Group Secretor Research Articles

Determination of ABO blood group based on secretors or non-secretors analysis in body fluids

Criminal acts often leave traces analyzed by law enforcement, especially by the Indonesian National Police (POLRI). Sometimes, various items were found and analyzed to link the victim and the perpetrator. Blood, the most abundant body fluid, found in crime scenes, consists of cellular and liquid elements. The forensic focuses on red blood, which can be wet or dried at the crime scene. Sometimes, there was no blood or bloodstains found, but objects related to other body fluids, such as: condoms, toothbrushes, the mouth of glass cups, straws, etc, could be found. Blood group analysis could still be carried out based on secretor gene (Se) considering that 80% of the population was of the secretor group. There are two chromosomes related to blood regulation, namely: chromosomes no. 9 and 19. The former relates to the ABO blood group and the latter relates to the secretory phenotype. The basic principle of secretors was antigens found on the surface of red blood cells and all body fluids, except cerebrospinal fluid. The pattern of inheritance on chromosomes 9 and 19 is based on the probability law by Mendell. It stated that all of genotypes (homozygous dominant-recessive or heterozygous) would be passed on to their offspring.

A Subset of Colon Cancer Cell Lines Displays a Cytokine Profile Linked to Angiogenesis, EMT and Invasion Which Is Modulated by the Culture Conditions In Vitro.

Colorectal cancer (CRC) is one of the deadliest cancers worldwide. The dysregulation of secretory pathways is a crucial driver of CRC progression, since it modulates cell proliferation, angiogenesis and survival. This study explores the changes in the CRC cytokine profile depending on the culture conditions and the presence of fibroblasts and macrophages as cellular components of the tumor microenvironment in 2D and in 3D formed spheroids. Upon analysis of 45 different cytokines, chemokines and growth factors, 20 CRC cell lines were categorized into high and low secretors. In the high secretor group cytokines related to angiogenesis, EMT and invasion were significantly upregulated. LIF and HFG were identified as the best discriminator between both groups. Independent of this grouping, the addition of normal as well as cancer-associated fibroblasts had a similar impact on the cytokine profile by increasing the total amount of secreted cytokines in most of the investigated cell lines. In contrast, the differentiation and polarization of macrophages was modulated differently by normal vs. cancer-associated fibroblasts. In summary, we identified two groups of CRC cell lines that differ in their cytokine profile. The dependance of this profile was analyzed in detail-not only from the tumor cell line but as well from the culture condition in vitro. Key cytokines that discriminate the two groups were identified and their importance as promising biomarker candidates for CRC discussed.

Human Milk Oligosaccharide Profiles over 12 Months of Lactation: The Ulm SPATZ Health Study.

Human milk oligosaccharides (HMOs) have specific dose-dependent effects on child health outcomes. The HMO profile differs across mothers and is largely dependent on gene expression of specific transferase enzymes in the lactocytes. This study investigated the trajectories of absolute HMO concentrations at three time points during lactation, using a more accurate, robust, and extensively validated method for HMO quantification. We analyzed human milk sampled at 6 weeks (n = 682), 6 months (n = 448), and 12 months (n = 73) of lactation in a birth cohort study conducted in south Germany, using label-free targeted liquid chromatography mass spectrometry (LC-MS2). We assessed trajectories of HMO concentrations over time and used linear mixed models to explore the effect of secretor status and milk group on these trajectories. Generalized linear model-based analysis was used to examine associations between HMOs measured at 6 weeks of lactation and maternal characteristics. Results: Overall, 74%, 18%, 7%, and 1% of human milk samples were attributed to milk groups I, II, III, and IV, respectively. Most HMO concentrations declined over lactation, but some increased. Cross-sectionally, HMOs presented high variations within milk groups and secretor groups. The trajectories of HMO concentrations during lactation were largely attributed to the milk group and secretor status. None of the other maternal characteristics were associated with the HMO concentrations. The observed changes in the HMO concentrations at different time points during lactation and variations of HMOs between milk groups warrant further investigation of their potential impact on child health outcomes. These results will aid in the evaluation and determination of adequate nutrient intakes, as well as further (or future) investigation of the dose-dependent impact of these biological components on infant and child health outcomes.

Time of Lactation and Maternal Fucosyltransferase Genetic Polymorphisms Determine the Variability in Human Milk Oligosaccharides.

Rationale: Human milk oligosaccharides (HMOs) vary among mothers and genetic factors contribute to this variability. We assessed changes in HMO concentrations during the first year of lactation and the relationship with FUT2 Secretor group and FUT3 Lewis group defining genetic polymorphisms.Methods: Milk samples were collected from lactating mothers participating in the LIFE Child cohort in Leipzig, Germany. The concentrations of 24 HMOs in milk samples collected at 3 months (N = 156), 6 months (N = 122), and 12 months (N = 28) were measured using liquid chromatography. Concentrations of HMOs were compared at all time-points and were tested for their associations with FUT2 and FUT3 genetic variations by sPLS regression.Results: FUT2 SNP rs601338 was found to predominantly define the Secretor status Se-: 11.8% and it was highly correlated with 2′-fucosyllactose (2′FL, p < 0.001) and lacto-N-fucosylpentaose-I (LNFP-I, p < 0.001). FUT3 SNPs rs28362459 and rs812936 were found to define Lewis status (Le-: 5.9%) and correlated with lacto-N-fucosylpentaose-II (LNFP-II, p < 0.001). A polygenic score predicted the abundance of 2′FL levels within Secretors' milk (adj. R2 = 0.58, p < 0.001). Mean concentrations of most of the individual HMOs, as well as the sums of the measured HMOs, the fucosylated HMOs, and the neutral HMOs were lower at 6 and 12 months compared to 3 months (p < 0.001).Conclusions: Secretor and Lewis status defined by specific FUT2 and FUT3 SNPs are confirmed to be good proxies for specific individual HMOs and milk group variabilities. The polygenic score developed here is an opportunity for clinicians to predict 2′FL levels in milk of future mothers. These results show opportunities to strengthen our understanding of factors controlling FUT2 and FUT3 functionality, the temporal changes and variability of HMO composition during lactation and eventually their significance for infant development.

Human Milk Oligosaccharides and Hispanic Infant Weight Gain in the First 6 Months.

The aim of this study was to determine whether human milk oligosaccharides (HMOs) at 1 month predicted infant weight gain at 6 months and whether associations varied by HMO secretor status. Participants were 157 Hispanic mother-infant pairs. Human milk samples were collected at 1 month. Nineteen individual HMOs were analyzed using high-performance liquid chromatography, and secretor status was determined by the presence of 2'-fucosyllactose or lacto-N-fucopentaose (LNFP) I. Infant weight was measured at 1 and 6 months. Path analysis was used to test effects of HMO composition on infant weight gain, adjusting for maternal age, prepregnancy BMI, and infant age, sex, and birth weight. In the total sample, higher LNFPII predicted lower infant weight gain (g1 = -4.1, P = 0.004); this was observed in both nonsecretor (g1 = -3.0, P = 0.006) and secretor groups (g1 = -4.7, P = 0.014). In the nonsecretor group, higher lacto-N-neotetraose (g1 = 7.6, P = 0.011) and disialyllacto-N-tetraose (g1 = 14.3, P = 0.002) predicted higher infant weight gain. There were no other associations in the secretor group. Our data suggest that higher LNFPII in human milk may decrease obesity risk across all infants, whereas higher lacto-N-neotetraose and disialyllacto-N-tetraose may increase obesity risk in infants of nonsecretors only.

Human Milk Oligosaccharide Composition of Breast Milk from Lactating Women in Dhaka, Bangladesh (P11-040-19)

ObjectivesWe aimed to describe the human milk oligosaccharide (HMO) composition of breast milk from Bangladeshi women, overall and by galactoside 2-alpha-L-fucosyltransferase 2 (FUT 2) secretor status, and to estimate the effect of prenatal and postpartum vitamin D3 supplementation on HMO composition. MethodsIn a sub-study of the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh, we selected 96 participants from the placebo group and 96 who were administered 28,000 IU/week vitamin D3 from 17–24 weeks gestation to 6-months postpartum. Breast milk collected at 13 ± 1 week(s) postpartum were analyzed by high-performance liquid chromatography to determine absolute concentrations, relative abundancies of 19 HMOs and total amount HMOs, summarized using medians (interquartile range (IQR)). Associations between each HMO and selected maternal factors (e.g., age, parity, breastfeeding pattern) were estimated by multiple linear regression, adjusting for vitamin D group. ResultsTotal median HMO concentration was 16.8 mmol/mL (IQR 9.5-18.7) overall, but varied by secretor status: 18.0 mmol/mL (IQR 16.9-19.2) in secretors (66%) and 9.2 mmol/mL (IQR 8.9-9.5) in non-secretors (34%). Individual HMO concentrations also varied within secretor groups: 2’FL, the most abundant HMO among secretors, ranged from 1.3 to 15.8 mmol/mL among secretors and LNFP II, most abundant among non-secretors, ranged from 0.02 to 4.3 mmol/mL among non-secretors. Vitamin D3 supplementation did not affect total or individual HMO concentration. Other maternal factors were not significantly associated with secretor status, total or individual HMO concentration; however, breastmilk collected during winter had a significantly higher concentration of 3’FL compared to breastmilk collected during spring. The proportion of secretors in Bangladesh was similar to cohorts in Africa and North America. Relative HMO concentrations within secretor groups were similar to other international cohorts. ConclusionsThe HMO composition of breast milk from Bangladeshi women is predominantly determined by secretor status, similar to other countries worldwide. Further research is required to understand the effect of variations in HMO composition on infant health outcomes. Funding SourcesThe Bill and Melinda Gates Foundation.

Clinical and genomic hallmarks of low PSA secretors in metastatic castration-resistant prostate cancer (mCRPC).

5051 Background: Metastatic disease burden out of proportion to low serum PSA level is frequently used as a clinical surrogate for the diagnosis of treatment-emergent small cell neuroendocrine prostate cancer (t-SCNC), although many t-SCNC patients (pts) have normal or elevated PSA levels. The clinical and genomic characteristics of mCRPC pts who are Low PSA Secretors have not been previously described. Methods: Eligible mCRPC patients (pts) underwent image-guided needle biopsy. Formalin-fixed paraffin embedded tissue was evaluated with targeted next-generation DNA sequencing. Fresh frozen tissue from the same metastatic tumor underwent RNA-seq. A validated AR transcriptional signature was applied. Low PSA Secretors were defined as pts with PSA &lt; 5 ng/mL plus ≥ 6 metastases on conventional imaging at the time of tumor biopsy. Clinical and genomic characteristics were compared between low PSA Secretors and all other pts. Results: Of 89 evaluable pts, 9 (10%) were identified as Low PSA Secretors. There was no difference between Low PSA Secretors and all other pts in: serum PSA at diagnosis, frequency of Gleason ≥ 8 adenocarcinoma at diagnosis, and serum level of LDH, alkaline phosphatase, or hemoglobin at the time of biopsy. Lung and/or liver metastases were more common in low PSA secretors (67% vs. 33%, p = 0.04). There was no difference in serum level of LDH, alkaline phosphatase, or hemoglobin. Tumor biopsies from Low PSA Secretors were more likely to fall within a previously defined t-SCNC transcriptional cluster (80% vs. 6%, p &lt; 0.001). RB1 loss or inactivating mutations appeared to be enriched in Low PSA Secretors (40% vs. 12%, p = 0.09); there was no difference in frequency of TP53 alterations between subgroups. AR transcriptional signature scores were lower in the Low PSA Secretor group (median score -3.63 vs. 0.66, p &lt; 0.001). Conclusions: Low serum PSA levels in relation to metastatic tumor burden may be a reliable surrogate for the detection of mCRPC that harbors the transcriptional and genomic hallmarks of t-SCNC. Validation studies are warranted.

Human Milk Oligosaccharides in Colostrum and Mature Milk of Chinese Mothers: Lewis Positive Secretor Subgroups.

To study the variability in human milk oligosaccharide (HMO) composition of Chinese human milk over a 20-wk lactation period, HMO profiles of 30 mothers were analyzed using CE-LIF. This study showed that total HMO concentrations in Chinese human milk decreased significantly over a 20-wk lactation period, independent of the mother’s SeLe status, although with individual variations. In addition, total acidic and neutral HMO concentrations in Chinese human milk decreased over lactation, and levels are driven by their mother’s SeLe status. Analysis showed that total neutral fucosylated HMO concentrations in Chinese human milk were higher in the two secretor groups as compared to the nonsecretor group. On the basis of the total neutral fucosylated HMO concentrations in Chinese human milk, HMO profiles within the Se+Le+ group can be divided into two subgroups. HMOs that differed in level between Se+Le+ subgroups were 2′FL, DF-L, LNFP I, and F-LNO. HMO profiles in Dutch human milk also showed Se+Le+ subgroup division, with 2′FL, LNT, and F-LNO as the driving force.

Optimize CA19-9 in detecting pancreatic cancer by Lewis and Secretor genotyping

BackgroundCarbohydrate antigen 19-9 (CA19-9) is currently the most widely used biomarker for pancreatic cancer. It is well-known that Lewis and Secretor status can affect CA19-9 biosynthesis. This study was performed to optimize CA19-9 in detecting pancreatic cancer using Lewis and Secretor dependent cut-off values. MethodsLewis and Secretor genotypes were determined by Sanger sequencing in a large cohort of subjects (578 cases with pancreatic cancer, 210 cases with benign pancreatic disease, 315 normal subjects). The effectiveness of CA19-9 for detecting pancreatic cancer using Lewis and Secretor group dependent cut-off values was evaluated. ResultsThe Lewis (-), Mixed, and Secretor (-) groups had low, medium, and high CA19-9 biosynthesis, respectively. In Lewis (-) pancreatic cancer (all stages), CA19-9 had a sensitivity of 48.6% and a specificity of 95.9% when 1.8 U/mL was used as the cut-off value. The sensitivity of CA19-9 in detecting all stages of pancreatic cancer improved from 80.1% to 88.0% and the negative predictive value increased from 81.2% to 87.1% without compromising other values when using group dependent cut-off values. The sensitivity of CA19-9 for the detection of stage I, II pancreatic cancer increased from 76.1% to 87.2%. ConclusionsThe value of CA19-9 in detecting pancreatic cancer was optimized by using group dependent cut-off values based on Lewis and Secretor genotypes. CA19-9 can be applied as an early detector of pancreatic cancer using group dependent cut-off values.

Stable Blood Group Chimerism in Recipients of ABO Incompatible Allogeneic Stem Cell Transplantation

Background: The ability to express the ABH antigens in oral mucosa and saliva is present in about 80% of the general population (hence called secretors) and is regulated by the Sec gene on chromosome 19q13.3, which encodes for the enzyme fut2 (α(1,2)Fucosyltransferase), resulting in the expression of blood types in body fluids, including saliva. The gene encoding for the ABH antigens that determines ABO blood type, is located on chromosome 9q34, and transcribes to the enzyme fut1. While fut1 is mainly expressed in erythroid tissue, fut2is expressed in secretory cells. The aim of the present study was to evaluate the ABO type in saliva and red blood cells of patients undergoing allogeneic SCT from ABO mismatched donorsMethods: Secretion status and ABO type in saliva and blood were analyzed in patients with different hematological malignancies undergoing alloSCT from ABO incompatible donors and from healthy donors serving as controls. All study participants signed informed consent. For the determination of ABO type in saliva, following mouth rinse, 5 cc of saliva were collected from each participant into fresh tube and immediately frozen at -800C. Saliva ABH antigens were extracted and enzymes were inactivated. Secretor status and ABO type in patients’ saliva were determined by inhibition test. Agglutination of diluted A, B or O typed donor red cells was tested macroscopically in the presence or absent of the extracted ABH antigens pre-incubated with anti-A, anti-B or anti-H, respectively. ABO blood type was routinely determined in patients at least every 2 weeks and time to ABO type conversion was recorded as along with all transplant-related clinical dataResults: The study cohort included 30 patients (16 males and 14 females; median age 54.2, 18.8-68.5), who underwent alloSCT between Dec 2009 and Feb 2014 from an ABO incompatible donor and were available for routine follow-up. Median follow-up time from transplant to last ABO determination in saliva was 613 days (153-2789).Donors were matched related in 11, matched unrelated in 16 and mismatched unrelated in 3 cases. All grafts were from mobilized peripheral blood. Transplant from major, minor and bidirectional ABO incompatible donors was present in 9, 16 and 5 recipients, respectively. All patients engrafted. Chimerism analysis at day 30 and 100 post transplant by PCR for STR was 100% in 24/25 and 23/25 of tested patients, respectively. Median days to ABO type conversion were 64 (21-290). Of 30 patients, 26 were found to be secretors (87%).In the secretor group, 29/30(96.6%) retained original blood group in the saliva, while one patient originally typed as AB and transplanted from an A type donor, did not retain his original AB blood type in the saliva. It is not clear whether the lack of B-antigen is attributed to the acute mucosal GvHD or to a true conversion of the ABH antigen expression in the salivaConclusion: To the best of our knowledge, this is the first report of stable chimerism of the ABO blood groups post ABO-incompatible allogeneic transplantation, such that the majority of recipients (96.6%) retained the recipient ABO group in the saliva, while expressing the donor ABO group in the blood. The significance of these findings and correlation with long-term outcome need to be further studied in larger patient cohort DisclosuresNo relevant conflicts of interest to declare.

Caries and ABO Secretor Status in a Hungarian Population of Children and Adolescents: An Exploratory Study

ABO blood group antigen (ABGA) secretion into the saliva and other body fluids is a well-known phenomenon, and there is evidence to suggest a link between secretor status and the appearance of caries. It has been proposed that secretion of these antigens into the saliva might be caries-preventive, however, this proposition is still a matter of debate. Our aim was to examine the relationship between caries experience and secretor status in a group of Hungarian children and adolescents in a cross-sectional study. Altogether 130 children and adolescents participated in the study (aged 6-18 years). Participants were divided into two groups according to dentition (i.e. mixed and permanent). ABGA were determined from saliva. The DMF-T and dmf-t (decayed, missing, and filled) indices were calculated, as well as the oral health hygiene index-simplified plaque index. Association of these indices with secretor status was examined. In mixed dentition, the mean dmf-t values were significantly lower in the secretor group (2.1 ± 0.52 SEM), as compared to the nonsecretor group (3.8 ± 0.93 SEM; p < 0.05, Mann-Whitney U test). The finding that children of mixed dentition are apparently better protected against caries suggests that the assumed protective effect might be associated with deciduous teeth, but given the general paucity of knowledge about this topic, further research is indicated.

Computer-assisted reading of haemagglutination: Intensity of the ABH antigens secretion into saliva

We examined 138 saliva samples for the presence or absence of the blood antigens ABH using haemagglutination inhibition methodology. The outcomes of the tests were scanned and examined by special software, which used the HSV colour model, allowed setting the parameters in a way that enabled differentiation of agglutination clusters from suspensions of erythrocytes and subsequently calculated the area of agglutination clusters. The size of the area was (inversely) related to the presence of ABH substances in saliva. Both the secretor phenotypes and the intensity of secretion into saliva were statistically analysed in relation to gender, blood type, blood group genotype frequencies and secretor genotype frequencies.

Evaluation of a method for measuring tissue non-specific alkaline phosphatase activity in healthy subjects

Intestinal alkaline phosphatase (IAP) isozymes in the healthy human serum samples appears in two isoforms: normal-molecular-weight IAP (NIAP) and high-molecular-weight IAP (HIAP). We have demonstrated that the reference range for serum alkaline phosphatase (ALP) activity is higher in blood group B and O antigen secretors than in the tested other blood groups, for the appearance of these isoforms is depended on blood group B or O antigen secretors. We assessed a diethanolamine-L-phenylalanine (DEA-Phe) method for measuring tissue non-specific alkaline phosphatase (TNAP). This assays the sum of liver alkaline phosphatase and bone alkaline phosphatase activities as determined by an inhibiting IAP activity method with Phe. We classified 420 healthy subjects into two groups, a group of subjects who had blood group B or O antigen secretors (n = 184) and a group of subjects who had other blood groups (n = 236). ALP activity was higher in the B or O secretor group than in the other group: 20.9% higher (P<0.001) by the N-methyl-D-glucamine method, 13.7% higher (P<0.002) by 2-amino-2-methyl-1-propanol method, and 9.6% higher (P<0.05) by the diethanolamine method, but there was no significant difference in TNAP activity between the two blood group when measured by the DEA-Phe method. These results of this study support the expectation that the DEA-Phe method would be specific for TNAP activity. In addition, the reference range for TNAP activity did not vary with the differences in the tested all blood groups.

Association of Lewis blood group phenotype with preterm premature rupture of membranes.

To evaluate the distribution of Lewis blood group phenotype and secretor status among women with preterm premature rupture of membranes. ABO and Lewis blood group phenotypes were determined in 20 consecutive women with preterm premature rupture of membranes. The control group was composed of 48 women from our database without known history of preterm delivery. Of the 20 patients with preterm premature rupture of membranes six had blood type A (30%), nine type B (45%), two type AB (10%), three type O (15%), three Le(a(-)b(+)) (15%), one Le(a(+)b(-)) (5%), and 17 had Le(a(-)b(-)) (80%). Of the 48 controls, 18 had blood type A (37.5%), 10 type B (20.9%), two type AB (4.1%), 18 type O (37.5%), 37 Le(a(-)b(+)) (77.1%), six Le(a(+)b(-)) (12.5%), and five had Le(a(-)b(-)) (10.4%). The difference in the proportions of the A, B, AB, and O phenotypes between the groups was not statistically significant. The distribution of ABO and Lewis phenotype in the control group was similar to that in the general population. The proportion of combined recessive and nonsecretor phenotypes Le(a(+/-)b(-)) between patients with preterm premature rupture of membranes (17 of 20, 85%) and controls (11 of 48, 22.9%) was statistically significant (P <.001). Women with the Le(a(-)b(+)) phenotype who do secrete Le(b) antigen may have a protective effect against preterm premature rupture of membranes.

Serum levels of beta-2-microglobulin-free heavy chain of HLA class I antigen in healthy individuals: relationship to their class I allotype

An ELISA-based double determinant immunoassay has been established to measure the soluble β2-microglobulin (β2m)-free heavy chain (FHC) of the HLA-B, -C (and HLA-A3, -A28 and -A30) class I molecular complex in sera from 212 HLA-typed healthy unrelated individuals. FHC was calculated by means of a standard curve constructed using serial concentrations of β2m-associated HLA-class I heavy chain (HLA-I)/FHC purified from cultured human lymphoid cell C1R-sB7-supernatant. The mean FHC concentration (±SD) was 0.25mg/l (±0.2). Its median concentration did not statistically differ between males and females, though the male/female ratio was greater in the high secretor (FHC >0.45 mg/l; mean+1SD) than in the low secretor group (FHC < 0.05mg/l; mean-1SD). FHC < 0.05mg/l was statistically (Fisher’s exact test) associated with HLA-B17 ( p = 0.003); FHC > 0.45mg/l was statistically associated with HLA-B35 ( p = 0.003) and −Cw4 ( p = 0.002). None of these allele-positive groups showed a mean FHC concentration 1.5 times higher than that of the corresponding allele-negative ones. This allotype-dependent HLA-B and C FHC enhancement was less marked than that previously reported for HLA-I in individuals carrying HLA-A9 (and its splits). These results indicate that FHC could be a more valuable marker when its levels are compared among individuals carrying different allotypes. Moreover the lack of correlation between FHC and HLA-I levels measured in 52 HLA-A3, -A28 or -A30 positive individuals suggests that the two molecules may be regulated by different metabolic pathways and their serum expression may have a different biological significance.

Serum levels of human alkaline phosphatase isozymes in relation to blood groups

By use of sensitive immunocatalytic assays, based on isozyme specific monoclonal antibodies, the activities of the three main human alkaline phosphatases were determined in serum. The activities were related to ABO blood groups and secretor phenotypes. The activity of intestinal alkaline phosphatase was found to be strongly correlated with ABO blood groups and secretor phenotypes, while neither the placenta alkaline phosphatase activity nor the tissue unspecific alkaline phosphatase activity demonstrated any dependence on blood groups or secretor phenotypes. Non-secretors, independent of ABO blood groups, demonstrated low activities of intestinal alkaline phosphatase in serum, amounting to approximately 20% of the activities in the secretor groups. Within the secretor group, the lowest activities were observed for blood group A (2.8 ± 1.1 IU/l; mean ± SEM) and the highest for blood groups B and O (14.1 ± 1.1 IU/l and 19.0 ± 2.5 IU/l, respectively). These results confirm that the activities of intestinal alkaline phosphatase in serum have to be related both to ABO blood groups and to secretor phenotypes in order to be informative in clinical contexts.

Discriminant Carbohydrate Components of Human Milk According to Donor Secretor Types

Because of the variability of human milk carbohydrate composition, we determined the discriminant carbohydrate components of the milk of 18 mothers according to their ABH and Lewis secretor types during the first week of lactation. Comparative chromatograms revealed that the presence of neuraminyloligosaccharides is linked to the ABH secretor groups, and that the absence of oligosaccharides with Lea or Leb specificity is linked to the Lewis nonsecretor types. The study of carbohydrate composition according to donor secretor types consisted of measuring 16 variables from 69 samples. Analysis of variance showed significant differences between groups: high levels of N-acetylneuraminic acid and low levels of galactose distinguished ABH secretors from nonsecretors (p less than 0.001). In the ABH secretor groups, A and H secretors had higher N-acetylglucosamine contents than B and AB secretors (p less than 0.001) and lower galactose levels (p less than 0.001). The Lewis secretor groups were distinguished by significantly higher fucose levels (p less than 0.001). The ABH(+)Le(a-b-) group had higher lactose contents than the other groups (p less than 0.01).

Discriminant Carbohydrate Components of Human Milk According to Donor Secretor Types

SummaryBecause of the variability of human milk carbohydrate composition, we determined the discriminant carbohydrate components of the milk of 18 mothers according to their ABH and Lewis secretor types during the first week of lactation. Comparative chromatograms revealed that the presence of neuraminyloligosaccharides is linked to the ABH secretor groups, and that the absence of oligosaccharides with Lea or Leb specificity is linked to the Lewis nonsecretor types. The study of carbohydrate composition according to donor secretor types consisted of measuring 16 variables from 69 samples. Analysis of variance showed significant differences between groups: high levels of N‐acetylneuraminic acid and low levels of galactose distinguished ABH secretors from nonsecretors (p &lt; 0.001). In the ABH secretor groups, A and H secretors had higher N‐acetylglucosamine contents than B and AB secretors (p &lt; 0.001) and lower galactose levels (p &lt; 0.001). The Lewis secretor groups were distinguished by significantly higher fucose levels (p &lt; 0.001). The ABH(+)Le(a ‐ b ‐) group had higher lactose contents than the other groups (p &lt; 0.01).

The relevance of persistent C-peptide secretion in type 1 (insulin-dependent) diabetes mellitus to glycaemic control and diabetic complications

The effect of residual C-peptide secretion in longer standing IDDM on glycaemic control and the prevalence and evolution of complications over 2 years was evaluated. Thirty-one subjects with IDDM of 15.4 (1.5) years duration (mean (SEM)) and residual C-peptide secretion, were matched for age, duration of diabetes and body mass index with 31 subjects without detectable C-peptide secretion. At trial entry and over 2 years, levels of HbA 1, fructosamine and mean blood glucose were essentially similar in both groups. Levels of glycated albumin (GSA) were significantly higher in the C-peptide negative group after 3 and 9 months ( P < 0.05). An increased prevalence of proliferative retinopathy in the C-peptide negative group and of peripheral vascular disease in the C-peptide secretor group was apparent at entry to the study (both P < 0.05), although no significant differences were observed after 1 or 2 years. There was no difference in the prevalence of peripheral or autonomic neuropathy, hypertension, nephropathy or ischaemic heart disease. Subjects with C-peptide concentrations greater than 0.100 pmol/ml at entry to this study had lower daily insulin requirements after 1 and 2 years, but behaved like the larger group with any detectable C-peptide secretion in all other respects. Residual C-peptide secretion was lost after 1 year in 7 patients, in whom glycaemic control during the year had been particularly poor. Insulin antibody titres were no different in the 2 groups at any time point. This study suggests that residual C-peptide secretion in longer standing IDDM confers the potential for limited improvements in glycaemic control. This effect appears to be insufficient to prevent the evolution of microvascular complications over a 2-year period. Resudual C-peptide secretion and relative hyperinsulinaemia may be associated with an excess of peripheral vascular disease.

Linkage relationships of the gene for apolipoprotein CII with loci on chromosome 19

Two common restriction fragment length polymorphisms detected with cloned gene probes for apolipoprotein CII (apo CII) have been used to study the inheritance of the gene in families segregating for loci on chromosome 19. Lod scores for APOC2 with the gene for complement component 3 (C3) exclude close linkage and give a maximum at a male recombination fraction of 0.25-0.30. Lod scores for APOC2 and FHC, the gene causing familial hypercholesterolaemia, are negative in males and suggest the genes may not be linked. However, it appears that APOC2 may be closely linked to the blood group loci Lutheran (Lu) and Secretor (Se), and probably less closely linked to Lewis (Le). These data are consistent with the gene order: FHC-----C3-----(Lu, Se, APOC2)