Lewis Antigens Research Articles

Pattern of distribution of 35 red cell antigens in regular voluntary blood donors of South Gujarat, India

BackgroundExtended phenotyping is one of the important method of reducing red cell alloimmunisation. Extended phenotyping of red cells from voluntary donors have many uses in addition to its application in population genetics. As there was very little data extended phenotyping on a cohort of Indian Voluntary blood donors this project was undertaken. Study design & methodology200 regular voluntary blood donors having ‘O’ blood group were included for red cell antigen typing of Rh (D,C,E,c,e), Kell (K, k, Kpa, Kpb), Duffy (Fya, Fyb), Kidd (Jka, Jkb), Lewis(Lea, Leb), P(P1), MNS (M, N,S,s), and Lutheran (Lua, Lub), Colton (Coa, Cob), Diago (Diaa, Wra), Vw and Xga antigens using conventional antisera provided by DIAGAST. Calculations of antigen and phenotypes frequencies were expressed as percentages. ResultsOut of 200 ‘O’ group blood donors, 96.5% were Rh D and 2.5% were K positive. Amongst Rh antigens, e was the most common (100%) followed by D, C (91.0%), c (50.5%) and E (16.5%) with DCe/DCe (R1R1, 48.0%) being the most common phenotype. In Kell blood group system, we found k antigen to be 100% and a rare phenotype Kp (a + b+) was found in 1% of the donors. For Kidd and Duffy blood group systems, Jk (a + b+) and Fy (a + b-) were the most common phenotypes (39.0% and 64.0%, respectively). In the MNS blood group system, M + N+ (67.5%) and S + s+(43.5%) were the most common phenotypes. There were antigens like Cw(3.5%), K(2.3%), Kpa(1.2%), Ina(1.0%), Vw(1.2%), Coa(4.5%), Cob(1%), Lua(1.75%), Dia+(1.2%), and Wra+(0.6%) with frequency < 5% in the donor population. ConclusionExtensively antigen phenotypes group ‘O’ red cells showed significant variation with other population from India as well as with Caucasian and black population. Extensive phenotyping ‘O’ group regular blood donors of red cell antigens is very useful to prepare in-house red cell panels for identification of alloantibodies.

Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection

Human strains of rotavirus A (RVAs) recognize fucosylated glycans belonging to histo-blood group antigens (HBGAs) through their spike protein VP8*. Lack of these ligands due to genetic polymorphisms is associated with resistance to gastroenteritis caused by P[8] genotype RVAs. With the aim to delineate the contribution of HBGAs in the process, we analyzed the glycan specificity of VP8* proteins from various P genotypes. Binding to saliva of VP8* from P[8] and P[4] genotypes required expression of both FUT2 and FUT3 enzymes, whilst binding of VP8* from the P[14] genotype required FUT2 and A enzymes. We further defined a glycan motif, GlcNAcβ3Galβ4GlcNAc, recognized by P[6] clinical strains. Conversion into Lewis antigens by the FUT3 enzyme impaired recognition, explaining their lower binding to saliva of Lewis positive phenotype. In addition, the presence of neutralizing antibodies was associated with the presence of the FUT2 wild type allele in sera from young healthy adults. Nonetheless, in vitro infection of transformed cell lines was independent of HBGAs expression, indicating that HBGAs are not human RV receptors. The match between results from saliva-based binding assays and the epidemiological data indicates that the polymorphism of human HBGAs controls susceptibility to RVAs, although the exact mechanism remains unclear.

Lewis(y) antigen-mediated positive feedback loop induces and promotes chemotherapeutic resistance in ovarian cancer.

The present study aimed to investigate the association between Lewis(y) antigen and chemoresistance in ovarian cancer and to elucidate the underlying molecular mechanisms. Lewis(y) expression in chemoresistant ovarian cancer tissues and cells was detected by immunohistochemistry. α1,2‑fucosyltransferase (FUT1) expression in different ovarian cancer chemotherapy-resistant cells was analyzed by reverse transcription-quantitative PCR (RT-qPCR). Genes differentially expressed in the chemoresistant and sensitive groups were screened using a gene chip followed by validation using RT-qPCR and western blot analysis. We found that Lewis(y) and FUT1 expression in ovarian cancer cells was significantly increased following the induction of drug resistance. The positive expression rate and intensity of Lewis(y) in ovarian cancer chemoresistant tissues were also significantly higher than those in the sensitive group. Compared with the non-resistant cell lines, the differentially expressed genes were mainly enriched in the terms related to the transmembrane receptor protein tyrosine kinase signaling pathway and positive regulation of cell proliferation. Interaction network analysis predicted genes participating in the regulation of apoptotic processes. The highly differential expression of AnnexinA4 (ANXA4), BCL2 interacting killer(BIK), transmembrane4L six family member4(TM4SF4) and pleckstrin homology-like domain familyA member1 (PHLDA1) was validated using RT-qPCR in ovarian cancer cell lines. Finally, ANXA4 expression was increased at both the mRNA and protein level in the drug‑resistant cells, and in addition, ANXA4 contained a Lewis(y) structure. The expression of Bcl-2 and other anti-apoptotic proteins increased with the increase of Lewis(y) expression. After blocking Lewis(y) using an antibody, the expression of the involved signaling pathway and apoptosis-related proteins decreased significantly. These findings provide strong evidence that Lewis(y) is a component of the structure of the ANXA4 membrane protein. Its overexpression can abnormally activate signaling pathways and regulate the expression of a number of factors, forming a positive feedback loop to induce the chemoresistance of ovarian cancer cells, and ultimately promoting the progression of ovarian cancer.

Glycan-metabolizing enzymes in microbe-host interactions: the Streptococcus pneumoniae paradigm.

Streptococcuspneumoniae is a frequent colonizer of the upper airways; however, it is also an accomplished pathogen capable of causing life-threatening diseases. To colonize and cause invasive disease, this bacterium relies on a complex array of factors to mediate the host-bacterium interaction. The respiratory tract is rich in functionally important glycoconjugates that display a vast range of glycans, and, thus, a key component of the pneumococcus-host interaction involves an arsenal of bacterial carbohydrate-active enzymes to depolymerize these glycans and carbohydrate transporters to import the products. Through the destruction of host glycans, the glycan-specific metabolic machinery deployed by S.pneumoniae plays a variety of roles in the host-pathogen interaction. Here, we review the processing and metabolism of the major host-derived glycans, including N- and O-linked glycans, Lewis and blood group antigens, proteoglycans, and glycogen, as well as some dietary glycans. We discuss the role of these metabolic pathways in the S.pneumoniae-host interaction, speculate on the potential of key enzymes within these pathways as therapeutic targets, and relate S.pneumoniae as a model system to glycan processing in other microbial pathogens.

Lewis-antigen-containing ICAM-2/3 on Jurkat leukemia cells interact with DC-SIGN to regulate DC functions.

Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is an important C-type lectin and plays a critical role in the recognition of pathogens and self-antigens. It has recently been shown that DC-SIGN directly interacts with acute T lymphoblastic leukemia cells. However, the mechanism regulating DC-SIGN-dependent DC association as well as related functions is still elusive. Here we showed that DC-SIGN preferentially bound to a set of malignant T lymphocytes, including Jurkat, CCRF-HSB2 and CCRF-CEM. ICAM-2/3 on Jurkat cells appeared to be the responsible ligands and the block of ICAM-2/3 dramatically impaired DC-SIGN association. We also found that ICAM-2/3 bear a considerable amount of Lewis X, Lewis Y and Lewis A residues, which are important for DC-SIGN recognition. Furthermore, transcriptome analysis revealed an upregulation of fucosyltransferase 4 (FUT4) in Jurkat cells and downregulating FUT4 limited DC-SIGN binding, indicating a previously unappreciated role of FUT4 in the control of Lewis antigens on malignant T lymphocytes. In addition, the presence of Jurkat cells impaired DC maturation and the block of DC-SIGN improved Jurkat cell-mediated effects on DC function and T cell differentiation. Together, we provide evidence that DC-SIGN orients DC association with acute T lymphoblastic leukemia cells and orchestrates DC functions.

Biofilm formation by Staphylococcus aureus Isolation from atopic Dermatitis Patients on Defined Lewis Types saliva

Bacteria adherence and biofilm formation vary depending on the strain of microorganism as well as the substrate.Here, we evaluated the ability of different isolates of Staphylococcus aureus (S. aureus), isolated. from atopic dermatitis patients skin and stool to form a biofilm on different Lewis types saliva, including Le (a) , (b) ,(c) and Le a+b+ saliva. S. aureus isolates were cultured on tryptose soy broth.The bacteria were used to form a biofilm on 96- well flat bottom Microtitration plate that was coated with the respective, optimally diluted, processed saliva of Lewis blood groups (a),(b),(c) and Le a+b+.The intensity of biofilm formation was assessed by measuring the biofilm-associated optical density reading of bacterial bound dye. The results indicated a superior ability of biofilm formation on Lewis(a) saliva type.The highest binding gave a mean of 1.25 ± 0.39 compared to biofilm formation on non – coated wells that showed a mean of 0.23 ± 0.016(P=0.01, CL= 0.390 – 1.635). On the other hand, however, a variable degree of binding to Le(b) saliva was demonstrated for the isolates. The isolates didn’t demonstrate binding on Lea-b-(Lec) and Le a+b+ -(Led) saliva.&#x0D; We conclude that biofilm formation on Lewis types saliva of the atopic dermatitis bacterial isolates requires Le(a) in a ligand – receptor-based system for biofilm establishment.

Biofilm formation by Staphylococcus aureus isolation from atopic dermatitis patients on defined Lewis types saliva

Bacteria adherence and biofilm formation vary depending on the strain of microorganism as well as the substrate.Here, we evaluated the ability of different isolates of Staphylococcus aureus (S. aureus), isolated. from atopic dermatitis patients skin and stool to form a biofilm on different Lewis types saliva, including Le (a) , (b) ,(c) and Le a+b+ saliva. S. aureus isolates were cultured on tryptose soy broth.The bacteria were used to form a biofilm on 96- well flat bottom Microtitration plate that was coated with the respective, optimally diluted, processed saliva of Lewis blood groups (a),(b),(c) and Le a+b+.The intensity of biofilm formation was assessed by measuring the biofilm-associated optical density reading of bacterial bound dye. The results indicated a superior ability of biofilm formation on Lewis(a) saliva type.The highest binding gave a mean of 1.25 ± 0.39 compared to biofilm formation on non – coated wells that showed a mean of 0.23 ± 0.016(P=0.01, CL= 0.390 – 1.635). On the other hand, however, a variable degree of binding to Le(b) saliva was demonstrated for the isolates. The isolates didn’t demonstrate binding on Lea-b-(Lec) and Le a+b+ -(Led) saliva.&#x0D; We conclude that biofilm formation on Lewis types saliva of the atopic dermatitis bacterial isolates requires Le(a) in a ligand – receptor-based system for biofilm establishment.

Fucosylated Antigens in Cancer: An Alliance toward Tumor Progression, Metastasis, and Resistance to Chemotherapy.

Aberrant glycosylation of tumor cells is recognized as a universal hallmark of cancer pathogenesis. Overexpression of fucosylated epitopes, such as type I (H1, Lewisa, Lewisb, and sialyl Lewisa) and type II (H2, Lewisx, Lewisy, and sialyl Lewisx) Lewis antigens, frequently occurs on the cancer cell surface and is mainly attributed to upregulated expression of pertinent fucosyltransferases (FUTs). Nevertheless, the impact of fucose-containing moieties on tumor cell biology is not fully elucidated yet. Here, we review the relevance of tumor-overexpressed FUTs and their respective synthesized Lewis determinants in critical aspects associated with cancer progression, such as increased cell survival and proliferation, tissue invasion and metastasis, epithelial to mesenchymal transition, epithelial and immune cell interaction, angiogenesis, multidrug resistance, and cancer stemness. Furthermore, we discuss the potential use of enhanced levels of fucosylation as glycan biomarkers for early prognosis, diagnosis, and disease monitoring in cancer patients.

Postresection CA19-9 and margin status as predictors of recurrence after adjuvant treatment for pancreatic carcinoma: Analysis of NRG oncology RTOG trial 9704

PurposeNRG Oncology RTOG 9704 was the first adjuvant trial to validate the prognostic value of postresection CA19-9 levels for survival in patients with pancreatic carcinoma. The data resulting from this study also provide information about predictors of recurrence that may be used to tailor individualized management in this disease setting. This secondary analysis assessed the prognostic value of postresection CA19-9 and surgical margin status (SMS) in predicting patterns of disease recurrence. Methods and materialsThis multicenter cooperative trial included participants who were enrolled as patients at oncology treatment sites in the United States and Canada. The study included 451 patients analyzable for SMS, of whom 385 were eligible for postresection CA19-9 analysis. Postresection CA19-9 was analyzed at cut points of 90, 180, and continuously. Patterns of disease recurrence included local/regional recurrence (LRR) and distant failure (DF). Multivariable analyses included treatment, tumor size, and nodal status. To adjust for multiple comparisons, a P value of ≤ .01 was considered statistically significant and > .01 to ≤ .05 to be a trend. ResultsFor CA19-9, 132 (34%) patients were Lewis antigen–negative (no CA19-9 expression), 200 (52%) had levels <90, and 220 (57%) had levels <180. A total of 188 patients (42%) had negative margins, 152 (34%) positive, and 111 (25%) unknown. On univariate analysis, CA19-9 cut at 90 was associated with increases in LRR (trend) and DF. Results were similar at the 180 cut point. SMS was not associated with an increase in LRR on univariate or multivariate analyses. On multivariable analysis, CA19-9 ≥ 90 was associated with increased LRR and DF. Results were similar at the 180 cut point. ConclusionsIn this prospective evaluation, postresection CA19-9 was a significant predictor of both LRR and DF, whereas SMS was not. These findings support consideration of adjuvant radiation therapy dose intensification in patients with elevated postresection CA19-9.

Histo-Blood Group Antigen Phenotype Determines Susceptibility to Genotype-Specific Rotavirus Infections and Impacts Measures of Rotavirus Vaccine Efficacy.

BackgroundLewis and secretor histo–blood group antigens (HBGAs) have been associated with decreased susceptibility to P[8] genotype rotavirus (RV) infections. Efficacy of vaccines containing attenuated P[8] strains is decreased in low-income countries. Host phenotype might impact vaccine efficacy (VE) by altering susceptibility to vaccination or RV diarrhea (RVD). We performed a substudy in a monovalent RV vaccine (RV1) efficacy trial in Bangladesh to determine the impact of Lewis and secretor status on risk of RVD and VE.MethodsIn infants randomized to receive RV1 or no RV1 at 10 and 17 weeks with 1 year of complete active diarrheal surveillance, we performed Lewis and secretor phenotyping and genotyped the infecting strain of each episode of RVD.ResultsA vaccine containing P[8] RV protected secretors and nonsecretors similarly. However, unvaccinated nonsecretors had a reduced risk of RVD (relative risk, 0.53 [95% confidence interval, .36–.79]) mediated by complete protection from P[4] but not P[8] RVs. This effect reduced VE in nonsecretors to 31.7%, compared to 56.2% among secretors, and decreased VE for the overall cohort.ConclusionsHost HBGA status may impact VE estimates by altering susceptibility to RV in unvaccinated children; future trials should therefore account for HBGA status.Clinical Trials RegistrationNCT01375647.

The Lewis A phenotype is a restriction factor for Rotateq and Rotarix vaccine-take in Nicaraguan children

Histo-blood group antigens (HBGAs) and the Lewis and secretor antigens are associated with susceptibility to rotavirus infection in a genotype-dependent manner. Nicaraguan children were prospectively enrolled in two cohorts vaccinated with either RotaTeq RV5 (n = 68) or Rotarix RV1 (n = 168). Lewis and secretor antigens were determined by saliva phenotyping and genotyping. Seroconversion was defined as a 4-fold increase in plasma IgA antibody titer 1 month after administration of the first dose of the vaccine. Regardless of the vaccine administered, significantly fewer of the children with Lewis A phenotype (0/14) seroconverted after receiving the first vaccine dose compared to 26% (45/175) of those with the Lewis B phenotype and 32% (15/47) of the Lewis negative individuals (P < 0.01). Furthermore, following administration of the RV1 vaccine, secretor-positive ABO blood group B children seroconverted to a significantly lesser extent (5%) compared to secretor-positive children with ABO blood groups A (26%) and O (27%) (P < 0.05). Other factors such as pre-vaccination titers, sex, breastfeeding, and calprotectin levels did not influence vaccine-take. Differences in HBGA expression appear to be a contributing factor in the discrepancy in vaccine-take and thus, in vaccine efficacy in different ethnic populations.

Computational analysis of carbohydrate recognition based on hybrid QM/MM modeling: a case study of norovirus capsid protein in complex with Lewis antigen.

Norovirus is a major pathogen of nonbacterial acute gastroenteritis in humans and animals. Carbohydrate recognition between norovirus capsid proteins and Lewis antigens is considered to play a critical role in initiating infection of eukaryotic cells. In this article, we first report a detailed atomistic simulation study of the norovirus capsid protein in complex with the Lewis antigen based on ab initio QM/MM combined with MD-FEP simulations. To understand the mechanistic details of ligand binding, we analyzed and compared the carbohydrate recognition mechanism of the wild-type P domain protein with a mutant protein. Small structural differences between two capsid proteins are observed on the weak interaction site of residue 389, which is located on the solvent exposed surface of the P domain. To further clarify affinity differences in ligand binding, we directly evaluated free energy changes of the ligand binding process. Although the mutant protein loses its interaction energy with the Lewis antigen, this small amount of energy penalty is compensated for by an increase in the solvation stability, which is induced by structural reorganization at the ligand binding site on the protein surface. As a sum of these opposite energy components, the mutant P domain obtains a slightly enhanced binding affinity for the Lewis antigen. The present computational study clearly demonstrated that a detailed free energy balance of the interaction energy between the capsid protein and the surrounding aqueous solvent is the mechanistic basis of carbohydrate recognition in the norovirus capsid protein.

Identification of Key Genes and miRNAs in Osteosarcoma Patients with Chemoresistance by Bioinformatics Analysis.

Chemoresistance is a significant factor associated with poor outcomes of osteosarcoma patients. The present study aims to identify Chemoresistance-regulated gene signatures and microRNAs (miRNAs) in Gene Expression Omnibus (GEO) database. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) included positive regulation of transcription, DNA-templated, tryptophan metabolism, and the like. Then differentially expressed genes (DEGs) were uploaded to Search Tool for the Retrieval of Interacting Genes (STRING) to construct protein-protein interaction (PPI) networks, and 9 hub genes were screened, such as fucosyltransferase 3 (Lewis blood group) (FUT3) whose expression in chemoresistant samples was high, but with a better prognosis in osteosarcoma patients. Furthermore, the connection between DEGs and differentially expressed miRNAs (DEMs) was explored. GEO2R was utilized to screen out DEGs and DEMs. A total of 668 DEGs and 5 DEMs were extracted from GSE7437 and GSE30934 differentiating samples of poor and good chemotherapy reaction patients. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to perform GO and KEGG pathway enrichment analysis to identify potential pathways and functional annotations linked with osteosarcoma chemoresistance. The present study may provide a deeper understanding about regulatory genes of osteosarcoma chemoresistance and identify potential therapeutic targets for osteosarcoma.

Association of Coronary Artery Diseases with ABO and Lewis Blood Group Phenotypes at a Tertiary Care Teaching Hospital in Southern India

Association of Coronary Artery Diseases with ABO and Lewis Blood Group Phenotypes at a Tertiary Care Teaching Hospital in Southern India

One-pot synthesis of GDP-l-fucose by a four-enzyme cascade expressed in Lactococcus lactis

GDP-l-fucose is an l-fucose donor to synthesize fucosylated compounds such as human milk oligosaccharides or Lewis antigen. In this study, we used Lactococcus lactis subsp. cremoris NZ9000 to express 4 enzymes, ManB, ManC, Gmd, and WcaG and produced GDP-l-fucose by using one-pot synthesis method with mannose-6-phosphate as substrate and the enzymes as biocatalyst. For preparation of enzyme mixture, 4 genes (manB, manC, gmd, and wcaG) cloned from Escherichia coli were transformed into L. lactis strains using pNZ8008 and the recombinant cell lysates were obtained after cultivation. When mannose-6-phosphate was used as the substrate, the consecutive reactions with ManB, ManC, Gmd, and WcaG resulted in the successful production of GDP-l-fucose (0.13mM). When GDP-d-mannose was used as the substrate, it was entirely converted to GDP-l-fucose (0.2mM; 0.12g/L) via 2 enzymatic reactions mediated by Gmd and WcaG. This is the first report of GDP-l-fucose production by using multiple enzymes expressed in lactic acid bacteria.

Distribution of Lewis and Secretor polymorphisms and corresponding CA19-9 antigen expression in a Chinese population.

The Lewis (FUT3) and Secretor (FUT2) genes, corresponding to secretion of Lewis ABO (H) histo‐blood group antigen CA19‐9, are highly polymorphic with differences between populations. In this study, the FUT3 and FUT2 genes in 316 Chinese participants were sequenced to detect polymorphisms, and the associated CA19‐9 antigen secretion was also measured. In total, 14 genotypes of FUT3 and 10 genotypes of FUT2 were verified. Le/Le, Le/le 59,508 and Le/le 59 were the main genotypes of FUT3 with frequencies of 53.2%, 10.7% and 3.5%, respectively. Se/Se, Se/se 385 and se 385/se 385 were the main genotypes of FUT2, with frequencies of 21.4%, 18.6% and 16.2%, respectively. The alleles le 1067 and le 508 were found extensively in the Chinese population, and the frequency of allele se 385 was shown to be higher than previously reported. Phenotype analysis revealed that 9.8% of individuals were the Lewis‐negative type and 22.5% were the secretor‐negative type. Combined phenotypes showed that 3.2% of participants were of ‘double‐negative’ phenotype (le, se) and 19.3% were of single dominant non‐secretor phenotype (Le, se). Serum Lewis antigen CA19‐9 levels were significantly different between subgroups and consistent with the defined phenotype. Our study revealed the unique distribution of Lewis and Secretor polymorphisms in a large Chinese population, and decoded the combined genotypes of the two CA19‐9‐related genes.

Human intestinal organoids express histo-blood group antigens, bind norovirus VLPs, and support limited norovirus replication

Through pluripotent stem cell (PSC) technology, human intestinal organoids (HIOs) with remarkably similarity to the fetal intestine in cellular composition, architecture, and absorptive/secretory functions have been successfully developed, providing a useful in vitro model system to study the structure and function of human congenital gut and intestinally related diseases. We report here the usefulness of HIOs as a model system to study intestinal carbohydrate expression, virus-host interaction, and replication of human noroviruses (huNoVs). We found that fully developed HIOs express effectively various types 1 and 2 HBGAs, including Lewis, secretor, and nonsecretor antigens, distributing on the glycocalyx. Selected huNoV-like particles (VLPs) bound the glycocalyx of HIOs with matched HBGA phenotypes. Using GII.4 huNoV positive stool filtrates, we demonstrated limited huNoV replication in HIOs with corresponding HBGAs through detection of viral RNAs by RT-PCR and capsid antigens by immunostaining methods. Our data suggested that, after further improvements, HIOs can be a useful model to study intestinal glycan expression, huNoV-intestine interaction, and huNoV infection in the intestine.

Platelet lymphocyte ratio a diagnostic challenge in pancreatic head masses

Background: Masses in head of pancreas may arise from Carcinoma head of pancreas or Chronic pancreatitis. There is a need for differentiating the type of pancreatic head masses with utmost priority, since it can convert a radical surgery to conventional procedure. Recent studies suggest that Platelet lymphocyte ratio (PLR) can be used as a marker for differentiating between these masses. We evaluated the role of PLR and other tumour markers with combinations in differentiating the masses in head of the pancreas. Methods: A total of Sixty patients with mass in the head of pancreas with size 2cm or greater were included in the study, with 30 patients in the Pancreatic ductal adenocarcinoma (PDA) group and 30 patients in the Chronic Pancreatitis group. Patients with evidence of acute pancreatitis, liver cirrhosis, cholangitis and obstructive jaundice, having Lewis antigen A/B blood types, with absent tissue /cytological diagnosis were excluded. Results: Haematological parameters like platelet count, neutrophil count, lymphocyte count were not statistically significanct between the two groups, whereas, Mean CA 19-9 levels, (PLR) Platelet lymphocyte ratio levels and (NLR) Neutrophil lymphocyte ratio in (PDA) Pancreatic ductal adenocarcinoma were higher than Chronic pancreatitis group. (P PLR+CA 19-9> CA 19-9> CA 19-9+NLR> NLR. Conclusion: We found that PLR is as good as tumour marker CA 19-9 both individually as well as with other tumour marker combinations in the diagnosis of pathology of pancreatic head masses. Cost effectiveness, availability, simplicity and better diagnostic accuracy made PLR better tumour marker in the current scenario.

FUT2 non-secretor status is associated with altered susceptibility to symptomatic enterotoxigenic Escherichia coli infection in Bangladeshis

Polymorphisms of the FUT2 gene alters glycan ABO(H) blood group and Lewis antigen expression (commonly known as non-secretor status) in the small intestinal mucosa. Whilst non-secretor status affects 20% of the population worldwide, it has been reported to be present in up to 40% of all Bangladeshis. Furthermore, Bangladeshi children are reportedly more susceptible to symptomatic enterotoxigenic Escherichia coli (ETEC) infection if they are non-secretors. Therefore, in an attempt to identify a non-secretor status genotypic biomarker of altered susceptibility to ETEC infection, we used the 1000 Genomes Project to identify three population related non-synonymous FUT2 single nucleotide polymorphisms (SNPs). We then assessed the genotypic frequency of these SNPs in Bangladeshi children who had been clinically monitored for ETEC infection. One novel missense FUT2 SNP, rs200157007-TT and the earlier established rs601338-AA SNP were shown to be causing non-secretor status, with these SNPs being associated with symptomatic but not asymptomatic ETEC infection. Moreover, rs200157007-TT and rs601338-AA were associated with symptomatic but not asymptomatic ETEC infection irrespective of the child’s Lewis secretor status, suggesting FUT2, the regulator of Lewis and ABO(H) antigens in the intestinal mucosa, could be a host genotypic feature affecting susceptibility to ETEC infection.

A Secondary Structural Element in a Wide Range of Fucosylated Glycoepitopes.

The increasing understanding of the essential role of carbohydrates in development, and in a wide range of diseases fuels a rapidly growing interest in the basic principles governing carbohydrate-protein interactions. A still heavily debated issue regarding the recognition process is the degree of flexibility or rigidity of oligosaccharides. Combining NMR structure determination based on extensive experimental data with DFT and database searches, we have identified a set of trisaccharide motifs with a similar conformation that is characterized by a non-conventional C-H⋅⋅⋅O hydrogen bond. These motifs are present in numerous classes of oligosaccharides, found in everything from bacteria to mammals, including Lewis blood group antigens but also unusual motifs from amphibians and marine invertebrates. The set of trisaccharide motifs can be summarized with the consensus motifs X-β1,4-[Fucα1,3]-Y and X-β1,3-[Fucα1,4]-Y-a secondary structure we name [3,4]F-branch. The wide spectrum of possible modifications of this scaffold points toward a large variety of glycoepitopes, which nature generated using the same underlying architecture.