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Results for “bone marrow cellularity”

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PubMed2002

Age-associated loss of bone marrow hematopoietic cells is reversed by GH and accompanies thymic reconstitution.

Deterioration of the thymus gland during aging is accompanied by a reduction in plasma GH. Here we report gross and microscopic results from 24-month-old Wistar-Furth rats treated with rat GH derived from syngeneic GH3 cells or with recombinant human GH. Histological evaluation of aged rats treated with either rat or human GH displayed clear morphologic evidence of thymic regeneration, reconstitution of hematopoietic cells in the bone marrow, and multiorgan extramedullary hematopoiesis. Quantitative evaluation of formalin-fixed, hematoxylin and eosin-stained sections of bone marrow from aged rats revealed at least a 50% reduction in the number hematopoietic bone marrow cells, compared with that of young 3-month-old rats. This age-associated decline in bone marrow leukocytes, as well as the increase in bone marrow adipocytes, was significantly reversed by in vivo treatment with GH. Restoration of bone marrow cellularity was caused primarily by erythrocytic and granulocytic cells, but all cell lineages were represented and their proportions were similar to those in aged control rats. On a per-cell basis, GH treatment in vivo significantly increased the number of in vitro myeloid colony forming units in both bone marrow and spleen. Morphological evidence of enhanced extramedullary hematopoiesis was observed in the spleen, liver, and adrenal glands from animals treated with GH. These results confirm that GH prevents thymic aging. Furthermore, these data significantly extend earlier findings by establishing that GH dramatically promotes reconstitution of another primary hematopoietic tissue by reversing the accumulation of bone marrow adipocytes and by restoring the number of bone marrow myeloid cells of both the erythrocytic and granulocytic lineages.

Aging↗

PubMed1997

Immunosuppressive therapy for hypoplastic myelodysplastic syndrome.

BACKGROUND: Hypoplastic myelodysplastic syndrome (MDS) is characterized by dysplasia and hypocellularity. The treatment of choice for young patients is bone marrow transplantation. METHODS: This report describes the effect of immunosuppressive therapy in two patients with hypoplastic MDS for whom no suitable bone marrow donors were available. RESULTS: Both patients had no human lymphocyte antigen-identical siblings and no suitable matched unrelated donor could be found. They received cyclosporin A (CsA), antithymocyte globulin (ATG), or a combination of the two. Treatment with CsA, ATG, or the combination led to clinical improvement (resolution of transfusion requirement), increase of bone marrow cellularity, and the disappearance of dysplastic characteristics in the two patients with hypoplastic MDS. At the time of recurrence, this disease was still responsive to immunosuppressive therapy. CONCLUSIONS: Treatment with ATG and CsA can be an attractive alternative for patients with hypoplastic MDS for whom there is no possibility of bone marrow transplantation.

Antilymphocyte Serum↗

PubMed1997

DHA feeding provides host protection and prevents fibrosarcoma-induced hyperlipidemia while maintaining the tumor response to araC in Fischer 344 rats.

Fischer 344 rats were inoculated with fibrosarcoma tumor cells and fed diets containing 5% or 10% (wt/wt) safflower oil or 10% oil containing docosahexaenoic acid (DHA). Animals were then treated with arabinosylcytosine (araC) or saline for six days. Tumor weights were highest in animals fed 10% safflower oil and treated with saline, intermediate in animals fed oil containing DHA and 5% safflower oil and treated with saline, and lowest in araC-treated animals from all diets. Plasma cholesterol and triglyceride levels correlated highly with final tumor size, regardless of diet or treatment group. Animals fed safflower oil had lower intestinal weights than those fed DHA, which histology demonstrated to be a result of differences in villus height and crypt depth. Substantial loss of bone marrow cells occurred in all dietary groups treated with araC; however, the proportion of granulocyte-macrophage precursors remaining in the DHA animals was higher than in saline-treated animals and twofold higher than in the animals fed 10% safflower oil and treated with araC. These data suggest that, even in the face of rapid tumor growth and chemotherapeutic challenge, consumption of a diet rich in DHA can slow tumor growth, prevent hyperlipidemia, enhance bone marrow cellularity, and promote intestinal growth compared with a moderate-fat n--6-rich diet.

Animals↗

PubMed1986

Use of multiparameter analysis to quantitate hematological damage from exposure to a chemical (ethylene oxide).

This study was designed to test the value of a multiparameter approach in evaluating perturbations in bone marrow and peripheral blood elements of mice exposed to ethylene oxide (EtO). Mice exposed to 255 ppm EtO for 5 h/d were removed for analysis after 1, 2, 8, and 14 d (sequential exposure) and 4, 6, 8, and 10 wk (5 d/wk). Prior to sacrifice, blood was removed from the orbital sinus for blood cell counts, hemoglobin determination, and hematocrit. A blood film was made for differential leukocyte counts. Bone marrow was flushed from femurs and tibias and counted, and aliquot were used for stem-cell assay (CFU-S) or flow cytometry (FCM) analysis. One aliquot of marrow was stained with propidium iodide for cell-cycle analysis and another was reacted with fluorescein-conjugated monoclonal antibody for B-cell analysis. The preparations were analyzed for forward and 90 degrees scatter and fluorescence on an Ortho 50H cytofluorograph. Perturbations of peripheral leukocytes occurred after one exposure. After multiple exposures, hematocrit, red-cell number, and hemoglobin were generally depressed, with transient compensatory bursts, and bone marrow cellularity and CFU-S were below normal. However, white-cell numbers fluctuated dramatically during the exposure period. There was a shift in differential toward granulocytes, at times resulting in severely depressed numbers of lymphocytes in the peripheral blood. The FCM analysis showed an early depletion of granulocytes in the bone marrow followed by replacement and a relative lymphocyte deficit, especially pronounced at 10 wk. The B-cell changes reflected general lymphocyte perturbations. Shifts in numbers of cells in S and G/M were observed, consistent with a moderate bone marrow response to cell loss.

Animals↗

PubMed1987

Modulation of cell-mediated resistance to listeriosis in mice given T-2 toxin.

The modulating effect of preinoculation and postinoculation treatment with a single oral 4.0 mg/kg dosage of T-2 toxin on cell-mediated resistance was studied in mice inoculated with Listeria monocytogenes. Toxin treatment caused significant decreases in thymus and spleen weights, bone marrow cellularity, and in the total number of circulating leukocytes, lymphocytes, and neutrophils. Enhancement or suppression of resistance to listeriosis was dependent on the time of toxin administration relative to the time of Listeria challenge. Preinoculation treatment on Day 2 or 4 prior to Listeria challenge significantly enhanced resistance and decreased mortality due to listeriosis by as much as 50%. In contrast, resistance was suppressed and mortality was increased by 50% in mice that were treated with toxin after Listeria challenge. Enhanced resistance to listeriosis was accompanied by a significant increase in the influx of macrophages into Listeria-elicited peritoneal exudates. In addition, in vivo phagocytosis of sheep red blood cells by peritoneal macrophages was significantly increased in toxin-treated mice that were sensitized with sheep erythrocytes. The data indicate that T-2 toxin has a modulating effect on cell-mediated resistance and that enhancement of resistance to listeriosis in mice pretreated with T-2 toxin is associated with increased migration/activation of macrophage effector cells.

Animals↗

PubMed2003

Immunomodulatory activity of naturally occurring monoterpenes carvone, limonene, and perillic acid.

The immunomodulatory activity of some naturally occurring monoterpenes were studied in Balb/c mice. Administration of various monoterpenes such as carvone (100 micromoles/Kg body wt/dose/animal), limonene (100 micromoles/Kg body wt/dose/animal) and perillic acid (50 micromoles/Kg body wt/dose/animal) were found to increase the total white blood cells (WBC) count in Balb/c mice. The maximum total WBC count in carvone treated animals was observed on the 12th day (16,560 cells/cmm) while in limonene (13,783 cells/cmm) and perillic acid (14,437 cells/cmm) treated animals the maximum count was observed on the 9th day after the drug treatment. Administration of terpenoids increased the total antibody production, antibody producing cells in spleen, bone marrow cellularity and alpha-esterase positive cells significantly compared to the normal animals indicating its potentiating effect on the immune system.

Adjuvants, Immunologic↗

PubMed1980

A preliminary study of polyamines in the bone-marrow plasma of adult patients with leukemia.

Polyamines (mainly putrescine, spermidine, and spermine) whose biosynthesis is a prerequisite for cell proliferation, are potential indicators of malignant growth. To investigate the mechanism of alterations of polyamine levels in physiological fluids in human cancer, polyamine levels of bone-marrow plasma from adult patients with leukemia were studied. Significant correlations were observed between bone-marrow cellularity and spermidine, between peripheral white blood cell counts and spermidine and spermine, and between absolute blast count and spermidine and spermine among untreated patients with acute leukemia. Untreated patients with chronic leukemia showed significantly elevated levels of polyamines relative to untreated patients with acute leukemia, indicating a higher turnover of bone-marrow cells in chronic leukemia than in acute leukemia. Chemotherapy-treated patients with acute leukemia who were in remission or who did not respond to the agent showed low polyamine levels. Patients who showed a destruction of tumor cell during chemotherapy gave high levels of polyamines. Overall, these studies indicate that elevated polyamine levels are markers of cell death.

Adult↗

PubMed1985

Low-dose cytosine arabinoside treatment for acute nonlymphocytic leukemia in elderly patients.

Thirty patients older than 65 years of age with acute nonlymphocytic leukemia were treated with low-dose cytosine arabinoside (10 mg/m2 subcutaneously every 12 hours for 15 to 21 days). Fifteen achieved complete remission and five had partial remission. Treatment was more effective when initial bone marrow cellularity was low (P = 0.007). Four of six patients with secondary leukemia entered complete or partial remission. Therapy was well tolerated with reduced myelosuppression and few number of early deaths. Sixteen patients followed the whole treatment as outpatients. Six of 12 patients who achieved complete remission showed no evidence of post-therapeutic bone marrow aplasia. These data are consistent with the view that low-dose cytosine arabinoside acts on leukemic cells as a differentiating agent.

Acute Disease↗

PubMed1996

Dietary n-3 fatty acids increase spleen size and postendotoxin circulating TNF in mice; role of macrophages, macrophage precursors, and colony-stimulating factor-1.

In experimental studies in mice, dietary supplementation with n-3 fatty acids (FA) alleviates inflammation and increases resistance to infection. Nevertheless, TNF production capacity was found to be increased in n-3 FA-fed mice. We previously found increased relative spleen weights in n-3 FA-fed mice. In this study, the nature of this increased spleen size was further investigated. Spleen cellularity was increased significantly in mice fed n-3 FA (fish oil 15% w/w), compared with controls fed corn oil (15%) or normal lab chow (p < 0.05). Experiments with T cell-deficient nude mice and experiments using macrophage depletion through liposomal dichloromethylene-biphosphonate revealed that the increase in spleen cellularity is T cell independent and largely due to macrophage accumulation in the spleen. Accumulation of marginal zone and red pulp macrophages was histologically and immunohistochemically confirmed. n-3 FA induced peripheral blood monocytosis and an aspecific increase in bone marrow cellularity. Postendotoxin circulating TNF concentrations were increased significantly in n-3 FA-fed mice compared with controls. Splenectomy did not abolish this increase in circulating TNF. However, after macrophage depletion through liposomal dichloromethylene-biphosphonate, circulating TNF was not detectable after endotoxin challenge. Circulating concentrations of CSF-1 did not differ between the various experimental groups. It is suggested that the cellular changes observed relate to increased constitutive production of TNF.

Animals↗

PubMed1982

Decreased tolerance to dimethyl-myleran, cyclophosphamide and radiation in lymphoma-bearing mice.

A lethal dose of the cytotoxic agent dimethyl-myleran (DMM) is survived by 75-100% of mice reinfused with autologous bone marrow. In mice inoculated beforehand with a syngeneic Moloney lymphoma and then treated with lethal DMM, hemopoietic restoration and survival are compromised. With subcutaneous tumour challenge, in the face of substantial early toxicity, a therapeutic effect of DMM prevails. With intravenous or intraperitoneal tumour challenge the restorative potency of the autograft and thus the therapeutic drug effect are lost since practically all animals die from DMM. The reduced tolerance of mice carrying the Moloney lymphoma applies more generally to cytotoxic measures. The toxicity from sublethal doses of DMM, cyclophosphamide (CY) and total-body irradiation (TBI) is increased in mice inoculated subcutaneously shortly before with the lymphoma cells. The LD50 of the three agents is reduced by up to 70% according to the number of injected tumour cells or the time allowed for their multiplication. The effect is also provided by a cell-free tumour filtrate. Since the filtrate reduces bone marrow cellularity, the decreased tolerance could be due to the impairment of hemopoiesis by a tumour factor. Two human cancers growing as xenografts in immunosuppressed mice did not increase the sensitivity to DMM.

Animals↗

PubMed1989

Effect of exposure route, regimen, and duration on benzene-induced genotoxic and cytotoxic bone marrow damage in mice.

Mice were exposed to benzene for 13 to 14 weeks by inhalation for either 3 or 5 consecutive days per week or by gavage for 5 consecutive days per week. A weekly evaluation of peripheral blood smears for micronucleated (MN) erythrocyte frequencies and for the percentage of polychromatic erythrocytes (PCE) indicated that the induction of MN-PCE by benzene depended on the sex and strain of mice and on the route of exposure, but not on the inhalation regimen or on the exposure duration. The frequency of MN normochromatic erythrocytes (NCE) not only depended on the sex and strain of mice and on the route of exposure, but directly depended on the inhalation regimen and on the exposure duration. Similarly, the extent of erythropoietic depression in benzene-exposed mice was dependent on sex, mouse strain, exposure duration, and route. However, in contrast to the MN-NCE data, the 3 day/week exposure regimen induced a more persistent depression in erythropoiesis than the 5 day/week exposure regimen. Exposure to benzene also induced in mice a significant depression in packed cell volume (PCV) and bone marrow cellularity, the magnitude of which depended on the sex and strain of mice and on the regimen and route of exposure.

Administration, Inhalation↗

PubMed1982

Cellular aggregates in bone marrow cultures of patients with acute myeloid leukemia.

We describe the incidence and morphology of cellular aggregates which may develop in 8 day bone marrow (BM) cultures of patients with acute myeloid leukemia (AML). Aggregates formed in at least one BM culture from 50% (20/39) of the AML group. They developed irrespective of the patient's status (i.e. stages M1-M4), FAB type, and presence of colony stimulating factor (CSF). All aggregates were composed of macrophages, plasma cells, and cells of the myelocyte series surrounding a core of adipocytes and collagen fibrils. The percentage of blasts and promyelocytes in the plated BM aspirate governed the final composition of the aggregate. Patients in Stages M3 or M4 with FAB types M1 or M2 formed aggregates with a high proportion of myelocytic cells; aggregates of all other AML patients were composed predominantly of macrophages and plasmacytes. Aggregates appeared to form as a result of attraction of cells in the medium toward the stroma cell core. Furthermore, the development of aggregates in the absence of exogenous CSF, suggested that stromal cells excreted a factor with CSF-like activity. The results indicate that cellular aggregates in AML-BM cultures reflect the important role of BM stroma in creating microenvironments which enhance the development of hemopoietic stem cells.

Bone Marrow↗

PubMed2001

Effects of zinc deficiency and corticosterone elevation on bone marrow in rats.

OBJECTIVE: The effects of zinc deficiency and serum corticosterone elevation, in a zinc-deficient state, on rat bone marrow were studied. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into the following four groups: zinc-adequate (ZA), restricted ZA (RZA), zinc-deficient (ZD) and ZD with the injection of Mifepristone (ZD+Mife). Platelet and reticulocyte counts, levels of serum zinc and corticosterone, bone marrow cellularity and morphological alterations of marrow were examined in all rats. RESULTS: Decreased marrow cellularity, decreased numbers of peripheral platelets and reticulocytes, and increased adipocytes in the marrow were observed in ZD rats. The injection of Mifepristone improved marrow cellularity, and increased the number of platelets, while decreasing adipocytes in the marrow in ZD rats. CONCLUSION: Both zinc deficiency itself and the associated serum corticosterone elevation induced bone marrow suppression in rats.

Adipocytes↗

PubMed1987

Peripheral blood admixture in bone marrow aspirates.

A simple method is described by which the degree to which a bone marrow aspirate is diluted with peripheral blood, the admixture of peripheral blood leukocytes in the aspirate, and the true cellularity of bone marrow at the aspiration site can be estimated quantitatively. A highly significant correlation is shown to exist between the true bone marrow cellularity and the number of hemopoietic cells in the bone marrow aspirate. This correlation can be described by an exponential regression equation (r = 0.6997; p less than or equal to 0.001). The degree of bone marrow dilution with peripheral blood does not depend on the initial bone marrow cellularity and is devoid of diagnostic value. It fluctuates over a wide range (1.2- to 6.3-fold). The admixture of peripheral blood leukocytes has been found to be small (0.05%-9.7%) in most cases studied and much higher in those cases where the cellularity is low while the dilution is high.

Biopsy, Needle↗

PubMed2005

Aplastic anemia successfully treated with rituximab.

An otherwise healthy 73-year-old female was admitted to our department in 1997 because of easy bruising and a platelet count of 12 x 10(9)/L. The patient was taking no medications. Bone marrow examination revealed erythroid hyperplasia, megakaryocytic hypoplasia, and no sign of malignancy. Chromosome analysis showed a normal karyotype. There was serological evidence of previous infection with parvovirus B19. No antibodies to HBV, HCV, CMV, or EBV were found. ANA and cardiolipin antibodies were not detected. Treatment with prednisolone was without effect, but 3 weeks after i.v. gamma-globulin therapy, the platelet count was normal, 233 x 10(9)/L. Two years later, the patient was readmitted with a platelet count of 11 x 10(9)/L. At this time, treatment with corticosteroids, azathioprine, and gamma-globulin had only a temporary effect, and further therapy was stopped because of side effects. During the next 3 years, the patient developed transfusion-dependent anemia, and her white blood cell count decreased to 1.8 x 10(9)/L. A new bone marrow examination showed aplastic anemia with bone marrow cellularity about 10%. After an intracerebral hemorrhage, the patient accepted treatment with rituximab and received 4 weekly doses of 375 mg/m2. This therapy was followed by an increase in the platelet count to 232 x 10(9)/L, white blood cell count to 6.8 x 10(9)/L, and no more need for blood transfusions. A bone marrow examination 5 months after treatment with rituximab showed hyperplastic myelopoiesis, normoblastic erythropoiesis, and slightly reduced megakaryopoiesis. The use of anti-CD20 monoclonal antibody in aplastic anemia warrants further investigation.

Aged↗

PubMed1991

The platelet volume-number relationship in patients infected with the human immunodeficiency virus.

The pathophysiology of thrombocytopenia in the acquired immune deficiency syndrome has not been elucidated completely. Many findings in these patients are identical to those with immune thrombocytopenic purpura. However, recent findings in acquired immune deficiency syndrome patients including the effect of zidovudine on platelet count and the demonstration of ultrastructural changes and viral RNA in megakaryocytes, have suggested that the human immunodeficiency virus may directly infect megakaryocytes, and play a role in acquired immune deficiency syndrome-related thrombocytopenia. To investigate further the mechanism of decreased platelet counts in human immunodeficiency virus-infected patients, the platelet volume-number relationship and corresponding bone marrow findings in 34 patients infected with human immunodeficiency virus were studied. Parameters evaluated included platelet count and mean platelet volume; bone marrow cellularity, megakaryocyte number, and number and percentage of denuded megakaryocyte nuclei. Two thirds of the platelet counts were low, and of these 92% had an inappropriately low mean platelet volume. These individuals had a platelet-volume number relationship that is very similar to that seen in myelosuppressive disorders. In addition, more than 90% of the bone marrows from thrombocytopenic patients had either normal or decreased numbers of megakaryocytes. These observations provide additional evidence to support the hypothesis that the pathophysiology of human immunodeficiency virus-associated thrombocytopenia may be due, at least in part, to a direct effect on the megakaryocytes.

Adult↗

PubMed2000

Reliable and sensitive analysis of occult bone marrow metastases using automated cellular imaging.

The presence of occult bone marrow metastases (OM) has been reported to represent an important prognostic indicator for patients with operable breast cancer and other malignancies. Assaying for OM most commonly involves labor-intensive manual microscopic analysis. The present report examines the performance of a recently developed automated cellular image analysis system (ACIS; ChromaVision Medical Systems, Inc.) for identifying and enumerating OM in human breast cancer specimens. OM analysis was performed after immunocytochemical staining. Specimens used in this study consisted of normal bone marrow (n = 10), bone marrow spiked with carcinoma cells (n = 20), and bone marrow obtained from breast cancer patients (n = 39). The reproducibility of ACIS-assisted analysis for tumor cell detection was examined by having a pathologist evaluate montage images generated from multiple ACIS runs of five specimens. Independent ACIS-assisted analysis resulted in the detection of an identical number of tumor cells for each specimen in all instrument runs. Additional studies were performed to analyze OM from 39 breast cancer patients with two pathologists performing parallel analysis using either manual microscopy or ACIS-assisted analysis. In 17 of the 39 cases (44%), specimens were classified by the pathologist as positive for tumor cells after ACIS-assisted analysis, whereas the same pathologist failed to identify tumor cells on the same slides after analysis by manual microscopy. These studies indicate that the ACIS-assisted analysis provides excellent sensitivity and reproducibility for OM detection, relative to manual microscopy. Such performance may enable an improved approach for disease staging and stratifying patients for therapeutic intervention.

Bone Marrow Neoplasms↗

PubMed1996

Interleukin-12-induced interferon-gamma inhibits hematopoiesis in vivo in mice.

In vivo administration of interleukin-12 decreases peripheral blood counts and bone marrow hematopoiesis, although in vitro IL-12 was shown to synergize with other cytokines to stimulate the proliferation and differentiation of early hematopoietic progenitors. We investigated whether the in vivo inhibition of hematopoiesis by IL-12 is indirectly mediated by IL-12-induced IFN-gamma. IL-12 was administered to wild-type or IFN-gamma receptor deficient (IFN gamma R-/-) mice. IL-12 treatment resulted in lower peripheral blood counts and a twofold decrease in bone marrow cellularity and hematopoietic progenitors in wild-type mice, but not in IFN gamma R-/- mice. Splenic weight and cellularity were dramatically increased after IL-12 administration in wild-type mice and somewhat less in IFN gamma R-/- mice. The increase was predominantly due to NK cell and macrophage infiltration in wild-type mice, and strong extramedullary hematopoiesis in IFN gamma R-/- mice. Thus, the reduction in total bone marrow cells and hematopoietic progenitor numbers following IL-12 treatment are largely indirect, mediated by IL-12-induced IFN gamma. In the absence of IFN-gamma signaling, IL-12 promotes both bone marrow and splenic hematopoiesis, consistent with its in vitro activities.

Animals↗