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Akira Nishizono

Publications and source records attributed to Akira Nishizono.

15 recordsLinked to original sources
PubMed2004

New tumor necrosis factor-alpha-inducing protein released from Helicobacter pylori for gastric cancer progression.

PURPOSE: To investigate the association between Helicobacter pylori infection and its inflammatory reaction in gastritis, gastric ulcer, and gastric cancer, a new tumor necrosis factor-alpha (TNF-alpha)-inducing protein of H. pylori was studied. METHODS: The HP0596 gene of H. pylori was identified as the TNF-alpha-inducing protein (Tipalpha) gene from genome sequence of H. pylori strain 26695. Using recombinant Tipalpha (rTipalpha) and deleted Tipalpha (rdel-Tipalpha) proteins, the latter of which lacks six amino acids containing two cysteines in the N-terminal domain, we examined their activities in TNF-alpha gene expression and NF-kappaB activation in both Bhas 42 (v-H-ras transfected BALB/3T3) cells and mouse gastric epithelial cell line MGT-40, and in vitro transformation of Bhas 42 cells. RESULTS: Tipalpha protein as a homodimer form (38 kDa) was found in both extracts and culture medium of various H. pylori strains. rTipalpha significantly induced TNF-alpha gene expression and NF-kappaB activation in both Bhas 42 cells and MGT-40, and induced in vitro transformation of Bhas 42 cells. However, rdel-Tipalpha did not. Treatment with MG-132, a proteasome inhibitor, inhibited translocation of NF-kappaB p65, and abrogated TNF-alpha induction induced by Tipalpha protein. CONCLUSION: Tipalpha is a new carcinogenic factor released from H. pylori mediated through NF-kappaB activation.

Animals↗
PubMed2004

Animal models for the study of Helicobacter-induced gastric carcinoma.

Helicobacter pylori is considered to have a close association with gastric cancer. Many epidemiological studies have shown a strong association between chronic H. pylori infection and subsequent development of gastric carcinoma in humans. To clarify this link more clearly, it is necessary to use this bacterium in experimental studies to develop gastric carcinoma in suitable experimental animals. Persistent H. pylori infection was seen in the Japanese monkey model, and has recently been achieved in the Mongolian gerbil model. In these models, the sequential histopathological changes in the gastric mucosa are very similar to those in humans. The Japanese monkey model showed advances in atrophic change and p53 point mutations in the gastric mucosa during long-term observation. The Mongolian gerbil model demonstrated that H. pylori infection enhances gastric carcinogenesis in combination with known carcinogens such as N-methyl-N-nitrosourea (MNU) and N-methyl-N-nitro-N'-nitrosoguanidine (MNNG), and also showed that H. pylori infection alone can result in the development of gastric carcinoma. These important results provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H. pylori infection and assist in the planning of eradication therapy to prevent gastric carcinoma.

Animals↗
PubMed2004

Regression of liver fibrosis in cases of chronic liver disease type C: quantitative evaluation by using computed image analysis.

OBJECT: It was reported that the liver fibrosis is reduced in patients with chronic liver disease type C after eradication of HCV. Degree of fibrosis was expressed by the classical fibrosis scoring system (F0-F4) at present. However a change of subtle reduction of fibrosis cannot be expressed in its fibrosis score and thus we measured an area of fibrosis and compared detailed change of the fibrosis area in paired liver biopsy. METHODS: For quantitative assessment of liver fibrosis, we measured an area of fibrosis using computed digital image analysis and pursued the rate of a fibrosis area for whole biopsied liver tissue of 25 patients with HCV infection (20 complete response patients to IFN therapy who showed viral eradication: CR and 5 non-treated ones with IFN but had conservative therapy: CT). RESULTS: In CR group, fibrosis rate was 7.2 +/- 1.5% before therapy, 2.7 +/- 0.5% after the therapy and they were significantly regressed. In CT group, fibrosis rate was 8.4 +/- 4.3% at the first biopsy, 15.9 +/- 7.7% at the second biopsy. CONCLUSIONS: Regression of liver fibrosis could be confirmed in patients with virologic response to IFN even in patients with liver cirrhosis. Our quantitative evaluation provided information superior to that obtained by the classical fibrosis staging score system.

Adult↗
PubMed2004

Seroprevalence of IgG specific for dengue virus among adults and children in Santo Domingo, Dominican Republic.

The seroprevalence of dengue (DEN) virus-specific IgG was determined by enzyme-linked immunosorbent assay among 1,008 adults recruited at blood banks and among 201 children less than 10 years old visiting a hospital in Santo Domingo, Dominican Republic. Most (98%, 987 of 1,008) of the adults and 56% (113 of 201) of the children were positive for DEN virus-specific IgG. Among adults, there were no significant differences in the prevalence by age, sex, and residential area of the participants. Among children, the prevalence of DEN virus-specific IgG increased with age (1-2 years old, 0-5%; 3-6 years old, 25-65%; and >/=7 years old, 76-92%). The prevalence in 50% of those less than one year of age was probably due to maternal antibody transfer. Neutralization tests of adult samples indicate that DEN virus infections with different serotypes have occurred sequentially or simultaneously among the inhabitants of Santo Domingo.

Adolescent↗
PubMed2003

[Possibility for the presence of Helicobacter pylori in drinking well water].

Forty three well waters which are currently used as drinking water were studied for the presence of Helicobacter pylori. Using magnetic-beads purification and PCR amplification of H. pylori-specific gene, 4 of the 43 samples were positive for H. pylori-ureA gene (9.3%) and 1 of the 43 samples was positive for H. pylori-16SrRNA gene (2.3%). The presence of H. pylori-specific amplified product did not correlate with the type, depth and location of the wells. This study demonstrated that H. pylori can be transmitted via drinking water, especially well water in Japan.

Helicobacter pylori↗
PubMed2003

Antiviral effects of geranylgeranylacetone: enhancement of MxA expression and phosphorylation of PKR during influenza virus infection.

A cyclic polyisoprenoid compound, geranylgeranylacetone (GGA), has been used as antiulcer drug. GGA is also a potent inducer of heat shock proteins (HSPs). HSPs are considered to induce an antiviral effect; however, the detailed mechanism is unknown. To determine whether GGA might show antiviral activity and what the mechanism is, the effect of GGA against influenza virus (strain PR8) infection in vivo and in vitro was investigated. The results demonstrated that GGA treatment strongly suppressed the deleterious consequences of PR8 replication and was accompanied by an increase in HSP70 gene expression in mice. Results from in vitro analyses demonstrated that GGA significantly inhibited the synthesis of PR8-associated proteins and prominently enhanced expression of human myxovirus resistance 1 (MxA) followed by increased HSP70 transcription. Moreover, GGA augmented the expression of an interferon-inducible double-strand RNA-activated protein kinase (PKR) gene and promoted PKR autophosphorylation and concomitantly alpha subunit of eukaryotic initiation factor 2 phosphorylation during PR8 infection. It is proposed that GGA-induced HSP70 has potent antiviral activity by enhancement of antiviral factors and can clinically achieve protection from influenza virus infection.

Animals↗
PubMed2003

[The prospects of vaccination against H. pylori infection].

H. pylori causes numerous gastroduodenal diseases including malignancies. Although eradication of H. pylori using antibiotics is clinically performed, it is sometimes unsuccessful because of resistant bacteria and patient non-compliance with treatment. Therefore prophylactic and therapeutic vaccination against H. pylori infection is necessary for clinical use but it is still under study. H. pylori is widely believed to be transmitted in childhood. If long and chronic H. pylori infection causes gastric cancer, vaccination should be targeted at children for the prophylaxis of cancer. Systemic immunization with aluminum hydroxide which has been already proved to be safe for human child, deserve attention.

Bacterial Vaccines↗
PubMed2003

Oncolytic viral therapy for human pancreatic cancer cells by reovirus.

PURPOSE: Pancreatic cancer has a poor prognosis and few effective therapies are available. The oncolytic effect of reovirus has been observed in cancer cells with an activated Ras signaling pathway, and pancreatic cancer may be a candidate target for reovirus because K-ras mutation is frequently found in pancreatic cancer. EXPERIMENTAL DESIGN: In this study, we examined the feasibility of using reovirus (serotype 3) as an antihuman pancreatic cancer agent. RESULTS: Reovirus was able to infect five human pancreatic cancer cell lines (Panc1, MIApaca-2, PK1, PK9, and BxPC3) in vitro. We also confirmed that the Ras activity in these cancer cell lines was elevated compared with that in the normal cell line and that susceptibility to reovirus was associated with the Ras activity of these cells. In a unilateral murine xenograft model using Panc1 and BxPC3 cell lines, each tumor growth was suppressed by intratumoral injection of reovirus. Furthermore, local injection of reovirus also had systemic antitumor effects in a bilateral xenograft model using Panc1 cell line. Immunohistochemical examination revealed that reovirus replication was observed within the tumor but not in surrounding normal tissue. CONCLUSIONS: These results suggest that reovirus can be considered for a novel therapy against pancreatic cancer.

3T3 Cells↗
PubMed2003

[Rabies].

Explore the source record for details and available documents.

Animals↗
PubMed2002

Analysis of p53 mutations and Helicobacter pylori infection in human and animal models.

BACKGROUND: p53 gene mutations are believed to play a critical role in the development of gastric carcinoma. We examined the relation between Helicobacter pylori infection and p53 gene mutations of the gastric mucosa in human and animal models. METHODS: To detect the original p53 DNA sequences of the Japanese monkey and Mongolian gerbil, the p53 genes of these animals were amplified using the nested polymerase chain reaction method with primers for the human p53 gene. Direct DNA sequencing of exons 5, 6, 7, and 8 of the p53 genes was performed by the dideoxy terminator method for gastric mucosa of humans, the Japanese monkey, and the Mongolian gerbil. The expression of p53 was examined immunohistochemically in a Japanese monkey model. RESULTS: Mutations of the p53 gene were identified in 52.4% of human H. pylori-positive mucosa and in 100% of monkey H. pylori-positive mucosa. However, no mutations of the p53 gene were found in the H. pylori-positive gastric mucosa of Mongolian gerbils. There were no mutations in H. pylori-negative gastritis mucosa of humans, monkeys, or Mongolian gerbils. Nuclear staining of p53 was seen in the glandular cells of the H. pylori-infected mucosa of Japanese monkeys, especially in the neck region of the glands. CONCLUSIONS: These findings demonstrate that the H. pylori infection can induce p53 point mutations in humans and the Japanese monkey and appear to be involved in the pathway leading to dysplasia or carcinoma. However, our direct DNA sequencing method showed no p53 mutations in the Mongolian gerbil model at present. Further studies with this model are needed.

Animals↗
PubMed2002

Long-term Helicobacter pylori infection in Japanese monkeys induces atrophic gastritis and accumulation of mutations in the p53 tumor suppressor gene.

BACKGROUND: Helicobacter pylori is accepted as a definite human gastric carcinogen from an epidemiological point of view despite insufficient experimental data. Although we previously showed that the number of p53 immunopositive cells in the atrophic gastric mucosa of H. pylori-infected Japanese monkeys gradually increased over time, data on p53 gene mutations were not obtained in that study. To obtain direct evidence of carcinogenesis associated with H. pylori infection, we investigated whether p53 gene mutations are present in the gastric mucosa of a nonhuman primate model susceptible to H. pylori. MATERIALS AND METHODS: Using the DNA from gastric tissues obtained from six H. pylori-uninfected monkeys of different ages, nucleotide sequence of the wild-type p53 gene was determined by amplification of exons (Ex) 5, 6, 7 and 8 and sequencing. Gastric specimens obtained from eight Japanese monkeys that had been infected with H. pylori for different lengths of time (1.5-7.5 years), were analyzed for mutations in exons 5-8 of p53. RESULTS: In the six H. pylori-uninfected monkeys, nucleotide sequences of p53 Ex 5-8 were completely common and no mutations were noted. However, among the monkeys that were infected with H. pylori over various periods of time, there was an accumulation of p53 nucleotide (amino acid) substitutions as the gastric atrophy score increased. CONCLUSIONS: We conclude that the appearance of p53 gene mutation may be closely associated with the degree of gastric mucosal atrophy, which depends on the duration of H. pylori infection. Searching for p53 gene mutations may be useful for studying the progression of gastric carcinogenesis associated with H. pylori.

Animals↗
PubMed2002

Genetic analysis of rabies virus isolates in the Philippines.

To determine the genetic characteristics of the rabies virus in the Philippines, 59 rabies virus isolates were obtained from domestic rabid dogs and their partial nucleotide sequences of nucleoprotein (N) gene were compared. Based on comparison with reported sequences, phylogenetic analysis revealed that all isolates from the Philippines had close genetic relations and formed two subgroups. The Philippines isolates belonged to a different lineage from other Asian isolates but were closer to them than to terrestrial isolates and laboratory strains. Several specific nucleotide and amino acid substitutions were observed among the Philippines isolates. Our results suggest that rabies viruses in the Philippines might have a characteristic evolution.

Amino Acid Sequence↗
PubMed2002

Intraperitoneal immunization led to T cell hyporesponsiveness to Helicobacter pylori infection in mice.

During Helicobacter pylori infection, T cell response is critical in the development of active gastritis and in protective immunity against infection. We studied gastric inflammation and T cell response in H. pylori-challenged mice following an intraperitoneal immunization, using whole H. pylori lysate (HpAg) in the absence of adjuvants. H. pylori-challenged mice without immunization developed moderate to severe gastric inflammation, and splenocytes from these mice produced Th1 polarizing cytokines in response to HpAg and Con A during the acute infection. On the other hand, immunized-challenged mice (those inoculated with H. pylori following immunization) had little or no gastric inflammation despite persistent H. pylori colonization. Our immunization primed splenocytes to produce IL-2, IFN-gamma, and IL-4 in response to HpAg and Con A before infection. However, these cells became hyporesponsive to both stimulants immediately after live bacterial challenge in terms of the production of these cytokines, especially IL-2 and IFN-gamma. CTLA-4 has been documented to be a negative regulator of IL-2 production and lymphoproliferation that induces peripheral tolerance and functions 24-72 hr after the initiation of T cell activation. Compared with challenged mice, T cells from immunized-challenged mice showed higher levels of CTLA-4 expression at 72 hr after oral challenge. These data suggested that our immunization inhibited the development of H. pylori-associated gastritis and induced T cell hyporesponsiveness to H. pylori infection, which might be mediated by the early induction of CTLA-4 following challenge.

Abatacept↗
PubMed2002

Evaluation of therapeutic efficacy of adjuvant Helicobacter pylori whole cell sonicate in mice with chronic H. pylori infection.

Successful prophylactic administration of Helicobacter pylori whole cell sonicate (WCS) plus complete Freund's adjuvant (CFA) or aluminum hydroxide (ALM) against subsequent H. pylori infection was reported recently. Here we tested the effect of WCS plus TiterMax Gold (TMX) or ALM in mice with chronic H. pylori infection. Mice with chronic (18 weeks) H. pylori infection were injected intraperitoneally with H. pylori (Sydney strain) WCS plus ALM or TMX once weekly for three times. The number of colonizing H. pylori in the stomach, IgG1 and IgG2a levels, and local inflammatory status were determined after therapeutic immunization. H. pylori specific IgG1, but not IgG2a, was significantly induced in mice immunized with H. pylori WCS plus TMX or ALM. Immunization did not result in reduction of bacterial count or recruiting inflammatory cells to the stomach. Adjuvant H. pylori WCS resulted in induction of CD4+ Th2 cell-mediated immunity although it did not reduce bacterial density in mice with chronic H. pylori infection. Our results implied that CD4+ Th1 cell-mediated immunity, rather than Th2 cell dominant immunity, might play a role in reducing the number of bacteria in chronic H. pylori infection.

Adjuvants, Immunologic↗