Biomedical subjects

Nobuo Ohta

Publications and source records attributed to Nobuo Ohta.

At least 19 recordsLinked to original sources

PubMed2006

School-health-based parasite control initiatives: extending successful Japanese policies to Asia and Africa.

Japan controlled its major parasitic diseases by the 1970s. Based on this experience, the Government of Japan proposed the Global Parasite Control Initiative in 1998 and established three research and training centres around the world. The Asian Centre of International Parasite Control (ACIPAC) is the first such centre, and completed five years of activities focused on school-health-based parasite control in the Greater Mekong Subregion in 2005. The lessons learned and experiences gained by ACIPAC should be applied to all health promotion programmes worldwide.

Animals↗

PubMed2006

Disease burden and epidemiology of soil-transmitted helminthiases and schistosomiasis in Asia: the Japanese perspective.

The disease burden due to soil-transmitted helminthiases (STH) and schistosomiasis is not well documented in Asia. Both STH and schistosomiasis are chronic diseases but case detection is not easy because of the absence of clinical symptoms. STH and schistosomiasis are, however, endemic in Asia and their burden is significant. At the preparatory meeting for the Hashimoto Initiative in Japan in 1997, STH and schistosomiasis were categorized as Group 2 diseases. Parasitic infections in this category were well understood at the time but sophisticated control strategies were lacking. Japan has promoted comprehensive collaborative projects to reduce the burden of STH and schistosomiasis throughout Asia, creating an international network to collect epidemiological information and to implement and improve disease control, thus extending the school-based control method that had proved so successful in Japan.

Animals↗

PubMed2006

Immunotherapy with CpG DNA conjugated with T-cell epitope peptide of an allergenic Cry j 2 protein is useful for control of allergic conditions in mice.

Immunotherapy using T-cell epitope peptides or CpG DNA conjugated with allergenic protein is useful, although the mechanisms of these therapies differ. However, the combination of CpG DNA and peptide, but not protein, had not been documented. Therefore, we investigated CpG DNA conjugated with peptide to obtain positive synergistic effects. In the first experiment, mice were vaccinated with a conjugate of CpG DNA and Cry j 2 T-cell epitope peptide p246-259 (CpG-peptide); a mixture of CpG DNA and peptide (CpG+peptide); peptide alone, or PBS alone, and immunized with Cry j 2. In the second experiment, mice were immunized with Cry j 2 and injected with CpG-peptide, CpG+peptide, peptide only, or PBS only. In both experiments, Cry j 2-specific IgE, IL-4, and IL-5 were significantly lower in mice given CpG-peptide, versus those given CpG+peptide, peptide alone, or PBS alone. However, IgG2a, IgG2b and IFN-gamma did not increase in mice injected with CpG-peptide. In the third experiment, CpG-peptide significantly attenuated nasal symptoms (sneezing and nasal rubbing) compared to CpG+peptide, peptide alone, or PBS alone. Mice were also injected with a conjugate of CpG DNA and Cry j 2 protein (CpG-Cry j 2) or CpG-peptide to compare prime responses. Mice vaccinated with CpG-Cry j 2 generated Cry j 2-specific IgG1, whereas those vaccinated with CpG-peptide did not produce IgG1. This study demonstrated, for the first time, that immunotherapy with CpG DNA conjugated with a T-cell peptide is useful in preventing and treating allergic conditions.

Animals↗

PubMed2006

Blocking of protease allergens with inhibitors reduces allergic responses in allergic rhinitis and other allergic diseases.

CONCLUSIONS: Allergic responses specific to the corresponding proteases were reduced by protease inhibitors, suggesting promise as potent treatments for allergic rhinitis and other allergic conditions. OBJECTIVE: Allergic diseases, such as allergic rhinitis, are caused by the overproduction of IgE antibodies to various allergens. Many reported allergens are proteases that are cysteine, serine, aspartic (acid) proteases and metalloproteases. Conjugation of E64 inhibitor with cysteine protease allergens inhibits the IgE response to the same allergens. However, whether inhibitors of the other protease families reduce IgE levels and whether protease inhibitors reduce allergic symptoms remain controversial. Therefore, we compared the abilities of active and inhibitor-blocked inactive forms of proteases to generate IgE and allergic symptoms in this study to evaluate associations between the allergic response and protease inhibitors. MATERIALS AND METHODS: We measured levels of IgE, IgG1, IgG2a, and IgG2b enzyme-specific antibodies, and counted frequency of sneezing and nasal rubbing behavior in mice immunized with active or inactive forms of bromelain, chymotrypsin, chymosin and collagenase (a cysteine protease, a serine protease, an aspartic protease and a metalloprotease, respectively). RESULTS: All the inhibitors reduced IgE and IgG1 production in response to corresponding enzymes, and a cysteine protease inhibitor, E64, decreased nasal symptoms, such as sneezing and nasal rubbing.

Allergens↗

PubMed2006

[Endemic tropical diseases: comtemporary health problem due to abandoned diseases in the developing world].

There are two kinds of infectious diseases in the world; diseases being paid attention and neglected diseases. The former diseases include HIV/AIDS, tuberculosis and malaria, the latter group include many parasitic, fungal, bacterial and some of viral infections. "Neglected Infectious Diseases", which have been renamed as Endemic Tropical Diseases by WHO, are endemic in the developing world are not newly appeared diseases, but diseases affecting humans in these decades. In fact, DALYs for several diseases in the category are big enough; more than 300 millions for soil-transmitted helminthiasis, 5 millions for lymphatic filariasis, 4-5 millions for schistosomiasis and so forth. However, those diseases were not recognized as serious health problems because of socio-economical and/or scientific reasons. Furthermore, those diseases are no fatal in the acute phases; therefore, no big attention is raised by policy makers in the world. From the view point of basic medical sciences, however, there is no enough reason for neglecting the issues of those diseases: no improved diagnostics and therapeutics have been developed in spite of the urgent necessities in endemic areas. Considering those situations, WHO has started to take action for solving the problems since beginning of the 21st century. Recently, many of developed countries are recognizing that the imbalanced input of human and financial resources only for 3 major infectious diseases, HIV/AIDS, tuberculosis and malaria, and then, various international schemes for supporting research on Neglected diseases. DNDi, Drugs for Neglected Diseases initiative, is one of the examples and it's scope is only focusing on drug development for Neglected diseases. African trypanosomiasis is one of Neglected diseases and causing serious health problem both for humans and domestic animals in Africa. No safe and effective medicine has been available but a drug with serious side effects is only the drug of choice even nowadays. Under the grant support from DNDi, a Japanese group is developing a new drug, ascofuranone, for African trypanosomiasis without any detectable side effects. Developing new prophylactic drugs for schistosomiasis and new diagnostic tools for lymphatic filariasis are underway under the support of grant for Neglected or Re-emerging infectious diseases in Japan. Considering that issues of "Neglected Infectious Diseases" are urgent to be solved and also are challenging for modern medicine and medical sciences, researchers in the developed countries including Japan should make efforts to promote more active researches in this field.

Developing Countries↗

PubMed2005

Evaluation of the anthelmintic effects of artesunate against experimental Schistosoma mansoni infection in mice using different treatment protocols.

The therapeutic effects of artesunate against experimental Schistosoma mansoni infection in mice were analyzed. Previous studies showed that artesunate is highly effective against S. japonicum infection, but the action of this drug against S. mansoni remained uncovered. The present study examines the optical conditions for artesunate against S. mansoni and evaluates the effects of inhibiting the sexual maturation of adult worms. Mice infected with S. mansoni were orally administered with artesunate according to different schedules. Four consecutive administrations of 300 mg/kg of artesunate at 2-week intervals conferred almost total protection without the development of pathological lesions in the liver. The significant reduction in the number of eggs produced by surviving worms and the status of egg maturation suggested that artesunate inhibits sexual maturation. Electron microscopy revealed that artesunate caused morphological damage, especially on the worm tegument. Artesunate was also very effective in iron-deficient mice. Furthermore, the efficacy of artesunate was equal to or better than that of artemether against S. japonicum infection. Considering that artemether is more toxic, artesunate is currently one of the most efficient drugs against immature S. mansoni.

Anemia, Iron-Deficiency↗

PubMed2005

Chemotherapeutic efficacy of ascofuranone in Trypanosoma vivax-infected mice without glycerol.

Ascofuranone, an antibiotic isolated from Ascochyta visiae, showed trypanocidal activity in Trypanosoma vivax-infected mice. A single dose of 50 mg/kg ascofuranone effectively cured the mice without the help of glycerol. Repeated administrations of this drug further enhanced its chemotherapeutic effect. After two, three, and four consecutive days treatment, the doses needed to cure the infection decreased to 25, 12, and 6 mg/kg, so that the total doses administered were 50, 36 and 24 mg/kg, respectively. Ascofuranone (50 mg/kg) also had a prophylactic effect against T. vivax infection within the first two days after administration. This prophylactic activity diminished to 80% by day 3 and completely disappeared four days after administration. Of particular interest in this study was that ascofuranone had trypanocidal activity in T. vivax-infected mice in the absence of glycerol, whereas co-administration of glycerol or repeated administrations of this drug are needed for Trypanosoma brucei brucei infection. Our present results strongly suggest that ascofuranone is also an effective tool in chemotherapy against African trypanosomiasis in domestic animals.

Animals↗

PubMed2005

IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity.

C57BL/6 (B6) and B6 background STAT6(-/-) mice pretreated with IL-18 plus IL-2 showed prominent intestinal mastocytosis and rapidly expelled implanted adult worms of the gastrointestinal nematode Strongyloides venezuelensis. In contrast, identically pretreated mast cell-deficient W/W(v) mice failed to do so. Thus, activated mucosal mast cells (MMC) are crucial for parasite expulsion. B6 mice infected with S. venezuelensis third-stage larvae (L3) completed parasite expulsion by day 12 after infection, whereas IL-18(-/-) or IL-18Ralpha(-/-) B6 mice exhibited marked impairment in parasite expulsion, suggesting a substantial contribution of IL-18-dependent MMC activation to parasite expulsion. Compared with IL-18(-/-) or IL-18Ralpha(-/-) mice, S. venezuelensis L3-infected STAT6(-/-) mice have poorly activated MMC and sustained infection; although their IL-18 production is normal. Neutralization of IL-18 and IL-2 further reduces expulsion in infected STAT6(-/-) mice. These results suggest that collaboration between IL-18-dependent and Th2 cell-dependent mastocytosis is important for prompt parasite expulsion.

Animals↗

PubMed2005

Mutational analysis of the Trypanosoma vivax alternative oxidase: the E(X)6Y motif is conserved in both mitochondrial alternative oxidase and plastid terminal oxidase and is indispensable for enzyme activity.

Based on amino acid sequence similarity and the ability to catalyze the four-electron reduction of oxygen to water using a quinol substrate, mitochondrial alternative oxidase (AOX) and plastid terminal oxidase (PTOX) appear to be two closely related members of the membrane-bound diiron carboxylate group of proteins. In the current studies, we took advantage of the high activity of Trypanosoma vivax AOX (TvAOX) to examine the importance of the conserved Glu and the Tyr residues around the predicted third helix region of AOXs and PTOXs. We first compared the amino acid sequences of TvAOX with AOXs and PTOXs from various taxa and then performed alanine-scanning mutagenesis of TvAOX between amino acids Y(199) and Y(247). We found that the ubiquinol oxidase activity of TvAOX is completely lost in the E214A mutant, whereas mutants E215A and E216A retained more than 30% of the wild-type activity. Among the Tyr mutants, a complete loss of activity was also observed for the Y221A mutant, whereas the activities were equivalent to wild-type for the Y199A, Y212A, and Y247A mutants. Finally, residues Glu(214) and Tyr(221) were found to be strictly conserved among AOXs and PTOXs. Based on these findings, it appears that AOXs and PTOXs are a novel subclass of diiron carboxylate proteins that require the conserved motif E(X)(6)Y for enzyme activity.

Amino Acid Motifs↗

PubMed2005

Establishment of Schistosoma japonicum calpain-specific mouse T cell hybridomas and identification of a T cell epitope that stimulates IFNgamma production.

Calpain is a calcium-dependent cystein protease, and the homologues of schistosome are known as one of vaccine candidate molecules against schistosomiasis. Here, we established two IL-2 producing T cell hybridoma cell lines specific for Schistosoma japonicum calpain, to identify T cell epitope(s) on the molecule. Overlapping 15mer oligopeptides of calpain were synthesized and tested for their stimulatory abilities to the hybridomas. As a result, epitopes recognized by the two hybridoma lines were the same: EQLKIYAQRC. Spleen cells from calpain multiple antigenic peptide (MAP)-immunized BALB/c mice produced IFNgamma upon stimulation with MAP or soluble worm antigen preparation (SWAP). The identification of the T cell epitope to stimulate Th1 response will contribute to the proper design of synthetic vaccines, evaluation of their protective potentials and elucidation of protective mechanisms in murine experimental schistosomiasis.

Amino Acid Sequence↗

PubMed2005

Molecular evolutionary analyses implicate injection treatment for schistosomiasis in the initial hepatitis C epidemics in Japan.

BACKGROUND/AIMS: The mortality due to hepatocellular carcinoma (HCC) has ranged widely in various areas of Japan since 30 years ago and the incidence was particularly high in once Schistosoma japonicum (Sj)-endemic areas. Our aim was to estimate the spread time of hepatitis C virus (HCV) infection in the past with possible relevance to a higher incidence of HCC in once Sj-endemic than Sj-nonendemic areas. METHODS: During 2001, 131 strains of HCV-1b were obtained from patients in three previously Sj-endemic areas, as well as Sj-nonendemic areas in Japan and a cross-sectional study was conducted on them with molecular evolutionary analyses. RESULTS: A phylogenetic tree reconstructed on HCV-1b sequences in the NS5B region disclosed 2 independent clusters for Sj-positive and -negative groups with a high bootstrap value. The estimated effective number of HCV-infections indicated a transition from quiescence to rapid exponential growth in the 1920s among patients with schistosomiasis, which is 20 years earlier than that among patients without schistosomiasis. CONCLUSIONS: The estimated spread time in previously Sj-endemic areas in Japan coincides with injection treatment for Sj since 1921. A high incidence of HCC there would be attributed to a long duration of HCV infection since 1920s.

Aged↗

PubMed2005

Remembering a nuclear accident in Japan: did it trigger flashbulb memories?

Flashbulb memories are vivid memories of the details surrounding the discovery of an emotional event. We investigated whether the nuclear accident that occurred in Japan in 1999 produced flashbulb memories among people who lived near the accident site. A questionnaire was distributed twice (approximately 3 weeks after the accident and 1 year later) to (1) the residents of the communities surrounding the accident site, (2) the students at a university near the accident site, and (3) the students at two universities far away from the accident site. Flashbulb memory holders were defined as those individuals who showed consistent memories between test and retest. The results indicated that only a small percentage of participants formed flashbulb memories. Further, no age-related decline was found. Flashbulb memories were distinguished by perfect or near perfect scores on four attributes: source, place, activity, and people. The results also indicated that the ratings on emotional reactions, personal consequentiality, and surprise did not differentiate between the flashbulb and non-flashbulb memory holders. In contrast, the flashbulb memory holders reported rehearsing more than the non-flashbulb memory holders. These results supported the notion that flashbulb memories are formed through rehearsal rather than at encoding. However, it is also possible that rehearsal was a result of the flashbulb memory.

Adult↗

PubMed2005

Protective effect of vaccination with Toxoplasma lysate antigen and CpG as an adjuvant against Toxoplasma gondii in susceptible C57BL/6 mice.

Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems to both humans and livestock and of great economic impact worldwide. Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote Th1 responses, an adjuvant activity that is desirable for vaccination against intracellular pathogens. We investigated the feasibility of using CpG as an adjuvant combined with Toxoplasma lysate antigen (TLA) as a vaccine against toxoplasmosis. Genetically susceptible C57BL/6 mice were vaccinated with TLA with or without CpG ODN as an adjuvant and then challenged with 85 cysts of the moderately virulent RRA (Beverley) strain of T. gondii. Prior to challenge infection, immunization with TLA plus CpG ODN directed cellular and humoral immunity toward a Th1 pattern, characterized by enhanced INF gamma production by splenic cells in response to TLA, and enhanced production of toxoplasma-specific IgG and IgG (2a) antibodies. Consequently, CpG/TLA-treated mice showed prolonged survival and 64% reduction in brain parasite burden compared to non-CpG/TLA treated group. Our results suggest that CpG ODN would provide a stable and effective adjuvant for use in vaccination against toxoplasmosis.

Adjuvants, Immunologic↗

PubMed2005

The novelty effect: support for the Novelty-Encoding Hypothesis.

In two experiments, we examined the "Novelty-Encoding Hypothesis" proposed by Tulving and Kroll (1995), suggesting that the encoding of online information into long-term memory is influenced by its novelty and that novelty increases recognition performance. In Phase 1 (familiarization phase), subjects participated in a standard memory experiment in which different types of materials (verbs and nouns) were studied under different encoding conditions (enactment and non-enactment) and were tested by an expected recognition test. In Phase 2 (critical phase), subjects evaluated the materials (both familiar materials which were encoded earlier in Phase 1, and novel materials which were not presented earlier in Phase 1) in a frequency judgment task and were given an unexpected recognition test. The results of both experiments showed that novel items were recognized better than familiar items. This result held true for both hit rates - false alarms and hit rates. The novelty effect was observed for different subjects (Swedish and Japanese), different materials (verbs and nouns; high frequency and low frequency), and different types of encoding in Phase 1 (enactment and non-enactment). These findings provide support for the "Novelty-Encoding Hypothesis" stating that the effect is based on the encoding of target items at the time of the critical study (Phase 2). A comparison between the present experiments and the Tulving and Kroll (1995), Dobbins, Kroll, Yonelinas & Liu (1998) and Greene (1999) studies suggests that the novelty effect is more pronounced under incidental encoding than under intentional encoding.

Analysis of Variance↗

PubMed2004

Schistosoma japonicum: localization of calpain in the penetration glands and secretions of cercariae.

A monoclonal antibody was generated against the large subunit of Schistosoma japonicum calpain to study the localization and possible function of the molecule in vivo. Mice were immunized with recombinant S. japonicum calpain and polyclonal antisera and a monoclonal antibody specific to schistosome calpain was obtained. In immunohistochemistry, a monoclonal antibody against S. japonicum calpain, KG-2E11, bound weakly to calpain expressed at the surface of adult worm tegument, however, it bound strongly to the cercarial secretions ("footprints") of S. japonicum, emitted from the penetration glands. The present study indicates that calpain is multifunctional as it is expressed at various locations in different developmental stages. Calpain-based vaccines could thus possibly induce protective immunity against cercariae and the following early developing stages.

Animals↗

PubMed2004

[Prophylactic effect of artesunate against experimental infection of Schistosoma mansoni].

OBJECTIVE: To study the prophylactic effect of artesunate against the infection of Schistosoma mansoni in mice and its optimal scheme for preventing schistosomiasis mansoni. METHODS: BALB/c mice were infected by tail dipping method with S. mansoni cercariae. Mice were administered orally with artesunate at different developmental stage of the parasite, with different regimens. The reduction rates of total and female worms, the number of eggs in the liver and intestine, and the fecundity were calculated and treated statistically. RESULTS: The optimal dosage of artesunate to prevent murine schistosomiasis was 300 mg/kg. The parasite was found to be especially susceptible to artesunate in its schistosomula stage of 14 and 21 d after infection, resulting in worm reduction rate of 84% and 93% respectively compared with control. High protection was reached with worm reduction rate of 99% by the regimens of 300 mg/kg once a week for 4 consecutive weeks beginning 14 d after infection. The fecundity was significantly suppressed, suggesting that the drug inhibited sexual maturation of female worms. The effective protection could also be gained with prolonged interval time of two weeks with worm reduction rate of 97% and 96% beginning 14 or 21 d after infection. CONCLUSION: Artesunate kills schistosomula and reduces the fecundity of females effectively, the infected mice do not develop schistosomiasis mansoni when treated with artesunate. It's proposed that an optimal scheme for field use be the first administration 14 or 21 days after infection with 1 or 2 weeks interval.

Animals↗

PubMed2004

Direct evidence for cyanide-insensitive quinol oxidase (alternative oxidase) in apicomplexan parasite Cryptosporidium parvum: phylogenetic and therapeutic implications.

Cryptosporidium parvum is a parasitic protozoan that causes the diarrheal disease cryptosporidiosis, for which no satisfactory chemotherapy is currently available. Although the presence of mitochondria in this parasite has been suggested, its respiratory system is poorly understood due to difficulties in performing biochemical analyses. In order to better understand the respiratory chain of C. parvum, we surveyed its genomic DNA database in GenBank and identified a partial sequence encoding cyanide-insensitive alternative oxidase (AOX). Based on this sequence, we cloned C. parvum AOX (CpAOX) cDNA from the phylum apicomplexa for the first time. The deduced amino acid sequence (335 a.a.) of CpAOX contains diiron coordination motifs (-E-, -EXXH-) that are conserved among AOXs. Phylogenetic analysis suggested that CpAOX is a mitochondrial-type AOX, possibly derived from mitochondrial endosymbiont gene transfer. The recombinant enzyme expressed in Escherichia coli showed quinol oxidase activity. This activity was insensitive to cyanide and highly sensitive to ascofuranone, a specific inhibitor of trypanosome AOX.

Amino Acid Sequence↗

PubMed2004

Reliability of hepatitis C virus core antigen assay for detection of viremia in HCV genotypes 1, 2, 3, and 4 infected blood donors: a collaborative study between Japan, Egypt, and Uzbekistan.

Nucleic acid amplification-based methods are used for confirmation of viremia in antibody to hepatitis C virus (anti-HCV)-positive patients. However, this technology is labor intensive, time consuming, requires complex laboratory conditions, and expensive. The aim of this study was to evaluate the sensitivity and specificity of the HCV core antigen (HCVcAg) assay as an alternative approach for confirmation of viremia in HCV-infected subjects with HCV genotype 1-4. Two hundred forty-six asymptomatic HCV RNA- positive donors were enrolled in this study, consisting of 122 blood donors from Egypt (116 with genotype 4, 4 with genotype 1, and 2 with 1 + 4 genotypes), 109 from Japan (85 with genotype 1, and 24 with genotype 2), and 15 from Uzbekistan (all with genotype 3). A total of 234 (95.1%) of 246 RNA-positive specimens were detected by the HCVcAg assay; the sensitivity of HCVcAg assay consisted 93.4, 100, 100, and 94.8% for genotypes 1, 2, 3, and 4, respectively in comparison with RT-PCR assay. The specificity of the assay was confirmed in the absence of the false-positive results among 53 anti-HCV-negative, but anti-Schistosoma mansoni (anti-Sm) positive donors from Egypt. A positive correlation between HCVcAg and HCV RNA concentration levels (r = 0.671, P < 0.05) was observed among specimens with HCV genotype 4. The mean HCVcAg level was significantly lower in specimens with genotype 4 (2,935 fmol/L) comparing to genotypes 1, 2, and 3 (5,034, 4,962, and 4,740 fmol/L, respectively). No specific mutation was found in the core-encoding region of the studied specimens. In conclusion, HCVcAg is shown to be specific, sensitive, and informative qualitative index for HCV viremia in asymptomatic carriers.

Amino Acid Sequence↗