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Biomedical subjects

Nobuo Koizumi

Publications and source records attributed to Nobuo Koizumi.

14 recordsLinked to original sources

Lanka virus, a Mus booduga-borne orthohantavirus infection-associated febrile illness in Sri Lanka.

BACKGROUND: In Sri Lanka, a high seroprevalence of antibodies against hantaviruses was reported in communities affected by chronic kidney disease of unknown etiology (CKDu). Recently, two rodent-borne hantaviruses, Lanka virus and Anjozorobe virus, were identified in these areas. However, it is unclear which virus is the source of infection in humans, and its pathogenicity is unknown. METHODOLOGY/PRINCIPAL FINDINGS: A total of 181 sera from febrile patients from two CKDu-endemic regions, Girandurukotte and Polonnaruwa, were examined and Lanka virus genome was detected in two IgM-positive febrile patients. Of 76 serum samples from patients with fever of unknown etiology collected during 2016 examined to identify hantavirus genomes, antibodies, and serotypes, 10 were IgG-positive with five of them having IgM also. They were all without clinical features of hemorrhagic fever with renal syndrome, but three patients required treatment in the intensive care unit. A serotyping strategy was established based on the antigenic difference of the glycoprotein Gn of Lanka and Anjozorobe viruses. Using this method, febrile patients were found to be infected with the Lanka virus and none of the patient sera showed Anjozorobe virus infection pattern. Additionally, a total of 373 previously diagnosed seropositive serum samples from CKDu patients and healthy residents were serotyped to categorize 87% of seropositives as Lanka virus infection. CONCLUSIONS/SIGNIFICANCE: Lanka virus carried by little Indian field mouse (Mus booduga) is transmitted to humans, likely causing febrile illness occasionally while leading to severe disease in some of the febrile patients.

Humans↗

The GrlR-GrlA regulatory system coordinately controls the expression of flagellar and LEE-encoded type III protein secretion systems in enterohemorrhagic Escherichia coli.

The gene function of the locus of enterocyte effacement (LEE) is essential for full virulence of enterohemorrhagic Escherichia coli (EHEC). Strict control of LEE gene expression is mediated by the coordinated activities of several regulatory elements. We previously reported that the ClpX/ClpP protease positively controls LEE expression by down-regulating intracellular levels of GrlR, a negative regulator of LEE gene expression. We further revealed that the negative effect of GrlR on LEE expression was mediated through GrlA, a positive regulator of LEE expression. In this study, we found that the FliC protein, a major component of flagellar filament, was overproduced in clpXP mutant EHEC, as previously reported for Salmonella. We further found that FliC expression was reduced in a clpXP grlR double mutant. To determine the mediators of this phenotype, FliC protein levels in wild-type, grlR, grlA, and grlR grlA strains were compared. Steady-state levels of FliC protein were reduced only in the grlR mutant, suggesting that positive regulation of FliC expression by GrlR is mediated by GrlA. Correspondingly, cell motility was also reduced in the grlR mutant, but not in the grlA or grlR grlA mutant. Because overexpression of grlA from a multicopy plasmid strongly represses the FliC level, as well as cell motility, we conclude that GrlA acts as a negative regulator of flagellar-gene expression. The fact that an EHEC strain constitutively expressing FlhD/FlhC cannot adhere to HeLa cells leads us to hypothesize that GrlA-dependent repression of the flagellar regulon is important for efficient cell adhesion of EHEC to host cells.

Bacterial Adhesion↗

Sporadic cases and an outbreak of leptospirosis probably associated with recreational activities in rivers in the northern part of Okinawa Main Island.

In the summer of 2003, sporadic cases and an outbreak of human leptospirosis probably related to recreation in rivers occurred in the northern part of Okinawa Main Island. Sixteen of 22 suspected cases were definitely diagnosed as leptospirosis by serological test or isolation. The infective leptospiral serovar in 14 cases was presumed to be Hebdomadis. Transmission was thought to occur by exposure to river water that was contaminated by the urine of infected animals. The findings indicate that recreation in rivers in this area is a significant risk factor for infection with leptospires.

Adolescent↗

Leptospirosis in squirrels imported from United States to Japan.

We diagnosed leptospirosis in 2 patients exposed to southern flying squirrels imported from the United States to Japan. Patients worked with exotic animals in their company. Leptospira isolates from 1 patient and 5 of 10 squirrels at the company were genetically and serologically identical and were identified as Leptospira kirschneri.

Adult↗

[A case of leptospirosis caused by Leptospira borgpetersenii serovar sejroe infected in Bali Island, Indonesia].

We report a patient with leptospirosis caused by Leptospira borgpetersenii serovar Sejroe infection on Bali Island, Indonesia. This 33-year-old Japanese man had stayed at a resort hotel on the island from July 8 to July 13 2004. At the hotel, he swam in the pool, walked barefoot, and lied down in the grass. He developed a high fever and headache 7 days after completing his trip, and was admitted to our hospital on July 23. On admission he showed conjunctival suffusion and complained of myalgias. Laboratory findings included granulocytosis and elevated CRP. Plasmodium spp. were not found in blood smears, and no pathogenic bacteria were isolated from blood or fecal cultures. We diagnosed the patient as leptospirosis upon detection of slender coiled organisms with characteristic morphology by darkfield examination of blood sample. Minocycline 100 mg i.v.b.i.d. showed excellent efficacy. A microscopic agglutination test (MAT) during the convalescent stage demonstrated a significant increase in antibodies against L. borgpetersenii serovar Sejroe, confirming the diagnosis of leptospirosis. Despite occurrence of a pandemic of leptospirosis in certain Southeast Asian countries including Indonesia, information concerning pandemic disease is limited. In addition serovars of "imported" cases representing infection in pandemic areas differ widely from those in domestic cases. Adequate laboratory support therefore is crucial for accurate diagnosis of leptospirosis.

Adult↗

Identification of a novel adhesion molecule involved in the virulence of Legionella pneumophila.

Legionella pneumophila is an intracellular bacterium, and its successful parasitism in host cells involves two reciprocal phases: transmission and intracellular replication. In this study, we sought genes that are involved in virulence by screening a genomic DNA library of an L. pneumophila strain, 80-045, with convalescent-phase sera of Legionnaires' disease patients. Three antigens that reacted exclusively with the convalescent-phase sera were isolated. One of them, which shared homology with an integrin analogue of Saccharomyces cerevisiae, was named L. pneumophila adhesion molecule homologous with integrin analogue of S. cerevisiae (LaiA). The laiA gene product was involved in L. pneumophila adhesion to and invasion of the human lung alveolar epithelial cell line A549 during in vitro coculture. However, its presence did not affect multiplication of L. pneumophila within a U937 human macrophage cell line. Furthermore, after intranasal infection of A/J mice, the laiA mutant was eliminated from lungs and caused reduced mortality compared to the wild isolate. Thus, we conclude that the laiA gene encodes a virulence factor that is involved in transmission of L. pneumophila 80-045 and may play a role in Legionnaires' disease in humans.

Alleles↗

Leptospiral immunoglobulin-like proteins elicit protective immunity.

The identification of new vaccine candidates for leptospirosis is of great interest. This paper describes the identification of two homologous immunogenic proteins, LigA-m and LigB-m, of Leptospira interrogans serovar manilae strain UP-MMC-NIID, which show strong similarity with LigA found recently in L. interrogans serovar pomona. Southern blot analysis indicated the conservation of the lig genes among pathogenic leptospires. LigA-m protein was shown to be a surface-exposed lipoprotein expressed during in vitro culture. Both LigA-m and LigB-m induced protective immunity against a challenge with a homologous serovar of L. interrogans in mice. Furthermore, patients' sera infected with heterologous serovars' strains contained antibodies against LigA-m and LigB-m. Our results suggest that LigA-m and LigB-m proteins are new vaccine candidates for the prevention of leptospirosis.

Animals↗

New genomospecies related to Borrelia valaisiana, isolated from mammals in Okinawa archipelago, Japan.

In 2000 and 2001, a survey was conducted of Borrelia isolated from various mammals in the southernmost islands of Japan, including Okinawa (main island), Izena, Iriomote and Ishigaki. Isolates obtained from the ear tissues of Suncus murinus (10 isolates), Mus calori (four isolates), Rattus norvegicus (one isolate) and Crocidura watasei (one isolate), were characterized by RFLP of the 5S-23S rDNA intergenic spacer and sequence analysis of the intergenic spacer, 16S rDNA and flagellin gene. While these isolates showed identical RFLPs to Borrelia valaisiana found in Korea, Taiwan and the southern and central parts of China, their RFLP patterns differed from those of B. valaisiana found in European countries, and strain Am501 isolated from Ixodes columnae in Japan. It was found that these isolates clustered with each other on a phylogenetic tree based on flagellin gene and 16S rDNA sequences, but were relatively divergent from the European B. valaisiana and strain Am501. These findings suggest that these isolates found in East Asia should be classified as a new genomospecies of Borrelia burgdorferi sensu lato.

Animals↗

Molecular cloning and characterization of a novel leptospiral lipoprotein with OmpA domain.

A novel antigenic protein of pathogenic Leptospira, Loa22, was identified by using the PhoA fusion method followed by immunoblotting with convalescent mouse sera. Loa22 was shown to be a lipoprotein having a C-terminal OmpA consensus domain. Loa22 was detected among pathogenic leptospires but not among non-pathogenic leptospires, suggesting the possible involvement of this protein in virulence. The results of three different experiments suggested that Loa22 is located in the outer membrane and a small portion is exposed on the cell surface. Thus, Loa22 may be a candidate for a novel vaccine against infection with pathogenic leptospires.

Amino Acid Sequence↗

Evidence for widespread infection of hepatitis E virus among wild rats in Japan.

Sporadic cases of hepatitis E have been reported in industrialized countries, including Japan. The source of hepatitis E virus (HEV) in these patients is unknown, although zoonotic transmission has been suggested. To investigate whether or not rodents might be a reservoir of HEV, we conducted an epidemiological survey for the antibody to a recombinant capsid protein of HEV using serum samples from wild rodents in Japan. One hundred and fourteen of 362 (31.5%) Norway rats (Rattus norvegicus) and 12 of 90 (13.3%) black rats (Rattus rattus) were positive for anti-HEV IgG. In contrast, all of the sera from 55 mice were negative for anti-HEV IgG. The rate of antibody positivity increased with weight among Norway rats. Seropositive rats were found in all five districts surveyed in this study, but the prevalence of anti-HEV IgG in wild rats differed among these prefectures. Despite the fact that Japan is a non-endemic country of hepatitis E, widespread infection of HEV was observed among wild rats in Japan. Our results suggested that HEV or a closely related virus is circulating among wild rats in Japan.

Journal Article↗

Identification of a novel antigen of pathogenic Leptospira spp. that reacted with convalescent mice sera.

The virulence of leptospires isolated from human patients against C3H/HeJ mice was investigated. Infection with clinical isolates from patients with severe leptospirosis was lethal to C3H/HeJ mice, suggesting that C3H/HeJ mice are suitable as an acute lethal model of severe leptospirosis. Using this model, a novel antigen of pathogenic Leptospira spp. (named LAg42), which reacted with convalescent mice sera, was identified. LAg42 is a 42 kDa inner-membrane protein and its immunogenic region is located in the C-terminal region. The gene for LAg42 is conserved among pathogenic leptospires but not among non-pathogenic leptospires, which suggests its involvement in virulence.

Animals↗

Probable laboratory contamination of clinical specimens with Leptospira meyeri.

Leptospira meyeri were isolated from the blood or the pleural effusion cultures of four patients at a commercial clinical laboratory. All isolates were identical in their 16S rDNA sequences and NotI or SfiI restriction profiles of the chromosome DNA on pulsed-field gel electrophoresis. However, intraperitoneal inoculation of the isolate (NIID1) failed to kill hamsters and none of the patients' sera reacted with L. meyeri strains isolated, indicating leptospiral contamination occurred during laboratory investigation.

Animals↗

[A case of leptospirosis diagnosed early by flaB-PCR].

We report a case of leptospirosis that was diagnosed in the early stage of infection by using flaB-PCR. The flaB gene of Leptospira was amplified from the DNA extract of the patient's blood at hospital day 1, while leptospiral antibody was negative by the method of microscopic agglutination test and micocapsule agglutination test at that time. Seroconversion occurred at hospital day 6 and Leptospira was isolated from the patient's blood at hospital day 16, demonstrating that flaB-PCR method was very useful in early diagnosis of leptospirosis.

Aged↗