Role of clonal gemopoeisis in development of individual approaches for early diagnostics, treatment and rehabilitation of patients with cardio-vascular diseases

Recently, due to significant improvement and cheapening of the new generation of full genome sequencing technology, it has become possible to identify acquired mutations in individual cells of the hematopoietic system. This has led to the detection of clones of hematopoietic cells with acquired mutations in certain genes in middle-aged and elderly people and made it possible to characterize a new prepathological state - clonal hemopoiesis. Clonal hemopoiesis is defined as the appearance and clonal expansion of cells of the hemopoietic system with genetic changes that give these cells certain advantages in proliferation and/or resistance to adverse factors in comparison with other hemopoietic cells. This phenomenon is found mainly in individuals after 55 years of age and is practically not found in individuals of young age. At this age, most individuals show signs of cardiovascular pathology of some degree of severity. This review discusses some aspects of the possible impact of clonal hemopoiesis on cardiovascular diseases.

Leukemia risk and the pattern of dose accumulation. Part 1: Characteristics of the study group of the Mayak Production Association personnel

Results of development of the database “Leukemia in the cohort of workers of the Mayak Production Association employed in 1948-1958” that was developed in the Laboratory of Radiation Epidemiology of Southern Urals Biophysics Institute were presented. The database contains hematological, clinical and dosimetric information for the workers of main plants of the first production facility of Soviet atomic industry employed in the period of production development – 1948-1958. The computer database contains information for two groups of Mayak Production Association workers: main group of workers with leukemia as the main cause of death (n=84) and group of personnel without hematological cancer pathology for comparison (n=300). The comparison group was composed in such a way to allow 3-4 controls of corresponding gender, age of exposure start, accumulated dose of external gamma-exposure to red bone marrow for each leukemia case. Methods of data collection and sources of medical data were described. Characteristics of software developed for the database was presented. The database containing a total of 19593 results of blood tests reflects dynamics of hematological values in atomic facility personnel due to prolonged radiation exposure. The range of accumulated absorbed doses of external gamma-exposure to red bone marrow in the group of personnel with leukemia diagnoses was 0.001-4.96 Gy; average dose for males was 1.24 Gy and 0.61 Gy – for females. Similar range is observed in the group of personnel without leukemia outcomes. Alongside differences in accumulation rates of external radiation exposure doses is evident: in the group of workers with hematological cancer pathology the average period of radiation exposure at production facility was 14.3 years for males and 12.1 years for females; in the comparison group – 20.4 and 13.9 years, respectively. Most leukemia cases were diagnosed in the workers of radiochemical facility (54.8%). Myeloid leukemia prevailed (47.6%) in the leukemia structure; among them acute myeloid leukemia made more than a half of the cases; lymphoid leukemia was diagnosed in 14.3% cases with prevailing role of chronic lymphoid leukemia. Acute and chronic monocytic leukemia were the rarest types of malignant neoplasms of hematopoietic tissue. Possible correlation between hematological values with individual doses of external gamma- and internal alpha-exposure (incorporated Pu-239) distributed over time was stated. The database allows calculating integrated leukocytic indices reflecting response of hemopoietic system to radiation exposure, tracking changes in hemopoiesis in proportion to accumulated dose to red bone marrow, analyzing specific characteristics of rehabilitation of hematological alterations after occupational contact to ionizing radiation is terminated. Information on acute and chronic diseases available for the workers in the database allows excluding non-specific response of hemopoietic system caused by associated pathology. A revision of leukemia risk estimated in the relation to dose rate for personnel exposed to chronic radiation could be regarded as one of perspective trends in using the database.

A perspective Study on Lead Poisoning: Exposure, Effects and Treatment

Current studies focus on various aspects of lead ‘s poisoning, its distribution and interaction routes, adverseeffects on human body and treatment procedures. Lead metal has been involved in human exercise from the past 6000years. In ancient cultures, lead was applied in the production of kitchen utensils, food pantries and other decorativeitems. Lead poisoning in developing countries is considered as a major risk factor and its exposure routes may involvefood, paint, soil, water and other lead containing products. The distribution of lead from blood to tissues takes 4 to 6weeks. Lead is poisonous to humans and has the most damaging effects on hemopoietic system. Some of the visibleeffected systems are nervous, reproductive and excretory systems. Lead poisoning can be treated using chelating agentswhich undergo complexation with lead and are then excreted through urinary tract.

A perspective Study on Lead Poisoning: Exposure, Effects and Treatment

Current studies focus on various aspects of lead ‘s poisoning, its distribution and interaction routes, adverseeffects on human body and treatment procedures. Lead metal has been involved in human exercise from the past 6000years. In ancient cultures, lead was applied in the production of kitchen utensils, food pantries and other decorativeitems. Lead poisoning in developing countries is considered as a major risk factor and its exposure routes may involvefood, paint, soil, water and other lead containing products. The distribution of lead from blood to tissues takes 4 to 6weeks. Lead is poisonous to humans and has the most damaging effects on hemopoietic system. Some of the visibleeffected systems are nervous, reproductive and excretory systems. Lead poisoning can be treated using chelating agentswhich undergo complexation with lead and are then excreted through urinary tract.

Case of a congenital dystrophic violent epidermolysis

Clinical case of generalized form of congenital dystrophic violent epidermolysis at the patient M., 26 age is presented. The disease constantly progressed and proceeded with the classical picture expressed by all implications and symptoms characteristic of this form of illness. Despite of treatment new organs were involved in the process: kidneys, eyes, the hemopoietic system, developed a cachexia, contractures. Quality of life considerably worsened, difficulties in movements appeared. This case shows disease severity, gravity of the implications and complications leading to disability.

Stem Cells of Adult Organisms in Biology and Medicine

SummaryThe life span of adult cells is restricted, becoming senescent and eventually undergoing apoptosis. Cells are replaced by new ones which originate from a population of stem cells. An example is provided by the hemopoietic system in the bone marrow. In an adult body, stem cells may be identified by markers present in both embryonic and tissue-specific stem cells. Oct3/4, CXCR4, Nanog, CD133 and CD34 are examples of such markers. The stem cells share several properties, such as they may: 1) replicate and give rise to new stem cells, 2) differentiate into heterogenous tissue and organ specific cells and, finally, 3) stem cells are self-protected against various toxic agents and radiation. In adult tissues, stem cells reside in specialized sites (niches), for example in the bone marrow, skin, digestive tract epithelium, and skeletal muscles. Stem cells residing in these stem cell niches are anchored there by chemokines and adhesion molecules. Stroma-Derived Factor-1 (SDF-1), α-chemokine and stem-cell expressed receptor CXCR4 play an important role in the retention of stem cells in such niches. Several stress factors may attenuate the SDF-1-CXCR4 axis in the bone marrow, which leads to the release of stem cells from their niches into circulation. Another important stem cell niche-anchoring mechanism is the interaction of Wnt (a ligand) with Frizzled LRP (receptor). The recently accumulated evidence suggests that malignancy arises from an arrest in maturation and mutation of stem cells. Cancer stem cells are responsible for tumor growth, its relapse and metastasis.The first direct evidence for the existence of cancer stem cells came from observations of acute myeloblastic leukemia. Currently, cell populations enriched for cancer stem cells have been isolated from several tumors. The cancer stem cells represent less than 1% of tumor cells in the mouse models.