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Biomedical subjects

A Yachi

Publications and source records attributed to A Yachi.

At least 55 records · Page 3Linked to original sources
PubMed1993

Expression and chromosomal assignment of PTPH1 gene encoding a cytosolic protein tyrosine phosphatase homologous to cytoskeletal-associated proteins.

We have investigated the mRNA expression of 2 human protein tyrosine phosphatases with sequence homology to cytoskeletal proteins, PTPH1 and PTPMEG. Northern-blot analysis of PTPH1 using poly (A)+ RNA from normal human colon tissue showed a low-abundance message of 4.3 kb. Reverse-transcriptase/polymerase-chain reaction (RT-PCR) was therefore used to detect it in a wide variety of cell lines including 9 colorectal, 5 gastric, 5 hepatic and 6 hematopoietic tumor cells. PTPH1 mRNA was not detected only in Colo 320 cells over-expressing c-myc mRNA, among the colorectal cancer cell lines examined. When Colo 320 cells were incubated with 5 mM sodium butyrate for 5 days, PTPH1 mRNA became detectable, concomitant with the marked decrease in the expression level of c-myc mRNA. Moreover, the chromosomal localization of PTPH1 gene was investigated by fluorescence in situ hybridization. Interestingly, PTPH1 gene was mapped to 9q31 where the gene for Gorlin syndrome, a putative tumor suppressor gene, exists.

Base Sequence↗
PubMed1993

A fucose residue can mask the MUC-1 epitopes in normal and cancerous gastric mucosae.

MUSE11, DF3 and SM3 MAbs react with a synthetic peptide of 20 amino-acids: VTSAPDTRPAPGSTAPPAHG. This sequence is a tandem repeat domain of the mucin-type glycoprotein coded by the muc-1 gene. MUSE11 and DF3 MAbs immunoreact strongly with mucus cells of the normal surface gastric epithelium of Le(a+b-) non-secretors, but in spite of the peptidic nature of the recognized epitope, the same tissue of Le(a-b+) secretors reacts only after treatment with alpha-fucosidase. These reactions are inhibited by the PNA lectin, which recognizes the T disaccharide antigen (beta Gal 1-3 alpha GalNAc), suggesting that the peptide epitope may be close to the T-saccharide structure. The SM3 MAb reacted on the surface gastric epithelium of all individuals after a more drastic deglycosylation using 20 mM periodate. Computer modeling of the MUC-1 immunoreactive glycopeptide containing the H type-3 trisaccharide alpha Fuc 1-2 beta Gal 1-3 alpha GalNAc- bound to the threonine of the PDTRP-pentapeptide shows that the peptide epitope might be masked when the fucose is positioned over the arginine. Thus, a single fucose linked to the T structure could mask the MUC-1 epitopes. In gastric adenocarcinomas, MUSE11 and SM3 epitopes are expressed in 75% (25/33) and 9% (3/33) respectively, while, after partial deglycosylation by periodate treatment, they are positive in 100% (33/33) and 70% (23/33) of cases, respectively.

Adolescent↗
PubMed1993

Expression of MMP-7(PUMP-1) mRNA in human colorectal cancers.

The expression of MMP-7 (pump-1) gene was examined in 10 cases of colorectal cancer by utilizing RT-PCR. In 9 out of 10 cases, MMP-7 mRNA was detected in cancerous tissue, whereas none was detected in adjacent normal colon tissue. However, this message was detected in only 1 out of 6 colon-cancer cell lines. In colonic mucosa from 3 patients with ulcerative colitis it was not detected. The expression of MMP-2 (72-kDa type-IV collagenase) mRNA was also investigated in the same tissue samples, and was detected in all samples, including cancerous and non-cancerous tissue. Our data suggest that MMP-7 is expressed in a tumor-associated manner in colorectal cancers and may play a role in tumor progression.

Adult↗
PubMed1993

Decreased expression of DCC mRNA in human colorectal cancers.

The mRNA expression levels of DCC gene, which is cloned from the deleted region of chromosome 18q in colorectal cancers and thought to be a tumor-suppressor gene, was evaluated in tissue specimens surgically resected from patients with colorectal cancer by RT-PCR. This method was chosen as the expression level of DCC mRNA is below the detectable level for Northern-blot analysis. Semi-quantitative measurements of DCC mRNA were performed based on a standard curve defined by serial dilution of DCC cDNA. As a result, the expression level of DCC mRNA was found to be lower in 17 out of 30 colorectal cancers than in adjacent non-cancerous tissues. Inclusion of smooth muscle in tissue specimens was observed to have little disturbing effect on comparisons between cancerous and non-cancerous regions. In addition, all 4 specimens of colorectal cancer with liver metastasis showed the decreased expression level of DCC mRNA, suggesting that functional loss of DCC in cancerous tissues may play an important role in metastatic events.

Actins↗
PubMed1993

Primary structure of the variable regions of a monoclonal antibody MUSE11 recognizing the tandem repeat domain of a mucin core protein, MUC1.

A monoclonal antibody (MAb) MUSE11 recognizes an epitope in the tandem repeat domain of a mucin core protein, MUC1. We show that the epitope of MAb MUSE11 could be within the continuous amino acid sequence PDTRPAPG. Since there is increasing evidence indicating that this region is highly immunogenic, cDNA cloning of the variable regions of heavy-chain (VH) and of light-chain (VL) of MAb MUSE11 was performed by using RT-PCR to provide a basis for analyzing the structure of the antibody-antigen complex and for producing anti-idiotypic antibodies. The deduced amino acid sequence revealed that the VH and VK of MAb MUSE11 could be assigned to subgroups IIIA and II of mouse immunoglobulin heavy and light chains, respectively. When compared with the V regions of other MAbs in the same subgroup, the complementary determining region 3 (CDR3) in the VH region of MAb MUSE11 consisted of a unique sequence that may be important in defining the specificity of MAb MUSE11.

Amino Acid Sequence↗
PubMed1993

Rare frequency of activation of the Ki-ras gene in rat colon tumors induced by heterocyclic amines: possible alternative mechanisms of human colon carcinogenesis.

Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility of involvement of ras gene activation in colon carcinogenesis in rats as in humans. We examined mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes by polymerase chain reaction--direct sequencing in seven colon tumors in F344 rats induced by 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1), 11 induced by 2-amino-3-methylimidazo[4,5-f]quinoline, and nine induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A Ki-ras gene mutation (G-->T at the second position in codon 12) was found in one Glu-P-1-induced colon adenocarcinoma. None of the other 26 tumors had mutations in any of these three ras family genes. These results indicate that in rats, colon carcinogenesis induced by heterocyclic amines may be induced by alterations of other oncogenes or tumor suppressor genes. We think this experimental system using carcinogens to which humans are exposed is a good model for studying alterations of other genes in human colon tumors in which no Ki-ras alterations are observed.

Adenocarcinoma↗
PubMed1993

The epidemiology and infection route of asymptomatic HCV carriers detected through blood donations.

The Japan Red Cross started screening donated blood for anti-HCV in Nov. 1989. Approximately 0.9% of donors were found to be positive by the 1st generation antibody test. The authors started a carrier clinic for the medical care of apparently healthy HCV carriers. Donors whose antibodies were strongly positive both by 1st EIA and 2nd PHA were informed, and were confirmed by RIBA 2 and RT-PCR. A total of 262 carriers (150 males and 112 females) with mean age of 46.8 +/- 11.2 yrs have visited the clinic. Of these carriers 149 were diagnosed to be asymptomatic clinically, biochemically and echographically. Eighty-seven carriers had received blood transfusions 22.7 +/- 10.9 yrs previously, while 106 had had acupuncture. Sixty had a family history of liver disease. Fifty-four had a history of heavy alcohol intake. Tattoos and/or iv drug abuse were found in 11, and nosocomial needle accidents in 4. HBV antibodies were found in 145 cases (55%). In conclusion, approximately 60% of HCV carriers found at the time of blood donation were apparently asymptomatic, suggesting the need of longer follow-up. Main routes of infection were estimated to be blood transfusion (33%), other parenteral exposure routes (6%), household (10% or less), and acupuncture (20% or less), considering duplication and priority.

Blood Donors↗
PubMed1993

Detection of a circulating antibody against a peptide epitope on a mucin core protein, MUC1, in ulcerative colitis.

This study aims at clarifying whether the humoral immune response to the tandem repeat domain of MUC1 can be induced or not in vivo. The expression of MUC1 mRNA in the colon was revealed by Northern blot analysis, and cDNA cloning of an extracellular tandemly repeated domain of MUC1 was then performed to prepare the recombinant MUC1 protein. A cDNA clone coding for ten repeat domains was ligated into an expression vector in prokaryotes, resulting in a recombinant protein which could react with the MAb MUSE11 against an adenocarcinoma-associated antigen whose epitope has been shown to be localized in the tandem repeat domain on MUC1. The reactivity of sera from patients with ulcerative colitis with the recombinant protein was evaluated by SDS-PAGE and Western blot analysis to detect the antibodies against this tandem repeat domain. Five out of 19 serum samples tested positive, and these reactions were totally inhibited by MAb MUSE11, suggesting that the epitope recognized by these antibodies in sera is almost identical to that recognized by MAb MUSE11. The data represent the first demonstration of antibody production against a peptide epitope of the tandem repeat domain of MUC1.

Adolescent↗
PubMed1993

Soluble intercellular adhesion molecule-1 (ICAM-1) antigen in patients with rheumatoid arthritis.

Intercellular adhesion molecule-1 (ICAM-1), a member of the immunoglobulin supergene family, is known to play an important role in inflammatory diseases. Using a previously developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies (MoAbs) against human ICAM-1, levels of soluble ICAM-1 (sICAM-1) were measured in sera from patients with collagen diseases and in synovial fluids (SF) from patients with rheumatoid arthritis (RA). Although the results did not demonstrate that RA and other collagen diseases, as a group, had significantly higher levels of sICAM-1 in sera as compared with healthy controls, 21 of 138 cases (15%) with collagen diseases and 11 out of 57 patients (19%) with RA clearly showed higher levels of sICAM-1 in the sera. Comparisons between RA patients of radiological stages I and II and between stage I and other stages showed significantly higher levels of sICAM-1 in the sera of patients in the latter stages. RA patients with vasculitis and/or pneumonitis showed significantly higher levels of sICAM-1 than those without vasculitis or pneumonitis. Significant correlations were demonstrated between sICAM-1 and the factors IgG-RF, IgM-RF, erythrocyte sedimentation rate (ESR) and TNF-alpha in sera of RA patients. In addition, it was noted that the levels of sICAM-1 in SF were as high as those in the sera of patients with RA.

Adult↗
PubMed1993

Elevated levels of soluble ICAM-1 in sera from patients with bronchial asthma.

We measured the levels of soluble intercellular adhesion molecule-1 (sICAM-1) in sera from patients with bronchial asthma. sICAM-1 levels in sera from atopic asthmatic patients in stable conditions were higher than in normal control subjects. Furthermore, the sICAM-1 levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These results suggest that higher levels of sICAM-1 in sera reflect the upregulation of ICAM-1 expression in allergic inflammation.

Adult↗
PubMed1993

Expression of c-kit and kit ligand in human colon carcinoma cells.

To determine whether c-kit and kit ligand (KL) mRNAs could be expressed in human epithelial tumors, reverse transcriptase-polymerase chain reaction and Northern blot analysis were performed. KL mRNA was shown to be expressed in a variety of epithelial tissues and cell lines. The expression of c-kit mRNA was then examined in hepatocellular and colon carcinoma cell lines. While hepatocellular carcinoma cell lines did not express c-kit mRNA as far as we could ascertain, 2 of 5 colon carcinoma cell lines showed the expression of both c-kit and KL mRNAs. Furthermore, the expression of c-kit in these cells was demonstrated at the protein level by flow cytometry. These data suggest that c-kit and KL may play an important role as an autocrine loop in the proliferation of some colon carcinoma cells.

Base Sequence↗
PubMed1993

Elevated concentrations of circulating ICAM-1 in far advanced and miliary tuberculosis.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in inflammatory diseases. Cellular expression and shedding of ICAM-1 are up-regulated by cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). With an ELISA containing two monoclonal antibodies to human ICAM-1, we measured concentrations of circulating ICAM-1 in patients with tuberculosis. Prominently elevated values were found in miliary tuberculosis and in far advanced pulmonary tuberculosis but not in minimal or moderately advanced disease. The measurement of serum IFN-gamma and TNF-alpha also revealed high concentrations of the cytokines in miliary tuberculosis and far advanced pulmonary tuberculosis. The circulating ICAM-1 values were significantly correlated to serum IFN-gamma and TNF-alpha values. In the case of miliary tuberculosis and far advanced pulmonary tuberculosis treated with antituberculous drugs, the circulating ICAM-1 concentrations were gradually decreased to correspond with improvement of clinical symptoms and chest X-ray findings. The measurement of circulating ICAM-1 is useful to evaluate the severity of tuberculosis and to monitor disease activity during antituberculous drug treatment.

Adult↗
PubMed1993

An episode of silent thyroiditis in a patient with chronic thyroiditis and papillary adenocarcinoma following alpha interferon treatment for hepatitis C.

In the present paper we described the first case report of silent thyroiditis following alpha-interferon (IFN-alpha) treatment for chronic type C hepatitis in Japan. A 51-year-old woman with chronic type C hepatitis was treated with 6 million units of IFN-alpha three times a week for 24 weeks. Thyroid function was within normal limits and thyroid autoantibodies were negative before IFN therapy. Sixteen weeks after initiation of the treatment, she complained of increasing fatigue, palpitation and losing 7 kg in weight. Thyroid function tests at that time revealed an increase in serum T3, T4, free T3 and free T4 and a markedly suppressed TSH concentration. Both antithyroglobulin antibody (TgAb) and antimicrosomal antibody (McAb) were positive in a dilution of 1: 400. The computed tomographic (CT) scan of the thyroid showed a decrease in the CT number (Hounsfield unit; H.U.) to 58 H.U. (normal, 95-167 H.U.). The 24-h thyroid uptake of 123I was 0.75%. Aspiration biopsy specimens from a nodule in the right lobe and the remaining struma disclosed papillary adenocarcinoma and Hashimoto thyroiditis, respectively. Thyroid function spontaneously returned to normal two months after the onset of thyrotoxicosis through the subclinical hypothyroid stage. After recovery of thyroid function, patient had an operation of papillary cancer without any complications. These clinical features and laboratory findings led to the diagnosis of silent thyroiditis developing in the course of the long-term IFN therapy, which, to our knowledge, has not been reported before in Japan.

Adenocarcinoma, Papillary↗
PubMed1993

Gastric non-Hodgkin's lymphoma associated with Behçet's disease.

The first case of primary gastric lymphoma associated with Behçet's disease is reported. A 43-year-old woman, who had been treated for Behçet's disease for 15 years, was diagnosed as low-grade and small lymphocytic malignant lymphoma of the stomach. Although the patient had been treated for Behçet's disease, chemotherapy was performed and a complete remission of gastric lymphoma was achieved. The literature regarding the association of malignant diseases with Behçet's disease is briefly reviewed.

Adult↗