[Antitumor effect of recombinant murine interferon-beta against mouse brain tumors].
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Animals↗
Biomedical subjects
M Kuroki
Publications and source records attributed to M Kuroki.
Intimal hyperplasia: the permeation of serum-derived substance into the arterial autovein graft under abnormal blood flow.
The etiology of intimal hyperplasia in autogenous vein grafts used for arterial replacement was experimentally studied in dogs. We previously developed an experimental model, which mimicked a human extremity with poor run-off of peripheral arteries. This model characterized the abnormal flow by a weak fluctuation of wall shear stress at the site adjacent to the vessel wall. In this model we found that an autogenous vein implanted into the femoral artery under such abnormal flow conditions exhibited remarkable intimal thickening; 200-400 micron at 1 month and 300-500 micron at 6 months. A fluorescence microscopic study revealed that Evans blue-albumin complex entered the inner wall of vein grafts transplanted in abnormal flow conditions until about 2 weeks after implantation, after which further permeation was no longer observed. A similar observation was made in the fibrinogen distribution of subendothelial tissue. These results showed that abnormal flow conditions enhance the permeation of certain substances into immaturely repaired intimal tissues of autovein grafts. This phenomenon is thought to be responsible for the proliferation of smooth muscle cells, leading to hyperplasia of autovein grafts.
Animals↗
Interhemispheric epithelial cyst. Case report.
We report a rare case of a 54-year-old woman with an interhemispheric epithelial cyst. This will be the first report of an interhemispheric epithelial cyst without callosal agenesis. A partial excision of the cyst wall has led to her recovery with no evidence of recurrence. Ultrastructural studies suggest that the cyst was derived from the primitive neuroepithelium. We discuss the pathogenesis of the interhemispheric epithelial cyst.
Brain Diseases↗
Protection of mice from lethal infection with Aujeszky's disease virus by immunization with purified gVI.
Virus envelope glycoprotein gVI (gp50) of Aujeszky's disease virus (ADV) was purified from a Nonidet P40-solubilized lysate of ADV-infected Vero cells by immunoaffinity chromatography using a monoclonal antibody against gVI. Mice immunized by the purified gVI produced virus-neutralizing antibody and were successfully protected against subsequent challenge with ADV.
Animals↗
The molecular heterogeneity of nonspecific cross-reacting antigen synthesized by tumor cells and granulocytes.
The molecular heterogeneity of nonspecific cross-reacting antigen (NCA) was examined. Metabolically-labeled glycoproteins were precipitated from cell lysates of human tumor cell lines and of normal peripheral granulocytes with antibodies specific for NCA, and analyzed by SDS-PAGE. NCA components synthesized by three tumor cell lines, QGP-1 (pancreas), HLC-1 (lung) and CAOV-2 (ovary) showed slightly different migration patterns on SDS-PAGE, but the molecular weights of their unglycosylated peptides synthesized in the presence of tunicamycin were all found to be 35K. On the other hand, two molecular species of NCA were identified in normal granulocytes: an 80K mature form derived from a 69K precursor peptide and a 58K mature form from a 41K precursor peptide. Upon SDS-PAGE, the migration pattern of the unglycosylated NCA peptides from tumor cells was affected by the presence of 2-mercaptoethanol, while that of the peptides of granulocytes was not. All the NCAs identified in this study possessed antigenic determinants common to carcinoembryonic antigen as well as those unique to NCA. These results suggest that the molecular heterogeneity of NCA observed thus far resulted from diverse glycosylation of the three fundamental molecular forms of unglycosylated peptides: one with a molecular weight of 35K produced by tumor cells and two with molecular weights of 69K and 41K produced by granulocytes.
Antigens↗
A titration method of feline infectious peritonitis virus using immunoperoxidase antibody.
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Animals↗
Evaluation of a new monoclonal radioimmunoassay system for carcinoembryonic antigen.
A newly established monoclonal radioimmunoassay system (kit II) for carcinoembryonic antigen (CEA) was evaluated in comparison to a conventional polyclonal system (kit I). Among 619 unselected serum samples, approximately 15% were CEA positive with kit I, whereas 27% were positive with kit II; consequently, approximately 12% showed dissociated CEA values to be positive only with kit II. More than 75% of patients with the dissociated values were found to have a malignant disease. Positive rates in normal individuals (266 samples) were less than 5% with both the kit I and kit II and, in those with benign disease were 11.9% with kit II, except for liver cirrhosis in which a quite high positive rate (58%) was obtained. In contrast, a definitely increased positive rate in malignant disease (381 samples) was obtained with kit II (61.4%) in comparison to that with kit I (42.3%). The assessment of technical qualities, such as reproducibility, recovery and dilution tests, demonstrated the excellent performance of kit II.
Adult↗
[Assistance in rehabilitation of a patient who is excessively dependent on his family following surgery of a cerebrovascular disorder].
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Cerebrovascular Disorders↗
Heterogeneity of circulating carcinoembryonic antigen analyzed by sandwich-enzyme immunoassays with different specificities.
Nine monoclonal antibodies against carcinoembryonic antigen (CEA) were prepared and used to investigate the immunological and physicochemical heterogeneity of circulating CEA. Two of these, M221-73 and M272-11, recognized "CEA-distinctive" epitopes and they gave sandwich-enzyme immunoassays far less reactive with nonspecific cross-reacting antigen (NCA) and nonspecific cross-reacting antigen-2 (NCA-2). Sandwich-enzyme immunoassays selective for NCA-2 and NCA were also established using suitable monoclonal antibodies as competitive inhibitors against enzyme-labeled antibodies. The studies on the serum CEA levels determined by the "CEA-specific" assay indicated that CEA molecules recognized by M221-73 and M272-11 were generally found in the sera of both cancer patients and normal adults. CEA and related substances in sera were further analyzed by the sandwich-enzyme immunoassays after adsorption on M272-11-coupled immunosorbents and by gel filtration on an Ultrogel AcA-34 column. These studies revealed the presence of a CEA variant detected by the "NCA-2-selective" assay. The variant seemed to be closely related to NCA-2 because it lacked CEA-distinctive epitopes and had an apparent molecular weight similar to that of NCA-2. This variant appeared in the sera of some cancer patients and normal adults.
Adsorption↗
Structural studies of the carbohydrate moieties of carcinoembryonic antigens.
Three samples of carcinoembryonic antigens were purified from liver metastases of primary colon cancer. The asparagine-linked sugar chains of carcinoembryonic antigens (CEA) were released as oligosaccharides by hydrazinolysis and the structures of oligosaccharides, thus obtained, was studied in combination with methylation analysis and several limited exoglycosidase digestions. All three CEAs contain approximately 25 asparagine-linked sugar chains in one molecule and about 10% of them was high mannose type. However, structural features of the outer chain moieties of the remaining complex-type sugar chains were different by CEA samples. The complex-type sugar chains were mono-, bi-, tri-, and tetraantennary with Man alpha 1----6(+/- GlcNAc beta 1----4)(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(+/- Fuc alpha 1----6)GlcNAc as their cores, half of which were bisected; 86% of their proximal N-acetylglucosamine was fucosylated. The major outer chains in two samples were N-acetyllactosamine and Gal beta 1----4(Fuc alpha 1----3)GlcNAc (X-antigenic determinant) and the remaining one sample contained Fuc alpha 1----2Gal beta 1----4(Fuc alpha 1----3)GlcNAc (Y-antigenic determinant) as an additional major outer chain. Furthermore, small amounts of type 1 chain and Lea antigenic determinant were found in some samples. Acidic oligosaccharides consisted of sialic acid containing fractions and sialidase-resistant fractions, and their contents seemed to be in a reciprocal relationship. Sialic acid was linked at the C-3 and C-6 positions of the nonreducing terminal galactose residues of the outer chains.
Asparagine↗
Antigenic heterogeneity of carcinoembryonic antigen in the circulation defined by monoclonal antibodies against the carbohydrate moiety of carcinoembryonic antigen and closely related antigens.
Six mouse monoclonal antibodies reactive with carcinoembryonic antigen (CEA) were prepared and used for the analysis of the antigenic heterogeneity of CEA in patient sera. Their reaction specificity and the chemical nature of antigenic epitopes recognized by them were analyzed by radioimmunoassay on the basis of reactivities with different preparations of CEA, normal fecal antigen 2, and nonspecific cross-reacting antigen 2 before and after chemical and/or enzymatic treatment. Two antibodies, F3-30 and F4-82, raised with CEA were reactive with different peptide epitopes on the antigen molecules and revealed a quite universal reactivity with all CEA, normal fecal antigen 2, or nonspecific cross-reacting antigen 2 preparations tested. The serum CEA values obtained with these antibodies were highly correlated with those obtained with conventional radioimmunoassays for CEA. The other four antibodies (F4-11 and F33-37 raised with CEA, F8-52 with normal fecal antigen 2, and F48-60 with nonspecific cross-reacting antigen 2) were found to recognize carbohydrate epitopes with different specificities and revealed very heterogeneous reactivities. The serum CEA values estimated with these four antibodies were highly variable depending on the antibody used, suggesting that the expression of carbohydrate epitopes on the CEA molecules in patient sera was quite heterogeneous. The antigenic heterogeneity of the carbohydrate epitopes was detected even in a single patient serum by affinity chromatography. The causes that give rise to the difference in CEA values between the Roche and the Daiichi kits were analyzed on the basis of reactivities of three groups of patient sera, which showed extremely different ratios for the Roche and Daiichi kits, with monoclonal anti-carbohydrate antibodies. The results obtained suggest that, at least in part, the diversity of antigenic expression on carbohydrate chains on the CEA molecules in patient sera and the variation in specificity or quantity of anti-carbohydrate antibodies in the polyclonal antibody preparations used for the respective assay systems may result in the differences in the estimated CEA values.
Antibodies, Monoclonal↗
Subarachnoid dissemination of a pituitary adenoma.
The authors present an unusual case of a pituitary adenoma that developed into intracranial and intraspinal dissemination following intracranial surgery with adjunctive radiation, and review metastasis of pituitary adenomas in the central nervous system briefly in light of other reported cases.
Adenoma↗
Antitumor effect of recombinant murine interferon-beta against mouse malignant glioma.
A study was made on the antitumor effect of recombinant murine interferon-beta (rMuIFN-beta) against virus-induced mouse malignant glioma. In in vitro experiments, a dose-dependent and a time-dependent manner were observed for 24 h in the antiproliferative activity of rMuIFN-beta. In in vitro experiments, the growth of subcutaneously transplanted gliomas in mice treated with intraperitoneal administration of rMuIFN-beta was inhibited slightly, whereas, with intratumoral administration, it was inhibited more effectively. In immunological studies, natural killer (NK) cell and cytotoxic T-lymphocyte activities of spleen cells were enhanced with intraperitoneal administration of rMuIFN-beta. The analysis of IFN-induced change in a subpopulation of peripheral blood lymphocytes revealed a decrease of Thy.1,2-positive cells and an increase in the ratio of Lyt.1/Lyt.2-positive cells. But these immunological effects of rMuIFN-beta declined on the 7th day with daily administration. Such hyporeactivity may be noteworthy for the clinical application of IFN.
Animals↗
Epitope mapping of the carcinoembryonic antigen by monoclonal antibodies and establishment of a new improved radioimmunoassay system.
A comprehensive mapping of epitopes on the carcinoembryonic antigen (CEA) molecule has been achieved by analyses of the specificities of 146 monoclonal antibodies (MAbs) from more than 300 hybridomas established recently. The reactivities of MAbs were analyzed by radioimmunoassays (RIA) with highly purified preparations of CEA and related antigens including normal fecal antigen-1 (NFA-1), NFA-2 in normal adult feces, nonspecific cross-reacting antigen (NCA) in lung and NCA-2 in meconium. The MAbs could be divided into five groups: group I, 23 clones directed to the NCA-common part of the CEA molecule; group II, 31 clones directed to the normal fecal cross-reacting antigen (NFCA)-common part; group III, 46 clones directed to the NFA-1-common part; group IV, 33 clones reactive with the heterogeneous carbohydrate part; and group V, 13 clones directed to the CEA-distinctive part which seemed to be highly specific for CEA. Mutual inhibitions of CEA binding between MAbs of the individual groups revealed that at least 25 different subgroups can be defined i.e., 4, 7, 8, 4, and 2 subgroups in groups I to V, respectively. The epitopes recognized by the group IV MAbs were found to be sensitive to oxidation with periodate, while the epitopes defined by MAbs of the other groups were resistant to this treatment. A solid-phase sandwich-type RIA system for CEA was established by using 2 MAbs from groups II and III as the CEA catcher and an MAb of group V as the tracer. This assay was shown to exhibit improved cancer-specificity and accuracy in the estimation of serum CEA levels.
Antibodies, Monoclonal↗
[Clinical evaluation of serum carbohydrate antigen 19-9 in carcinoma of the lung--a comparison with carcinoembryonic antigen].
Serum levels of carbohydrate antigen 19-9 (CA 19-9) were measured in 235 untreated patients with lung cancer, 20 patients with benign pulmonary disease and 39 healthy controls. In almost all these patients, carcinoembryonic antigen (CEA) was determined at the same time. The positivity of CA 19-9 in lung cancer patients was significantly higher than in those with benign pulmonary disease (30.2% vs. 5%: P less than 0.05). With regard to histological types of lung cancer cases, the positivity of CA 19-9 in adenocarcinoma cases was higher than that in cases of squamous cell carcinoma (39.6% vs. 16.4% : P less than 0.01). With regard to clinical stages of lung cancer positivity of CA 19-9 in stage IV (37.9% vs. 10.3% : P less than 0.01) or stage III (30.3% vs. 10.3% : P less than 0.05) was significantly higher than in stage I. Sensitivity, specificity and accuracy in the detection of lung cancer were 31%, 95%, and 36% for CA 19-9, and 46%, 80% and 49% for CEA, respectively. Combined evaluation with CA 19-9 and CEA gave the highest specificity (98%) when both were measured, and the highest sensitivity (55%) when at least one was measured. Combined assessment of CA 19-9 and CEA improved the measurement of each one in the detection of lung cancer.
Adenocarcinoma↗
Role of the valence of concanavalin A in the activation of guinea pig polymorphonuclear leukocytes.
Stimulation of polymorphonuclear leukocytes (PMN) by tetravalent concanavalin A (alpha-ConA) induces membrane depolarization preceding the onset of superoxide anion (O2-) production. Both divalent and monovalent ConA analogues were studied to evaluate the role of valence. Monovalent ConA (m-ConA) was inactive in stimulating O2- production and divalent derivatives were less active than native alpha-ConA. Similarly, membrane depolarization was dependent on the valency of ConA. m-ConA did not induce a marked change in membrane potential, whereas sustained depolarization occurred with multivalent ConA. The formation of multiple linked interactions between surface receptors may be an important early event in the activation of PMN by ConA.
Animals↗
Production kinetics and immunochemical properties of carcinoembryonic antigen and nonspecific cross-reacting antigen synthesized by various human tumor cell lines.
The production kinetics and immunochemical properties of carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) in various human tumor cell lines were studied. By radioimmunoassay (RIA), five CEA-producing tumor cell lines tested--2 derived from colonic (M7609 and CCK-81), one from pancreatic (QGP-1) and 2 from lung (HLC-1 and KNS-62) carcinomas--were found to produce NCA simultaneously. The cellular contents of CEA and NCA and the amounts of both antigens released into the culture medium were highly variable among the cell lines. It was a distinct contrast that one cell line (CCK-81) released very large amounts of CEA and NCA into the medium while having the smallest amounts of both antigens in the cells, whereas the others contained much larger amounts of the antigens in the cells as compared with the amounts released into the medium. For most of the cell lines, the production of both CEA and NCA increased in the stationary phase of growth as compared with the exponential phase. The production kinetics of both CEA and NCA appeared to be parallel with each other in all the cell lines, though the amount ratio of CEA to NCA produced was variable. By means of a double immunodiffusion test with polyclonal antibodies, antigenic uniformity with no unique organ-specificity was confirmed for all the CEA preparations from spent media of the cell lines, though some differences in the sugar moiety of CEA were detected by RIA using monoclonal antibodies. No antigenic differences among NCA preparations were observed. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), molecular heterogeneity was observed among CEA or NCA preparations isolated from cell lysates.
Animals↗
Antigenic alterations of carcinoembryonic antigen involved in the secretion from various human tumor cell lines.
Antigenic variations of carcinoembryonic antigens (CEAs) produced by 8 human tumor cell lines of various organ origins--4 derived from colonic, one from gastric, one from pancreatic, and 2 from lung cancers--were investigated on the basis of reactivity with several monoclonal antibodies recognizing either the peptide or the carbohydrate moiety of the CEA molecule by using a sandwich-type solid-phase radioimmunoassay (RIA). CEAs from all the cell lines revealed nearly uniform reactivities with the monoclonal antibodies recognizing the peptide epitopes, and no difference was observed between the reactivities of CEAs released into culture medium (m-CEAs) and of those extracted from cells (c-CEAs). On the other hand, with each of 4 monoclonal antibodies recognizing the carbohydrate epitopes, the reactivities of CEAs were found to be highly variable from one cell line to another, and a marked difference was detected between the reactivities of m-CEA and of c-CEA in every cell line. In general, c-CEA reacted much more strongly than m-CEA with these antibodies. The reactivities of some of the CEAs with 2 out of 4 antibodies to sugar epitopes increased significantly after treatment of CEAs with neuraminidase. These results suggest that distinct structural changes in the carbohydrate moiety may occur during the releasing process of CEA from cells, and that, in some cases, some epitopes may be masked by attachment of sialic acid residues.
Antibodies, Monoclonal↗