PubMed Health⌕ Search

Biomedical subjects

Shigeyuki Kano

Publications and source records attributed to Shigeyuki Kano.

15 recordsLinked to original sources

Trends in malaria cases in Japan.

Just after World War II, more than 10,000 malaria cases per year were reported in Japan, including indigenous, imported and induced malaria. Malaria has been successfully eradicated since 1961 in Japan and now only imported malaria cases are encountered. However, as the number of Japanese people who are going abroad and also the number of foreigners who are visiting Japan increases (about 16 and 5 millions, respectively, in 2001), so does the chance for Japanese doctors to see imported malaria or transfusion-transmitted malaria cases. In fact, the total number of the patients with acute malaria in Japan has been around 100-150 annually for the last 10 years. Of those, about 75% are Japanese and 25% are foreigners, and about 75% are male and 25% are female. The peak age is in the 20s. Recently, about 45% of patients are Plasmodium falciparum and another 45% Plasmodium vivax infections. The former species is likely to be seen in travelers coming back from African countries and the latter is mainly from Asian countries. The important issue is that patients in Japan have not been diagnosed promptly nor treated properly because doctors in Japan are no longer familiar with tropical medicine. Therefore, some patients are dying from severe malaria as a consequence. As it is, most of the effective medicines for drug-resistant malaria or severe malaria have not been registered in Japan. There is now a need for medical practitioners to focus on travel medicine in Japan.

Adolescent↗

Binding of Plasmodium falciparum-infected erythrocytes to the membrane-bound form of Fractalkine/CX3CL1.

Plasmodium falciparum-infected erythrocytes (pRBCs) adhere to the endothelium via receptors expressed on the surface of vascular endothelial cells (EC) and sequester in the microvasculature of several organs and block the blood circulation. The sequestration, which involves receptors, may be related to the severity of malaria. Here, we report that pRBCs bind to the membrane-bound form of Fractalkine/CX3CL1 (FKN), which is expressed on the surface of vascular EC in various organs. pRBCs adhered to FKN on the surface of FKN cDNA-transfected Chinese hamster ovary cells (CHO-FKN cells). Both the recombinant human FKN-chemokine domain (FKN-CD) and anti-FKN-CD antibody efficiently blocked adherence of pRBCs to CHO-FKN cells. Similar to binding between FKN and FKN receptor on blood mononuclear cells, two amino acid residues, Lys-7 and Arg-47 within FKN-CD, were critical for FKN-pRBC binding. Immunohistological analysis revealed the expression of FKN on EC at the site of sequestration in the brain of a patient with cerebral malaria. These results suggest that the membrane-bound form of FKN acts as a receptor for pRBCs, and this may contribute to furthering our present understanding of cytoadherence in the pathology of falciparum malaria.

Amino Acid Substitution↗

Disruption of the Plasmodium falciparum 2-Cys peroxiredoxin gene renders parasites hypersensitive to reactive oxygen and nitrogen species.

In parasitism, Plasmodium falciparum is exposed to toxic reactive oxygen species and reactive nitrogen species (RNS). Peroxiredoxins (Prx) are ubiquitously distributed antioxidant enzymes. In bacteria and yeast, Prx have also been implicated in detoxifying RNS. Here, we used a gene targeting strategy to investigate the physiological role of 2-Cys Prx of P. falciparum, PfTPx-1, in living parasite cells. The PfTPx-1-null parasite line was more sensitive to paraquat (a superoxide donor) and sodium nitroprusside (a nitric oxide donor), than wildtype. These findings suggest that PfTPx-1 protects the parasite cells from oxidative and nitrosative stresses.

Animals↗

Distinctiveness of the genomic sequence of Shiga toxin 2-converting phage isolated from Escherichia coli O157:H7 Okayama strain as compared to other Shiga toxin 2-converting phages.

Shiga toxin 2-converting phage was isolated from Escherichia coli O157:H7 associated with an outbreak that occurred in Okayama, Japan in 1996 (M. Watarai, T. Sato, M. Kobayashi, T. Shimizu, S. Yamasaki, T. Tobe, C. Sasakawa and Y. Takeda, Infect. Immun. 61 (1998) 3210-3204). In this study, we analyzed the complete nucleotide sequence of Shiga toxin 2-converting phage, designated Stx2phi-I, and compared it with three recently reported Stx2-phage genomes. Stx2phi-I consisted of 61,765 bp, which included 166 open reading frames. When compared to 933W, VT2-Sakai and VT2-Sa phages, six characteristic regions (regions I-VI) were found in the Stx2 phage genomes although overall homology was more than 95% between these phages. Stx2phi-I exhibited remarkable differences in these regions as compared with VT-2 Sakai and VT2-Sa genes but not with 933W phage. Characteristic repeat sequences were found in regions I-IV where the genes responsible for the construction of head and tail are located. Regions V and VI, which are the most distinct portion in the entire phage genome were located in the upstream and downstream regions of the Stx2 operons that are responsible for the immunity and replication, and host lysis. These data indicated that Stx2phi-I is less homologous to VT2-Sakai and VT2-Sa phages, despite these three phages being found in the strains isolated at the almost same time in the same geographic region but closely related to 933W phage which was found in the E. coli O157 strain 933W isolated 14 years ago in a different geographic area.

Attachment Sites, Microbiological↗

Expression profiles of peroxiredoxin proteins of the rodent malaria parasite Plasmodium yoelii.

Patterns of expression of the 2-Cys and 1-Cys peroxiredoxin (Prx) proteins of the rodent malaria parasite Plasmodium yoelii during its life cycle were observed by immunofluorescent antibody staining and confocal laser scanning microscopy. 2-Cys Prx was expressed in the parasite cytoplasm throughout the life cycle, and the thioredoxin (Trx)-peroxidase activity of 2-Cys Prx revealed with the recombinant protein suggested that the Prx is constitutively expressed and, thus, likely plays a housekeeping role in the parasite's intracellular redox control. In contrast, 1-Cys Prx showed stage-specific expression in blood-stage parasites. The limited expression of 1-Cys Prx in the trophozoite cytoplasm suggests that 1-Cys Prx may be involved in haemoglobin metabolism by the parasite, which generates a prooxidative haem iron and increases intracellular oxidative stress. The antioxidant activity of 1-Cys Prx was tested for its ability to protect yeast enolase against inactivation of the mixed-function oxidation system. Differential expression of the two Prx proteins during the erythrocytic and insect stages suggests the importance of these proteins in protecting parasites against oxidative stress, which is generated by the parasite's metabolism and also from the environment.

Animals↗

[An imported case of falciparum malaria successfully treated with Artemether-Lumefantrine in Japan].

Spread of multi-drug resistant malaria in the endemic areas has made malaria control more difficult. Thus, WHO recommends combination therapy for the treatment of malaria. The aim of combination therapy is to improve efficacy and to reduce the incidence of resistance development to the each component of the combination. Particularly, the combination with artemisinin derivatives shows good outcome in Thailand where high resistance for mefloquine has already been found. We report the first case of falciparum malaria, successfully treated with Artemether-Lumefantrine in Japan. Artemether-Lumefantrine is a newly developed artemisinin-based combination agent for the treatment of uncomplicated multi-drug resistant malaria. This drug has proved highly effective and well tolerated by some clinical trials abroad. This Japanese female case showed a good clinical course without any side effect.

Adult↗

Genome analysis of a novel Shiga toxin 1 (Stx1)-converting phage which is closely related to Stx2-converting phages but not to other Stx1-converting phages.

Two Stx-converting phages, designated Stx1 phi and Stx2 phi-II, were isolated from an Escherichia coli O157:H7 strain, Morioka V526, and their entire nucleotide sequences were determined. The genomes of both phages were similar except for the stx gene-flanking regions. Comparing these phages to other known Stx-converting phages, we concluded that Stx1 phi is a novel Stx1-converting phage closely related to Stx2-converting phages so far reported.

Coliphages↗

[Malaria].

Explore the source record for details and available documents.

Animals↗

Effect of jasplakinolide on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum.

The effect of jasplakinolide (JAS), an actin-polymerizing and filament-stabilizing drug, on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum was examined. Jasplakinolide markedly decreased the parasitemia in a synchronized culture of P. falciparum strain FCR-3 in a time- and concentration-dependent manner. The decrease became evident at day 2 at concentrations of 0.3 micro M and above, and parasites finally disappeared at day 4. Giemsa-stained smears of P. falciparum-infected erythrocytes demonstrated that there was no effect on the development of schizonts from ring forms. Merozoites were released from the infected erythrocytes in a normal manner with and without JAS. However, there were no ring form-infected erythrocytes when JAS was administered, even after the release of merozoites. This indicates that the merozoites exposed to JAS failed to invade erythrocytes. The inhibitory effect of JAS on the parasitemia was reversed by the removal of the drug after exposure to 1 micro M of JAS for 1 day. Electron microscopy revealed that the merozoites treated with JAS showed a protrusion of the apical end which contained the microfilament structure. Immunoblot analysis indicated that the JAS treatment increased F-actin filaments of merozoites but had no effect on those of the trophozoites and schizonts. Therefore, this study demonstrated that JAS has an antimalarial activity.

Actin Cytoskeleton↗

The expression system of biologically active canine interleukin-8 in Leishmania promastigotes.

It has been reported that Leishmania promastigotes have ability to express foreign genes on drug selectable plasmids. To investigate further abilities of the recently described expression vector, P6.5, in the transfection of Leishmania organisms (Chen D-Q, Kolli BK, Yadava N et al. Episomal expression of specific sense and antisense mRNAs in Leishmania amazonensis: modulation of gp63 levels in promastigotes and their infection of macrophages in vitro. Infect Immun 2000;68:80--86), the constructed expression vector, which contains canine interleukin-8 (cIL-8) coding cDNA, was introduced by electroporation to promastigotes of four species of the genus Leishmania: Leishmania amazonensis, L. equatorensis, L. donovani and L. infantum. Extrachromosomal DNAs and total RNAs from the transfected promastigotes were subjected to polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively, using cIL-8 gene specific primers, and a predicted product of 330 bp was detected. Western blot analysis using a mouse monoclonal antibody raised against cIL-8 demonstrated the successful expression of cIL-8 in the transfectants and culture supernatants. Culture supernatants of the transfected L. amazonensis and L. equatorensis promastigotes showed a high chemotactic activity to both dog and mouse polymorphonuclear leukocytes. These results indicate that Leishmania promastigotes transfected with the expression vector P6.5 containing cIL-8 cDNA are capable of producing biologically active cIL-8. The Leishmania expression system using the P6.5 vector might be a useful alternative for the production of biologically active recombinant cytokines.

Animals↗

[Severe falciparum malaria with prolonged hemolytic anemia after successful treatment with intravenous artesunate].

We report a 68-year-old woman with severe falciparum malaria contracted in Tanzania. She presented high parasitemia and was treated successfully with intravenous artesunate, a qinghaosu derivative, and aggressive supportive therapy. She developed hemolytic anemia and jaundice on day 11 and blood transfusion was required. This case illustrates that intravenous artesunate has excellent antimalarial activity with rapid efficacy and that no severe adverse effect but conventional aggressive supportive therapy is still important in the treatment of severe falciparum malaria.

Aged↗

[A case of falciparum malaria successfully treated with intravenous artesunate].

The case was a 28-year-old Japanese female who was considered to be infected with malaria in India. She manifested fever in Tokyo, Japan, and was brought to Toho University Hospital due to continuous high fever and severe thrombocytopenia. Ring forms at 11% of her RBCs and ICT Malaria P.f/P.v test was also positive for Plasmodium falciparum diagnosis. Not only the high parasitemia and delay of the diagnosis (6 days after the onset of fever), but also her DIC status required prompt and proper treatment. The diagnosis of severe malaria was strongly considered, and intravenous Artesunate (a qinghaosu derivative) was decided to be administered to the patient. After the four series of administration, mefloquine was subsequently given to prevent recrudescence. Parasite clearance time and fever clearance time were 24 hours and 108 hours, respectively. Thrombocytopenia was improved shortly after the treatment, but then anemia was once worsened with following gradual improvement. No other significant side effects were observed and no recrudescence occurred up to 8 months after her discharge. In Japan, very few cases treated with intravenous Artesunate were reported and our results showed its safe and excellent effect for a Japanese malaria patient.

Adult↗

PCR-amplification, sequencing, and comparison of the var/PfEMP-1 gene from the blood of patients with falciparum malaria in the Philippines.

The adhesion of Plasmodium falciparum-infected erythrocytes to vascular endothelium and to uninfected red blood cells (RBCs) plays a key role in the pathology of severe malaria. Adhesion is known to be mediated in part by the antigenically-variant erythrocyte membrane protein-1 (PfEMP-1), which is encoded by the var-gene family of P. falciparum. It has recently been reported that in vitro a single parasite simultaneously transcribes multiple var-genes but that, through a developmentally regulated process, the parasite selects only one PfEMP-1 that will to reach the surface of the host RBC. Were this to be true in vivo, one would expect a correlation between the type of var/PfEMP-1 that is expressed on the parasite-infected RBC and the severity of clinical disease. In order to test this assumption, we determined the sequence of the var-gene that was expressed by the parasites in patients' blood samples. Seven blood samples were collected from patients with or without severe clinical symptoms (cerebral malaria): two samples were from patients diagnosed as having imported falciparum malaria at the International Medical Center of Japan (IMCJ); the five others were from patients of the Davao Regional Hospital in Davao, the Philippines. The parasites (ring stage) in the blood samples were cultured for 24 hours; the matured trophozoites, in which the var-gene selection had taken place, served as material for mRNA isolation. The cDNA corresponding to the Duffy-binding-like (DBL)-1 domain of the var-gene was amplified by RT-PCR, using a region-specific primer set. The amplified cDNAs were cloned into the plasmid vector; the resultant clones (32) were sequenced on both strands. The results indicated that there was considerable diversity in the sequence of the DBL-1 domain among the clones, even among those from a single patient. In conclusion, it was difficult to demonstrate the correlation between the type of var-gene transcripts found in the RBCs of malaria patients and the severity of their symptoms.

Amino Acid Sequence↗