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M Doenhoff

Publications and source records attributed to M Doenhoff.

At least 19 recordsLinked to original sources
PubMed2002

Serine protease and phenoloxidase activities in hemocytes of Biomphalaria glabrata snails with varying susceptibility to infection with the parasite Schistosoma mansoni.

The snail Biomphalaria glabrata possesses hemocytes, which are supposed to interact with the larval stages of the human parasite Schistosoma mansoni. We describe trypsin-like serine protease(s) and phenoloxidase activities in lysates from these hemocytes. Both enzymes have activity optima around pH 9.5. The serine protease was inhibited by EDTA, PMSF, antipain and aprotinin, and the phenoloxidase activity by diethydithiocarbamate. By comparison, the serine protease activity in secretions of S. mansoni cercariae also had an alkaline pH optimum around 10.5 and was sensitive to the same inhibitors. In addition, serine protease activities from snails and cercariae had the same molecular mass of 28 kDa. However, the K(m) value of the serine protease(s) and the K(i) values of different inhibitors were generally lower for the snail enzyme than for the cercarial enzyme. The serine protease activity varied among individual snails but activity in hemocyte lysates and hemolymph correlated strongly. There was no detectable difference in the levels of activity between snails which are susceptible or resistant to schistosome infection.

Animals↗
PubMed2001

A study of some characteristics of individual clones of Schistosoma mansoni with emphasis on the biological and metabolic activities.

The variability within schistosome populations was explored using mixed populations of cercariae from multimiracidial snail infections and individual clones of Schistosoma mansoni cercariae obtained from monomiracidial snail infections. We investigated the heterogeneity between different clones of S. mansoni with respect to infectivity and metabolism. One difference between clones of cercariae was found in the recovery of adult worms from Balb/C mice. Recovery of adult worms was greater after infections with a mixed population than with a clonal population. To investigate some biochemical features of individuals in clones or mixed populations, the uptake of [35S]methionine into individual parasites and their membrane proteins was measured. Isoelectric focusing of a soluble membrane fraction: the frozen-thawed supernatant extracted from individual clones, showed the presence of proteins of isoelectric point between 7.2 and 8.2 in all clones. These proteins were less labelled with [35S]methionine in the clones than in the mixed population. It was concluded that basic proteins are synthesized by all clones and in the mixed population but at different rates. Differences in the rate of incorporation of [35S]methionine into the surface membranes of schistosomula and adult worms derived from individual clones are reported. In addition, a direct correlation between the percentage of recovery of adult worms from mice infected with individual clones of S. mansoni and the rate of incorporation of [35S]methionine into schistosomula of these particular clones was observed. It is suggested that the high rate of metabolism shown by an individual clone may account for the enhanced survival of the cercariae derived from that clone during penetration of the skin and migration through the vertebrate host. In order to examine individuals in a population of schistosomula, from a clone or mixed population, the lysosome-specific fluorescent probe LysoTracker DND-99 was used to label the parasites and quantitative fluorescent measurements were made on individual parasites. There were significant differences between clones and a mixed population. Furthermore, the variation between individuals from a mixed population was greater than from that in any clone, just as was found in the infectivity studies. Freshly transformed schistosomula of individual clones labelled with the LysoTracker DND-99 showed less variations in the quantitative uptake of the dye within a single clone when compared to the mixed population. We conclude that for any biochemical and biological parameter, a population of cercariae consists of individuals showing a wide range of values, with a much greater range in a mixed population. This variability is likely to have great relevance for infectivity of the final host and the efficacy of drugs and the immune system.

Animals↗
PubMed1998

Schistosoma mansoni: the varying occurrence of repetitive elements in different strains shows sex-specific polymorphisms.

The repetitive elements W1, W2, and D9 were shown before to be female specific in the Puerto Rican strain of Schistosoma mansoni. In the Liberian strain, however, W1 was detected in both sexes. Therefore, a strain- and sex-specific analysis of the presence of all three repetitive elements has been performed in different schistosome strains. For this analysis, W2 has been isolated and characterized, whereas W1 and D9 were already available. We demonstrate the presence of the W2 element in both sexes in the Liberian strain, which coincides with W1. Furthermore, it is shown that elements W1 and W2, but not D9, can be found in both sexes of the majority of the other strains investigated. We even found an isolate of the Puerto Rican strain with W1 and W2 elements in females and males. This finding contradicts results reported in the literature that demonstrated that W1 and W2 are female specific for the Puerto Rican strain. The data of this study indicate sex-specific polymorphisms, probably associated with the sex chromosomes in schistosomes.

Animals↗
PubMed1995

Epidemiological studies on Schistosoma mansoni infection in the western region of Saudi Arabia using the potassium hydroxide stool digestion technique.

The potassium hydroxide stool digestion technique was used in 30 sites in the Western Region of Saudi Arabia (Hijaz highlands and Tihamah lowlands) for epidemiological studies of S. mansoni. The mean prevalence rate in 2792 individuals (1490 males and 1302 females) in Hijaz highlands (20 sites) was 6.09 (0.5-20.1%) and the geometric mean egg count of stool was 110.8 (63-285). The prevalence rate was greater in males (8.06%) than in females (3.79%). The peak prevalence in males was in the age group 11-15 years, and 31-50 years in females. In 10 sites in the Tihamah lowlands a total of 1771 persons were examined for schistosomiasis. Only one site was recorded with S. mansoni, at a prevalence rate of 0.05%; S. haematobium was recorded in two sites at prevalence rates of 0.55 and 1.13%. Praziquantel therapy (40 mg kg-1) of 170 S. mansoni cases showed a cure of 85-98% at 1-6 months after treatment and a considerable reduction in stool arithmetic mean egg count. Schistosoma haematobium was not recorded in the Hijaz highlands.

Adolescent↗
PubMed1987

Immune enhancement of yellow fever virus neurovirulence for mice: studies of mechanisms involved.

Enhancement of yellow fever virus neurovirulence for mice by specific antibody was studied with the French neurotropic vaccine strain. Experimental conditions for enhancement required mice between 14 and 40 days old and intraperitoneal administration of a selected monoclonal antibody 24 h before or up to 72 h after intracerebral virus challenge. Virus infectivity titrations were similar in brains of antibody-treated and untreated mice. Virus recovered from brains of mice with enhanced viral infections was neither qualitatively nor quantitatively different from standard virus. Humoral immune responses in enhanced infections were normal, macrophages did not become infected and viraemia was not significant. Both hydrocortisone treatment and complement depletion with cobra venom resulted in prolongation of mouse survival times but virulence enhancement persisted. Antithymocyte serum had no effect on enhancement although it reduced the humoral immune response. It is proposed that virulence enhancement is due to the combined effects of virus-specific antibody on infected cells, complement-mediated cytolysis and resultant host anti-cellular activity. There is no analogy between mechanisms effecting increased arbovirus growth in vitro in the presence of specific antibody and increased yellow fever virus neurovirulence in vivo after parenteral administration of antibody.

Age Factors↗
PubMed1980

The pathological effects of immunosuppression of Schistosoma mansoni-infected mice, with particular reference to survival and hepatotoxicity after thymectomy and treatment with antithymocyte serum, and treatment with hydrocortisone acetate.

The effects of various immunosuppressive regimes on the survival and liver pathology of mice infected with Schistosoma mansoni were investigated. T-cell deprivation before infection (by adult thymectomy and subsequent anti-thymocyte serum administration), or treatment with hydrocortisone or cyclophosphamide or azathioprine after infection, all reduced survival of infected mice when compared with immunologically intact, infected mice. T-cell deprivation or steroids produced severe liver damage in infected mice despite a reduction in the size of the peri-oval granulomatous inflammatory reaction. Administration of chronic infection serum reduced liver damage in both T-cell-deprived and steroid-treated animals, but improved survival only in the deprived animals and not to the level seen in normal infected mice. The liver damage in immunosuppressed mice was not due to opportunistic bacterial infection. Thus, although immunosuppression reduced the granulomatous response to schistosome eggs in the livers of infected mice (as it does to eggs injected intravenously into the lungs), survival time was decreased. The relevance of these findings to human S. mansoni infections is discussed.

Animals↗
PubMed1980

Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. V. Reduction in the degree of resistance to reinfection after chemotherapeutic elimination of recently patent primary infections.

Effective treatment of mice with six to eight week-old patent S. mansoni infections with any one of five schistosomicidal agents (Oxamniquine, Praziquantel, potassium antimony tartrate, Niridazole and Hycanthone) resulted in a reduction in the degree of resistance to homologous challenge in the treated animals when compared with the level of resistance to reinfection observed in untreated mice with intact primary infections. Mice challenged five to six weeks after treatment with Praziquantel, Niridazole or Hycanthone demonstrated a lower level of resistance than mice challenged within 10 days of the termination of the chemotherapeutic schedules. Direct comparison of Praziquantel with potassium antimony tartrate indicated that treatment with the former drug allowed retention of a greater level of acquired resistance than the antimonial in the immediate post-treatment period. Resistance to reinfection in Hycanthone-treated mice was not restored by intravenous injection of S. mansoni eggs before challenge.

Animals↗
PubMed1980

Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. The effect of varying the route and the number of primary infections, and the correlation between the size of the primary infection and the degree of resistance that is acquired.

Mice given primary infections of Schistosoma mansoni by percutaneous or subcutaneous routes were found to acquire a higher degree of resistance against homologous challenge after 7--8 weeks than mice infected intraperitoneally. Mice infected by the intraperitoneal route tended to have smaller worm burdens than those infected with the same number of cercariae by the other two routes and this may, in part, have contributed to the relative lack of efficacy of intraperitoneal infections in inducing resistance to re-infection. The same degree of resistance was acquired after primary percutaneous infection irrespective of whether it was administered in 3 equivalent weekly doses, or the same total number of cercariae was administered as a single infection. The same degree of resistance was also observed when a percutaneous challenge was administered on the same or a different skin site to that which received the percutaneous primary infection. The degree of resistance to re-infection acquired after a percutaneous primary infection correlated well with the size of the primary worm burden and the number of eggs in the intestine and liver, but did not correlate with the number of eggs in the lungs.

Animals↗
PubMed1980

Serum protein concentrations during Schistosoma mansoni infection in intact and T-cell deprived mice. II. Immunoglobulin G and antibodies specific for heterologous erythrocytes.

Mice infected with from twenty to fifty Schistosoma mansoni cercariae were found to have elevated serum IgG concentrations following patency of the infection, and the parasite-induced increase in concentration of IgG was dependent on the possession by the host of an intact T-cell lymphocyte pool. Following passive transfer of hyperimmune anti-sheep erythrocyte (SRBC) antibody, there was a more rapid decrease of haemolytic and haemagglutinating antibody titres in S. mansoni-infected, immunologically intact recipients than in uninfected intact mice, and infected or uninfected T-cell deprived mice. However, primary and secondary active immunization with SRBC resulted in similar patterns of serum antibody titre increase and decay in infected and uninfected intact mice over a time course of 140 days. The number of direct and indirect haemolytic plaque-forming (PFC) cells per million spleen cells was similar in S. mansoni-infected and uninfected immunologically intact mice 6 days after either primary or secondary challenge with SRBC. It is concluded that S. mansoni-infected immunologically intact mice challenged with heterologous erythrocytes synthesize anti-erythrocyte antibody at a greater rate than similarly challenged, uninfected mice.

Animals↗
PubMed1979

Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse: III. The failure of primary infections with cercariae of one sex to induce resistance to reinfection.

Mice which were given a primary infection consisting of male or female Schistosoma mansoni cercariae alone failed to acquire the same degree of resistance against homologous challenge as did mice with a bisexual primary infection. The degree of resistance acquired by "single-sex"-infected mice was not augmented either by increasing the number of cercariae administered in the primary infection, or by increasing the interval between primary infection and challenge, or by injection of S. mansoni eggs. The results are discussed in relation to previous observations on the capacity of "single-sex" schistosome infections to induce resistance.

Animals↗
PubMed1978

Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. I. Demonstration of resistance to reinfection using a model system that involves perfusion of mice within three weeks of challenge.

The degree of resistance acquired by Schistosoma mansoni-infected mice against homologous challenge has been determined by perfusion of the animals within three weeks of the challenge, at which time the challenge-derived organisms were morphologically distinguishable from the primary infection which induced the resistance. The method has been compared with assays based on determination of the number of organisms migrating through the lung, and with perfusions at a later time when the challenge has matured. The results obtained with the three week perfusion method, showing that resistance was acquired by eight weeks after a primary infection, were confirmed by the longer survival of, and reduced egg excretion rates and tissue egg burdens in the experimental animals relative to respective challenge control animals. However, some discrepancy in challenge-derived worm numbers was found between animals perfused three weeks after challenge and those autopsied at later times. The possible reasons for this difference are discussed. The degree of resistance that was acquired was to some extent dependent on the size of the challenge infection.

Animals↗