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 361 records · Page 20Linked to original sources

PubMed1996

Shwachman syndrome: exocrine pancreatic dysfunction and variable phenotypic expression.

BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis.

Abnormalities, Multiple↗

PubMedDate not supplied

Mitoxantrone in elderly patients with advanced breast cancer: pharmacokinetics, marrow and peripheral hematopoietic progenitor cells.

The aims of this study were to evaluate the pharmacokinetics, tolerability and hematopoietic toxicity of mitoxantrone in elderly women. Thirteen patients with advanced breast cancer, median age of 73 years, received escalating doses of mitoxantrone 8, 10, 12 and 14 mg/m2 on day 1, q 21. There was a linear relationship between the mitoxantrone dose administered and the mitoxantrone exposure (AUC) in plasma (r = 0.856, pc0.001). After 4 courses of treatment, a significant decrease in bone marrow cellularity (p = 0.0067), and HPC content (BFU-E p = 0.0077) was observed. A remarkable, though not statistically significant decrease in circulating HPCs was observed after 4 courses and was still present 8-12 months after the termination of treatment. Therapy with mitoxantrone in elderly women was well tolerated at the dose of 12 mg/m2 for four courses. The significant hematological toxicity observed in marrow cellularity and HPC content warrant further studies.

Aged↗

PubMed1991

Protective effects of swainsonine on murine survival and bone marrow proliferation during cytotoxic chemotherapy.

We have investigated the ability of swainsonine, an indolizidine alkaloid with pleiotropic in vivo effects, to confer protection against the cytotoxic effects of both cell cycle-specific and cell cycle-nonspecific cytotoxic anticancer agents. The intraperitoneal administration of swainsonine decreased the lethality of methotrexate (MTX), fluorouracil (5-FU), cyclophosphamide (CPM), and doxorubicin (DOX) in non-tumor-bearing C57BL/6 mice. The increased survival rate was found to correlate with stimulation of bone marrow cell proliferation, as measured by increases in 1) bone marrow cellularity, 2) in vivo and in vitro colony-forming activity, and 3) engraftment efficiency. These responses were critically dependent on the dose, sequence, and timing of swainsonine administration. If these results are confirmed in humans, swainsonine may offer promise in future intensive chemotherapy programs, allowing increased dosage and/or frequency of administration of cytotoxic agents without increasing toxic effects in bone marrow.

Alkaloids↗

PubMed2003

Philadelphia chromosome and/or bcr-abl mRNA-positive primary thrombocytosis: morphometric evidence for the transition from essential thrombocythaemia to chronic myeloid leukaemia type of myeloproliferation.

AIMS: The incidence, bone marrow morphology and genetic features of bcr+ essential thrombocythaemia were investigated. METHODS AND RESULTS: Sixty-four consecutive patients meeting the criteria of essential thrombocythaemia have been investigated for bcr-abl rearrangement and chimera mRNA expression. Reverse transcriptase-polymerase chain reaction indicated bcr-abl expression in six patients, in two of whom large fraction of the blood and bone marrow cells proved to be positive for Philadelphia chromosome (Ph) by fluorescent in-situ hybridization (FISH) and conventional cytogenetic analysis. In the remaining four patients FISH analysis could not detect Ph+ cells among the blood cells, but in one of these four patients conventional cytogenetic analysis indicated a very small fraction (2%) of Ph+ mitoses in the bone marrow (bcr+ essential thrombocythaemia patients). In three of these four patients, X-chromosome-linked clonality assay showed that the disease is of uncommitted stem cell origin. During an average of 57 month long follow-up no transformation to chronic myeloid leukaemia type of disease or acceleration/blastic crisis could be observed in the four bcr+ essential thrombocythaemia patients. They did not differ significantly from typical essential thrombocythaemia patients in quantitative indices of bone marrow cellularity or the size of megakaryocytes. In these two parameters as well as in the total nucleolus organizer region area per nucleus, however, significant differences could be detected between these four as well as typical chronic myeloid leukaemia patients. Statistical analysis of the morphometric data obtained from all six Ph+ and bcr+ essential thrombocythaemia patients combined indicated a shift of the bone marrow morphology towards the chronic myeloid leukaemia type of myeloproliferation. CONCLUSIONS: These investigations indicate that bcr+ essential thrombocythaemia is infrequent among essential thrombocythaemia patients, and this condition resembles essential thrombocythaemia more than chronic myeloid leukaemia. Various expansions of the Ph+ clone appear to lead to either essential thrombocythaemia or, rather, chronic myeloid leukaemia type of myeloproliferation; however, data in the present study do not indicate that bcr+ essential thrombocythaemia would be a form fruste variant of chronic myeloid leukaemia.

Adult↗

PubMed1976

Different recovery patterns of mouse haemopoietic stem cells in response to cytotoxic agents.

The response and subsequent recovery of mouse haemopoietic progenitor cells (spleen colony forming cells and agar colony forming cells) has been studied following two cytotoxic agents. Busulphan was administered to normal mice and vinblastine to mice where the progenitor cell proliferation rate had been increased by a period of continuous gamma-irradiation. With both these agents there is a difference between the response of the spleen colony forming cells and the agar colony forming cells during the first five days. They then recover together, but much more slowly after fusulphan than after vinblastine even though their proliferation rate is increased. The rate of progenitor cell recovery after busulphan is increased if the progenitor cells are depleted further by vinblastine. However, methotrexate, which severely depletes the peripheral blood count and bone marrow cellularity but not the progenitor cells, has no effect on the recovery following busulphan. These results suggest that following cytotoxic agents the agar colony forming cells ("committed" stem cells) are not self-maintaining but are dependent on a supply of cells from the pluripotential spleen colony forming cells. In addition it appears that the depletion of the progenitor cells of the bone marrow and not the depletion of the maturing cells, provides a stimulus for stem cell recovery.

Animals↗

PubMed1983

Effect of cooling rate on human and murine hemopoietic precursor cell recovery.

The effect of cooling rate on recovery of human and murine hemopoietic precursor cells was studied. In the presence of 10% Me2SO, a cooling rate of 7 degrees C/min from -4 to -30 degrees C was optimal for recovery of both human and murine precursor cells which give rise to colonies in diffusion chambers implanted in mice (CFU-DG). Cooling of human marrow at a rate between 3 and 7 degrees C/min resulted in the best CFU-C recovery, although no good correlation between the cooling rate and murine CFU-C recovery was demonstrated. These data suggest that recovery of the primitive hemopoietic precursor cells can be improved by changing the standard cryopreservation programs used presently. However, improved recovery of CFU-DG does not necessarily translate into faster reconstitution of hemopoiesis. No significant difference was observed in overall recovery of bone marrow cellularity in lethally irradiated mice following injection of untreated marrow and marrow cooled at a rate of 1 and 7 degrees C/min.

Animals↗

PubMed1979

Neocarzinostatin: a phase I clinical trial with five-day intermittent and continuous infusions.

Neocarzinostatin, a polypeptide antibiotic, was administered by both continuous and intermittent intravenous infusion to 76 patients with a variety of malignant diseases. Doses ranged from 500 to 6500 units/m2 X 5 days. With levels greater than or equal to 1800 units/m2, bone marrow suppression (particularly thrombocytopenia) was the dose-limiting toxicity. Delayed bone marrow recovery was less dose-dependent and occurred in 58% of initial treatment courses in solid tumor patients. Allergic reactions were more frequent with intermittent than with continuous infusions (20% vs. 2% of courses). No complete or partial remissions were observed among solid tumor patients although clinical improvement was noted in one patient with mycosis fungoides and one patient with multiple myeloma. One complete and two partial remissions were noted among 21 patients with acute leukemia. There was one complete remission in a patient with chronic leukemia. Leukemic patients on intermittent therapy evidenced greater change in bone marrow cellularity than those treated by continuous infusion. Although neocarzinostatin has some activity in the treatment of acute leukemia, continuous infusion offers no advantage over intermittent therapy.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

[The action of the tumor necrosis factor (TNF) on the recovery processes of hemopoietic colony-forming cells in irradiated mice].

The influence of a tumor-necrotic factor (TNF) on the CFUs population has been studied normally and after irradiation. An inhibitory effect on the pool of the seven-day and doubling of the yield of the eleven-day colonies have been observed in mice received TNF 20 h before bone marrow removal as compared with the controls. The kinetics of restoration of bone marrow cellularity and CFUs number in mouse donors treated with TNF 20 h before irradiation (5.0 Gy) has demonstrated the stimulatory effect of the agent on both indices.

Animals↗

PubMed1981

Inhibition of bone marrow stem cell growth in vitro by methylmalonic acid: a mechanism for pancytopenia in a patient with methylmalonic acidemia.

A 7-week-old infant with methylmalonic acidemia had pancytopenia and hypoplastic bone marrow. The patient responded to large doses of vitamin B12 treatment, and within 3 wk, the blood counts and bone marrow cellularity returned to normal. To understand the mechanism of marrow depression in this infant, we examined the effect of the patient's plasma and methylmalonic acid itself on the in vitro growth of bone marrow-committed stem cells. The patient's plasma obtained before B12 treatment completely inhibited the marrow cell growth, whereas the posttreatment plasma showed no inhibition. Methylmalonic acid when added to the culture dishes in concentrations comparable to those reported in plasma of methylmalonic acidemia patients, inhibited growth of marrow stem cells in a concentration-dependent fashion. On the other hand, 16 to 18 hr incubation of cells in the same concentration of methylmalonic acid did not affect the recovery of viability of the cells. The observations suggest that methylmalonic acid is inhibitory to the proliferation of marrow stem cells. The mechanism of inhibition is yet to be elucidated.

Bone Marrow↗

PubMed1989

5-fluorouracil-induced thrombocytosis in mice is independent of the spleen and can be partially reproduced by repeated doses of cytosine arabinoside.

Experiments were done to characterize the pronounced and prolonged thrombocytosis that develops in mice during recovery from the marrow hypoplastic effects of a single injection of 5-fluorouracil (5-FU). Measurements were made of platelet and megakaryocyte numbers, size of mature megakaryocytes, marrow cellularity, hematocrit, and reticulocytes. Mice that had been splenectomized a month before receiving 5-FU displayed the same pattern of thrombocytosis as intact mice, so a role for the spleen in its genesis or persistence could not be identified. During recovery from two or three doses of cytosine arabinoside (Ara-C), given at intervals of 2 days, thrombocytosis and megakaryocytosis of similar magnitudes to those seen after 5-FU occurred. Bone marrow cellularity, hematocrits, and reticulocytes were identical after three doses of Ara-C or one dose of 5-FU. Megakaryocytes were initially macrocytic during recovery from the hypoplastic thrombocytopenia produced by 5-FU or Ara-C. These similarities to effects of repeated doses of Ara-C suggested that some of the effects of 5-FU were due to its prolonged action in vivo, which could cause sequential killing of proliferating cells. Abnormalities of megakaryocytes and platelets reversed promptly when normal or increased numbers of megakaryocytes and/or platelets were produced after Ara-C, but they persisted in mice that received 5-FU. This difference suggested that regulation of megakaryocyte progenitors was perturbed during recovery from 5-FU.

Animals↗

PubMed1993

Sequential impact of tiazofurin and ribavirin on the enzymic program of the bone marrow.

Tiazofurin and ribavirin are clinically used inhibitors of IMP dehydrogenase (DH), binding to the NAD and IMP sites, respectively, of the target enzyme. In patients with chronic granulocytic leukemia in blast crisis, daily tiazofurin infusions decreased the high IMP DH activity in blast cells and resulted in 77% response (G. Weber. In: R. A. Harkness et al., Purine and Pyrimidine Metabolism in Man, Vol. VII, Part B, pp. 287-292, 1991). However, patients relapsed in a few weeks with emergence of high IMP DH activity (G. Tricot et al., Int. J. Cell Cloning, 8: 161-170, 1990). The present study showed that the tiazofurin-induced depression of IMP DH activity in rat bone marrow can be maintained by ribavirin injection. Tiazofurin (150 mg/kg, i.p., once a day for 2 days) decreased IMP DH activity to 10% and ribavirin (250 mg/kg, i.p., once a day for the subsequent 3 days) maintained the enzymic activity at 20 to 30% of control values. In control rats where no ribavirin was given, IMP DH activity of the tiazofurin-treated rats rapidly returned to the range of untreated animals. The decrease of IMP DH activity (t1/2 = 2.6 h) sharply preceded that of the bone marrow cellularity (t1/2 = 17.4 h). In addition to the target enzyme, IMP DH, tiazofurin also decreased activities of the guanylate metabolic enzymes, guanine phosphoribosyltransferase and GMP reductase, and the pyrimidine salvage enzymes, deoxycytidine and thymidine kinases with t1/2 of 2.6, 4.7, 6.0, 3.4, and 6.5 h, respectively. In cycloheximide-treated rats, where much of protein biosynthesis was blocked, the t1/2(8) of these five enzymes in bone marrow were shorter, 1.6, 4.3, 3.0, 0.6, and 0.8 h, respectively. Thus, the impact of tiazofurin in the bone marrow entails a decrease in the activity of the target enzyme, IMP DH, and also of other enzymes in purine and pyrimidine biosynthesis as a result of the enzyme half-lives shortened by this drug. These novel observations should assist in achieving better protection and recovery of bone marrow during and after chemotherapy.

Animals↗

PubMed2005

Cyclosporin A in myelodysplastic syndrome: a preliminary report.

Therapeutic approaches are not well established in patients with myelodysplastic syndrome (MDS). We evaluated response to cyclosporin A (CyA) in 19 cases with MDS who were enrolled for the study [13 refractory anemia (RA), 5 refractory anemia with excess of blasts (RAEB), and 1 refractory anemia with ringed sideroblasts (RARS)]. Bone marrow was normocellular in ten, hypercellular in five, and hypocellular in four cases. Fifteen patients were transfusion dependent and the rest were not transfusion dependent but with a hemoglobin range of 6.4-8.8 g% with a mean of 7.4 g%. CyA was given at a dose of 3-5 mg/kg per day. A major response was observed in seven patients with RA, which was sustained on follow-up. Four cases of RA showed minor response and two cases of RA did not respond to CyA therapy. A minor response was also seen in one RAEB and one RARS case, while one RAEB case that initially showed a major response relapsed on therapy. The first effect of therapy was evident after a mean period of 2.5 months. A rise in platelets and leukocyte count was seen in three and two cases, respectively. One case developed renal failure on therapy and later died of septicemia. Response to CyA was independent of bone marrow cellularity. CyA could be an effective mode of therapy in patients with MDS especially those having RA.

Adult↗

PubMed2003

Bone marrow transplant completely rescues hematolymphoid defects in STAT5A/5B-deficient mice.

OBJECTIVE: STAT5A/5B-deficient mice are recognized to manifest defects in multiple cell types and tissues. In particular, the hematopoietic defects in these mice are widespread, affecting multiple lineages and multiple stages of development. Previous studies indicate that deficiencies intrinsic to hematopoietic cells contribute substantially to the observed defects. However, in light of the broad physiologic effects of STAT5 in the context of the organism outside the blood system, we wished to investigate the possibility of STAT5-dependent environmental influence of nonhematopoietic origin on hematopoietic development in these mice. MATERIALS AND METHODS: We transplanted wild-type bone marrow into STAT5A/5B-deficient mice to determine the effects of loss of STAT5 in nonhematopoietic tissue on hematopoietic development. RESULTS: We observed that transplantation of wild-type marrow completely corrects hematopoietic defects in STAT5A/5B-deficient recipient mice, including peripheral blood counts, bone marrow cellularity, and reductions in specific progenitor subsets. CONCLUSION: These results indicate that the important role of STAT5 in hematolymphoid development are mediated directly through effects on hematopoietic cells and not indirectly.

Animals↗

PubMed1990

Chloropentafluorobenzene: short-term inhalation toxicity, genotoxicity and physiologically-based pharmacokinetic model development.

Ten Fischer 344 rats and six B6C3F1 mice of each sex were exposed to air, 0.25, 0.80, or 2.50 mg chloropentafluorobenzene (CPFB)/liter of air for three weeks, excluding weekends. Exposure to 2.50 mg/liter caused a reduction in the growth rate of rats but did not affect the growth rate of mice. Following the exposure there was reduced SGOT activity in the blood serum of exposed rats and a dose related increase in liver weights. Increased liver weights were observed in mice as well; the response in the female groups was clearly dose dependent. Histologically the livers of both rats and mice presented single cell necrosis. In exposed mice hepatocytes exhibited mild hepatocytomegaly with increased granular eosinophilic cytoplasm. In evaluations for its potential to induce chromosomal damage following this exposure regimen, CPFB did not alter the rate of bone marrow cellular proliferation. Assessment of the micronucleated polychromatic erythrocytes and normochromatic erythrocyte populations during the inhalation exposures indicated a general absence of genotoxic activity.

Administration, Inhalation↗

PubMed1979

[Effect of calusterone on the stem cell compartment after suppression with busulfan in mice].

These studies were undertaken to evaluate the effect of Calusterone (a weakly androgenic steroid) on hemopoiesis in mice. Cellular proliferation was suppressed by a single (IP) injection of busulfan (BU) (40 mg/Kg). Calusterone (CA) was administered s.c. SC daily (10 mg/Kg); controls received an equivalent injection of oil vehicle. Hemopoiesis was characterized by measurement of peripheral blood neutrophils, bone marrow cellularity, differentials and stem cell content. This included pluripotent (CFU-S), granulocytic (CFU-C) and erythroid (CFU-E) progenitor cells. Only a minimal decrease in narrow cellularity was observed after busulfan; similar values were obtained in calusterone recipients. Neutrophils fell by day 4, showed an abortive rise on day 8 and subsequently fell to 32% of control values. Calusterone recipients showed a 2 fold higher value (62%) on day 12. CFU-S, CFU-C, and CFU-E were depressed to 20-40% of control values by day 2 after busulfan. Although CFU-S and CFU-C remained depressed through the 14th day, CFU-E recovered by day 8 CA stimulated an overshoot in these cells to 288% of control values. These findings correlated with an increase in marrow erythroid cells to 182% on day 10. CFU-S remained low (20%) by day 14 and gradually increased to 50% of control by day 24. A delayed 10 day course of CA more than doubled the CFU-S recovery. These findings show that BU markedly suppress hemopoietic stem cells: a differential recovery is noted between CFU-E and the other progenitor cells. CA increase the recovery of all 3 hemopoietic stem cell compartments when given either immediately or in a delayed schedule. This suggests that this compound may be of use in the therapy of bone marrow hypoplasia.

Animals↗

PubMed2001

C/EBPepsilon -/- mice: increased rate of myeloid proliferation and apoptosis.

CCAAT/enhancer binding protein epsilon (C/EBPepsilon) is essential for terminal granulocytic differentiation. Its expression begins at the transition between the proliferative and non-proliferative compartments of myelopoiesis. We studied the effect of targeted disruption of the C/EBPepsilon gene on murine myeloid proliferation and apoptosis. Bone marrow cellularity of C/EBPepsilon -/- and wild-type mice was 95% and 65%, respectively. The C/EBPepsilon -/- mice had an expansion in the number of their CFU-GM/femur. The number of myeloid committed progenitor cells in the peripheral blood and the spleen of these mice was also increased. Bromodeoxyuridine (BrDU) pulse labeling studies demonstrated that the fraction of actively proliferating cells was two-fold higher in the bone marrow of C/EBPepsilon -/- mice. However, the number of myeloid colonies arising from purified Sca-1+/lin- early hematopoietic progenitor cells and from bone marrow mononuclear cells grown in different cytokine combinations was not significantly different between wild-type and knock-out mice. Also, long-term marrow growth, and CFU were not different between the wild-type and C/EBPepsilon -/- mice. The sensitivity to induction of apoptosis in the committed progenitor cell compartment after either withdrawal of growth factor or brief exposure to etoposide was normal. However, Gr-1 antigen-positive C/EBPepsilon -/- granulocytic cells showed an increased rate of apoptosis in comparison to their wild-type counterparts. In summary, the myeloid compartment appears to be expanded in mice lacking C/EBPepsilon. However, this is not the consequence of an intrinsic myeloproliferation but due to an indirect, possibly cytokine-mediated stimulation of myelopoiesis in vivo. C/EBPepsilon may have a role in the inhibition of apoptosis in maturing granulocytic cells.

Animals↗

PubMed1980

Effect of chronic lead exposure on the canine bone marrow.

The effect of chronic oral led acetate administration on canine bone marrow was studied. Two dogs (group 1) were used as controls, 4 dogs (group 2) were given 2 mg of lead/kg of body weight daily, and 4 dogs (group 3) were given 5 mg of lead/kg daily. After a 7-day stabilizaion period, lead dosing was conducted for 91 days (13 weeks), after which half of each group was treated with calcium ethylenediaminetetraacetic acid. All dogs were then observed for another 28 days (4 weeks). Blood lead values and bone marrow cellular changes were monitored once a week during the 126 days (18 weeks) of study. Lead-dosed dogs had lower weight gains than the controls. Clinical signs of toxicosis were observed after 6 weeks in one dog in group 3. Anorexia, body weight loss, CNS depression, muscular weakness, and trembling were seen. Blood lead concentrations increased in all group 2 and 3 dogs. Lead caused increases in bone marrow segmented neutrophils and myeloid series cells, and increased myeloid:erythroid ratios. Blood lead concentrations and myeloid:erythroid ratios decreased after cessation of lead administration.

Animals↗

PubMed1981

The anemia of inflammatory disease in the dog. I. The nature of the problem.

The anemia of inflammatory disease(AID) in the dog is an almost invariable complication of infection, inflammation and disseminated or necrotizing neoplastic disease. Clinically innocuous, it is important only in the greater understanding of the mechanisms controlling circulating erythrocyte quantity and quality. The etiology and pathogenesis include a shortened red cell life-span, disordered iron metabolism, depressed bone marrow response to the anemia and a disordered iron storage. The laboratory features of a moderate anemia, normal bone marrow cellular pattern, depression iron metabolism and reticuloendothelial iron sequestration make a final diagnosis of AID dependent on ruling out other etiologic mechanisms which may obscure or aggravate the anemia of the inflammatory disease in the dog.

Anemia↗