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Biomedical subjects

A Yachi

Publications and source records attributed to A Yachi.

At least 37 records · Page 2Linked to original sources
PubMed1994

Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin.

Matrilysin is believed to have a role in tumor progression. Its expression correlates with the occurrence of colorectal cancer. We have examined the expression of matrilysin mRNA in various colorectal disorders and its localization using RT-PCR and in situ hybridization. We have also examined whether Matrilysin is induced by cell to matrix interaction. Matrilysin mRNA was detected in all adenoma tissues examined, whereas none was detectable in hyperplastic polyps, mildly inflamed regions of ulcerative colitis or normal colon tissues, and its message was localized in adenoma cells themselves. In addition, levels of enzyme activities of matrilysin were lower in adenomas compared with cancers in casein zymography. Matrilysin mRNA was induced by immobilized truncated fibronectin or RGD peptide. Thus, matrilysin may play an important role in colorectal carcinogenesis.

Adenoma↗
PubMed1994

Downregulation of Wilms' tumor gene (wt1) during myelomonocytic differentiation in HL60 cells.

The putative Wilms' tumor-suppressor gene (wt1) encodes a zinc finger DNA binding protein that functions as a transcription repressor. The wt1 gene expression corresponds to kidney development, suggesting a role for this gene in nephroblast differentiation. Here we show that wt1 mRNA expression was downregulated during terminal differentiation of promyelocytic HL60 cells. When HL60 cells were induced to differentiate to granulocytes by dimethyl sulfoxide (DMSO) or retinoic acid (RA), a marked downregulation in the levels of wt1 transcripts was found. The wt1 transcripts were also downregulated in HL60 cells during differentiation to monocytes by vitamin D3 or 12-o-tetradecanoyl-phorbol-13-acetate. Nuclear run-on transcription studies showed the transcriptional rate of wt1 gene was not significantly altered during DMSO-induced granulocytic differentiation, suggesting the downregulation was mostly caused by posttranscriptional modification. Importantly, wt1 transcripts were not significantly altered in K562 cells by treatments with DMSO or RA, which do not induce differentiation of K562 cells. These findings suggest that wt1 gene expression may be downregulated as a differentiation-linked event in HL60 cells.

Base Sequence↗
PubMed1994

Insulin receptor kinase phosphorylates protein tyrosine phosphatase containing Src homology 2 regions and modulates its PTPase activity in vitro.

To clarify the role of protein tyrosine phosphatase (PTPase) containing a pair of Src homology 2 (SH2) regions upon insulin signaling, we studied the interactions between the insulin receptor and SH-PTP2 coupled to glutathione-S-transferase. A full length SH-PTP2 was phosphorylated by insulin receptor kinase and associated with the insulin receptor in vitro. The N-terminal SH2 domain was more phosphorylated than the other SH2 domain of SH-PTP2. However, both SH2 domains of SH-PTP2 were necessary for association with insulin receptors. Phosphorylation of the SH2 domains of SH-PTP2 resulted in decreased PTPase activities toward the phosphorylated insulin receptor. These results indicate that the insulin receptor can negatively regulate SH-PTP2 activity by means of phosphorylating the SH2 domains.

Cell Line↗
PubMed1994

Chromosomal localization of the protein tyrosine phosphatase G1 gene and characterization of the aberrant transcripts in human colon cancer cells.

We have recently described the isolation of the human PTPG1 gene which encodes a member of intracellular protein tyrosine phosphatases that may be candidates for tumor suppressor genes. In order to investigate the abnormality of the PTPG1 transcript in various human cancer cell lines, we have analyzed the consensus catalytic region of PTPG1 cDNA, using the reverse transcription polymerase chain reaction. In a colorectal carcinoma cell line, DLD-1, we found three aberrant transcripts. Sequencing analysis revealed that one had a missense point mutation and the remainders contained 77 bp and 173 bp deletions, respectively. These alterations might directly affect their phosphatase activities. Our findings provide the first evidence for the aberrant transcripts of the protein tyrosine phosphatase in human cancer cells, and suggest that the aberration of PTPG1 gene might be involved in the tumorigenesis. Moreover, the human PTPG1 gene is localized on chromosome 7q11.23, a region with frequent abnormalities implicated in some human cancers.

Amino Acid Sequence↗
PubMed1994

Induction of protein-tyrosine phosphatase LC-PTP by IL-2 in human T cells. LC-PTP is an early response gene.

Tyrosine phosphorylation has been implicated in interleukin 2 (IL-2)-induced growth signaling and the phosphorylation levels are regulated by the balance of tyrosine kinase and tyrosine phosphatase activities. Here, we demonstrate the rapid activation of a leukocyte tyrosine phosphatase LC-PTP (HePTP) gene expression by IL-2 in an IL-2 dependent human T cell ILT-Mat. Accumulation of LC-PTP mRNA appeared at 1 h and peaked at 6 h after IL-2 stimulation, simultaneous with the G1 to early S phase, and the induction of LC-PTP mRNA did not require protein synthesis. LC-PTP protein increased approximately 6-fold at 8 h after IL-2 stimulation. Nuclear run-on assays showed that the induction of LC-PTP mRNA expression is mostly due to transcriptional activation. These data suggest that LC-PTP is an early response gene and its protein seems to be a crucial molecule which regulates the tyrosine phosphorylation level during T cell proliferation.

Enzyme Induction↗
PubMed1994

Complementary DNA cloning and characterization of truncated form of c-kit in human colon carcinoma cells.

We have obtained a novel c-kit complementary DNA (cDNA) from a colon carcinoma cell line, Colo201, and characterized its structure. The size of the transcript in Colo201 was approximately 3.5 kilobases and it hybridized to the c-kit cDNA fragments encompassing the kinase domain, but not to the cDNA fragments encoding extracellular and transmembrane domains. The predicted protein encoded by those cDNAs was composed of 257 amino acids containing the NH2-terminal 25 unique amino acids in frame by the COOH terminal of the KIT protein. Of interest, these 25 amino acids were encoded by intron 15 of the c-kit gene. The aberrant mRNA was also detected in another colon carcinoma cell line, BM314. The translation of this message in Colo201 was confirmed by flow cytometry and immunoblot analysis. This is the first report describing the aberrant transcript of c-kit in human tumor cells, and it is suggested that truncated form of c-kit might play a role in the onset and development of human colon carcinoma.

Base Sequence↗
PubMed1994

High expression of CD56 (N-CAM) in a patient with cutaneous CD4-positive lymphoma.

Cutaneous lymphoma is a disease characterized with massive skin infiltration of lymphoid malignant cells. They commonly express some T-cell markers, such as CD2, CD3, CD4, and CD7, and thus termed as CTCL (cutaneous T cell lymphoma). Here, we present a case with CD56/N-CAM-positive cutaneous lymphoma, which appears lymphocytic morphology and expresses CD4, but does not express CD2, CD3, CD8, CD14, CD16, CD57, and CD20. The most malignant cells contained no distinctive azurophilic granules in the cytoplasm. Southern blot analysis revealed that T cell receptor-beta, gamma, and immunoglobulin heavy chain genes in the cells were in germ-line configurations. Electron microscopic examination showed characteristics of lymphoid cells with higher nucleocytoplasmic ratio and lacked structures typical of other cell types (i.e., epithelial cells, neuroendocrine cells, and mesenchymal cells). Thus, the cells are likely to be immature lymphoid cells. Histological analysis revealed the cells infiltrate mainly into the dermis with angiocentric growth pattern. The clinical course was aggressive, with rapid involvement of bone marrow and central nervous system. These striking features of the patient may represent a novel fraction (CD2-, CD4+, and CD56+) of cutaneous lymphoma.

Aged↗
PubMed1994

Expression of cytoskeletal-associated protein tyrosine phosphatase PTPH1 mRNA in human hepatocellular carcinoma.

We investigated the mRNA expression of cytosolic protein tyrosine phosphatase (PTPH1), which has a homologous domain to cytoskeletal-associated proteins, in human hepatocellular carcinomas (HCCs) by using reverse transcriptase-polymerase chain reaction (RT-PCR). PTPH1 mRNA was detected in all HCC cell lines (n = 6), and HCC and adjacent noncancerous tissues (n = 8) examined, indicating that PTPH1 was expressed in HCCs and hepatocytes. There was no remarkable difference in the level expression of PTPH1 mRNA between HCC and adjacent noncancerous tissues. We also performed RT-PCR single-strand conformation polymorphism (SSCP) analysis in HCC cell lines and tissues in the C-terminal region of the catalytic domain of PTPH1. In the cHc4 cell line and a HCC tissue specimen, a shifted band was detected, although it was not found in the non-cancerous tissue of the HCC specimen. Nucleotide sequence analysis showed a common mutation from T to C at the third letter of codon 919 which did not lead to amino acid substitution. These results suggest that another mutation leading to the development of HCC could occur in some region of PTPH1 other than that investigated in this study.

Base Sequence↗
PubMed1994

Development of transient thyroid disease and reaction during treatment of chronic hepatitis C with interferon.

Six of 50 (12%) patients with chronic hepatitis C who were treated with interferon developed thyroid disease or an autoimmune thyroid reaction while undergoing treatment. One patient developed silent thyroiditis, with an increase in serum triiodothyronine (T3), thyroxine (T4), free T3, free T4, and markedly suppressed thyroid-stimulating hormone (TSH) levels, accompanied by the appearance of both antithyroglobulin (TgAb) and antimicrosomal antibodies (McAb). One patient developed hypothyroidism in association with moderately elevated TSH levels and high titers of McAb. TSH, TgAb, and McAb levels returned to the initial values at least 4 months after the end of interferon treatment (9 months of follow up). Four patients whose TgAb and/or McAb levels were elevated during treatment with interferon had been diagnosed as having subclinical autoimmune thyroiditis; however, their thyroid function remained in the normal range. These results suggested that treatment with interferon can cause a transient autoimmune thyroid reaction and disease as a side effect.

Autoantibodies↗
PubMed1994

Establishment and characterization of mouse-human chimeric monoclonal antibody to erbB-2 product.

A mouse-human chimeric antibody for erbB-2 product was established by a new procedure using heavy chain loss mouse mutant hybridoma and human immunoglobulin expression vector. The E401 hybridoma secreted anti-erbB-2 product monoclonal antibody (MoAb) (IgG1, kappa). The gene of the mouse variable regions of heavy chain was amplified and cloned by the polymerase chain reaction technique directly from the E401 hybridoma RNA. The variable region of heavy chain was joined with the expression vector, which contains human gamma 1 constant gene. The expression vector was transfected into heavy chain loss mutant cells E401-12, which produced only murine immunoglobulin light chains. A chimeric monoclonal antibody CH401 retained full binding reactivity to erbB-2 product, compared with murine E401 parental antibody. Furthermore, the chimeric MoAb CH401 was much more efficient in supporting antibody dependent cell-mediated cytotoxicity activity against erbB-2-bearing human adenocarcinoma cells than murine MoAb E401. These suggest that a chimeric monoclonal antibody CH401 may be a potent reagent for therapy of human adenocarcinomas.

Adenocarcinoma↗
PubMed1994

Expression of sulfated carbohydrate chains detected by monoclonal antibody 91.9H in human gastric cancer tissues.

Expression of sulfated carbohydrate chains in intestinal metaplasia (IM) and gastric cancer tissues was immunohistochemically evaluated by using a monoclonal antibody (MAb) 91.9H. While normal gastric tissues were negative for MAb 91.9H, IM and cancer tissues were positively stained with high frequency. The incidence was 67% for IM with chronic gastritis (n = 12), 95% for IM with gastric cancer (n = 21), 77% for well and moderately differentiated adenocarcinoma (n = 13), 48% for poorly differentiated adenocarcinoma (n = 23), 89% for signet-ring cell carcinoma (n = 9) and 100% for mucinous adenocarcinoma (n = 7). When poorly differentiated adenocarcinoma cases were divided into two groups, solid (n = 13) and non-solid types (n = 10), the incidences were 8% and 100%, respectively. These data suggest that MAb 91.9H could be of practical use as a new marker for IM and gastric cancer, and may be valuable for subgrouping poorly differentiated adenocarcinomas. Analyses of the core proteins for 91.9H epitope were then carried out. Comparison of immunostaining of ten poorly differentiated adenocarcinoma cases by MAb MUSE11 against MUC1 gene product with that by MAb 91.9H suggested that 91.9H epitope is not expressed on MUC1. Northern blot analysis of 10 pairs of gastric cancer and adjacent normal tissues with a MUC2 cDNA probe showed that the expression level of MUC2 mRNA was below the limit of detection. Thus, 91.9H epitope may be expressed on other proteins than MUC1 or MUC2 core proteins in gastric cancer.

Antibodies, Monoclonal↗
PubMed1994

Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis.

ICAM-1 plays an important role in inflammatory diseases. To assess level of soluble ICAM-1 in the circulation and inflamed lesions, we measured levels of soluble ICAM-1 in the circulation and bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF) and with pulmonary sarcoidosis (PS) and of healthy volunteers (HV), and we also analysed ICAM-1 expression of BALF cells in some patients and HV. IPF patients had significantly higher levels of circulating ICAM-1 than HV, while PS patients did not. By contrast, significantly increased levels of BALF soluble ICAM-1 were found in PS patients compared with those of HV, but not in IPF patients. There were no significant differences in the proportions of ICAM-1+ BALF lymphocytes in IPF patients, PS patients and HV, whereas significantly increased proportions of ICAM-1+ pulmonary alveolar macrophages were found in PS patients compared with those of HV, but not in IPF patients. There was a significant positive correlation of BALF soluble ICAM-1 levels to BALF lymphocyte proportions in PS patients. Although the source of BALF soluble ICAM-1 is unclear, BALF soluble ICAM-1 appears to reflect the grade of local activity of sarcoidosis. An interesting discrepancy between soluble ICAM-1 levels in the circulation and BALF was found in IPF patients, and this might be an important clue to an understanding of this disorder.

Adolescent↗
PubMed1994

Elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and sE-selectin levels in bronchial asthma.

Adhesion molecules such as ICAM-1 and E-selectin have been shown to play important roles in the production of allergic inflammation. In the present study, we measured serum soluble ICAM-1 (sICAM-1) and soluble E-selectin (sE-selectin) levels by ELISA in 42 patients with bronchial asthma (22 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of ICAM-1 and E-selectin in allergic inflammation. Both serum sICAM-1 levels and serum sE-selectin levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels, serum tumour necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. There was a correlation between the nature of change in serum TNF-alpha levels and the nature of change in serum sICAM-1 levels or serum sE-selectin levels, though serum TNF-alpha levels did not correlate with serum sICAM-1 levels or serum sE-selectin levels. These results suggest that higher levels of sICAM-1 and sE-selectin during asthma attacks may reflect the up-regulation of ICAM-1 and E-selectin expression in allergic inflammation, and that the soluble form of these adhesion molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of ICAM-1 and E-selectin in vitro, however; the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels remains to be clarified.

Acute Disease↗
PubMed1994

Significance of erbB-2 gene product as a target molecule for cancer therapy.

The new monoclonal antibodies (MoAbs) E401, E811, E907 and E919 were prepared and characterized. These recognized an extracellular domain (amino acids No. 292-370) on the human c-erbB-2 gene product. Utilizing MoAb E811 and MoAb E919, a double determinant immunoassay (DDIA) was established to detect the soluble and the shed forms of the c-erbB-2 molecule. The levels of circulating erbB-2 antigen in the sera of patients with benign diseases and healthy controls were very low. The incidence of positivity for shed c-erbB-2 antigen in gastric cancer, colonic cancer, gall-bladder cancer, pancreatic cancer and other cancers were 7.4%, 4.2%, 0%, 6.7% and 0%, respectively. Four of 54 patients with gastric carcinoma showed high levels of serum c-erbB-2 antigen. They belonged to clinical stage IV and their histological types were all well differentiated adenocarcinomas (two papillary and two tubular adenocarcinomas). Furthermore, the incidence of positive staining in gastric cancer was 34.6%; higher than that for shedding erbB-2 antigen. Most of the cases which showed erbB-2 expression on cells were well-differentiated adenocarcinomas. Meanwhile, the distribution of erbB-2 antigen was limited in normal tissues. The results suggest that the expression of erbB-2 antigen is largely restricted to adenocarcinoma cells. It may not shed easily from these cells, and therefore it may be a very useful target molecule for passive immunotherapy.

3T3 Cells↗
PubMed1994

Prevalence of HBV and HCV infection in Japanese patients with hepatocellular carcinoma.

The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection was investigated in 63 Japanese patients with hepatocellular carcinoma (HCC). HBV infection was confirmed by measuring hepatitis B surface antigen and HBV-DNA in the serum, and HCV infection was confirmed by measuring antibody to HCV using a 2nd generation test and HCV-RNA in serum. Some 54.0% of the patients had HCV infection only, 27.0% had HBV infection only, and 9.5% had both HCV and HBV infection. Only 9.5% of HCC patients had neither HCV nor HBV markers. These results indicate that, in Japan, HCV and HBV infection is an important factor associated with HCC, and that the hepatitis virus may have a role in the carcinogenesis of HCC.

Adult↗
PubMed1994

The effect of the immune response to Helicobacter pylori in the development of intestinal metaplasia.

AIM: To determine whether cytotoxic Helicobacter pylori antibodies occur in gastric mucosa, and whether these antibodies contribute to the development of intestinal metaplasia. MATERIALS AND METHODS: The number of mononuclear inflammatory cells, which specifically produce immunoglobulin (Ig)G and IgA antibodies, was investigated by using an enzyme-linked immunospot assay and the fraction of mononuclear inflammatory cells determined in gastric biopsy specimens from 34 subjects with H. pylori infection. Assays for the cytotoxicity of H. pylori antibodies were performed on cultured Japanese green monkey kidney (Vero) cells and by in vitro tests. RESULTS: The number of IgG and IgA antibody-producing cells was positively correlated with the degree of inflammation of the gastric mucosa. However, the number of IgG antibody-producing cells was lower in subjects with intestinal metaplasia than in those without. This was not the case for IgA. Significant cytotoxic damage was observed in Vero cells in vitro when incubated in a solution containing the H. pylori IgG antibody, antigen and polymorphonuclear leukocytes. No cytotoxicity was seen with the IgA antibody or with the antigen or polymorphonuclear leukocytes alone. CONCLUSIONS: H. pylori infection is associated with the appearance of immunocompetent mononuclear cells in gastric mucosa. These cells produce H. pylori antibodies of the IgG class which are capable of causing cytotoxic damage in the epithelial cells, obviously through activation of polymorphonuclear leukocytes by antibody-antigen complexes. The occurrence of these cells is inversely related to intestinal metaplasia, suggesting that they may be involved in the processes of epithelial damage leading to the appearance of intestinal metaplasia.

Adult↗
PubMed1994

Structure of the human LC-PTP (HePTP) gene: similarity in genomic organization within protein-tyrosine phosphatase genes.

Recently, various cDNA sequences coding protein-tyrosine phosphatases (PTPs) have been reported and their extensive similarities in the catalytic domains clarified, but knowledge of the structures and organizations of their genes is still limited. In this study, a detailed structure and organization of the human intracellular LC-PTP (also called HePTP) gene is reported. The 13 to 18.5 kb genomic clones encoding human LC-PTP have been isolated. The LC-PTP gene is organized into 11 exons, including the 5'-noncoding first exon and the 3'-noncoding exon. Splicing sites for exons 4 to 10, which encode the conserved catalytic PTP domain, arise almost at the same position as for the CD45 gene. This elucidation of the LC-PTP gene structure provides insight into the domain evolution of intracellular LC-PTP and transmembrane CD45, which may be generated by gene duplications of an ancestral gene.

Amino Acid Sequence↗