Search PubMed⌕ Search

Biomedical subjects

D Chia

Publications and source records attributed to D Chia.

At least 55 records · Page 3Linked to original sources

Use of four monoclonal antibodies to detect tumor markers.

A combined panel of monoclonal antibodies to tumor markers was examined in the sera of 454 cancer patients to compare their reactivity. At least one of the four tumor-associated markers (CEA [caranoembryonic antigen], CA 19-9, CA 125, and SLEX [sialylated Lewisx epitope]) was positive with the sera of breast (43%), lung (64%), ovarian (54%), and colorectal (57%) cancer. Each tumor marker's reactivity was distinct in different patients, indicating that different epitopes were being detected. The number of tumor markers that were positive was associated with advancing stages of disease. In advanced stages with distant metastasis, 13% of the patients reacted with all four markers, whereas none of the early-stage patients did. In 14 cases of disease progression, the tumor markers increased with no instance of decrease. Among ten patients with regression, seven showed a decrease in tumor markers and three showed an increase. The authors conclude that the use of four tumor-associated markers expands the number of patients with a positive marker, thereby permitting the monitoring of some patients. Among 60 normals, one showed a weak reactivity with CEA and one with CA 125. Eventually, with more markers, it should be possible to monitor all patients.

Adult↗

Detection of sialylated LewisX antigen in cancer sera using a sandwich radioimmunoassay.

A monoclonal antibody directed against sialylated LewisX (SLEX) was tested with the serum of 615 cancer patients, 166 patients with non-malignant diseases, and 136 normal persons. The SLEX antibody reacted with the sera of the cancer patients in the following percentages: 29% lung, 19% breast, 12% ovary, 25% colorectal, 13% head and neck, and 13% miscellaneous. SLEX was positive for 22% of stages III and IV (late-stage) cancers as compared with 5% early-stage tumors. Among 80 patients with adenocarcinoma of the lung in the late stages, 45% were positive for SLEX. However, among 54 patients having squamous-cell lung cancer in the late stages, 15% were positive. In 25 cases of small-cell lung cancer, 24% were positive. Among patients who had measurable lung cancer, 4/7 with adenocarcinoma over 3 cm in diameter were positive whereas 0/16 patients with tumors under 3 cm were positive. Four patients who had tumor regression showed a more than 50% decrease in SLEX values whereas in 7 patients with progressive tumors, a more than 50% increase in SLEX levels was found. When tested simultaneously with CEA, SLEX produced positive reactions with the sera of some patients who were negative for CEA. The reaction pattern was distinct, indicating that another antigen was being detected. When used in combination, the percentage of sera that were positive increased. We conclude that the use of SLEX is useful for monitoring of cancer patients.

Adenocarcinoma↗

Detection of monoclonal antibodies for tumor diagnosis with the use of inhibition of micro-enzyme-linked immunosorbent assay.

A micro-enzyme-linked immunosorbent assay (ELISA) test and an ELISA inhibition test were developed and used to detect 4 monoclonal antibodies potentially useful for serodiagnosis of cancer. The 4 antibodies used in conjunction detected 73% of 71 sera from cancer patients and 8% of 42 sera from normal persons. Separately, the 4 antibodies reacted to tumors from various sites such as lung, breast, colon, stomach, and ovary. The ELISA inhibition assay may be useful for detecting culture supernatants reactive against tumor-associated serum antigens. Eventually, a panel of monoclonal antibodies detecting various tumors may be obtainable.

Animals↗

Sialosylated Lewisx in the sera of cancer patients detected by a cell-binding inhibition assay.

A new cell-binding inhibition assay to detect tumor-associated antigens in sera was developed. This assay determined that sialosylated Lewisx, as detected by the CSLEX1 monoclonal antibody, is present in the sera of 95% of patients with advanced lung adenocarcinomas. Sera with inhibition titers of 1:16 or higher were presumed to contain sialosylated Lewisx. Tests of over 900 sera samples from both malignant and benign disease patients yielded the following percentages of positive inhibition: lung cancers, 43.8%; stomach cancer, 26.0%; colon cancer, 44.4%; gall bladder and bile duct cancers, 47.8%; pancreas cancer, 37.5%; breast cancer, 26.7%; cancers of the hematopoietic system, 2.9%; benign diseases, 0.9% (332 sera); and normal healthy donors, 0.7% (280 sera). Within the lung cancer group, 95% of the sera from 21 advanced (Stages III and IV) nontreated adenocarcinoma patients gave positive results with high inhibition titers, whereas only 27% of sera from treated advanced adenocarcinoma patients yielded positive results. The sensitivity of the cell-binding inhibition assay is similar to those of the solid-phase radioimmunosandwich and reverse passive-hemagglutination assays. Reproducibility tests yielded an r value of 0.90. These results suggest that this simple cell-binding inhibition assay could be applied with monoclonal antibodies, such as CSLEX1, to monitor cancer.

Antibodies, Monoclonal↗

Use of monoclonal antibodies to sialylated Lewisx and sialylated Lewisa for serological tests of cancer.

A new monoclonal antibody, CSLEX1, directed against sialylated Lewisx was tested in parallel with a monoclonal antibody, CSLEA1, directed against sialylated Lewisa antigen. In tests with a solid-phase radioimmune sandwich assay, the sialylated Lewisx monoclonal antibody detected sera from certain cancer patients that were negative with the sialylated Lewisa monoclonal antibody. Some sera from cancer patients showed the reverse reaction. We conclude that the combined use of these two monoclonal antibodies detects a wider range of sera from cancer patients than the use of a single antibody alone. It should be possible in the future to use multiple monoclonal antibodies to increase detection.

Antibodies, Monoclonal↗

Blood clearance and tissue localization of soluble aggregates of IgG in NZB/W and NZB mice.

We studied the capacity of the mononuclear phagocytic system (MPS) of NZB/W and NZB mice to clear trace and saturating doses of soluble heat-aggregates of IgG (A-IgG) from the blood. Mature female NZB/W mice (aged 5-7 months) with early glomerulonephritis showed no differences in MPS clearance of A-IgG compared with younger NZB/W mice without glomerulonephritis. In contrast, mature NZB mice had a more rapid clearance of A-IgG and greater MPS localization of A-IgG than their younger counterparts. Further studies showed that older NZB/W mice (greater than 10 months) had a slightly more rapid clearance of A-IgG than 2-5-month-old mice (t 1/2 = 3.34 +/- 0.27 SEM vs 3.76 +/- 0.34 SEM, P less than 0.01), whereas NZB mice mice older than 10 months of age had a markedly more rapid clearance than 2-5-month-old NZB mice (t 1/2 = 2.84 +/- 0.15 SEM vs 3.76 +/- 0.32, P less than 0.005). The more rapid clearance seen in NZB mice was partly explained by greater splenic localization of A-IgG and appeared to be restricted to Fc- and/or C3b-receptor mediated clearance, in that clearance of aggregated albumin was not changed. We conclude that NZB/W mice have no impairment in MPS clearance capacity at the onset of their glomerulonephritis, and slightly increased clearance capacity late in the course of their disease. Thus, the presence of circulating immune complexes and the development of glomerulonephritis in NZB/W mice is unlikely to be due to a diminished MPS clearance capacity. NZB mice have an increase in MPS capacity to clear A-IgG as a function of age.

Animals↗

Characterization of sialosylated Lewisx as a new tumor-associated antigen.

A monoclonal antibody CSLEX1 which reacts with sialosyl Lex but not with sialosyl Lea has been produced. The CSLEX1 antigen has a tissue distribution similar to that of Lex, appearing characteristically in the proximal tubules of the kidney and on granulocytes. It is tumor associated in that 14 of 34 (41%) of tumor lines tested reacted with the CSLEX1 antibody, and 50 of 74 (68%) of tumor tissues tested reacted with the antibody. Loss of immunoperoxidase staining of tissues after neuraminidase treatment showed that the antibody is reacting to sialyl derivatives. The antibody reacted in solid-phase radioimmunoassay to sialosyllactofucopentaosyl(III)ceramide and sialosyldifucosylganglioside (6B). These results indicate that the CSLEX1 epitope has the following structure: (formula: see text) This structure had not previously been known to be tumor associated.

Antibodies, Monoclonal↗

A monoclonal antibody, CSTO-1, against a stomach adenocarcinoma-associated antigen.

A monoclonal antibody, CSTO-1, has been produced against a stomach adenocarcinoma-associated antigen. The antibody is cytotoxic to stomach, colon, and lung adenocarcinoma lines but is completely noncytotoxic to normal blood elements and leukemic cell lines. The monoclonal antibody reacts with tumor cell membranes in enzyme-linked immunosorbent assay and is negative to cell membranes from various normal tissues. By immunoperoxidase testing, the antibody reacts with 18 of 22 stomach adenocarcinomas, 11 of 16 colon adenocarcinomas, 3 of 4 squamous cell carcinomas of the lung, and 1 of 4 lung adenocarcinomas. In addition, the antibody reacts with the superficial epithelium of normal tissues such as colon, stomach, esophagus, acinar cells and duct epithelium of the pancreas, bronchial epithelium of the lung, and sweat duct epithelium of the skin. Thus, the CSTO-1 antibody reacts to an antigen present in normal superficial epithelia, as well as on various tumors. It is of potential use in detecting these antigens on tumor sections and eventually may be used in immunotherapy.

Adenocarcinoma↗

Reversal of transplant rejection by monoclonal antiblast antibody.

The first clinical trial of an antiblast monoclonal antibody, CBL1, in the treatment of kidney allograft rejection is described. The theory that this antibody might destroy active clones of cells without major side effects was given validity by a previously described study showing prolongation of skin allograft survival in rhesus monkeys. CBL1 was used to treat kidney allograft rejections in 11 patients with a one-haplotype-identical related-donor graft who had been prestimulated with donor-specific transfusions and 8 patients with cadaver grafts who had been prestimulated with multiple transfusions. 15 of the rejections were steroid-resistant. Although CBL1 had no effect on the peripheral blood lymphocyte counts, rejections were reversed in 17 of 19 patients. There was 1 graft loss in the 11 recipients of related-donor grafts and 3 in patients with cadaver-donor grafts. Side effects associated with administration of antilymphocyte serum--ie, chills, fever, and thrombocytopenia--did not develop in any of the patients treated with CBL1. It is postulated that administration of an antiblast monoclonal antibody during rejection of a kidney kills only those cells that are reacting against the graft. This could result in the maintenance of normal lymphocyte numbers and immunological functions against other antigens.

Antibodies, Monoclonal↗

Factors influencing the paradoxical effect of transfusions on kidney transplants.

Cadaver donor graft survival data obtained between 1970 and 1980 show that transfused patients had statistically significant improvements in transplant survival rates for each of the 11 years, as compared with untransfused patients. Patients with many transfusions could be successfully grafted at any time following their last transfusion, whereas those with few transfusions had varying success rates at different intervals following their last transfusion. Even one transfusion produced a statistically significant improvement (52 +/- 3% one-year graft survival) as compared with no transfusion (41 +/- 1%) and survival rates increased up to 14 transfusions (75 +/- 7%). Subsequent transfusions did not appear to be more beneficial, although there is a possibility that patients who receive a larger number of transfusions are medically different from those who receive fewer transfusions. Most important, patients who had cytotoxic antibodies following transfusions had a higher transplant survival rate than did untransfused patients with no antibodies. Thus cytotoxic antibodies per se are not harmful to transplants. Patients with cytotoxins are not automatically at a higher risk and are not "sensitized" in the conventional sense. They are only unable to accept grafts from certain donors.

Antibody-Dependent Cell Cytotoxicity↗

Detection of Lewis a antigenic determinants in Chinese medicinal herbs.

Two Chinese medicinal herbs, Leonurus sibiricus L. and Carthamus tinctorius L., were found to have high levels of Lewis a (Lea)-like determinants. The water-soluble extracts specifically inhibited hemagglutination, hemolysis, and lymphocyte cytotoxicity directed against Lea. They did not inhibit Leb nor other specificities detected on lymphocytes, resulting from the interaction of Lewis, Secretor, and ABO systems such as A1Leb and A1Led. The activity was nondialyzable, resistant to boiling and proteolytic enzymes, but was destroyed by periodate. It was suprising that an Lea substance, previously found in human secretions, was also present in flower abstracts.

China↗

Immune complexes in pemphigus and bullous pemphigoid.

28 serum and 10 blister fluid specimens obtained from 28 pemphigus vulgaris (PV) patients were assayed for immune complexes using the polyethylene glycol (PEG)assay. 11% of sera and 30% of the blister fluids have elevated levels of immune complexes. Anti-intercellular cement substance (ICS) antibody could not be detected in PEG precipitates, but was present in the supernatants from the serum. However, anti-ICS antibody was found in 70 of the precipitated complexes from the blister fluid. 18 serum and 31 blister fluid specimens obtained from 18 bullous pemphigoid (BP) patients were assayed for immune complexes using the PEG assay. 17% of sera and 31% of the blister fluids have elevated levels of immune complexes. Antibasement membrane zone (BMZ) antibody could not be detected in the PEG precipitates, but was present in the supernatants obtained from the sera. Anti-BMZ antibody was found in 57% of the precipitated complexes from the blister fluids. This data further supports the hypothesis that the majority of the complexes in PV and BP are formed in situ.

Antigen-Antibody Complex↗

Decreased Fc receptor avidity and degradative function of monocytes from patients with systemic lupus erythematosus.

We studied the binding and degradation of stable, soluble heat aggregates of 125I-IgG (A-IgG) by monocytes from 30 patients with systemic lupus erythematosus (SLE) and 30 normals. Relative avidities (KE) for Fc receptor (FcR) binding of A-IgG and maximal binding of A-IgG by monocytes were determined from Scatchard plots of binding data obtained at 4 degrees C. Rates of degradation (Vmax) of A-IgG at 37 degrees C were calculated from Lineweaver-Burke plots of the Michaelis-Menton equation. KE were decreased in SLE monocytes (15.5 X 10(-9) L/M) as compared with normals (20.1 X 10(-9) L/M, p less than 0.005) and Vmax were decreased for SLE (0.89 ng/hr) as compared with normals (1.11 ng/hr, p less than 0.005). The maximal FcR binding by SLE monocytes was not statistically different in SLE patients and normals, but monocytes from SLE patients with active disease showed a lower maximal binding capacity for A-IgG (4.9 ng/10(5) cells) than normals (5.4 ng/10(5) cells, p less than 0.05). KE and Vmax in SLE were also lower for patients with active disease than for normal subjects. KE in patients whose anti-ssDNA binding was greater than 20% were lower than for those with DNA binding of less than 20% (p less than 0.005). These data suggest that patients with active SLE have diminished numbers of available FcR on their circulating monocytes, possibly due to interiorization of FcR during endocytosis of endogenous circulating immune complexes.

Adolescent↗

Association of anti-F(ab')2 antibodies with higher kidney transplant survival rates.

When the pretransplant sera of cadaver donor transplant patients were divided into 132 with anti-F(ab')2 (Fab) antibodies and 121 without anti-Fab antibodies, those patients with the antibodies had a 2-year graft survival rate of 59.7 +/- 4.6% (+/- SE) as compared with 34.0 +/- 5.0 % (+/- SE) for those without antibodies (P less than 0.001). This difference was greater when the patients were further classified by whether they had antibodies reactive to B lymphocytes in the cold. Patients with anti-Fab antibodies and B-cold antibodies had a 2-year graft survival of 81.3 +/- 9.8% as compared with 15.7 +/- 7.9% for patients without anti-Fab antibodies and with B-cold antibodies. We suggest that these anti-immunoglobulin antibodies may function in some immunoregulatory role. The number of transfusions was not directly related to the frequency of occurrence of these antibodies.

Antibodies, Anti-Idiotypic↗

Evaluation of fluorescent antinuclear antibody assays, Crithidia luciliae substrate, and single-stranded DNA-binding capacity in diagnosis of four rheumatic diseases.

Sera from groups of patient with systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, and progressive systemic sclerosis and normal controls were compared, using different antinuclear antibody assays. Hep-II cells, used as a substrate for the detection of antinuclear antibodies, appeared to be more sensitive than rat liver substrate. In addition, the fluorescent patterns were easier to identify on Hep-II cells. All systemic lupus erythematosus sera with antibodies reactive with kinetoplasts of Crithidia luciliae had binding greater than 43% for single-stranded DNA. Based on the high sensitivity of the Hep-II substrate and the relative specificity of high (greater than 43%) binding for single stranded DNA by sera from patients with systemic lupus erythematosus, it appears that these two tests are most useful in differential diagnosis and for the detection of systemic lupus erythematosus.

Animals↗

Association of anti-Fab and anti-IgG antibodies with high kidney transplant survival.

Pretransplant sera from 371 first cadaver and 58 second cadaver kidney transplant patients were examined for the presence of anti-Fab and antiimmunoglobulin antibodies. The 1-year graft survival rate for 109 patients with anti-Fab antibodies was 59 +/- 5% as compared with 47 +/- 5% for 106 patients without anti-Fab antibodies (p less than 0.05). Among patients with more than five transfusions, those with anti-Fab antibodies had a survival rate of 81 +/- 8% as compared with 53 +/- 9% for patients with no anti-Fab antibodies (p less than 0.01). Among 74 patients with anti-IgG antibodies, the 1-year graft survival rate was 63 +/- 6% as compared with 56 +/- 3% for 270 patients without anti-IgG antibodies (p = N.S.). After more than five transfusions, the graft survival rate was 83 +/- 1% for those with anti-IgG and 68 +/- 6% for those without IgG (p = N.S.). There was no correlation between the presence of anti-Fab and anti-IgG antibody and the number of transfusions. We conclude that anti-Fab antibodies and possibly anti-IgG antibodies have an enhancing effect on graft survival.

Antibodies, Anti-Idiotypic↗