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PubMedDate not supplied

[Technic for the preparation of bone marrow biopsies. Evaluation of bone marrow cell count].

After having briefly reviewed the different subjective and objective procedures for interpreting Bone Marrow Biopsies from the standpoint of evaluating Bone Marrow Cellularity, the authors propose a method for overall morphological examination, controlled by a rapid evaluation by means of an integrator ocular. This simple, reliable and easily reproducible "semi-subjective" technique seems useful in routine pathological diagnosis, particularly to compare successive Bone Marrow Biopsies from the same patient when treated by antimitotics, or to study the changes of the hematopoietic tissue in the area of medullary metastasis.

Biopsy↗

PubMed1990

[Effects on bone marrow during stimulation of hematopoietic stem cells with recombinant human interleukin-3].

Bone marrow aspirates and biopsies of 20 patients with malignant tumors (n = 6), bone marrow failure due to chemotherapy (n = 4), myelodysplastic syndromes (n = 5) and aplastic anemia (n = 5) were analysed before and after treatment with recombinant human interleukin-3. rhIL-3 led to increased overall bone marrow cellularity with trilinear stimulation of hematopoietic cells. In all patients marked eosinophilia and, in some, fibrosis was observed. These results show that rhIL-3 stimulates the proliferation and differentiation of pluripotent hematopoietic progenitor cells and may contribute to the treatment of bone marrow failure.

Anemia, Aplastic↗

PubMed1982

Effects of benzene inhalation on murine pluripotent stem cells.

Effects of benzene inhalation on mouse pluripotent hematopoietic stem cells have been evaluated. Male mice 8--12 wk old were exposed to 400 ppm benzene for 6 h/d, 5 d/wk, for up to 9 1/2 wk. At various time intervals exposed and control animals were killed, and cardiac blood was evaluated for changes in white blood cell (WBC) and red blood cell (RBC) content. In addition, femora and tibiae were evaluated for total marrow cellularity, stem cell content (as measured by the spleen colony technique), and the percent of stem cells in DNA synthesis (as determined by the tritiated thymidine cytocide technique). Exogenous spleen colonies grown from marrow of exposed animals were counted, identified, and scored by histological type. Exposure to benzene caused significant depressions of RBCs and WBCs throughout the exposure period, which continued for at least 14 d after exposure. Bone marrow cellularity and stem cell content were also depressed in exposed animals throughout the study. Tritiated thymidine cytocide of spleen colony-forming cells was generally increased in exposed animals, perhaps indicating a compensatory response to the reduction of circulating cells. Spleen colonies of all types were depressed after exposure to benzene. The significance of the reduction in cellularity, stem cell content, and changes in morphology of spleen colonies is discussed in relation to cellular toxicity and residual injury.

Animals↗

PubMed2003

Diffusion-weighted imaging of bone marrow: current status.

Diffusion-weighted imaging allows for measurement of tissue microstructure and reflects the random motion of water protons. It provides a new method to study bone marrow and bone marrow alterations on the basis of altered water-proton mobility in various diseases. Different diffusion-weighted methods have proved to be capable of differentiating between benign edema and tumorous involvement of bone marrow. It is especially useful for the distinction of acute benign osteoporotic and malignant vertebral compression fractures. Diagnosis is based on the contrast to normal bone marrow. Hypo- or isointensity reflects acute benign collapse, whereas hyperintensity is indicative of the tumorous nature of a fracture. Apparent diffusion coefficients (ADC) are significantly lower in metastatic disease than in bone marrow edema. Furthermore, bone marrow cellularity can be estimated by ADC measurements. Diffusion-weighted imaging might be helpful for monitoring response to therapy in metastatic disease.

Bone Marrow↗

PubMed1999

Swainsonine protects both murine and human haematopoietic systems from chemotherapeutic toxicity.

The haematopoietic system is sensitive to cytotoxic damage and is often the site of dose-limiting toxicity. We previously reported that swainsonine, an inhibitor of protein glycosylation, reduced the bone marrow toxicity resulting from a single dose of anticancer drugs in otherwise healthy mice. However, more important questions are (1) can swainsonine protect tumour-bearing mice without interfering with the anti-tumour effects of the drugs, and (2) can swainsonine stimulate haematopoietic activity of human, as well as murine, bone marrow. We demonstrate here that swainsonine protects C57BL/6 mice bearing melanoma-derived tumours from cyclophosphamide-induced toxicity without interfering with the drug's ability to inhibit tumour growth. Similar results were obtained in vivo with 3'-azido-3'-deoxythymidine (AZT), a myelosuppressive agent often used in therapy for acquired immune deficiency syndrome. Swainsonine increased both total bone marrow cellularity and the number of circulating white blood cells in mice treated with doses of AZT that typically lead to severe myelosuppression. Swainsonine also increased the number of erythroid and myeloid colony forming cells (CFCs) in short-term cultures of murine bone marrow, restoring the number of progenitor cells to the control level in the presence of AZT doses that reduced CFCs by 80%. With respect to the sensitivity of human haematopoietic cells to swainsonine, we show that swainsonine protected human myeloid progenitor cells from AZT toxicity in vitro. These results suggest that swainsonine may be useful as an adjuvant in several types of human chemotherapy.

Adjuvants, Immunologic↗

PubMedDate not supplied

[Effect of autologous blood irradiated in isolation on the restoration of leukopoiesis in an experimental model of prolonged leukopenia].

Reinfusion of irradiated (220 Gy) isolated blood (IIB) was shown to accelerate leukopoiesis restoration in conditions of myelodepression induced by the injection of cyclophosphane. Restoration of leucocyte count in the peripheral blood was preceded by the increase in DNA synthesis and bone marrow cellularity. Reinfusion of IIB also promoted a more rapid restoration of cellularity of lymphoid organs with cAMP predominating therein. The comparison of the processes under study in time permits to assume that the stimulatory effect of IIB is related to activation of proliferation and stimulation of cell maturing in bone marrow and lymphoid organs.

Animals↗

PubMed1977

In vivo study of platelet kinetics by 75Se-methionine in different haematological disorders.

Labeling of platelets in vivo by 75Se-methionine was performed in premalignant and malignant haematological disorders for evaluation of the kinetics of platelet maturation. The "normal" platelet maturation time (time between the injection of the isotope and maximum radioactivity of separated blood platelets) in eight non-haematological patients showing normal platelet counts was 9.1 days. A shortening of platelet maturation time of 5-7 days was observed in three of four cases with panmyelopathy (high bone marrow cellularity), in three of four cases with malignant lymphatic disorders (multiple myeloma, chronic lymphocytic leukaemia, lymphosarcoma), and in two of four cases with myeloproliferative syndromes. No correlation to the peripheral platelet counts was observed. For explanation of the premature platelet release from the bone marrow a disturbance of the megakaryocyte maturation is suggested.

Adult↗

PubMed1985

In vivo modulation of myelopoiesis and immune functions by maleic anhydride divinyl ether copolymer (MVE-2) in tumor-free and MBL-2 tumor-bearing mice treated with cyclophosphamide.

Treatment of normal or MBL-2 tumor-bearing mice with cyclophosphamide (CY) caused severe suppression of myelopoiesis and macrophage (M phi) functions, both of which may limit further use of chemotherapy. Additional treatment with the chemically defined biological response modifier maleic anhydride divinyl ether copolymer (MVE-2) was able to ameliorate the myelosuppressive effects of CY and to restore normal bone marrow cellularity. The stimulatory effects on myelopoiesis, however, could only be obtained by administering MVE-2 at greater than or equal to 3 days after CY, which correlated with an MVE-2-induced simultaneous increase in granulocyte and/or macrophage colony-stimulating factor secretion by bone marrow cells or M phi. Injection of MBL-2 tumor-bearing mice with MVE-2, at 3 days after Cy treatment, caused a decrease in tumor burden and a significant increase in median survival time as compared to treatment with CY alone. At the same time, MVE-2 induced an increase in the number of cytotoxic M phi and a complete restoration within the myelopoietic lineage, which might prevent delayed side effects of CY, such as secondary infections, and might permit more intensive chemotherapeutic treatment. Treatment of MBL-2 tumor-bearing mice with MVE-2, at 6 days after CY, induced a significant increase in M phi cytotoxicity but did not prolong median survival time, probably due to a rapid regrowth of tumor after treatment with CY. Our studies thus show that successful combined therapy with the primary cytotoxic agent CY and the biological response modifier MVE-2 depends on precise timing of the drug regimen and is influenced by the extent and reversibility of CY-induced immunosuppression, as well as by the kinetics of recruitment of new effector cells from bone marrow and by the tumor burden present at the time of treatment.

Animals↗

PubMed1980

Effect of pyran copolymer on murine hemopoiesis.

Pyran Copolymer (NSC-46015), a divinyl-ether maleic anhydride leads to a significant shift in distribution of nucleated cells and CFUs in the bone marrow and spleen. The bone marrow cellularity and the CFUs content reach a nadir 4 to 6 days after Pyran injection, simultaneous rise in spleen cellularity and CFUs concentration of circulating pluripotent stem cells by a factor of 10 to 45 and a concomitant rise of CFUc is seen. the origin of the mobilized pluripotent stem cells is likely to be the bone marrow, not athe spleen.

Animals↗

PubMed1988

The effects of allyl isovalerate on the hematopoietic and immunologic systems in rodents.

Female B6C3F1 mice plus male and female Fischer 344/N rats were gavaged with allyl isovalerate (AIV) in corn oil at 0, 31, 62, or 125 (mice) and 0, 31, 62, 125, or 250 (rats) mg/kg body weight for five daily exposures per week for a 2-week period. Hematologic, immunologic, and histopathologic studies were performed 48 to 72 hr following the final treatment. AIV exposure had no effect on hematology or bone marrow cellularity in mice or rats. AIV exposure at 250 mg/kg was toxic to rats causing reduced weight gain and hepatotoxicity. In vivo and in vitro studies revealed that pluripotent hematopoietic stem cells (CFU-S) and granulocyte-macrophage progenitors (CFU-GM) in the bone marrow were decreased in the treated mice. Hematopoietic suppression was correlated with the reduction in the hexose monophosphate shunt metabolism of bone marrow cells but the Embden-Meyerhof pathway and tricarboxylic acid pathway enzymes did not appear to be affected. Examination of host resistance following Plasmodium and Listeria challenge did not demonstrate significant differences between treated and control mice, nor were there other effects on the immune system. This suggests that the myelotoxic effects were minimal and of a degree that would not alter host resistance.

Animals↗

PubMed2004

Protective effect of an extract of Phyllanthus amarus against radiation-induced damage in mice.

The radioprotective effect of an extract of the plant Phyllanthus amarus (P. amarus) was investigated in adult BALB/c mice. P. amarus extract (750 mg/kg b.wt and 250 mg/kg b.wt) was administered orally to mice for five days prior to whole body radiation (6 Gy) and for one month after radiation. The animals were sacrificed on days 3, 9, 12, and 30 after radiation. P. amarus significantly increased the total W.B.C count, bone marrow cellularity, and alpha-esterase activity as compared to untreated radiation-exposed animals. P. amarus treatment also increased the activity of various antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPX), and glutathione reductase (GR), both in blood and tissue, which were reduced by radiation treatment. There was also a significant increase in the glutathione (GSH) levels of blood and tissue. Lipid peroxidation levels, which were increased after radiation, were significantly reduced by P. amarus treatment, both in serum and liver. The results collectively indicate that P. amarus extract could increase the antioxidant defense mechanism in mice and there by protect the animals from radiation-induced cellular damage.

Administration, Oral↗

PubMed1976

Notions about human stem cells.

From an analysis of the known red cell and granulocytic cell turnover rates in the peripheral blood, absolute bone marrow cellularity of man, mitotic index of human marrow, tritiated thymidine labeling index of human marrow, the proportional distribution of the different cell types in the bone marrow of man and the measured DNA synthesis time of differentiated cell lines in human bone marrow, the flux of stem cells into the differentiated compartment has been calculated. By assuming that the same fraction of committed stem cells of man and mouse are in DNA synthesis, the number of cells in DNA synthesis and the size of the stem cell compartments have been calculated. The calculation gives an abundance of stem cells in human marrow that is much larger than that estimated by in vitro culture techniques. On the basis of the calculations, it is hypothesized that the pool of cells preceding the cytologically differentiated pools may consist of self replicating committed stem cells and differentiated cells undergoing amplification that have not developed cytologic markers characteristics of differentiated cells.

Bone Marrow↗

PubMed1986

Effect of colony-stimulating factor-producing tumor on hemopoiesis in splenectomized mice.

The colony-stimulating factor-producing BMA-1 tumor was transplanted into splenectomized mice. These mice showed as much granulocytosis as non-splenectomized mice bearing the tumor. The increase in the number of peripheral leukocytes induced per tumor weight was similar in the two groups. The hemopoietic cell population in the central bone marrow (tibia) was not increased by splenectomy. The total numbers of spleen colony-forming cells and granulocyte-macrophage colony-forming cells in the whole body of tumor-bearing splenectomized mice were 29% and 58% of those in the tumor-bearing non-splenectomized mice, respectively. The expansion of hemopoiesis to the peripheral bone marrow in tumor-bearing splenectomized mice was confirmed by histological examination of the tail bone. These results suggest that the lack of increase in the bone marrow cellularity is due to the space limitation, and that this is well compensated for by a great expansion of hemopoietic marrow to the peripheral bones in splenectomized mice.

Animals↗

PubMed1985

[Occurrence and clinical course of drug-induced agranulocytosis].

A report of 27 drug induced agranulocytosis is presented in a period of 13 years. The rate of the disease was 0.12% of the total number of patients. Cases due to cytostatical and radiation treatment were not included. According to bone-marrow cellularity patients were divided into hypo- and hyper-cellular groups. The clinical findings were similar in both groups and the majority of patients recovered. Two patients died, both in the hypocellular group: the first due to mycotic pulmonary infection, the other after massive pulmonary embolism but after complete haematological recovery. Bone-marrow plasmocytosis was slightly expressed in the hypocellular group. The normal leukocyte number appeared after treatment within 3-25 days. Recurrent agranulocytosis was observed in four patients and permanent leukopenia developed in five. The leukocyte-agglutination test was positive in 10 cases only, but the leukocyte migration test was positive in all investigated cases except two. Five patients had a previous history with idiosyncrasy. Treatment was started with antibiotics, corticosteroids and with antimycotic drugs. Sterile island and granulocyte-transfusion was applied in seriously ill patients with septicemic complications only.

Adolescent↗

PubMed1984

In vivo acute hematotoxicity of N,N'-bis[N-(2-chloroethyl)-N-nitrosocarbamoyl]cystamine (CNCC), a new nitrosourea analog.

The in vivo hematotoxic effects on different hemopoietic cell compartments of a new nitrosourea analog CNCC were compared to another glycosidyl derivative, RFCNU. Bone marrow microenvironment in liquid culture, bone marrow and splenic colony-forming units in agar culture (GM-CFUc), relative spleen index, and spleen and bone marrow cellularity were evaluated in young adult (DBA/2 X C57B1/6)F1 mice. The drugs, dissolved in olive oil, were injected ip at either the minimal or the median or the maximal dose of the "maximally efficient dose range." A single administration of CNCC induced a dramatic depopulation of bone marrow and spleen within 12 and 24 hr and significantly reduced the GM-CFUc in both organs. A rapid recovery of both the total cell number and GM-CFUc was observed between Days 2 and 5 (kinetic experiment). The comparison of toxicity of 20 to 50 mg/kg CNCC and 15 to 30 mg/kg (2-chloroethyl)ribopyranosyl-3-nitrosourea RFCNU at Day 1 and Day 5 showed that the bone marrow microenvironment was modified by the effect of oil and was further impaired by CNCC in a concentration-dependent fashion. In contrast RFCNU had less effect on the microenvironment. Similarly, the bone marrow GM-CFUc population was reversibly impaired by CNCC in a dose-dependent fashion, and again RFCNU had less effect. In the spleen both drugs provoked a higher toxic effect than in the bone marrow; on Day 1 they decreased the GM-CFUc population by 1 to 2 log. On Day 5 a compensatory regeneration was obtained in all cases except the highest tolerable CNCC dose, whose effect was more delayed.

Acute Disease↗

PubMed1993

Additive effect of erythropoietin and heme on murine hematopoietic recovery after azidothymidine treatment.

The ability of combination treatment with erythropoietin (Epo) and heme to rescue hematopoietic activity in mice from the suppressive effect of azidothymidine (AZT) was determined. Exposure of mice to AZT for 5 weeks produced marked anemia, thrombocytopenia, neutropenia, and weight loss, whereas mice that received Epo and heme for 3 subsequent weeks showed significant alleviation of AZT cytotoxicity. Treatment with Epo (10 U for 5 times/week) stimulated hematopoietic recovery in the AZT-treated animals and reduced the severe anemia and thrombocytopenia by 3 weeks. Administration of a lower Epo dose (1 U Epo) resulted in only a modest retardation of AZT-induced anemia, although, when combined with heme, there was a great improvement in recovery of erythropoiesis. The combination of heme with Epo (10 U) produced the optimum response, resulting in almost normal recovery of bone marrow cellularity as well as recovery of burst-forming units-erythroid (BFU-E) and splenic hematopoietic progenitor content (colony-forming unit-spleen [CFU-S]) by the end of 3 weeks of post-AZT treatment. Treatment with heme alone markedly enhanced the recovery of BFU-E and CFU-S, as well as body weight post-AZT; however, this recovery was not to the extent seen in combination with Epo (10 U). Long-term bone marrow cultures (LTBMCs) established from mice exposed to AZT for 8 weeks showed a marked reduction in cellularity and this was completely alleviated when mice received heme and Epo (10 U) for 3 weeks after 5 weeks of AZT administration. The additive effect of heme and Epo was seen in BFU-E production, as well as in CFU-S production, in LTBMCs. Thus, heme exerts a significant protective effect on hematopoietic progenitors in vivo and may be of potential clinical use in combination with Epo to promote effective erythropoiesis in the setting of AZT therapy.

Anemia↗

PubMed1987

Refractory cytopenias: clinical course according to bone marrow cytology and cellularity.

One hundred and one patients with refractory cytopenia were reviewed for morphological classification (using bone marrow, BM, imprints for cytology and Jamshidi biopsies for BM cellularity) and clinical course. Final diagnoses were: moderate aplastic anemia (MAA), myelodysplastic syndromes (MDS) and hypoplastic acute leukemia (HAL). Ninety-two patients received high dose testosterone enanthate (TE) as first treatment (starting dose = 7-10 mg/week i.m. for at least three months). Median survival was significantly longer in MAA than in MDS and in HAL. Among MDS patients, those with primary acquired sideroblastic (AISA) and refractory (RA) anemia had median survival similar to those with MAA, but distinctly longer (p = 0.01) than patients with RA with an excess of blasts (RAEB), RAEB in transformation (RAEBtr) and chronic myelomonocytic leukemia (CMMoL). Acute leukemia (AL) developed more rarely (p less than 0.02) in MAA, AISA and RA than in RAEB, RAEBtr and CMMoL. Response to TE was seen in about two thirds of MAA and in a half of MDS and HAL patients. Among MDS patients, those with hypocellular BM developed leukemia less frequently, responded to androgens more often and survived longer than those with normocellular and, especially, with hypercellular BM. These data indicate that the cytohistological classification of refractory cytopenias identifies essentially two groups with different clinical behaviour, one (MAA, AISA and RA) having long life expectancy and a low probability of developing AL and the other (RAEB, RAEBtr, CMMoL) with a short survival and relatively frequent leukemic complication. Bone marrow hypocellularity seems to be a favourable prognostic factor in MDS. Patients with refractory cytopenias, especially those with a hypocellular BM, can be advantageously treated with androgens.

Acute Disease↗

PubMed1979

[Hematologic aspects of alcoholism (author's transl)].

Alcohol causes different hematologic alterations on each of the three bone marrow cellular series. Its effect on the red series leads to the appearance of megaloblastic disturbances, erythroblastic vacuolization, iron metabolism abnormalities, and hemolytic syndromes. Megaloblastic disturbances may arise as a consequence of folic acid or vitamin B12 deficiency or of a direct toxic effect of ethanol on the erythroblasts. Iron metabolism alterations include reversible sideroblastic anemia, and hemosiderosis. The three hemolytic syndromes related to the consumption of ethanol are: acanthocytosis, stomatocytosis, and Zieve's syndrome. Alcohol induces leukopenia and functional deffects of the leukocytes; these facts explain the frequent susceptibility of chronic alcoholics to infection. Ethanol may act upon the megakaryocytic series to produce reversible thrombopenia and various alterations in platelet function. Thus alcohol exerts toxic effects on bone marrow, which interfere with the proliferation, maturation, release and survival of the three cellular series, either directly or by means of complex mechanisms related to the metabolism of folic acid, vitamin B12, pyridoxine, or iron. Alcoholism should therefore be considered as a possible cause whenever an obscure hematological condition comes under scrutiny.

Alcoholism↗