Yuko Hashimoto

Fukushima Medical University, Hukusima, Fukushima, Japan

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Publications (37)70.61 Total impact

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    ABSTRACT: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare disease comprising <3% of extranodal lymphomas. It frequently reveals an activated B-cell (ABC)-like phenotype. ABC-like DLBCL was reported to have gain-of-function mutations in MYD88, CD79B, CARD11, and TNFAIP3, resulting in constitutive activation of the NFκB pathway. Because of the rare occurrence of PB-DLBCL, the frequency of MYD88 and CD79B mutations is still unknown. We used Sanger sequencing to study these mutations from 46 breast DLBCL cases and also investigated the associated clinicopathologic factors. MYD88 L265P was confirmed by allele-specific polymerase chain reaction and compared with the Sanger sequencing results. MYD88 L265P and CD79B mutations were detected in 27/46 (58.7%) and 11/33 (33.3%) cases, respectively. Twenty-eight of 46 cases met the criteria for PB-DLBCL, and the latter 18 cases were further classified as clinical breast DLBCL (CLB-DLBCL). The frequency of MYD88 L265P and CD79B mutations was 16/28 (57.1%) and 9/23 (39.1%), respectively, in PB-DLBCL and 11/18 (61.1%) and 2/10 (20%), respectively, in CLB-DLBCL. When the cutoff value was set at ΔCt≤1, the result of allele-specific polymerase chain reaction for MYD88 corresponded to those of the Sanger sequence at 92.6% sensitivity and 100% specificity. According to Choi's algorithm, 16/27 (59.3%) demonstrated an ABC-like phenotype in PB-DLBCL, and 15/18 (83.3%) demonstrated an ABC-like phenotype in CLB-DLBCL. In conclusion, MYD88 L265P and CD79B mutations were frequently detected in PB-DLBCL, and they may be key molecules associated with PB-DLBCL lymphomagenesis. Further analysis will be required to clarify the mechanism of its pathogenesis.
    No preview · Article · Jan 2016 · The American journal of surgical pathology
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    Osamu Suzuki · Masafumi Abe · Yuko Hashimoto
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    ABSTRACT: To determine the biological roles of cell surface glycosylation, we modified the surface glycosylation of human malignant lymphoma cell lines using glycosylation inhibitors. The O-glycosylation inhibitor, benzyl-α-GalNAc (BZ) enhanced the fibronectin adhesion of HBL-8 cells, a human Burkitt's lymphoma cell line, and of H-ALCL cells, a human anaplastic large cell lymphoma cell line, both of which were established in our laboratory. The N-glycosylation inhibitor, tunicamycin (TM) inhibited the surface expression of Phaseolus vulgaris leukoagglutinating (L-PHA) lectin- and Canavalia ensiformis (ConA) lectin-reactive oligosaccharides in the HBL-8 cell line. Assay of the adhesion of HBL-8 cells to fibronectin showed that fibronectin adhesion is mediated by the integrin very late antigen (VLA)-4 and that not only BZ but also TM treatment enhanced HBL-8 cell adhesion to fibronectin. Furthermore, although BZ treatment also enhanced H-ALCL cell adhesion to fibronectin, this effect was not mediated by VLA-5 or the RGD sequence of fibronectin. We also showed that H-ALCL cell adhesion to galectin-3 was enhanced by pre-treatment with neuraminidase, which cleaves cell surface sialic acid. Additionally, H-ALCL cell adhesion to galectin-3 was inhibited by pre‑treatment with the RGD peptide suggesting that cell adhesion to galectin-3 is mediated by integrin (VLA-5). Furthermore, H-ALCL cell invasion of galectin-1 and galectin-3 was inhibited by pre-treatment with the RGD peptide. Therefore, cell adhesion to and invasion of galectin-1 and galectin-3 are integrin-dependent. In addition to these findings, cell adhesion to galectin-3 was markedly inhibited by treatment with β-lactose compared to treatment with sucrose. Therefore, interactions between integrins and galectin-3 may be mediated through β-galactose that is linked to glycans of integrins. AZA1, an inhibitor of Ras homolog oncoprotein (Rho) GTPase family proteins, RAS-related C3 botulinus toxin substrate 1 (Rac 1) and Cell division control protein 42 homolog (Cdc42) markedly inhibited cell invasion of galectin-1 and galectin-3 suggesting that Rac 1 and Cdc42 may be involved in the regulation of H-ALCL cell invasion of galectins. In conclusion, artificial modification of cell surface glycosylation revealed the biological roles of glycosylation in the adhesion to and invasion of the extracellular matrix (ECM) by human malignant lymphoma cell lines. These findings will provide new insight into the glycobiology of human malignant lymphoma.
    Preview · Article · Oct 2015 · International Journal of Oncology
  • Osamu Suzuki · Masafumi Abe · Yuko Hashimoto
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    ABSTRACT: The important role of sialic acid in various biological phenomena is well-established. In order to further clarify the role of sialic acid in cell death induced by various stimuli, the present study compared the cell survival of the HBL2 human diffuse large Bcell lymphoma cell line upon anticancer druginduced cell death, with or without neuraminidase pretreatment: Cell survival was assessed using flow cytometry. Upon treatment with doxorubicin or etoposide, the HBL2 cell viability decreased. In etoposideinduced cell death, the HBL2 cells demonstrated nuclear fragmentation, which was consistent with morphologically apoptotic cells. In addition, a higher decrease in the cell viability of etoposidetreated HBL2 cells was observed in cells pretreated with neuraminidase compared with cells that were not pretreated. Furthermore, the caspase3, caspase8 and caspase9 activities in etoposideinduced apoptosis demonstrated a greater increase upon neuraminidase pretreatment compared with no neuraminidase pretreatment. In conclusion, cell surface sialylation appears to protect lymphoma cells from anticancer drug-induced apoptosis.
    No preview · Article · Jun 2015 · Oncology letters
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    ABSTRACT: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), frequently shows a poor outcome. Especially, expressions of CC chemokine receptor 4 (CCR4) and γδ T-cell receptor (TCR) are associated with worse prognosis in PTCL-NOS. We here report successful treatment with autologous peripheral blood stem cell transplantation (auto-PBSCT) combined with anti-CCR4 antibody mogamulizumab for a very rare case of CCR4+γδTCR+ PTCL-NOS that coexisted with Hodgkin's lymphoma. PTCL-NOS in this patient progressed to leukemic phase, whereas Hodgkin's lymphoma disappeared with standard chemotherapies within 4 years of the initial diagnosis. Leukemic-phase PTCL-NOS was refractory to several chemotherapies. However, auto-PBSCT following high-dose chemotherapy combined with pre- and post-transplant mogamulizumab, which is a humanized monoclonal antibody to CCR4, provided persistent complete remission of PTCL-NOS, despite residual γδTCR+ in the transplanted stem cell product, suggesting a purging effect of mogamulizumab. At 15 months after transplantation, we also found markedly fewer effector regulatory T cells, which may have contributed to prolonged remission. This case suggests that autologous stem cell transplantation combined with mogamulizumab may have a potential to cure T-cell neoplasms that express CCR4 including leukemic-phase PTCL-NOS.
    Full-text · Article · May 2015 · International journal of hematology
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    Full-text · Article · Jan 2015 · Allergology International
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    Osamu Suzuki · Masafumi Abe · Yuko Hashimoto
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    ABSTRACT: The interaction between cell surface glycans and extracellular matrix (ECM) including galectins is known to be closely associated with tumor cell adhesion, invasion and metastasis. We analyzed the roles of cell surface sialylation or glycosylation in galectin or ECM‑mediated cell adhesion and invasion of human malignant lymphoma cells. Neuraminidase from Arthrobacter ureafaciens (AU) treatment resulted in reduction of cell adhesion to galectin‑8 in human anaplastic large cell lymphoma (H‑ALCL) which was established in our laboratory. The knockdown of β‑galactoside α‑2,6‑sialyltrans-ferase (ST6Gal1) by siRNA showed inhibition of ST6Gal1 expression in the cytoplasm of H‑ALCL cells on immunohistochemical findings, and showed dramatic enhancement of cell adhesion to galectin‑8. On the other hand, α‑2,3‑specific neuraminidase treatment resulted in moderate enhancement of cell adhesion to galectin‑8. We performed chemically artificial modification of cell surface O‑glycans by treatment of benzyl 2‑acetamido‑2‑deoxy‑α‑D‑galactopyranoside (Bz‑α‑GalNAc) in H‑ALCL. Cell adhesion to galectin‑8 was enhanced by treatment of Bz‑α‑GalNAc suggesting that inhibition of elongation of O‑glycans may enhance cell adhesion to galectin‑8 in H‑ALCL cells. On the other hand inhibition of elongation of N‑glycosylation by tunicamycin (TM) resulted in inhibition of Phaseolus vulgaris‑L (L‑PHA) lectin‑binding activity and inhibited cell adhesion to galectin‑8, laminin and fibronectin. Neuraminidase treatment enhanced cell adhesion to laminin, and knockdown of ST6Gal1 resulted in enhancement of cell adhesion to laminin, but not to fibronectin, collagen type 1 and 4. Galectin‑8 pre‑treatment dramatically enhanced cell adhesion to laminin and neuraminidase treatment also enhanced cell adhesion to laminin in combination with galectin‑8. Rho inhibitor, C3‑transferase pre‑treatment resulted in inhibition of cell invasion to galectin‑8. Phosphatidylinositol 3‑phosphate kinase (PI3K) inhibitor, wortmannin inhibits the cell invasive capacity to galectin‑8. Neuraminidase treatment induces growth inhibition of lymphoma cells by galectin‑8.
    Preview · Article · Jan 2015 · International Journal of Oncology

  • No preview · Article · Apr 2014 · Clinical lymphoma, myeloma & leukemia
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    ABSTRACT: The Fukushima nuclear power plant accident occurred on March 11, 2011, following the Great East Japan earthquake and tsunami. Radioactive materials, including 131I, were released into the environment after the accident. Therefore, the government initaiated the Fukushima Health Management Survey for monitoring long-term health condition of the residents in Fukushima Prefecture. In the survey, thyroid ultrasonography is scheduled for all the people under 18 years of age who were living in Fukushima Prefecture at the time of disaster. The total number of examinees is 360,000. First, thyroid ultrasonography is performed as a screening test. When abnormal findings are detected, thyroid FNAC is performed. By the end of December 2013, the cytological specimens of 75 examinees had been interpreted as Malignant or Suspicious for malignancy. Histological examination of surgically removed specimens from 33 patients revealed papillary carcinoma. At the present time, it is difficult to conclude whether these papillary carcinomas were radiation-induced or not.
    No preview · Article · Jan 2014
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    ABSTRACT: Monocyte chemoattractant protein-1 (MCP-1) can accelerate tumor progression by attracting tumor-associated macrophages. We studied the effects of MCP-1 on SKOV-3 cells in order to investigate MCP-1 biological activity ovarian cancer. A SKOV-3 cell invasion assay (Transwell assay) and cell adhesion assay (96-well assay) were performed. Immunohistochemical staining for C-C motif chemokine receptor-2 (CCR2), a receptor for MCP-1, was also performed on cultured SKOV-3 cells. Migration and adhesion of MCP-1-treated SKOV-3 cells were significantly increased compared to untreated cells (p<0.01). A CCR2 antagonist attenuated the invasion and adhesion of MCP-1-treated cells. CCR2 was expressed in the cytoplasm of SKOV-3 cells. MCP-1 promoted invasion and adhesion of ovarian cancer cells, and a CCR2 antagonist attenuated the effects of MCP-1 in vitro. These data suggest that MCP-1 is a potential therapeutic target for ovarian cancer therapy.
    No preview · Article · Nov 2013 · Anticancer research
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    ABSTRACT: The basic region-leucine zipper (bZip) factor BTB, CNC homology 2 (BACH2) is known to have important roles in class switch recombination and somatic hypermutation (SHM) of the immunoglobulin (Ig) gene. In this study, we investigated the relationship between the expression of BACH2 and the status of SHM of the Ig heavy chain gene variable region (IgHV) for SHM in diffuse large B-cell lymphoma (DLBCL). We examined 20 cases of DLBCL, 13 of which were germinal center B-cell (GCB) DLBCL and 7 were non-GCB DLBCL. Seven cases were negative, 6 were positive (cytoplasmic expression) and 7 were strongly positive (both nuclear and cytoplasmic expression) for BACH2. Confirmed mutation (CM) was identified in 8 cases and the CM index (number of confirmed mutations per 10 subclones) was distributed from 0 to 5. A CM index of 7 strongly positive (over-expression) cases with BACH2 were distributed from 0 to 5, and that of 7 negative and 6 positive cases were distributed from 0 to 1. Over-expression of BACH2 was statistically related to CM index (P = 0.008). In conclusion, over-expression of BACH2 is critical for ongoing SHM of IgHV in DLBCL, and our data suggest that BACH2 may play an essential role for SHM of the Ig gene in B-cell lymphoma.
    No preview · Article · Jul 2013 · Pathology International
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    ABSTRACT: Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 102 PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 104 PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics.
    Preview · Article · Jan 2013 · Journal of Virology
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    ABSTRACT: Arteriovenous malformation (AVM) can arise in various organs, particularly the brain, but it is rare in the uterus. Uterine AVM is potentially lethal and is generally associated with uterine trauma, such as dilatation and curettage, therapeutic abortion or uterine surgery. On the other hand, uterine myoma is the most common benign gynecological tumor, but uterine cervical myoma is rare and grows in the extraperitoneal space, with development of complex capillary networks within the tumor. Cervical myoma surgery is therefore a difficult operation with a risk of massive bleeding. We report herein a patient with uterine AVM formed within a large cervical myoma in a postmenopausal woman. The patient was a 55-year-old Japanese woman who complained of lower abdominal distension. Ultrasonography, computed tomography and magnetic resonance imaging showed an 18 × 20-cm uterine cervical tumor with dilatation of numerous vessels. Pelvic angiography was scheduled to provide accurate diagnosis and to minimize intraoperative blood loss. In fact, preoperative pelvic angiography allowed us to identify the true feeding artery and drainage veins. Occlusion of the feeding artery with a balloon device is effective in decreasing intraoperative bleeding. Abdominal total hysterectomy was performed as the surgical management of this uterine AVM. Prophylactic endovascular balloon occlusion of the ipsilateral internal iliac artery reduced the amount of hemorrhage during surgery, although blood transfusion was needed in our patient. In conclusion, preoperative embolosclerotherapy should be considered as a treatment option in patients with AVM present in a large uterine cervical myoma.
    No preview · Article · Nov 2012 · The Tohoku Journal of Experimental Medicine
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    ABSTRACT: To elucidate the correlation between regulatory T cells (Tregs) and acute graft-versus-host disease (aGVHD) or cytomegalovirus infection following allogeneic bone marrow transplantation (allo-BMT), we evaluated either CD4⁺CD25(high) or FOXP3⁺ Treg-enriched cells in peripheral blood (PB) from 20 patients who received allo-BMT, and in biopsies of skin with aGVHD. Proportions of CD4⁺CD25(high)FOXP3⁺ cells in total lymphocytes, but not other types of T cells, were lower in patients who eventually developed grades II-IV aGVHD (n = 13) than in others (n = 7, P < 0.001). Proportions of CD62L⁺ cells in CD4⁺CD25(high) cells at day +30 were lower (P < 0.01) in patients who eventually showed cytomegalovirus viremia (n = 6) than in others (n = 14). Incidence of aGVHD (P < 0.05) or cytomegalovirus viremia (P < 0.05) was higher in patients without these complications, but with lower proportions of PB CD4⁺CD25(high)FOXP3⁺ cells at day +30 (n = 8) than in others (n = 8). However, in skin with aGVHD (n = 5), there was marked or slightly increased infiltration of CD8⁺ cells (P < 0.001) or CD3⁺FOXP3⁺ cells (P < 0.05), respectively, when compared with control (n = 5), resulting in threefold higher ratio of CD8⁺/CD3⁺FOXP3⁺ cells in aGVHD relative to controls (P < 0.05). Thus, impaired reconstitution of Tregs may be associated with aGVHD and CMV infection. Moreover, imbalance of Tregs and CD8⁺ cells may play a role in aGVHD tissue.
    No preview · Article · Dec 2011 · International journal of hematology
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    ABSTRACT: Non-bacterial thrombotic endocarditis is caused by a hypercoagulable state that is sometimes related to malignancy and this type of endocarditis associated with benign tumors has not yet been reported. In this study we report the first case of non-bacterial thrombotic endocarditis caused by adenomyosis, which is a benign gynecological condition.
    No preview · Article · Aug 2011 · Journal of Obstetrics and Gynaecology Research
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    ABSTRACT: To compare the outcome of surgical treatment of colorectal adenocarcinoma in elderly and younger patients. The outcomes of 122 patients with colorectal adenocarcinoma who underwent surgical treatment between January 2004 and June 2009 were analyzed. The clinicopathological and blood biochemistry data of the younger group (< 75 years) and the elderly group (≥ 75 years) were compared. There were no significant differences between the two groups in operation time, intraoperative blood loss, hospital stay, time to resumption of oral intake, or morbidity. The elderly group had a significantly higher rate of hypertension and cardiovascular disease. The perioperative serum total protein and albumin levels were significantly lower in the elderly than in the younger group. The serum carcinoembryonic antigen level was lower in the elderly than in the younger group, and there was a significant decreasing trend after the operation in the elderly group. The short-term outcomes of surgical treatment in elderly patients with colorectal adenocarcinoma were acceptable. Surgical treatment in elderly patients was considered a selectively effective approach.
    Preview · Article · Mar 2011 · World Journal of Gastroenterology
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    ABSTRACT: Renal amyloidosis is typically characterized by nephrotic syndrome, often with massive proteinuria and refractory peripheral edema. We report the case of a patient with renal amyloidosis associated with nephrotic syndrome who maintained remission for 6 years after undergoing high-dose chemotherapy followed by autologous peripheral blood stem-cell transplantation (auto-PBSCT). The patient was a man aged in his 50s who had developed nephrotic syndrome. Bone marrow aspiration and kidney biopsy determined that the cause of the nephrotic syndrome was renal amyloidosis due to multiple myeloma, and the patient was admitted to our department in July 2003. After one course of chemotherapy, auto-PBSCT was performed in March 2004. Following transplantation, serum M-protein was no longer detectable from March 2005, and the patient achieved complete hematological remission. Subsequently, proteinuria decreased, serum albumin levels normalized, and nephrotic syndrome improved. As of 6 years after transplantation, in March 2010, the patient remained in remission, meaning that auto-PBSCT proved extremely effective as a treatment for renal amyloidosis in this case.
    Full-text · Article · Dec 2010 · Fukushima journal of medical science
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    ABSTRACT: Castleman's disease (CD), a rare benign disease characterized by lymphoid hyperplasia, typically arises in the mediastinum as a solitary tumor. We describe herein a rare case of intramuscular CD occurring in the left deltoid in a 28-year-old woman. The present case is instructive in the differential diagnosis of primary soft tissue tumors, for which the possibility of CD should be considered.
    No preview · Article · Mar 2010 · Skeletal Radiology
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    ABSTRACT: This report describes our experience with two cases that were ultimately diagnosed as retroperitoneal liposarcoma using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Case 1 is that of a 54-year-old woman with chief complaints of nausea and abdominal distention. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large (15 cm diameter) tumor, which was significantly compressing the stomach and apparently occupied the entire left abdominal cavity. Although advanced primary gastrointestinal stromal tumor (GIST) or retroperitoneal tumor was inferred as the differential diagnosis, a definitive diagnosis was difficult using imaging alone. After EUS-FNA was done, the tumor was diagnosed histopathologically as high-grade liposarcoma. Case 2 is that of a 73-year-old man. Abdominal ultrasonography and CT showed a 6 cm diameter tumor within the pelvic cavity. The tumor had high MRI signal-intensity on both T1 and T2 images. Endorectal EUS showed a hyperechoic mass. The images suggested lipoma or liposarcoma containing lipoma-like components. Myxoid liposarcoma was revealed by subsequent EUS-FNA. Performing EUS-FNA was clinically useful for determining the subsequent therapeutic strategy in these cases where a tumor of unknown origin existed in the retroperitoneum.
    Full-text · Article · Oct 2009 · Diagnostic and Therapeutic Endoscopy
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    ABSTRACT: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with rapid on-site evaluation (ROSE) has been reported to provide a more accurate diagnosis than EUS-FNA without such evaluation. However, even endosonographers can evaluate ROSE regarding sample adequacy. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA with ROSE by endosonographers compared to ROSE by cytopathologists in patients with solid pancreatic masses. Between September 2001 and October 2005, of the 73 EUS-FNA procedures with the final diagnoses, 38 procedures after the introduction of ROSE by endosonographers (September 2001-September 2003, period 1), and 35 procedures after the introduction of ROSE by cytopathologists (October 2003-October 2005, period 2) were included. The specimens were stained with Diff-Quik stain and assessed. When the on-site assessors (endosonographers or cytopathologists) indicated that the amounts of cell samples were adequate, the procedure was stopped. Results are presented with 95% confidence limits. The average numbers of needle passes were 4.0 +/- 1.6 and 3.4 +/- 1.5 in periods 1 and 2, respectively (P = 0.06). The specimen collection rates were 97.4 and 97.1% in periods 1 and 2, respectively (P = 0.51). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for malignancy and benign were 92.9, 100, 100, 83.3, and 94.7%, respectively, in period 1, and 93.1, 100, 100, 75.0, and 94.3%, respectively, in period 2 (P = 0.97, P = 1.0, P = 1.0, P = 0.65, P = 0.93, respectively). No complications were seen. For accurate diagnosis, ROSE should be performed during EUS-FNA by the endosonographer, if no cytopathologist is available.
    No preview · Article · Apr 2009 · Journal of Gastroenterology
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    ABSTRACT: Respiratory syncytial virus (RSV) is one of the pathogens generally associated with the common cold, lower respiratory infection, and exacerbation of asthma. Disodium cromoglycate (DSCG) is a safe and widely used drug for the prevention of bronchial asthma and allergic rhinitis attacks. The effect of DSCG on acute upper respiratory tract viral infections remains controversial. The purpose of the study was to investigate the effects of DSCG on parameters of RSV induced-illness. Using a well-characterized murine model of RSV infection, the effect of DSCG on RSV-induced illness was evaluated by body weight, respiratory function, viral replication, level of IFN-gamma in lungs, serology, and histopathology. Mice treated with DSCG were protected against RSV-induced weight loss. The baseline Penh in RSV-infected mice treated with DSCG was less than that in mice treated with saline. In methacholine challenge, the increase in Penh in RSV-infected mice treated with DSCG was suppressed to the same level as that in the mock-infected group. Further, there were no differences in viral replication between the mice treated with DSCG and those treated with saline, and the level of inflammation observed in the lungs in RSV-infected mice treated with DSCG was not as severe as that in mice treated with saline. These findings indicate that DSCG may be an effective agent for the prevention of RSV induced disease and the relief of symptoms of RSV infection.
    No preview · Article · Feb 2009 · Journal of Medical Virology

Publication Stats

329 Citations
70.61 Total Impact Points

Institutions

  • 1999-2015
    • Fukushima Medical University
      • • Division of Medicine
      • • Department of Diagnostic Pathology
      • • Department of Pathology
      Hukusima, Fukushima, Japan