Tamoxifen is not detrimental to endothelial function in postmenopausal women with breast cancer.

BACKGROUND: Tamoxifen has mixed estrogen agonist and antagonist properties in estrogen-regulated tissues. Its effect on the cardiovascular system is not well defined. We carried out a study to investigate the effect of tamoxifen on peripheral vascular endothelial function. METHODS: Three groups of postmenopausal women (median age, 56 years; range, 39 to 69 years) with breast cancer were studied. Patients in group 1 (n = 10) were newly diagnosed with breast cancer and studied before and after 4 weeks treatment with tamoxifen. Group 2 women (n = 6) had been receiving long-term tamoxifen (3 to 5 years) and were studied while taking tamoxifen and 4 weeks after stopping it. The final group of 6 subjects were in remission from primary breast cancer and were not receiving or had previously received tamoxifen. Ultrasound assessments of endothelial function were done before and 4 weeks after the initiation or discontinuation of tamoxifen with the nontreatment group acting as control. All ultrasound imaging was made by a single investigator blinded to the therapeutic status of the subject. Brachial artery diameter was measured by ultrasound at baseline and 1 minute after reactive hyperemia. Flow-mediated reactivity (FMR) was defined as percent change in artery diameter from baseline 1 minute after reactive hyperemia. RESULTS: There was no change in FMR in patients before compared with 4 weeks after starting tamoxifen (4.06% +/- 1.44% vs 3.97% +/- 1.20%, respectively, mean +/- standard error of the mean [SEM], P =.97). There was no significant change in FMR on withdrawal from tamoxifen (1.84% +/- 1.98% vs -0.42% +/- 1.44% on tamoxifen vs off tamoxifen, mean +/- SEM, P =.36). FMR in subjects taking tamoxifen was no different from the control group (3.17% +/- 1.05% vs 3.16% +/- 0.91%, respectively, mean +/- SEM, P =.995). CONCLUSIONS: Tamoxifen does not appear to affect endothelial function in the short term in postmenopausal women with breast cancer.

Association of the human Lewis blood group Le(a-b-c-d-) with the failure of expression of alpha-3-L fucosyltransferase.

Two unrelated individuals are reported who lack alpha-3-L-fucosyltransferase activity in their serum and saliva. Both were blacks, one from the United States and the other from South Africa. No other of the tested members of their families lacked this enzyme. A survey of more than 2000 serum samples from both black and white South African blood donors, black United States donors and white United Kingdom donors failed to disclose another example of a serum deficient in alpha-3-L-fucosyltransferase activity. The two individuals lacking in alpha-3-L-fucosyltransferase activity both had the Lewis blood group phenotype Le(a-b-c-d-). No other persons with this phenotype have been reported. The absence of Lec activity in the two individuals who are deficient in alpha-3-L-fucosyltransferase is consistent with the interpretation that alpha-3-linked L-fucose is an essential part of the antigenic determinant recognised by the anti-Lec reagent used in this investigation.

Immunochemistry of the Lewis blood-group system: isolation and structures of Lewis-c active and related glycosphingolipids from the plasma of blood-group O Le(a-b-) nonsecretors.

Five different glycosphingolipid fractions (GL-3, 285 micrograms; GL-5, 1090 micrograms; GL-6, 615 micrograms; GL-7, 555 micrograms; and GL-8, 155 micrograms) have been isolated from 25 liters of plasma of O Le(a-b-) nonsecretors by means of ethanol extraction, several steps of Folch distribution, and reversed-phase, silicic acid, and ion-exchange column chromatography of native or peracetylated substances. Final purification, accomplished by preparative silica gel high-performance thin-layer chromatography, led to chromatographic homogeneity of GL-3 and GL-6. In the hemagglutination inhibition as well as quantitative passive hemagglutination techniques two of these substances (GL-3, GL-5) exhibited distinct, and the other three (GL-6-GL-8) very strong, Lec blood-group activities when tested against two different Lec antisera of human or goat origin. The fragments' structures were elucidated by fast atom bombardment and electron impact mass spectrometry of permethylated derivatives in order to determine molecular weight, sugar sequence, position of branching points, and type of oligosaccharide chains, as well as fatty acid and sphingosine patterns of the ceramide residue. Combined gas-liquid chromatography and mass spectrometry of partially methylated alditol acetates identified sugar composition and glycosidic linkages. Thus, the following structures could be established: (formula; see text) In contrast to the structurally homogeneous GL-3, minor amounts of 4-O-substituted GlcNAc pointed to a small contamination of GL-6 by branched type 2 ceramide nonasaccharide analogs. Glycolipids containing hepta- or nonasaccharides as in GL-3 or GL-6 could also be identified in fractions GL-5 (ceramide heptasaccharide) and GL-7 and GL-8 (ceramide nonasaccharide). These latter fractions revealed, however, distinct heterogeneity due to the presence of a small amount of either a type 2 analog of GL-3 (GL-5) or linear, mainly type 2, ceramide hexa- (GL-5, GL-7) or octasaccharides (GL-8). In addition to previous immunochemical communications the presented Lec active structures of GL-3 and GL-6 provide evidence that 3-fucosyl-N-acetyllactosamine in combination with a type 1 based oligosaccharide sequence and a 3,6-galactosyl branching point are essential parts of the Lec antigenic determinant (as marked in the formula of GL-6).

Adsorption of Lec and Led from plasma onto red blood cells.

When red blood cells lacking a particular antigen (Lea, Leb, Lec or Led) were incubated with plasma from a donor whose red blood cells had that antigen, the red blood cells became agglutinable by the antiserum that agglutinated the red blood cells of the plasma donor. The presence of each of these antigens on an individual's red blood cells correlates with the presence of a soluble antigen in his plasma, presumably glycosphingolipid, which is capable of adsorbing onto red blood cells.

A genetic model for the inheritance of the P, P1 and Pk antigens.

A new genetic model of the P blood group system is presented. The system is controlled by two chromosomal loci. The first locus has three allelic genes. The pk gene codes for an alpha galactosyl transferase that converts ceramide dihexoside to ceramide trihexoside (or the pk antigen). The second allele, the pk gene, codes for an alpha galactosyl transferase that converts both ceramide dihexoside to ceramide trihexoside (or the pk antigen) and paragloboside to the P1 antigen. The third allele does not produce an active codes for a beta N-acetyl galactosaminyl transferase that converts ceramide trihexoside to globoside (or the P antigen). The second allele does not produce an active product. The predictions of the model are in agreement with family studies and fibroblast fusion studies. The current model and previous genetic models, however, predict different possible phenotypes from rare 2 x p or p2k x p matings or fibroblast fusions.