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Biomedical subjects

Yoshito Eizuru

Publications and source records attributed to Yoshito Eizuru.

At least 19 recordsLinked to original sources
PubMed2006

Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile.

AIM: To examine the presence of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively. METHODS: We examined 47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and Chile, respectively. HPV was detected using GP5+/GP6+ primer pair for PCR, and confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment was used to identify HPV genotype. In addition, P16(INK4A) protein immunostaining of all the specimens was conducted. RESULTS: HPV was detected in 21 ESCC specimens (29%). Sequencing analysis of L1 region fragment identified HPV-16 genome in 6 Colombian cases (13%) and in 5 Chilean cases (19%). HPV-18 was detected in 10 cases (21%) in Colombia but not in any Chilean case. Since Chilean ESCC cases had a higher prevalence of HPV-16 (without statistical significance), but a significantly lower prevalence of HPV-18 than in Colombian cases (P = 0.011) even though the two countries have similar ESCC incidence rates, the frequency of HPV-related ESCC may not be strongly affected by risk factors affecting the incidence of ESCC. HPV-16 genome was more frequently detected in p16 positive carcinomas, although the difference was not statistically significant. HPV-18 detection rate did not show any association with p16 expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but the association was not statistically significant. HPV genotypes other than HPV-16 or 18 were not detected in either country. CONCLUSION: HPV-16 and HPV-18 genotypes can be found in ESCC specimens collected from two South American countries. Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC.

Aged↗
PubMed2006

Association of a distinctive strain of Epstein-Barr virus with gastric cancer.

Epstein-Barr virus (EBV) has been linked to gastric carcinoma (GC) with worldwide geographical variations attributable to types and variants of EBV. Here, we compare EBV strains between EBVaGC and healthy donors in Latin America, a high frequency area for EBVaGC. Tumor samples from 73 EBVaGC cases and throat washings from 329 healthy adults were examined for types 1 and 2 EBV and polymorphism at BamHI-F and BamHI-W1/I1 boundary regions and XhoI restriction site in LMP1 gene. Type 1 and prototype F of BamHI- F polymorphism accounted 59 (81%) and 69 (95%) of EBVaGC cases and 257 (78%) and 267 (81%) of healthy donors, respectively. Types I and "i" of BamHI W1/I1 polymorphism accounted 2 (3%) and 62 (85%) of EBVaGC and 85 (26%) and 170 (52%) of healthy donors, respectively (p<0.001). XhoI+ and - polymorphism accounted 60 (82%) and 4 (5%) of EBVaGC and 142 (43%) and 92 (28%) of healthy donors, respectively (p<0.001). Cosegregation analysis demonstrated that most of the 62 type "i" EBVaGC cases harbor XhoI+ strain (81%). However, among 143 type "i" healthy adults, both XhoI polymorphism were present in relatively similar frequencies (XhoI+ 58% and XhoI- 42%) (OR 9.0; 95% CI 1.2-69). Our findings are against to the proposed hypothesis that EBV strains are geographically but not disease-restricted. We conclude that most of the EBVaGC cases harbor a distinctive EBV strain (type "i"/XhoI +), but in healthy donors, this strain was as common as other strains. This finding is contrary to the proposed hypothesis that EBV strains are geographically but not disease-restricted and identified a healthy population group that share the same strain that predominate in EBVaGC cases.

Adult↗
PubMed2006

Epstein-Barr virus-associated enteritis with multiple ulcers after stem cell transplantation: first histologically confirmed case.

The present case involves unique enteritis forming multiple ulcers associated with Epstein-Barr virus (EBV). A 57-year-old man had undergone a reduced intensity allogeneic stem cell transplantation for a relapse of multiple myeloma following sequential autologous peripheral blood stem cell transplantation. The ileum, resected for massive melena, showed multiple irregular ulcers with occasional cobblestone-like appearance. There was inflammation including numerous plasma cells in the ulcer bases and surrounding areas, where many EBV-infected plasma cells were detected by double staining with EBV-encoded small RNA-1 (EBER-1) in situ hybridization and CD79a, while EBV-infected epithelial cells were not noted. The number of EBER-1-positive cells in the ileum (mucosa, 1451 cells/mm(2); submucosa, 465 cells/mm(2)) was much larger than in control samples (malignant lymphoma or leukemia after allogeneic stem cell transplantation, n = 4, range 0-113 cells/mm(2); malignant lymphoma after chemotherapy, n = 14, range 0-0.89 cells/mm(2); colon cancer, n = 12, range 0-3.5 cells/mm(2)). In the mucosa near the ulcers, EBER-1-positive cells often surrounded and involved the glandular epithelium, forming lymphoepithelial-like lesions. The histological findings differ from post-transplant lymphoproliferative disorders or intestinal thrombotic microangiopathy, and this is the first case of EBV-associated enteritis with ulcers characterized by numerous plasma cells and lymphoepithelial-like lesions after stem cell transplantation.

CD79 Antigens↗
PubMed2006

Inhibition of ganciclovir-resistant human cytomegalovirus replication by Kampo (Japanese herbal medicine).

We examined the effect of Kampo on the replication of ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) in the human embryonic fibroblast cell line MRC-5. Treatment of HCMV-infected cells with Sho-seiryu-to (SST; Xiao-Qing-Long-Tang in Chinese) resulted in the inhibition of viral replication without affecting the cell growth. SST treatment decreased the synthesis of viral DNA, but had no virucidal effect on cell-free HCMV. However, the inhibitory effect of SST on HCMV replication was ablated by anti-interferon-beta (IFN-beta) antibody suggesting that SST inhibits the replication of GCV-resistant HCMV through the induction of IFN-beta. These results suggest that SST is a novel compund with potential as an anti-HCMV.

Antiviral Agents↗
PubMed2006

Human papillomavirus in lung carcinomas among three Latin American countries.

The presence of human papillomavirus (HPV) genome in lung carcinomas has been reported worldwide but its frequency varies from country to country. We examined HPV genome in 36 lung carcinomas, consisting of 14 squamous cell carcinomas, 13 adenocarcinomas, and 9 small cell carcinomas, collected from Colombia, Mexico and Peru. PCR analysis using GP5+/GP6+ primers, combined with Southern blot hybridization, found the presence of HPV genome in 10 (28%) of 36 cases. This percentage is similar to the value of 22% reported by Syrjänen, who conducted a meta-analysis of nearly 2500 lung carcinomas examined to date. Genotype analysis revealed that the most predominant genotype was HPV-16 (7 cases), followed by HPV-18 (2 cases) and HPV-33 (1 case). HPV-16 was more frequently found among female than male cases (P=0.008) but was not detected in any adenocarcinoma cases. On the other hand, HPV-18 and HPV-33 were detected only among male cases. These HPV genotypes were detected only in adenocarcinomas, and all the HPV genotypes detected in this histological type were HPV-18 or HPV-33. The frequency of HPV-16 positive cases among all the HPV positive cases differed in the sexes (P=0.033) and differed in the three histological types (P=0.017). The presence of HPV tended to be more frequent in well-differentiated tumors when squamous cell carcinomas and adenocarcinomas were combined. However, it was not statistically significant (P=0.093). Neither p16 nor p53 expression in carcinoma cells was related to the proportion of HPV-positive cases. In conclusion, high-risk HPV DNA was detected in 28% of lung carcinomas. The predisposition of HPV-16 to female cases and to non-adenomatous carcinomas warrants further investigation.

Adenocarcinoma↗
PubMed2005

Epstein-Barr virus-associated gastric carcinoma: Evidence of age-dependence among a Mexican population.

AIM: To investigate features of Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) among a Mexican population. METHODS: Cases of primary gastric adenocarcinoma were retrieved from the files of the Departments of Pathology at the Instituto Nacional de Cancerologia and the Instituto Nacional de la Nutricion in Mexico City. The anatomic site of the gastric neoplasia was identified, and carcinomas were histologically classified as intestinal and diffuse types and subclassified as proposed by the Japanese Research Society for Gastric Cancer. EBV-encoded small non-polyadenylated RNA-1 (EBER-1) in situ hybridization was conducted to determine the presence of EBV in neoplastic cells. RESULTS: We studied 330 consecutive, non-selected, primary gastric carcinomas. Among these, there were 173 male and 157 female patients (male/female ratio 1.1/1). EBER-1 was detected in 24 (7.3%) cases (male/female ratio: 1.2/1). The mean age for the entire group was 58.1 years (range: 20-88 years), whereas the mean age for patients harboring EBER-1-positive gastric carcinomas was 65.3 years (range: 50-84 years). Age and histological type showed statistically significant differences, when EBER-1-positive and -negative gastric carcinomas were compared. EBER-1 was detected in hyperplastic- and dysplastic-gastric mucosa surrounding two EBER-1-negative carcinomas, respectively. CONCLUSION: Among Latin-American countries, Mexico has the lowest frequency of EBVaGC. Indeed, the Mexican population >50 years of age was selectively affected. Ethnic variations are responsible for the epidemiologic behavior of EBVaGC among the worldwide population.

Adult↗
PubMed2005

[Clinical and molecular features of cardial gastric cancer associated to Epstein Barr virus].

BACKGROUND: Mortality caused by cardial gastric cancer in Chile, is increasing. Previously we demonstrated an association between Epstein Barr virus and this specific location of gastric cancer. AIM: To perform a clinical and molecular characterization of cardial gastric cancer associated to Epstein Barr virus. MATERIAL AND METHODS: Epstein Barr virus was identified in 93 cardial gastric tumors, by in situ hybridization. Clinical and pathological features, survival and expression of p53 and c-erbB2 were compared between tumors with or without the presence of the virus. RESULTS: Twenty two (23.6%) tumors expressed Epstein Barr virus. No difference in sex or age of patients with tumors positive or negative for the virus was observed. Epstein Barr positive tumors had a tendency to have a higher frequency of Bormann III endoscopic appearance and a lower frequency of p53 accumulation (p=0.06). Five years survival was 67% and 42% of tumors positive and negative for the presence of the virus, respectively (p=0.57). CONCLUSIONS: Our results, although not significant, show a tendency towards unique characteristics of cardial gastric tumors associated to Epstein Barr.

Adult↗
PubMed2005

Epstein-Barr virus (EBV)-encoded BARF1 gene is expressed in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues in the absence of lytic gene expression.

The BARF1 gene is located in the BamHI-A fragment of the Epstein-Barr virus (EBV) genome, encodes 221 amino acids, and has activity as an oncogene. Several reports have demonstrated that BARF1 is expressed in the tissues of various EBV-associated epithelioid malignancies. However,BARF1 is thought to be a lytic gene, since its expression is induced upon induction of the lytic cycle in Burkitt's lymphoma cell lines. Therefore, the possibility cannot be excluded that BARF1 expression in EBV-associated epithelioid malignancies reflects spontaneous induction of the lytic cycle in carcinoma cells. The present study aimed to clarify whether BARF1 was expressed as a latent gene or a lytic gene in epithelioid malignancies. Quantitative real-time RT-PCR assay revealed that BARF1 was highly expressed in nasopharyngeal carcinoma (NPC) and EBV-positive gastric carcinoma tissues in the absence of expression of lytic genes. On the other hand, BARF1 protein was detectable only in two of seven NPC tissue samples by immunoblot analysis. Analysis of BARF1-transfected CNE1 cells revealed that BARF1 was quickly secreted into culture medium and was hardly detectable in the cell lysate, which would account for why some NPC tissues were negative for BARF1 protein expression even though they were strongly positive forBARF1 expression at the transcriptional level. The present findings indicate that BARF1 is expressed in NPC and EBV-positive gastric carcinoma tissues as a latent gene and suggest that BARF1 plays a role in the pathogenesis of these malignancies.

Carcinoma↗
PubMed2005

Candidate human papillomavirus (HPV) type 27b: nucleotide sequence and heterogeneity with HPV 27.

More than 100 human papillomavirus (HPV) types have been reported as tumorigenic agents. HPV types 2 and 27 were identified in benign tumors and classified closely according to the sequence homology. An HPV type 2 related sequence was identified previously in an oral papilloma. However, the correct typing and sequencing was impossible at that time. A candidate HPV was cloned by the long-PCR technique from an oral papilloma and characterized by nucleotide sequence. This virus was basically HPV type 27, but there was some heterogeneity in comparison with the prototype. Most differences were nucleotide-sequence variations. Two of four-nucleotide insertions were frame shift, resulting in longer L1 protein than that of HPV 27.

Adult↗
PubMed2005

Herpes simplex virus type 2 recurrent meningitis (Mollaret's meningitis): a consideration for the recurrent pathogenesis.

We report a 44-year-old Japanese woman with herpes simplex virus (HSV) type 2 recurrent meningitis (Mollaret's meningitis). The diagnosis was confirmed by nested polymerase chain reaction in her cerebrospinal fluid, but the patient's conventional HSV antibodies by complement fixation, neutralizing test or enzyme immunoassay showed low titres with low lymphoproliferative response. Several similar cases are discussed. Although the reason for the recurrent pathogenesis is uncertain, our report suggests that the low immune response including immune evasion may be involved in the pathogenesis of HSV type 2 recurrent meningitis. For this patient, long-term suppressive and patient-initiated therapies were conducted to prevent the recurrence of meningitis.

Acyclovir↗
PubMed2005

Analysis of human cytomegalovirus UL144 variability in low-passage clinical isolates in Japan.

To explore a possible role for viral genes as determinants of virulence, portions of the UL144 tumor necrosis factor-like receptor gene and the UL55 envelope glycoprotein B gene from 42 patients with congenital human cytomegalovirus (HCMV) infection or other diseases were sequenced. Of the 42 patients, 16 (38%) had UL144 group 1 [group 1A, 15 of 16 (94%); group 1B, 1 of 16 (6%); group 1C, 0 of 16 (0%)], 5 patients (12%) had UL144 group 2, and 21 patients (50%) had UL144 group 3. Although group 1C was not found in Japan strains (0%), it was found in USA strains (22%). Other HCMV polymorphisms should be further evaluated for their potential relevance to neonatal infection, and acquired immunodeficiency syndrome-associated HCMV diseases.

Adult↗
PubMed2005

[New antivirals for herpesviruses].

The long-term treatment of herpesvirus infections with current antivirals leads to the development of drug-resistant viruses. Because currently available antivirals finally target the viral DNA polymerase, mutant resistant to one drug often shows cross-resistance to other drugs. This evidence highlights the need for the development of new antivirals that have the different viral targets. Recently, high-through-put screening of large compound collections for inhibiting specific viral enzymes, or in vitro cell culture assay, has identified several new antivirals. These include the inhibitors of helicase/primase complex, terminase complex, portal protein and UL97 protein kinase. This review will focus on these new compounds that directly inhibit viral replication.

Animals↗
PubMed2004

In Vitro Anti-Cytomegalovirus Activity of Kampo (Japanese Herbal) Medicine.

We examined the effect of three types of Kampo medicines on human cytomegalovirus (CMV) replication in the human embryonic fibroblast cell line, MRC-5. Treatment of cells with at least 0.01 mug/ml of Kampo medicines inhibited the cytopathic effects of CMV-infected MRC-5 cells. Moreover, Kampo medicine decreased the replication of CMV without affecting the inhibition of host cells, with a concomitant decrease in CMV DNA levels. However, Kampo medicine demonstrated no virocidal effect on cell-free CMV. Furthermore, western blotting analysis demonstrated that the Kampo medicine decreased the amount of 65 kDa late antigen expression in the infected cells. These results suggest that Kampo medicine may be sufficient to inhibit viral DNA replication and late protein synthesis, resulting in anti-CMV effects. Therefore, these three Kampo medicines have the potential of being a source of new powerful anti-CMV compounds.

Journal Article↗
PubMed2004

Successful treatment of Good syndrome with cytomegalovirus duodenoenteritis using a combination of ganciclovir and immunoglobulin with high anti-cytomegalovirus antibody titer.

We describe the case of a 64-year-old woman with Good syndrome who presented with watery diarrhea and abdominal distention caused by cytomegalovirus (CMV) duodenoenteritis. Thymoma and hypogammaglobulinemia were first identified when the patient was 58 years old. She had repeatedly complained of symptoms even after thymectomy. Abdominal radiography revealed multiple air-fluid levels, and computed tomography revealed ascites and dilation of the small intestine. Immunofluorescent staining of specimens obtained by duodenal mucosal biopsy revealed intracellular inclusion bodies of CMV, although serum CMV pp65 antigenemia assays yielded negative results. CMV infection of the small intestine caused mucosal edema resulting in malabsorption. The patient was treated using ganciclovir and an immunoglobulin preparation with a high titer of antibodies against CMV (CMV-Ig), and subsequently made a rapid recovery from abdominal symptoms. When patients with Good syndrome complain of abdominal symptoms, particularly chronic diarrhea, a diagnosis of CMV gastroenteritis should not be excluded, even if negative results are obtained for CMV pp65 antigenemia assays. Combination therapy of ganciclovir and CMV-Ig seems useful for patients with CMV gastroenteritis.

Antiviral Agents↗
PubMed2004

Loss of p16/CDKN2A protein in Epstein-Barr virus-associated gastric carcinoma.

We examined the expression of p16, the CDKN2A gene product, in EBV-associated gastric carcinomas (EBV-GCs). EBV-GCs were identified by detecting EBV-encoded small RNA (EBER) using an in situ hybridization assay of paraffin-embedded tissue. Two non-EBV-GC cases for each EBV-GC case were selected, matched for age, sex, tumor location, and depth of invasion. After excluding cases without sufficient tissue samples for immunohistochemical analysis, 54 EBV-GC and 117 non-EBV-GC cases were available for the present study. The loss of p16 expression was more frequently observed in EBV-GCs (89%) than non-EBV-GC cases (32%; p < 0.001). Among non-EBV-GC cases, the loss of p16 expression was more frequent in female cases (57%) than male cases (29%) (p = 0.042). Expression of p16 was not related to the location of tumor, clinical stage of tumor, age, or prognosis of the patients. In conclusion, the present study suggests that the loss of p16-related cell cycle regulation may be associated with the development of EBV-GC.

Aged↗
PubMed2004

Non-herpetic acute limbic encephalitis: cerebrospinal fluid cytokines and magnetic resonance imaging findings.

OBJECTIVE: Non-herpetic acute limbic encephalitis (non-herpetic ALE) is regarded as a new subgroup of limbic encephalitis. In the present study, clinical findings and cerebrospinal fluid (CSF) cytokines in patients with non-herpetic ALE were investigated. PATIENTS AND METHODS: For adult inpatients in our hospital and related hospitals from 1996 to 2001, non-herpetic ALE was examined according to the criteria described in this study. Six patients were diagnosed as having non-herpetic ALE, and their clinical data and magnetic resonance imaging (MRI) were analyzed. In the CSF samples of the 6 patients with non-herpetic ALE and 6 patients with herpes simplex encephalitis (HSE), the concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and interferon (IFN)-gamma were determined using sandwich-type enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: The six patients with non-herpetic ALE showed all the acute encephalitis features, such as fever, altered consciousness, seizures, memory impairment, and mild CSF pleocytosis. MRI demonstrated selective abnormal signals in the limbic system, including the bilateral hippocampi and amygdalae. The levels of CSF IL-6 and IFN-gamma in patients with non-herpetic ALE were significantly lower than those in patients with HSE (p<0.05 and p<0.01, respectively). The levels of both TNF-alpha and IL-1beta were below the detection limits in both groups. CONCLUSION: Six patients were newly diagnosed as having non-herpetic ALE in this study. These patients revealed both acute limbic encephalitis and MRI abnormalities in the bilateral hippocampi and amygdalae. The levels of IL-6 and IFN-gamma in the CSF of patients with non-herpetic ALE were significantly lower than those of patients with HSE, possibly reflecting an immunological process in this type of ALE rather than direct viral infection.

Acute Disease↗