Search PubMed⌕ Search

Biomedical subjects

Y Shimosato

Publications and source records attributed to Y Shimosato.

At least 37 records · Page 2Linked to original sources
PubMed1995

The development and progression of adenocarcinoma of the lung.

This chapter has briefly reviewed the development and progression of peripheral-type adenocarcinoma of the lung, focusing particularly on bronchioloalveolar carcinoma consisting of the nonmucus-producing cell type with or without sclerosis. Histoloical examination reveals that scar cancers are rare except in cases of diffuse pulmonary fibrosis and that many nonmucus-producing bronchioloalveolar carcinomas appear to develop from atypical adenomatous hyperplasia, which can be called adenoma or very well-differentiated adenocarcinoma, and to progress stepwise. Stepwise progression in malignancy can be disclosed not only by cytological and histological examination but also by proliferative activity of the tumor, such as mitotic activity, the percentage of DNA-synthesizing cells and the frequency of proliferating cell nuclear antigen-positive cells, the mean nuclear DNA content of tumor cells and occurrence of aneuploid cell lines, and abnormalities of oncogenes (c-Ki-ras, myc family, and c-erbB2), such as point mutation, rearrangement, amplification, and tumor suppressor genes (point mutation and deletion) such as p53.

Adenocarcinoma↗
PubMed1995

Identification of mycobacteria by nonradioisotopic single-strand conformation polymorphism analysis.

Clinical isolates of mycobacteria were identified to species levels using nonradioisotopic single-strand conformation polymorphism (non-RI SSCP) analysis of 16S rRNA gene fragments amplified by polymerase chain reaction with primers common to all of mycobacterial species. The method is based on a hypervariable region within the 16S rRNA in mycobacteria, which is characterized by species-specific nucleotide sequences. A total of 92 mycobacterial strains (Mycobacterium tuberculosis, M. avium, M. gordonae, M. intracellulare, M. kansasii, M. chelonae, M. nonchromogenicum, M. xenopi, and unidentified strain) were studied. They were classified into nine types of pattern showing single-strand DNA bands having different mobilities. Each strain was shown in the species-specific mobility by non-RI SSCP analysis. The results of non-RI SSCP analysis were identical to those of standard biochemical methods and 16S rRNA sequencing.

DNA Primers↗
PubMed1995

Molecular cloning of a cell-surface glycoprotein that can potentially discriminate mesothelium from epithelium: its identification as vascular cell adhesion molecule 1.

It has long been a practical problem for surgical pathologists to distinguish mesothelium from epithelium in order to make a positive diagnosis of mesothelioma. In this study, we developed a new monoclonal antibody, designated MS-2761 (IgG1, k), against cultured non-neoplastic mesothelial cells. Immunohistochemistry and slot-blot analysis revealed that this monoclonal antibody reacted with 100% (12/12) of benign and malignant mesothelioma tissues and a mesothelioma cell line, but not with 99% (77/78) of epithelial tumour tissues and 97% (33/34) of epithelial tumour cell lines. A gene encoding the cell-surface antigen defined by this monoclonal antibody was isolated from a mesothelial cell cDNA library constructed with a mammalian cell expression vector through transfection of Cos-7 cells and immunoselection by panning. DNA sequencing and a database search revealed that the gene was identical to vascular cell adhesion molecule 1 (VCAM1, also referred to as INCAM110). The prominent VCAM1 transcript in mesothelium was 3.2 kb in size with seven Ig-like domains, in addition to a minor transcripts with six Ig-like domains. This monoclonal antibody potentially discriminates mesothelium from epithelium and may become a tool for differential diagnosis of mesothelioma.

Animals↗
PubMed1995

The value of PE-10, a monoclonal antibody against pulmonary surfactant, in distinguishing primary and metastatic lung tumours.

A new monoclonal antibody (PE-10) raised against components of pulmonary surfactant has been assessed for its ability to distinguish primary from secondary carcinomas in the lung. We applied this antibody to a series of 107 primary lung carcinomas, 40 adenocarcinomas of other sites, and 26 cases of adenocarcinoma metastatic to lung and pleura. Of the primary lung carcinomas, all the non-mucinous bronchiolo-alveolar carcinomas were positive whereas all the mucinous cases were negative; 60% of other types of adenocarcinoma were positive and 10% of large cell undifferentiated carcinomas, 20% of small cell carcinomas and 40% of atypical carcinoids also showed focal positivity. Squamous cell carcinomas were all negative. Adenocarcinomas of the breast, kidney, large bowel and ovaries were all negative, as were all 26 cases of adenocarcinoma metastatic to the lung and pleura. We conclude that this antibody is highly specific and moderately sensitive for primary tumours of the lung.

Adenocarcinoma↗
PubMed1995

Lung tumors of uncertain histogenesis.

Unusual lung tumors of uncertain origin have been described briefly concerning benign clear cell (sugar) tumor and, in more detail, concerning pneumocytoma (so-called sclerosing hemangioma). Melanocytic differentiation of clear cell tumor, which is peculiar to the lung, has been suggested recently. Sclerosing hemangioma, also unique to the lung, is now considered to be a tumor (neoplasm) related to alveolar epithelial cells. It shows invasive growth and multiplicity (or aerogenous metastasis), but is very rarely capable of lymph node metastasis. It should be designated as pneumocytoma.

Adult↗
PubMed1994

Detection of point mutations in the K-ras oncogene at codon 12 in pure pancreatic juice for diagnosis of pancreatic carcinoma.

BACKGROUND: Mutations in the K-ras oncogene at codon 12 are detected at a remarkably high frequency in pancreatic carcinomas and are believed to be a critical event in oncogenesis. The authors attempted to detect K-ras mutations in DNA obtained from pure pancreatic juice collected endoscopically, as a novel diagnostic approach to pancreatic carcinoma. METHODS: K-ras mutations were examined using the two-step polymerase chain reaction (PCR) combined with restriction enzyme digestion, followed by nonradioisotopic single-strand conformation polymorphism (SSCP) analysis. RESULTS: Specific mutations of the K-ras gene at codon 12 were found in six of nine (67%) duct cell carcinomas, all of which were negative by cytodiagnosis of the same pure pancreatic juice. K-ras mutations were not detected in the pancreatic juice from 14 healthy control subjects, 10 patients with chronic pancreatitis, or 3 patients with islet cell tumors. CONCLUSIONS: Detection of K-ras mutation at codon 12 in pancreatic juice is highly specific for diagnosing pancreatic duct cell carcinoma and may be a valuable diagnostic modality for pancreatic carcinoma and for differentiating chronic pancreatitis from carcinoma.

Adenocarcinoma↗
PubMed1994

Reproducibility of major diagnoses in a binational study of lung cancer in uranium miners and atomic bomb survivors.

A binational panel of four Japanese and four American pathologists examined 208 pulmonary neoplasms, according to the World Health Organization (WHO) recommendations, second edition, for the histologic typing of lung tumors. The study design included independent evaluations by pathologists working alone, followed by group reviews. The individual evaluations, and their implications for reproducibility of the WHO recommendations, are reported. Consensus (agreement by six or more pathologists) with respect to major (ie, first digit) diagnosis was obtained for 76.4% of the cases. Consensus was obtained for 72.5% of the cases with any major diagnosis of small cell cancer; the comparable figures for adenocarcinoma and squamous cell carcinoma were 56% and 48%, respectively. American pathologists were twice as likely as Japanese pathologists to diagnose large-cell cancer, the only significant national difference. Consensus was far less frequent with the minor (ie, second digit) diagnosis categories. This study shows that lung cancers continue to be difficult to classify reproducibly.

Carcinoma↗
PubMed1994

Surgically curable "early" adenocarcinoma in the periphery of the lung.

To define surgically curable "early" adenocarcinoma in the periphery of the lung, we examined histopathologic prognostic factors in 56 cases of stage I mucinous, nonmucinous, and sclerosing bronchioloalveolar carcinomas less than 2 cm in diameter. The death rate 5 years after surgery was only 1.8%, but the recurrence rate within 5 years after surgery was 8.9%. In addition, there were two cases of recurrence more than 5 years after surgery. Vascular invasion (p < 0.05) and mitotic index (p < 0.01) were the most important determinants of prognosis, and there was no recurrence or death in cases showing grades 1 and 2 collagenization in fibrotic foci. These results indicate surgically curable stage I adenocarcinomas to be less than 2 cm in diameter and without vascular invasion, with a low mitotic index and grade 1 or 2 fibrotic scarring, although the significance of nuclear atypia as a prognostic factor remains to be clarified. It may be possible to improve the cure rate by postoperative adjuvant chemotherapy for "early" adenocarcinoma with vascular invasion, high mitotic index, higher scar grade, and probably a high degree of nuclear atypia.

Adenocarcinoma↗
PubMed1994

Establishment of a human small cell lung cancer cell line producing a large amount of anti-diuretic hormone.

A new cancer cell line (Lu-165) producing a large amount of anti-diuretic hormone (ADH, 2.8 micrograms/g protein) was established from a 50-year-old small cell lung cancer patient presenting with a syndrome of inappropriate anti-diuretic hormone secretion. These cells grew well in serum-supplemented medium and during more than 100 passages they continued producing a large amount of this hormone. This cell line will be a useful tool for studies of the biochemistry and pathology of ADH-producing cancer.

Animals↗
PubMed1994

Thymic carcinoma: proposal for pathological TNM and staging.

Recently, Yamakawa et al. following Masaoka's clinical staging of thymic epithelial tumors, proposed a TNM classification and staging system for thymic epithelial tumors including thymoma and thymic carcinoma. The present authors consider that division of thymomas into circumscribed types (either encapsulated or non-encapsulated but confined to within the thymus) and those invasive to adjacent organs or structures is sufficiently practical, and that a staging system is applicable to thymic carcinoma, carcinoid tumors and germ cell tumors of the anterior mediastinum, which are more malignant than thymoma. Therefore, the utility of the Yamakawa/Masaoka TNM and staging system was evaluated and a modification proposed based on experience with 16 thymic carcinomas. Although there were no cases at stage II, the survival curves obtained using the proposed modified system were more clearly separated between stages I and III or IV and between stages III and IV than the curves obtained using the Yamakawa/Masaoka system. However, the differences were not significant because of the small number of cases included. A statistically significant difference was noted between the survival curves for patients who underwent complete and incomplete surgical resection of the tumor. The utility of this proposed TNM and staging system must be evaluated by other investigators, since no cases of small cell carcinoma, lymphoepithelioma-like carcinoma, sarcomatoid carcinoma and clear cell carcinoma were included in this series, all of which are considered to have high-grade histology. An evaluation of carcinoid tumor and germ cell tumor of the anterior mediastinum must also be made.

Adult↗
PubMed1994

A review of 79 thymomas: modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma.

A clinicopathological study of surgically resected thymomas was performed using Masaoka's staging and modified Masaoka's staging systems, and the utility of these two staging systems was compared. The modification enabled adjustment for the disproportion in the number of cases between Stage I and Stage II. Analysis of survival rates, according to the tumor stage, indicated that the old classification should be reappraised, that is, division into non-invasive and invasive thymomas, although staging may contribute to the indication for postoperative radiotherapy, especially for Stage II disease. Analysis of the cases showed a wide spectrum of aggressiveness, varying from cases showing slow progression with a relatively favorable prognosis, such as the spindle cell type, to cases with rapid progression leading to tumor death in a relatively short time, such as the epithelial cell predominant and polygonal cell type. The pathological stage at the time of first surgical resection would reflect the degree of aggressiveness of thymoma in many instances. Therefore, not only staging the tumor extent but also grading of its aggressiveness are needed in order to predict the prognosis of patients with thymoma. For the latter, histology and cytopathology are helpful.

Adolescent↗
PubMed1994

Detection of novel mutations in the gyrA gene of Staphylococcus aureus by nonradioisotopic single-strand conformation polymorphism analysis and direct DNA sequencing.

A total of 36 clinical isolates of Staphylococcus aureus (29 fluoroquinolone-resistant strains and 7 fluoroquinolone-susceptible strains) were studied for the presence of point mutations in the gyrA gene by nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis with silver stain. Direct DNA sequencing analysis of the PCR-amplified DNA fragments confirmed the results obtained by Non-RI SSCP analysis and revealed that fluoroquinolone resistance is closely associated with six types of mutations in the gyrA gene, of which three types of mutations were newly identified: (i) Ser-84-->Leu and Glu-88-->Gly, (ii) Ser-84-->Leu and Glu-88-->Lys, and (iii) Glu-88-->Gly. Furthermore, the novel ATT-->ATC mutation at codon 86 (silent mutation) was seen in only one fluoroquinolone-susceptible strain. All seven mutational types were separated from the wild type in a single electrophoretic step within 3 h after PCR amplification. Thus, we conclude that this new technique is a rapid, simple, and useful screening method for the genotyping of gyrA mutations associated with fluoroquinolone resistance.

Base Sequence↗
PubMed1994

Prognostic value of immunohistochemical staining for proliferating cell nuclear antigen, p53, and c-erbB-2 in sebaceous gland carcinoma and sweat gland carcinoma: comparison with histopathological parameter.

Thirteen cases of sebaceous gland carcinoma and 10 cases of sweat gland carcinoma were studied using immunohistochemical staining for proliferating cell nuclear antigen (PCNA), c-erbB-2, and p53 to examine correlations among them, and to determine the best predictor of patient prognosis. Many sebaceous gland carcinomas and sweat gland carcinomas showed nuclear accumulation of p53, and patients with tumors showing a PCNA index (percentage of nuclei stained for PCNA) higher than 20%, and a p53 index (percentage of nuclei stained for p53) higher than 10% had short survival. Sebaceous gland carcinomas and sweat gland carcinomas showing c-erbB-2 expression had high PCNA (> 20%) and p53 (> 10%) indices, and were associated with poor prognosis. Histologically, sebaceous gland carcinomas showing a high degree of differentiation and severe nucleolar atypia had high PCNA and p53 indices. A growth pattern of small solid nests and strands, a low degree of differentiation, and the presence of lymphatic permeation in sweat gland carcinoma were often associated with high PCNA and p53 indices. These results suggest that nuclear accumulation of p53 plays an important role in the development of sebaceous gland carcinoma and sweat gland carcinoma. Assessment of PCNA and p53 indices together was very useful for prognostication of patient outcome, using cut-off values of 20% and 10%, respectively, to separate good prognosis from poor. Differentiation of sebaceous gland carcinoma, and c-erbB-2 expression by sweat gland carcinoma were significant independent prognostic indicators.

Adult↗
PubMed1993

Compensatory occurrence of IV2Fucalpha,II3NeuAcalpha-Gg4Cer and human fetal antigen Lc4Cer in small cell carcinomas of the human lung.

By means of a thin-layer chromatography immunostaining procedure involving a human monoclonal anti-Lc4Cer antibody, which was established by hybridizing murine myeloma cells and human lymphocytes from a cancer patient, Lc4Cer was proven to be a fetal antigen of human lung and to be a cancer-related antigen in small cell carcinomas of human lung, but not of other lung cancers, i.e., large cell carcinomas, adenocarcinomas, and squamous carcinomas. With the simultaneous detection of IV2Fuc alpha,II3NeuAc alpha-Gg4Cer with rabbit anti-IV2Fuc alpha,II3NeuAc alpha-Gg4Cer antiserum, the expression of Lc4Cer and IV2Fuc alpha,II3NeuAc alpha-Gg4Cer was found to be compensatory and, consequently, small cell lung carcinomas could be classified into Lc4Cer- and IV2Fuc alpha,II3NeuAc alpha-Gg4Cer-expressing types, L-SCLC and F-SCLC, respectively, which were detected in four and 27 of 31 patients' tissues and in one and three of four nude mouse-transplanted small cell lung carcinoma tissues, respectively. The compensatory expression of Lc4Cer and IV2Fuc alpha,II3NeuAc alpha-Gg4Cer in small cell carcinomas indicated that different metabolic pathways for glycosphingolipids were activated to give the distinct glycosphingolipid compositions in the two types of small cell lung carcinomas.

Antibodies, Monoclonal↗
PubMed1993

Immunohistochemical detection of hepatocyte growth factor/scatter factor in human cancerous and inflammatory lesions of various organs.

Hepatocyte growth factor (HGF)/scatter factor (SF) is a multifunctional factor considered to be potentially involved in tissue regeneration, wound healing, embryogenesis, angiogenesis and cancer invasion. Here we examined immunohistochemically the distribution of HGF/SF in human tissues, including cancerous and inflammatory tissues, using anti-HGF antibody. HGF/SF accumulation was clearly detected in the extracellular matrix, particularly along the basement membrane, in cancerous and inflammatory tissues, but only a little was detected in normal tissues. HGF/SF is well known to have a strong affinity for heparin in vitro, and from the results of our immunohistochemical assay, we considered that HGF/SF was bound to heparin or heparan sulfate of the extracellular matrix and basement membrane. HGF/SF was well localized in cancerous and inflammatory lesions of human lung, liver and pancreas, and in apparently normal tissues of kidney, adrenal gland and pancreas obtained at autopsy. In lung, HGF/SF was localized along the basement membranes of cancer cell nests, in the extracellular matrix of the cancer cell surface, cancer stroma and tissues invaded by cancer, and the basement membranes of bronchial epithelium and capillary vessels in inflammatory stroma. Since HGF/SF makes some cancer cells more invasive in vitro, the accumulation of HGF/SF in cancerous tissue suggests that the invasiveness of some cancer cells may be increased by HGF/SF in vivo.

Extracellular Matrix↗
PubMed1993

Comparison of immunoreactivity between two different monoclonal antibodies recognizing peptide and polysialic acid chain epitopes on the neural cell adhesion molecule in normal tissues and lung tumors.

A comparative immunohistochemical study of two different monoclonal antibodies against different epitopes on the neural cell adhesion molecule (N-CAM) was performed. Various normal tissues and lung tumors were examined for reactivity with NCC-LU-243, a monoclonal antibody which recognizes a peptide epitope on N-CAM, and monoclonal antibody 735 (MoAb 735), which reacts with a polysialic acid chain epitope on N-CAM. When acetone-fixed normal tissues were used, the immunoreactivities of MoAb 735 and NCC-LU-243 were not identical. In lung tumors, almost all small cell cancers (SCLC) and carcinoid tumors, and some non-SCLC were stained by both monoclonal antibodies. NCC-LU-243 stained the cell membrane only of almost all SCLC cells and clusters of non-SCLC cells. MoAb 735 stained the cell membrane of SCLC in a patchy manner and not only the cell membrane but also the cytoplasm of some non-SCLC. However cytoplasmic staining was evaluated as 'not positive'. The number of positive cases and the size of the positive tumor cell population determined by cell membrane staining with MoAb 735 were smaller than those determined with NCC-LU-243 in both SCLC and non-SCLC cases. In routinely formalin-fixed materials, the immunoreactivity of both monoclonal antibodies, especially of NCC-LU-243, decreased after prolonged fixation as in surgically resected and autopsy materials. However, both monoclonal antibodies were found to be useful when materials were fixed for a short period of time as in biopsy specimens.

Antibodies, Monoclonal↗
PubMed1993

Application of the p53 gene mutation pattern for differential diagnosis of primary versus metastatic lung carcinomas.

The p53 gene mutation pattern was used as a diagnostic marker of multiple and second primary lung carcinomas. Nine cases of multiple carcinoma, which were suspected clinicopathologically to be double or triple primary carcinomas, were examined for p53 protein expression by immunohistochemistry and for genetic abnormality of the p53 gene by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Nine tumors from four cases gave a positive result upon both immunostaining for the p53 protein and PCR-SSCP analysis of the p53 gene. These nine tumors showed different mobility shifts between exons 5 and 8. The four cases were diagnosed genetically as multiple primary carcinomas. To confirm the results of PCR-SSCP analysis, five tumors from two cases that showed different mobility shifts were further analyzed for their nucleotide sequences, and it was found that all of them had point mutations at different codons in exons 5 and 8. These findings suggest that the p53 gene mutation pattern is an effective marker for diagnosis of tumor multiplicity.

Base Sequence↗