Kari Aranko

Secretor genotype (FUT2 gene) is strongly associated with the composition of Bifidobacteria in the human intestine.

Intestinal microbiota plays an important role in human health, and its composition is determined by several factors, such as diet and host genotype. However, thus far it has remained unknown which host genes are determinants for the microbiota composition. We studied the diversity and abundance of dominant bacteria and bifidobacteria from the faecal samples of 71 healthy individuals. In this cohort, 14 were non-secretor individuals and the remainders were secretors. The secretor status is defined by the expression of the ABH and Lewis histo-blood group antigens in the intestinal mucus and other secretions. It is determined by fucosyltransferase 2 enzyme, encoded by the FUT2 gene. Non-functional enzyme resulting from a nonsense mutation in the FUT2 gene leads to the non-secretor phenotype. PCR-DGGE and qPCR methods were applied for the intestinal microbiota analysis. Principal component analysis of bifidobacterial DGGE profiles showed that the samples of non-secretor individuals formed a separate cluster within the secretor samples. Moreover, bifidobacterial diversity (p<0.0001), richness (p<0.0003), and abundance (p<0.05) were significantly reduced in the samples from the non-secretor individuals as compared with those from the secretor individuals. The non-secretor individuals lacked, or were rarely colonized by, several genotypes related to B. bifidum, B. adolescentis and B. catenulatum/pseudocatenulatum. In contrast to bifidobacteria, several bacterial genotypes were more common and the richness (p<0.04) of dominant bacteria as detected by PCR-DGGE was higher in the non-secretor individuals than in the secretor individuals. We showed that the diversity and composition of the human bifidobacterial population is strongly associated with the histo-blood group ABH secretor/non-secretor status, which consequently appears to be one of the host genetic determinants for the composition of the intestinal microbiota. This association can be explained by the difference between the secretor and non-secretor individuals in their expression of ABH and Lewis glycan epitopes in the mucosa.

Association between the ABO blood group and the human intestinal microbiota composition

BackgroundThe mucus layer covering the human intestinal epithelium forms a dynamic surface for host-microbial interactions. In addition to the environmental factors affecting the intestinal equilibrium, such as diet, it is well established that the microbiota composition is individually driven, but the host factors determining the composition have remained unresolved.ResultsIn this study, we show that ABO blood group is involved in differences in relative proportion and overall profiles of intestinal microbiota. Specifically, the microbiota from the individuals harbouring the B antigen (secretor B and AB) differed from the non-B antigen groups and also showed higher diversity of the Eubacterium rectale-Clostridium coccoides (EREC) and Clostridium leptum (CLEPT) -groups in comparison with other blood groups.ConclusionsOur novel finding indicates that the ABO blood group is one of the genetically determined host factors modulating the composition of the human intestinal microbiota, thus enabling new applications in the field of personalized nutrition and medicine.

Association of stress-related perinatal factors and cord blood unit hematopoietic progenitors is dependent on delivery mode.

BACKGROUND: Perinatal characteristics, variably utilized in cord blood (CB) selection for banking, affect CB hematopoietic progenitor cells (HPCs). The association between perinatal stress factors and CB unit HPCs was evaluated.

Pharmacokinetic-Pharmacodynamic Relationship of Dobutamine and Heart Rate, Stroke Volume and Cardiac Output in Healthy Volunteers

AbstractBackground and objective: Dobutamine causes an increase in cardiac output (CO) by augmenting stroke volume (SV) through enhanced left ventricular contractility and by decreasing systemic vascular resistance. However, in some patients, the dominant mechanism by which dobutamine improves left ventricular performance is an increase in the subject’s heart rate (HR). We therefore decided to evaluate the pharmacokinetic-pharmacodynamic relationship of dobutamine plasma concentrations and heart rate, SV and CO in healthy volunteers. Methods: We enrolled 23 subjects who received dobutamine at a dose of 2.5, 5 and 10 μg/kg/min for three consecutive periods of 60 minutes each. Dobutamine plasma concentrations were determined from 22 blood samples drawn during each study session. Echocardiography was used to measure CO before administration of dobutamine and once during each infusion period. Results: There was a clear linear relationship between dobutamine plasma concentrations and CO (r2 = 0.628; p < 0.001). In most subjects, HR remained stable at dobutamine plasma concentrations produced by the lowest infusion rate but increased markedly thereafter so that overall there was a linear relationship between dobutamine plasma concentrations and HR (r2 = 0.540; p < 0.001). However, SV increased significantly at the dobutamine plasma concentrations produced by the lowest infusion rate but remained mostly stable or even decreased thereafter. Although clinically slight, the overall increase in SV was statistically significant (r2 = 0.062; p < 0.05). Conclusion: Low plasma concentrations of dobutamine resulted in an increase in CO almost solely due to improved left ventricular contractility. However, at higher plasma concentrations of dobutamine, SV remained stable or even decreased, and the linear increase in CO was entirely based on increased HR.

Collection, processing and testing of bone, corneas, umbilical cord blood and haematopoietic stem cells by European Blood Alliance members

A questionnaire study was carried out in collaboration with the European Blood Alliance (EBA) Tissues and Cells (T&C) working group. The aim was to assess the level of involvement and commonality of processes on the procurement, testing and storage of bone, corneas, umbilical cord blood (UCB) and haematopoietic stem cells (HSC) in order to identify different practices and to explore whether recommendations can be made for harmonization.

Growth of erythroid cells from thawed unseparated cord blood in vitro without exogenous erythropoietin

INTRODUCTION Previous erythroid cell cultures have depended on added serum or erythropoietin. In this paper, the growth of erythroid cells from thawed unseparated cord blood units in vitro without serum or exogenous erythropoietin is reported. METHODS Thawed volume-reduced cord blood was cultured in conditions designed to support the megakaryocytic lineage, with thrombopoietin and interleukins 3 and 6. Erythroid cells were detected with glycophorin A (GlyA), CD71, and benzidine (flow cytometry and immunocytochemistry). RESULTS Nucleated and anucleated GlyA-positive, as well as benzidine-positive cells were observed from day 9. In flow cytometry, at days 0 and 9, 5.9% and 14% of all events were GlyA+, and 14% and 53% were CD71+, respectively. At days 0 and 9, 4.5% and 12% of the events were double-positive for GlyA and CD71, respectively. By day 14, the percentages of GlyA+, CD71+ and double-positive events had started to decrease (9.7%, 35%, and 5.3%, respectively). CONCLUSIONS Erythroid cells were generated from thawed unseparated cord blood units without exogenous erythropoietin. Thawed cord blood possesses the potential for erythroid growth in vitro in a culture medium designed for other cell types.

Prothrombin activation fragment 1 + 2 as a marker of coagulation activation in cord blood collection for banking.

There have been efforts to increase the quality of cord blood (CB) collections aimed at banking and transplantation. Yet, the effect of CB collection techniques on haemostatic activation is scarcely studied, despite the unique nature of the neonatal haemostatic system. The aim of this study was to explore coagulation system and platelet (PLT) activation during CB collection at a national CB bank. At three time points over a 9‐year period (in 1998, 2000 and 2006), CB collections were assessed to evaluate the collection process during bank setup and changes in procedures. Thrombin generation and PLT activation were assessed with prothrombin activation fragment 1 + 2 (F1 + 2) and PLT factor 4 (PF4), respectively. The median F1 + 2 level was 2·8 nmol L−1 in 1998 (n = 11), 0·7 nmol L−1 in 2000 (n = 10) and 0·7 nmol L−1 in 2006 (n = 6), the decrease being statistically significant (1998 vs 2000, P < 0·001; 1998 vs 2006, P = 0·01). The median PF4 level was 117 IU mL−1 in 1998 and 104 IU mL−1 in 2000. PF4 was not measured in 2006. The level of F1 + 2 correlated with that of PF4 (n = 21; Spearmans Rho = 0·59, P = 0·006). Haemostatic activation, assessed as a part of CB bank process control, decreased from the first to the subsequent sample series. F1 + 2 may be a candidate for quality control in CB banking; however, further studies are needed to optimise the analyses and to assess the effect of haemostatic activation on CB quality.

Association of CFU-Mk with total colony-forming units in thawed cord blood units

Background and Objectives  Cord blood unit (CBU) total colony‐forming unit (CFU) count both pre‐cryo and post‐thaw has been shown to be associated with platelet (PLT) engraftment. Pre‐cryo CBUs show good growth of megakaryocytic CFUs (CFU‐Mk); however, CFU‐Mk have rarely been studied in post‐thaw CBUs.

TRANSPLANTATION AND CELLULAR ENGINEERING: Association of stress-related perinatal factors and cord blood unit hematopoietic progenitors is dependent on delivery mode: PERINATAL FACTORS AND CB UNIT HPCs

BACKGROUND: Perinatal characteristics, variably utilized in cord blood (CB) selection for banking, affect CB hematopoietic progenitor cells (HPCs). The association between perinatal stress factors and CB unit HPCs was evaluated.