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J Le Pendu

Publications and source records attributed to J Le Pendu.

At least 73 records · Page 4Linked to original sources

On the specificity of human anti-H antibodies.

Anti-H antibodies from 2 homogeneous subgroups of H-deficient individuals (Bombay and Réunion phenotypes) were studied for their specificity with regard to synthetic H oligosaccharides. It appears that Bombay individuals synthesize large amounts of both anti-H type 2 and anti-H type 1 antibodies, whereas Réunion individuals may possess strong anti-H type 1 antibodies, but have only weak anti-H type 2 antibodies in their serum. This can be explained by the presence of small amounts of H-type 2 determinants on the erythrocytes of Réunion individuals contrasting with the complete lack of H determinants on the red cells of Bombay individuals.

ABO Blood-Group System↗

Heterogeneity of Lewis antibodies. A comparison of the reaction of human and animal reagents with synthetic oligosaccharides.

Human as well as animal anti-Lewis reagents were shown to have different binding patterns to synthetic structures chemically related to the Lewis epitopes. Two main types of cross-reactions were found: (1) Cross-reactions among type 1 Lewis epitopes (Lea, Leb and Lewis disaccharide). This type of cross-reaction among different type 1 structures was predominant in anti-Lea reagents (16 out of 18), although it was also present in some anti-Leb reagents (4 out of 14). (2) Cross-reactions of Lea and Leb with their type 2 isomers X and Y. The Leb-Y cross-reaction was more frequent (7 out of 14) than the Lea-X cross-reaction (2 out of 18). The serological property of some anti-Lewis reagents reacting with cord cells ('Lex') is also shown to be heterogeneous although probably related to common features of the type 1 Lea and Leb epitopes and independent of the type 2 X and Y epitopes.

Agglutination Tests↗

Developmentally regulated cell surface structures on mouse and human embryonal carcinoma cell lines.

Three monoclonal antibodies 5.1.H, 8.7.D and 13.7.A raised against semi-purified Tera 1 membrane fractions recognize distinct onco-foetal antigens which are developmentally regulated on cells such as Tera 2 clone 13 and appear to be restricted in their expression to undifferentiated ectoblastic cells and certain organized cystic structures mimicking the foetal intestine. These antigens, absent from normal adult tissues, differ markedly from glycosidic stage-specific antigens such as 75.12 which, while functioning as embryonal carcinoma differentiation markers, are also expressed on certain adult tissues. No evidence for a role of fucosyltransferases in regulating either 75.12 or SSEA-1 antigen expression on embryonal carcinoma cells or for the presence of lectin-like structures recognizing these antigens on such cells was found.

Adult↗

Detection of combined ABH and Lewis glycosphingolipids in sera of H-deficient donors.

The sera of H-normal, H-weak and H-deficient individuals transferred the same amounts of ABH and Lewis antigens to lymphocytes in culture, confirming that the circulating ABH and Lewis antigens detected by lymphocytotoxicity are independent of the H-h system. These antigens were, as expected, under the control of the secretor and Lewis systems in the same way as exocrine secretions. These results suggest that both circulating ABH and Lewis glycosphingolipids and exocrine ABH and Lewis glycoproteins can be synthesized by the same tissues.

ABO Blood-Group System↗

Immunohistologic pattern of type 1 (Lea, Leb) and type 2 (X, Y, H) blood group-related antigens in the human pyloric and duodenal mucosae.

Type 1 antigens (Lea and Leb) of the pyloric mucosa are restricted to the mucus cells of the surface epithelium and the neck. In the duodenum they are present in absorptive and goblet cells of duodenal villi as well as in the glands of Lieberkühn. Type 2 antigens (X, Y, and H) are also present in these areas of the mucosa, and both type 1 and type 2 antigens, in this superficial location, are under the control of the secretor gene. In addition, type 2 antigens are also present in the mucus cells of pyloric and Brunner's glands, but in this deep location they are not controlled by the secretor gene. These results suggest the existence of two differentiation patterns for the expression of glycosyltransferases in the stem cells. The upward differentiation process would favor the expression of the alpha-2-L-fucosyltransferase coded by the Se gene, and the downward differentiation process would favor the expression of the alpha-2-L-fucosyltransferase coded by the H gene. The knowledge of the distribution and the genetic control of type 1 and type 2 antigenic determinants in normal gastrointestinal tract may help to interpret the modifications in the expression of these antigens in pathologic conditions such as neoplasia.

ABO Blood-Group System↗

The presence of at least two different H-blood-group-related beta-D-gal alpha-2-L-fucosyltransferases in human serum and the genetics of blood group H substances.

Sera from H normal, secretors and nonsecretors (H/-, Se/- and H/-, se/se), as well as from H-deficient secretors (h/h, Se/- or Bombay secretors) contain enzyme(s) for the transfer of L-fucose in the alpha-configuration to the 2-position of suitable beta-D-galactopyranosyl units. Sera from H-deficient nonsecretors (h/h, se/se; i.e., Bombay nonsecretors) are devoid of such beta-D-Gal alpha-2-L-fucosyltransferase(s). In order to study these enzymes, a comparison was made of the kinetic properties of the enzymes present in the sera of H-normal nonsecretors (H/-, se/se) with those of H-deficient secretors (h/h, Se/se) with those of H-deficient secretors (h/h, Se/-). These studies revealed a clear difference between the two sources of enzyme: (1) the apparent Km for GDP-fucose was four times lower with the H-normal nonsecretor serum (0.008 mM) than with the H-deficient secretor serum (0.028 mM); (2) acceptors with a type 1 or type 3 chain proved to be better than acceptors with a type 2 chain or than phenyl-beta-D-galactopyranoside for the enzyme present in the serum of H-deficient secretor individuals. Indeed, the synthetic type 2 compound, betaDGal (1-->4)-3-deoxy-beta-DGlcNAc-1-OCH3, which cannot act as an acceptor of beta DGlcNAc alpha-3/4-L-fucosyltransferases, remained unchanged in the serum of an H-deficient secretor but was a good acceptor in the serum of an H-normal nonsecretor, and (3) the alpha-2-L fucosyltransferease activity of the H-deficient secretor serum was more sensitive to heat inactivation than that of the H-normal nonsecretor serum (t1/2 at 46 degrees C were 10 min and 75 min, respectively). These results show that at least two distinct alpha-2-L-fucosyltransferases are present in human serum. It is concluded that the enzymatic activity found in the H-deficient secretor serum (h/h, Se/-) could be the product of the Se gene and the enzymatic activity found in the H-normal nonsecretor serum (H/-, se/se) could be the product of the H gene. This conclusion correlates well with the finding that H and Se genes are closely linked and might have derived by gene duplication in the course of evolution.

ABO Blood-Group System↗

The glycosidic antigen recognised by a novel monoclonal antibody, 75.12, is developmentally regulated on mouse embryonal carcinoma cells.

Monoclonal antibody 75.12 raised against the human ovarian teratocarcinoma cell line PA1 detects a 'Y' or iso-leb glycosidic structure. Using the 75.12 antibody we have established that the Y antigen is expressed on some but not all mouse embryonal carcinoma (EC) lines. The Y or 75.12 antigen-positive EC cell lines F9 and PCC4 cease to express the antigen after differentiation induced with retinoic acid and this decreased expression parallels the morphological differentiation of the EC cells. These results support not only the idea that carbohydrate structures present on embryonic cells undergo marked alteration during differentiation, but also that established mouse EC cells may differ in their differentiation states.

Animals↗

Competition between ABO and Le gene specified enzymes. I. A Lewis related difference in the amount of A antigen in saliva of A1 and A2 secretors.

Radioimmunoassays were prepared using two anti-A and one anti-B reagents. The specificity of the procedures was assessed with 13 artificial antigens. The amounts of A and B natural antigens in saliva of ABH secretors of known Lewis phenotype were measured with these assays. The results confirmed that the average amount of A antigen is lower in Lewis-positive (Leb) than in Lewis-negative (Led) donors and in A2 than in A1 donors. However, the differences among the four combined A and Lewis phenotypes were only supported by significantly lower amounts of A antigenic determinants in A2Leb as compared to the other three phenotypes (A1Leb, A1Led and A2Led) that had similar amounts of A antigenic determinants. No Lewis-related difference could be detected in the amounts of B antigens between BLeb and BLed donors. The results are discussed in terms of competition between A, B and Lewis-gene-specified enzymes for their common acceptors. The difference in the efficiency of the A2 enzyme as compared to that of the A1 enzyme is proposed as a possible explanation for the A1-A2 phenotypic difference.

ABO Blood-Group System↗

Competition between ABO and Le gene specified enzymes. II. Quantitative analysis of A and B antigens in saliva of ABH nonsecretors.

One B- and two A-specific radioimmunoassays detected A and B antigenic determinants in saliva of ABH nonsecretors. The A or B antigens found in saliva of nonsecretors had lower efficiency and higher heterogeneity, in the inhibition of the A or B assays, as compared to A or B antigens in saliva of ABH secretors. In the 3 assays, samples of nonsecretor Lewis positive donors (Lea) had less A or B antigens than samples of nonsecretor Lewis negative donors (Lec), suggesting that there is a competition between A or B and Le gene-specified products.

ABO Blood-Group System↗

H-deficient blood groups of Reunion island. II. Differences between Indians (Bombay Phenotype) and whites (Reunion phenotype).

Two variants of recessive, H-deficient nonsecretor individuals (h/h, se/se) were identified on Reunion Island: (1) H-negative individuals corresponding to the classical Bombay phenotypes (OhO, OhA, OhB, OhAB) who lack completely the H antigen on their red cells; all of them were Indian and had strong anti-H antibodies reacting with normal O and Oh red cells from whites; and (2) H-weak individuals (Oh, Ah, Bh, ABh). This phenotype represented the majority (85%) of the H-deficient phenotypes on Reunion Island, and all of them were white. They had only a weak expression of the H antigen and showed small but detectable amounts of ABH antigens on their red cells. Their anti-H antibodies reacted with normal O erythrocytes, but failed to react with Oh red cells, regardless of the ethnic origin of the donor. They were all from the same geographical area on the Island (Cilaos) and showed homogeneous titers of anti-H antibodies in sera. We propose to call this particular variant of weak H phenotype, belonging to the so-called para-Bombay series, Reunion.

ABO Blood-Group System↗

H-deficient blood groups of Reunion Island. III. alpha-2-L-fucosyltransferase activity in sera of homozygous and heterozygous individuals.

Small amounts of H-enzyme activity (from 500 to 1,280 counts per minute [cpm]) were detected in sera of white H-deficient individuals (h/h; Reunion phenotype), while no significant H activity (less than 500 cpm) could be detected in sera of Indian H-deficient individuals (h/h; Bombay phenotype). The H-enzyme levels of the unaffected members of H-deficient pedigrees showed an H-related dosage effect. Heterozygous H/h individuals had only half as much H activity in sera (17,000 +/- 3,400 cpm) compared with homozygous H/H individuals (31,600 +/- 3,700 cpm). Data suggesting interactions between the H enzyme and the other gene specified glycosyltransferases working on the same oligosaccharide chains carrying combined ABH and Lewis antigens are analyzed in terms of their possible genetic or biochemical origin.

ABO Blood-Group System↗

Synthesis of type 2 human blood-group antigenic determinants. The H, X, and Y haptens and variations of the H type 2 determinant as probes for the combining site of the lectin I of Ulex europaeus.

Chemical syntheses of the human blood-group antigenic determinants derived from N-acetyllactosamine are described; namely, the 6-deoxy derivative, the 4'-epimer, and the 5 H type 2 [alpha LFuc(1 to 2)beta DGal-(1 to 4)beta DGlcNAc], X [beta DGal(1 to 4)[alpha LFuc(1 to 3)[beta DGlcNAc], and Y [alpha LFuc-(1 to 2)beta DGal(1 to 4)[alpha LFuc(1 to 3)]beta DGlcNAc] determinants as glycosides of 8-carboxymethyloctanol. In order to study the binding of the H type 2 determinant with the lectin I of Ulex europaeus, structures designed to specifically alter the hydrophilic and hydrophobic portions of the H type 2 determinant were also prepared; namely, the 6-deoxy derivative, the 4'-epimer, and the 5"-nor-homolog. The use of these structures, together with the H type 1 hapten and the N-deacetylated forms of both the H type 1 and H type 2 determinants, as inhibitors of the agglutination of O red cells by the lectin allowed the conclusion that the binding of the H type 2 determinant is hydrophobic; the binding involves a wedge-like portion of the determinant that is basically hydrophobic, except for the 5-hydroxymethyl group, which is at the tip of the wedge and forms an intramolecular hydrogen-bond with O-5 for acceptance by a hydrophobic cleft at the surface of the lectin. Blocking procedures involving alkoxymethyl groups and new experiences involving glycosylation reactions are described.

Carbohydrate Conformation↗

Influence of the original disease, race, and center on the outcome of kidney transplantation.

The low graft survival rate in black recipients (36 +/- 2% at 1 year) as compared with the graft survival rate in white recipients (48 +/- 1%) might be secondary to a higher incidence of vascular lesions, inducing hypertensive disease, in blacks than in whites. The relative frequency of malignant hypertension in black recipients was six times that of white recipients, and recipients with malignant hypertension had a significant lower graft survival rate (43 +/- 2%) than recipients with glomerulonephritis (54 +/- 1%). In addition, patients with vascular lesions (diabetes, malignant hypertension, and glomerulonephritis) showed significantly lower graft survival rates in black than in white recipients, in contrast to patients with primary tubular or interstitial lesions (polycystic kidneys and pyelonephritis), who showed similar graft survival rates in blacks and whites. Only a small fraction of this racial effect could be traced back to the higher incidence of Lewis-negative phenotypes in black recipients and a similar beneficial effect of transfusions, on graft survival, was observed in both black and white recipients. The effects of graft survival of age (6%), race (9%), and transfusions (18%) were significant in good (A) and poor (B) centers. No overlap between A and B centers was observed for any of these three parameters when analyzed separately. However, when the cumulative effects of these three risk parameters were analyzed together a partial overlap appeared, i.e., higher graft survival rates were observed in low-risk recipients that received transplants in B centers than in high-risk recipients that received transplants in A centers. Consequently, the selection of the recipient may play a role in the overall results of different transplantation units, leading to their classification into A or B centers, but cannot explain all of the differences between A and B centers.

Actuarial Analysis↗

Purification of anti-Lec antibodies with specificity for beta DGal(1 replaced by 3)beta DGlcNAcO- using a synthetic immunoadsorbent.

Artificial antigens: Antibodies were raised in rabbits with beta DGal(1 linked to 3)beta DGlcNAc-BSA and purified by absorption elution on a column of the synthetic oligosaccharide covalently bound to a silicate instead of BSA. The purified antibodies agglutinated specifically erythrocytes from Le (a-b-) nonsecretor donors (Lec). Natural antigens: Antibodies were raised in goats using boiled saliva from O/O, le/le, se/se donors. The population of antibodies which was absorbed on a column consisting of beta DGal(1 linked to 3)etaDGlcNAc-O-R (type 1 chain precursor disaccharide) groupings attached to a silicate was collected and then refined by passage through a column which consisted of similarly immobilized alpha LFuc(1 linked to 2)beta DGal(1 linked to 3)betaGDlcNAc-(H type 1), beta(DGal(1 linked to 3)-[alpha LFuc(1 linked to 4)]beta DGlcNAc-(Lea), and beta DGal(1 replaced by 4)beta DGlcNAc-(type 2 core chain precursor) groupings. The refined antibodies proved to have a reaction pattern with salivas that is the same as that previously reported for anti-Lec sera. The data obtained with natural and artificial antigens are thus compatible with the biosynthetic pathway for the formation of the Lewis antigenic determinants proposed by Graham and suggest that the Lec antigen may simply be the type 1 precursor chain which is required for the formation of the Lea, Led and Leb antigenic determinants.

Animals↗

Distribution of H type 1 and H type 2 antigenic determinants in human sera and saliva.

A radioimmunoassay specific for the H type 1 antigenic determinant demonstrated that the H type 1 antigen is under the strict control of the Se gene in both serum and saliva. Similar amounts of H type 1 antigenic determinants were found in saliva from Se/-, le/le donors and in saliva from Se/-, Le/- donors. However, sera from Se/-, le/le donors were about 100 times more efficient in inhibiting the H type 1 assay than were sera from Se/-, Le/- donors. A radioimmunoassay, based on the binding of Ulex europaeus with the H type 2 antigenic determinant, showed that all the H type 2 antigen in saliva is under the control of the Se gene, while only one-third of the H type 2 antigen present in serum is under the control of this gene. The remaining two-thirds of H type 2 antigen in sera is independent of the ABH secretor status of the donor. The amount of H type 2 antigen in both serum and saliva is independent of the Le gene. These results are compatible with the existence of two alpha (1 leads to 2) fucosyl-transferases but suggest that the enzyme of epithelial origin, coded by the Se gene, should be able to transform both type 1 and type 2 natural substrates, while the enzyme of mesodermic origin, coded by the H gene, would work preferentially on the natural type 2 substrates.

ABO Blood-Group System↗