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Results for “bone marrow cellularity”

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PubMed1990

[Role of stromal microenvironment in the regulation of bone marrow hemopoiesis after curantyl administration].

Role of the stromal microenvironment in regulation of bone marrow hemopoiesis at the administration of the thrombocyte disaggregant curantyl was studied by the method of heterotopic transplantation of the mice bone marrow. It is shown that the action of curantyl on hemopoiesis is realised through the stem stromal cells of the bone marrow. It is noted that the inhibitory action of the preparation on proliferation of osteogenic precursor-cells is followed by activation of bone resorption processes in regenerating ectopic hemopoietic organ. Under the action of curantyl at low bone marrow cellularity in the focus of heterotopic hemopoiesis and femur an increase of mitotic activity in hemopoietic elements is noted. It is revealed that a phenomenon of ineffective megakaryocytopoiesis with intramedullary destruction of megakaryocytes leads to the local excretion of the thrombocyte released growth factor (TRGF) which has a compensatory character.

Animals↗

PubMed1994

[The early androgen syndrome--effect on the hormonal and immune system].

Administration of 1 mg testosterone propionate to neonate mice of both sexes on the 4th day after birth causes marked and prolonged changes in some parameters of the immune and hormonal system. At the age of one month the oestradiol level in males and females is markedly elevated, but not the testosterone level. There is a marked increase in the metabolic activity of peritoneal macrophages stimulated by zymosan and at the same time also in the percentage of cells phagocytizing inert HEMA particles. There was a marked increase in the amount of haemoglobin in females and of the bone marrow cellularity (in particular in males). Obviously also changes in cell differentiation occur, the ratio of different cell types in the peripheral blood stream changes. There is a decline of neutrophil granulocytes with a divided nucleus (in particular in males, where also the number of lymphocytes rises). The cell-mediated immune response is also altered as the graft response to the host is more intense. The humoral immunity against T-dependent antigen is also affected. The titre of IgG antibodies is reduced and the titre of IgM antibodies elevated. The results are discussed, but so far it is difficult to decide whether the observed changes of the immune system are primary, i.e. directly induced by testosterone, or whether they are secondary, i.e. induced by an elevated testosterone level.

Animals↗

PubMed1985

Effect of feed restriction on the peripheral blood and bone marrow cell counts of Wistar rats.

The effects of 33% and 66% restricted feeding on body and organ weights, and hematological and bone marrow cellular findings in rats were investigated. The body weight gains were suppressed by restriction of feed amount and the body weights of 66% restricted-feeding groups were almost unchanged for three months (110 g in males and 80 g in females). Marked organ weight reduction (both absolute and relative) was found in the liver and thymus of rats of both sexes. Neutrophils and lymphocytes in the peripheral blood were reduced. Reticulocytes in the 66% restricted groups were decreased to 1/4 of the control values at one month, but recovered slightly thereafter. Nucleated cell counts in bone marrow in the 66% restricted groups were decreased to 1/3 of the control values after three months. Thus, the most important effect of feed restriction seemed to be on bone marrow cells rather than on peripheral blood cells except for the reticulocytes. There was no significant difference between males and females.

Animal Feed↗

PubMed2004

Experimental study on the toxicity and the local and systemic tolerability of gemcitabine after topical treatment of the rabbit bladder.

This study investigated gemcitabine administered intravesically to establish the local and systemic tolerability necessary for clinical trials. Gemcitabine was directly administered via catheter into the bladders of 24 male New Zealand rabbits weighing an average of 1.9+/-0.08 kg. Three groups received weekly gemcitabine for 5 (50 mg/kg) or 8 (25 mg/kg or controls) weeks. Animals were inspected daily for signs of toxicity and distress, body weight changes, and water and food consumption; electrocardiogram, blood pressure, and urinalysis were recorded before dosing and after 4 and 8 weeks of treatment. The rabbits were euthanized, and a full necropsy was performed on day 1 after the last instillation. Principal organs (spleen, thymus, testis, and muscle) and plasma samples were analyzed for the systemic absorption of gemcitabine. The 25-mg/kg dose was well tolerated with no clinical side effects. At 50 mg/kg, signs of mild myelosuppression and severe symptomatic toxicity (leg weakness, and hair and body weight loss) was evident after 3 weeks of treatment and three of the seven animals in this group died after four doses. Necropsies revealed normal bone marrow cellularity and organ histology at both doses. No significant systemic drug absorption was seen. These findings suggest that intravesical administration of gemcitabine does not produce organ-specific toxicity, but the higher dose (50 mg/kg) may represent the threshold above which increasing morbidity may occur.

Absorption↗

PubMed1980

Lethal toxicity and myelotoxicity to mice of the combination of 6-thioguanine and 3-[(4-amine-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride.

In order to determine the mechanism of therapeutic synergism elicited by a combination of 6-thioguanine and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU) against various murine tumors, side effects of host animals due to the combination of these two drugs were examined. The combination toxicity index of these drugs given simultaneously was determined to be 1.5, i.e., this indicates that the combination of ACNU and 6-thioguanine is less-than-additive with respect to the lethal toxicity. More-over, this combination treatment appeared to be at least no more than additive with respect to bone marrow toxicities as judged on the basis of bone marrow cellularity and peripheral white blood cell counts. In addition, the effects of treatment schedules, which were clearly observed in the therapeutic effect, on the side effects due to this combination treatment were also examined. However, no specific decrease or increase in side effects on host animals on this specific treatment schedule or the other treatment schedule was seen.

Animals↗

PubMed1988

Colony stimulating factors.

The genes for a number of growth factors that stimulate human hematopoietic and lymphoid cells in vitro have recently been cloned and recombinant molecules provided for clinical trials. For three of these (erythropoietin, G-CSF, and GM-CSF), phase I and II studies have been completed and promising results have been obtained. Of particular relevance to the field of bone marrow transplantation (BMT) has been the finding that G-CSF and GM-CSF could shorten the period of neutropenia in patients treated with chemotherapy, including regimens requiring BMT support. Doses of up to 240 micrograms/m2 of GM-CSF have been well tolerated and have increased the peripheral blood neutrophil count in a dose-dependent manner. At higher doses, eosinophils and monocytes were also increased. A continuous infusion over at least 2 h was found to be superior to bolus administration in terms of both efficacy and reduced side effects. These have usually been mild, but bone pain, headache, fatigue and elevated temperature have been encountered. The rise in neutrophil numbers shortly after initiating treatment with GM-CSF is probably due to neutrophil demargination. After a few days increased bone marrow cellularity has also been noted. In addition to these effects on cell numbers, enhancement of granulocyte and monocyte functions has been documented. However, a major concern with the use of G-CSF and GM-CSF in cancer patients, particularly those with hematopoietic malignancies, is the potential of these molecules to stimulate malignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗

PubMed1993

Morphometric study of the bone marrow in polycythemia vera following interferon-alpha therapy.

Bone marrow cellularity and extent of fibrotic change were determined in nineteen patients with polycythemia vera, treated with interferon-alpha (IFN) for 1 year. The cellularity was evaluated with an interactive semiautomatic method using Leitz TAS plus microscope: in particular, number and size of megakaryocytes were evaluated after immunostaining with Y2/51 (CD 61); reticulin content was studied by light microscope with a semiquantitative method. Before IFN therapy mean cellularity was 80.5% (+/- 13.7). After 6 and 12 months mean cellularity was 75.4% and 68.4% respectively. Six months after cessation of IFN therapy the cellularity was 69.1%. A decrease of the number, density and morphometrical parameters of megakaryocytes was also remarked. Reticulin fibrosis was mild in 13 cases and moderate in 6 cases before IFN therapy. Reticulin content was unmodified during therapy in all cases but two, in which fibrosis changed from mild to moderate. In conclusion IFN therapy is to be considered a good method in polycythemia vera for the control of proliferative activity of bone marrow but with IFN therapy one cannot determine regression of marrow fibrosis.

Adult↗

PubMed1989

Prevention of benzene-induced myelotoxicity by nonsteroidal anti-inflammatory drugs.

Benzene affects hematopoietic progenitor cells leading to bone marrow depression and genotoxic effects such as micronucleus formation. Progenitor cell proliferation and differentiation are inhibited by prostaglandins produced by macrophages. Administration of benzene to DBA/2 or C57BL/6 mice caused a dose-dependent bone marrow depression and a significant increase in marrow prostaglandin E level and both were prevented by the coadministration of indomethacin and other inhibitors of the cyclooxygenase component of prostaglandin H synthase. Levels of benzene that decreased bone marrow cellularity also caused genotoxic effects measured as increased micronucleated polychromatic erythrocytes in peripheral blood, which was also prevented by the coadministration of indomethacin. These results suggest a possible role for prostaglandin synthase in benzene myelotoxicity; a mechanism by which this might occur is presented.

Animals↗

PubMed2004

Telomerase activity in Philadelphia positive chronic myeloid leukaemia.

Telomerase is a specialized type of reverse transcriptase that catalyzes the synthesis and extension of telomeric DNA. Activation of telomerase and stabilization of telomeres are considered necessary for immortalization of tumor cells. Chronic Myeloid Leukaemia (CML) is a good example to investigate the reactivation of telomerase as; after a variable period in chronic phase, CML undergoes further evolution. The aim of this work is to study telomerase activity in patients with philadelphia- positive CML and to compare the relative amount of telomerase activity between chronic phase, accelerated phase and blastic crisis. The study is conducted on 3 groups. Group I comprised ten newly diagnosed CML patients in chronic phase; five males and five females their ages ranged from 24-63 years (X = 44.1 +/- 11.2 years). Group II comprised ten patients in acute transformation (accelerated or blastic crisis phase); seven were males and three were females their ages ranged from 14 to 63 years ( X = 35.7 +/- 16.2 years). Ten healthy subjects comprised the control group III; five males and five females their ages ranged from 14-50 years ( X = 31.8 +/- 12.4 years). All patients were subjected to thorough history taking and clinical examination, complete blood picture with differential cell counts, bone marrow aspiration and/or biopsy, neutrophil alkaline phosphatase scoring by cytochemistry, immunophenotyping to identify the type of blast crisis, chromosomal analysis to detect Ph-positive cases, and measurement of telomerase activity by PCR-ELISA technique. Telomerase activity was highest in acute transformation with a range of (0.252-1.896) and mean of 1.521 0.496, while in chronic phase ranged between 0.67 and 0.743 with a mean of 0.305 +/- 0.109 and in normal controls the range was 0.45 to 0.195 with a mean of 0.102 +/- 0.048. The difference between groups was statistically significant. No correlation was found between the activity of the telomerase and hemoglobin, platelet, leucocyte counts, percentage of peripheral blood, bone marrow blasts, basophils, bone marrow cellularity, the type of crisis as well as leucocyte alkaline phosphatase scoring. In conclusion; The increased level of telomerase activity as noticed in the different stages of CML indicates its association with disease progression and can be used as a useful marker for evaluating development of the course.

Adolescent↗

PubMed1989

Protective, restorative, and therapeutic properties of recombinant colony-stimulating factors.

Pretreatment of mice with recombinant murine (rM) colony-stimulating factor-granulocyte-macrophage (CSF-gm) or recombinant human (rH) CSF-g provides partial protection from the lethal effects of ionizing radiation or the alkylating agent cyclophosphamide (CTX). In addition, these agents can significantly prolong survival if administered following lethal doses of irradiation or CTX. To induce protective activity, cytokines were injected 20 hours before lethal irradiation or CTX administration. To accelerate recovery from lethal irradiation, the cytokines must be administered shortly following irradiation, and the induction of maximal levels of activity is dependent on chronic administration. In contrast, because of their longer half-lives, accelerated recovery from alkylating agents requires a delay of at least 24 to 48 hours to allow complete clearance of CTX before administration of a CSF. Studies quantitating peripheral blood leukocytes and bone marrow cellularity as well as colony-forming units per culture (CFU-C) frequency and CFU-C per femur revealed a significant correlation between these parameters and the ability to survive lethal irradiation. This is a US government work. There are no restrictions on its use.

Animals↗

PubMed1989

Hematopoietic responses in patients with advanced malignancy treated with recombinant human granulocyte-macrophage colony-stimulating factor.

The in vivo effect of yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) was investigated in 30 patients with advanced malignancy in a phase Ib trial. Patients were treated at four different dose levels (120 to 1,000 micrograms/m2/d) by either daily intravenous (IV) bolus injection or 24-hour continuous infusion. Administration of rh GM-CSF resulted in a broad spectrum of dose- and schedule-dependent hematopoietic effects. Sustained infusion of rh GM-CSF elicited a maximum 17-fold average peak increase of the total WBC count with mainly neutrophils, eosinophils, and monocytes accounting for this rise, and increases in bone marrow cellularity with a shift to immature myeloid elements. Elevation of lymphocytes, platelets, and reticulocytes was not induced. Within five days after discontinuation of treatment the leukocytosis had disappeared. Adverse reactions encountered with rh GM-CSF seen in 65% of the patients studied were never life-threatening and always rapidly reversible. They included mild myalgias, facial flushing, low-grade fever, headache, bone discomfort, nausea, dyspnea, and transient decline of platelet counts. These results suggest that rh GM-CSF can be safely administered at the doses and schedules used and that it can induce in vivo some of the biological effects reported in in vitro studies. Although no objective antitumour responses have been seen, the ability of rh GM-CSF to increase number and function of leukocytes in vivo may prevent neutropenia and infections when GM-CSF is added to cytotoxic cancer therapy.

Adolescent↗

PubMed2005

A morphometric approach for the evaluation of angiogenesis in acute lymphoblastic leukemia of childhood.

Angiogenesis was estimated in childhood acute lymphoblastic leukemia (ALL) by the use of a novel morphometric method. This was compared with the widely used one of microvessel density (MVD). Bone marrow biopsies were evaluated by immunostaining with anti-Factor VIII related antigen (FVIIIRAg). Angiogenesis was calculated as volume corrected microvessel density index (VC-MVDI), taking into account the bone marrow cellularity. According to our results both MVD and VC-MVDI were increased at diagnosis of ALL in comparison with the control group. However the VC-MVDI increment was not statistically significant. Therefore, VC-MVDI could be more representative of the true increase of angiogenesis, correlating better with the outcome of the disease.

Analysis of Variance↗

PubMed2002

Efficacy of rituximab in the treatment of refractory chronic lymphocytic leukemia patient with bone marrow aplasia.

Recently, several reports have been published claiming the efficacy of anti-CD20 monoclonal antibody (rituximab) in the treatment of B-cell chronic lymphocytic leukemia (B-CLL) and some related autoimmune complications. We used anti-CD20 monoclonal antibody in a patient with advanced stage and heavily pre-treated B-CLL with a concomitant bone marrow aplasia requiring a remarkable transfusional support of both red blood cells and platelets. The treatment was conducted according to standard dosage and schedule and the patient did not experience any severe side effect. A progressive reduction of transfusions and a certain recovery of bone marrow cellularity was observed after six months from the end of therapy. This case suggests that rituximab can play a role in this subset of B-CLL patients with very few effective therapeutic options and in which the clinical features may be due both to neoplastic proliferation and concomitant autoimmune disorder.

Aged↗

PubMed2003

Fps/Fes and Fer protein-tyrosinekinases play redundant roles in regulating hematopoiesis.

OBJECTIVE: The highly related protein-tyrosine kinases Fps (also called Fes) and Fer are sole members of a subfamily of kinases. In this study, knock-in mice harboring kinase-inactivating mutations in both fps and fer alleles were used to assess functional redundancy between Fps and Fer kinases in regulating hematopoiesis. METHODS: Mice harboring kinase-inactivating mutations in fps and fer alleles were generated previously. Compound homozygous mice were bred that lack both Fps and Fer kinase activities and progeny were analyzed for potential defects in viability and fertility. Potential differences in hematopoiesis were analyzed by lineage analysis of bone marrow cells, peripheral blood counts, and hematopoietic progenitor cell colony-forming assays. RESULTS: Mice devoid of both Fps and Fer kinase activities were viable and displayed reduced fertility. Circulating levels of neutrophils, erythrocytes, and platelets were elevated in compound mutant mice compared to wild-type controls, suggesting that hematopoiesis is deregulated in the absence of Fps and Fer kinases. Compound mutant mice also showed reduced overall bone marrow cellularity, and lineage analysis revealed elevated CD11b(hi)Ly-6G(lo) myeloid cells, which may reflect increased granulocyte progenitors. Although no differences in the overall number of granulocyte/monocyte colony-forming progenitors were observed, qualitative differences in myeloid colonies from compound mutant mice suggested a role for Fps and Fer kinases in regulating cell-cell adhesion or a skewing in cellularity of colonies. CONCLUSIONS: Mice lacking both Fps and Fer kinase activities develop normally, show reduced fertility, and display defects in hematopoiesis, thus providing evidence for functional redundancy between Fps and Fer kinases in regulating hematopoiesis.

Alleles↗

PubMed1996

Defective B cell development in Snell dwarf (dw/dw) mice can be corrected by thyroxine treatment.

Snell dwarf (dw/dw) mice are deficient in anterior pituitary hormones due to a mutation in the gene encoding the Pit-1 transcription factor. Bone marrow B cell development is also suppressed in the mice, providing circumstantial evidence that one or more anterior pituitary-derived products, or factors induced by them, are required for normal B lymphopoiesis. However, concluding that this is the case is dependent on showing that hormonal treatment of dwarf mice reverses their B cell defects. dw/dw mice were treated with growth hormone (GH), insulin-like growth factor-I (IGF-I), or thyroxine in an attempt to restore bone marrow B lymphopoiesis. GH and IGF-I increased the number of B lineage cells in the bone marrow and spleen but did not restore the frequency of bone marrow pre-B cells to normal. However, bone marrow cellularity in thyroxine-treated dw/dw mice was comparable to that in control animals, and both the frequency and absolute number of B lineage cells had increased to normal or even above normal. Taken together, these data indicate that endocrine factors, especially those regulated by the hypothalamic-pituitary-thyroid axis, are potent B lymphopoietic factors.

Animals↗

PubMed1986

[Comparative evaluation of the action of cis-dichlorodiammineplatinum and oxoplatinum on hemopoiesis un mice].

Myelosuppressive effects of cis-dichlorodiamminoplatinum (DDP) and oxoplatinum have been revealed. The administration of these drugs leads to early and deep depletion of CFU compartment. The most rapid rate of reduction was registered during 24-48 hours after DDP administration and within first three hours after oxoplatinum administration. Reduction of the total bone marrow cellularity caused mainly by a decrease of erythroid cells and, to a less extent, by a decrease of lymphoid and myeloid cells is observed. Leukopenia and anemia have developed during the treatment. Myelosuppressive effects are more pronounced with the oxoplatinum administration. A strict correlation is established between the haemopoietic tissues damage and the level of platinum content in the animal organism.

Animals↗

PubMed1976

The effect of thymosin application upon radiation sickness in mice.

The mechanism of thymosin effect upon radiation sickness was analyzed in mice. Thymosin (fraction 5) applied before and after a whole-body radiation exposure increased the LD 50/30 of treated animals by 250R. In mice exposed to 500R, thymosin treatment resulted in a faster recovery of haemopoiesis and lymphopoiesis, as indicated by higher bone marrow cellularity, higher lymph node, thymus and spleen weights, and greater 59Fe uptake in the spleen and femur and 125IUdR uptake in the spleens, femur and thymus. The results provide an indication that thymus and its humoral factor markedly influence the haemopoietic stem cells in the population surviving the sublethal irradiation of an organism. They further suggest the existence of feed-back mechanisms between the thymus and harmopoiesis.

Animals↗

PubMed1978

[Double medular scintigraphy using 99mTc-colloids and 111In-transferrin in myeloid splenomegaly (author's transl)].

Simultaneously with bone marrow biopsy and 59Fe kinetic study, bone marrow scintigraphy using 99mTc-colloids and 111In-transferrin was performed in 15 patients with a documented diagnosis of agnogenic myeloid metaplasia. This rapid, simple and non-traumatic method permits visualization of changes in the reticular and the erythropoietic marrow which are not always the same. The technique can demonstrate diminution of active marrow in the axial skeleton, peripheral extension of bone marrow and its heterogeneity from site to site. These abnormalities, which vary from case to case, correlated well with the results of 59Fe external countings. The degree of splenic myeloid metaplasia, as judged by 111In uptake, is also well correlated with 59Fe uptake into the spleen. There was poor correlation between scintigraphic and iron kinetic data on the hand, and bone marrow cellularity assessed by marrow biopsy on the other. While scintigraphic studies are chiefly qualitative, they appear to provide useful information for diagnosis, and possibly for prognostic and therapeutic decision.

Aged↗