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At least 1,009 records · Page 56Linked to original sources
PubMed1982

In vivo sister chromatid exchange and cellular replication kinetics of normal and lymphoma AKR bone marrow cells.

The recent development of an AKR(Rb6.15)1Ald lymphoma model in our laboratory presents a unique means of comparing sister chromatid exchange (SCE) frequencies and cellular replication kinetics of normal and lymphoma cells in the same host environment. Lymphoma cells, distinguished from normal cells by the presence of two metacentric chromosomes, had an average cell cycle time of 8 hr compared to 11 hr for normal cells. Normal bone marrow cells from nonleukemic AKR/J, nonleukemic AKR(Rb6.15) Ald, and tumor passage recipients had similar baseline and 1,3-bis(2-chloroethyl)-1-nitrosourea-induced SCE frequencies following exposure to 4.4 mg 1,3-bis(2-chloroethyl)-1-nitrosourea per kg and 19 hr 5-bromo-2-deoxyuridine. While baseline SCE frequencies were only slightly higher, 1,3-bis(2-chloroethyl)-1-introsourea-induced lymphoma cell SCE frequencies were 3 times higher than normal induced SCE frequencies [34.06 +/- 6.6 (S.E.) versus 11.0 +/- 0.6 SCEs/cell].

Animals↗
PubMed2000

Age-related changes of human bone marrow: a histometric estimation of proliferative cells, apoptotic cells, T cells, B cells and macrophages.

We performed an immunohistological study using biopsy samples of bone marrow obtained from patients, ranging in age from a newborn baby to 100 years old. Those patients suffering from hematological diseases or diseases that would be capable of affecting hematopoiesis were not included in the present study. The cellularity of the bone marrow did not change significantly with age during the first and the eighth decades, while the oldest group, ranging in age from 80 to 100, revealed significantly low cellularity. Proliferative activity assessed by Ki-67-positive cells was high in the middle-aged group and declined slightly in the elderly group. It was of interest to note that the percentage of apoptosis was relatively low in the young and middle-aged group, but significantly increased in the elderly group. The percentage of T cells did not change greatly between the first and the fifth decades, peaked at the sixth decade and gradually decreased thereafter. The percentage of B cells was about 10% at the first decade, decreased thereafter until the third decade, then increased again showing a peak at the sixth decade, and decreased thereafter. The percentage of CD68-positive cells was high in young patients, and decreased in the adult and elderly patients. The data in the present study suggest that hypocellularity in the bone marrow of elderly people could be ascribed partly to the increase of apoptosis, and might possibly be related to a decrease in the number of lymphocytes and macrophages, which would constitute part of the bone marrow microenvironment supporting hematopoiesis.

Adolescent↗
PubMed1978

Cellular immunity to cytomegalovirus in a patient following bone marrow transplantation.

Cell-mediated immunity to cytomegalovirus (CMV) was studied in a bone marrow transplant patient with evidence of active CMV infection. The lymphocytes from this patient were found to specifically recognize and respond in vitro by transformation to CMV-infected Wistar-38 fibroblasts and by production of macrophage migration inhibition factor to CMV antigen. In addition, plasma and spinal fluid from the patient were found to contain blocking factor that specifically inhibited the lymphocyte response in the above assays. Biochemical, biophysical, and immunological studies indicate that the blocking factor may be an antigen-antibody complex.

Adolescent↗
PubMed2005

Thrombocytopenia in Newcastle disease: haematological evaluation and histological study of bone marrow.

A Newcastle disease virus (NDV) isolated in Mexico and called Chimalhuacan strain was characterised by gene F restriction enzyme analysis and found to be a genotype II velogenic virus. Haematological evaluations and histological studies of bone marrow were conducted on chickens experimentally infected with the Chimalhuacan virus and on control chickens. Within 72 hours post infection (hpi), a 50% decrease in thrombocyte and monocyte counts and a complete cellular depletion in bone marrow islands were evident in the infected group. These findings suggest that the Chimalhuacan strain of NDV causes an early and severe damage of the haematopoietic cells including thrombocyte precursors, which might explain the marked thrombocytopenia detected in early stages of this disease.

Animals↗
PubMed1993

Plasma and cellular pharmacokinetics of m-AMSA related to in vitro toxicity towards normal and leukemic clonogenic bone marrow cells (CFU-GM, CFU-L).

Plasma and cellular pharmacokinetics of m-AMSA were investigated in 5 patients with acute leukemia, using HPLC. The pharmacokinetic data served as a guideline for in vitro toxicity tests on clonogenic bone marrow cells. m-AMSA was administered as a 3-hour intravenous infusion of 100 mg/m2. Median plasma and nucleated blood cell peak concentrations were 1.25 and 6.36 micrograms/ml followed by biphasic elimination with a median T1/2 alpha alpha of 1.6 h and 0.3 h and a median T1/2 beta of 5.0 h and 5.0 h respectively. Median plasma and cellular area under the curve (AUC) for a 24-h period amounted 6.2 micrograms.h/ml and 49.8 micrograms.h/ml respectively. In vitro cellular uptake was maximal at least within 30 minutes. No differential toxicity for CFU-GM and CFU-L was observed in relation to exposure time. Median IC50 for CFU-GM and CFU-L was 2.2, 1.8 and 1.6 micrograms/ml after incubation periods of resp. 0.08, 4 and 24 h. The corresponding m-AMSA concentration x time products to achieve 50% inhibition (IAUC50) were 0.18, 7.2 and 38.4 micrograms.h/ml, respectively. 48-h prestimulation of the clonogenic bone marrow cells with Human Placenta Conditioned Medium increased sensitivity (median 1.7 x) after 4 h incubation with mAMSA. Short exposure provides maximal, concentration-related, cellular uptake, resulting in effective inhibition of growth of clonogenic bone marrow cells.

Acute Disease↗
PubMed1985

Cellular events during radiation-induced thymic leukemogenesis in mice: abnormal T cell differentiation in the thymus and defect of thymocyte precursors in the bone marrow after split-dose irradiation.

Cellular events during the development of thymic lymphomas in young B10.BR mice given leukemogenic split-dose irradiation were studied by examining the differentiation of functional T lymphocyte precursors in the regenerating thymus. It was found that leukemogenic radiation treatment resulted in a sustained depression of the level of thymic cytotoxic T lymphocyte precursors (CTLp) and of mixed lymphocyte reactivity of thymus cells when assessed between 1 and 4 mo after irradiation, in spite of the fact that the total number of thymocytes was restored to the normal level within 2 mo and continued to increase thereafter. In vitro mixing studies of normal thymocytes with thymus cells from split-dose irradiated mice provided no evidence for active suppression as a mechanism for this depressed activity. The ability of bone marrow cells from split-dose irradiated mice to regenerate the thymus and to differentiate into functional CTLp was examined by use of supralethally irradiated Thy-1 congenic recipients. Reconstitution of supralethally irradiated B10.BR Thy-1.2 mice with normal bone marrow from B10.BR Thy-1.1 mice resulted in the complete repopulation of host-thymus with donor-derived cells when assessed at 4 wk after reconstitution. Lymphocytes from the regenerating thymus of these animals were shown to contain high levels of CTLp which were donor-derived. On the other hand, when the recipient mice were reconstituted with bone marrow cells from donor mice which had been split-dose irradiated 1 mo earlier, regeneration of the recipient thymus was severely depressed when assessed at 4 wk to 3 mo after reconstitution. Although variable but small numbers of donor-derived Thy-1+ cells were detected, CTL activity for alloantigen could not be induced in these donor-derived cells. The results suggest that T cell precursors derived from split-dose irradiated donor mice were unable to undergo active proliferation and differentiation into functional CTLp. The significance of these findings on radiation-induced thymic leukemogenesis is discussed.

Animals↗
PubMedDate not supplied

Is autologous bone marrow transplant (ABMT) and high-dose chemotherapy an approach that can rescue some children with advanced cancer disease?

The object was to determine the role ABMT in children with advanced cancer Those included had failed to respond to conventional treatment with 4 different ablative chemotherapy regimens. Bone marrow stem cells were identified with CD34. Cellular viability was determined after the bone marrow extraction and before the infusion. Fifteen patients were included, whose ages ranged from 1 to 13 years old with a median of 7. Six had acute leukemia, 6 with primitive neuroectodermic tumors, and 3 with other tumors. The median disease-free survival for the whole group was of 2 months, range of 1 to 29 months and SD of 10.1. A total of 6 children are alive (40%) and without evidence of tumor activity from 1 to 29 months. The disease-free survival rate for these group was of 19.1 months, with an SD of 7.9 months.

Adolescent↗
PubMed1994

The development and establishment of hemopoiesis in fetal and newborn osteopetrotic (op/op) mice.

Previous studies of young CSF-1-less osteopetrotic (op/op) mice demonstrate a severe deficiency of both macrophages and osteoclasts, resulting in excessive bone formation, occlusion of the marrow cavity, and reduced hemopoietic activity. The accompanying splenomegaly and prolonged splenic hemopoiesis observed in these mice suggests that osteopetrosis may perturb the normal progression of fetal hemopoietic development and obstruct the seeding of hemopoietic precursors into the bone marrow. This study demonstrates that the absence of CSF-1 does not affect the progression of hemopoietic development in fetal op/op mice until after colonization of the bone marrow. Significant deficiencies in marrow cellularity and progenitor cell content in the long bones of op/op mice were not evident prior to Day 2 postnatal, suggesting that the altered hemopoietic state of young op/op mice is not a consequence of abnormal fetal hemopoietic development, but is primarily due to the lack of functional osteoclasts in op/op fetuses and hence, impaired remodeling of the marrow cavity after birth.

Animals↗
PubMed1978

The effects of vitamin B6 deficiency on the bone marrow of the rat.

Bone marrow from adult rats fed a vitamin B6 deficient diet for two weeks was found to have reduced numbers of neutrophils, erythroid cells and small lymphocytes. The numbers of transitional cells were not reduced. Since the small lymphocyte population in the bone marrow consists of B cells and null cells in approximately the same proportion, it was concluded that both cell types were reduced as a result of the deficiency. A complete recovery in the cellularity of the bone marrow was brought about by returning the vitamin B6 deficient animals to a normal diet for four weeks. Other effects of the two-week vitamin B6 deficient diet included a failure to gain weight, a decrease in thymus weight and a reduction in the numbers of white blood cells in the peripheral blood. All of these defects were corrected after the animals had been fed a normal diet for four weeks.

Animals↗
PubMed1993

Response of bone marrow to titanium implants: osseointegration and the establishment of a bone marrow-titanium interface in mice.

A method has been developed to examine the relationships between titanium implants in bone and the immune and hemopoietic cell populations in the adjacent bone marrow; it involves the use of miniaturized implants in the diaphysis of mouse femurs. After surgical placement of the implants, mice were sacrificed and the femurs were either embedded directly in Epon for preparation of ground sections or were decalcified in EDTA, embedded in Epon, subjected to a fracture technique to remove the implant, and sectioned for light and electron microscopy. Scanning electron microscopy revealed that the surfaces of implants removed in this way were virtually free of tissue remnants. Ground sections showed bone in direct contact with the implant surface, providing the first evidence of osseointegration in mice. In addition, an extensive surface of the implant interfaced directly with regenerated bone marrow, a condition that persisted for at least 18 weeks. Some bone marrow cells forming an incomplete layer in contact with the titanium interface had morphologic characteristics of macrophages and giant multinucleated cells. The results demonstrated a long-term integration between titanium implants and cellular elements of bone marrow and provide an experimental model to examine the possible implications of this interaction on the processes of lymphopoiesis and hemopoiesis.

Animals↗
PubMed1976

[Cellular test for RNA-synthesis in rat bone marrow and its use in testing cryoprotective and toxic agents].

A system for the measurement of the RNA-synthesis of bone marrow cells of the rat has been developed and the incorporation of [3H]-uridine into the cellular RNA has been standardized with respect to the time of incubation, the concentration of [3H]-uridine and the number of cells. A plateau of the incorporation of [3H]-uridine into the RNA is reached after 20 min of incubation and is interpreted as the expression of a steady state in synthesis and degradation of the cellular RNA. A constant labelling of the RNA is reached above 8.3 with 10(-6)M [3H]-uridine. The optimal cell number in the 500 mul standard assay is 4 with 10(6). Actinomycin D inhibits the RNA-synthesis to 94% in a concentration of 1.2 with 10(2) mug/ml. The cryoprotectants dimethylsulfoxide, polyethylene-oxide and glycerol and the potential haematotoxic substances dichlorodiphenyltrichloroethane and gamma-hexane were tested in this system. 5% dimethylsulfoxide and 10% polyethylen-oxide in Eagle's-medium with ethylendiamintetra-acetate do not influence the RNA-synthesis. 5% glycerol reduces the incorporation of [3H]-uridine into the cellular RNA to about 30%.

Animals↗
PubMed1995

Sex steroids, cytokines and the bone marrow: new concepts on the pathogenesis of osteoporosis.

Osteoclasts and osteoblasts, originating in the bone marrow from haemopoietic progenitors and mesenchymal stromal cells, respectively, are responsible for the remodelling of the skeleton throughout adult life. Upon loss of sex steroids, the production of osteoclasts in the bone marrow is increased. This is mediated by an increase in the production of interleukin 6 (IL-6), as well as an increase in the sensitivity of the osteoclastic precursors to the action of cytokines such as IL-6, owing to an up-regulation of the gp130 signal transduction pathway. Consistent with this, oestrogens as well as androgens inhibit IL-6 production through an indirect effect of their specific receptors on the transcriptional activity of the IL-6 gene promoter, and inhibit the expression of the gp130 gene. With advancing age, the ability of the marrow to maintain the high rate of osteoclastogenesis caused by the acute loss of sex steroids is diminished. This is probably the result of the negative effect of senescence on the ability of the marrow to produce stromal/osteoblastic cells, which provide the essential support for osteoclastogenesis. These observations suggest that inappropriate production of osteoclasts or inadequate production of osteoblasts in the bone marrow are fundamental cellular changes in the pathogenesis of postmenopausal and senescence-associated osteoporosis, respectively.

Adult↗
PubMed1994

Remarkable elevation of interleukin 6 and interleukin 8 levels in the bone marrow serum of patients with rheumatoid arthritis.

OBJECTIVE: Characteristic cellular changes have previously been reported in the bone marrow of patients with rheumatoid arthritis (RA). We investigated the levels of various cytokines in RA bone marrow. METHODS: We studied 25 patients with RA (22 women and 3 men) and 10 trauma patients (7 women and 3 men) as non-RA controls. Twelve kinds of cytokines [interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor, tumor necrosis factor (TNF)-alpha, and TNF-beta] were assayed by ELISA in iliac bone marrow serum (BMS), tibial BMS, and peripheral blood serum. RESULTS: Markedly elevated levels of IL-6 and IL-8 were detected in iliac BMS, and much lower levels were found in tibial bone marrow and peripheral blood serum. The levels of IL-6 and IL-8 in iliac BMS showed a close relationship to the extent of synovial proliferation. CONCLUSION: Iliac bone marrow may be an important site for the production or accumulation of IL-6 and IL-8 in RA, and these cytokines may influence synovial proliferation in patients with polyarthritis.

Adult↗
PubMedDate not supplied

Bone marrow and peripheral blood modifications in C57BL mice administered with cyclophosphamide and levan.

The effects of cyclophosphamide (CY) and levan at low (0.1 mg) and high (10 mg) doses (previously found to inhibit and stimulate, respectively, B16 melanoma growth) were studied. in single and combined administration, on the blood and bone marrow of C57BL mice. Very marked changes in the cellular composition of blood and bone marrow were induced by the various treatments. CY caused a sharp depletion of leukocytes in blood and bone marrow followed by a restoration of granulocytes while lymphocytes remained low. Levan caused a sharp dose-dependent depletion in bone marrow lymphocytes. Blood lymphocytes were not affected, however, by the polysaccharide. With the high levan dose, after a temporary granulocytopenia and monocytopenia, prominent granulocytosis was observed. While CY affected equally the different types of cells, levan decreased the number of lymphocytes and erythroblasts to a greater degree than the number of granulocytes. In the combined CY-levan treatments, the low levan dose generally attenuated the suppressive effect of CY, while the high concentration aggravated it.

Animals↗
PubMed1986

Bone marrow transplantation in the rat. II. Quantitation of cellular infiltrates in parenchymal target organs in acute graft-versus-host disease.

We have analysed the cytological structure of inflammation in the different parenchymal target organs during acute graft-versus-host disease after bone marrow transplantation in the rat. Inflammation (recovery of increased numbers of white cells) was recorded in the liver, skin, and lungs of the allograft recipient compared with the syngeneic graft recipient from day 5 onwards, accompanied by reduced recovery of inflammatory cells from the gut. The major cytological manifestation of the disorder was an increase in the total number of blast cells, large granular lymphocytes (LGL), and lymphocytes in the liver and skin, and of the number of blast cells and LGL in the lung. At the same time, a depletion of LGL and lymphocytes was recorded in the blood, suggesting migration of these cell components to the site of inflammation.

Agranulocytosis↗
PubMed1988

Effect of alpha-interferon therapy on bone marrow fibrosis in hairy cell leukemia.

Iliac crest trephine biopsy specimens from 16 patients treated with recombinant alpha 2-interferon (alpha-IFN) for hairy cell leukemia (HCL) were examined for reticulin and collagen content. These data were compared with the hairy cell index (HCl), the proportion of hairy cells to the overall cellularity of the bone marrow. Specimens were studied immediately before alpha-IFN therapy, at 6-month intervals during, and in six patients 6 months after cessation of therapy. All patients presented with increased bone marrow fibrosis ranging from focally increased reticulin to a diffuse increase in both reticulin and collagen content. This fibrosis was observed to decrease during alpha-IFN therapy inasmuch as the hairy cell population was diminished in the bone marrow in 13 patients. Regression analysis of HCl v bone marrow fibrosis showed a positive correlation (r = .73, P less than .02). Six patients demonstrated a reduction in bone marrow reticulin and collagen to normal levels during alpha-IFN therapy. Two of six patients demonstrated increased bone marrow fibrosis and HCl 6 months after cessation of alpha-IFN therapy. Three of 16 patients exhibited no decrease in bone marrow reticulin content during therapy despite a decreased bone marrow hairy cell population.

Adult↗
PubMed1980

Repopulation ability and proliferation stimulus in the hematopoietic system of mice following gamma-irradiation.

The repopulation ability of bone marrow was measured following whole body gamma irradiation of mice. Immediately after irradiation (100--500 rad) bone marrow suspensions were transfused into lethally irradiated syngeneic recipients. At various time intervals after transfusion (1 hour--20 days) DNA synthetic activity in femur and spleen was measured by incorporation of 125iodo-deoxyuridine (125IUdR). The cellularity of femoral bone marrow and the spleen weight was determined. A dose dependent retardation of repopulation was found to be correlated with an increasing duration of an elevated proliferation index (125IUdR-incorporation per unit bone marrow cells of per unit spleen weight, resp.). This suggests that the organism exerted a stimulus on the hematopoietic system to promote regeneration. This proliferation stimulus was kept at a high level unit a certain degree of hematopoietic function was restored either by regeneration of the bone marrow or, by compensating proliferation, in the spleen. The repopulation ability apparently was not only impared by the loss of stem cells but also by the induction of genetic damage in stem cells whose survival and partial functioning may have been enabled by the elevated proliferation pressure.

Animals↗