Leukocytosis: FOUNDATIONS OF CLINICAL SURVEY

Breviary N. Abramson, B. Melton Am Fam Physician 2000; 62:2053-60 Leukocytosis - the presence in the blood of more than 11 × / 109 / L, white blood cells - often discover during a routine laboratory examination. Increasing the number of white blood cells usually displays a normal response of the bone marrow to the infectious or inflammatory process. Sometimes leukocytosis is a manifestation of the primary disease of the bone marrow associated with the synthesis, maturation and death (apoptosis) of white blood cells, which leads to leukemia and myeloproliferative diseases. Often, family doctors can establish the etiology of leukocytosis by history and physical examination, together with the results of the expanded blood count.

Synthesis, maturation and survival of leukocytes Of the common progenitor cells - stem cells located in the bone marrow, are like erythroblasts and myeloblasts megakarioblasty. 3/4 of all bone marrow cells that contain nuclei related to the synthesis of leukocytes. As a result of the proliferation and differentiation of these stem cells produce granulocytes (neutrophils, eosinophils and basophils), monocytes and lymphocytes. Every day is synthesized approximately 1.6 billion granulocytes per kg body weight, 50-75% of which are neutrophils. More often increase in neutrophils (neutrophilia) than eosinophils and basophils. On the maturation of white blood cells in the bone marrow and their release into the circulating bed koloniostimuliruyuschie influence factors, interleukins, tumor necrosis factor, and complement components. Approximately 90% of the white blood cells are in custody in the bone marrow, 2-3% - circulate in the blood, and 7-8% are located in the tissues of the body. The cells contained in the bone marrow, are divided into two populations: those that are in the phase of DNA synthesis and maturation, and cell depot, awaiting its release into the circulation. With depot mature cells the body can respond quickly to the need for leukocytes, increasing their number doubled or tripled in just 4-5 hours. In the reaction of the bone marrow to infection or inflammation of the majority of the cells are polymorphonuclear leukocytes. Pool of circulating neutrophils is divided into two classes: those cells circulate freely, and others - are placed along the walls of blood vessels. With stimulation caused infection, inflammation, influence of drugs or metabolic toxins latter cells leave the depot and replenish freely circulating pool. As soon as the white blood cell enters the tsirkulyartornoe course and tissue survival of the cell is only a few hours. The life span of leukocytes is 11-16 days, most of which goes to mature and remain in custody in the bone marrow. The etiology of leukocytosis A survey on the leucocytosis begins with differentiation of two main reasons: 1) the proper response of normal bone marrow to external stimuli, and 2) the primary manifestations of the disease of the bone marrow. Physiological mechanisms of leukocytosis are presented in Table 1. Table 1. Pathophysiological mechanisms of leukocytosis The normal reaction of the bone marrow • Infection • Inflammation: necrosis, stroke, burns, arthritis • Stress: excessive stress, cramps, anxiety, anesthesia • The remedy: corticosteroids, lithium, β-agonists • Trauma: splenektomiya • Hemolytic anemia • leukemoid reaction Pathological reaction of the bone marrow • Acute leukemia • Chronic leukemia • Myeloproliferative disease Leukocytosis with normal bone marrow function In most cases, leukocytosis results from normal bone marrow response to infection or inflammation, the majority of cells - polymorphonuclear leukocytes (PMN). Circulating PMN and less mature forms (for example, a stick-nucleated cells and meta-myelocytes) migrate to the site of injury or infection. This process is accompanied by the release of leukocytes from the depot ("left shift"). Leukocytosis inflammatory genesis occurs when tissue necrosis, heart attack, burns and arthritis. Leukocytosis may also occur due to physical or emotional stress. This is a transient process that is not associated with the synthesis in bone marrow or release into the circulation of immature cells. Stress is leukocytosis with excessive stress, cramps, anxiety, anesthesia, and the appointment of adrenaline and disappears for several hours after the removal of a provoking factor. The remedy, splenektomiya, hemolytic anemia, and malignant diseases can also cause leukocytosis. Medications that commonly cause leukocytosis: corticosteroids, lithium and β-agonists. Splenektomiya causes transient leukocytosis, which lasts a few weeks or months. Hemolytic anemia with increased synthesis of red blood cells are non-specific increase in the synthesis and release of circulating white blood cells, it is believed that this is due to the action of growth factors. Cancers are also factors leukocytosis (and sometimes thrombocytosis) tumor nonspecifically stimulates the bone marrow to synthesize white blood cells. Overreaction to the side of leukocytes (ie, leukocytosis over 50 × / 109 / l) due to the action of factors beyond the borders of the bone marrow, called "leukemoid reaction." Usually it is caused by relatively benign processes (eg, infection or inflammation), although the most serious, though, and the rarest factor may be the malignant process. As mentioned, the increase in the number of neutrophils is the most common cause of leukocytosis, but also may increase the number and other subpopulations of leukocytes (eosinophils, basophils, lymphocytes and monocytes).

DO STEM CELL CLINICAL PERSPECTIVE?

Many diseases are accompanied by cell death, the body can not naturally replaced. Sometimes cells die suddenly, such as myocardial infarction. In other cases, the process is slow and inevitable, such as Alzheimer's disease. Most clinical perspective stem cells (which are the equivalent of a reduction of energy for the body) - is that they can be made by specialized, ie, they will be replacing the body's cells that were lost due to disease.

However, quite a difficult obstacle to scientific point of view, ethics and even the intervention of politicians slowed progress in this field for more than ten years. However, over the past two years there has been a marked shift in the field through a series of remarkable discoveries: suddenly be possible to create cells that have the potential of embryonic stem cells without the use of embryos. This made it possible to eliminate most of the ethical issues related to research in the field of stem cells. Embryonic stem cells are characterized by two extraordinary properties that make them potentially useful for practical applications in medicine. First, they are "pluripotent", that is the ability to turn into any type of specialized cells of the body: myocardial cells, pumping blood, acid-cells of the gastric mucosa, the light-sensitive cells of the retina, or brain cells that retain information. Second, embryonic stem cells have the ability to continuously divide and create unlimited copies of their fellow cells - is the most important property, because to replace cells lost due to disease, there is a need for a huge number of new ones. The scientists also studied stem cells in adults. In such studies, no ethical issues arise, as in the case of embryonic stem cells, because they do not use human embryos. Bone marrow and organs such as the heart and liver, contain adult stem cells. These cells can differentiate into most cells of the body in which they are located. Adult stem cells are specialized cells replace the dead, since most specialized cells are incapable of natural reproduction. However, adult stem cells in most organs can not provide a complete replacement of the cells in the case of the massive damage in a number of diseases, although researchers are working to change this. Also of note is that adult stem cells are not pluripotent: Unlike embryonic stem cells, they are not able to grow into any cell of the body. The unique properties of embryonic stem cells is difficult to use for medical purposes. Ideally, patients who needed treatment for stem cells would have to get their own, genetically identical stem cells, because then they will not be attacked by the immune system of the patient, as foreign. However, embryonic stem cells, there are only a short period of time, namely during the first two weeks after conception. In addition, stem cells from embryos that are used for programs fertilization in vitro, to be genetically different from the patient's cells, which increases the risk of rejection of the immune system, and thus to suppress the immune response will require potentially toxic treatments. The use of embryonic stem cells is also fraught with ethical issues, as some people believe that an embryo can be implanted with the potential to make it developed into a fetus has the moral status of the person and therefore it can not be destroyed, no matter how great a benefit it could someone would bring. In 2001, President Bush limited federal funding for the then existing embryonic stem cell lines, that is, government money is not allowed to spend on studies, which implied the destruction of embryos. However, the newly-elected U.S. President Obama said that he will change the policy of the Government in the field of research. A possible solution to overcome such difficult obstacles, is the proposal of the Japanese researchers. They asked a simple, albeit non-standard question: can I get a specialized cell back to an embryonic stem cell, or even in cells with the exceptional properties that have embryonic stem cells? In each cell there are genes predetermine the structure and functions of each particular cell. Although all human specialized cells, like embryonic stem cells, have the exact same set of genes in each cell type "on" different genes. In other words, embryonic stem cells are transformed into specialized cells because certain genes are "switched on", while others "turned off." In 2006, a team of researchers at Kyoto University led by Shinya Yamanaka, used a powerful and relatively new technology to determine which genes are "on" and which are "off" in a specific cell type. Using this technology for research on embryonic stem cells and specialized cells, Yamanaka's team identified a number of genes in mice, which were always "on" in embryonic stem cells, but not in specialized cells. Then in late 2007, a group Yamanaka with a group of American scientists led by James Thomson of the University of Wisconsin and George Daley of Harvard, testified that the "inclusion" of four genes in human skin cells resulted in reversion of these cells into cells resembling embryonic stem cells. They called these new cells induced pluripotent stem cells (iPS). Like embryonic stem cells, iPS cells had the ability to transform into any type of specialized cells, as well as self-reproduction to an infinite number of copies. Thus, has become theoretically possible for anyone to create their own stem cells that are genetically identical and have all the potential to own long-lost human embryonic stem cells. In addition, the adult cells to be transformed into iPS cells can be easily obtained by biopsy of the skin or other surface tissues. And, very importantly, iPS cells can be generated by avoiding the creation and destruction of embryos, which allows you to bypass the moral barriers to the use of embryonic stem cells. However, it should be noted that, despite the importance of such a breakthrough in this area, therapy using iPS cells is still not a prospect near future. Still need to find answers to important questions and develop new technologies. The ability of cells to turn into any type of cell in the laboratory does not guarantee that using such cells can be successfully treated animal or human disease in the experiment. However, Rudolf Jaenisch testified that because iPS quite successfully treated sickle cell anemia in mice and Parkinson's disease in rats. However, the treatment is effective in rodents, do not always work in humans, however, they are often still active. It should also be noted that two of the four genes that were originally used to create iPS cells, are oncogenes that could turn iPS cells into malignant cells. In addition, for the transfer of the four genes in specialized cells used a retrovirus, which also carries a risk of becoming iPS cells into malignant cells. However, in late 2008, scientists reported that iPS cells can be created without the use of both oncogenes and retroviruses. In 2009, many laboratories are working on the modification of existing technologies to create iPS cells to make them as safe and effective. Another potential problem: how iPS cells created in the laboratory, safely move into the affected organ located inside the body? And if we can move them back if they can harmoniously "worked" with the healthy cells of the body? These questions are important and they do not have an answer. One of the facts that scientists have learned through the use of bone marrow transplantation (a type of stem cell therapy, is widely used for 30 years), is that the cells injected into the bloodstream, find their way to the appropriate place in the body and, once there, can respond to the body's own cells that surround them, starting to work in harmony with them. However, for certain organs is not so simple. For example, the heart. Suppose that due to myocardial infarction millions died of myocardial cells. After that, the patient's bloodstream introduced millions created iPS cells. Will they find a way to your heart? And even if found, it will take a correct position, and whether in the long term decline in unison with the unaffected healthy cardiomyocytes? If not, whether this will lead to arrhythmia? If these cells, in addition to heart, get into another body, it will not cause harm? The only way to find the answer to these questions - is the way of trial and error, first in animals and then in humans. In addition to treatment, iPS cells can also help to find the cause. Several research groups from Harvard created iPS cells based on the tissues of patients with different genetic diseases, including Parkinson's disease, Huntington's disease and type 1 diabetes. Because iPS cells can reproduce indefinitely, it allows you to create and study cells with genetic defects that determine the disease. The researchers also asked the question, whether there will be an opportunity to transform one type of specialized adult cells into iPS cells without creating another. This is considered unlikely until August 2008, when a team of scientists from the Harvard-led Douglas Melton transformed pancreatic cells not producing insulin, insulin-producing cells in live mice, which allowed to treat diabetes in this mouse. According to the materials of foreign publications prepared Volodymyr Pavlyuk

Japanese are replaced with artificial grafts immunity

Scientists from Japan spoke about the fact that they are trying to replace part of the immune system of artificial grafts. Studies have been completed successfully. The results showed that all the Japanese doctors who want to have a high-tech spleen and lymph nodes, they can provide. In experiments with mice, biologists from Kyoto University have shown that artificial lymph nodes are not worse than this, actually. To create a lymph node scientists used matrix (sponge) of the polymer and bone marrow stem cells. Previously they have made stem cells a few genetic modifications. Experimental lymph node biologists transplanted in mice, the renal capsule. Three weeks polymeric sponge producing cells, and the structure of the site has evolved and acquired features of the structure, typical for a healthy lymph node. Scientists have shown that artificial lymph nodes even participate in the immune response, forming B cells, T cells and memory cells. The spleen is removed from the body the bacteria and foreign particles, and in contact with the blood of foreign antigens allows the immune response - producing cells. According to Japanese researchers, artificial lymph nodes prove useful for patients with cancer, aging and just people who have to be naturally reduced immunity. Scientists say that in recent years gathered enough scientific data needed to finally create an artificial lymphoid tissues and organs that are suitable for clinical practice

Male baldness: the process - reversible

Knowledge - force. American scientists finally get to the real reasons men untimely loss of their hair. Hopefully, this knowledge will make morally stronger than those who have not yet learned to put up with his thinning hair past zero. Male baldness: the process - is reversible. Bald? Do not believe your eyes! In fact, the concept of baldness is largely arbitrary. Yes, the hair falls out, but in their place, as judged by the presence of roots, always appear new. True, the quality of the "new hair" is largely inferior to "gone" - weak, lifeless and ... are so small that they can be seen only under a microscope. The reason for that - a defect of stem cells, significant problems with their activation. New knowledge opens up space for the imagination of scientists. If you invent a nearly magic cream and use it to transform stem cells, normal hair color vzrastut like to order. Hair from the "function" of migration You say, it sounds fable? Perhaps if we take into account the fact that for years the same scientists previously associated with hair loss male hormone testosterone. With hefty medical Talmud and the world stands scale medsobrany broadcast: baldness is inherited, it is triggered by exposure to radiation and medication. And, as a sentence: a universal means to cure or prevent hair loss not. It seemed that the guy does not want to put up with a bald head, one way: to move hair from behind - the "front" of the head. Almost panacea Hair loss can be avoided! At least we should try to lower the level of stress a few utterly life, if possible, to say "no" to the physical and emotional stress. For the sake of lush mane is to offer sacrifice - to give up smoking and alcohol. With caution and only after consultation with a doctor to take antibiotics. Remove from her wardrobe hairpieces, wigs, hats close - they impede blood flow, are the cause of hair loss. Cost control your weight - fat accumulation of little help, but in the blood cholesterol levels, which may, on occasion, clog the sebaceous and sweat glands. The victims will certainly be justified if the gray hair to be able to keep and own peace of mind, and the hair. Let them "joy - twisted, grief whipped." The main thing that they - are.