Heterologous mating of Schistosoma japonicum and Schistosoma incognitum in experimentally infected rodents.
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The first clinical trials of praziquantel against Schistosoma japonicum infections in Japan were planned to assess tolerance only. Three double-blind studies against placebo involving a total of 51 patients were conducted with dosages of praziquantel of 1 x 20 mg/kg body weight, 2 x 20 mg/kg, 3 x 20 mg/kg given on one day.The frequency of unwanted side effects was higher in the group of patients given praziquantel at a dose of 3 x 20 mg/kg than in all other drug- or placebo-treated patients. In general, the side effects, which included drowsiness, headache, lumbago, abdominal fullness, or epigastric discomfort, lasted for several hours but disappeared spontaneously. The results of laboratory tests showed no significant changes caused by treatment.The overall assessment showed excellent or good tolerance in all patients treated with praziquantel at the lower dose levels. In those given 3 x 20 mg/kg, tolerance was excellent in 1 of 12 patients, good in 9, and fair in 2, whereas the respective placebo-treated group showed excellent tolerance in 3 of 12, good in 7, and fair in 2.
Glucose-6-phosphate dehydrogenase activity in paired adult Schistosoma mansoni is about twice as great as in paired adult Schistosoma japonicum. 2. 6-phosphogluconate dehydrogenase activity accounts for 25.8% of the measured production of reduced nicotinamide adenine dinucleotide phosphate (NADPH) in S. japonicum but only 8.6% of the measured production of NADPH in S. mansoni. 3. These data suggest a species difference in 6-phosphogluconate metabolism.
Eleven pairs of schistosomes, indistinguishable from the classical Schistosoma japonicum, were found in a monkey (Macaca fascicularis) taken near Ranau in North Borneo. The new locality is within the recorded range of the species which extends from Japan, China, Taiwan, and Philippines through Southeast Asia to the Celebes.
Antibodies in Schistosoma japonicum infections were successfully detected by micro-technique (0.3ml/well) of ELISA on polystyrene microtiter plates using peroxidase labelled anti-human IgG and 5-amino salicylic acid as conjugate and substrate, respectively. Serum samples collected from 22 proven patients in Leyte, Philippines showed titers of higher than 1:960 in 18 cases, 1:240 in 2 cases and 1:120 in 2 cases whereas titers of 22 proven negative sera collected in Tokyo were less than 1:15. Though the reaction was read by spectrophotometry in the present study, the difference of reactions between positive and negative sera was so clear as to be recognizable readily by visual readings.
The annual incidence of Schistosoma japonicum infection was calculated from the record of the yearly examination among school children of Dagami Area, Leyte, Philippines. Data were processed mainly by the computer. Children were examined for eggs by the merthiolate formalin concentration technique and by the circumoval precipitin test (COPT) once a year in 3 consecutive school years (SY), SY 1974/75, 1975/76 and 1976/77. About 600 to 700 children were examined yearly and the ratios of cases rechecked after 1 year were about 30%. A method to calculate the overall incidence in children who were examined at different intervals, was newly established. The incidence appeared to rise rapidly in the survey period, being 25.59% and 41.30% by fecal examination and 10.74% and 21.27% by COPT in SY 1975/76 and 1976/77, respectively. From the combined results of fecal examination and COPT, the reliable values of incidence, however, were shown to be stable during 2 years such as 22.06% and 24.21%, respectively. The incidence estimated by the age prevalence data was 20.25% in SY 1976/77 by the combined results and was found to be lower than the directly calculated value.
Immunoglobulin E (IgE), mast cells, and eosinophils in the skin of rhesus monkeys immunized with highly X-irradiated cercariae of Schistosoma japonicum were studied. IgE was stained by the unlabeled antibody enzyme method and was found on mast cells. Before challenge, mast cells were found only in the dermis. Immediately after the challenge, mast cells were found in both the dermis and epidermis and many of them were degranulated. Soon after, margination and emigration of granulocytes, predominantly eosinophils, occurred along the blood capillaries in the dermis. Gradulally, preivascular infiltration of eosinophils was seen in the dermis and migration of eosinophils from the dermis into the epidermis appeared, resulting in the formation of minute eosinophilic abscesses in the epidermis. In addition, the IgE was found as a thin coat on the integument of the schistosomula. Deteriorated schistosomula were seen amid the eosinophilic abscesses in the epidermis and in eosinophilic infiltrations in the dermis. The present findings suggest the possibility that the reaction of IgE, mast cells, and eosinophils were integrated into one immunological effect, namely the schistosomulicidal action.
Studies of granulomatous hypersensitivity to Schistosoma japonicum eggs were performed at various time periods up to 20 wk after the induction of light infections in mice. Cell populations which were determined in granulomas isolated from the livers revealed a maximum in the total number of cells at 6 wk with a decline of 36% by 20 wk. Large mononuclear cells were predominant at all time periods, with eosinophils being the second most common cell. Measurements of granuloma diameters around single viable eggs in the livers also revealed peak size at 6 wk with a decline of 51% between 16 and 24 wk. Immunodiffusion analysis demonstrated the presence of precipitating antibodies as early as 7 wk after infection. Investigations of lymphocyte blastogenesis revealed a profound depression in response to T-cell mitogens by 8 wk of infection. Studies of footpad swelling to soluble S. japonicum egg antigens revealed massive immediate reactions starting at 6 wk. but no delayed reactivity over a period from 3 to 20 wk. All of these results are related to differences in the biology of S. japonicum in comparison with S. mansoni with respect to the earlier onset of egg production, the much larger numbers of eggs produced, and the possibility of differences in the antigens emitted by the eggs.
Schistosomiasis affects more than 250 million people worldwide and is one of the neglected tropical diseases. Currently, the treatment of schistosomiasis relies on a single drug-praziquantel-which has led to increasing pressure from drug resistance. Therefore, there is an urgent need to find new treatments. The development of genome sequencing has provided valuable information for understanding the biology of schistosomes. In the genome of Schistosoma japonicum, approximately 11% of the protein-coding sequences are uncharacterized genes (UGs) annotated as "hypothetical protein" or "protein of unknown function." These poorly understood genes have been unjustifiably neglected, although some may be essential for the survival of the parasites and serve as potential drug targets. In this study, we systematically mined the highly expressed UGs in both genders of this parasite throughout key developmental stages in their mammalian host, using our previously published S. japonicum genome and RNA-seq data. By employing in vitro RNA interference (RNAi), we screened 126 UGs that lack homologs in Homo sapiens and identified 8 that are essential for the parasite vitality. We further investigated two UGs, Sjc_0002003 and Sjc_0009272, which resulted in the most severe phenotypes. Fluorescence in situ hybridization demonstrated that both genes were expressed throughout the body without sex bias. Silencing either Sjc_0002003 or Sjc_0009272 reduced the cell proliferation in the body. Furthermore, in vivo RNAi indicated both genes are required for the growth and survival of the parasites in the mammalian host. For Sjc_0002003, we further characterize the underlying molecular cause of the observed phenotype. Through RNA-seq analysis and functional studies, we revealed that silencing Sjc_0002003 reduces the expression of a series of intestinal genes, including Sjc_0007312 (hypothetical protein), Sjc_0008276 (vha-17), Sjc_0002942 (PLA2G15), and Sjc_0003646 (SJCHGC09134 protein), leading to gut dilation. Our work highlights the importance of UGs in schistosomes as promising targets for drug development in the treatment of the schistosomiasis.
Praziquantel, a new antischistosomal compound, was tested for tolerance and efficacy against placebo in two double-blind clinical trials in Philippine patients infected with Schistosoma japonicum.The compound was given orally at a dose of 3 x 20 mg/kg at intervals of 4 hours to a total of 82 patients-some without advanced disease and some with hepatosplenic involvement. A total of 43 patients received placebo. In a single-blind trial, 42 patients were given a single oral dose of 50 mg/kg. Monitoring of vital organ functions included comprehensive laboratory tests and serial electrocardiograms. In 38 patients with hepatosplenic involvement due to advanced stages of infection, serial electroencephalograms were additionally recorded. No toxic effects were observed in any of these examinations.Undesirable side effects occurred in 53% of the patients given 3 x 20 mg/kg and in 70% after a dose of 1 x 50 mg/kg. They consisted mainly of abdominal discomfort, fever, sweating, and occasionally giddiness, but in general were transient and mild. At 6 months post-treatment, 60 of 75 patients treated with 3 x 20 mg/kg and 29 of 41 treated with 1 x 50 mg/kg were completely negative for eggs. At 12 months post-treatment, 25 of 33 and 14 of 26 patients in the two treatment groups were cured. Thus the divided dosage gave a superior therapeutic result. Praziquantel proved to be free of major toxicity, and was well tolerated, highly effective, and easy to administer. Confirmation of results in extended trials may soon permit large-scale treatment.
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The schistosomal and malarial pigments were distinguishable before and after extraction from the host liver. Presence of iron in both pigments was ascertained by the elemental X-ray analysis. Histochemically, however, schistosomal pigment was similar to that of malarial pigment.
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A limited drug trial was carried out on 42 cases with schistosomiasis japonica from an endemic area of Central Sulawesi. The drugs used were niridazole and stibophen. The effects of treatment were reported and discussed. The results of this study offer promise for treating S. japonicum infection in Central Sulawesi on a larger scale.
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