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Biomedical subjects

Yoshito Eizuru

Publications and source records attributed to Yoshito Eizuru.

16 recordsLinked to original sources
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↗
PubMed2003

Autocrine growth of Epstein-Barr virus-positive gastric carcinoma cells mediated by an Epstein-Barr virus-encoded small RNA.

Although 5-10% of gastric carcinoma (GC) cases worldwide are associated with EBV, a human herpesvirus, it is still not clear what the precise contribution of the virus is to the pathogenesis of EBV-positive GC. Here we report that EBV infection induces expression of insulin-like growth factor 1 (IGF-I) in the GC-derived EBV-negative cell line NU-GC-3 and that the secreted IGF-I acts as an autocrine growth factor. Transfection of individual EBV latent genes into NU-GC-3 cells revealed that the EBV-encoded small RNA (EBER) was responsible for IGF-I expression. Addition of recombinant IGF-I accelerated growth of NU-GC-3 cells, whereas growth of the EBV-converted NU-GC-3 cells was blocked by treatment with an anti-IGF-I antibody. These results suggest that IGF-I induced by EBER acts as an autocrine growth factor for EBV-positive GC. These findings seem to be operative in vivo, as EBV-positive GC biopsies consistently express IGF-I, whereas EBV-negative GC biopsies do not. EBER is invariably expressed in EBV-associated malignancies including GC. The present findings strongly suggest that EBV directly affects the pathogenesis of EBV-positive GC and underline the importance of RNA molecules on cell growth regulation.

Cell Division↗
PubMed2003

The comparison of the prognosis between Epstein-Barr virus (EBV)-positive gastric carcinomas and EBV-negative ones.

The relationship between the degree of lymphocytic infiltration into the tumor and the prognosis has not been completely evaluated between Epstein-Barr virus (EBV)-positive and -negative gastric carcinoma (GC). Although the average numbers and the grades of the infiltrating CD8+T cells, natural killer cells, dendritic cells, Ki67-positive cells were significantly greater in EBV-positive GCs than in -negative GCs, there was no significant survival improvement in EBV-positive group. These findings suggest that the infiltration of lymphocytes in the EBV-positive GC does not necessarily meant better prognosis and that the EBV status is not a significant prognostic factor in the patients with gastric cancer.

Aged↗
PubMed2003

Detection and sequences of human papillomavirus DNA in nongenital seborrhoeic keratosis of immunopotent individuals.

BACKGROUND: The etiology of seborrhoeic keratosis (SK) is unknown. Its clinical and histopathological similarities to verrucae vulgaris and condyloma acuminatum prompted us to examine whether human papillomavirus (HPV) is present in SK lesions. In the present study, HPVs were frequently detected from genital lesions or hair follicle in immunocompromised host. OBJECTIVE: We analyzed 104 nongenital SK specimens diagnosed by clinical and histopathological examinations for HPV DNA in immunopotent individuals. METHOD: We analyzed SK specimens for HPV DNA using in situ hybridization (ISH), polymerase chain reaction (PCR), Southern blot hybridization, and sequencing of viral DNA of PCR-amplified fragments. And we also examined virion, which is the capsid protein of HPV in ISH-positive specimens by immunochemical examination. We identified eight mucosal and two cutaneous type HPVs. RESULT: ISH revealed that 30 of 104 (28.8%) SK samples contained HPV DNA. All ISH-positive specimens were demonstrated virion in the nuclei of the epidermal keratinocytes. PCR analysis showed that 87 (83.7%) samples contained HPV-18, 81 (77.9%) HPV-6, and 73 (70.2%) contained both HPV-18 and -6. The incidence of HPV-1 (7.7%) and HPV-2 (14.4%) was relatively low. All 20 normal controls were negative for HPV DNA by ISH but seven were positive by PCR sequencing. CONCLUSION: Our results suggest that HPV, possibly coinfection with HPV-6 and -18 and unknown type(s) of HPV, plays an important role in the pathogenesis of SK.

Adult↗
PubMed2003

Clinical significance of CEA-mRNA expression in peritoneal lavage fluid from patients with gastric cancer.

Peritoneal dissemination is one of the most common modes of gastric cancer recurrence even after curative resection. Cytological examination of peritoneal lavage fluid is useful for detection of free cancer cells in the peritoneal cavity. However, some patients with negative cytological findings have peritoneal metastases of their gastric cancer. The purpose of the present study was to investigate the incidence and clinical significance of metastases harbored in the peritoneal cavity of patients with gastric carcinoma. Peritoneal lavage fluid was collected from the left subphrenic or Douglas cavities of 136 gastric cancer patients without macroscopic peritoneal metastases and 31 patients with benign disease. Peritoneal lavage fluid was examined by both conventional cytological examination (Papanicolaou and Giemsa staining), and carcinoembryonic antigen (CEA)-specific reverse transcription-polymerase chain reaction (RT-PCR). Among 136 gastric cancer patients, 5 patients (3.6%) were positive for free cancer cells by cytological examination and 30 (22.1%) were positive by RT-PCR. A difference in positivity between the left subphrenic and Douglas cavity was found in 18 patients by RT-PCR. The frequency of RT-PCR results increased according to lymph node metastases, lymphatic invasion, depth of tumor invasion and stage grouping. The incidence of peritoneal recurrence was significantly higher in patients with positivity than those with negativity by RT-PCR (p<0.0001). Among cytologically negative patients, survival was significantly shorter in patients with positive than in those with negative CEA-mRNA expression (p<0.0001). The technique of RT-PCR was more sensitive than cytological examination in the detection of cancer cells and prediction of peritoneal recurrence. Adjuvant therapy may be advisable for the gastric cancer patients with positive findings of peritoneal lavage by RT-PCR.

Carcinoembryonic Antigen↗
PubMed2002

2,3,7,8-Tetrachlorodibenzo-p-dioxin is a possible activator of human cytomegalovirus replication in a human fibroblast cell line.

We examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on human cytomegalovirus (CMV) replication in the human embryonic fibroblast cell line, MRC-5. Treatment of cells with 0.0001pg/ml TCDD augmented the cytopathic effects of CMV-infected MRC-5 cells. Moreover, TCDD increased the replication of intracellular CMV without affecting the proliferation of host cells, with a concomitant increase in CMV UL54 DNA levels. However, TCDD demonstrated no virocidal effect on cell-free CMV. Furthermore, CMV-infected MRC-5 cells expressed transcripts of the aryl hydrocarbon receptor (AhR) and AhR nuclear translocator. These results suggest that TCDD may contribute to the development of opportunistic diseases by reactivation of latently infected CMV and that TCDD regulates CMV replication through the dependence on AhR.

Cell Line↗
PubMed2002

Envelope sequence variation and phylogenetic relations of human T cell lymphotropic virus type 1 from endemic areas of Colombia.

The HTLV-1 envelope gene of 12 TSP/HAM patients from two endemic areas of southwest Colombia (Tumaco and Buenaventura) was amplified by nested PCR, sequenced, and compared with previously reported HTLV-1 envelope sequences from isolates worldwide. In general, the sequence divergences among all Colombian samples ranged from 0.1 to 1.6%. Some amino acid substitutions, referring to the ATK-1 prototype strain in the surface domain gp46 and in p21, were highly prevalent in southwest Colombia, suggesting a geographical clustering of mutations in the envelope gene. The phylogenetic analysis showed that the Colombian isolates belong to the HTLV-1a lineage with minor subgroups. The genetic distance between Colombian and Japanese isolates ranged from 0.1 to 1.8%; in comparison, the genetic distance between Colombian and Caribbean isolates ranged from 0.4 to 2.2%. Our results strongly suggest that the actual quasispecies populations in southwest Colombia have been generated by separate, differently timed introductions of virus.

Base Sequence↗
PubMed2002

Epstein-Barr virus-associated gastric carcinoma in southern India: A comparison with a large-scale Japanese series.

Epidemiological and clinicopathological features of Epstein-Barr virus (EBV) associated gastric carcinoma was compared in India and Japan, two countries differing markedly in gastric cancer incidence. Using in situ hybridization assay, the presence of EBV-encoded small RNA (EBER) was examined in 215, and 2,011 gastric cancer cases in Kerala, India, and Japan, respectively. Ten cases (5%), all males, in the Indian series were EBER-positive. This frequency was similar to that in the Japanese series (6.2%). As was the case with Japanese series, the EBV-associated gastric carcinoma in the Indian series was observed most frequently in the middle part of the stomach (1 in antrum, 4 in middle part, 2 in cardia, and 3 unknown), and, histologically, the diffuse type Lauren's classification (8 cases) was more common than the intestinal type (2 cases). Virus subtyping by PCR-RFLP revealed that all of the 10 EBV strains isolated from the EBER-positive Indian cases were subtype A, and wild-type F for Bam HI F region. In Bam HI I region, 8 cases were type C and the remaining 2 cases were type D. In either series, there was no significant difference in the frequency of tumors with p53 overexpression between EBER-positive and -negative cases. However, the proportion of cells with p53 overexpression in EBER-negative tumors was significantly higher than that in EBER-positive tumors regardless of histological type in both series. In conclusion, the frequency and major clinicopathological features of EBV-associated gastric carcinoma in south India were similar to those observed in Japanese series although gastric cancer incidence in these two countries differs markedly.

Adult↗
PubMed2002

GCV resistance due to the mutation A594P in the cytomegalovirus protein UL97 is partially reconstituted by a second mutation at D605E.

A ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) was isolated from an AIDS patient. Molecular analysis of the HCMV UL97 gene revealed two point mutations, A594P and D605E, respectively. In order to evaluate quantitatively the impact of the individual mutations on GCV phosphorylation, recombinant vaccinia viruses (rVVs) were generated carrying either the two mutations (rVV-594/605) or only one mutation (rVV-594 or rVV-605, respectively). In cells infected with the rVV-594/605 double mutant, the GCV phosphorylation was decreased to 50% compared with the phosphorylation in cells infected with the rVV-UL97 wild-type. In cells infected with the rVV-594, however, the GCV phosphorylation was further decreased to 30%. Interestingly, the mutation D605E led to an even better GCV phosphorylation than that measured in cells infected with the rVV-UL97 wild type. These results were confirmed by plaque reduction assays, indicating that rVV-594 was more resistant to GCV than rVV-594/605. In contrast, rVV-605 was more sensitive to GCV than the rVV-UL97 wild type. Therefore, our results demonstrated for the first time that compensatory mutations can also occur in HCMV, as already shown for human immunodeficiency virus type 1.

AIDS-Related Opportunistic Infections↗
PubMed2002

Lymph node micrometastasis and lymphatic mapping determined by reverse transcriptase-polymerase chain reaction in pN0 gastric carcinoma.

BACKGROUND: The purposes of this study were to examine lymph node micrometastasis (LMM) by reverse transcriptase-polymerase chain reaction (RT-PCR) method, and clarify the initial nodes involved by metastatic disease according to tumor location. METHODS: We examined 312 lymph nodes obtained from 50 patients with node-negative gastric carcinoma. RT-PCR and immunohistochemistry were performed. The clinical characteristics of LMM were investigated, and the map of LMM was made according to tumor location. RESULTS: The number of patients and LMM detected by RT-PCR was 14 and 17 and by immunohistochemistry was 7 and 8, respectively. RT-PCR was a more sensitive method than immunohistochemistry. LMM by RT-PCR correlated with depth of tumor invasion and lymphatic invasion. Regarding pT1 tumor, 9 patients with LMM had tumors that were of the macroscopically depressed type and 2 cm or more in diameter. According to the lymphatic map, right pericardial lymph nodes and lymph nodes along the lesser curvature were the initial nodes involved in the upper third of the stomach. Right pericardial lymph nodes, lymph nodes along the lesser curvature, and infrapyloric nodes were more important initial metastatic sites in the middle third of the stomach, and lymph nodes along the lesser curvature and infrapyloric nodes in the lower third. CONCLUSIONS: We demonstrated the relationship between LMM and clinicopathologic factors, especially in pT1 tumor. The mapping of LMM may prove useful for selecting the optimal treatment.

Aged↗
PubMed2002

Interferon-alpha therapy following autologous peripheral blood stem cell transplantation for adult T cell leukemia/lymphoma.

In the present report, we describe a case of adult T cell leukemia/lymphoma (ATLL), a 58-year-old woman, successfully treated with interferon (IFN)-alpha following autologous peripheral blood stem cell transplantation (auto-PBSCT). The patient remains in remission with full performance status for more than 12 months. Auto-PBSCT reduced the abdominal lymphoma mass and IFN-alpha eliminated residual tumor cells, possibly through the induction of specific T-cell subsets expressing CD3, CD8 on their surfaces and either IFN-gamma or tumor necrosis factor (TNF)-alpha in cytoplasm. We have treated a total of 4 ATLL patients with auto-PBSCT, including the case presented herein. All other patients treated with auto-PBSCT were not followed by adjuvant chemotherapy or cytokine therapy and relapsed within 3 months after auto-PBSCT. This evidence suggests that the therapeutic success of the present case was attributable to the administration of IFN-alpha immunotherapy following auto-PBSCT.

Abdominal Neoplasms↗
PubMed2002

Acute viral encephalitis: the recent progress.

In the new Japanese control law for infectious diseases, most varieties of acute viral encephalitis belong to Category IV requiring report of all cases at sentinel hospitals. Herpes simplex virus type 1 (HSV-1) encephalitis comprises the majority of cases. With the increased prevalence of diagnostic procedures such as polymerase chain reaction (PCR), several forms of HSV-1, and -2 central nervous system (CNS) infections, including acute disseminated encephalomyelitis, brainstem encephalitis, and myelitis, have been clarified. Since 1990 we have conducted a survey of HSV CNS infections in the Kyushu and Okinawa regions, and the data are reviewed here. Trends include an increase in a new subtype of non-herpetic acute limbic encephalitis. In contrast, the incidence of Japanese encephalitis (JE) in Japan has dramatically decreased to a few patients per year; however, JE remains a threat for those with decreased or absent immunity to the JE virus. Imported emerging and reemerging CNS infections such as Murray Valley and West Nile encephalitis can occur in Japan. Influenza-associated encephalitis/encephalopathy is also described as a threat for adults as well as young children.

Acute Disease↗
PubMed2002

Prognostic significance of Epstein-Barr virus involvement in gastric carcinoma in Japan.

We examined the prognosis of 64 EBV-associated gastric carcinoma (EBV-GC) cases and 128 EBV-negative gastric carcinoma cases. EBV-GCs were identified by detecting EBV-encoded small RNA (EBER) using in situ hybridization assay of paraffin-embedded tissue. For each EBV-GC case, 2 EBER-negative cases (EBV-negative cases) were selected, matching the EBV-GC case with respect to age, sex, tumor location, and depth of invasion. The average follow-up period was 70.9 months (SD=61.1) in EBV-GCs and 63.8 months (SD=59.7) in EBV-negative cases. Tumor-advanced stage determined by TNM classification of UICC, tumor location, and p53 over-expression were statistically significant prognostic factors. On the other hand, EBER expression was not related to the survival of patients. However, further analysis specific for intestinal and diffuse types of Lauren classification revealed that the association of EBER expression with prognosis was different in the two histological types. EBER expression was related to poor prognosis in intestinal-type carcinoma [hazard ratio (HR) =2.5, 95% confidence intervals (CI) =1.3-4.8] after adjusting for stage, p53 over-expression, and tumor location, whereas the diffuse-type EBV-GC had better prognosis (HR=0.4, 95% CI=0.2-0.9) even when lymphoepithelioma-like carcinomas were excluded. To examine the interactive prognostic effects between EBER expression and p53 over-expression, the study subjects were divided into 4 groups on the basis of EBER expression and p53 over-expression. In intestinal-type tumors, the cases having both EBER expression and p53 over-expression showed the poorest prognosis (HR=10.0, 95% CI=3.3-30.4), and the cases with either EBER expression or p53 over-expression had an intermediate prognosis. In diffuse-type tumor, only EBER was an important prognostic factor. These results give additional evidence implicating EBV in the natural history of EBV-GCs.

Epstein-Barr Virus Infections↗
PubMedDate not supplied

The Epstein-Barr virus-associated gastric carcinoma in Southern and Northern China.

In the present study, we examined the proportions of Epstein-Barr virus-associated gastric carcinomas (EBV-GCs) in Guangzhou, southern China and Shenyang, northern China, two areas differing markedly in nasopharyngeal carcinoma (NPC) incidence. Using in situ hybridization assay, the presence of EBV-encoded small RNA (EBER) was examined in 198, and 180 gastric cancer cases in Guangzhou and Shenyang, respectively. The proportion of EBV-GC in Guangzhou (9%) was significantly higher than that in Shenyang (6%), and the odds ratio (OR) for Guangzhou, after adjusting for the effects of age, sex, and tumor subsite, was 2.7 (95% CI = 1.1-6.2) when Shenyang was taken as reference. There was a male predominance of EBV-GC, and the OR for male was 3.0 (95% CI = 1.2-7.3) when female was taken as reference. We observed a weak and negative age dependence in the proportion of EBV-GC (p-values for trend = 0.077). The EBV-GC was most commonly observed in the middle part of stomach in both series. The frequency of EBV-GCs was higher in cases with p53 overexpression than in cases without p53 expression (OR = 2.4, 95% CI = 1.0-5.8). Among p53-positive cases, the frequency of EBV-GC decreased as the proportion of p53-positive carcinoma cells increased (p for trend = 0.021). In conclusion, the present study suggested that the frequency of EBV-GC in Guangzhou, southern China, where NPC is the most common in the world, may be higher than that in other parts of China.

Adult↗
PubMedDate not supplied

Epstein-Barr virus-associated gastric carcinoma in Cali, Colombia.

To estimate the incidence of Epstein-Barr virus-associated gastric carcinoma (EBV-GC) in Colombia and to clarify its clinicopathological features, we examined 178 consecutive gastric carcinoma cases, diagnosed during the period from 1996 to 1998, at Hospital Universitario del Valle in Cali, Colombia. The mean age of the cases was 60 years in males and 58 years in females. Using in situ hybridization assay of EBV-encoded small RNA-1 in paraffin-embedded tissue samples, we identified 23 cases of EBV-GC (13%). After excluding remnant carcinoma, which was found to be EBV-negative in this series, there were 19 (18%) male and 4 (6%) female EBV-GC cases, and the male predominance was statistically significant (P=0.004). The proportion of EBV-GCs decreased with age (P for trend = 0.022). Using sex- and age-specific proportions of EBV-GCs estimated by logistic models and gastric cancer incidence in Cali, which was obtained from tumor registry during the period 1987-1991, we estimated sex- and age-specific incidence of EBV-GCs. The incidence of EBV-GCs (per 100,000 person-years) was 4.1 and 1.4 among men and women, respectively, after age adjustment using the standard world population. Pathological features of EBV-GCs were also examined. EBV-GCs accounted for 33% (8/24) of carcinomas located in the stomach cardia, 14% (6/43) of carcinomas in the middle-part of the stomach, and 7% (6/81) of carcinomas in the antrum. The difference by tumor location was statistically significant (P=0.009). Histology-specific analysis using Lauren classification revealed that the proportion of EBV-GCs was not different in intestinal- and diffuse-type carcinomas (13% in both types). When the classification scheme of the Japanese Research Society for Gastric Cancer was used, EBV-GCs were identified more frequently in moderately differentiated tubular adenocarcinoma, and solid poorly differentiated adenocarcinoma when compared to other histological types. No lymphoepitelioma-like histology was found in the present series. The frequency of EBV-GC was slightly higher in advanced tumors, which involved serosa. Further analysis of clinico-pathological features of EBV-GC using a larger number of cases would give invaluable insights into its etiology.

Adenocarcinoma↗