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Biomedical subjects

L Y Yang

Publications and source records attributed to L Y Yang.

At least 19 recordsLinked to original sources

Surface components of chylomicrons from rats fed glyceryl or alkyl esters of fatty acids: minor components.

The lipid class, fatty acid and molecular species composition of the minor polar surface components of rat lymph chylomicrons were determined during absorption of menhaden oil and corn oil or of the corresponding fatty acid ethyl esters. In addition to the previously reported minor polar lipids (sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidic acid and lysophosphatidylcholine), we identified phosphatidylglycerol, dimethylphosphatidylethanolamine, ceramide and cholesteryl sulfate in the chylomicrons from both oil and ester feeding. The dietary fatty acids were found to be incorporated to a variable extent into the different phospholipid classes, the proportions of which remained the same during both types of feeding. No evidence was obtained for the presence of the minor glycerophospholipids characteristic of the lysosomal membranes (e.g., bis-phosphatidic, lysobisphosphatidic and semilysobis-phosphatidic acids), although special efforts were made to identify them. These results indicate that the chylomicrons arising from the monoacylglycerol and phosphatidic acid pathways of triacylglycerol biosynthesis become enveloped in closely similar monolayers of phospholipids. Hence, all triacylglycerols may be secreted from the villus cells via a common mechanism as suggested by the previously demonstrated convergence (at the 2-monoacylglycerol stage) of the monoacylglycerol and the phosphatidic acid pathways of mucosal triacylglycerol formation [Yang, Y.L., and Kuksis, A. (1991) J. Lipid Res. 32, 1173-1186].

Animals

Reattachment of surface array proteins to Campylobacter fetus cells.

Campylobacter fetus strains may be of serotype A or B, a property associated with lipopolysaccharide (LPS) structure. Wild-type C. fetus strains contain surface array proteins (S-layer proteins) that may be extracted in water and that are critical for virulence. To explore the relationship of S-layer proteins to other surface components, we reattached S-layer proteins onto S- template cells generated by spontaneous mutation or by serial extractions of S+ cells with water. Reattachment occurred in the presence of divalent (Ba2+, Ca2+, Co2+, and Mg2+) but not monovalent (H+, NH4+, Na+, K+) or trivalent (Fe3+) cations. The 98-, 125-, 127-, and 149-kDa S-layer proteins isolated from strains containing type A LPS (type A S-layer protein) all reattached to S- template cells containing type A LPS (type A cells) but not to type B cells. The 98-kDa type B S-layer protein reattached to SAP- type B cells but not to type A cells. Recombinant 98-kDa type A S-layer protein and its truncated amino-terminal 65- and 50-kDa segments expressed in Escherichia coli retained the full and specific determinants for attachment. S-layer protein and purified homologous but not heterologous LPS in the presence of calcium produced insoluble complexes. By quantitative enzyme-linked immunosorbent assay, the S-layer protein copy number per C. fetus cell was determined to be approximately 10(5). In conclusion, C. fetus cells are encapsulated by a large number of S-layer protein molecules which may be specifically attached through the N-terminal half of the molecule to LPS in the presence of divalent cations.

Animals

Class IV lupus nephritis associated with Graves' disease.

Graves' disease was initially diagnosed in an 11-year-old Chinese boy in March 1989. After regular propylthiouracil (PTU) and thyroxine, he achieved a euthyroid state. Heavy proteinuria with class IV lupus glomerulonephritis, anemia, arthralgia, low serum complement and anti-dsDNA (+) appeared 15 months later. Thyrotoxicosis also relapsed at this time. His condition fitted the diagnostic criteria of systemic lupus erythematosus. His antimicrosomal antibody titer was 1:1,600 (+) thyroid-stimulating hormone receptor antibody level was strongly positive, and the titer of antiinsulin antibody was high as well. These clinical, laboratory and histological findings indicate that class IV lupus nephritis may be associated with Graves' disease.

Carbimazole

Similarities in surface lipids of chylomicrons from glyceryl and alkyl ester feeding: major components.

This study tests the hypothesis that the rat chylomicrons are assembled and released into lymph similarly regardless of the site (rough or smooth endoplasmic reticulum) or pathway (phosphatidic acid or monoacylglycerol) of triacylglycerol biosynthesis. For this purpose we determined the lipid class, fatty acid and molecular species composition of the choline, ethanolamine, inositol and serine phospholipids of lymph chylomicrons during absorption of menhaden, mustard-seed and corn oil (monoacylglycerol pathway) or the corresponding fatty acid methyl or ethyl esters (phosphatidic acid pathway). The dietary fatty acids were found to be incorporated to various extents into different phospholipid classes, the proportions of which were not affected by the nature of the dietary fat. The chylomicron phospholipids contained 80-82% choline, 8% ethanolamine and 2.5% inositol glycerophospholipids, and much smaller amounts of serine and other minor phospholipids. Administration of a meal of each dietary fat resulted in a retention of approximately 50% endogenous fatty acids in the major glycerophospholipids of the chylomicrons. A minimum of 50% of the molecular species of the choline and ethanolamine glycerophospholipids contained at least one exogenous fatty acid. No significant discrepancies were found in the fatty acid and molecular species composition of the glycerophospholipids between chylomicrons from the oil and corresponding ester feeding. It is concluded that the chylomicrons arising from the monoacylglycerol (oil feeding) and the phosphatidic acid (ester feeding) pathways of triacylglycerol biosynthesis become enveloped in surfactant monolayers containing qualitatively and quantitatively identical classes and molecular species of phospholipids.

Animals

Induction of NAD(P)H:quinone reductase in human peripheral blood lymphocytes.

The induction of quinone reductase [QR; NAD(P)H:(quinone acceptor) oxidoreductase; EC 1.6.99.2] in cultured cells and animal tissues of rodents has provided useful information on mechanisms of protection against carcinogens. We have developed a simple and efficient microtiter plate assay for the direct measurement of QR basal activity and inducibility in human peripheral blood lymphocytes (unstimulated, mitogen-stimulated and Epstein-Barr virus-transformed) grown in suspension culture. In these cells, QR was induced by monofunctional (electrophilic) inducers (i.e. 1,2-dithiole-3-thione, dimethyl fumarate, methyl vinyl sulfone) but not by bifunctional inducers (i.e. 1,1'-azonaphthalene, beta-naphthoflavone, 2,3,7,8-tetrachlorodibenzo-p-dioxin). QR is a major enzyme of xenobiotic metabolism that carries out obligatory two-electron reductions and thereby protects cells against the toxicity of quinones. It is induced in many tissues coordinately with other enzymes that protect against electrophiles. Since lymphocytes can be sampled easily and repetitively in man, this system may provide a simple short-term marker for assessing the capacity of tissues to detoxify electrophiles, such as quinones, and for measuring the response to inducers.

Adult

Endotracheal administration of epinephrine during cardiopulmonary resuscitation.

A hypoxia-induced canine cardiac model was used to study the effectiveness hemodynamic response, arterial blood gas and pulmonary pathologic changes after endotracheal (ET) epinephrine administration in comparison with those from intravenous (IV) administration. The results indicated that the survival rate was the same with the drug given by either route. The increase of hemodynamic indices was lower in the group after ET administration than that after IV administration. No significant influence was exerted on the drug effects whether the drug is diluted in normal saline or in distilled water and no serious detrimental effects occurred on the lung tissues following ET epinephrine administration.

Animals

Apparent convergence (at 2-monoacylglycerol level) of phosphatidic acid and 2-monoacylglycerol pathways of synthesis of chylomicron triacylglycerols.

Dietary fats are converted into chylomicron triacylglycerols via the 2-monoacylglycerol and phosphatidic acid pathways of acylglycerol formation. In view of the known positional and fatty acid specificity of the acyltransferases, the triacylglycerol structures resulting from the two pathways would be expected to differ, but this has not been demonstrated. We have performed stereospecific analyses on the chylomicron triacylglycerols from rats fed menhaden oil and the corresponding fatty acid alkyl esters, which would be expected to be assimilated via the monoacylglycerol and the phosphatidic acid pathways, respectively. The results show a remarkable similarity between the two triacylglycerol types in the fatty acid composition of the sn-1 and sn-3 positions, along with marked differences in the composition of the sn-2 positions. The triacylglycerols from rats fed oil retained about 85% of the original fatty acids in the sn-2 position, including a high proportion of the long chain polyunsaturates (e.g., 5-7% 20:5 and 4-5% 22:6). The triacylglycerols from rats fed the alkyl ester contained large amounts of endogenous fatty acids in the sn-2 position (e.g., 18% 16:1, 14% 18:1, 14% 18:2, and 2.5% 20:4), which approximated the composition of the sn-2 position of the presumed phosphatidic acid intermediates. The sn-1 position contained a much higher proportion of polyunsatured fatty acids (e.g., 12-13% 20:5, 5-6% 22:6) than the sn-2 position (e.g. 2-3% 20:5, 0-0.6% 22:6) of triacylglycerols from rats fed the ester. We conclude that the chylomicron triacylglycerols arising via the 2-monoacylglycerol and the phosphatidic acid pathways differ mainly in the composition of the fatty acids in the sn-2 position. The similarity in the acids of the sn-1 and sn-3 positions of the chylomicron triacylglycerols from rats fed oil or ester is consistent with a hydrolysis of the acylglycerol products of the phosphatidic acid pathway to 2-monoacylglycerols prior to reconversion to triacylglycerols via the monoacylglycerol pathway and secretion as chylomicrons.

Animals

Biological characterization of multidrug-resistant human colon carcinoma sublines induced/selected by two methods.

Two independent multidrug-resistant (MDR) sublines, AdR1.2 and SRA1.2, were developed from the established human colon carcinoma cell line LoVo. AdR1.2 was developed by a long-term continuous exposure of LoVo cells to Adriamycin in stepwise increments of concentration; SRA1.2 was selected/induced by pulse treatments by using a single concentration of Adriamycin. The two resistant sublines were cross-resistant and cross-sensitive to a similar spectrum of cytotoxic agents. However, AdR1.2 was most resistant to Adriamycin among the nine agents tested, and SRA1.2 was most resistant to Vinca alkaloids. Although SRA1.2 had biological characteristics similar to those of LoVo, AdR1.2 had remarkably altered biological properties, including no detectable carcinoembryonic antigen secretion, a smaller proportion of proliferating cells and a lower growth rate, lower fraction of cells in S phase, a lower colony-forming ability, and smaller colonies. In addition, the resistant phenotype of AdR1.2 was reversed when the cells were grown in a drug-free medium, whereas SRA1.2 maintained its resistance for at least 10 months under similar conditions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the plasma membrane proteins demonstrated overproduction of an Mr 130,000 protein in both the resistant sublines. The Mr 130,000 protein was not immunoreactive with C219 monoclonal antibody against p170, but the absence of Mr 130,000 protein in an AdR1.2 revertant and the parental LoVo suggests that it is an MDR-related plasma membrane protein. The absence of a 46-kDa cytosolic protein and the presence of a Mr 150,000 plasma membrane protein were found in AdR1.2 but not in SRA1.2. This Mr 150,000 protein immunoreacted with C219. This protein was also present, although in a reduced amount, in an AdR1.2 revertant that retained three times the MDR of LoVo cells and was thus comparable to SRA1.2. The two MDR sublines thus may represent two independent subclones which may serve as two different models for the study of multidrug resistance in human colon cancer.

Adenocarcinoma

Surface array proteins of Campylobacter fetus block lectin-mediated binding to type A lipopolysaccharide.

Campylobacter fetus strains with type A lipopolysaccharide (LPS) and a surface array protein layer (S+) have been found to be pathogenic in humans and animals. Spontaneous laboratory mutants that lack surface array proteins (S-) are sensitive to the bactericidal activity of normal human serum. The ability of lectins to determine the presence of the S-layer and differentiate LPS type was assessed. We screened 14 lectins and found 3 (wheat germ agglutinin, Bandeiraea simplicifolia II, and Helix pomatia agglutinin) that agglutinated S- C. fetus strains with type A LPS but not S- strains with type B or type C LPS or S+ strains. However, the S+ type A strains were agglutinated after sequential water extraction, heat, or pronase treatment, all of which remove the S-layer, whereas there was no effect on the control strains. Specific carbohydrates for each lectin and purified LPS from a type A C. fetus strain specifically inhibited agglutination of an S- type A strain. In a direct enzyme-linked lectin assay, binding to the S- type A LPS strain was significantly greater than binding to the S+ strain (P = 0.01) or to a Campylobacter jejuni strain (P = 0.008). Consequently, these results indicate that the three lectins bind to the O side chains of C. fetus type A LPS but that the presence of the S-layer on intact cells blocks binding.

Agglutination Tests

Intestinal absorption of menhaden and rapeseed oils and their fatty acid methyl and ethyl esters in the rat.

The relative cellular uptake and incorporation into prechylomicrons and chylomicrons was investigated for the menhaden and rapeseed oil fatty acids, when given by stomach tube as the original oils or the corresponding methyl and ethyl esters. The intermediates and final products of cellular acylation were determined by chromatographic methods at various times over a period of 1-24 h. There was little selectivity in the uptake among the oligo- and poly-unsaturated fatty acids of menhaden oil, when either oil or esters were fed. In contrast, the long-chain saturated and monounsaturated fatty acids of rapeseed oil were discriminated against during both cellular uptake and reacylation (60% overall reduction in utilization). Also, there was detectable discrimination against the long-chain polyunsaturated monoacylglycerols of menhaden oil and against the long-chain saturated and monounsatured monoacylglycerols of rapeseed oil during both cellular uptake and reacylation (30% overall reduction in utilization). Evidence was obtained for an indiscriminate cellular uptake of variable amounts (4-22%) of intact dietary methyl and ethyl esters of fatty acids, which, however, appeared in the chylomicrons only to a very limited extent (0.1-1.0% of total lipid). During peak absorption the cellular and lymphatic appearance of fatty acids from the digestion and absorption of the alkyl esters was nearly 50% lower than that from the corresponding triacylglycerols. The slower absorption of the fatty acids from the alkyl ester feeding is hypothetically attributed to a lower efficiency of the phosphatidic acid pathway, which is required in the absence of dietary 2-monoacylglycerols, but other mechanisms cannot be excluded.

Animals

Lipolysis of menhaden oil triacylglycerols and the corresponding fatty acid alkyl esters by pancreatic lipase in vitro: a reexamination.

In order to distinguish between possible fatty acid differences during lumenal lipolysis and cellular absorption, we have reinvestigated the in vitro hydrolysis of menhaden oil and its alkyl esters by pancreatic lipase. For this purpose we incubated menhaden oil or its fatty acid methyl and ethyl esters with porcine pancreatic lipase in the presence of bile salts and determined the composition of the released free fatty acids, monoacylglycerols, diacylglycerols, and residual triacylglycerols, or the free fatty acids and residual alkyl esters, respectively, by thin-layer and gas-liquid chromatography. There was significant discrimination against the delta 4- to delta 7-unsaturated fatty acids of both medium and long chain lengths during the hydrolysis of menhaden oil and its fatty acid ethyl esters. In general, the ethyl esters were hydrolyzed 10-50 times more slowly than the corresponding glyceryl esters, depending on the exact ratio of the two substrate types. None of the triacylglycerols or ethyl esters, however, was completely resistant to hydrolysis resulting in an eventual cleavage of all the alkyl esters and presumably all the primary ester bonds in the triacylglycerol molecules. Since the rate of release of the least resistant fatty acid exceeded that of the most resistant acid by only a factor of 6, it is concluded that in the presence of a large excess of lipase the liberated fatty acids would approach the composition of the dietary alkyl or glyceryl esters, as observed during lumenal lipolysis (Yang, L.-Y., A. Kuksis, and J. J. Myher. 1989. Biochem. Cell Biol. 67: 192-204).

Animals

Increased cytotoxicity and reversal of resistance to cis-diamminedichloro-platinum(II) with entrapment of cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum (II) in multilamellar lipid vesicles.

The role of liposome entrapment in modulating the cytotoxicity of a lipophilic cisplatin derivative was assessed. cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum++ +(II) (NDDP) was tested in suspension (free NDDP) or entrapped in multilamellar vesicles composed of dimyristoylphosphatidyl choline and dimyristoylphosphatidyl glycerol (L-NDDP). Against LoVo colon carcinoma cells sensitive to cisplatin, L-NDDP was two times more cytotoxic in vitro than free NDDP and cisplatin (Do 7 microM for L-NDDP, 15 microM for free NDDP, and 16 microM for cisplatin). Against LoVo cells resistant to a concentration of 3 micrograms/ml of cisplatin, L-NDDP was three times more cytotoxic than free NDDP and cisplatin (Do 14 microM for L-NDDP, 45 microM for free NDDP, and 48 microM for cisplatin). In in vivo studies, free NDDP was less potent and less active than L-NDDP against i.p. L-1210 leukemia (free NDDP, optimum %T/C 148 at a dose of 75 mg/kg; L-NDDP, optimum %T/C 185 at a dose of 25 mg/kg) and i.p. L1210/PDD leukemia (free NDDP, optimum %T/C 128 at a dose of 50 mg/kg on Days 1, 5, and 9; L-NDDP, optimum %T/C 200 at a dose of 12.5 mg/kg on Days 1, 5, and 9). Free NDDP administered i.v. was inactive against liver metastases of M5076 reticulosarcoma (%T/C 102) while L-NDDP showed significant activity (%T/C 140). The single dose i.v. LD50 in mice of free NDDP and L-NDDP were similar (79.4 mg/kg for free NDDP and 64.5 mg/kg for L-NDDP). These studies show that NDDP is a liposome-dependent drug since it can only be satisfactorily formulated in the liposomal form and since the liposomal carrier plays a crucial role in determining its antitumor activity.

Animals

Size and composition of lymph chylomicrons following feeding corn oil or its fatty acid methyl esters.

Male rats with thoracic duct cannulae were intubated with corn oil or fatty acid methyl esters and the lymph was collected over the next 2-72 h. The apoprotein (apo) composition of the chylomicrons, isolated by conventional ultracentrifugation, was determined by sodium dodecyl sulfate - polyacrylamide - glycerol gel electrophoresis and isoelectric focusing. The lipid content and composition was assessed by gas--liquid chromatography. The particle size was obtained by calculation and confirmed by electron microscopy. The study demonstrates that both the monoacylglycerol (corn oil feeding) and the phosphatidic acid (methyl ester feeding) pathways of triacylglycerol biosynthesis yield chylomicrons with closely similar apoprotein profiles representing apo B-48, apo A-IV, apo E, apo A-I, and the apo C components. A protein band corresponding to apo B-100 was occasionally observed as a minor component of the chylomicrons from both groups of animals. The chylomicrons from corn oil feeding had about two times larger diameters than those from methyl ester feeding. There were no significant differences in the composition of the apoproteins, although the smaller particles had two times higher apoprotein/triacylglycerol ratios. It was calculated that the amount of apo B per lipid particle for the ester fed rats ranged from one to eight molecules and was closely correlated with the particle size. The corn oil fed rats yielded about three molecules apo B per lipid particle regardless of the particle size. It is concluded that the pathway of intestinal triacylglycerol biosynthesis has a significant effect on the apoprotein mass and to a lesser extent on the apoprotein and lipid composition of the chylomicrons. The phosphatidic acid pathway produces smaller particles and transfers to the bloodstream twice as much apoprotein per gram of fat than the monoacylglycerol pathway, which yields the larger particles. Possible variations in the site and rate of biosynthesis of the triacylglycerols could not be entirely excluded as contributing factors.

Animals

Stereochemical course of intestinal absorption and transport of mustard-seed oil triacylglycerols in the rat.

Male rats with thoracic duct cannulae were intubated with mustard-seed oil or the corresponding fatty acid methyl esters and the lymph was collected over 0-24 h. The chylomicron and very low density lipoprotein fractions were obtained by conventional ultracentrifugation. The triacylglycerols and glycerophospholipids were isolated and the positional distribution and molecular association of fatty acids were determined by stereospecific and chromatographic methods. The oleic, linoleic, and linolenic acids were recovered in the lymph in the proportion in which they occurred in the fat fed, while eicosenoic, erucic, and lignoceric acids were rejected to about the same extent by the two pathways of intestinal triacylglycerol biosynthesis. It is shown that the lymph triacylglycerols arising via the monoacylglycerol or the phosphatidic acid pathway possess structures that are closely similar to each other and to that of the original mustard-seed oil. It is proposed that this is a result of comparable fatty acid and positional specificity of the acyltransferases associated with the acylglycerol synthesis in the animal and plant tissues and the wide range of fatty acid chain lengths in the mustard-seed oil.

Animals

The activity of flavone acetic acid (NSC 347512) on human colon cancer cells in vitro.

Flavone acetic acid (FAA) was incubated for 1 to 48 hr with 3 established human colon cancer cell lines endowed with distinct degrees of phenotypic properties. All 3 lines responded to FAA in almost identical fashion; when incubated with the drug for only 1 hr, an initial decrease in survival was observed for concentrations of 250 micrograms/ml but no further increments in cytotoxicity were elicited when the concentration of FAA was augmented. Increasing the length of treatment yielded relatively modest increments (about 1 log) in cell killing only after an interval of 48 hr and only at the highest concentration (1000 micrograms/ml). Because of these relatively poor cytotoxic effects and because the therapeutic range of FAA is so narrow, we conclude that this agent will not be a valuable contribution to the antitumor arsenal, at least for colon cancer.

Antineoplastic Agents

Ligands of second generation platinum analogs decrease both platinum-induced DNA cross-linking and its ability to interact with 1-beta-D-arabinofuranosyl cytosine to potentiate cytotoxic efficacy.

We evaluated the cytotoxic and DNA cross-linking (CL) ability of four second generation platinum coordination complexes (TNO-6, JM-89, JM-8 and JM-9) delivered alone or in combination with 1-beta-D-arabinofuranosyl cytosine (ara-C) to human colon cancer cells (LoVo). Cell survival varied markedly as a function of the particular substitution moiety. JM-8 and JM-9 were virtually ineffective, even at concentrations as high as 50 micrograms/ml. At that concentration cis-diamminedichloroplatinum(II) (cis-DDP) killed greater than 99.99% of the cells. JM-82 was slightly more active while TNO-6 was the only derivative with appreciably higher cytotoxic activity due to an abrogation of the shoulder region of the type C survival curve. The highest CL effect was observed for cis-DDP followed closely by TNO-6. Very little CL effects were demonstrated for the other three analogs JM-82, JM-8 and JM-9 when measured 6 h after treatment. The combination of cis-DDP and ara-C augmented 10-fold the cytotoxic activity of cis-DDP alone, an effect accompanied by an almost 2-fold increase in CL; every other analog failed to interact in a potentiating manner (either cytotoxicity, or CL at 6 h) with the antimetabolite. Thus, it appears clear that the associated moieties of the Pt coordination complex play a fundamental role in reducing the interaction of the analogs with DNA (as reflected by the decreased CL and cytotoxic effects produced by each agent alone) and in totally preventing their interaction with ara-C to yield a potentiating lethal effect.

Carboplatin

New monoclonal antibodies against colon cancer-associated antigens.

Established human colon cancer cells with distinct degrees of differentiation (LoVo, well-differentiated; SW620, intermediate differentiation; and SW1116, poorly differentiated) were used to produce monoclonal antibodies (MoAbs) by standard hybridoma techniques. Specificity was tested by an enzyme-linked immunosorbent assay against human foreskin cells, 7 established human colon cancer lines, a panel of 17 established human tumor lines of different histological origins, purified carcinoembryonic antigen, panels of red blood cells, and a suspension of lymphocytes obtained from 30 random normal donors. MoAb LoVo-F4 3E4/1A1/2E10 (MoAb F4/2E10) reacted with five colon cancer lines and only slightly with MCF-7 cells (estrogen receptor positive breast carcinoma). MoAb LoVo-F4 3E4/1A1/5C10 also reacted with the previous five colon cancer lines and with two gastric cancer lines. A MoAb obtained with a LoVo 3 M KCl membrane extract reacted exclusively with LoVo cells. MoAb SW620-F1 4E5/1A3 reacted with only three colon cancer cell lines and an estrogen receptor negative breast cancer line. MoAb SW1116-F2 1E3/1A1 reacted with four colon carcinoma cell lines, one gastric cancer line, MCF-7 cells, and a lung cancer line. MoAb SW1116-F2 1F3/1B1 reacted intensely with purified carcinoembryonic antigen and with every carcinoembryonic antigen-producing cell line available in our laboratory. Further studies concentrated on the immunoglobulin G1 MoAb F4/2E10. We demonstrated that the purified MoAb did not inhibit binding of MoAb CA19-9 to any colon Ca lines and reacted with fresh human colon carcinoma specimens regardless of whether they were processed by cryostat or paraffin embedding after fixation in formalin for 24 through 96 h. Using the peroxidase-antiperoxidase technique, MoAb F4/2E10 did not react with 23 normal adult and 18 fetal (less than 3 months old) human tissue specimens. When tested on 312 specimens of diverse histological origins and diseases, the MoAb was positive in 57 of 62 colorectal cancers, in 12 of 19 villous adenomas, in 5 of 7 adenomatous polyps, and in 10 of 12 cases of ulcerative colitis. With the exception of 2 of 15 cases of Crohn's disease that were slightly positive, all tissues from nonmalignant diseases (regardless of histological origin) were consistently negative. There was only weak reactivity in 2 of 18 breast cancers, 7 of 21 squamous cell carcinomas, 4 of 27 lung tumors, 1 of 13 kidney carcinomas and in 7 miscellaneous tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal