Blood group AB is protective factor for gestational diabetes mellitus: a prospective population-based study in Tianjin, China.

BACKGROUND: The ABO blood types are associated with cancers, cardiovascular diseases and type 2 diabetes mellitus but whether they are also associated with gestational diabetes mellitus (GDM) is unknown. We examined the relationship between the ABO blood types and the risk of GDM in a prospective population-based Chinese cohort. METHODS: From 2010 to 2012, we recruited 14,198 pregnant women within the first 12 weeks of gestation in Tianjin, China. All women had a glucose challenge test (GCT) at 24-28 gestational weeks, followed by a 75-g 2-h oral glucose tolerance test if the results from GCT were ≥7.8 mmol/L. GDM was diagnosed based on the glucose cut-points of the International Association of Diabetes and Pregnancy Study Group criteria. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for traditional risk factors. Stratified analysis was performed by family history of diabetes (yes versus no). Sensitivity analyses were also performed by using the World Health Organization (WHO) criteria for GDM. RESULTS: Women with blood groups A, B or O (i.e. non-AB) were associated with increased risk of GDM as compared with those with blood group AB (adjusted OR: 1.44, 95% CI: 1.13-1.83). Sensitivity analyses showed that the result was consistent using WHO criteria. The adjusted OR of blood group non-AB versus AB for GDM was enhanced among women with a family history of diabetes (2.69, 1.21-5.96) and attenuated among those without (1.33, 1.03-1.71). CONCLUSIONS: Blood group AB was a protective factor against GDM in pregnant Chinese women.

Bacterial homologue of human blood group A transferase.

A bacterial version of human blood group A transferase was identified and found to be able to accept five naturally existing H-antigen core structures as good substrates, demonstrating its versatility for synthesis of blood group A antigens. Furthermore, this enzyme was applied in the engineering of bacterial cell surface polysaccharides by remodeling blood group B mimicry into blood group A mimicry.

Augmentation of UDP-GalNAc: Fucalpha1-2Gal alpha1-3 N-acetylgalactosaminyl transferase activity in nitrosamine-induced hamster pancreatic cancers.

Pancreatic cancers induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters produce blood group-A antigen (BG-A Ag), which is not present in the normal pancreas. To understand the neo-expression mechanism of BG-A Ag, we examined uridine diphosphate (UDP)-N-acetylgalactosamine (GalNAc): fucose (Fuc) alpha1-2 galactose (Gal) alpha1-3 GalNAc transferase (alpha1-3 GalNAc Tf) activity, the enzyme responsible for BG-A production. The specific activity of alpha1-3 GalNAc Tf in pancreatic cancers was approximately 8,000 nmole/g protein/h, whereas it was absent from the normal pancreas. Although the antrum and colon express A-Tf and BG-A Ag, the divalent cation requirements of alpha1-3 GalNAc Tf in these tissues were different from those of cancers. These results suggest that alpha1-3 GalNAc Tf is activated during BOP-induced pancreatic carcinogenesis, and that there are multiple alpha1-3 GalNAc Tf isozymes present in hamster tissues.

Recognition of synthetic O-methyl, epimeric, and amino analogues of the acceptor alpha-L-Fuc p-(1-->2)-beta-D-Gal p-OR by the blood-group A and B gene-specified glycosyltransferases.

The disaccharide alpha-L-Fuc p-(1-->2)-beta-D-Gal p-O-(CH2)7CH3 (6) is an acceptor for the glycosyltransferases responsible for the biosynthesis of the A and B blood-group antigens. These enzymes respectively transfer GalNAc and Gal in an alpha linkage to OH-3 of the Gal residue in 6. All eight possible O-methyl, epimeric, and amino analogues of 6 having modifications on the target Gal residue were chemically synthesized and kinetically evaluated both as substrates and inhibitors for the A and B glycosyltransferases. The results support earlier findings that both enzymes will tolerate replacement of the hydroxyl groups at the 3 and 6 positions of the Gal residue. Substitution at or replacement of OH-4 of the Gal residue, however abolishes recognition. The 6-O-methyl and 6-amino compounds are substrates for both enzymes while the 3-epimeric (10) and 3-amino (12) compounds are inhibitors. For the B transferase, 10 is a competitive inhibitor with a Ki of 7.8 microM. Attempts to determine a Ki for 12 with the B transferase were unsuccessful because of a complex mode of inhibition. Similarly, both 10 and 12 are potent inhibitors of the A transferase, but the inhibition constants could not be calculated because of a complex mode of inhibition, resembling that for the B transferase. With the A transferase, 12 had an estimated Ki in the 200 nM range.

UDP-GalNAc:Fuc alpha 1-2Gal alpha 1-3GalNAc transferase activity in hamster pancreatic cancers and in normal hamster alimentary tissues.

Ductal adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine treatment in Syrian hamsters produce blood group-A antigen, which is not present in normal hamster pancreas. To understand the underlying mechanism of A antigen neoexpression in pancreatic cancer cells, we examined the activity of UDP-GalNAc:Fuc alpha 1-2Gal alpha 1-3GalNAc transferase (A-transferase), the enzyme responsible for blood group-A antigen production. The specific activity of A-transferase in the pancreatic cancers was approximately 8 nmol/mg protein/h in membrane preparations, 0.3 nmol/mg protein/h in whole cell extracts, and undetectable in normal hamster pancreas. Significant A-transferase activity was found in normal tissues expressing blood group-A antigen. Although both normal (gastric antrum, colon) and pancreatic cancer cells showed similar enzymatic characteristics (optimal pH, substrate affinity, optimal [Mn2+]), there was a difference in the requirement for divalent cations. The A-transferase in cancer cells showed a more stringent requirement for Mn2+. These results suggest that A-transferase is activated during nitrosamine-induced pancreatic carcinogenesis, which results in the neoexpression of blood group-A antigen. The difference in divalent cation requirements between A-transferase activities of cancer and normal cells may indicate that there are multiple A-transferases present in hamster tissues.

Normal blood group B antigen and B transferase activity in a patient with IgM autoanti-B agglutinin.

Studies carried out on the red cells of a patient with autoanti-B agglutinin gave further evidence that it is probably not modified red cell antigens which cause autoantibody formation.

Synthesis and uptake of gangliosides by choleragen-responsive human fibroblasts.

Human fibroblasts, cultured in medium containing 10% fetal calf serum, responded dramatically to choleragen with an increase in cyclic adenosine monophosphate content to greater than 48 times basal levels. Analysis of these cells for gangliosides indicated that the major ganglioside was N-acetylneuraminylgalactosylglucosylceramide (GM3) with trace amounts (less than or equal to 100 pmol/mg of protein) of other gangliosides including GM1, the putative choleragen receptor. Although the cells contained three glycosyltransferases required for ganglioside synthesis, the N-acetylgalactosaminyltransferase activity necessary for the conversion of GM3 to more complex gangliosides was not detected. When the cells were grown in medium containing [14C]galactose or N-acety[3H]mannosamine, however, all of the gangliosides became labeled, indicating that the cells can synthesize complex gangliosides. Although fetal calf serum contains gangliosides including GM1, [3H]GM1 was taken up poorly from the growth medium and uptake at the rate observed could have accounted for less than 2% of the GM1 content of the cells. When the cells were incubated in chemically defined medium containing [3H]GM1 at the concentrations present in fetal calf serum, rapid uptake of the ganglioside occurred and the total GM1 content of the cells increased threefold in less than 3 h. Thus, although the cells are capable of binding exogenous gangliosides, the gangliosides in fetal calf serum are in a form not readily available to the cells.

[Demonstration of N-acetylgalactosaminyltransferase activity in the murine lymphoma YC8]. / Mise en évidence d'une activité N-acétyl-galactosaminyltransférase au cours du lymphome murin YC8.

The N-acetyl-galactosaminyltransferase activity has been studied in the biological fluids of YC8-lymphoma bearing Balb/c mice. It is enhanced during tumor development from 1 to 30 times in peritoneal fluids and from 1 to 10 times in sera. This activity is nil in urines. Optimal requirements for activity have been determined. Results suggest the existence, during tumor process not only of an enhancement of enzymatic activity, but also of a new molecule synthesis, molecules which are endogenous acceptors for the enzyme.

Detection of A1A2 and A2AAm1 heterozygotes among human A blood group phenotypes.

From the variations of alpha-N-acetylgalactosaminyltransferases activities with the pH, evidence was obtained for the recognition of A1A2 heterozygotes in normal A blood group sera. Besides, unusual transferase properties associated with two A2 sera from individuals out of AAm1 siblings, lead to the identification of the very infrequent A2AAm1 genotypes. These results strongly support the simultaneous coexistence of both A1 and A2 transferases in heterozygotes' sera, and bring some new information on the genetical background of the Am phenotype. The meaning of transferase properties directly determined on whole sera is briefly discussed.

Effects of uridine nucleotides and nucleotide pyrophosphatase on glycolipid alpha and beta-N-acetylgalactosaminyltransferase activities in guinea pig microsomes.

Membrane-bound alpha and beta-N-acetylgalactosaminyltransferases (EC 2.4.1.0) which catalyze formation of non-reducing terminal linkages of Forssman hapten and globoside, respectively, could be differentiated with respect to the different effects of UDP on the two enzyme activities. UDP markedly inhibited the alpha-transferase activity, in contrast to its stimulatory action on the beta-transferase. These effects of UDP were similar to those of UDPglucose, which was demonstrated to be a competitive inhibitor (Ki, 3.3 - 10(-5) M for UDP-N-acetylgalactosamine) for the alpha-transferase reaction. Other uridine derivatives tested suppressed both the transferase activities, being more inhibitory for the alpha-transferase than for the beta-transferase. Under the synthetic conditions of these aminoglycolipids, UDP-N-acetylgalactosamine as a donor was simultaneously degraded into N-acetylgalactosamine-1-phosphate and finally into N-acetylgalactosamine by UDP-N-acetylgalactosamine pyrophosphatase, which is part of the membrane system. UDPglucose was confirmed as being able to prevent the enzymatic hydrolysis of UDP-N-acetylgalactosamine. UDPglucose, therefore, acts to suppress both the alpha-N-acetylgalactosaminyltransferase (but not the beta-transferase) and the pyrophosphatase activities. The inhibitory effect of UDPglucose on the alpha-transferase activity was most probably due to its direct action on the transferase rather than its function in protecting UDP-N-acetylgalactosamine donor from pyrophosphatase action.

Formation of lipid-bound N-acetylhexosamine derivatives in yeast particulate fractions.

1. Particulate fraction (105 000 g) from Saccharomyces cerevisiae catalyses the transfer of N-acetylglucosamine from UDP-N-acetyl[14 C] glucosamine into lipid fraction as well as to insoluble polymer. 2. The evidence presented is in favour of the lipid containing the N-acetylglucosamine mono-, di- and tri-saccharide derivatives of dolichyl diphosphate. 3. The presence of a transferase synthesizing dolichyl-linked sugars in mitochondrial fraction is also reported.

Alterations of glycolipid glycosyltrasnferase levels in lymphoma and lymphoid tissues of lymphoma-bearing hamsters.

Thymus from lymphoma-bearing hamsters in advanced stages of tumor growth showed enhanced activities of four glycolipid-glycosyltransferases which lead to the step-wise synthesis of lactosylceramide to Forssman hapten. The alpha-galactosyltransferase activity of the thymus was decreased until day 6 of inoculation but increased thereafter. The activities of all the transferases tested were significantly lowered in lymphoma tissue. The level of UDP-galactose pyrophosphatase did not correlate with the transferase activities.

Evidence for noninvolvement of brain glycoprotein metabolism in escape training.

In two experiments, 21-day-old Sprague-Dawley rats received escape training in a two-choice four-alley water maze. Following training, glycosyl transferase activities of brain microsomal fractions were assayed in control and experimental animals. No significant group differences were observed in the extent of transfer of galactose and N-acetylgalactosamine to endogenous or exogenous acceptors. The results suggested a lack of participation of whole brain glycoprotein metabolism in an escape learning situation.