hosts. Attempts to identify the toxic egg constituent led to the isolation of a fraction CEF6 from crude egg homogenate by cation exchange chromatography. CEF6 contains two cationic antigens, omega 1 and alpha 1, the former being recognized as the putative hepatotoxin. In an initial assessment of its serodiagnostic potential in enzyme immunoassay (ELISA), CEF6 yielded an enhanced degree of sensitivity and specificity when compared with crude egg homogenate, and a subsequent 'blind' inter-laboratory collaborative study confirmed that in certain circumstances the use of a purified fraction such as CEF6 may be advantageous. We here review the experimental work leading up to the isolation of CEF6, and summarize the results so far obtained from its use as a diagnostic aid in human schistosomiasis.

Animals↗
PubMed1984

The stage-, strain- and species-specificity of a Schistosoma mansoni egg antigen fraction (CEF6) with serodiagnostic potential.

The immunological properties of CEF6, a cationic fraction of Schistosoma mansoni egg homogenate (SEA) containing two antigens, omega 1 and alpha 1, have been further investigated in two assays, immunoelectrophoresis (IEP) and enzyme immunoassay (ELISA). Although precipitating antibodies to antigen omega 1 were amongst the first to appear in mice with patient infections, IgG reactivity against CEF6 in ELISA trailed somewhat behind that of IgG activity against unfractionated SEA. Specificity of the two antigens in CEF6 to the egg stage of the parasite life-cycle was demonstrated by the failure of immunizations with cercarial or worm antigens to induce antibodies which reacted against either alpha 1 or omega 1 in IEP, or against CEF6 in ELISA. Mice infected with S. mansoni strains derived from geographically distinct areas, including the Caribbean, South America and Africa, produced antibodies which were reactive against CEF6 prepared from eggs of a Puerto Rican S. mansoni strain that had been maintained in the laboratory for many years. Of the different precipitating anti-SEA antibody species induced by the various S. mansoni strains in mice, those reactive against antigen omega 1 appeared to be present in highest titre. Sera from mice chronically infected with S. japonicum and S. haematobium failed to precipitate CEF6 in IEP and were less reactive with CEF6 than with S. mansoni SEA in ELISA. However, similar degrees of ELISA reactivity against S. mansoni CEF6 and SEA were given by sera from mice infected with S. bovis. The results support the notion that the antigens in CEF6 may be useful in the serodiagnosis of schistosomiasis mansoni infections.

Animals↗
PubMed1984

Immunity to onchocerca lienalis microfilariae in mice. I. Resistance induced by the homologous parasite.

The model of Onchocerca lienalis microfilariae injected into inbred CBA/HT6T6 mice has been examined for its value to study immunity to the skin-dwelling microfilariae in onchocerciasis. Mice injected with living microfilariae during primary or secondary infections exhibited a high level of resistance to challenge relative to normal controls (91-98% reduction in recoveries). The survival of microfilariae during a primary infection was significantly prolonged in T-cell deprived animals compared with immunologically intact mice. Serum and spleen cells transferred from donors 90 days after infection conferred significant protection in syngeneic recipients to challenge with microfilariae (59% reduction in recoveries compared with controls). Boostered injections with freeze-killed or fragmented microfilariae reduced parasite recoveries after challenge by 39-78%: none of 5 adjuvant preparations enhanced the protective effect. Mice exposed to living infective larvae or adult males of O. lienalis also exhibited lowered recoveries of microfilariae following a challenge infection. It is concluded that the mouse model offers potential for immunological studies on the microfilariae in onchocerciasis, which have hitherto been limited because of the lack of suitable laboratory hosts.

Adjuvants, Immunologic↗