Biomedical subjects
H Ohtomo
Publications and source records attributed to H Ohtomo.
Entamoeba invadens: reversible effects of aphidicolin on the growth and encystation.
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The involvement of CD80 and CD86 costimulatory molecules in the induction of eosinophilia in mice infected with Nippostrongylus brasiliensis.
The costimulatory signal provided by the interaction between CD28 and its ligands, CD80 and CD86, is critical for T cell activation. The requirement of CD80 and CD86 in T cell activation for eosinophilia and IgE production was examined in mice infected with the nematode parasite Nippostrongylus brasiliensis. Combined treatment with anti-CD80 and anti-CD86 suppressed eosinophilia in the blood and the small intestine and suppressed IgE production. However, administration of either anti-CD80 or anti-CD86 alone had little effect on eosinophilia and on the elevation of IgE levels. These results suggest that CD80 and CD86 costimulation is required and either CD80 or CD86 can provide a sufficient costimulatory signal for induction of eosinophilia in mice infected with N. brasiliensis.
Inhibition of encystation of Entamoeba invadens by aphidicolin.
Effects of aphidicolin, a specific inhibitor of eukaryotic nuclear replicative DNA polymerases, on the growth and encystation of a reptilian parasitic protozoan Entamoeba invadens were evaluated. Aphidicolin blocked the growth of axenic E. invadens strain IP-1 in a dose-dependent manner. Encystation induced by the glucose depletion and osmotic pressure was also inhibited by aphidicolin. The inhibition was almost complete when trophozoites were treated with the drug before being transferred to encystation medium containing the drug. The inhibitory effect of aphidicolin on E. invadens growth was abrogated by removal of the drug, and exposure to 3 microg/ml of the drug for at least 7 days had little effect on the viability. Encystation was also restored by removal of the drug. These results suggest that the trophozoites accumulated at G1/S border by treatment with aphidicolin cannot encyst upon induction of encystation so that they need DNA synthesis before encystation.
Effects of aphidicolin on Entamoeba histolytica growth and DNA synthesis.
We have detected and characterized DNA polymerase activity in cell extracts from trophozoites of Entamoeba histolytica and have found that the activity of E. histolytica is inhibited by aphidicolin, which is a specific inhibitor of eukaryotic nuclear replicative DNA polymerases. The present study was aimed to evaluate the effect of aphidicolin on growth and DNA synthesis by this parasite. Aphidicolin blocked the growth of axenic E. histolytica strain HM-1: IMSS. DNA synthesis was also inhibited by aphidicolin when assayed by incorporation of [3H] thymidine into the DNA. The inhibitory effect of aphidicolin on the growth of E. histolytica was abrogated by removal of the drug, and exposure to 3 microg/ml of the drug for at least 48 hr had little effect on the viability. Synchronous growth was observed in the recovery phase after removal of aphidicolin.
Effects of aphidicolin on Entamoeba histolytica growth and DNA synthesis.
We have previously demonstrated that DNA polymerase activity of Entamoeba histolytica is inhibited by aphidicolin, which is a specific inhibitor of eukaryotic nuclear replicative DNA polymerases. The present study was aimed to evaluate the effect of aphidicolin on growth and DNA synthesis by this parasite. Aphidicolin blocked the growth of axenic E. histolytica strain HM-1:IMSS. DNA synthesis was also inhibited by aphidicolin when assayed by incorporation of [3H]thymidine into the DNA. The inhibitory effect of aphidicolin on the growth of E. histolytica was abrogated by removal of the drug, and exposure to 3 microg/ml of the drug for at least 48 hr had little effect on the viability. Synchronous growth was observed in the recovery phase after removal of aphidicolin.
An investigation into the prevalence of thyroid disease on Kwajalein Atoll, Marshall Islands.
The prevalence of thyroid nodules and thyroid cancer was studied in the indigenous population residing on Ebeye Island, Kwajalein Atoll, in the Republic of the Marshall Islands. This island, centrally located in the nation, is home to about 25% of the nation's population, many who have migrated there from other atolls. The objective of the study was to obtain thyroid disease rate statistics on as much of the population as possible that was alive during the years of nuclear testing and to test the hypothesis that described a linearly decreasing prevalence of palpable nodules with increasing distance from the Bikini test site. 1,322 Marshallese born before 1965 were given a thyroid examination using neck palpation, fine needle aspiration biopsy, and high resolution ultrasound imaging. Approximately 40% of the total population living on this island who are at risk from exposure to radioactive fallout during the years 1946-1958 were screened. Of that group, 815 were alive at the time of the BRAVO test on 1 March 1954. Two hundred sixty-six people with thyroid nodules were found (32.6%): 132 were palpable nodules (16.2%), and 134 were nodules that could be diagnosed with ultrasound only (15.7%). Prevalence of palpable nodules was particularly high in men and women older than 60 y, in men who were 6 to 15 y of age at the time of the BRAVO test, and in women 1 to 10 y of age at the time of the BRAVO test. In 22 people, the clinical diagnosis was most likely cancer though histopathological evidence was only available from 11 operated cases. Of the 11 operated cases, 10 were cancer. Cancer prevalence was particularly high in those women born between 1944 and 1953 (7/220 = 3.2%), i.e., who were children during the early years of nuclear testing. The Ebeye data showed a marginally significant correlation between palpable nodule prevalence among women and distance to Bikini (r = -0.44, p = 0.06). This report summarizes the clinical findings of the thyroid examinations, the age distributions for nodular disease and cancer, and examines the relationship between prevalence of nodules and present day levels of 137Cs in the environment of each atoll.
Eosinophil chemotactic activity in Leishmania amazonensis promastigotes.
Tissue eosinophilia was observed in the subcutaneous tissue of mice shortly after their inoculation not only with living but also with lysed promastigotes of Leishmania amazonensis. Intraperitoneal inoculation of lysed promastigotes from five different Leishmania species (L. donovani, L. chagasi, L. tropica, L. amazonensis, and L. braziliensis) induced eosinophil accumulation in the mouse peritoneum. This eosinophil infiltration was also detected in C5-deficient AKR mice, indicating complement independent eosinophil chemotaxis by the parasite. The induced eosinophils were hypodense, suggesting activation of the cells. Finally, we demonstrated in vitro eosinophil chemotactic activity in the promastigote lysates using purified eosinophils and blind well chambers. These results suggest the presence of an eosinophil chemotactic factor in Leishmania, a protozoan parasite.
Nerve growth factor enhances survival and cytotoxic activity of human eosinophils.
Phenotypic change of blood-type eosinophils to tissue-type eosinophils is induced by various cytokines. We examined the effect of nerve growth factor (NGF) as a candidate for a constitutive cytokine which is able to induce the phenotypic change of eosinophils. The viability of human peripheral blood eosinophils cultured for 4 d was increased from a mean of 26% to a mean of 50% (P<0.001) by the addition of NGF (50 ng/ml). Cytotoxic activity of eosinophils determined by larvicidal activity was increased 2-3-fold by the addition of NGF (50 ng/ml) (P<0.05). Furthermore, eosinophil chemotactic activity of NGF was demonstrated by the blind well chamber method. Since NGF is produced constitutively from various kinds of cells in local tissues, it is suggested that NGF might be a cytokine responsible for phenotypic change to tissue type eosinophils in conditions without immune stimuli.
[A study of relapsed cases of vivax malaria after the standard primaquine therapy].
Vivax malaria is the most frequent among imported malaria in Japan, comprising about 60% of the total cases. Usually, after the acute phase therapy, e.g. with chloroquine, patients with vivax malaria are treated with the standard course of primaquine, i.e. 15 mg base/day for 14 days, as curative therapy. Recently, however, cases of relapse of vivax malaria after this standard primaquine therapy were reported from various countries and were also encountered in Japan. This report showed that the relapse after the standard primaquine therapy occurred most frequently in the cases acquired in Papua New Guinea, followed by Indonesia and Thailand. In contrast, the relapse rate of the cases acquired in India was low. Most of the relapsed cases were successfully treated with either of the regimens 1) 30 mg/ day for 7 days, 2) 2 courses of the standard primaquine therapy given 1 month apart or 3) 15 mg/ day for 21 days, without noticeable side effects. It is imperative to establish the most appropriate regimen with primaquine for the curative treatment of vivax malaria contracted in the areas mentioned above.
Brugia malayi infection in mice with selective suppression of IgE production.
For the purpose of evaluating the roles of IgE in helminth infections in vivo, IgE-suppressed mice provide useful models. After infection with 50 third-stage larvae of the filarial parasite Brugia malayi, total IgE in BALB/c mice increased to five times higher than uninfected levels. However, anti-B. malayi IgE antibody was not detected, indicating polyclonal IgE B cell activation by the infection. In BALB/c mice which had received repeated injections of anti-mouse epsilon monoclonal antibody from birth and which were subsequently infected, total IgE levels were less than 10 ng/ml, but anti-B. malayi IgG antibody and total IgA were produced similar to the control. Therefore, IgE-isotype-specific suppression was attained. Concerning the protection against B. malayi, the numbers of fourth-stage larvae and adult worms at 2 and 5 weeks after primary infection, respectively, and fourth-stage larvae at 2 weeks after secondary infection were not significantly different between control and IgE-suppressed mice.
An increased DNA polymerase activity associated with virulence of Toxoplasma gondii.
DNA polymerase activity of the virulent RH strain of Toxoplasma gondii was significantly higher than that of the avirulent ME49 strain, whereas sensitivity of the activities of both strains to salt, Mg2+, and inhibitors of mammalian DNA polymerases were almost the same. It is suggested that this increased enzyme activity of the virulent strain contributes to a faster rate of multiplication of the organisms as compared with that of the avirulent strain.
[A case with a larva of a spiruroid nematode in the intestinal wall].
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[Morphological changes of Plasmodium-infected red blood cells in thin blood smears].
Malaria is absent in Japan, but about sixty imported cases are reported in a year. We think it desirable that all medical care institutions should examine for malaria infection promptly. Diagnosis of malaria, in Japan, depends mostly on the examination of thin blood smears stained by Giemsa. However, we sometimes find atypical changes of infected red blood cells, especially in their size. It was also presumed that infected red cells may differ in their size and other morphology by their geographical origin. The present study was designed to investigate the influences of malaria infection on the morphology of host red cells. Thin blood smear samples from the cases of a single species plasmodial infection with epidemiological circumstances were chosen for this investigation from the specimens which we examined in our laboratory. Cases with a history of chemoprophylactic or chemotherapeutic use within 1 month prior to the blood examination were excluded. Cases were classified according to species of the infected parasites and the geographical origin; Africa, South-East Asia, and Western Pacific. The distribution of red cell diameters and the ratio of maximum diameter to minimum diameter were determined on blood smears using oil immersion lens. Measurement was completed with 20 or 30 infected red cells for each developmental stage of the parasites and 30 non-infected red cells per slide. The presence of Schüffner's dots was observed on blood smears from vivax or ovale malaria patients. We examined also for Maurer's dots and fimbriated margin of red cells on falciparum and ovale malaria specimens respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
[Studies on tsutsugamushi diseases in Gifu Prefecture. 5. Characterization of monoclonal antibodies to prototype strains of Rickettsia tsutsugamushi and immunological grouping of newly isolated strains using the antibodies].
We characterized 8 monoclonal antibodies (MAbs) to Karp, Kato, and Gilliam strains of Rickettsia tsutsugamushi, and analysed 17 isolates from patients with Tsutsugamushi disease using these MAbs. These were divided into 3 strain-specific (Kp/D11, Kt/2D9, and Gi/E4) and 5 cross-reactive MAbs (Kp/1F11, Kp/1C10, Kp/C6, Kt/3B2, and Kt/3C2). All MAbs recognized characteristic protein antigens using the indirect fluorescent-antibody test (IFA) and proteinase K treatment. Analysis by polyacrylamide gel electrophoresis and immunoblotting techniques revealed that Kato-specific MAb Kt/2D9 recognized a polypeptide with a molecular mass of 54 kilodalton (kDa) of the homologous strain, and cross-reactive MAbs Kp/1F11, Kp/C6, and Kt/3B2 recognized those of 46-47 kDa, 46-47 KDa, and 60 kDa, respectively to the homologous and heterologous strains. MAbs Kp/1C10 which exhibited a high IFA titer against the Karp strain and only low titers against heterologous strains recognized only the 110 kDa polypeptide of the homologous strain. MAb Kt/3C2 which reacted with both Karp and Kato strains recognized a 54 to 56 kDa polypeptide band of the two prototype strains as well as several other polypeptides, however, each molecular mass was present in only one of two strains. Testing by the plaque reduction technique showed another characteristic of MAb Kt/3C2 to neutralize both Karp and Kato Strains. Fourteen isolated strains from patients in the south and west regions of Gifu Prefecture, the Shimokoshi stain isolated in Niigata Prefecture, and Kawasaki and Kuroki stains isolated in Miyazaki Prefecture were examined for reactivities to 8 MAbs by IFA to classify their antigenicities. No isolated strains reacted with Karp-specific Kp/D11, Kato-specific Kt/2D9, or Gilliam-specific Gi/E4.(ABSTRACT TRUNCATED AT 250 WORDS)
How effective is the agar plate method for Strongyloides stercoralis?
The sensitivity of the agar plate method for the diagnosis of Strongyloides stercoralis was studied experimentally. Results demonstrated that this method was sensitive enough to detect S. stercoralis even when only a few worms were present.
[Fundamental study on serological diagnosis of amoebiasis. 3. Serological survey of amoebiasis in blood donors showing seropositive for syphilis].
Sera of 375 blood donors which were seropositive for syphilis were examined for antibodies against Entamoeba histolytica. Antibody prevalences against E. histolytica using complement fixation (CF) test were 12.0%, and enzyme-linked immunosorbent assay (ELISA) were 2.7%. The positive rates of antibodies in the CF test were significantly higher in sera showing positive by the Venereal Disease Research Laboratory (VDRL) test than in the VDRL-negative sera, and not related to the results of Treponema pallidum hemagglutination (TPHA) test. Only one sample in the VDRL-negative sera was positive by CF test. On the other hand, the positive rates or mean absorbance in ELISA were not correlated to the results of VDRL or TPHA test. The percent positivity in CF test became higher with the level of antibodies in VDRL test, but not that in ELISA. The level of antibodies in CF and VDRL test were weakly correlated. These results suggested that the results of CF test for E. histolytica antibodies were most likely false-positive in relation to the results of VDRL test. 10 (2.7%) of sera were positive by ELISA, but all ELISA-positive samples showed low ELISA titers and absorbance. 9 of the ELISA-positive samples showed indirect fluorescent antibody (IFA) titers of over 1:50, and the level of antibodies in the IFA test correlated to that in ELISA, so ELISA-positive persons seemed to have been previous infected or were asymptomatic cyst carriers.
[Trends of tissue hypoxia following chemotherapy of acute malaria in mice].
The effects of antimalarial treatment on the blood oxygen-transporting properties and on the tissue hypoxia were investigated in severe murine malaria, using mice infected with Plasmodium berghei (NK65). Five week old male ddY mice were inoculated intraperitoneally with 1 X 10(7) of P. berghei-infected red blood cells and treated with Fansidar (20 mg/kg body weight sulfadoxine and 1 mg/kg body weight pyrimethamine orally) on day 5 after inoculation. Parasitemia in these mice decreased rapidly on day 1 after treatment. Blood hemoglobin concentration, however, decreased on days 1 and 2 of treatment, then began to increase. The actual oxygen equilibrium curve (OEC) in vivo (actual pH; actual Pco2; 36.5 degrees C) was calculated from the measured OEC and the results of blood gas analysis. Looking from arterial and venous Po2 of each group, blood oxygen-transporting properties decreased markedly on day 2 of treatment. This decrease resulted mainly from the decrease of hemoglobin concentration and also partly from the raised hemoglobin affinity for oxygen. Adenosine triphosphate concentration in liver tissues, however, began to increase on day 1 of treatment. Adenylate energy charge of liver tissues also recovered on day 1. Blood glucose concentration began to increase and blood lactate concentration began to decrease simultaneously on day 1 of treatment. Glucose concentration in liver tissues, in contrast, decreased on days 1 and 2 of inoculation. Lactate concentration in liver tissue decreased earlier on day 1. These data indicate that tissue hypoxia was removed on day 1 following antimalarial treatment although blood oxygen-transporting properties decreased on days 1 and 2 after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)