PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “bone marrow cellularity”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed2004

[Bone marrow morphologic features in patients treated with imatinib for Philadelphia chromosome positive chronic myeloid leukemia].

OBJECTIVES: To assess bone marrow morphologic changes in Philadelphia-chromosome positive chronic myeloid leukemia (Ph(+)-CML) patients treated with Imatinib, and to evaluate the correlation of the morphologic changes with hematological or cytogenetic responses. METHODS: One hundred and seventeen patients with Ph(+) CML: 54 in chronic phase but failed to interferon-alpha treatment, 41 in accelerated phase, 22 in blastic phase received oral administration of Imatinib 400 or 600 mg once daily for more than 18 months. RESULTS: All of the patients responded to the treatment, including complete hematological response, bone marrow response and return to chronic phase, bone marrow cellularity and myeloblast count reduced significantly to non-CML picture. Myeloid/erythroid ratio and megkaryocyte count were decreased significantly in most patients in chronic and accelerated phases (P < 0.05). Bone marrow hypoplasia or aplasia was associated with lower cytogenetic response rates in patients in chronic phase (58.8% vs 86.5%, P = 0.035), lower complete hematological response in patients in accelerated phase (26.3% vs 75.0%, P = 0.004), and 6-month overall survival in patients in blastic phase (77.8% vs 16.7%, P = 0.009). Patients in advanced stage obtained non-CML marrow picture in 1 month of treatment had better prognosis. 18-month disease progression rates were lower (25% vs 75%, P = 0.028) and overall survival rates higher (75.0% vs 11.8%, P = 0.004) in patients obtained non-CML picture marrows than in those with CML marrows picture in accelerated phase. Hematological response rate and overall survival of more than 6 months were higher in patients with non-CML marrows picture than those with CML marrows picture (100.0% vs 40.0%, P = 0.017 and 83.3% vs 26.7%, P = 0.046 respectively) in blastic phase. CONCLUSIONS: Normal marrow appearance can be sustained under continuous treatment of Imatinib in CML patients who achieved hematological responses.

Adolescent↗
PubMed1984

Comparison of in vitro and in vivo modulation of myelopoiesis by biological response modifiers.

In vitro growth and differentiation of granulocyte-macrophage progenitor cells (GM-CFU-C) requires colony-stimulating factors (CSF), and an in vivo role for CSF has also been proposed. Prostaglandins of the E series (PGE) have been reported to serve as negative feedback regulators of myelopoiesis. Here, we report evidence of augmented CSF secretion by mouse peritoneal Mo (macrophages) and bone marrow cells in vitro upon stimulation with various biological response modifiers (BRMs). Optimal induction of CSF secretion occurred after in vitro treatment of peritoneal Mo and mononuclear bone marrow cells with 50 micrograms/ml poly ICLC (polyriboinosinic-polycytidylic acid poly-L-lysine). 5 micrograms/ml lipopolysaccharide (LPS), or 500 U/ml interferon (IFN alpha,beta) for 2 days. The in vitro stimulation of CSF secretion was paralleled by an increase in PGE secretion by Mo and bone marrow cells. The PGE secretion could, however, be selectively blocked by preincubating the cells for 3 h with indomethacin (10(-7) Mol) leaving CFS production intact. In vivo treatment of mice with either maleic anhydride divinyl ether copolymer (MVE-2; 25 mg/kg) or poly ICLC (2 mg/kg) significantly increased levels of CSF in serum, as well as in culture supernatants of in vivo-treated peritoneal Mo and bone marrow cells. The increase in serum CSF levels and in secretion of CSF by peritoneal Mo and bone marrow cells was followed by a dose-dependent increase in GM-CFU-C, in nucleated bone marrow cells, and in peripheral blood leukocytes. The same BRMs also stimulated the secretion of PGE by in vivo-activated peritoneal Mo, but not by bone marrow cells. Pretreatment of the mice with indomethacin (4 mg/kg) almost completely suppressed PGE secretion by peritoneal Mo, but did not change the CSF secretion by peritoneal Mo or bone marrow cells and had no significant effect on bone marrow cellularity. Therefore, MVE-2 and poly ICLC, in addition to their immunomodulatory activity, can also have stimulatory effects on myelopoiesis, presumably mediated through secretion of CSFs. Protection and/or restoration of bone marrow function could thus either provide the opportunity for more extensive chemotherapy or could increase the number of Mo effector cells available for activation against tumor targets.

Animals↗
PubMed1989

Peroxidase-dependent metabolism of benzene's phenolic metabolites and its potential role in benzene toxicity and carcinogenicity.

The metabolism of two of benzene's phenolic metabolites, phenol and hydroquinone, by peroxidase enzymes has been studied in detail. Studies employing horseradish peroxidase and human myeloperoxidase have shown that in the presence of hydrogen peroxide phenol is converted to 4,4'-diphenoquinone and other covalent binding metabolites, whereas hydroquinone is converted solely to 1,4-benzoquinone. Surprisingly, phenol stimulates the latter conversion rather than inhibiting it, an effect that may play a role in the in vivo myelotoxicity of benzene. Indeed, repeated coadministration of phenol and hydroquinone to B6C3F1 mice results in a dramatic and significant decrease in bone marrow cellularity similar to that observed following benzene exposure. A mechanism of benzene-induced myelotoxicity is therefore proposed in which the accumulation and interaction of phenol and hydroquinone in the bone marrow and the peroxidase-dependent formation of 1,4-benzoquinone are important components. This mechanism may also be responsible, at least in part, for benzene's genotoxic effects, as 1,4-benzoquinone has been shown to damage DNA and is shown here to induce multiple micronuclei in human lymphocytes. Secondary activation of benzene's phenol metabolites in the bone marrow may therefore play an important role in benzene's myelotoxic and carcinogenic effects.

Animals↗
PubMed1982

Effects of high-dose methotrexate and leucovorin on murine hemopoietic stem cells.

This study compares the effects of a high dose of methotrexate (HDMTX) to that of a high dose of methotrexate plus leucovorin protection on the hemopoietic stem cells in a murine model. C57BL X C3H F1 mice were treated with a single large bolus (500 mg/kg body weight) of methotrexate or with the same dose of the drug plus leucovorin administered in fractionated doses during the following 24 hr. At 1 to 2 days after the administration of HDMTX, there was a large bone marrow and spleen depopulation of pluripotent stem cells and of committed and recognizable progenitors. At 2 to 3 days, a severe fall of white blood cells and reticulocytes ensued. The recovery process of hemopoietic precursors followed alternate phases of overshooting and secondary falls. Leucovorin administration appeared to protect all stages of hemopoiesis and prevented the severe drops of bone marrow cellularity and stem cell content which followed the HDMTX bolus. However, the effect of leucovorin on peripheral blood cell reduction was less significant. After treatment with HDMTX, the recovery of bone marrow cells and the burst of splenic hemopoietic activity followed a pattern similar in both leucovorin-protected and unprotected animals, but in the former, the increase in stem cells and hemopoietic progenitors appeared to reach higher values and to last longer. In particular, the overshooting of colony-forming units, culture and erythroid, reached a higher peak in leucovorin-treated mice and was more prolonged. Our results indicate that, in HDMTX-treated mice, leucovorin protection involves the earliest stages of hemopoiesis, assuring the maintenance of a satisfactory endowment of stem and progenitor cells.

Animals↗
PubMed1985

Modulations in mouse hemopoiesis after engraftment with Lewis lung (3LL) carcinoma cells.

Hemopoietic changes in male C57BL/6Cum BR mice engrafted with Lewis lung carcinoma (3LL) were evaluated between day 7, when palpable tumors were present, to day 30 postengraftment. All experimental animals demonstrated decreasing hematocrits (down 40% by day 30) with concurrent leukocytosis which by day 30 postengraftment had reached levels 13.4 times normal. The myelocytic/erythrocytic ratio for normal animals was 1:3 (bone marrow: spleen). The ratio for engrafted animals ranged between 10:1 and 40:1. This apparent shift in production priorities is even more significant in light of the fact that femoral bone marrow cellularity had decreased by 33% on day 17. Splenomegaly, evident by day 7, was seven times control by day 17. Clonogenic analysis of erythroprogenitor cell concentrations revealed an inverse relationship between bone marrow and spleen. 27 days after engraftment, splenic populations demonstrated significant increases in colony forming unit-erythroid (115-fold), burst forming unit-erythroid (7.4-fold), whereas bone marrow concentrations had decreased (6-fold). This report suggests that initiation of 3LL tumor in mice results in a change in the degree of hematopoietic priorities and participation of erythroid organs.

Animals↗
PubMed1977

Rapid grain and cell counting for cell kinetic studies.

A commercially available bacterial colony counter has been adapted for the counting of radioautographic grains over individual cells in smears and for the counting of cells in histologic sections. For radioautographic grains, the correlation coefficients between counts obtained visually by 2 observers and between counts obtained visually and with the use of the instrument were similar (r=0.999 and r=0.998, respectively). The instrument counts were obtained more rapidly than the visual counts and were associated with less observer fatigue. Even though the performance of the instrument in counting cells in mouse bone marrow sections was less accurate than that in counting radioautographic grains, a good estimation of marrow cell number was obtained (r=0.968). Data on bone marrow cellularity were obtained far more rapidly than those with semiquantitative methods.

Autoradiography↗
PubMed1988

An increased risk of relapse in cyclosporin-treated compared with methotrexate-treated patients: long-term follow-up of a randomized trial.

Patients with haematological malignancies and HLA-identical marrow donors were randomized to treatment with cyclosporin A (CSA, n = 30) or methotrexate (MTX, n = 29) with a follow-up ranging from 32 to 70 months. The two groups were comparable regarding disease status and age. Acute graft-versus-host disease (GVHD) was similar and the cumulative incidences of chronic GVHD was 42% in both groups. The overall incidence of cytomegalovirus (CMV) infection and other late infections were also the same in the two groups. Interstitial CMV pneumonitis occurred in 13% in the CSA group compared with 32% in the MTX group (ns). The probability of relapse was 42% after 4 years among the CSA patients and was significantly higher than the probability of relapse in the MTX patients which was found to be 10% (p = 0.03). The actuarial survival after 5 years was 53% for the CSA patients and 57% for the MTX patients (ns). The relapse-free survival was 41% and 59%, respectively (ns). There were no differences between the two groups in terms of renal or hepatic function, incidence of cataracts, blood cell counts, bone marrow cellularity or Karnofsky scores at 2 and 4 years after transplantation.

Adolescent↗
PubMed1984

Residual toxicity in hematopoietic cells following a single dose of methylnitrosourea.

The residual injury to the proliferation capability of hemopoietic stem cells (CFU-S) which results from their exposure to leukemogenic agents was evaluated in mice given a single leukemogenic dose of methyl nitrosourea (MNU 50 mg/kg body weight, i.v.). Bone marrow cellularity, splenic weight, number of CFU-S and the proportion of cycling to noncycling CFU-S were measured in an effort to detect and acute and residual injury to the CFU-S from mice given MNU 21 and 3 days earlier. Marrow cells were also transferred into lethally irradiated mice to observe the self-renewal capability of the CFU-S in the recipient spleen and bone marrow. The results of these measurements show that the CFU-S in marrow from mice given 50 mg/kg of MNU 21 days earlier still have a defective ability for self-renewal, although the total cellularity, number of CFU-S and proportion of cycling and noncycling CFU-S in the donor have returned to the normal range. The relationship of this self-renewal defect to the development of leukemia after this leukemogenic dose of MNU is not known.

Animals↗
PubMed2003

A predictive F344 rat immunotoxicology model: cellular parameters combined with humoral response to NP-CgammaG and KLH.

The purpose of this study was to examine the predictive value of humoral and cellular immune parameters in determining the immunotoxic effects of the oral administration of azathioprine (AZA), cyclophosphamide (CY), or cyclosporin A (CsA) at doses of 25/17, 10, or 25 mg/kg per day, respectively, for 30 days in F344 female rats. The effect of these known immunosuppressive compounds on the immune response was assessed in a humoral model that consisted of the administration of nitrophenyl-chicken gamma globulin (NP-CgammaG) and keyhole limpet hemocyanin (KLH) antigens during immunosuppressive treatment and the measurement of resulting rat antigen-specific IgG and IgM, as well as total IgG, levels. Cellular assessment parameters were collected from the same groups of animals as the humoral parameters and included organ weights and cellularity, hematology, lymphocyte phenotype characteristics, spleen cell mitogen stimulation (T and B cell-dependent), splenic natural killer (NK) cell cytotoxicity, and bone marrow cellularity and lymphocyte phenotype differential. Although decreases in several of the cellular assay parameters were observed, the only functional assays to demonstrate a statistically significant immunosuppressive effect by all three immunosuppressive agents were the antigen-specific serum IgG levels. The primary (day 10; 15 days post-immunization) and secondary (day 25; 5 days post-rechallenge) nitrophenyl (NP) responses were significantly suppressed by > or =60%. The use of NP hapten provided consistent responses when analyzed with a sensitive, well developed, ELISA methodology. Absolute lymphocyte phenotyping and lymphocyte hematology were also predictive of T cell immunosuppression for all three compounds. The data presented herein suggests that these two parameters, NP-IgG humoral response and lymphocyte phenotyping, are sufficient for identifying immunosuppressive compounds.

Animals↗
PubMed2004

Hematopoiesis is severely altered in mice with an induced osteoblast deficiency.

We previously reported a transgenic mouse model expressing herpesvirus thymidine kinase (TK) gene under the control of a 2.3-kilobase fragment of the rat collagen alpha1 type I promoter (Col2.3 Delta TK). This construct confers lineage-specific expression in developing osteoblasts, allowing the conditional ablation of osteoblast lineage after treatment with ganciclovir (GCV). After GCV treatment these mice have profound alterations on bone formation leading to a progressive bone loss. In addition, treated animals also lose bone marrow cellularity. In this report we characterized hematopoietic parameters in GCV-treated Col2.3 Delta TK mice, and we show that after treatment transgenic animals lose lymphoid, erythroid, and myeloid progenitors in the bone marrow, followed by decreases in the number of hematopoietic stem cells (HSCs). Together with the decrease in bone marrow hematopoiesis, active extramedullary hematopoiesis was observed in the spleen and liver, as measured by an increase in peripheral HSCs and active primary in vitro hematopoiesis. After withdrawal of GCV, osteoblasts reappeared in the bone compartment together with a recovery of medullary and decrease in extramedullary hematopoiesis. These observations directly demonstrate the role of osteoblasts in hematopoiesis and provide a model to study the interactions between the mesenchymal and hematopoietic compartments in the marrow.

Animals↗
PubMed2005

European consensus on grading bone marrow fibrosis and assessment of cellularity.

Quantification of characteristic bone marrow biopsy features includes basic parameters such as cellularity and fiber content. These are important to assess the dynamics of disease processes with a significant impact on risk stratification, survival patterns and, especially, therapy-related changes. A panel of experienced European pathologists and a foreign expert evaluated, at a multi-headed microscope, a large number of representative slides of trephine biopsies from patients with myelofibrosis in an attempt to reach a consensus on how to grade cellularity and fibrosis. This included a critical evaluation of previously described scoring systems. During the microscopic analysis and subsequent discussion and voting, the importance of age-dependent decrease in cellularity was recognized. Grading of myelofibrosis was simplified by using four easily reproducible categories including differentiation between reticulin and collagen. A consensus was reached that the density of fibers must be assessed in relation to the hematopoietic tissue. This feature is especially important in order to avoid a false impression of a reduced fiber content in fatty and/or edematous bone marrow samples after treatment. The consensus for measuring myelofibrosis by clear and reproducible guidelines achieved by our group should allow for precise grading during the disease process and after therapy.

Bone Marrow↗
PubMed1993

Expression of the proliferating cell nuclear antigen in bone marrow cells from patients with myelodysplastic syndromes and aplastic anemia.

To determine the proliferative activity of the hematopoietic cells under nonneoplastic and/or neoplastic conditions, the expression of a cell cycle-related antigen, the proliferating cell nuclear antigen (PCNA), was examined in the bone marrow trephines of 79 individuals, 12 of whom had no hematologic disorder, 32 of whom had a diagnosis of myelodysplastic syndromes (MDSs), 20 of whom suffered from aplastic anemia, and 15 of whom had a diagnosis of acute myeloid leukemia. Most of the patients with MDS had more than 15% PCNA-positive cells (23.5% +/- 1.5%) while patients with no hematologic disorder showed fewer than 15% PCNA-positive cells (11.7% +/- 0.7%). The overall ratio of the PCNA-positive cell fraction in the bone marrow was considered of prognostic value for predicting transition into overt leukemia from MDS. Aplastic anemia cases usually exhibited hypocellular bone marrow and an infrequent labeling with the anti-PCNA antibody (3.3% +/- 0.5%). However, a few aplastic anemia cases showed hypercellular bone marrow and a significantly high PCNA-positive cell ratio (32.0% +/- 4.4%). In the bone marrow of acute myeloid leukemia patients more than 20% of total nucleated cells were positive for PCNA (30.0% +/- 2.2%). The results suggest that the expression of PCNA is associated with the regulation of bone marrow cell proliferation and the bone marrow cellularity, and that these findings would serve as an early indicator of evolution of overt leukemia in MDS and also would be useful in distinguishing MDS cases from aplastic anemia cases when the bone marrow is hypocellular or normocellular.

Acute Disease↗
PubMed1998

Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice.

Administration of Withania somnifera extract (Solanaceae) was found to significantly reduce leucopenia induced by cyclophosphamide (CTX) treatment. The total WBC count on the 12th day of the CTX-treated group was 3720 cells/mm3 and that of CTX along with Withania was 6120 cells/mm3. Treatment of Withania along with CTX was found to significantly (P < 0.001) increase the bone marrow cellularity (13.1 x 10(6) cells/femur) compared to CTX alone treated group (8 x 10(6) cells/femur). Administration of Withania extract increased the number of alpha-esterase positive cells (1130/4000 cells) in the bone marrow of CTX treated animals, compared to the CTX-alone treated group (687/4000 cells). The major activity of Withania somnifera may be the stimulation of stem cell proliferation. These studies indicate that Withania somnifera could reduce the cyclophosphamide induced toxicity and its usefulness in cancer therapy.

Animals↗
PubMed1987

Cell regulatory and immunorestorative activity of picibanil (OK432).

Picibanil (OK432), a pharmaceutical preparation of a low virulent Su strain of Streptococcus pyogenes, possesses cell regulatory activity particularly in its ability to augment natural killer (NK) cell activity and to activate macrophages to exert a tumoricidal effect both in vitro and in vivo. It is effective in retarding and/or inhibiting the growth of three different tumors: MBL-2 lymphoma, M109 alveolar adenocarcinoma, and B16 melanoma. The antitumor effect is mediated through regulation of NK cells and macrophages, possibly by its ability to stimulate the production and secretion of interferon and interleukin 1 and 2. It is a very effective adjuvant for tumor cell vaccines that elicit cytotoxic T-cell responses. Following cytoreductive chemotherapy (Cytoxan) Picibanil treatment leads to an earlier reconstitution of both bone marrow cellularity and differentiation to granulocyte-macrophage colonies.

Animals↗
PubMed2000

Reduced hematopoietic function and enhanced radiosensitivity of transforming growth factor-beta1 transgenic mice.

The cytokine transforming growth factor-beta1 (TGF-beta1) has been implicated in some tissue responses to radiation. Previous studies have demonstrated that exogenous TGF-beta1 increased the lethality of radiation in mice, but the effects of endogenous TGF-beta1 have not been investigated. To this end, we examined mice that are transgenic for active TGF-beta1 (Alb/TGF-beta1), over-expressed via an albumin promoter in the liver with resultant elevation of circulating levels of this cytokine. Alb/TGF-beta1 mice subjected to 8 Gy of total body irradiation at 3 or 5 weeks of age experienced significantly higher mortality than wild type age- and sex-matched controls by 1 to 2 weeks after irradiation. Alb/TGF-beta1 3 weeks of age also succumbed to 2 and 4 Gy of whole-body irradiation, while no mortality was observed in wild type mice. Four-week-old Alb/TGF-beta1 mice exhibited mild anemia and mild uremia. At one week after whole body irradiation with 2 Gy, 4-week-old Alb/TGF-beta1 mice had significantly reduced white blood cell counts, hematocrit, and platelet counts. Histopathologically, irradiated Alb/TGF-beta1 mice exhibited decreased bone marrow cellularity and decreased splenic extramedullary hematopoiesis. These results suggest that chronic over-expression of active TGF-beta1 is associated with increased radiosensitivity and that this effect may be mediated by increased sensitivity of bone marrow to the suppressive effects of radiation. Since TGF-beta1 levels can be greatly elevated in patients with certain tumors, these findings may be significant for radiotherapy. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 13-21 (2000). Published 2000 Wiley-Liss, Inc.

Age Factors↗
PubMed1987

Didemnin B--an immunosuppressive cyclic peptide that stimulates murine hemagglutinating antibody responses and induces leukocytosis in vivo.

Didemnin B (DB) is a cyclic peptide with potent immunosuppressive activity in vitro and in the murine graft-versus-host-reaction (GVHR), the only measure of in vivo immunity tested in our prior studies. Because continued production of mature leukocytes by bone marrow and an intact antibody response are crucial to defense against infection in immunosuppressed patients, we have evaluated the effects of DB on these processes as well. Anti-sheep red blood cell (SRBC) hemagglutinating antibody (hAb) production was induced by i.p. injection of 5 x 10(7) SRBC in CB6F1 mice (5/group) treated with vehicle or DB once/day for six days. Serum was collected on day 7 and hAb titers measured by SRBC agglutination. Control antibody titers were 1/16, while animals receiving DB doses of 0.025, 0.05, 0.10, and 0.20 mg/kg/day yielded titers of 1/37, 1/74, 1/56, and 1/74, respectively. This stimulation of hAb production (4.6 x control) was confirmed by a second experiment. We then studied DB effects (0.1 mg/kg/day x 6 days) on serum hAb titers in separate groups of five mice at 7, 10, 15, and 20 days postimmunization. Control hAb titers were 1/110 on day 7, then dropped to 1/60 on days 10, 15, and 20. DB-treated animals had titers of 1/130 on day 7, and 1/170 on days 10-20. These data show that DB treatment in vivo causes a persisting increase in anti-SRBC hAb titers. Evaluation of DB effects on proliferation and antibody secretion in vitro by three hybridoma cell lines showed a potent inhibition of cell replication but stimulation of antibody production on a per-cell basis in each clone (+26%-+900%, range), suggesting a direct effect on Ig synthesis. During our first in vivo DB studies (0.1 mg/kg/day x 7 days) in mice, we noted that peripheral blood white counts were elevated on day 8 to 21.3 +/- 2.1 x 10(3)/mm3 compared with control (vehicle only) levels of 13.6 +/- 2.0 x 10(3)/mm3 (P less than .01). Kinetic studies showed that by 24 hr after a single i.p. injection of DB (1.0 mg/kg), blood leukocyte, granulocyte, and lymphocyte counts were elevated by 2.5-, 3-, and 2-fold, respectively, but declined rapidly thereafter. 3H-thymidine incorporation (4 hr) by freshly harvested bone marrow leukocytes from DB-treated mice (0.025, 0.05, and 0.10 mg/kg/day x 7 days) was enhanced up to 40% over control (P less than .05), while bone marrow cellularity was increased 200% (P less than .01).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

[Apoptosis of cells of the bone marrow hematopoietic tissue during acute radiation damage in humans and experimental animals].

We studied the bone marrow of various localization taken during autopsy of the humans died as a result of accident at the Chernobyl Nuclear Power Station and experimental animals (frogs and rats) subject to external gamma (gamma-irradiation at lethal doses (SD 100). It was shown using histological, histochemical and electronmicroscopic methods that the early radiation death of the bone marrow hemopoietic cells, so-called "early necrobiosis", is realized by apoptosis. During the period of recovery, apoptotic death of the hemopoietic cells also takes place, which, being expressed simultaneously with the onset of hemopoiesis, directly correlates with the intensity of repair. It was proposed that apoptosis as a physiological contrast of mitosis, arises during the early postradiation period as a response to blockade of mitotic activity and causes its abortive rise and bone marrow cellularity. During the recovery period, apoptosis may not only passively accompany mitosis but stimulate proliferative processes.

Animals↗