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Biomedical subjects

A Yachi

Publications and source records attributed to A Yachi.

At least 181 records · Page 10Linked to original sources

[Analysis of tumor-associated antigen of the digestive tract by monoclonal antibody].

A sandwich enzyme immunoassay was established for measuring an adenocarcinoma-associated antigen (antigen YH206) detected by monoclonal antibody YH206. A level of antigen YH206 exceeding the cut-off value (25 U/ml) was found in the following proportions of 136 patients with digestive organ cancers: stomach cancer 37.2%, colon cancer 14.8%, pancreas cancer 43.3%, common bile duct cancer 28.6%. In contrast, only one out of 33 (3.0%) healthy donors and 7 of 104 (6.7%) patients with benign diseases had slightly elevated levels of the antigen. It was also found that perchloric acid treatment of serum might be useful for decreasing any false-positive reactions. The YH206 antigen was then purified by affinity chromatography using MoAb YH206-coupled CNBr-Sepharose. This antigen was not recognized by MoAb CA19-9. Studies on the chemical nature of the antigenic determinant of the YH206 antigen suggested that MoAb YH206 recognized a unique carbohydrate determinant of a novel adenocarcinoma-associated antigen in the sera of cancer patients. In addition, a new monoclonal antibody BM2 (IgM) was established using YH206 antigen as an immunogen. This antibody might be more useful than antibody YH206 in the detection of circulating antigen in the sera of patients with digestive tract cancer.

Adenocarcinoma↗

Leukemia serum reactive with retrovirus-related antigen in normal human placenta.

Serum antibody reactive with a retrovirus-related p30 antigen in human normal term placenta was investigated and characterized by immunohistologic and immunoblotting methods. Sera obtained from patients with acute leukemia and malignant lymphoma were used as first antibody, and cryostat sections of placenta were the target antigen. An IgM antibody that reacted mainly with the basal aspect of syncytiotrophoblast of chorionic villi, where a putative human endogenous retrovirus p30 antigen is located, was directed by indirect immunofluorescence. This antibody activity, termed anti-basal aspect of syncytiotrophoblast (anti-BAST), was detected in the sera of many patients with acute leukemia (AML, ALL) and malignant lymphoma, and less frequently in sera of pregnant women and normal controls. As shown by immunoblotting analysis, the main reactive antigen recognized by anti-BAST was a non-glycosylated 32-kDa placental protein which was antigenically related to SSAV p30. A non-glycosylated 19-kDa protein was also considered to be one of the anti-BAST-corresponding antigens. This suggests the presence of a new antigen-antibody system of human retrovirus(es) revealed by subinfectious antigenic expression and by specific antibody activity in conditions of human health and disease, particularly, acute leukemias and malignant lymphomas of common types.

Antibody Specificity↗

Low T3 syndrome in cancer patients in relation to weight loss, intravenous hyperalimentation therapy and age.

In order to investigate the relation of weight loss and intravenous hyperalimentation therapy to low T3 syndrome, serum T3, T4. rT3 and TBG were determined by radioimmunoassay in 105 cancer patients. The cancer patients were classified into 3 groups, Group I, II and III depending on the grade of weight loss, ranging up to a 5% change in weight loss from a healthy condition, from 5 to 9%, and more than 10%, respectively. Cancer patients under age 59 showed no significant difference in serum T3, T4, rT3 and TBG among these 3 groups. However serum T3 and T3/T4 in cancer patients at age 60 and over were significantly reduced in group III, compared to groups I and II. Serum rT3 values were significantly elevated in group III of elderly cancer patients. The incidence of low T3 syndrome in group III of elderly cancer patients was also significantly higher than in groups I and II. In three out of 5 cancer patients with low T3 syndrome, serum T3 values increased after the intravenous hyperalimentation therapy, whereas no significant change in serum T3 values was observed in two patients who died within one day after the final examination. It is concluded that weight loss produced different effects on peripheral conversion of T4 to T3 between cancer patients under age 59 and over age 60 and glucose plays an important role in the pathogenesis of low T3 syndrome except cases with very poor prognosis.

Age Factors↗

Immunohistochemical analysis of human adenocarcinoma-associated antigen YH206 detected by a monoclonal antibody.

A monoclonal antibody YH206 (IgM, kappa) was prepared using human lung adenocarcinoma A549 cell line as an immunogen. The histological distribution of antigenic determinant of the YH206 antigen was highly restricted to adenocarcinomas of various organs including the lung, the pancreas and the stomach, but it did not react with 10 cases of colonic adenocarcinomas by the immunoperoxidase technique. It did not stain non-cancerous tissues of 16 different organs, except for the renal tubules and for the secreting glands of the pancreas with which the antibody faintly reacts. It did not react with either granulocytes, lymphocytes or red blood cells. Positive staining was observed in various fetal tissues. Periodic acid and neuraminidase treatments on tissue sections suggested that the chemical nature of the antigenic determinant of YH206 antigen was carbohydrate in nature which might be masked by sialic acids.

Adenocarcinoma↗

Characterization of carcinoembryonic antigen-specific monoclonal antibodies and specific carcinoembryonic antigen assay in sera of patients.

Six murine monoclonal antibodies (mAbs) reactive with carcinoembryonic antigen (CEA) were prepared. Four of these, CA204, CA205, CA206 and CA208, were specific to purified CEA whereas the other two, NA201 and NA203, were also reactive with the non-specific cross-reacting antigen (NCA). These mAbs were all IgG1, except one IgG2a (CA206), with high affinities for CEA. NA203, CA204 and CA208 appear to define three different epitopes on the CEA molecule as determined by competitive binding assay. These mAbs also reacted with CEA-producing cells. The treatment of the cells with tunicamycin did not affect the binding of the mAbs to CEA-producing cells. None of the above mAbs bound to CEA-related antigens, NCA-2, alpha 1-acid glycoprotein, or blood group antigens. The combination of CA208 (solid phase) and CA204 (tracer) was used to construct a sensitive CEA-specific sandwich ELISA to detect CEA in the sera of patients with various malignant and non-malignant diseases. Particularly when CEA values were low in sera from non-cancerous patients, the above mAbs sandwich assay showed reduced background reactivity with NCA-like substances and permitted the detection of CEA at a level as low as 1 ng/ml.

Antibodies, Monoclonal↗

Preparation of human monoclonal antibodies of IgG type to gastro-intestinal cancer-associated antigen.

The B lymphocytes from pleural effusion of a gastric cancer patient were fused with murine myeloma cells (X63-Ag8.653). Thirty-four out of 62 clones were found to secrete human monoclonal antibodies (23 IgGs and 11 IgMs) by means of enzyme-linked immunosorbent assay. Fourteen monoclonal antibodies were tested for histological reactivity with cancer and normal tissues by immunoperoxidase staining. Among them, two monoclonal antibodies reacted rather specifically with gastro-intestinal cancerous tissues. The human monoclonal antibody (HMoAb) 3B7 (IgG) reacted strongly with 4 out of 5 gastric carcinoma tissues and 2 out of 5 colonic carcinoma tissues, but did not react with non-cancerous tissues (stomach, colon, liver, pancreas and lung). In addition, HMoAb 3B7 reacted heterogeneously with autologous gastric carcinoma tissue sections. The hybridoma 3B7 has continued producing human monoclonal antibody for 12 months after fusion. By chromosomal analysis, it was shown that hybridoma 3B7 retains both human and mouse chromosomes. HMoAb 3B7 may be useful for research on tumor-associated antigens and therapeutic techniques.

Antibodies, Monoclonal↗

[An autopsy case of colonic carcinoid with marked leukocytosis].

A 45-year-old man with right hypochondralgia and marked leukocytosis was found to have Borrmann type II carcinoma of the sigmoid colon and its metastasis to the liver. The peripheral leukocyte count gradually increased up to 150 X 10(3)/mm3 according to the tumor enlargement. The patient died of hepatic insufficiency, and autopsy revealed carcinoid of the colon and its metastasis to the liver. Leukemoid reaction has been reported in various kinds of malignancies. However, the present case seems to be of particular interest because of the rare association with carcinoid and marked leukocytosis of more than 100 X 10(3)/mm3 without any evidence of infection.

Carcinoid Tumor↗

[Glutamate metabolism in cerebral cortex obtained from chronic hepatic failure rats].

The present investigation was carried out in order to elucidate the amino acid metabolism in hepatic failure with particular emphasis placed on glutamate. For this purpose, chronic hepatic failure models were produced in adult male Wistar rats by successive carbontetrachloride injection (0.20 ml/100 g. B. W., twice/week) for 13 weeks. They were confirmed to develop chemical changes compartible with hepatic failure, showing markedly elevated serum levels of NH3, GOT and ALP. Animals were killed by decapitation during fasting and the brains were removed immediately. After the parietal cortical slices were incubated for 45 min at 37 degrees C together with L-(U-14C) glutamate in O2-saturated Gey's balanced salt solution, they were homogenized in 75% ethanol and deproteinized with water saturated chloroform. The radioactivities of liberated CO2, glutamate and its metabolites (glutamine, aspartate and GABA) obtained from the slices were measured. The amount of radioactivity recovered from CO2, glutamine and aspartate revealed a significant increase (p less than 0.001), while that of glutamate and GABA remained unchanged. The main source of the CO2 is believed to originate from TCA cycle rather than the decarboxylation of glutamate to form GABA, and glutamate forms glutamine when it fixes ammonia. Furthermore, glutamate is converted into aspartate via TCA cycle when the carbon was labeled. Therefore, the results indicate that in chronic hepatic failure brains glutamate metabolism is enhanced through TCA cycle as well as ammonia fixation mechanism.

Animals↗

[A comparative study of free amino acid levels in the serum and cerebral cortex in hepatic failure rats].

In order to elucidate the role of amino acid changes in hepatic encephalopathy, free amino acids in serum and cerebral cortex were measured in the experimental hepatic failure models. The acute and chronic models were produced in adult male Wistar rats by carbontetrachloride (CCl4) administration. Acute model was produced by a single intraperitoneal injection of CCl4 (0.35 ml/100 g, B.W.) after the daily pretreatment of phenobarbital (6 mg/100 g, B.W.) for 4 days, while chronic model was established by successive injections CCl4 (0.20 ml/100 g, B.W., twice/week) for 13 weeks. They were confirmed to develop chemical changes compatible with hepatic failure, showing markedly elevated serum levels of NH3, GOT and ALP. Animals were killed by decapitation during fasting and the brains were removed immediately. The parietal cortexes were homogenized in 75% ethanol and deproteinized with water saturated chloroform. The supernatants were subjected to amino acid analyzer. In serum, almost all amino acid concentrations were elevated in acute hepatic failure, reflecting massive release of amino acids from severely damaged liver cells. Chronic hepatic failure rats, however, showed moderately elevated levels of valine and leucine and markedly high levels of phenylalanine and tyrosine, which eventually led to a reduction of the ratio of branched chain amino acids to aromatic amino acids. Regarding urea cycle related amino acids, there were decreases of aspartate and arginine and an increase of ornithine, while citrulline was not affected. In cerebral cortex, no different pattern was observed in acute heptic failure with the exception of increases in threonine, glycine and leucine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Immunohistologic distribution of CEA defined by human anti-CEA antibody in the serum of a colonic cancer patient.

The serum from a colonic cancer patient was examined showing anti-CEA (carcinoembryonic antigen) activity but not anti-NCA (nonspecific cross-reacting antigen) activity. Conventional immunoelectrophoresis and radioimmunoelectrophoresis in conjunction with iodine 125-labeled CEA strongly suggested that this serum contained M-protein (IgG kappa). Most of the anti-CEA activity was found in the M-component using radioimmunoelectrophoresis, suggesting the monoclonal nature of anti-CEA autoantibodies. With the use of this serum the histologic distribution of the antigen by the immunoperoxidase method was demonstrated for the first time. Anti-CEA specificity of this serum was confirmed by the fact that the absorbed antibody with purified CEA gave negative staining of the serial sections of the tissues that formerly had immunostaining. Interestingly, this distribution was almost superimposed on that detected by the murine monoclonal anti-CEA antibody AS802. The data suggested that the antibody in the serum reacted with the CEA molecule in the tissue sections, the majority of which were found in the cancerous tissues.

Adenocarcinoma↗

Immunological analysis of glycolipids on cell surfaces of cultured human tumor cell lines: expression of lactoneotetraosylceramide on tumor cell surfaces.

Glycolipids of human cell lines of colonic adenocarcinoma (Colo 205 and BM 314), gastric tumor (AZ 521 and KATO-III), and lung tumor (A 549) were studied by the immunohistochemical fluorescence technique, flow cytometric analysis and immunostaining on thin layer chromatoplates with antibodies against gangliotriaosylceramide (Gg3Cer), gangliotetraosylceramide (Gg4Cer), fucogangliotetraosylceramide (Fuc-Gg4Cer), blood group B active lipid, globopentaosylceramide (Gb5Cer) and lactoneotetraosylceramide (nLc4Cer). Anti-nLc4Cer antibody was the only antibody which reacted with all the tumor cell lines used. The glycolipid fractions of each cell line separated by Iatrobeads column chromatography were immunostained with the six antibodies mentioned above on thin layer plates. The presence of nLc4Cer was detected in all cell lines. On the other hand, Gg4Cer was detected in gastric tumor cell lines, and Gg3Cer was detected in AZ 521. Based on these results, the tumor cell lines were analyzed by flow cytometry using anti-nLc4Cer antibody. About 70% of total cells in each cell line were separated as nLc4Cer-expressing cells. The present findings, together with the occurrence of nLc4Cer in ascitic fluids of cancer patients (Taki, T., Kojima, S., Seto, H., Yamada, H., & Matsumoto, M. (1984) J. Biochem. 96, 1257-1265), suggest that nLc4Cer may be a tumor-associated lipid.

Adenocarcinoma↗

Treatment of HBeAg-positive chronic hepatitis with a streptococcal preparation (OK-432).

Forty-two patients with hepatitis Be antigen (HBeAg)-positive chronic hepatitis were treated by intramuscular injections with OK-432, an immunopotentiator possessing interferon-inducing activity. They were monitored with serial measurements of virological parameters to evaluate therapeutic effectiveness, and compared with a group of seventy-five untreated patients (natural course group). In the group receiving OK-432 therapy, twenty-seven patients (64.3% of the forty-two patients) became negative for HBeAg in an average observation period of 20.1 months. Of these, fourteen patients (33.3% of the forty-two patients) underwent seroconversion from HBeAg to anti-HBe antibody (anti-HBe). In the natural course group, twenty-three patients (30.7% of the seventy-five patients) lost HBeAg reactivity in a mean follow-up period of 32.3 months, and thirteen patients (17.3% of the seventy-five patients) became seroconverted. Thus, the drug group showed significantly higher percentages of patients with disappearance of HBeAg and seroconversion, notwithstanding the shorter duration of the follow-up. Young males and females, females generally, or patients with high serum GPT levels were more likely to respond to the therapy. The serum GPT level tended to stabilize more in patients receiving OK-432.

Adult↗

Circulating blood group-related antigen(s) in cancer patients detected by the monoclonal antibodies produced against hepatocellular carcinoma cell line.

Two murine monoclonal antibodies (MAbs) S1 and S3 produced against a human hepatoma cell line were found to recognize both H (type II) antigen and difucosyl type II structure (Y-antigen). Both MAbs reacted with hepatoma tissues obtained from surgical resection. A double determinant enzyme immunoassay (DDEI) employing these MAbs successfully detected the corresponding antigen(s) in the supernatant which is either released or shed from the immunizing hepatoma cell line. DDEI also revealed that these antibodies reacted with the corresponding antigen(s) in the sera from cancer patients. Among the sera from O blood group donors, individuals with primary hepatoma showed markedly higher levels of antigen concentration than the normal control group. Several cases with gall bladder, lung and pancreas carcinomas, which are of O blood type, also had significantly higher levels of antigen. One case with ovarian cancer of B blood type showed higher antigen concentration than normal O blood group donors suggesting a change in the carbohydrate structure of the corresponding antigen(s) in the serum. These data suggest that the release or the shedding of the antigen(s) from the cells may increase due to the malignant transformation, resulting in higher amounts of the antigen(s) in the serum of certain cancer patients.

ABO Blood-Group System↗