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Tomayoshi Hayashi

Publications and source records attributed to Tomayoshi Hayashi.

17 recordsLinked to original sources

Increased expression of collagen-binding heat shock protein 47 in murine bleomycin-induced pneumopathy.

The 47-kDa heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been shown to play a major role during the processing and/or secretion of procollagen. Expression of HSP47 has been reported to increase in parallel with expression of collagens during the progression of various fibrosis models. The aim of the present study was to investigate the association between HSP47 expression and collagen accumulation in bleomycin (BLM)-induced murine fibrosis. We investigated the expression of HSP47 protein and mRNA using immunohistochemical analysis and semi-quantitative RT-PCR in murine BLM-induced pulmonary fibrosis. Immunohistochemical analysis showed that higher expression of HSP47 protein was present in BLM-induced pulmonary fibrosis compared with controls. HSP47 was localized predominantly in alpha-smooth muscle actin-positive myofibroblasts, F4/80 negative, surfactant protein-A-positive type II pneumocytes, and F4/80-positive macrophages. RT-PCR also demonstrated an increase of HSP47 mRNA expression in BLM-treated lungs. Moreover, the relative amounts of HSP47 mRNA correlated significantly with the lung hydroxyproline content as an indicator of pulmonary fibrosis in BLM-treated lungs (r = 0.406, P <0.05). Our results suggest that these cells may play a role in the fibrotic process of BLM-treated lungs through upregulation of HSP47.

Animals↗

Serum insulin-like growth factor binding protein-3/prostate-specific antigen ratio is a useful predictive marker in patients with advanced prostate cancer.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) play an important role in regulation of prostate cancer cell growth. We studied the prognostic significance of serum IGF-1 and IGFBP-3 levels, and IGF-1/prostate-specific antigen (PSA) and IGFBP-3/PSA ratios in patients with prostate cancer. METHODS: Serum levels of IGF-1, IGFBP-3, and PSA were determined in 112 patients diagnosed with prostate cancer. Serum samples from 32 patients with histologically confined benign prostatatic hyperplasia (BPH) served as control. RESULTS: Serum IGF-1 levels were significantly higher in advanced prostate cancer (n = 84) than in BPH patients (P < 0.01). IGFBP-3 levels were significantly lower in patients with advanced prostate cancer than in localized tumor (n = 28) or BPH (P < 0.05, each). Univariate analysis showed that serum PSA, IGF-1/PSA ratio, IGFBP-3/PSA ratio, T, N and M classifications correlated significantly with relapse-free survival of advanced prostate cancer patients treated with hormonal therapy. Multivariate analysis identified IGFBP-3/PSA ratio as the only significant variable for relapse-free survival (odds ratio 5.81, 95% CI 1.57-21.51). IGFBP-3/PSA ratio was also an independent predictor of cause-specific survival (stepwise analysis, odds ratio 4.86, P < 0.01). CONCLUSIONS: Our results suggested that IGFBP-3/PSA ratio might be a useful prognostic marker of advanced prostate cancer.

Aged↗

A case of mucosa-associated lymphoid tissue lymphoma of the ampulla of Vater: successful treatment with radiation therapy.

Mucosa-associated lymphoid tissue (MALT) lymphoma of the papilla of Vater is rare, and little is known of either its association with Helicobacter pylori infection or the optimal treatment modalities. We describe the first case of MALT lymphoma involving the major papilla that remained unchanged despite eradication of H. pylori, but which regressed following radiotherapy. A 46-year-old asymptomatic man was admitted to hospital for treatment of MALT lymphoma involving the papilla of Vater. Duodenal endoscopy showed multiple granules around the major ampulla, and biopsies revealed mucosal proliferation of centrocyte-like cells, lymphoepithelial lesions, hyperplastic lymphoid follicles and plasmacytic differentiation. The lymphoma cells were positive for B-cell but negative for T-cell markers, and expressed Bcl-2 but showed no immunoreactivity for CD5, CD10 and cyclin D, consistent with MALT lymphoma. The patient was successfully treated with triple therapy of lansoprazole, amoxicillin and clarithromycin for 1 week for coexisting H. pylori infection in the stomach, but the lymphoma lesions remained unchanged. Then, involved-field irradiation was applied at a total dose of 30 Gy delivered in 1.5 Gy fractions without any adverse events. Six months later, repeat endoscopy revealed disappearance of the granular lesions and lack of lymphoma cells in biopsy specimens. Four years after the commencement of radiotherapy, the patient is still in complete remission. Radiotherapy seems a safe and effective treatment modality for low-grade MALT lymphoma of the ampulla of Vater.

Ampulla of Vater↗

Elevated levels of chemokines in esophageal mucosa of patients with reflux esophagitis.

OBJECTIVE: Chemokines play a key role in the pathogenesis of various inflammatory conditions. However, there is little information on their profile in reflux esophagitis (RE). We sought to study esophageal mucosa levels of chemokines in RE. METHODS: A total of 32 outpatients with RE and 13 normal controls were studied. Endoscopic severity of RE was classified according to the Los Angeles grading system. Paired biopsy specimens were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of mucosal levels of interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES), and IL-1 beta by enzyme linked immunosorbent assays, while the other was formalin-fixed for histopathological evaluation. RESULTS: IL-8, MCP-1, and RANTES levels were significantly higher in esophageal mucosa of RE patients than those of the controls. IL-8 levels correlated significantly with the endoscopic severity of RE. Basal zone hyperplasia and papillary elongation, histopathological hallmarks of RE, were both associated with higher levels of IL-8 and MCP-1. The presence of intraepithelial neutrophils and eosinophils, which also indicate RE, was associated with high levels of IL-8 and RANTES, respectively. There were no significant differences in IL-1 beta levels between the RE and control groups, but IL-1 beta levels correlated significantly with the IL-8 production. Again, the IL-8 levels were significantly decreased after lansoprazole treatment. CONCLUSION: Our results indicate that chemokines produced locally in the esophageal mucosa may be involved in the development and progression of RE.

Adult↗

Relationship between expression of O6-methylguanine-DNA methyltransferase, glutathione-S-transferase pi in glioblastoma and the survival of the patients treated with nimustine hydrochloride: an immunohistochemical analysis.

Drug resistance is one of the important factors that determine tumor response to chemotherapy. Several candidates for resistance to various chemotherapeutic agents have been elucidated. O6-methylguanine-DNA methyltransferase (MGMT) removes methylation damage induced by nitrosourea from the O6 position of DNA guanines before cell injury. Glutathione-S-transferase (GST) pi is also involved in nitrosourea resistance. We examined the expression of MGMT and GST pi in 18 glioblastomas (GBM) using immunohistochemistry and compared the results with patients' survival after administration of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-based chemotherapy. According to the Kaplan-Meier's method, although median progression free survival (PFS) of eight patients whose tumors retained high MGMT (3+ approximately 2+), and 10 patients whose tumors showed low MGMT expression (1+ approximately 0) were nine and 15 months, respectively (p = 0.09), median overall survival (OS) of the two groups were 12 and 22 months, respectively, which were significantly different (p = 0.01). GST pi expression in GBM was not a prognostic factor. It is suggested that GBM with strong staining of MGMT activity may show more resistance to ACNU-based chemotherapy compared to that with low MGMT. The simple immunohistochemical analysis of MGMT in GBM can be a useful method to determine whether ACNU or another treatment regimen should be recommended.

Adult↗

Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers.

Activating mutations in the BRAF kinase gene have recently been reported in human cancers. The aim of the present study was to determine the frequency of BRAF mutations in thyroid cancer and their correlation with clinicopathological parameters. We analyzed exons 11 and 15 of BRAF gene in six human thyroid cancer cell lines and 207 paraffin-embedded thyroid tumor tissues. A missense mutation was found at T1796A (V599E) in exon 15 in four of the six cell lines and 51 of 207 thyroid tumors (24.6%; 0 of 20 follicular adenoma, 0 of 11 follicular carcinoma, 49 of 170 papillary carcinomas, and 2 of 6 undifferentiated carcinomas). Activation of MAPK kinase-MAPK pathway was observed in cell lines harboring BRAF mutation. BRAF mutation-associated enhanced cell growth was suppressed by MAPK kinase inhibitor, U0126. Examination of 126 patients with papillary thyroid cancer showed that BRAF mutation correlated significantly with distant metastasis (P = 0.033) and clinical stage (P = 0.049). Our results indicate that activating mutation of BRAF gene could be a potentially useful marker of prognosis of patients with advanced thyroid cancers.

Adult↗

[Clinical study of sarcomatoid renal cell carcinoma].

Patients with sarcomatoid renal cell carcinoma are rare and have poor survival. We evaluated 14 patients who had renal cell carcinoma with a sarcomatoid component between 1982 and 2000. There were 9 men and 5 women with a median age of 59.5 years (range 32 to 77). Seven patients had a tumor on the right side and 7 on the left side. Thirteen patients had some symptoms and 11 had metastases at the initial visit. Most of them were stage T4 and high nuclear grade cancer and showed elevated acute phase reactants. There were 7 patients followed by interferon therapy, and the cause-specific 5-year survival rate was less than 10%. We confirmed that renal cell carcinoma with a sarcomatoid component often showed local invasion, distant metastasis and poor prognosis.

Adult↗

Expression of cyclooxygenase-2 in renal cell carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, expression of matrix metalloproteinase-2, and survival.

PURPOSE: Cyclooxygenase (COX)-2 plays an important role in tumor cell proliferation, resistance to apoptosis, angiogenesis, and invasion in various malignant tumors. However, the relationships between COX-2 expression and these biological processes, clinicopathological features, and survival rate in patients with renal cell carcinoma are not clear. EXPERIMENTAL DESIGN: Tumor sections surgically removed from 131 patients were examined for COX-2 expression by immunohistochemistry. We also examined Ki-67 labeling index, apoptotic index, microvessel density, and matrix metalloproteinase (MMP)-2 expression, and correlated COX-2 expression with various clinicopathological features and survival. RESULTS: Of 131 sections, 70 (53.4%) were positive for COX-2 expression. COX-2 expression was associated significantly with various clinicopathological features, and correlated with the Ki-67 labeling index, microvessel density, and MMP-2 expression (P < 0.01), but not with the apoptotic index (P = 0.054). COX-2 expression was also identified as an independent risk factor for large tumor size (>7 cm) in multivariate logistic regression model. COX proportional hazards analysis showed that distant metastasis and high T stage were independent prognostic factors [odds ratio (OR), 9.41; 95% confidence interval (CI), 2.16-41.11; P < 0.01 and OR, 5.19; 95% CI, 1.02-26.54; P = 0.048, respectively), whereas COX-2 expression was not (OR, 1.46; 95% CI, 0.24-9.00; P = 0.68). CONCLUSION: COX-2 expression in patients with renal cell carcinoma is associated with several clinicopathological factors, and appeared to play an important role in tumor cell proliferation and MMP-2 expression, but is not a significant prognostic factor.

Adult↗

Human T-cell leukemia virus type I Tax transactivates the matrix metalloproteinase-9 gene: potential role in mediating adult T-cell leukemia invasiveness.

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL) and of tropical spastic paraparesis/HTLV-I-associated myelopathy. Infiltration of various tissues by circulating leukemic cells is a characteristic of ATL. Matrix metalloproteinases (MMPs), which mediate the degradation of the basement membrane and extracellular matrix, play an important role in metastasis and tumor cell dissemination. The aim of this study was to explore whether expression of MMP-2 and MMP-9 was deregulated by HTLV-I infection. The data showed that HTLV-I-infected T-cell lines expressed high levels of MMP-9 compared with uninfected T-cell lines. In contrast, the levels of the related MMP-2 were not significantly altered by HTLV-I infection. In addition, the elevated expression of MMP-9 in HTLV-I-infected cells was attributable to the action of the viral transactivator protein Tax. The results show that Tax can activate the MMP-9 promoter and induce MMP-9 expression in T cells, indicating that the constitutive expression of MMP-9 in virus-infected cell lines is at least in part mediated by Tax. Activation of the MMP-9 promoter by Tax occurs mainly through the action of NF-kappaB and SP-1. The biologic significance of these observations was validated by the following 2 findings: MMP-9 expression was increased in primary ATL cells, and plasma MMP-9 levels were elevated in ATL patients. In addition, plasma levels of MMP-9 correlated with organ involvement in ATL patients. Together these data suggest that overexpression of MMP-9 in HTLV-I- infected cells may be in part responsible for the invasiveness of ATL cells.

Enzyme Induction↗

Transient decrease in gap junction expression during compensatory renal growth in mice.

OBJECTIVES: To examine gap junction expression during compensatory renal growth. Compensatory renal growth is a normal response to the removal of renal cells. Gap junctional intercellular communication plays important roles in homeostatic regulation, differentiation, and synchronization of cellular electronic and metabolic functions. METHODS: The right ureters of 5-week-old ddy mice were dorsally incised and unilaterally obstructed, and the animals were killed at varying intervals. The control group underwent a sham operation. Freeze-fractured kidney tissue samples were studied using electron microscopy. The amount of proliferative cell nuclear antigen-positive cells and connexin 43 (Cx43) protein was studied by immunohistochemistry and Western blotting, respectively. RESULTS: Proliferative cell nuclear antigen-positive cells in the renal tubules increased on days 1 and 2 after surgery that obstructed the ureter, and decreased to normal levels by day 14. The number of gap junctions significantly decreased on days 1 and 2, and then gradually increased to normal levels from days 3 to 14 after surgery. The amount of Cx43 protein in the renal tubules decreased until day 2 and recovered to the same level as that of the control by day 14 after surgery. Significantly, a hyperphosphorylated band of Cx43 in the control kidney was not detected in the operated kidney. CONCLUSIONS: These data suggest that the gap junctional intercellular communication of renal tubular cells during compensatory renal growth after unilateral ureteral obstruction could be temporarily reduced concomitant with a decrease of the expression of a phosphorylated Cx43 protein in renal cortical tubular cells after unilateral ureteral obstruction of the contralateral kidney.

Adaptation, Physiological↗

Renal cell carcinoma with solitary metachronous metastasis to the urinary bladder.

We report a case of renal cell carcinoma with solitary metachronous metastasis to the urinary bladder occurring 6 years after radical nephrectomy. The patient was treated with partial cystectomy and survived for 60 months. Other cases like this one were reviewed in published reports, and the 3-year survival rate for patients with this type of cancer with solitary metastasis to the urinary bladder was found to be 80%. The follow-up duration of our case was the longest in the published studies. We suggest that urinary bladder metastasis of renal cell carcinoma should be resected because no effective treatment for metastatic renal cell carcinoma is available. A good prognosis may be expected, especially in patients with solitary metastasis to the urinary bladder.

Aged↗

Mesenchymal chondrosarcoma of the temporal bone.

A 64-year-old patient with mesenchymal chondrosarcoma of the temporal bone is described. CT and MRI showed an extensive mass with calcification involving the temporal bone and extending into the middle cranial fossa and nasopharynx. The tumor was ill-defined from surrounding normal bone, and a subtotal petrosectomy was carried out. The nasopharyngeal extension was removed secondarily using an endoscope. The clinical and diagnostic aspects and management of this rare lesion are discussed.

Bone Neoplasms↗

Aberrant localization of beta-catenin correlates with overexpression of its target gene in human papillary thyroid cancer.

Alterations of the Wnt/beta-catenin signaling pathway are known to occur in mutations of the component genes such as APC, Axin, and beta-catenin, and play a pathogenetic role in tumorigenesis. Activated Wnt signaling stabilizes beta-catenin, which associates with T cell factor, resulting in transactivation of the downstream target genes including c-myc and cyclin D1. To investigate the involvement of Wnt/beta-catenin signaling pathway in thyroid tumorigenesis, we analyzed its activation and localization in 5 human thyroid cancer cell lines and 132 thyroid tumor tissue samples. Dislocalization of beta-catenin was observed in all cell lines. Constitutive activation of T cell factor in two of four thyroid cancer cell lines was observed using reporter gene assay. Furthermore, high expression levels of c-Myc and cyclin D1 were observed in cell lines that showed cytoplasmic or nuclear accumulation of beta-catenin. In 132 paraffin-embedded thyroid carcinoma tissue samples, cytoplasmic beta-catenin was immunohistochemically observed in 52 out of 78 (67%) papillary thyroid cancers, but only in 3 of 34 (9%) follicular adenomas and 5 of 20 (25%) follicular cancers. Cytoplasmic localization of beta-catenin significantly correlated with overexpression of cyclin D1 in papillary carcinomas. Our results suggest that aberrant activation of Wnt/beta-catenin signaling is strongly involved in thyroid tumorigenesis.

Adenocarcinoma, Follicular↗

Giant cell interstitial pneumonia in a 15-year-old boy.

Giant cell interstitial pneumonia (GIP) is a very uncommon respiratory disease. We report a juvenile patient with GIP aged 15 years. Although he has a negative past history of direct exposure to hard metals, we could not exclude possible exposure in very small amounts through his parents. Microscopic examination of lung biopsy specimen obtained by video-assisted thoracoscopy revealed marked cellular interstitial infiltrates and prominent intraalveolar macrophages as well as giant cells showing cellular cannibalism. Analysis of the biopsied lung tissue for cobalt and tungsten was negative. Clinical symptoms, laboratory, and radiological findings improved markedly after treatment with corticosteroids. To our knowledge, only eleven cases of GIP have been reported in Japan. Although possible exposure to hard metals was identified in 9 of the 11 reported cases, there is no clear dose-dependent relationship with onset and prognosis. The average age at onset was 46.2+/-15.0 years. Our patient is the youngest case of GIP reported in the world.

Adolescent↗

Amyloid a protein amyloidosis in a patient with plasma cell dyscrasia.

We report a 59-year-old man who was found to have plasma cell dyscrasia and amyloid A protein (AA) amyloidosis during the follow-up period of chronic inactive hepatitis C. Clinical manifestations such as swallowing disturbance, proteinuria and leg edema were associated with AA amyloid deposits in his tongue and kidneys. Although the relationship between these two diseases remains to be determined, the ability of peripheral blood mononuclear cells to degradate serum amyloid A protein was apparently reduced in this patient, compared with normal volunteers. This would, in part, account for the AA amyloid deposition in this patient.

Amyloidosis↗

Peripheral T-cell lymphoma with a nodular growth pattern.

Peripheral T-cell lymphomas (PTCL) with nodular growth patterns are very rare, with only 17 cases reported previously. Here, we report a case of PTCL with a nodular growth pattern. The patient was an 81-year-old Japanese woman who complained of malaise, fever and generalized lymph node swelling. Cervical lymph node biopsy was performed, and histological examination revealed proliferation of medium- to large-sized atypical lymphoid cells with indented to irregular nuclei, distinct nucleoli and clear cytoplasm. The nodular growth pattern of the lymphoma cells was obvious. On immunohistochemistry, the atypical lymphoid cells proved to be of T-helper cell origin (CD2+CD3CD4+CD5+CD7+ CD8-CD10-CD25-CD30-CD57-). Polymerase chain reaction analysis of the T-cell receptor gamma-chain revealed a monoclonal rearrangement band. This unusual growth pattern should be distinguished among PTCL, as such cases could be confused with reactive nodular hyperplasia, nodular lymphoma, mantle cell lymphoma and marginal zone lymphoma with nodular colonization.

Aged↗