PAF acetylhydrolase activities in human systemic lupus erythematosus and lupus-prone mice.
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1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Biomedical subjects
Y Tsukada
Publications and source records attributed to Y Tsukada.
Determination of nucleotide sequence of active site for catalytic properties of ADH3 genes.
Alcohol dehydrogenase genes show polymorphism. gamma subunits, which are encoded by ADH3 genes, have two subtypes according to the single base substitution of codon 271 and 349. This mutation of codon 271 directly determines subtypes with different catalytic properties. However, there has been no simple technique to detect nucleotide changes at codon 271. Specific amplification of nucleotides around codon 271 was difficult because of homologous nucleotide sequences around the region among 3 ADH genes (ADH1, 2 and 3). We have developed a method to amplify the ADH3 gene alone with a modification on 3'-end of primer by polymerase chain reaction. Approximately 200 nucleotides including codon 271 of ADH3 gene were sequenced, and genotypes of ADH3 gene were determined in 30 Japanese individuals. This method may facilitate the studies on racial differences of genotypes and involvement of ADH genes in patients with alcoholic liver disease.
Alcohol Dehydrogenase↗
Plasma platelet-derived growth factor levels in coronary circulation in unstable angina pectoris.
To examine whether plasma platelet-derived growth factor (PDGF) levels are elevated in the coronary circulation of patients with unstable angina, the plasma PDGF levels in the coronary sinus and aortic root were simultaneously examined in 14 patients with unstable angina, 15 with stable exertional angina, and 15 control subjects. The mean plasma PDGF level (pg/ml) in the coronary sinus was significantly higher (p less than 0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (502.1 +/- 98.7 vs 301.3 +/- 62.5, and 312.7 +/- 62.6). However, there were no significant differences in mean plasma PDGF levels in the aortic root among the 3 groups. It is concluded that PDGF release is increased in the coronary circulation in patients with unstable angina.
Aged↗
Elevation of platelet-associated IgG in aplastic anemia.
We determined platelet-associated IgG (PAIgG) levels in patients with aplastic anemia, idiopathic thrombocytopenic purpura (ITP), iron deficiency anemia, and systemic lupus erythematosus (SLE), as well as in normal healthy adults as a control group. To determine PAIgG levels, we used a competitive micro enzyme-linked immunosorbent assay, which had excellent reproducibility, recovery, and dilution. We confirmed its reliability by comparing it to the immunoradiometric assay. Both the aplastic anemia group (n = 27, mean +/- SD = 218.6 +/- 244.6 ng/10(7) platelets) and the ITP group (n = 82, mean +/- SD = 212.5 +/- 327.8 ng/10(7) platelets) had higher PAIgG levels than the SLE group (n = 4, mean +/- SD = 38.4 +/- 22.4 ng/10(7) platelets), iron deficiency anemia group (n = 10, mean +/- SD = 16.1 +/- 3.6 ng/10(7) platelets), and normal control group (n = 69, mean +/- SD = 16.1 +/- 3.6 ng/10(7) platelets. The higher platelet-associated IgG levels in aplastic anemia suggest that autoimmune mechanisms are involved.
Adolescent↗
Growth of a human yolk sac tumor cell line with yolk sac-derived functions in selenium-supplemented chemically defined synthetic medium.
A human yolk sac tumor cell line, TG1, which was established from a testicular yolk sac tumor, was found to replicate continuously in a chemically defined medium supplemented with Na2SeO3 (ISRPMI). TG1 produced several plasma proteins and growth factors: albumin, alpha-fetoprotein (AFP), ferritin, carcinoembryonic antigen, beta-2-microglobulin, polyamine, neuron specific enolase, tissue polypeptide antigen, transferrin (Tf), epidermal growth factor, and platelet derived growth factor. By analysis of lentil lectin (LcHA)-affinity electrophoresis, to examine the microheterogeneity of carbohydrate chains of synthetic glycoproteins, TG1 cells cultured with ISRPMI produced only LcHA reactive Tf and AFP based on core fucose attached to asparagine-linked N-acetylglucosamine residues instead of LcHA-nonreactive Tf and AFP produced by TG1 cells cultured with fetal bovine serum (FBS)-containing medium. alpha 1-6 Fucosyltransferase activity was significantly greater in the TG1 cells cultured with ISRPMI (39.9 +/- 1.5 pmol.h-1.mg-1 protein) than cultured with FBS-containing media (18.2 +/- 1.2 pmol.h-1.mg-1 protein). These results have indicated that the selective increase of alpha 1-6 fucosyltransferase occurred when the cells were cultured with the FBS-free synthetic media.
Carcinoembryonic Antigen↗
Production of chromogranin A and B derived peptides in human small cell lung carcinoma cell lines.
Production of chromogranin (Cg)A and B derived peptides [pancreastatin (PST), GAWK, CCB] was studied using human lung carcinoma derived cell lines. PST-like immunoreactivity (LI) was detected in the culture medium in 3 of 6 small cell lung carcinoma (SCLC) cell lines, while GAWK- and CCB-LIs were detected in 5 of 6 and all the 6 SCLC cell lines, respectively. CCB-LI was produced in large amounts in SCLC cell lines as compared to PST- and GAWK-LIs. In non-SCLC cell lines, on the other hand, PST- and GAWK-LIs were not detected. CCB-LI was detected in 1 of 7 non-SCLC cell lines, but not detected in the remainder. PST, GAWK and CCB-LIs, secreted by these cell lines, consisted of several peaks, and these peaks were different among cell lines. This suggests that processing of CgA and B is different in the cell lines. Production of CgA and B derived peptides seems to be a characteristic feature of SCLC, and among them, CCB LI may be a useful marker for SCLC.
Carcinoma, Small Cell↗
Immunotargeting chemotherapy for AFP-producing pediatric liver cancer using the conjugates of anti-AFP antibody and anti-tumor agents.
The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated experimentally and clinically. The conjugate was made from mouse monoclonal antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared with the same ratio. Each drug was injected intraperitoneally, three times at the total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP. Tumor growth was inhibited significantly in the conjugate group compared with the other mixture group, the ADM or CDDP group, and the control group. Clinically, the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs) and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from the viewpoint of volume suppression rate showed partial response in 2 cases and no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal antibodies may be a promising method for treatment of malignant epithelial liver cancer in children.
Adolescent↗
HLA profiles of multiple sclerosis in Hokkaido, the northernmost island of Japan.
We studied HLA haplotypes in 43 consecutive clinically definite MS patients in Hokkaido. The patients were classified into Group A, 12 patients with acute transverse myelopathy (ATM) during the course of illness, and Group B, 31 without ATM. We found an association with HLA-DQw7 in Group A, and with DR4 and DRw8 in Group B. The frequency of DQw7 and DR4 were significantly different between Groups A and B. This study may indicate the different genetic backgrounds between the groups. DRw8 and DRw52 antigens were significantly more common in MS than in controls. Our result is inconsistent with previous Japanese studies, and ethnic variation might be considered as a possible cause of the contradiction.
Adult↗
Cerebral occlusive vasculopathy in systemic lupus erythematosus and speculation on the part played by complement.
A 35 year old woman with systemic lupus erythematosus and hypocomplementenaemia presented with new onset seizures and subsequently died. At necropsy, widespread microinfarctions of the cerebral cortex were found to be predominantly due to the formation of leucoaggregates within small blood vessels without any vasculitis.
Adult↗
A novel sulfatase from Pseudomonas testosteroni hydrolyzing lithocholic acid sulfate.
Pseudomonas testosteroni ATCC 11996 was found to produce a novel bile acid sulfate sulfatase that hydrolyzes the sulfate ester bond in lithocholic acid sulfate (LCA-S). The enzyme synthesis was induced by several kinds of bile acids including LCA-S. Mn2+ functioned as an essential component for the enzyme synthesis and SO4(2-) suppressed it. This sulfatase hydrolyzes LCA-S to isolithocholic acid and sulfuric acid with inversion of alpha- to beta-configuration of the hydroxyl group at the third position of lithocholic acid.
Chromatography, Gas↗
[Clinical and statistical features of liver cirrhosis in Japan].
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Adult↗
[Antibodies to poly (adenosine diphosphate-ribose) in systemic lupus erythematosus and drug induced lupus].
The difference between anti poly (ADP-ribose) antibodies was studied in patients with systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS) and drug-induced lupus (DIL). Radioimmunoassay showed that high concentrations of anti poly (ADP-ribose) antibodies (10.3-22.2%) were induced by phenobarbital, phenytoin, valproic acid (anti-epileptic agent) and procainamide (anti-arrhythmic agent). Poly (ADP-ribose) antibodies were separated by hydroxylapatite column chromatography. The average chain length of the polymer consisted of 2.4, 10.8 and 28.2 ADP-ribose units. Anti poly (ADP-ribose) antibodies from patients with SLE and PSS reacted with 2.4, 10.8, and 28.2 ADP-ribose units in RIA, but those from patients with DIL reacted only with 28.2 ADP-ribose units in RIA. The binding specificity of anti poly (ADP-ribose) antibodies from pregnant women was found to be very similar to that of the antibodies from case of DIL. The present results clearly demonstrated that anti poly (ADP-ribose) antibodies found in systemic autoimmune diseases bound not only to poly (ADP-ribose) with an average chain length of more than 20 ADP-ribose units, but also to oligo (ADP-ribose) with an average chain length of about 2 ADP-ribose units. Anti poly (ADP-ribose) antibodies found in DIL cases and pregnant women, however, bound only to poly (ADP-ribose) with an average chain length of more than 20 ADP-ribose units.
Antibodies↗
[Elevation of serum fucosyltransferase activities in malignant diseases--a sensitive tumor marker?].
Fucosyltransferase (FT) is considered to be one of the most important glycosyltransferases responsible for the synthesis of cancer-associated carbohydrate chains such as CA19-9 and SLX. To determine whether FT is a sensitive tumor marker, we measured the enzyme activity of FT in sera from 136 cancer patients, 14 patients with benign diseases and 59 healthy controls, by using PA (pyridylamino)-labeled type II biantennary oligosaccharide derived from human serotransferrin as an acceptor substrate. Serum FT activity was significantly elevated in patients with cancer compared to healthy controls. Analysis of the enzyme products using HPLC and various fucosidases with different specificity revealed that alpha 1----3 FT was responsible for most of the elevation of the enzyme activity in sera from cancer patients. It should be stressed that the alpha 1----3FT derived from cancer patients transferred fucose to terminal lactosamine residues of type II biantennary oligosaccharides already attached to sialic acid. This indicates that the substrate specificity is clearly different from that reported in normal sera and tissues. In addition to alpha 1----3FT, some glycosidases including fucosidase were also elevated in sera from cancer patients.
Biomarkers, Tumor↗
Protective effect of the new antiplatelet agent 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine on myocardial damage due to coronary occlusion and reperfusion in rabbit.
The effects of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) on infarct size, myeloperoxidase (MPO) activity and plasma prostanoid levels were studied using coronary artery occlusion (1 h)-reperfusion (3 h) model in rabbits, comparing with acetylsalicylic acid (ASA). Myocardial infarct size, MPO activity in the infarcted region and plasma glutamate oxalo-acetate transaminase, lactate dehydrogenase and creatine kinase were significantly suppressed by treatment with KC-764 (2 mg/kg i.v.), but not by ASA (10 mg/kg i.v.). KC-764 completely depressed the increase in plasma TXB2 level during occlusion-reperfusion with a little influence on plasma 6-keto-PGF1 alpha. Thus, the ratio of 6-keto-PGF1 alpha to TXB2 levels was increased by KC-764. On the other hand, ASA treatment depressed both plasma TXB2 and 6-keto-PGF1 alpha levels to the same extent. The in vitro study with guinea-pig neutrophils showed that KC-764 reduced the chemotaxis induced by formyl-methionyl-leucyl- phenylalanine at 3 x 10(7)-3 x 10(-6) mol/l, while ASA did not influence the neutrophil chemotaxis. These results suggest that KC-764 may salvage the damaged ischemic myocardium by the selective inhibition of TXA2 synthesis and the suppression of leukocyte migration.
6-Ketoprostaglandin F1 alpha↗
Local formation and degradation of endothelin-1 in guinea pig airway tissues.
Endothelin(ET)-1 and big ET-1 caused potent and sustained constriction of isolated guinea pig bronchus. The response to ET-1 was enhanced by phosphoramidon in a simple dose-related manner (0.01-1000 microM), while the response to big ET-1 was enhanced at lower doses (0.01-0.1 microM) but was suppressed at higher doses (100-1000 microM) of phosphoramidon. Big ET-1, when given intravenously (i.v.) to anesthetized guinea pigs, increased both bronchopulmonary inflation pressure and mean arterial blood pressure (2.5, 5, 10 nmol/kg i.v.). The pressor response to big ET-1 was attenuated by phosphoramidon dose-relatedly, while the pulmonary response was modified in a complex fashion composed of delayed onset and prolonged duration of action. These results suggest that ET converting as well as degrading enzymes coexist in the airway tissue and both enzymes are sensitive to phosphoramidon, so that phosphoramidon acts bifunctionally to reduce and stimulate the airway responses to big ET-1.
Animals↗
Cervical implantation metastasis by endometrial adenocarcinoma.
A distinct type of cervical involvement by endometrial cancer is reported and termed cervical implantation metastasis. It is believed to result from implantation of endometrial cancer on the denuded endocervix after fractional dilatation and curettage (D & C). The histologic criteria for diagnosis are: (1) the cervical implantation metastasis must be imbedded in the endocervical epithelium or superficial stroma surrounded by an implantation site of inflammatory cells and granulation tissue (free-floating cancer cells above the cervical mucosa are not acceptable as implantation tissue), (2) the histologic findings of the cervical implantation metastasis must be similar to those of the endometrial adenocarcinoma in the uterine corpus, (3) the cervical implantation metastasis must be separate from the primary tumor with no evidence of direct extension, and (4) the cervical implantation metastasis should be surrounded by nonneoplastic endocervical glands with no transition between the two. Of the 176 patients who underwent fractional D & C before hysterectomy, nine (5%) were found to have cervical implantation metastasis. No patients had cervical implantation metastasis who did not undergo fractional D & C before hysterectomy. When stratified according to stage, grade, and myometrial invasion, there was no statistically significant difference in the recurrence rate between patients with or without cervical implantation metastasis. It appears that cervical implantation metastasis does not alter prognosis or require specific treatment.
Adenocarcinoma↗
Allelotype of renal cell carcinoma.
Several recent studies based on restriction fragment length polymorphism analysis have supported the concept that the accumulation of multiple genetic alterations converts a normal cell to a malignant cell. Activation of oncogenes and/or inactivation of tumor suppressor genes have been observed during tumor progression in colorectal cancer, lung cancer, and breast cancer. To investigate the possibility that multiple genes are altered during the progression of renal cell carcinoma, we have used restriction fragment length polymorphism markers throughout the genome to test for loss of heterozygosity in 38 renal cell carcinomas. Nearly 64% of the tumors had lost heterozygosity on the short arm of chromosome 3. We also observed loss of heterozygosity averaging about 30% at informative loci on six other chromosomal arms (chromosomes 5q, 6q, 10q, 11q, 17p, and 19p). These results lead us to suspect the existence of several tumor suppressor genes associated with carcinogenesis of renal cell carcinoma.
Carcinoma, Renal Cell↗
Prognostic significance of the extent of cervical involvement by endometrial cancer.
The prognostic significance of the extent of cervical involvement by endometrial cancer is impossible to determine from the literature because previous reports have included fractional dilatation and curettage for staging, preoperative radiotherapy, and surgical stage III and IV disease. Therefore, we reviewed and restaged according to the new FIGO system all patients with endometrial cancer from January 1981 to December 1989. Of 180 patients undergoing hysterectomy for endometrial cancer, 20 had surgical stage II disease. No patient received preoperative radiotherapy. None of 12 patients (0%) with stage IIA disease developed recurrence, while 5 of 8 (63%) with stage IIB disease recurred (P less than 0.01). All 5 recurrences were in extrapelvic sites. Endocervical stroma invasion appears to import a statistically significant worse prognosis than endometrial glandular involvement.
Adenocarcinoma↗