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Hemagglutination inhibition studies for the evaluation of blood group antigens in ethanol soluble substances (ESS) obtained from human, baboon and vervet monkey red blood cells.

Soluble blood group substances, isolated from the red blood cells of humans, baboons, and vervet monkeys by ethanol extraction, possessed serologically active specificities for the following antigens: A, B, H, Lea, LebL, P, P19 Pk and I. Human red blood cells lacking any of these specificities by the direct hemagglutination test also lacked the related antigens in their soluble extract. The only exception was in "Bombay" Oh cells, from which soluble H substance could be readily isolated. Soluble substances obtained from baboon and vervet monkey red blood cells, which lack the human variety of A, B, and H antigens on their red blood cells, inhibited both human and lectin anti-H reagents. The detection of "hidden" H activity in Oh cells will pose some important questions regarding membrane characteristics and the role of immune surveilance.

ABO Blood-Group System↗

Detection of the H and I blood group antigens in normal plasma. A comparison with A and i antigens.

The levels of A, H, I and i antigens were measured in the plasma of 185 normal subjects by the agglutination-inhibition method. The presence of H in the plasma was only detectable with immune anti-H. The level of H in the plasma was directly correlated with the amount on the red cells, and was affected by the donor secretor status. The plasma of group O secretors contained more H than the plasma of donors of other phenotypes. On the other hand, I and i plasma antigens were not related to the other systems studied. Unlike the Ii antigens on the red cell membrane, there was no relationship between the levels of I and i in plasma.

ABO Blood-Group System↗

[The biochemical aspects of blood group antigens].

The biochemical aspects of the immunodominant structures of blood groups antigens are mainly restricted to the following: ABH and Lewis in secretory fluids or on the red blood cells; P system (P1, P, Pk antigens); MN antigens and related; Tn and Tn antigens; Some hypothesis may be put forward for the I, i antigens. Many other antigens seem to be on the dependence of interactions between proteins and lipids of the red cell membrane; such immunodominant structures are not yet known. Except for the ABH and Lewis groups, the biosynthesis pathways are at present unclear.

ABO Blood-Group System↗

Interrelations between ABO blood group, plasminogen, alpha1-antitrypsin, alpha2-macroglobulin and the platelet count in blood donors.

The level of plasminogen alpha1-antitrypsin, alpha2-macroglobulin and the platelet count were measured in 511 blood donors. The mean level of alpha1-antitrypsin was significantly lower in men of group B compared with that of group O. No other differences between the blood groups reached statistical significance. Woman had higher mean levels of alpha1-antitrypsin and alpha2-macroglobulin and a higher platelet count than men. The levels of plasminogen and alpha1-antitrypsin were significantly higher in women using oral contraceptive compared with those who were not. The level of alpha2-marcoglobulin fell with age until the 60-64 year age-group in men and the 40-49 year age-group in women. A positive correlation existed between the alpha1-antitrypsin and the alpha2-macroglobulin level and between the platelet count and the plasminogen level.

ABO Blood-Group System↗

Sequence of action of genes at the secretor, H, ABO and Lewis loci.

It is argued that Lewis genes are responsible for adding specificity to glycoprotein molecules after the activities of the secretor, H and ABO genes, respectively, have been expressed. This conclusion is based on the results of studies on the expression of ABO and Lewis antigens in salivas from Australian aborigines, and on biochemical results. A simple figure illustrating the antigens determined on red cells and in body secretions as a result of the action of these genes, in their correct order--secretor, H, ABO, Lewis--is presented.

ABO Blood-Group System↗

The Lewis antigens and secretor status.

The coincidence of the presence of ABH active substances in the saliva of persons with those individuals who possess either LEWIS-d or LEWIS-b antigens on epithelial cells of their stomach tissues is examined in terms of the three-dimensional conformations of the oligosaccharide structures which form the ABH and LEWIS antigenic determinants. The H activity in saliva is normally established by examining the inhibition of the agglutination of human H red cells, which possess H (Type 2) determints at their surface, by the lectin Ulex europaeus. As was to be expected, the LEWIS-d (H-Type 1) (alpha LFuc (1 leads to 2) beta DGal (1 leads to 3) beta DGlcNAcOR, R = (CH2)8COOCH3) and LEWIS-b (alpha LFuc (1 leads to 2) beta DGal (1 leads to 3) [alpha LFuc (1 leads to 4)] beta DGlcNAcOR) determinants, obtained by chemical synthesis, do not bind Ulex. However, these structures in the de-N-acetylated form proved to do so as evidenced by their ability to inhibit the agglutination. These results together with results obtained in inhibition studies involving chemically modified H (Type 1) and H (Type 2) structures are rationalized in terms of conformational analysis and raise the possibility that the LEWIS-b and d antigens in saliva are present with the determinants in the amine form. The circumstantial evidence obtained in support of this possibility is, as yet, inconclusive. The main thrust of the paper is to indicate how modern conformational analysis may play an important role in the improvement of knowledge in carbohydrate-receptor site interaction.

ABO Blood-Group System↗

[Structure and immunochemical properties of the urinary oligosaccharides excreted during induced galactosuria].

Induced galactosuria is characterized by the excretion in urine of large amounts of new oligosaccharides, the structure of which are in connection with blood-group phenotypes ABH, Lewis and Secretor: O group : O-alpha-L fucopyranosyl-(1 leads to 2)-D galactopyranose et O-alpha-L fucopyranosyl-(1 leads to 2)-O-beta-D galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 4)]-O-beta-D 2-deoxy-2 acetamido-glucopyranosyl-(1 leads to 4)-[O-alpha-L fucopyranosyl-(1 leads to 6)]-D-galactopyranose. A group: O-alpha-D-2-deoxy-2 acetamido-galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 2)]-D galactopyranose et O-alpha-D-2-deoxy-2 acetamido-galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 2)]-O-beta-D galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 4)]-O-beta-D-2-deoxy-2 acetamido-glucopyranosyl-(1 leads to)-[O-alpha-L fucopyranosyl-(1 leads to 6)]-D galactopyranose. B group : O-alpha-D galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 2)]-D galactopyranose et O-alpha-D galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 2)]-O-beta-D galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 4)]-O-beta-D-2-deoxy-2 acetamido-glucopyranosyl-(1 leads to 4)-[O-alpha-L fucopyranosyl-(1 leads to 6)]-D-galactopyranose.

ABO Blood-Group System↗

[Study of the fucose-rich oligosaccharides in the urine of healthy and melituric subjects with A, B and O blood groups].

The application of adsorption chromatography on charcoal-Celite leads the authors to characterize in normal urines a class of fucose-rich oligosaccharides which possess blood group activities and are related to the phenotypes ABH, Le and secretor. Most of these oligosaccharides have a glucose residue in reducing terminal positions. Excretion of some oligosaccharides increases in the urine of diabetic and lactosuric subjects. In spontaneous or induced galactosurias, the elimination of oligosaccharides with a glucose residue in reducing terminal position decreases while appears a large amount of new oligosaccharides which all possess a galactose residue in reducing terminal position. These results lead to the conclusion that urinary oligosaccharides do not originate from glycosphingolipids, but from transglycosylation on carbohydrates which exist free in the organism: glucose for normal and diabetic subjects, lactose or galactose for lactosuric and galactosuric subjects, respectively.

ABO Blood-Group System↗

Genetic study of von Willebrand factor antigen levels ≤ 50 IU/dL identifies variants associated with increased risk of von Willebrand disease and bleeding.

BACKGROUND: von Willebrand disease (VWD) is a common inherited bleeding disorder caused by low levels or activity of circulating von Willebrand factor (VWF). Genetic susceptibility to VWF antigen (VWF:Ag) below normal (&#x2264; 50 IU/dL) in the general population is underexplored. OBJECTIVES: To identify genetic variants influencing VWF:Ag levels &#x2264; 50 IU/dL. METHODS: We performed a genome-wide association study in 926 cases with VWF:Ag levels &#x2264; 50 IU/dL and 12 846 controls from 7 studies from the Trans-Omics for Precision Medicine program. We then examined whether significant genome-wide findings were also associated with clinical diagnosis of VWD in 5 biobanks with 708 VWD cases and 1 286 069 controls, and with 6 bleeding and thrombotic disorders in FinnGen. RESULTS: Variants at 2 loci were associated (P < 5 &#xd7; 10-9) with VWF:Ag levels &#x2264; 50 IU/dL: ABO and VWF. The VWF index variant, p.Tyr1584Cys, is a rare (0.22%) missense variant with odds ratio (OR) of 78.58, while the ABO index variant is a common intronic variant with a smaller effect (OR = 2.52). Notably, both VWF (OR = 7.16) and ABO (OR = 1.57) variants were also associated (P < .025) with diagnosed VWD. Among p.Tyr1584Cys heterozygotes, the penetrance of VWF:Ag levels &#x2264; 50 IU/dL was 24.2% and the penetrance of diagnosed VWD was 0.3%. p.Tyr1584Cys was associated (P < .0042) with increased odds of heavy menstrual bleeding (OR = 1.27), iron deficiency anemia (OR = 1.55), and intrapartum hemorrhage (OR = 2.20), but decreased odds of deep vein thrombosis (OR = 0.54). CONCLUSIONS: Although there are currently conflicting interpretations of pathogenicity p.Tyr1584Cys, our results suggest that it is a low penetrance pathogenic variant that contributes to VWF:Ag levels &#x2264; 50 IU/dL, bleeding, and VWD.

Humans↗

Multiple specificities of mammalian blood group substances comparatively studied with human isoagglutinins and fractionated anti-H lectins.

Purified blood group-active substances derived from different pig, horse, baboon, Rhesus monkey and human tissues were quantitatively studied for their haemagglutination inhibiting potency with: (1) human IgM anti-A and anti-B; (2) human anti-Lea and anti-Leb; (3) Ulex europaeus extracts separated into lectin fractions with respective L-fucose-inhibitable ('anti-HF') and chitobiose-cellobiose-inhibitable ('anti-HC') combining sites. Irrespective of species origin, A and B blood group activity per milligram of purified material tended to be strikingly higher in substances low in, or devoid of, Lewis blood group activity. Most of the blood group substances displayed variable but about equally balanced amounts of Ulex anti-HF and anti-HC inhibiting activity. In contrast, pig submaxillary gland mucins displayed strikingly high levels of Ulex anti-HC inihibiting activity, even in the complete absence of Ulex anti-HF inhibiting activity. These serological findings are consistent with current biochemical concepts regarding the heterosaccharide microheterogeneity of blood group-active glycoproteins.

ABO Blood-Group System↗

Rh isoimmunization during pregnancy: antenatal prophylaxis.

Of 3533 Rh-negative women who began a pregnancy without detectable Rh antibodies, 62 (1.8%) demonstrated evidence of Rh isoimmunization during pregnancy or within 3 days after delivery. All denied transfusions as well as abortions or previous pregnancies not followed by the administration of Rh immune globulin. Rh isoimmunization during pregnancy or within 3 days after delivery, which will not be prevented by the administration of Rh immune globulin after delivery, is the most important cause of residual Rh isoimmunization. A clinical trial of antenatal administration of Rh immune globulin, initially at 34 weeks's and subsequently at 28 and 34 weeks' gestation, in 1357 Rh-negative pregnant women who were delivered of Rh-positive babies, was effective in preventing the development of Rh isoimmunization during pregnancy or within 3 days after delivery. Antenatal prophylaxis with Rh immune globulin will be necessary if the incidence of Rh isoimmunization is to be reduced to its lowest possible level. Antenatal prophylaxis at 28 weeks' gestation is now an insured service in Manitoba.

Antibody Formation↗