Assignment of the human UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase-type-2 gene to chromosomal region 1q42 by fluorescence in situ hybridization.
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Chromosome Mapping↗
Biomedical subjects
K Imai
Publications and source records attributed to K Imai.
Hepatic infarction with portal thrombosis.
A case of hepatic infarction with portal thrombosis is reported. A 63-year-old woman with liver cirrhosis and esophageal varices was admitted for treatment of the esophageal varices. Endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) were performed. Two months later, she experienced right hypochondralgia and right flank pain. Serum transaminase levels were suddenly elevated, and computed tomography scans of the liver showed multiple small nodular lesions. Her condition worsened, and she died of hepatic failure. Autopsy revealed splenic and portal vein thrombosis, multiple hepatic infarction, and evidence of chronic pancreatitis. We believe that liver cirrhosis and chronic pancreatitis were the main risk factors for the portal thrombosis, and the treatment for esophageal varices appeared to have triggered the thrombosis. The hepatic infarction was caused by the portal thrombosis.
Endoscopy, Digestive System↗
Induction of nonspecific cross-reacting antigen mRNA by interferon-gamma and anti-fibronectin receptor antibody in colon cancer cells.
Nonspecific cross-reacting antigen (NCA), a member of the carcinoembryonic antigen (CEA) family, shows increased expression levels in colorectal cancer tissues. To elucidate the mechanism, we observed the effect of interferon (IFN)-gamma on the expression level of NCA mRNA in colon cancer cell lines by quantitative reverse transcriptase-polymerase chain reaction assay. IFN-gamma induced NCA mRNA in three of four cell lines tested. The effect of anti-fibronectin receptor (FnR) antibody on the expression of NCA mRNA was then examined in the same manner. Colo201 and DLD-1 cells showed an increased expression level of NCA mRNA after stimulation with the antibody. On flow cytometry, FnR was expressed in only two, Colo201 and DLD-1, of the five cell lines tested. These findings indicate that IFN-gamma and anti-FnR antibody induce NCA mRNA in cultured colon cancer cell lines, suggesting that inflammatory response and cell-to-extracellular matrix interaction may be related to the increased expression of NCA mRNA in colorectal cancers in vivo.
Antigens, Neoplasm↗
The mouse semaphorin F (Semaf) maps to chromosome 15.
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Alleles↗
Carcinogenesis in accessory sex organs of rats induced by 3,2'-dimethyl-4-aminobiphenyl: response to androgen deprivation.
It is generally accepted that early human prostate cancers reveal higher androgen dependency than do advanced ones. In the present study, we examined whether the animal model of prostate cancer has already lost androgen dependency at the early stages of carcinogenesis. At experimental week 46, androgen deprivation was induced in rats and the incidences of atypical hyperplasia and cancer were examined in the ventral, dorsolateral prostate, coagulating glands, and seminal vesicles. Androgen deprivation significantly lowered the incidence of atypical hyperplasia in all four organs. As for the incidence of cancer, no significant differences were observed in the coagulating glands and seminal vesicles. Regarding atypical hyperplasia, androgen deprivation significantly decreased the proliferative cell nuclear antigen labeling index in the coagulating gland and seminal vesicles. The presence of cancer was also decreased in the coagulating gland but not in the seminal vesicles. With control group specimens, more intense staining of androgen receptor was observed in atypical hyperplasias than in cancers. Compared with the atypical hyperplasias, the cancers revealed low androgen dependency at the early stages of carcinogenesis. The cancers in the seminal vesicles also revealed higher androgen independency than did those in the coagulating gland.
Aminobiphenyl Compounds↗
A human UDP-GalNAc: polypeptide, N-acetylgalactosaminyltransferase type 1 gene is located at the chromosomal region 18q12.1.
The cDNA clone encoding human UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-1 (GalNAc-T1) was isolated from colon tissue by a reverse transcriptase-polymerase chain reaction (RT-PCR). Using fluorescence in situ hybridization, the position of the GalNAc-T1 gene was shown to be localized at the human chromosomal region, 18q12.1.
Chromosome Banding↗
Complement Cls, a classical enzyme with novel functions at the endochondral ossification center: immunohistochemical staining of activated Cls with a neoantigen-specific antibody.
The secondary ossification center of 14- to 16-day-old hamster tibiae was examined immunohistochemically with active and inactive Cls-specific antibodies, RK5 and RK4, respectively. At the ossification center, chondrocytes differentiate from proliferating and hypertrophic to degenerating stages, and their site is occupied by the bone marrow. Cls was strongly immunostained in hypertrophic chondrocytes. In order to discover whether Cls is activated at a particular site, the cartilage was immunostained with RK5 and RK4. RK5 mainly reacted with degrading matrix around invading vessels. In contrast, RK4 strongly stained hypertrophic chondrocytes. Immunoelectron microscopy revealed Cls on degrading fragments of chondrocytes and fibers of cartilage matrix. Decorin, one of the major matrix proteoglycans, was dose and time dependently degraded by Cls. Type II collagen and type I gelatin were also degraded. Articular cartilage from patients with rheumatoid arthritis was positively immunostained (11/12 cases) with an anti-Cls monoclonal antibody (mAb) PG11, whereas normal articular cartilage (5/5 cases) was negative, suggesting Cls participation in the etiology of rheumatoid arthritis.
Amino Acid Sequence↗
Relation of enhanced secretion of active matrix metalloproteinases with tumor spread in human hepatocellular carcinoma.
BACKGROUND & AIMS: Matrix metalloproteinases have been implicated in invasion and metastasis of various human malignant tumors, but its role in human hepatocellular carcinoma has not been characterized in detail. The aim of the present study was to examine the secretion and activation of metalloproteinases in liver tissues from patients with hepatocellular carcinoma and evaluate its relationship with clinicopathologic characteristics. METHODS: Activity of metalloproteinases was measured in 30 surgical specimen pairs of human primary hepatocellular carcinoma and adjacent nontumoral liver and in five cultured human hepatoma cell lines using zymography. A comparison of this activity with clinicopathological features was made. RESULTS: In the liver tissues, enhanced secretion of active forms of gelatinase A and matrilysin was associated with portal venous invasion (P < 0.05, respectively), intrahepatic metastasis (P < 0.05, respectively), and recurrence within the first postoperative year (P < 0.01 and P < 0.05, respectively). Enhanced messenger RNA expression for membrane type 1-matrix metalloproteinase was observed in 22 of 30 cases and associated with capsule invasion and the activation of progelatinase A (P < 0.05, respectively). CONCLUSIONS: Active gelatinase A, active matrilysin, and membrane type 1-matrix metalloproteinase may play an important role in tumor spread of human hepatocellular carcinoma.
Carcinoma, Hepatocellular↗
Comparative studies of the indoleamine dioxygenase-like myoglobin from the abalone Sulculus diversicolor.
The abalone Sulculus diversicolor contains abundant myoglobin in its buccal mass. The myoglobin is homodimeric and the molecular mass of the constituent polypeptide chain is 41,000 Da. The amino acid sequence and gene structure are highly homologous with those of a vertebrate tryptophan-degrading enzyme, indoleamine dioxygenase (IDO). Thus Sulculus myoglobin evolved from an IDO gene, and represents a typical case of functional convergence. The oxygen equilibrium properties of Sulculus myoglobin were examined and compared with those of myoglobins from other sources. It binds oxygen reversibly, and the P50 was determined to be 3.8 mmHg at 20 degrees C and pH 7.4, showing that the oxygen affinity of Sulculus myoglobin is significantly lower than those of usual 16 kDa myoglobins. It also displays no cooperativity (nmax: 1.02-1.06) and no alkaline Bohr effect between pH 7.0 and 7.9. The cDNA-derived amino acid sequences of vertebrate IDOs, molluscan IDO-like myoglobins and a homolog in the yeast Saccharomyces were aligned, and several amino acid residues were proposed as candidates for key residues to control the function of IDO or myoglobin.
Amino Acid Sequence↗
Cytotoxic activity in a case of adult T-cell leukemia/lymphoma with spontaneous regression.
We report a patient with adult T-cell leukemia/lymphoma ATL/L diagnosed by lymph node biopsy, Ga scintigram and monoclonal integration of HTLV-1 proviral DNA. As lymphadenopathy and skin eruption spontaneously improved and disappeared after admission without any treatment, we considered that spontaneous regression had occurred. An immunological study revealed that the cytotoxic activity of the peripheral mononuclear cells in this ATL/L patient at the time of spontaneous regression were significantly higher than those in a healthy control, when tested against cultured ATL cells (Sez627c). As the disease progressed, the cytotoxic activity decreased. These findings suggest that there may exist an immunological response against ATL cells during spontaneous progression suppressing the progression of the disease.
Cytotoxicity, Immunologic↗
Overexpression of cyclin D1 in chronic lymphoproliferation with t(11; 14)(q13; q32)
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Aged↗
Enantiomeric separation and sensitive detection of propranolol, metoprolol and atenolol derivatized with a fluorogenic reagent, 4-(N-chloroformylmethyl-N-methyl)amino-7-N,N-dimethylaminosulf onyl-2,1, 3-benzoxadiazole (DBD-COCl), on cellulose chiral columns in the reversed-phase mode.
An electrophilic fluorogenic reagent, 4-(N-chloroformylmethyl-N-methyl)amino-7-N,N-dimethylaminosulfo nyl-2,1,1,3-benzoxadiazole (DBD-COCl), was used to react with three beta-blockers, propranolol, metoprolol and atenolol, to yield the derivatives which were subsequently verified to be amide compounds (1:1 adducts) derived from the reaction with the secondary amino group of the beta-blockers. DBD-COCl exhibited high reactivity for the reaction completed within 5 min under mild conditions and without any need for a catalyst. The derivatives were well separated enantiomerically on cellulose CSPs (the derivative of propranolol on a Chiralcel OD-R column and those of metoprolol and atenolol on a Chiralcel OJ-R column) in the reversed-phase mode, with the S-configurations being eluted before the R-configurations. The derivatives were stable at 4 degrees C for 1 week. The detection limits (S/N = 3) were 50 fmol for both (S)- and (R)-propranolol, 12 and 17 fmol for (S)- and (R)-metoprolol, respectively, and 15 and 20 fmol for (S)- and (R)-atenolol, respectively.
Adrenergic beta-Antagonists↗
Two promoters in expression of estrogen receptor messenger RNA in human breast cancer.
The human estrogen receptor (ER) gene has recently been shown to transcribe two types of mRNA originating from two distinct promoters in mammary tumor cell lines, which encode the same protein. However, use of the two promoters has not been addressed in human breast cancer, which reveals a heterogeneity in terms of ER expression status and clinical characteristics. In this report, we investigated which promoter is responsible for the expression of ER in human mammary tumors by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis for discriminatory detection of the two transcripts in mammary tissues obtained from patients with breast cancer. First, the use of distinct promoters was confirmed in several mammary tumor cell lines by the present RT-PCR method. Secondly, expression levels of total ER mRNA and two types of mRNAs from the different promoters were analysed in tumor, surrounding tissue and normal tissue obtained from 12 patients with breast cancer, which showed various levels of ER protein. In tumors, levels of total ER mRNA and the mRNA transcribed from a distal promoter showed remarkable correlation to the ER protein levels with correlation coefficients 0.946 (P < 0.001) and 0.746 (P < 0.005), respectively. In contrast, mRNA from a proximal promoter showed no correlation to the ER protein levels. Our results indicate that the enhancement of the ER mRNA expression from the distal promoter plays an essential role in the mechanisms of overexpressing ER protein in human mammary tumors, implying that a tumor-specific regulation of ER expression involved use of the distal promoter.
Adult↗
Cytotoxic T lymphocytes derived from bone marrow mononuclear cells of multiple myeloma patients recognize an underglycosylated form of MUC1 mucin.
MUC1 is a highly immunogenic epithelial mucin and serves as a tumor-associated antigen in breast, pancreatic and ovarian carcinomas. We previously reported the expression of MUC1 on myeloma cells and the establishment of an HLA-unrestricted cytotoxic T lymphocyte (CTL) line TN that recognized MUC1 from peripheral blood mononuclear cells in a multiple myeloma patient. In this study, we attempted to induce such CTL from six other multiple myeloma patients consecutively in order to show that the induction of the CTL line TN had not resulted from some idiosyncrasy of the first patient. Bone marrow mononuclear cells were used to induce CTL, because they contain myeloma cells that might stimulate the autologous lymphocytes. Bulk CTL lines were induced from two out of six patients. The CTL line TS was CD8+ cell dominant and KY was CD4+ cell dominant. Both CTL lines lysed MUC1+ myeloma and breast carcinoma cell lines. The cytotoxicity of the CTL lines was inhibited by anti-CD3, anti-alpha beta TCR and anti-MUC1 mAb. It was also inhibited by a MUC1 transfectant, but not by a mock transfectant in cold target inhibition assays. MUC1 was transfected into a human colonic carcinoma cell line. The reactivity of anti-MUC1 core protein mAb and the cytotoxicity of the CTL against the transfectant was enhanced by the treatment of the cells with an O-glycosylation inhibitor. Thus it is generally accepted that the HLA-unrestricted CTL which directly recognize the underglycosylated from of MUC1 using their TCR could be induced from a certain proportion (approximately 30%) of untreated multiple myeloma patients.
Antibodies, Blocking↗
Remarkable functional aspects of myoglobin induced by diazaheme prosthetic group.
The iron complex of beta,delta-diazamesoporphyrin III, a molecular hybrid of porphyrin and phthalocyanine, was incorporated into apomyoglobin to investigate novel biological aspects of myoglobin. The reconstituted ferric protein forms an internal hemichrome with the iron-bound distal histidine. The reduced ferrous protein has extraordinarily high affinities for O2 and CO. The ferrous myoglobin is capable of strong binding with pyridine, imidazole, cyanide, and azide, and reacts moderately with ammonia. The NO complex exhibited 5-coordinate to 6-coordinate transition over 150 min. The instability of 5-coordinate NO heme is consistent with a high affinity of imidazole to the ferrous heme. The kinetic analyses of the ferrous derivatives suggest the importance of the pi orbitals in neutral ligands as well as the negative charges in anionic ligands. A high affinity of imidazole to ferrous diazaheme accounts for the internal hemochrome formation in ferrous myoglobin containing phthalocyanines.
Acids↗
Serum levels of sICAM-1 and 5-S-cysteinyldopa as markers of melanoma progression.
The serum levels of the soluble form of intercellular adhesion molecule-1 (sICAM-1) and 5-S-cysteinyldopa (5-S-CD) were determined by double determinant immunoassay and high-performance liquid chromatography, respectively. Fifty-three melanoma patients (stage 1, 12 patients; stage II, 11; stage III, 19; and stage IV, 11; total number of samples, 116) and 31 age- and sex-matched healthy control subjects were analysed. Both the sICAM-1 and 5-S-CD levels were significantly higher in stage IV patients than those in stage I, II and III patients (sICAM-1; all P < 0.001; 5-S-CD; all P < 0.05). The serum levels of 5-S-CD were elevated only in stage IV patients. sICAM-1 levels elevated gradually with disease progression. Testing of sequential bleedings showed that both sICAM-1 and 5-S-CD levels were elevated in most of the patients whose disease had progressed. However 5-S-CD levels were not elevated in those patients whose metastases were amelanotic. There was a statistically significant correlation between sICAM-1 and 5-S-CD levels (R = 0.6 55, P < 0.001). Serum levels of 5-S-CD may be a useful parameter for monitoring the clinical course of the disease in patients whose metastases are melanotic. Analysis of both sICAM-1 and 5-S-CD levels in serum will contribute greatly to monitoring the clinical course of melanoma patients.
Adolescent↗
Testosterone replacement therapy for male hypogonadism with a radiation-polymerized testicular prosthesis.
BACKGROUND: The effect of an artificial testicular prosthesis on sexual disturbance in hypogonadal men was investigated. METHODS: Twelve hypogonadal men were treated with testosterone replacement therapy delivered via radiation-polymerized testicular prostheses surgically implanted in their scrotums. RESULTS: An average serum testosterone level of over 200 ng/dL was maintained for 48 months. Most patients treated with this prosthesis were satisfied with the improvement of their sexual activity. Moreover, the patients were psychologically more satisfied with the enlarged scrotum achieved with the implanted prosthesis. CONCLUSION: We recommend this prosthesis as the first choice among testosterone-replacement therapies for hypogonadal men.
Adolescent↗