DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Haplotypes of the bovine IgG2 heavy gamma chain in tick-resistant and tick-susceptible breeds of cattle

Bovines present contrasting, heritable phenotypes of infestations with the cattle tick, Rhipicephalus (Boophilus) microplus. Tick salivary glands produce IgG-binding proteins (IGBPs) as a mechanism for escaping from host antibodies that these ectoparasites ingest during blood meals. Allotypes that occur in the constant region of IgG may differ in their capacity to bind with tick IGBPs; this may be reflected by the distribution of distinct allotypes according to phenotypes of tick infestations. In order to test this hypothesis, we investigated the frequency of haplotypes of bovine IgG2 among tick-resistant and tick-susceptible breeds of bovines. Sequencing of the gene coding for the heavy chain of IgG2 from 114 tick-resistant (Bos taurus indicus, Nelore breed) and tick-susceptible (B. t. taurus, Holstein breed) bovines revealed SNPs that generated 13 different haplotypes, of which 11 were novel and 5 were exclusive of Holstein and 3 of Nelore breeds. Alignment and modeling of coded haplotypes for hinge regions of the bovine IgG2 showed that they differ in the distribution of polar and hydrophobic amino acids and in shape according to the distribution of these amino acids. We also found that there was an association between genotypes of the constant region of the IgG2 heavy chain with phenotypes of tick infestations. These findings open the possibility of investigating if certain IgG allotypes hinder the function of tick IGBPs. If so, they may be markers for breeding for resistance against tick infestations

Some Notes on the Morphology of<i>SpirochæTa Duttoni</i>in the Organs of Rats

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The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service

The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, the origin of which dates from 1939, is guided by a foundation in which participate the Dutch Government, the Netherlands Red Cross and the Municipality of Amsterdam.A staff of physicians, chemists, pharmacists and biologists is charged with the leading of the different departments and laboratories. The Central Laboratory which is operating on a non-profit basis, is the medico-technical centre of the blood transfusion organization in the Netherlands.</jats:p

An Epidemiological Contribution to the Knowledge of the Respiratory Diseases

The results of an inquiry into colds and slight influenza—held by me with the obliging collaboration of 7000 informants in the Netherlands from September 1925 till June 1926—do not contradict the hypothesis propounded in the introduction, that various respiratory diseases depend upon a disturbance in the thermo-regulation, in consequence of which the body becomes receptive to commensal infection.In the first place a proportionally equal number of colds was reported at the same time from the various parts of the country during the period of observation, while the increase and the decrease of these colds ran parallel to the falling and rising of the temperature of the air. Further, when calculating the figures from large and from small families, it was proved that the members of small families have no lesser chance of infection than the members of large families.This joint result tells against the contagiousness of colds in the period of observation.The outbreak in September stood alone; the preceding period had not been marked by a low average temperature but by a series of cold nights. During the following month the occurrence of colds was accompanied by the mortality from old age and by the joint mortality from bronchitis and pneumonia.An increased mortality from pneumonia in March–April, linked up with a moderate lowering of the temperature of the air, was not accompanied by “old-age mortality” and only moderately by “colds” it went together however with an increased mortality from influenza. The influenza cases of the inquiry too had increased by that period of time. So the influenza showed itself as a parasitic infection, which takes its own epidemic course. Still the possibility remains of the virus, at times of reigning influenza, having also widely spread among the healthy. At any rate the idea that catching cold reduces resistance to influenza or pneumonia is supported by the data.The opinion obtained from the results of the inquiry, that most colds and pneumonia, as well as many cases in which old age has been given as the cause of death, are founded on a disturbance of the thermo-regulation, has drawn attention to physiological oscillations of the temperature of the body in relation to that of the temperature of the air. As the thermo-regulating system is not able to fix the temperature of the body completely, even under normal conditions, but allows a certain poikilothermia, it is clear that by a considerable drop in the temperature of the air these oscillations of the temperature of the body become so large that they may cause a disturbance.The prophylaxis of the diseases from catching cold will have to be directed towards the application of “passive” prophylactics (for preserving and supplying heat by imminent cooling), as well as of “active” prophylactics (raising the production of heat by the body).</jats:p