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PubMed1990

Effects of recombinant human erythropoietin on the haemopoietic bone marrow monitored by magnetic resonance spectroscopy in patients with end-stage renal disease.

Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate changes in the haemopoietic bone marrow in patients with end-stage renal disease undergoing treatment with recombinant human erythropoietin (rHuEPO). Significant changes could be detected in the spectra 14 days after the beginning of treatment, before any response was seen in the haemoglobin concentration of peripheral blood. The spectral changes indicate an alteration in cellular composition of haemopoietic bone marrow with an increase in the amount of haemopoietic active tissue. One patient showed a major change in the spectrum four days after treatment began, indicating that MR spectroscopy may detect early changes in the cellular composition of the bone marrow. This noninvasive method may be useful in evaluating treatment effects of recombinant human haemopoietic growth factors in the bone marrow, as well as investigating bone marrow response from different modes of rHuEPO administration.

Adult↗
PubMed1989

[Chronic myelomonocytic leukemia (CMMoL) with systemic lymph node swelling and paroxysmal nocturnal hemoglobinuria (PNH)-like complication].

A 37-year-old male was diagnosed as having chronic myelomonocytic leukemia (CMMoL) with chief complaint of systemic lymph node swelling. On admission, his peripheral blood revealed mild anemia and mild thrombocytopenia with giant platelets, and monocytosis (1480/microliters). NAP score was low. Serum lysozyme increased. The bone marrow showed normal cellularity consisting of 4% myeloblasts and 14.4% promyelocytes, and a few myeloid cells were positive for double staining by alpha-naphthyl butyrate and naphthol ASD chloroacetate esterase. Biopsied specimens of the cervical lymph node showed infiltration of monocytoid cells, which were positive for lysozyme staining, into interfollicular tissue. As for chromosome variation, 21 large satellite was observed in all dividing cells from his bone marrow and peripheral blood. Furthermore, hemolytic anemia with hemoglobinuria developed during his course. Sugar water test was positive, but Ham test negative. Coombs test and Donath-Landsteiner reaction were negative. Abnormal hemoglobin, spherocyte and fragmentation were not found. Hemolysis disappeared about two months later. However, blastic crisis appeared and he died. We showed a case of CMMoL with 21 large satellite and paroxysmal nocturnal hemoglobinuria (PNH)-like complication. Satellite have usually been reported as asymptomatic, and thus this chromosome variant and CMMoL may have been coincidentally observed.

Adult↗
PubMed1983

Recognition of drug resistance during remission induction therapy for acute non-lymphocytic leukemia: utility of day 6 bone marrow biopsy.

While the majority of patients under 70 years of age with acute non-lymphocytic leukemia enter remission when treated with a combination of cytosine arabinoside and an anthracycline antibiotic, 20-45% of patients do not. The reasons for treatment failure in these patients vary from drug resistant disease to death from infection or bleeding shortly after remission induction therapy is initiated. Clearly, more intensive remission induction therapy should be administered only to those patients for whom the therapy being employed is of insufficient intensity. Bone marrow biopsies after six days of therapy have been performed on 53 patients who received 65 courses of remission induction therapy. Eighty-eight per cent of the remissions occurred in patients whose marrow cellularity was less than 62.5% on day 6 while 78% of patients who had drug resistant disease had day 6 marrow cellularities which exceeded 62.5%. Hence, a bone marrow biopsy performed after six days of therapy permits the recognition of the majority of patients who will enter complete remission or alternatively who need more aggressive therapy.

Acute Disease↗
PubMed1997

[Invasive aspergillosis. Description of a case in an infant with severe granulocytopenia and endocardial fibroelastosis].

Invasive Aspergillosis in a child with severe granulocitopenia and endocardial fibroelastosis. A case of invasive aspergillosis in a 3-month old baby is reported. At autopsy gross examination revealed the presence of whitish nodules in the liver, spleen, kidneys and suprarenal glands. A black eschar with surrounding erythema involved the left auricle. The heart showed dilated left ventricle with porcelain-like thickening of the endocardium. The histological section of the hepatic nodular lesions showed Aspergillus colonization, vascular invasion with hyphal forms and necrotic granulomatous lesions in the other sites. Histologically, the endocardium is markedly thickened and rich in connective tissue and elastic fibres. Examination of the bone-marrow showed poor cellularity with a striking reduction of cells of the neutrophil granulocyte series. Aspergillosis may complicate the course of the child in immunocompromised state. Granulocitopenia causes an insufficient delimitation of infections and allows metastatic diffusion of fungi, through blood-vessels invasion.

Agranulocytosis↗
PubMed1994

Clinical and experimental imaging of breast cancer metastases in the spine.

An investigation was undertaken to determine the characteristics of spinal breast cancer metastases with respect to MR signal intensity (SI), patho-anatomy and uptake of the bone-seeking radionuclide 18F measured with positron emission tomography (PET). Patients with spinal metastases from breast cancer, or spinal specimens, were examined with MRI and the results were correlated to histopathological findings, or they were examined with conventional radiography and CT in correlation with cryomicrotomical images, with CT and dynamic 18F-PET; or with MRI, CT, skeletal scintigraphy and conventional radiography, compared with one another. Metastases were detected in all anatomical parts of the vertebrae. The areas with bone marrow replacement by tumour were larger in the cryosectional images than was apparent on CT. Metastases were often in contact with the vertebral cortex or end-plates, and fractures occurred in destructive lesions. Neurovascular compromise was detected only at few levels and was caused by vertebral collapse rather than epidural tumour growth. Metastases (in vivo) displayed low SI on T1-weighted, low or intermediate SI on proton density-weighted, and high or intermediate SI on T2-weighted and "phase contrast" images, except for highly sclerotic metastases, which showed low SI on all sequences. Sensitivity was high and specificity limited since connective tissue in the vertebrae and bone marrow with high cellularity had similar SI. Both MRI and CT were more sensitive than conventional radiography and skeletal scintigraphy for revealing metastases in the cervical spine. On PET there was an increased uptake of 18F in metastases, both in osteosclerotic lesions and in osteolytic defects in the bone. Post-mortem MR examinations showed different SIs than MRI in vivo. The T1-and T2-relaxation times and SI were dependent on tissue temperature. Reversal of contrast between some tissues occurred at 5 degrees C in T1-weighted images.

Adipose Tissue↗
PubMed1995

A study of intercellular relationships between trabecular bone and marrow stromal cells in the murine femoral metaphysis.

The cellular relationship between the substantia spongiosa of bone (cancellous or trabecular bone) and the haematopoietic bone marrow in the femoral metaphysis of C57BL/6NJCL mice was studied by transmission electron microscopy (TEM). Special attention was directed to intercellular junctions between osteocytes, osteoblasts, and bone marrow reticular cells. These were gap junctions and adhesive devices of simple architecture referred to as primitive junctions or zonula adherens-like junctions. Gap junctions were observed between osteocytes (within the trabeculae) and osteoblasts (at the trabecular surface) and between osteoblasts and marrow reticular cells. Gap junctions were also observed between the same cell type within each of these categories. These junctions involved the plasmalemmal membranes of adjacent cell bodies and of processes. Primitive cell junctions had a similar cellular distribution. Quantitative analysis of the cell types covering or positioned around the trabecular bones and of gap junctions between these and other cells was carried out by TEM. It was found that osteoblasts were the most numerous cell type, occupying 31% of the total of each cell type positively identified around the trabeculae (31%), while pre-osteoblasts, (flattened bone marrow reticular cells) took up 26%. These data emphasise the intimate relationship of the various mesenchymal cells based on processes and intercellular junctions, and point to an anatomical and probably functional integration of trabeculae and marrow. The functional significance and putative regulatory activity of this unit are discussed.

Animals↗
PubMed1988

In vivo cellular adriamycin concentrations related to growth inhibition of normal and leukemic human bone marrow cells.

Inhibition of clonogenicity of normal and leukemic human hematopoietic progenitor cells was studied after in vivo and in vitro exposure of bone marrow to adriamycin (ADM). Flow cytometric determination of cellular ADM concentrations in blast cells, expressed in fluorescence units/cell (FU/cell), correlated well with the extent of cytotoxicity. After 2 h in vitro exposure to 500 ng ADM/ml, the ADM concentration of leukemic (n = 7) and normal (n = 4) bone marrow blast cells amounted to 231 +/- 180 and 249 +/- 53 FU/cell respectively, producing moderate decreases in clonogenicity by 44 +/- 30 and 54 +/- 27%. Exposure to 2000 ng/ml produced ADM concentrations of 1184 +/- 472 FU/cell for leukemic blast cells and 1024 +/- 281 FU/cell for normal blast cells. Inhibition of clonogenicity was 96 +/- 7% in leukemic blasts and 99 +/- 1% in normal blasts. In vivo ADM concentrations in leukemic blast cells at 1-2 h after administration were 216 +/- 98 FU/cell (n = 8 patients). This implies that inhibition of clonogenicity after administration of conventional dosages of ADM will be approx. 60-70% for both leukemic and normal bone marrow progenitor cells. Such values were noted in four patients of whom bone marrow was cultured, which was obtained shortly after ADM monotherapy.

Bone Marrow↗
PubMed1993

Bone morphogenetic protein expression in human atherosclerotic lesions.

Artery wall calcification associated with atherosclerosis frequently contains fully formed bone tissue including marrow. The cellular origin is not known. In this study, bone morphogenetic protein-2a, a potent factor for osteoblastic differentiation, was found to be expressed in calcified human atherosclerotic plaque. In addition, cells cultured from the aortic wall formed calcified nodules similar to those found in bone cell cultures and expressed bone morphogenetic protein-2a with prolonged culture. The predominant cells in these nodules had immunocytochemical features characteristic of microvascular pericytes that are capable of osteoblastic differentiation. Pericyte-like cells were also found by immunohistochemistry in the intima of bovine and human aorta. These findings suggest that arterial calcification is a regulated process similar to bone formation, possibly mediated by pericyte-like cells.

Animals↗
PubMed1992

In vivo administration of interleukin 6 delays hematopoietic regeneration in sublethally irradiated mice.

The in vivo effects of recombinant human interleukin 6 (IL-6) on the hematopoietic system of sublethally (4.8 Gy) x-irradiated mice were investigated. Animals were injected twice daily s.c. with IL-6 (10 micrograms/kg body weight/day) for 7 days following irradiation, and the numbers of hematopoietic stem, progenitor, and circulating blood cells were evaluated at 4, 7, 13, and 23 days. IL-6 caused significant depression of early hematopoiesis (decreased numbers of spleen colony-forming units [CFU-S] and granulocyte-macrophage colony-forming cells [GM-CFC]) in the spleens of irradiated mice. Marrow hematopoiesis was less affected by IL-6 injection, although the number of hematopoietic cells was also significantly lower than in irradiated mice injected with carrier alone. The observed decrease in the numbers of hematopoietic cells was not reflected by any significant change in the circulating blood cell numbers, which were similar to those in control irradiated animals. In contrast, IL-6 administered in 100 times higher doses (1000 micrograms/kg/day) caused significant increases in bone marrow and spleen cellularity and GM-CFC numbers, thus accelerating postirradiation hematopoietic regeneration. Our studies show that IL-6, administered in relatively low doses, suppresses postirradiation hematopoietic recovery, decreasing the numbers of stem and progenitor cells in sublethally irradiated mice.

Animals↗
PubMed1985

Histopathology of the bone marrow in toxic myelopathy. A study of drug induced lesions in 57 patients.

Following the introduction of numerous highly effective drugs in recent decades, haematologists are confronted with a panmyelopathy or "toxic myelopathy" originating from the exhibition of certain therapeutic regimens. Among 16,711 trephines referred to us in the last 5 1/2 years, 57 cases or 0.34 percent were found to have clear evidence of lesions caused by the ingestion of potentially toxic agents. The evaluation of the histopathology shows two groups of alterations which concern the haematopoietic parenchyma as well as the mesenchyme of the bone marrow. Different degrees of cellularity ranging from aplasia to regenerative hyperplasia and a pronounced mesenchymal reaction with proteinaceous oedema, perivascular plasmacytosis and frequent necrobiosis of neutrophilic granulocytes or cellular debris are the most conspicuous features. However, the histopathology of the bone marrow described gives no indication of the specific drug responsible and no specific suggestion of any group of drugs. Generally the histopathology allows the recognition of lesions which are induced by the toxicity of these agents. Therefore a bone marrow biopsy should be included in the diagnostic procedures whenever a toxic lesion is suspected of causing haematological disorders, particularly in all cases of uncertain pancytopenia.

Adolescent↗
PubMed2006

Reversible Epstein-Barr virus-negative lymphadenopathy and bone marrow involved by Hodgkin's lymphoma in a rheumatoid arthritis patient undergoing long-term treatment with low-dose methotrexate: a case report and review of the literature.

We report a case of spontaneous regression of Epstein-Barr virus (EBV)-negative methotrexate-associated lymphadenopathy occurring with Hodgkin's lymphoma in the bone marrow of a 48-year-old woman with rheumatoid arthritis. Following 10 years of treatment with low-dose methotrexate, the patient developed pancytopenia, hypercalcemia, and elevated levels of liver enzymes over the course of 2 months. A computed tomography scan of the abdomen revealed splenomegaly and enlarged abdominal lymph nodes. A bone marrow biopsy demonstrated cellular marrow with 2 paratrabecular granuloma-like lesions composed of histiocytes, fibroblasts, small lymphocytes, a few plasma cells, and scattered CD30(+)CD15(+) Hodgkin's cells, including a classic Reed-Sternberg cell. The results of EBV studies of the bone marrow were negative. Within a month from withdrawal of methotrexate treatment, the patient's symptoms and the abnormalities in the laboratory results had regressed completely. A positron emission tomography scan failed to detect lymphadenopathy. Twelve months later, the patient remains free of symptoms.

Antirheumatic Agents↗
PubMedDate not supplied

The potential of bone marrow cells to orchestrate homeostasis and healing in skin.

Bone marrow derived cells play a major role in the maintenance and repair of many tissues, mostly by the delivering of a variety of inflammatory cells. Recent evidence however suggests that bone marrow may also supply cellular substrate for rebuilding non-hematopoietic tissues following injury. This discussion addresses the potential role of bone marrow to provide cells to the skin for rebuilding of skin structures following injury and for skin maintenance.

Bone Marrow Cells↗
PubMed1985

In vitro hematopoiesis following induction chemotherapy for acute leukemia.

The treatment of acute nonlymphocytic leukemia results in predictable bone marrow hypoplasia and eventual cellular repopulation. In order to study this postchemotherapy repopulation, assays for hematopoietic progenitor cells were performed on bone marrow samples obtained from seven patients with acute nonlymphocytic leukemia who had received similar chemotherapeutic induction regimens. Burst-forming units (erythrocyte), colony-forming units (megakaryocyte), colony-forming units (granulocyte-macrophage), and colony-forming units (granulocyte-erythrocyte-megakaryocyte-macrophage) were cloned from human bone marrow mononuclear cells 5 and/or 10 days following completion of chemotherapy. All patients were pancytopenic and had hypocellular marrows when studied. Assays were performed 7 to 30 days prior to complete remission. Colony-forming units (granulocyte-macrophage) were equivalent to control values 5 days following chemotherapy, while burst-forming units (erythrocyte) and colony-forming units (granulocyte-erythrocyte-megakaryocyte-macrophage) were not assayable at that time. Ten days following chemotherapy, colony-forming units (granulocyte-erythrocyte-megakaryocyte-macrophage) and colony-forming units (granulocyte-macrophage) were 200 and 250% of normal controls, respectively, while burst-forming units (erythrocyte) were 29% of control values. Colony-forming units (macrophage) were 10 to 15 times normal values 10 days following chemotherapy. In contrast to colonies from normal individuals, those grown from marrow obtained following chemotherapy were frequently macroscopic and were composed of thousands of cells. Patient marrow had larger proportions of progenitor cells in S phase of the cell cycle than did normal controls. These studies suggest the presence of a stem cell in human bone marrow which is resistant to chemotherapeutic agents and has a high capacity to regenerate hematopoietic progenitor cells. The period following completion of chemotherapy for acute nonlymphocytic leukemia appears suitable for the study of the hierarchical nature of human hematopoiesis.

Acute Disease↗
PubMed2002

Synergistic bone marrow toxicity of pyrimethamine and zidovudine in murine in vivo and in vitro models: mechanism of toxicity.

Pyrimethamine (Pyr) is commonly used for treatment of toxoplasmic encephalitis in AIDS patients; however, in two clinical studies, an increased number of deaths were observed when Pyr was coadministered with zidovudine (ZDV). The BALB/c mouse was chosen as a model to study the mechanism underlying the unexpected toxicity from coadministration of these drugs. Daily administration by oral gavage of 60 mg/kg Pyr and 240 mg/kg ZDV resulted in 100% lethality after 30 days. These dose levels produced no effect when the drugs were given individually for the same period. Administration of combinations of Pyr and ZDV resulted in macrocytic anemia and leukopenia with synergistic decreases in lymphocyte and neutrophil numbers. To examine the mechanism of this hematotoxicity at the cellular level, mouse bone marrow colony-forming unit (mCFU) assays were employed. A combination of ZDV with various concentrations of Pyr resulted in synergistic decreases in numbers of erythroid and granulocyte-macrophage precursors (mCFU-E and mCFU-GM). mCFU-GM precursors appeared more sensitive than erythroid precursors to combinations of Pyr and ZDV. Incorporation of (14)C-ZDV into cellular DNA was increased in a dose-dependent manner in the presence of increasing concentrations of Pyr in the mCFU-GM assay. This suggested that inhibition of dihydrofolate reductase by Pyr and accompanying inhibition of dTTP synthesis allows preferential incorporation of ZDV into DNA, with resulting strand breakage and cell death. (14)C-ZDV incorporation was also observed when human GM cultures were analyzed, however, incorporation was less and required higher concentrations of Pyr.

Administration, Oral↗
PubMed2002

Response of the immune system of mammary tumor-bearing rats to cyclophosphamide and soluble low-molecular-mass tumor-associated antigens: the bone marrow and thymus.

We showed in a previous study that soluble low-molecular-mass tumor-associated antigens (sTAA) promote the anti-tumor effect of the anticancer drug cyclophosphamide (CPA) on rat mammary carcinogenesis. In this report, we analyzed the possible mechanism underlying this phenomenon. Studies were performed on the bone marrow and thymus from the following groups of rats: i) control rats, ii) rats treated with sTAA, iii) rats treated with CPA, iv) rats treated with CPA and sTAA. The cellular content of the bone marrow and thymus (CD4+ and CD8+ lymphocytes) was analyzed morphometrically and immunohistochemically. In the bone marrow, CPA caused significant substitution of cellular components with fatty tissue whereas sTAA repaired this process. We found that CPA affects mainly the process of myelogenesis whereas sTAA protect the production of lymphocytes. In the thymus, CPA alone or in combination with sTAA repaired the inhibition effect of DMBA on synthesis of CD4+ and CD8+ thymocytes. sTAA further increased the amount of CD8+ T lymphocytes in the medulla of the thymus. Data in the literature as well as the findings presented here demonstrate that the tested treatment, including vaccination with sTAA, actively promotes the generation of the host's antitumor immune response.

Animals↗
PubMed1995

Basic fibroblast growth factor and hematopoiesis.

Basic fibroblast growth factor (bFGF or FGF-2) is an angiogenic and pleiotropic factor involved in the proliferation and differentiation of numerous cell types. It is expressed mostly in tissues of mesoderm and neuroectoderm origin, and plays an important role in the mesoderm induction, together with transforming growth factor-beta (TGF-beta). Although hematopoietic cells derive from the mesoderm, relatively few studies have addressed the role of bFGF in the hematopoietic system until recently. It appears that bFGF is expressed and produced by bone marrow stromal cells, as well as by cells from several mature peripheral blood lineages. It is released and stored in the bone marrow extra-cellular matrix. FGF-receptors (FGF-Rs) are expressed on nearly every cell of hematopoietic origin tested so far. Growing evidence shows that bFGF can positively regulate hematopoiesis, by acting on various cellular targets: stromal cells, early and committed hematopoietic progenitors, and possibly some mature blood cells. It synergizes with hematopoietic cytokines, or antagonizes the negative regulatory effects of another factor, TGF-beta, thus potentially playing a central role in hematopoiesis.

Animals↗