Cells of the bone

All mature blood cells arise from primitive hematopoietic cells in the bone marrow, the pluripotent stem cells. Approximately 0.1% of the nucleated cells of the bone marrow are pluripotent stem cells and approximately 5% of these cells may be actively cycling at any one time. The stem cell pool maintains itself through a process of asymmetrical cell division when a stem cell divides, one daughter cell remains a stem cell and the other becomes a committed colony-forming cell (CFC). The proliferation and differentiation of CFCs are controlled by hematopoietic growth factors. The hematopoietic growth factors stimulate cell division, differentiation and maturation, and convert the dividing cells into a population of terminally differentiated functional cells. 

This class of lymphocytes differentiates from immuno-logically incompetent hematopoietic stem cells of the bone marrow within the thymus - hence, the name thymus-dependent (T-) lymphocytes. Two major subclasses develop simultaneously, T-helper lymphocytes (Th) and cytotoxic effector lymphocytes (Tc). The cytotoxic T-lymphocytes (carrying on the surface the differentiation marker CD8) destroy cells, which cany their cognate antigen bound to MHC class I molecules on the surface by inducing apoptosis. From an evolutionary point of view Tc cells appear to have developed predominantly to cope with vims infections. As vituses can only replicate within cells, Tc eliminate them by destroying their producers. 

A large number of cells are involved in the immune response and all are derived fiom the multipotential stem cells of the bone marrow. The predominant cell is the lymphocyte but monocytes-macrophages, endothelial cells, eosinophils and mast cells are also involved with certain immune responses. The two types of immunity (humoral and cell-mediated) are dependent on two distinct populations of lymphocytes, the B cells and the T cells respectively. Both the humoral and the cell-mediated systems interact to achieve an effective immune response. 

Pereira, A., McLaren, A., Bell, W.R., Copolov, D. and Dean, B. (2003) Potential clozapine target sites on peripheral hematopoietic cells and stromal cells of the bone marrow. The Pharmacogenomics Journal, 3, 227-234. 

The answer is C. The patient s symptoms represent a composite of neurologic and gastrointestinal dysfunction, which are consistent with the anemia that is due to lead poisoning. Testing for lead would be appropriate for the patient, the other members of the household, and the house itself. Inorganic lead produces the microcytic anemia by inhibition of heme synthesis in erythropoietic cells of the bone marrow. All the other options represent enzymes of heme synthesis or degradation, but none of them are affected by lead. 

The answer is D. Several vitamin deficiencies can cause anemia due to reduced DNA synthesis in the erythropoietic cells of the bone marrow, especially folic acid and vitamin Bj2 (cobalamin), which are particularly prevalent among elderly patients due to poor diet and reduced absorption. In addition, deficiencies of either folic acid or vitamin Bj2 could produce the megaloblastic anemia seen in this patient. However, the absence of neurologic symptoms, a hallmark of vitamin Bj2 deficiency, makes that diagnosis less likely than folic acid deficiency. 

Recombinant erythropoietin, a hormone normally secreted by the kidney, which stimulates the production of red blood corpuscles, also shows interesting clearance mechanisms. Arguing from the G-CSF case you might guess that it will be taken up by the cells of the bone marrow which is its site of action. This is the case, and up to half of the clearance of erythropoietin is through the marrow itself. 

Postmortem examinations of persons who died as a result of exposure to H have shown depletion of lymphoid cells in the spleen, thymus, and other lymphatic organs depletion of hematopoietic cells of the bone marrow necrosis and desquamation of epithelium in the small intestine acute ulceration of the duodenum membranous laryn-gotracheobronchitls and pulmonary edema, congestion, and patchy emphysema that may be complicated by bronchopneumonia or other evidence of pulmonary infection.2>47... 

Clinical manifestations The porphyrias are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in the erythropoietic cells of the bone marrow or in the liver. Hepatic porphyrias can be further classified as acute or chronic. Individuals with an enzyme defect leading to the accumulation of... 

Tissues that synthesize heme, and the sources of porphyrin s carbon and nitrogen The major sites of heme biosynthesis are the liver (where the rate of synthesis is highly variable) and the erythrocyte-producing cells of the bone marrow (where the rate is generally constant). All the carbon and nitrogen atoms are provided by glycine and succinyl CoA. 

Studies with mice injected with radium-226 at 24 pCi/kg (889 kBq/kg) have demonstrated reductions in the hemopoietic stem cells of the bone marrow for at least 100 days after radium acquisition (Schoeters and Vanderborght 1981). 

The parenchymatous liver cells (hepatocytes) hold a key position in the overall metabolism of iron (57, 58, 59, 60), and since functionally intact liver mitochondria can be conveniently prepared at high yield, these mitochondria have been most extensively studied so far. The iron transporting system discussed above for liver mitochondria is present also in mitochondria from other tissues and animal species (Table III). Quantitatively, erythroid cells of the bone marrow play the most important role in the overall metabolism of iron (61), and it was therefore not unexpected to find that the energized uptake of iron by isolated reticulocyte mitochondria exceeds that of mitochondria isolated from, for example, liver, kidney, and heart (Table IV). Thus, a relationship appears to exist between the rate and extent of heme protein turnover in mitochondria isolated from different tissues and their energized iron accumulation (30). Thus, it is evident that cellular differentiation is expressed at the mitochondrial level by modulation of the activity of essential functions related to iron transport and heme biosynthesis. 

Imatinib. Chronic myelogenous leukemia (CML) results from a genetic defect in the hematopoietic stem cells of the bone marrow. Nearly all CML patients possess the Philadelphia chromosome. It results from translocation between chromosomes 9 and 22 of the c-abl protooncogene, leading to the hybrid bcr-abl fusion gene on chromosome 22. The recombinant gene encodes a tyrosine kinase mutant with unregulated (constitutive), enhanced activity that promotes cell proliferation. Imatinib is a tyrosine kinase inhibitor that specifically affects this mutant but also interacts with some other kinases. It can be used orally in Philadelphia chromo-some-positive CML. 

Parietal cells also secrete intrinsic factor, which is necessary for the absorption of vitamin B12. Vitamin B12 is a cofactor of enzymes which synthesise tetrahydrofolic acid, which in turn is needed for the synthesis of DNA components. An impairment of DNA synthesis will affect rapidly dividing cell populations, among them the haematopoietic cells of the bone marrow, which may result in pernicious anaemia. This condition may result from a destruction of the gastric mucosa by, for example, autoimmune gastritis or the resection of large parts of the lower ileum, which is the main site of vitamin B12 absorption, or of the stomach. 

Acquired immunity is immunity that develops with exposme to antigens the immune system builds a defence that is specific to that antigen. B-ceU lymphocytes, produced in the stem cells of the bone marrow, synthesise and release antibody they oversee the humoral immune response. T-ceU lymphocytes, produced in the bone marrow but sensitised in the thymus, are the basis of the ceU-mediated immune response. 

The toxicity of antimetabolites is, as expected, due to their incorporation into the metabolism of normal cells, which is nearly identical to that of the malignant cells that they were designed to injure. The normal cells injured most severely are the rapidly proliferating cells of the bone marrow, the lymphoid system, and the GI epithelium. Thus, the common toxicities are bone marrow depression, nausea and vomiting, diarrhea, and mucositis. Cytarabine and pentostatin can cause conjunctivitis. Capecitabine and prolonged use of fluorouracil or cytarabine can cause cerebellar ataxia and the hand-foot syndrome, that is, palmar-plantar erythrodysesthesia or acral erythema. Pentostatin and high-dose methotrexate can cause renal toxicity. 

The leukemias are heterogeneous hematologic malignancies characterized by unregulated proliferation of the blood-forming cells of the bone marrow. These immature proliferating leukemia cells (blasts) physically crowd out or inhibit normal cellular maturation in bone marrow, resulting in anemia, neutropenia, and thrombocytopenia. Leukemic blasts may also infiltrate a variety of tissues such as lymph nodes, skin, liver, spleen, kidney, testes, and the central nervous system. 

Once deposited on bone, plutonium is not released until the bone is physically destroyed. It may become buried under a new layer of mineral or may be taken up by special cells that digest foreign materials. As these cells die, the plutonium accumulates in immobilized deposits of hemosiderin, an insoluble iron storage protein that contains a large core of polymeric iron hydroxides and phosphates. These deposits are located close to the bone surfaces in the reticuloendothelial cells of the bone marrow10). 

Immunoglobulins, or antibodies, are proteins produced by the pixsma cells of the bone marrow as part of the immune response. The plasma cells are B lymphocytes transformed after exposure to a foreign (or occasionally an endogenous) antigen. 

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