Search PubMed⌕ Search

Biomedical subjects

Y Ohtsuki

Publications and source records attributed to Y Ohtsuki.

At least 109 records · Page 6Linked to original sources

[Subependymal giant cell astrocytoma associated with tuberous sclerosis exhibiting rapid regrowth after 17 years: a case report].

A 17-year-follow-up case of subependymal giant cell astrocytoma (SGCA) is reported. In 1979, when aged 28 years, the patient first presented obstructive hydrocephalus caused by a tumor in the right lateral ventricle close to the foramen of Monro. It was partially removed by a transcallosal approach. Pathological examinations showed gemistocytic astrocytoma or SGCA associated with tuberous sclerosis. A ventriculo-peritoneal shunt was carried out and 36Gy of radiation therapy was administered. Eight months later, the patient suffered from an intraventricular hemorrhage originating from SGCA, but he responded to conservative therapy. He was followed-up by CT scans over 17 years. In 1996, because of rapid regrowth of the tumor, total removal was performed by a transcortical approach via the right frontal horn. The pathological diagnosis was SGCA. The greater part of the recurrent tumor was composed of blood vessels. The tumor cells were grouped into two morphological types, large cells and spindle cells. We compared the tumor in 1996 with that in 1979, each revealing immunohistochemical stainability for glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE) and S-100 protein (S-100). The large cells in 1979 were negative for GFAP, NSE and S-100, but were positive for NSE and S-100 in 1996. The spindle cells in 1979 were positive for GFAP, NSE and S-100, but were negative for GFAP in 1996. The pathological origin of SGCA remains a subject of controversy. These results suggest that the origin of SGCA could be variably differentiated cells like the germinal matrix cells.

Biomarkers, Tumor↗

Elevation of cytokeratin 19 fragment in patients with interstitial pneumonia associated with polymyositis/dermatomyositis.

OBJECTIVE: Cytokeratin 19 fragment (CK19) levels in serum have been documented as a useful tumor marker for lung cancer. We hypothesize that CK19 may increase in serum in patients with interstitial pneumonia associated with polymyositis/dermatomyositis (PM/DM) and CK19 might be a useful variable to evaluate the activity of lung injury. METHODS: 1. We measured CK19 in sera in 15 patients diagnosed with PM/DM; 6 had nonspecific interstitial pneumonia (NIP), 4 had acute interstitial pneumonia (AIP), and 5 had no pulmonary involvement. We also measured CK19 in 10 healthy nonsmokers serving as a control group. 2. We evaluated the correlation between CK19 level and individual clinical course in patients with pulmonary involvement associated with PM/DM. RESULTS: CK19 levels in sera of patients with NIP associated with PM/DM were significantly higher versus patients with PM/DM without interstitial pneumonia and healthy nonsmokers. CK19 levels in sera in patients with AIP associated with PM/DM were significantly higher compared with the other groups. CK19 values in sera changed according to the progression or improvement of interstitial pneumonia. Immunohistochemical studies using pulmonary tissues obtained at autopsy from patients with AIP associated with PM/DM revealed that the hyaline membrane was mostly stained by anti-human cytokeratin 19 monoclonal antibody as well as the strong positivity of proliferating type II pneumocytes. CONCLUSION: These results suggest that the measurement of CK19 was a useful variable to evaluate the activity of lung injury in interstitial pneumonia associated with PM/DM.

Adult↗

[Solitary fibrous tumor of the pleura with elevated high-molecular-weight insulin-like growth factor II and hypoglycemia].

Recurrent hypoglycemia occurred in a 58-year-old woman with a solitary fibrous tumor of the pleura and exhibiting CD34 immunopositivity. During episodes of hypoglycemia, serum high-molecular-weight insulin-like growth factor II (big IGF-II) was elevated. After removal of the tumor containing IGF-II, the hypoglycemia and serum big IGF-II disappeared. This was followed by an increase in normal IGF-II. We speculate that the primary cause of hypoglycemia in this patient was the presence of big IGF-II produced by the solitary fibrous tumor of the pleura. To our knowledge, the presence of this type of IGF-II in CD34+ solitary fibrous tumors of the pleura has not been described to date in the literature.

Female↗

An experimental application of gene therapy for human retinoblastoma.

PURPOSE: The purpose was to determine the potential of gene therapy for retinoblastoma using transfer of the herpes simplex virus thymidine kinase (HSV-TK) gene into retinoblastoma cells (Y79 cell line). METHODS: A retrovirus-packaging cell line PA317 was electroporated with a retroviral vector plasmid bearing HSV-TK and neomycin-resistance genes to produce a PA317-TK cell line releasing a replication-defective vector bearing both genes. Y79 was transduced by exposure to transmissible virus-containing medium from PA317-TK, and new clones of Y79 containing the HSV-TK gene (Y79-TK) were established. Sensitivity to ganciclovir (GCV) and acyclovir (ACV) was investigated in Y79 and Y79-TK and the effect of HSV-TK-positive cells on negative cells ("bystander effect") was determined in vitro. The effect of antitumorigenesis in a nude mouse system was also investigated. RESULTS: There were no differences in the growth pattern or the morphology between Y79 and Y79-TK. Y79-TK was more sensitive to GCV and ACV than was Y79. The cytotoxicity of Y79-TK was dose dependent. An obvious "bystander effect" was present with the addition of GCV. In vivo studies confirmed the ability of GCV to kill Y79-TK. CONCLUSIONS: In this study a model is proposed for the introduction of a drug-sensitivity gene into Y79 and the possibility is raised of treating retinoblastoma with gene therapy. The results suggest that the transfer of the HSV-TK gene into Y79 followed by the administration of GCV could serve as a model for gene therapy for retinoblastoma.

Acyclovir↗

Positive correlation between p27Kip1 expression and progression of human esophageal squamous cell carcinoma.

p27Kip1, one of the cyclin-dependent kinase (CDK) inhibitors (CDKIs), blocks progression from G1 to S phase by binding cyclin D1-CDK4 and/or cyclin E-CDK2 and inhibiting their activities. Reflecting the function of p27 as a CDKI in vitro, a reduced expression of protein p27 has recently been reported to be associated with tumor aggressiveness in some types of human cancers. In the present study, we examined the relationships between immunohistochemically detected expression of p27, cyclin D1, cyclin E proteins and clinicopathological findings in 77 patients with esophageal squamous cell carcinoma (SCC). Using specific monoclonal antibodies to p27, cyclin DI and cyclin E proteins, positive immunostaining in the nuclei was observed in 32.5% (25/77), 27.3% (21177) and 29.6% (21/71) of patients, respectively. There were no statistically significant relationships among the expressions of these 3 proteins. Using the Kaplan-Meier's method, p27 and cyclin D1 expressions were found to be independently associated with poor prognosis. When all parameters were combined into a multivariate regression analysis using the Cox model, the expressions of p27 and cyclin D1 retained a predictive value for survival. In contrast to former reports supporting a tumor-suppressive function of p27, our results suggest that altered expression of p27 and cyclin D1 may be associated with the progression of human esophageal SCC, in which cyclin E may well not play any central role.

Adult↗

Papid Growing Fibroadenoma in an Adlescent.

INTRODUCTION: We report a case of rapidly growing fibroadenoma. PATIENT: A 13-year-old girl consulted the outpatient clinic regarding a left breast mass. The mass was diagnosed as fibroadenoma by clinical examinations, and the patient was carefully monitored. The mass enlarged rapidly with each menses and showed a 50% increase in volume four months later. Lumpectomy was performed. The tumor was histologically diagnosed as fibroadenoma organized type and many glandular epithelial cells had positive immunohistochemical staining for anti-estrogen receptor antibody in the nuclei. CONCLUSION: The estrogen sensitivity of the tumor could account for the rapidgrowth.

Journal Article↗

Chromosomal mapping and expression of the human B120 gene.

We previously reported a novel human cDNA, designated B120, containing a CAG repeat length polymorphism and many repeat units, loosely identified as YXQQP which is found in several human RNA binding proteins. In the present study, the B120 gene was mapped to human chromosome 1p35-36.1 by fluorescence in situ hybridization (FISH). Several human disorders, including that of Schnyder crystalline corneal dystrophy, have been mapped to this region by genetic linkage. Schnyder crystalline corneal dystrophy is thought to be a primary abnormality of corneal lipid metabolism, resulting in opacification secondary to lipid accumulation. In order to examine the function of B120, we introduced B120 cDNA with an expression vector into various cell lines including Cos1, C3H/10T1/2 and NIH/3T3 cells. These transfected cells exhibited small cytoplasmic spherical bodies. The cytoplasmic bodies appeared to be fat droplets on electron microscopy and histochemical staining. These findings suggested that B120 gene expression is associated with lipid metabolism, and that overexpression of B120 may result in lipid deposition in various cells, including those of fibroblastic cell lines. Since the cornea is composed of fibroblastic cells, overfunction of B120 could be related to the pathogenesis of Schnyder crystalline corneal dystrophy.

3T3 Cells↗

Overexpression of c-met proto-oncogene associated with chromophilic renal cell carcinoma with papillary growth.

Various genetic changes are involved in human renal cell carcinomas (RCCs). However, the molecular events related to other cytomorphological subtypes of RCC are not well known, apart from the relationship between the von Hippel-Lindau tumour suppressor gene and clear cell subtype RCC. We examined the overexpression of several growth factor receptors immunohistochemically and analyzed their relationship to the cytomorphological characters in 120 cases of RCCs. These receptors included c-met proto-oncogene product (c-MET), epidermal growth factor receptor (EGFR) and transforming growth factor beta receptor II (TGFbetaR). The overexpression of c-MET was detected in all cases (20/20) of the tubulo-papillary growth type and 78.3% (18/23) of chromophilic cell subtype, resulting in a very significant associations between c-MET overexpression and tubulo-papillary growth RCCs (P<0.0001), c-MET and chromophilic subtype RCCs (P<0.0001), and c-MET and EGFR (P<0.0001). EGFR overexpression was significantly associated with the compact growth RCCs (49/89, P<0.0001), clear cell subtype RCCs (P<0.005) and the overexpression of TGFbetaR (P<0.0001). These results strongly suggest a close correlation between the overexpression of c-MET and development of the chromophilic subtype of RCC with papillary growth pattern. EGFR expression is closely related to the pathogenesis of the clear cell subtype of RCC with compact growth pattern. The overexpression of c-MET, EGFR, and TGFbetaR may have roles that are individually significant in the morphogenesis of RCC.

Adult↗

Osteoclast-like giant cell tumor of the pancreas with metastases to gallbladder and lymph nodes. A case report.

Osteoclast-like giant cell tumor of the pancreas (OGTP) is a rare neoplasm, of which the histogenesis is still controversial. Here we report a case of OGTP involving the head of the pancreas in a 71-year-old woman with metastases to the gallbladder and lymph nodes. The primary and metastatic tumors had identical histopathological, immunohistochemical, ultrastructural and molecular biological features. Microscopically, the tumors were characterized by atypical, often pleomorphic mononuclear cells associated with the proliferation of benign-appearing osteoclast-like giant cells (OGCs). Electron microscopic observation provided ultrastructural evidence of epithelial differentiation of the mononuclear cells, including microvilli and desmosomes, which was not obtained for OGCs. On immunohistochemical study, OGCs stained for CD68 (KP-1), LCA and HAM56, whereas mononuclear cells only reacted with PCNA. These findings clearly suggest that mononuclear cells are capable of differentiation and proliferation and may have been the only true tumor cells in this neoplasm, and that OGCs may have been a paraneoplastic product of this rare tumor. On examination of DNA from dewaxed sections of the tumor, we found no p53 mutation in the tumor tissue, but found two K-ras mutations in codon 12; this pattern of mutation commonly occurs in pancreatic carcinoma, indicating a somewhat genetic relationship of OGTP to pancreatic carcinoma. Although OGTP often has a favorable prognosis, the outcome in the present case was poor due to early tumor spread, with less than two years postoperative survival.

Aged↗

Malignant granular cell tumor: report of a case and review of the literature.

The histological, immunohistochemical and electron microscopic features of a rare malignant granular cell tumor (GCT) arising in the left radial nerve of a 54-year-old man are reported. Despite a lack of local recurrence following extirpation, the tumor metastasized to the skull five years later. Light-microscopically, both primary and metastatic tumors consisted of markedly atypical or pleomorphic neoplastic cells with abundant cytoplasm containing diastase-resistant periodic acid Schiff reaction-positive granules. These tumor cells were arranged in a sheet-like pattern with mitotic figures including atypical ones, and were frequently immunopositive for proliferating cell nuclear antigen and c-MET, the c-met proto-oncogene product. These findings reflect high-grade malignancy of the present tumor. In addition, the tumor cells were positive for S-100 protein and neuron-specific enolase. Ultrastructurally, a large number of intracytoplasmic granules featuring secondary lysosomes as well as long interdigitating cytoplasmic processes, intercellular intermediate junctions, discontinuous basal lamina-like structures, and stromal long-spacing collagen were observed. These findings indicated schwannian differentiation of the present tumor. In addition, based on a review of previously reported cases, the overall clinicopathological characteristics of malignant GCT were summarized.

Cell Nucleus↗

Overexpression of p53 protein in interstitial lung diseases.

The p53 gene is well known as a tumour suppressor gene. In addition, the mutated p53 gene is detected in a variety of human cancers including lung cancer, and is considered as an oncogene. Lung cancer is also frequently associated with interstitial lung diseases. Therefore, it may be possible to hypothesize that there might be some abnormality of p53 gene in interstitial lung diseases. This work examined the relationship between the p53 protein and gene in lung tissues of 28 patients with interstitial lung diseases. Among 28 patients, 13 cases were pathologically diagnosed to have usual interstitial pneumonia (UIP), 12 cases were diagnosed as having collagen vascular lung diseases, and three cases were diagnosed to have a non-specific interstitial pneumonia. Twenty-three tissue samples were obtained by open lung biopsy and five samples were taken by autopsy. Paraffin-embedded tissues were treated by microwave, and stained with an anti-p53 antibody (DO7) by the Avidin-Biotin-Peroxidase (ABC) method. In selected patients, mutations in exons 5-8 of the p53 gene were also examined by single-strand conformation polymorphism (SSCP) analysis and DNA sequence. In addition, the presence of anti-p53 antibodies in patients' sera was screened for by ELISA. Fifteen samples (53.6%) revealed overexpression of the p53 protein in the nuclei of alveolar epithelial cells. However, SSCP or sequence analysis, which was performed in 13 tissues, showed no mutations in exons 5-8 of the p53 gene. In conclusion, p53 proteins were overexpressed in interstitial lung diseases, and the expressed p53 protein was considered to be wild-type. This wild-type p53 protein may play a role in blocking the transformation of proliferative epithelial cells.

Adult↗

Measurement of hepatocyte growth factor in serum and bronchoalveolar lavage fluid in patients with pulmonary fibrosis.

The present study evaluated the clinical significance of hepatocyte growth factor (HGF) in patients with pulmonary fibrosis. Twenty-one patients with a diagnosis of pulmonary fibrosis [14 with idiopathic pulmonary fibrosis (IPF) and seven with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD]) and 21 normal subjects as control were studied. HGF levels in sera of patients with pulmonary fibrosis (0.34 +/- 0.02 ng ml-1) were elevated significantly as compared with normal subjects (0.21 +/- 0.01 ng ml-1) (P < 0.0001). HGF/albumin levels in broncho-alveolar lavage fluid (BALF) of patients with pulmonary fibrosis (72 +/- 17 ng g-1 albumin) were also significantly elevated as compared with normal subjects (under the detection limit) (P < 0.01). HGF levels in sera correlated significantly with elastase levels in sera and C-reactive protein, and correlated negatively with PaO2. HGF levels in sera were significantly higher in smokers with pulmonary fibrosis (0.42 +/- 0.03 ng ml-1) as compared with non-smokers with pulmonary fibrosis (0.29 +/- 0.03 ng ml-1) (P < 0.005). HGF/albumin levels in BALF correlated significantly with elastase/albumin levels in BALF, lactate dehydrogenase/albumin in BALF, Immunoglobulin A/albumin in BALF, total cell count/albumin in BALF, total number of alveolar macrophage/albumin in BALF, total number of neutrophil/albumin in BALF, CEA/albumin in BALF, CA19-9/albumin in BALF, and SCC/albumin in BALF. These results suggest that following lung injury, HGF may be a mediator involved in the repair which leads to pulmonary fibrosis.

Adult↗

Prognostic significance of cyclin E and p53 protein overexpression in carcinoma of the renal pelvis and ureter.

Cyclin E gene alteration in the cell cycle plays an important role in carcinogenesis, while p53 protein affects different phase checkpoint pathways by activating p21WAF1/CIP1 in the normal cell cycle. We immunohistochemically examined the expression of cyclin E and p53 proteins in 121 patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter to determine their significance for tumour behaviour and patient prognosis. Cyclin E and p53 immunostaining of the nucleus was observed in 36 tumours (29.8%) and 35 tumours (28.9%) respectively. A significant percentage, 69.4% (25 out of 36 tumours), of the cyclin E-positive tumours exhibited simultaneous labelling for p53 (P < 0.05). Mirror-section technique was performed in five selected double-positive tumours to identify cancer cells that were nuclei positive for both cyclin E and p53. The prevalence of cases simultaneously exhibiting both cyclin E and p53 immunostaining was higher in the high-grade tumours (P < 0.01) than in the other types of tumours. Patients with TCCs coexpressing cyclin E and p53 had a significantly poorer prognosis than those expressing neither cyclin E nor p53 (P < 0.001). These in vivo findings provide evidence for cyclin E protein overexpression in TCCs intimately associated with p53 alteration and suggest that simultaneous overexpression of both cyclin E and p53 is related to tumour behaviour and poor prognosis.

Aged↗

Cyclin D1 overexpression related to retinoblastoma protein expression as a prognostic marker in human oesophageal squamous cell carcinoma.

The relationship between aberrant expression of cyclin D1 and retinoblastoma (RB) protein and clinicopathological factors was investigated in 80 patients with oesophageal SCC using immunohistochemical analyses. Heterogeneous staining of cancer cell nuclei with antibody to cyclin D1 was found in 31.3% of patients (25 out of 80 patients). Nuclear staining of cancer cells with anti-RB antibody was homogeneous in 10.0% (8 out of 80 patients) and heterogeneous in 58.8% (47 out of 80 patients). Among cases with homogeneous staining for RB protein, 75% (six out of eight patients) exhibited simultaneous positivity for cyclin D1 (P < 0.05). No significant relationship was found between cyclin D1 or RB protein expression and various clinicopathological parameters. The prognosis of patients with cyclin D1-positive tumours was significantly poorer than that of the other patients (P < 0.01). In addition, when patients with cyclin D1-positive and -negative tumours were stratified according to presence or absence of lymph node metastasis and RB status, the cumulative survival rates in the cyclin D1-positive groups were significantly lower for patients without lymph node metastasis (P < 0.01) and for patients whose tumours were positive for RB (P< 0.0001). These findings suggest the possibility that cyclin D1 positivity is a useful prognostic marker related to lymph node metastasis and RB protein expression in human oesophageal SCC, in addition to clinicopathological factors.

Adult↗

High-risk human papillomavirus infection and overexpression of p53 protein in squamous cell carcinoma of the esophagus from Japan.

The present study was undertaken in order to investigate the possible involvement of high-risk human papillomavirus (HPV; types 16 and 18) or the overexpression of p53 protein in 123 Japanese patients with esophageal squamous cell carcinoma (SCC) from five different institutions. We detected HPV DNA in 30.1% (37/123) by in situ hybridization (ISH). Of these 123 cases, HPV type 16 was detected in 22 cases and HPV type 18 in 23 cases. In addition, HPV types 16 and 18 were detected simultaneously in eight cases. We found an almost similar incidence of HPV infection at five different places in Japan. Then, among these patients, 24 fresh tumor samples were also examined for screening the presence of HPV DNA using dot blot hybridization (DBH) and polymerase chain reaction (PCR). We detected HPV DNA in 20.8% (5/24) by DBH and in 12.5% (3/24) by PCR. P53 protein overexpression was found in 34.1% (43/123) by immunohistochemistry (IHC). Furthermore, in 43 cases from Kochi Medical School, the group positive for p53 antibody statistically showed worse survival rate than the group negative for both HPV DNA and p53 antibody. Judging from these results obtained in the present study, HPV infection and p53 overexpression are frequently detected and involved in the carcinogenesis of esophageal SCC in Japan. We also found that no significant geographical difference of both HPV infection and p53 overexpression of esophageal SCC was seemingly present in Japan.

Aged↗

Primary ovarian angiosarcoma: a case report and literature review.

Primary ovarian angiosarcoma is extremely rare. Only 16 cases have histologically been reported to date in the literature. A case of angiosarcoma arising in the right ovary of a 46-year-old female is presented. Grossly, the resected right ovary was completely replaced by a solid tumor mass, which revealed multiple necrotic and/or hemorrhagic foci. This case revealed the typical histological features of angiosarcoma with sinusoidal and solid patterns of anaplastic tumor cells. Immunohistochemically, tumor cells were strongly and diffusely positive for CD31 and CD34, in particular, along the cytoplasmic membrane of the tumor cells. Ultrastructurally, tumor cells possessed the intermediate junctions between tumor cells, discontinuous basal laminae attached to the irregularly shaped blood vessels and occasional cytoplasmic pinocytotic vesicles. These findings confirmed the case as being one of angiosarcoma of the ovary. The patient died 9 months after surgery as a result of developed multifocal brain metastases. A total of 17 cases reported as primary ovarian angiosarcoma, including this presented case, are clinicopathologically reviewed.

Antigens, CD34↗