ABSTRACT
AIM: To study the distribution of HLA-A*-B*-C*-DRB1 *-DQB1 * haplotypes in patients with blood system diseases, to establish the most common HLA haplotypes, and to compare the findings with the data on the frequency and distribution of the highest-frequency HLA haplotypes in donors of a number of leading registries. SUBJECTS AND METHODS: In 2008-2012, the Hematology Research Center, Ministry of Health of the Russian Federation, examined 203 patients with blood system diseases who needed allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their 386 blood relatives. Typing ascertained the kind of HLA haplotype in all the patients. Among the patients, there were 97 men who were aged 17 to 64 years (median 38 years) and 106 women who were aged 18 to 59 years (median 40 years). RESULTS: The examinees were found to have 265 different HLA haplotypes. There were 21 high-frequency HLA haplotypes; of them 7 belonged to 10 HLA haplotypes that are most frequent in the representatives of the Caucasoid race. Nearly 30% of the patients who needed allo-HSCT and had no HLA-identical siblings had HLA haplotypes out of the 10 ones that are most common in the representatives of the Caucasoids and thus could expect to find a compatible unrelated donor for a short time. The examinees were found to have a wide variety of HLA haplotypes (265 types in 203 persons). This variety, as well as the extreme polymorphism of HLA alleles, shows that there should be large registries of HLA-typed bone marrow donors in the country. These registries increase the chance to find a HLA-compatible unrelated donor for a short time for a patient with blood disease who has an indication for hematopoietic stem cell transplantation. The performed study supported that there were regional features in the distribution of HLA haplotypes within the same ethnic group. CONCLUSION: The chance to find a HLA-compatible donor for Russian patients in the large national registry that accumulates donors from different regional populations is substantially higher than that in the foreign registries. To create large cohorts of HLA-typic bone marrow donors from different regions of the country will substantially increase the chance of patients with blood system diseases to find a HLA-compatible unrelated donor.
Subject(s)
HLA Antigens/genetics , Haplotypes/genetics , Hematologic Diseases/genetics , Hematopoietic Stem Cell Transplantation/methods , Histocompatibility Testing , Unrelated Donors , Adolescent , Adult , Anemia, Aplastic/genetics , Anemia, Aplastic/immunology , Female , Gene Frequency , Genotyping Techniques , Hematologic Diseases/immunology , Hematologic Neoplasms/genetics , Hematologic Neoplasms/immunology , Humans , Male , Middle Aged , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/immunology , Transplantation, Homologous , Young AdultABSTRACT
We studied the level of noradrenaline and the density of alpha 2- and beta-adrenoreceptors in the brain stem and cerebral cortex of 12-day- and 21-day-old rat fetuses, as well as of rats at the ages of 1, 2, 5, 7, 9, 16, 21, 35, and 70 days. We found a positive correlation between the level of noradrenaline in the brain stem and the density of beta-receptors in the cerebral cortex, and between the amount of alpha 2- and beta receptors in the cerebral cortex, as well as between the values of each of these indices of the neurochemical system and body weight. Significant negative correlations (r = -0.72 and r = -0.88, respectively) were found between the amount of alpha 2-adreno-receptors in the brain stem and the content of noradrenaline in this brain region, as well as in the cerebral cortex. Explanations of these positive and negative correlations between the level of noradrenaline and the amount of adrenergic receptors in the rat brain during ontogenesis are discussed.
Subject(s)
Brain/metabolism , Norepinephrine/metabolism , Receptors, Adrenergic/metabolism , Aging/metabolism , Animals , Animals, Newborn , Brain/embryology , Brain/growth & development , Brain Chemistry/physiology , Fetus , Norepinephrine/analysis , Rats , Rats, Wistar , Receptors, Adrenergic/analysisABSTRACT
Steroid hormones regulate density of adrenergic receptors in peripheral tissues and in the brain. The hormones affect transcription of the adrenergic receptors genes, the receptor protein synthesis and modifications. Steroid-induced changes in adrenergic receptors densities may be an important link for the effects of steroid hormones on hormone-dependent functions and behaviour.
Subject(s)
Gene Expression Regulation , Hormones/physiology , Receptors, Adrenergic/biosynthesis , Steroids/physiology , Animals , Protein Processing, Post-Translational/physiology , Receptors, Adrenergic/genetics , Transcription, Genetic/physiologySubject(s)
Cerebral Cortex/drug effects , Corticosterone/pharmacology , Lung/drug effects , Receptors, Adrenergic, beta/metabolism , Animals , Cerebral Cortex/metabolism , Desipramine/pharmacology , Dihydroalprenolol/metabolism , Lung/metabolism , Male , Protein Binding , Radioligand Assay , Rats , Rats, Wistar , TritiumABSTRACT
Densities of alpha 2- and beta-adrenoceptors were higher in the brain stem of 21-day-old foetuses. The beta-receptors density, however, increased more rapidly in the brain stem after birth. The alpha 2-adrenergic receptors density gradually elevated with ageing in the cortex, the specifics of their ontogenesis being related to regulation of noradrenergic nerve cells function while that of the beta-adrenoceptors reflected a formation of adrenergic synapses in the brain areas in the course of development.
