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T Oyama

Publications and source records attributed to T Oyama.

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

The direct effect of IL-12 on tumor cells: IL-12 acts directly on tumor cells to activate NF-kappaB and enhance IFN-gamma-mediated STAT1 phosphorylation.

IL-12 directly acts on T cells and NK cells to induce IFN-gamma production. IFN-gamma plays an important role in anti-tumor effect of IL-12. In spite of various functions of IL-12 on immunocytes, the direct effect of IL-12 on tumor cells has not been fully clarified. The present study investigated the direct effect of IL-12 on eight murine tumor cell lines in vitro. IL-12 did not directly up-regulate expression of MHC class I on tumor cells, but enhanced IFN-gamma-induced up-regulation of MHC class I expression in MC-38, MCA102, MCA205 and MCA207 cells. IL-12 alone did not activate STAT1, but IL-12 enhanced IFN-gamma-mediated STAT1 phosphorylation in MC-38, MCA102, MCA205, MCA207 and Colon-26-NL-17 cells, which expressed IL-12 receptor beta1 mRNA. In the other side, Panc-02, B16-BL6 and 266-6 cells were not affected by IL-12, in which expression of IL-12 receptor beta1 mRNA was not detected. Anti-IL-12 mAb inhibited the direct effect of IL-12 on MC-38 cells. Moreover, nuclear localization of NF-kappaB was observed after stimulation of IL-12 or IL-12 p40 in MC-38 and Colon-26-NL-17 cells, but not in Panc-02 cells. These findings suggest that IL-12 directly acts on tumor cells through IL-12 receptor beta1 to activate NF-kappaB and enhance IFN-gamma-mediated STAT1 phosphorylation.

Active Transport, Cell Nucleus↗
PubMed2001

Three-dimensional electron microscopy of the clamp loader small subunit from Pyrococcus furiosus.

An archaeal clamp loader, replication factor C (RFC), consists of two proteins, the small subunit (RFCS) and large subunit (RFCL), whose sequences are both highly homologous to those of the eukaryotic RFC components. We have investigated the oligomeric structure of RFCS from Pyrococcus furiosus by electron microscopy using single-particle analysis. RFCS forms mostly ring-shaped hexamers at pH 9.0, although it tends to form C-shaped tetramers or pentamers at a lower pH (pH 5.5). The three-dimensional (3D) structure of the RFCS hexamer was obtained by random conical tilt reconstruction at 24.0-A resolution. RFCS forms a hexameric ring with outer and inner diameters of 117 and 27 A, respectively, and with a height of about 55 A. The six subunits are arranged in a twisted manner with a sixfold symmetry around the channel. The 3D map revealed that the six subunits are arranged in a head-to-tail configuration. Although the RFC complex consists of RFCS and RFCL in vivo, RFCS alone, together with PCNA, substantially enhanced the DNA synthesizing activity of P. furiosus DNA polymerase I in vitro. The 3D reconstruction of RFCS with catalytic activity provides important insights into the organization mechanism and the functional state of the RFC complex.

Archaeal Proteins↗
PubMed2001

Molecular biological markers and micrometastasis in resected non-small-cell lung cancer. Prognostic implications.

OBJECTIVES: Recent advances in molecular biology and genetics have created new diagnostic and treatment possibilities in clinical oncology. We evaluated the usefulness of molecular biological factors in primary tumor and micrometastasis in the bone marrow and pathological negative (pN0) lymph nodes as prognostic parameters in non-small-cell lung cancer (NSCLC) patients. METHODS: Pathological specimens were collected from 129 NSCLC patients to analyze molecular biological markers, including K-ras, p53, Rb, p16, loss of heterozygosity (LOH) at 3p, vascular endothelial growth factor (VEGF), and telomerase activity. Bone marrow samples from 250 NSCLC patients and pN0 lymph nodes from 85 of these patients were collected for micrometastasis detection by immunohistochemistry against cytokeratin. RESULTS: p53 abnormalities and 3p LOH were significantly associated with reduced patient survival in adenocarcinoma, whereas VEGF expression was significantly associated with reduced survival in a squamous cell carcinoma histological subtype by univariate or multivariate analysis. We identified micrometastatic tumor cells in bone marrow of 78 (31.2%) of 250 patients and in pN0 lymph nodes of 26 (30.6%) of 85 patients. Both bone marrow and lymph nodal micrometastases were associated with decreased survival among patients with stage I, however, only lymph nodal micrometastasis had a significant impact on survival. CONCLUSIONS: Molecular biological features of primary tumor and micrometastatic status appear useful in defining groups of patients with a poor prognosis who could benefit from adjuvant systemic treatment.

Adult↗
PubMed2001

Recurrence of breast cancer following local excision alone for ductal carcinoma in situ.

OBJECTIVE: To assess recurrence of breast cancer following local excision alone for ductal carcinoma in situ. METHODS: Eighteen patients who received complete resection for noninvasive ductal carcinoma between 1982 and 1997 were investigated in this study. The mean age of the patients was 45 (29-78) years old. The initial presentation was a clinically palpable tumor in 4 patients, nipple discharge in 6, and microcalcification on mammograms in 8. Patients with palpable tumor underwent wide excision with at least a 2-cm free margin. Patients whose mammograms showed microcalcification underwent lumpectomy, and those who showed nipple discharge underwent duct-lobular segmentectomy. Five patients who underwent lymph node dissection up to level I or II had no lymph node metastasis. The mean follow-up period was 86 months. RESULTS: Local recurrence in the conserved breast was seen in five (27.8%) of 18 patients. The actuarial five-year event-free survival was 76.2%. The histological type of the recurrent tumor was ductal carcinoma in situ in three patients and invasive carcinoma in two. There was no difference in age at initial operation or histological subtype between patients with and without recurrent disease, but patients presenting with nipple discharge initially had a significantly shorter ipsilateral disease-free interval than those presenting with tumor or microcalcification on mammograms. All patients with local recurrence in the conserved breast were treated with breast-conserving surgery or subcutaneous mastectomy. CONCLUSION: Local recurrence frequently occurs in patients presenting with nipple discharge treated by duct-lobular segmentectomy for noninvasive ductal carcinoma. Either wide excision with a larger free margin or adjuvant radiation therapy following duct-lobular segmentectomy should be considered for these patients.

Adult↗
PubMed2001

Morphological observations regarding the origins of atypical cystic lobules (low-grade clinging carcinoma of flat type).

This study seeks to define the morphological pathogenesis of a form of cystic transformation of lobules referred to as atypical cystic lobule or low-grade clinging carcinoma of flat type. We collected 25 examples that seem to represent the early stages in the formation of atypical cystic lobules and made a careful study of their morphology. Our observations indicate that this lesion arises from pre-existing, structurally normal terminal duct-lobular units and that it seems to develop by the direct transformation of indigenous luminal cells. The transformed cells first become evident in the small duct or terminal ductule, where they appear as slightly enlarged columnar cells containing atypical nuclei. In more advanced examples, these alterations affect all luminal cells of the terminal duct-lobular unit, but the cells of the terminal ductule continue to show more pronounced changes than the cells lining the acini. The atypical cells within the lobule do not seem to displace the normal acinar cells. Instead, the cells form a continuum, making it impossible to define the point at which atypical cells and normal cells meet. Within the small duct, however, the atypical epithelium comes to an abrupt halt as the duct courses towards the nipple. Considering these observations, we ascribe the formation of atypical cystic lobules to the accumulation of atypical cells in pre-existing terminal duct-lobular units.

Breast Neoplasms↗
PubMed2001

Ovarian hormone receptors in human mammary stromal cells.

Mesenchymal cells of the rodent breast express both estrogen and progesterone receptors. Searches for these molecules in the human breast have yielded conflicting results. Following immunohistochemical staining of samples of normal human breast tissue, the authors detected estrogen receptor alpha protein and progesterone receptor protein in extralobular (non-specialized) fibroblasts and estrogen receptor alpha protein in adipocytes. Tissues from young teenage girls and pregnant women contained the greatest number of receptor positive fibroblasts. These observations confirm prior reports of the presence of ovarian hormone receptors in mammary fibroblasts. The findings also illustrate similarities in the organization of the rodent and human breasts and thereby suggest that regulation of the gland by ovarian hormones involves similar mechanisms in both species.

Adipocytes↗
PubMed2001

Atomic structure of the clamp loader small subunit from Pyrococcus furiosus.

In eukaryotic DNA replication, replication factor-C (RFC) acts as the clamp loader, which correctly installs the sliding clamp onto DNA strands at replication forks. The eukaryotic RFC is a complex consisting of one large and four small subunits. We have determined the crystal structure of the clamp loader small subunit (RFCS) from Pyrococcus furiosus. The six subunits, of which four bind ADP in their canonical nucleotide binding clefts, assemble into a dimer of semicircular trimers. The crescent-like architecture of each subunit formed by the three domains resembles that of the delta' subunit of the E. coli clamp loader. The trimeric architecture of archaeal RFCS, with its mobile N-terminal domains, involves intersubunit interactions that may be conserved in eukaryotic functional complexes.

Amino Acid Sequence↗
PubMed2001

Secondary sclerosing cholangitis and portal hypertension after O157 enterocolitis: Extremely rare complications of hemolytic uremic syndrome.

The authors experienced an extremely rare case of secondary sclerosing cholangitis and portal hypertension developed as late complications of hemolytic uremic syndrome (HUS) owing to Escherichia coli O157:H7 in a 2-year-old boy. HUS after E coli O157 infection is the most frequent cause of acute renal failure in childhood and occasionally is accompanied by extrarenal complications such as encephalopathy, cardiomyopathy, ischemic colitis, and pancreatitis. Rarely, late colonic stenosis may develop secondary to the ischemic damage. Sclerosing cholangitis and subsequent cirrhosis with portal hypertension are very uncommon as late complications of HUS. To our knowledge, such a case has not been previously reported in the literature. J Pediatr Surg 36:1838-1840.

Child, Preschool↗
PubMed2001

A case of esophageal sarcomatoid carcinoma with molecular evidence of a monoclonal origin.

A case of polypoid tumor of the esophagus consisting of a sarcomatous tumor partly covered with superficial squamous cell carcinoma is described. The sarcomatous component consisted of anaplastic spindle and pleomorphic tumor cells that mimicked malignant fibrous histiocytoma (MFH). Both the sarcomatous and carcinomatous components were positive for p53 immunohistochemically. Further molecular analysis revealed that the two components had the same somatic mutation in the p53 gene. These results suggest a monoclonal origin of this biphasic tumor.

Aged↗
PubMed2001

Autoimmune disease-associated lymphadenopathy with histological appearance of T-zone dysplasia with hyperplastic follicles. A clinicopathological analysis of nine cases.

Autoimmune disease-associated lymphadenopathy shows marked histopathological and clinical diversity. We describe the clinicopathological and immunohistochemical findings of nine cases of autoimmune disease-associated lymphadenopathy, which posed a serious differential diagnostic problem regarding T-zone dysplasia with hyperplastic follicles. There were two males and seven females aged 25 to 65 years (median 37 years). The patients had multicentric lymphadenopathy in association with clinical and laboratory findings suggestive of an "autoimmune disease". Four patients were diagnosed to have systemic lupus erythematosus (SLE), and the remaining five patients had antiphospholipid antibody syndrome and Sjogren's syndrome (SS), rheumatoid arthritis (RA), chronic thyroiditis, RA and SS, and SLE and SS, respectively. None of the nine patients developed malignant lymphomas during the follow-up periods from 44 to 225 months (median 103 months). The lesions were characterized by paracortical hyperplasia with prominent vascular proliferation and many lymphoid follicles with germinal centers. The paracortical area usually contained numerous small T-lymphocytes without cytological atypia, accompanied by a variable number of plasma cells, B-immunoblasts, and histiocytes. Polymerase chain reaction analysis demonstrated no clonal rearrangement of the T-cell receptor chain gene in four cases examined, although immunoglobulin heavy chain rearrangement was detected in only one case. These findings suggest that autoimmune disease-associated lymphadenopathy, especially SLE, shares the histological features with T-zone dysplasia with hyperplastic follicles. The nine cases presented here should be differentiated from T-zone lymphoma with follicles and angioimmunoblastic lymphoma with hyperplastic germinal centers. To avoid overdiagnosis and overtreatment, we emphasize the need to turn attention to these clinical and laboratory findings as well as to the morphological features.

Adult↗
PubMed2001

The characterization of bronchoalveolar lavage fluid in very elderly patients with cerebrovascular disease.

BACKGROUND: Elderly patients with cerebrovascular disease have a high frequency of pneumonia due to impaired immune function and the occurrence of micro-aspiration. METHODS: We performed bronchoalveolar lavage in 11 very elderly subjects with cerebrovascular disease and 9 healthy volunteers to investigate whether there were changes of local immunity in the lungs of the elderly subjects. The total cell count, the cell characteristics, and the lymphocyte subsets in bronchoalveolar lavage fluid were compared between the two groups. RESULTS: A significant increase in the total cell count as well as in the number of neutrophils and CD8(+) T cells was observed in the elderly group. In addition, the mean CD4/CD8 lymphocyte ratio was lower in the elderly patients than in the healthy volunteers. CONCLUSIONS: These observations suggest that silent micro-aspiration occurs in many elderly individuals with cerebrovascular disease and that pulmonary defenses decrease with age.

Adult↗
PubMed2001

Generation of autologous tumor-specific T cell clones from a patient with adenosquamous carcinoma of the lung.

BACKGROUND: Adenosquamous carcinoma of the lung is not a common cancer, but its prognosis is worse than that of adenocarcinoma or squamous cell carcinoma. Therefore, new therapeutic strategies need to be developed to treat this type of lung cancer. Recently, vaccination using tumor antigens which are recognized by cytotoxic T lymphocytes (CTL) has been applied mainly to melanoma patients. We therefore attempted to establish T cell clones specific for autologous tumor cells (AT) from a patient with adenosquamous carcinoma in order to analyze the specific immune responses against AT. METHODS: A lung adenosquamous carcinoma cell line was established from a resected tumor obtained from a 72-year-old patient. Regional lymph node lymphocytes were stimulated weekly with CD80-transfected AT to induce CTL. The CTL activities were assessed by a standard (51)Cr release assay and by cytokine release. RESULTS: We succeeded in inducing an AT-specific CTL line. Using a limiting dilution method, eight T cell clones were established. AT-specific activity was observed in three CD8(+) T cell clones and one CD4(+) T cell clone out of the eight clones tested. Anti-HLA class I and anti-HLA-B/C mAbs inhibited IFN-gamma production from the AT-specific CD8(+) clones co-cultured with AT, thus indicating the restriction element to be HLA-B*5201 or HLA-Cw*1202. In contrast, the CD4(+) T cell clone recognized AT in an HLA class II-restricted manner. CONCLUSIONS: These results are the first demonstration of a successful induction of AT-specific T cell clones from a patient with lung adenosquamous carcinoma. It may therefore supply a possible way to apply specific immunotherapy to this type of lung cancer.

Aged↗
PubMed2001

Aberrant expression of pRb, p16, p14ARF, MDM2, p21 and p53 in squamous cell carcinomas of lung.

Expression of cell cycle regulatory proteins in both the RB and p53 pathways was investigated in 50 cases of squamous cell carcinoma (SCC) of the lung using immunohistochemical techniques. Abnormality of pRb and p16 expression was seen at the frequencies of 16% and 78%, respectively, and appeared to be in a reciprocal relationship. On the other hand, strong and diffuse p53 immunoreactivity was seen in 60% of SCCs. MDM2 and p14ARF expressions were each observed in about half of the cases of SCC and were not significantly associated with strong p53 immunoreactivity. Statistical analysis revealed that p14ARF expression was significantly correlated with both p16 and MDM2 expression. Moreover, strong p53 expression was not correlated with the expression of p21. In comparing clinicopathological status with the immunohistochemical results, lack of p16 immunoreactivity was observed in the elderly group (over 65 years) as compared with the younger group (less than 65 years). Strong p53 expression was frequently observed in higher stages of SCC, with the developing tumor located in the central field of the lung. Similarly, the frequency of p14ARF expression was high in centrally developed SCC, but low in SCC developed in the periphery. These results suggest that disruption of the RB and p53 pathways is a frequent event in SCC, and that abnormal expression of p16 and p53 plays a more critical role than that of pRB, p14ARF and MDM2 in the development of SCC of the lung.

Age Factors↗
PubMed2001

A human protein with sequence similarity to Drosophila mastermind coordinates the nuclear form of notch and a CSL protein to build a transcriptional activator complex on target promoters.

Mastermind (Mam) has been implicated as an important positive regulator of the Notch signaling pathway by genetic studies using Drosophila melanogaster. Here we describe a biochemical mechanism of action of Mam within the Notch signaling pathway. Expression of a human sequence related to Drosophila Mam (hMam-1) in mammalian cells augments induction of Hairy Enhancer of split (HES) promoters by Notch signaling. hMam-1 stabilizes and participates in the DNA binding complex of the intracellular domain of human Notch1 and a CSL protein. Truncated versions of hMam-1 that can maintain an association with the complex behave in a dominant negative fashion and depress transactivation. Furthermore, Drosophila Mam forms a similar complex with the intracellular domain of Drosophila Notch and Drosophila CSL protein during activation of Enhancer of split, the Drosophila counterpart of HES. These results indicate that Mam is an essential component of the transcriptional apparatus of Notch signaling.

Amino Acid Sequence↗
PubMed2001

Prediction of pulmonary complications after a lobectomy in patients with non-small cell lung cancer.

BACKGROUND: Although the preoperative prediction of pulmonary complications after lung major surgery has been reported in various papers, it still remains unclear. METHODS: Eighty nine patients with stage I-IIIA non-small cell lung cancer (NSCLC) who underwent a complete resection at our institute from 1994-8 were evaluated for the feasibility of making a preoperative prediction of pulmonary complications. All had either a predicted postoperative forced vital capacity (FVC) of >800 ml/m(2) or forced expiratory volume in one second (FEV(1)) of >600 ml/m(2). RESULTS: Postoperative complications occurred in 37 patients (41.2%) but no patients died during the 30 day period after the operation. Pulmonary complications occurred in 20 patients (22.5%). Univariate analysis indicated that the factors significantly related to pulmonary complications were FVC <80%, serum lactate dehydrogenase (LDH) level > or =230 U/l, and arterial oxygen tension (PaO(2)) <10.6 kPa (80 mm Hg). In a multivariate analysis the three independent predictors of pulmonary complications were serum LDH > or =230 U/l (odds ratio (OR) 10.5, 95% CI 1.4 to 77.3), residual volume (RV)/total lung capacity (TLC) > or =30% (OR 6.0, 95% CI 1.1 to 33.7), and PaO(2) <10.6 kPa (OR 5.6, 95% CI 1.4 to 22.2). CONCLUSIONS: The above findings indicate that three factors (serum LDH levels of > or =230 U/l, RV/TLC > or =30%, and PaO(2) <10.6 kPa) may be associated with pulmonary complications in patients undergoing a lobectomy for NSCLC, even though the patient group was relatively small for statistical analysis of such a diverse subject as pulmonary complications.

Adult↗