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Y Ohtsuki

Publications and source records attributed to Y Ohtsuki.

At least 37 records · Page 2Linked to original sources
PubMed2001

T-cadherin (CDH13, H-cadherin) expression downregulated surfactant protein D in bronchioloalveolar cells.

T cadherin is a unique cadherin cell adhesion molecule that is anchored to the surface membrane through a glycosyl phosphatidyl inositol (GPI) moiety. In the present study, we postulated that T cadherin could regulate surfactant protein (SP)-D gene expression in human bronchioloalveolar type-II cells. We transfected A549 cells (human lung cancer cell line with alveolar type-II cell characteristics) with the T-cadherin expression vector. Both original and control plasmid-transfected A549 cells expressed SP-D; however, neither human nor murine T-cadherin-transfected A549 cells expressed SP-D mRNA. The downregulation of SP-D production in human T-cadherin-expressed A549 cells was also demonstrated using Western immunoblotting techniques. Control vector-transfected A549 cells showed a positive band of SP-D but not of T cadherin. In contrast, T-cadherin-transfected A549 cells, which expressed T-cadherin protein, did not produce SP-D. We further examined the relationship of T cadherin and SP-D expression in secondary pulmonary alveolar proteinosis associated with hematolymphoid malignancies. SP-D was detected in bronchioloalveolar type-II cells in alveolar proteinosis. However, little or no T-cadherin expression was detected in alveolar type-II cells in these patients. To our knowledge, this is the first report describing an effect of cadherin on SP production in bronchioloalveolar cells.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Reduced human mismatch repair protein expression in the development of precancerous skin lesions to squamous cell carcinoma.

Loss of human mismatch repair (hMSH2) gene function has been linked to hereditary non-polyposis colorectal cancer (HNPCC), Muir-Torre syndrome (MTS), and sporadic cancers, excluding skin cancers unrelated to MTS. We immunohistochemically examined 125 squamous cell carcinomas (SCCs) using a monoclonal antibody to the hMSH2 protein and compared the results with those for 106 precursor lesions of SCC, consisting of actinic keratosis (AK), Bowenoid type of actinic keratosis (BAK), and Bowen's disease (BOD). In contrast to the homogeneous immunoreactivity of proliferating cells composed of AK, BAK, and BOD, heterogeneous and diminished immunostaining to hMSH2 was observed in tumor cells of SCCs examined. In addition, two SCCs (2 of 125; 1.6%) at multiple loci exhibited a complete lack of immunoreaction to hMSH2. Immunohistochemical staining of hMSH2 was semiquantitatively scored as 0 (0% of total cells examined), 1 (less than 10%), 2 (10-50%), or 3 (more than 50%). Percentage preservation of and average score for hMSH2 expression in normal, AK, BAK, BOD, and SCC were 56% and 2.06, 100% and 2.80, 94% and 2.88, 83% and 2.78, 63% and 2.36, respectively. The percentage preservation of and average scores for hMSH2 in AK, BAK, and BOD were significantly higher than those in presumably normal skin (P<0.01). There were no significant differences in the percentage preservation of and average scores for hMSH2 between presumably normal skin and SCC. The score for hMSH2 expression was significantly correlated with score for sun exposure in presumably normal skin of each lesion (R=0.70). These findings for hMSH2 expression in precursor lesions and SCC suggest that promotion or activation of hMSH2 expression may be induced by the increased DNA damage caused by sun exposure and that diminished expression of it might occur according to the transformation from precancerous lesions to SCC.

Adult↗
PubMed2001

Expression of SMARCF1, a truncated form of SWI1, in neuroblastoma.

Previously we cloned and mapped a B120 gene to human chromosome 1p35-36.1 where possible suppressor genes for various neuroendocrine tumors including neuroblastoma have been mapped. Very recently, B120 was identified as a truncated form of p270, a putative human counterpart of SWI1. In the present study, expression of the B120 gene product was immunohistochemically investigated in 23 neuroblastomas. We also examined B120 expression in neural stem cells in developing brain and intact adrenal medulla. Four of 23 neuroblastomas strongly expressed B120 gene product in both cytoplasm and nucleus. The other neuroblastomas expressed B120 gene product in the nucleus; however, the intensity of staining was much weaker and equivalent to that in developing human brain stem cells in the subventricular region. B120 gene product was less strongly expressed in intact adrenal medulla. Subsequently, we performed loss of heterozygosity studies on 19 neuroblastomas using the polymorphic markers D1S195 and D1S511 located near the B120 gene. Loss of heterozygosity was observed in three of 19 tumors that abundantly expressed B120 protein. Furthermore, neuroblastoma cells were transfected with B120 expression vector. These transfected neuroblastoma cells adhered to each other and aggregated. Differential display experiments followed by reverse transcriptase-polymerase chain reaction and Northern blot analysis were performed and three molecules with altered expression in B120-transfected neuroblastoma cells were identified. One of three genes seemed to be a proliferation-related and cell cycle-related nucleolar protein, p120, encoding gene. We further characterized the genomic structure of B120. B120 appeared to be encoded by 17 exons in more than 20-kbp genomic DNA. The present findings contribute to understanding of the B120 gene, a truncated form of human SWII1, an approved term for which is SMARCF1, in normal cells and neuroblastomas.

Base Sequence↗
PubMed2001

Expression of cyclin E and cyclin D1 in non-small cell lung cancers.

The relationships between overexpression of cyclin D1 or cyclin E and clinicopathological factors were investigated in 157 patients with non-small cell lung cancers (NSCLCs) using immunohistochemical analysis. Fifty-eight cases of NSCLCs (58/157, 37%) showed the overexpression of cyclin D1, and 64 cases (64/157, 41%) were positive for cyclin E. Cyclin E and cyclin D1 were infrequently concurrently overexpressed (17/157, 10.8%). Overexpression of cyclin E was more frequently observed in squamous cell carcinoma (29/57, 51%) compared with that in adenocarcinoma (28/86, 33%) (P<0.05). In addition, overexpression of cyclin E was more frequently observed in poorly or moderately differentiated NSCLCs (52/103, 50%) than in well-differentiated ones (12/54, 22%) regardless of their histological types (P<0.01). On the contrary, there was no statistically significant relationship between cyclin D1 overexpression and histological types or grade of tumor differentiation. These findings suggest that expression of cyclin E was frequently independent of that of cyclin D1 and played some roles in the grade of tumor differentiation in NSCLCs.

Adult↗
PubMed2001

The point mutation in the promoter region and the single nucleotide polymorphism in exon 1 of the cytokeratin 19 gene in human lung cancer cell lines.

The CYFRA 21-1 assay which detects the cytokeratin 19 (CK19) fragment is widely used as a tumor marker for lung cancer. We previously suggested that the failure of PCR amplification of exon 1 is closely related to the inability of the expression of mRNA for CK19, and hypothesized that point mutations might exist within exon 1. In order to prove this, sequence analysis of the promoter region and exon 1 was performed in 14 human lung cancer cell lines. Among the 14 lung cancer cell lines evaluated, point mutations within the promoter region (at -99, G-->C) of the CK19 gene were demonstrated in two cell lines (Lu135 and HI1017). In addition, point mutations within exon 1 (at 90, T-->C, Ala-->Ala and at 179, G-->C, Gly-->Ala) were also demonstrated in three cell lines (LU135, HI1017, and LC2/AD). Point mutations within the promoter region of CK19 (at -99) and within exon 1 (at 179) were confirmed by analysis of digestion by specific restriction enzymes. Since the same point mutation within exon 1 (at 179) was observed in genomes of normal volunteers, this mutation was considered as a single nucleotide polymorphism. In contrast, there were no mutations within the promoter region of exon 1 in genomes of normal volunteers. After a computer search, it was demonstrated that several transcription factors bind to the sense primer sequence which was designed for amplification of exon 1. In addition, after point mutations within the promoter region occurred (at -99), new sequences appeared to which known transcription factors (AP2) bind. In conclusion, analysis of genomic DNA for CK19 suggested that expression of mRNA for CK19 was regulated by several transcription factors which bound to the specific sequence with the promoter region of the CK19 gene. It was also suggested that the mutation in the promoter region of the CK19 gene down-regulated the expression of mRNA for CK19.

Antigens, Neoplasm↗
PubMed2001

Helper T lymphocytes specific for cytokeratin 19 in patients with primary biliary cirrhosis.

We demonstrated the expression of cytokeratin 19 (CK19) in biliary cells in chronic non-suppurative destructive cholangitis (CNSDC) and hypothesized that this expression may have a correlation with the disease process in addition to cellular immunity which is believed to be involved in the pathogenesis of primary biliary cirrhosis (PBC). It is, therefore, important to clarify whether the destruction of bile ducts and biliary cells are caused by cellular immunity including helper T lymphocytes (Ths) and cytotoxic T lymphocytes (CTLs) specific for CK19. We examined the existence of helper T lymphocytes specific for CK19 in patients with PBC. As a result, the frequencies of responders having CK19 specific helper T lymphocytes and the stimulation index (SI) of the proliferative responses of peripheral blood mononuclear cells (PBMCs) were significantly higher and larger in patients with PBC compared with those of patients with chronic hepatitis C and normal subjects. The phenotype of proliferating PBMCs specific for CK19 were predominantly CD4+ Th1 cells. The Th1 response may help the induction of CTLs specific for CK19, and these CTLs could attack biliary cells.

Journal Article↗
PubMed2001

Expression of Bax and apoptosis-related proteins in human esophageal squamous cell carcinoma including dysplasia.

The rate of tumor growth depends on the balance between proliferation and death of tumor cells. It is known that Bax, caspase-3, and p53 proteins are death-promoting factors, whereas Bcl-2 protein is a death antagonist. We immunohistochemically examined the expression of Bax and apoptosis-related proteins such as caspase-3, p53, and Bcl-2 in 76 patients with human esophageal squamous cell carcinoma (SCC) including dysplasia to determine the relationship of expression of each protein to tumor behavior and patients' prognosis. No significant relationships in immunopositivity were found among these proteins in SCCs. Cytoplasmic Bax expression was exhibited in 63 cases of SCCs (82.9%). The apoptotic index of caspase-3-positive lesions was significantly higher than that of caspase-3-negative lesions in both dysplasia and SCC (P =.016, P =.012). On the other hand, the apoptotic index (1.18%) was significantly correlated with Bax overexpression in dysplasia (P =.006), but not in SCC lesions (P =.129). The patients with Bax-positive SCCs were found to have a poor prognosis by the Kaplan-Meier method (P =.043). These findings suggested that Bax expressed in dysplasia may play a role as an apoptotic factor, but that it may be functionally inactive in some cancerous lesions and thus not contribute to suppression of the tumor progression in some cases of human esophageal SCCs.

Apoptosis↗
PubMed2001

Anti-cytokeratin antibodies in sera of the patients with autoimmune hepatitis.

Antibodies to cytokeratin (CK) are found in some patients with autoimmune hepatitis (AIH). We hypothesized that serum antibodies to CK8, CK18 and CK19 may be formed in patients with AIH. We established an enzyme-linked immunosorbent assay (ELISA) to quantify anti-CK8, anti-CK18 and anti-CK19 antibodies in sera of patients with AIH. In addition, we quantified circulating CK8:anti-CK8 antibody as well as CK18:anti-CK18 antibody immune complexes in patients' sera, by an enzyme-linked immunosorbent assay (ELISA). Furthermore, to evaluate the expression of CK8, CK18 and CK19 in liver tissue, immunohistochemical stainings were performed. Significantly high levels of anti-CK8, anti-CK18 and anti-CK19 antibodies were demonstrated in patients with AIH compared with normal volunteers and patients with chronic active hepatitis C (CH-C). In addition, these antibodies were significantly decreased after steroid treatment. Levels of CK8:anti-CK8 and CK18:anti-CK18 immune complexes in sera of patients with AIH were significantly high compared with those of patients with CH-C and normal volunteers. Immunohistochemically, CK8 or CK18 were absent from some hepatocytes of AIH. CK19 was aberrantly expressed in periportal hepatocytes in patients with AIH, but not CH-C. This is the first study to quantify anti-CK8, anti-CK18, anti-CK19 antibodies and immune complexes in patients with AIH. The clinical significance of anti-CK antibodies and their immune complexes of AIH is also discussed.

Adolescent↗
PubMed2001

Tetrasomy 12 in ovarian tumors of thecoma-fibroma group: A fluorescence in situ hybridization analysis using paraffin sections.

Recent cytogenetical studies have indicated that trisomy 12 is a feature of ovarian tumors in the thecoma-fibroma group. Ten cases of these ovarian tumors were studied in total, including two thecomas, two fibrothecomas, four fibromas, one cellular fibroma and one fibrosarcoma, to clarify the relationship between polysomy 12 and proliferative activity in these tumors. Each formalin-fixed, paraffin-embedded tumor tissue was examined by fluorescence in situ hybridization to determine copy numbers of chromosome 12 and by immunohistochemical staining of Ki-67 for evaluation of tumor cell proliferation. Gains of trisomy 12 were found in seven of the 10 cases, and the percentage of cells with tetrasomy 12, but not that of cells with trisomy 12, was significantly and positively correlated with percentage of Ki-67-positive cells, but significantly and inversely correlated with patient age. These findings suggest that tetrasomy 12 is an age-related aberration of chromosome 12 in ovarian tumors of the thecoma-fibroma group, and that such tumors exhibit more active proliferation in younger patients.

Adult↗
PubMed2001

Primary intrapelvic seminoma in Klinefelter's syndrome.

Seminoma arising in patients with Klinefelter's syndrome is extremely rare; to our knowledge, only three cases have been reported in the English language literature. We report a case of intrapelvic seminoma in a 39-year-old man with Klinefelter's syndrome. Gross examination revealed that the tumor was a solid and irregular mass measuring 90 mm in diameter. The cut surfaces of this ill-defined tumor were yellow-white with necrotic foci. Histologically, the tumor cells were separated into lobules by branching, fibrous septa containing lymphocytes. In some parts of the tumor, a cord-like arrangement of tumor cells was present. Immunohistochemically, the tumor cells were strongly and diffusely positive for antiplacental alkaline phosphatase antibody along their cytoplasmic membranes, but negative for both chorionic gonadotrophin and alpha-fetoprotein. Based on these findings, we diagnosed this tumor as a seminoma. The testes when examined were found to be atrophic bilaterally, but with no tumor lesions. Chromosomal analysis yielded a 47XXY karyotype, compatible with Klinefelter's syndrome. These findings indicate a case of primary intrapelvic seminoma in Klinefelter's syndrome. The patient underwent intensive radiation therapy postoperatively, and he demonstrated no evidence of recurrence or metastasis during the 13-month period following surgery.

Adult↗
PubMed2001

Computed tomography measurement of the surgical and clinical transepicondylar axis of the distal femur in osteoarthritic knees.

To assess rotational alignment of the distal femur, 2 types of transepicondylar axes have been used in the literature. We compared surgical and clinical epicondylar axes in the measurement of rotational alignment of the femur in planning for total knee arthroplasty (TKA). We examined 48 patients who were candidates for TKA. Computed tomography images of both knees were obtained, and condylar twist angle and posterior condylar angle were measured. The medial sulcus was detected in only 33 knees. The more severe the grade of osteoarthritis, the more difficult it was to detect the medial sulcus. The most prominent point of medial epicondyle was detectable in all knees. We recommend the use of the clinical epicondylar axis in computed tomography measurement in selective planning for TKA.

Aged↗
PubMed2001

Elevation of cytokeratin 19 fragment in serum in patients with hepatoma: its clinical significance.

OBJECTIVES: Cytokeratin 19 fragment (CK19) levels in serum have already been documented as a useful tumour marker for lung cancer. In the present study, we hypothesize that CK19 may be increased in serum from patients with hepatoma. METHODS: We measured the CK19 levels in serum from patients with hepatoma and evaluated the correlation between CK19 level and each clinical parameter. We studied 70 patients diagnosed with hepatoma, and used 14 patients with chronic hepatitis C and 45 patients with liver cirrhosis as controls. RESULTS: In 33 of 70 patients (47.1%) with hepatoma, the serum CK19 level was elevated to above the normal range. CK19 levels in serum from patients with hepatoma were significantly correlated with levels of alpha-fetoprotein and prothrombin induced by vitamin K absence for factor II (PIVKA-II). In 57 patients with hepatoma in whom both CK19 and alpha-fetoprotein were measured, only CK19 was elevated in seven patients (12.3%). Immunohistochemical studies using hepatoma tissues demonstrated that hepatoma cells were stained by anti-human CK19 antibody. We also demonstrated that the HepG2 cell line expressed CK1 9. CONCLUSIONS: Our data demonstrate that hepatomas aberrantly express CK19, and that measurement of CK19 might be a useful tumour marker in diagnosing hepatoma.

Adult↗
PubMed2001

Non-specific interstitial pneumonia as pulmonary involvement of systemic sclerosis.

The pathological features of lung disease in nine patients with systemic sclerosis (SSc) were evaluated. The patients comprised one man and eight women, with a median age of 58 years. SSc was diagnosed according to the criteria of the American Rheumatism Association. In all patients, high resolution computed radiographic scanning of the lungs (HRCT) was performed, and apparent honeycomb formation was seen in four patients. Pathologically, four patients were diagnosed with usual interstitial pneumonia (UIP), three with non-specific interstitial pneumonia (NSIP) group II, one NSIP group II-III, and one NSIP group II with diffuse alveolar damage. HRCT showed no apparent honeycomb formations in patients diagnosed with NSIP. This is the first report describing NSIP as a pulmonary complication of SSc.

Adult↗
PubMed2001

Recent progress in T-cadherin (CDH13, H-cadherin) research.

T-cadherin is a unique cadherin cell adhesion molecule that is anchored to the cell surface membrane through a glycosyl phosphatidyl inositol (GPI) moiety. The cytoplasmic domain, which T-cadherin lacks, is believed to be critical for homophilic binding through interaction with submembrane cytoskeletal proteins. Does this mean that T-cadherin is an unimportant molecule? However, the T-cadherin amino acid motif has been well conserved through evolution in vertebrates, suggesting that T-cadherin may have biological significance in higher animals. Consistent with this hypothesis, recent studies have thrown light on the relevance of T-cadherin in the fields of oncology, neurology, respirology and cardiovascular physiology. In this manuscript, we review current advances in T-cadherin research.

Animals↗
PubMed2001

Insufficient effect of p27(KIP1) to inhibit cyclin D1 in human esophageal cancer in vitro.

The cell cycle is controlled by protein complexes composed of cyclins and cyclin-dependent kinases. p27KIP1 (p27) is one of the Kip/Cip family cyclin-dependent kinase inhibitory proteins which negatively regulate cell cycle progression, and have been proposed as candidate tumor suppressor genes. To examine the role of p27 in the development of human esophageal squamous cell carcinoma (ESCC), we performed Western blot and immunoprecipitation analyses of the levels of expression of p27 protein in a series of ESCC cell lines. This protein was expressed at various levels in these cell lines during exponential growth. p27 level was significantly associated with that of cyclin D1, but not of cyclin E. Further cell cycle synchronization studies demonstrated that p27 was free or bound with affinity to cyclin E-CDK2 more than to cyclin D1-CDK4 or cyclin D1-CDK6. It is known that overexpression of cyclin D1 rather than cyclin E is involved in the pathogenesis of ESCC. Our findings indicated that high expression of p27 throughout the G1 to S phase may inhibit more likely cyclin E, than cyclin D1, which promotes tumor growth of esophageal squamous cell carcinoma.

Cell Cycle Proteins↗
PubMed2001

Genetic analysis of hMLH1 in transitional cell carcinoma of the urinary tract: promoter methylation or mutation.

PURPOSE: Loss of DNA mismatch repair due to diminished expression or mutation of hMLH1 is associated with genomic instability followed by cancer. We performed genetic analyses of hMLH1 to determine whether hMLH1 alterations have a role in urothelial tumorigenesis. MATERIALS AND METHODS: We examined genomic DNA from 118 sporadic transitional cell carcinomas, including 83 bladder and 35 renal pelvis or ureter cases, for aberrant promoter methylation and mutation in the hMLH1 gene. Immunohistochemical reactivity to hMLH1 protein and genome instability in these transitional cell carcinomas were also studied. RESULTS: Two of the 118 cases (1.7%) had microsatellite instability and hMLH1 promoter methylation with loss of or reduced hMLH1 protein expression. A single transitional cell carcinoma (0.8%) without microsatellite instability had an hMLH1 missense mutation with a C-to-T transition, resulting in the substitution Arg217 --> Cys. Immunostaining with antihMLH1 antibody was found in this transitional cell carcinoma. CONCLUSIONS: To our knowledge these findings provide the first in vivo evidence for the type and frequency of possible involvement of promoter methylation and mutation of hMLH1 in sporadic urothelial transitional cell carcinoma. They also suggest that hMLH1 alterations may not account for many cases of sporadic transitional cell carcinoma tumorigenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Immunohistochemical characterisation of a case of insular thyroid carcinoma.

A case of insular thyroid carcinoma arising in the right lobe of a 54-year-old male is reported. The tumour exhibited an invasive growth pattern with regional lymph node metastasis. Microscopically, the tumour was characterised by well-defined solid nests like insulae, including mature follicles containing colloid and immature follicles without colloid. Immunohistochemically, tumour cells in follicular areas predominantly exhibited immunopositivity to antithyroglobulin antibody. On the other hand, diffuse immunoreactions with anti-neuron-specific enolase (NSE), S-100 protein and Leu-7 were detected mainly in the tumour cells of solid areas. In addition, clear cytoplasmic immunoreactivity with anti-myelin basic protein (MBP) antibody was exhibited in a number of tumour cells. Ultrastructurally, many tumour cells possessed dense vacuoles, apparently containing colloid material, but intracytoplasmic neurosecretory granules were absent. The histopathological and ultrastructural characteristics of the tumour as well as its anti-thyroglobulin antibody immunoreactivity support the classical hypothesis that this neoplasm is a variant of poorly differentiated thyroid carcinoma. The positive immunohistochemical reactions for NSE, S-100, MBP and Leu-7 raise the possibility of aberrant differentiation, for example neural.

Biomarkers, Tumor↗