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At least 631 records · Page 35Linked to original sources
PubMed1979

Paroxysmal nocturnal hemoglobinuria associated with infectious mononucleosis.

A previously healthy 16-yr-old girl was found to have pancytopenia, low reticulocyte count, a cellular bone marrow, and a negative Coombs test, all coincident with clinical and laboratory evidence of infectious mononucleosis. Symptoms and signs of infectious mononucleosis subsided, but pancytopenia and hemolytic anemia persisted. Sucrose hemolysis and acid hemolysis tests supported a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). After 18 mo, the platelet count is normal, but leukopenia and hemolytic anemia continue. The development of PNH in this patient suggests it may have resulted from an effect of infectious mononucleosis.

Adolescent↗
PubMedDate not supplied

[Survival of irradiated animals and the preservation of CFUs after the administration of various radioprotectors].

The comparative data are presented concerning the 30-day restoration of the bone marrow cellularity and the number of endogenous colonies in the spleen of the control animals and of those treated with the radioprotective agents after irradiation with doses from 4.5 to 8.1 Gy. There was a good agreement between the results of studies in the integrity of the haemopoietic system on day 9 after irradiation and the 30-day survival of animals.

Animals↗
PubMed1981

Serotherapy of acute lymphoblastic leukemia with monoclonal antibody.

We tested the efficacy of passive serotherapy in the treatment of acute lymphoblastic leukemia in four patients who had relapsed while receiving standard chemotherapeutic agents. Each patient received multiple intravenous infusions of J-5 monoclonal antibody specific for common acute lymphoblastic leukemia antigen (CALLA). In the three patients with circulating leukemic cells, there was a rapid decrease in circulating blasts that began immediately after antibody infusion, but not all leukemic cells were cleared, and remaining cells appeared to be resistant to further serotherapy. Although J-5 antibody was also demonstrable on bone marrow lymphoblasts immediately after antibody infusion in one patient, there was no change in bone marrow cellularity or differential during serotherapy. Analysis of the cell surface phenotype of leukemic cells during serotherapy and in vitro studies with patient cells suggests that resistance to serotherapy was mediated in part by antigenic modulation of CALLA in response to J-5 antibody.

Adolescent↗
PubMed1994

[Stem cell factor].

Stem cell factor (CSF), also called c-kit ligand (KL) or mast cell growth factor (MGF) is a peptide growth factor/cytokine with broad activities, especially on hematopoiesis. Its physiological role is best understood through the naturally occurring steel and W mutations in the mouse. This cytokine has recently been made available because of molecular cloning and its expression in recombinant form SCF is produced by a variety of cells, especially fibroblast, and interacts with target cells in each of the hematopoietic lineages to stimulate proliferation and differentiation. It has been found that SCF is important for the survival, proliferation and differentiation of mast cells and that it influences all stages of their development. SCF activity is not restricted to hematopoiesis, as it plays an important role in the development of germ cells and melanocytes as well. Preclinical studies show that SCF can protect against lethal irradiation, elicit multilineage responses in peripheral blood and bone marrow cellularity and increase circulating peripheral blood progenitor cells in a dose-dependent manner. Recombinant human SCF has major clinical potential through its synergy with other factors, especially G-CSF, to enhance mobilization of stem cells in peripheral blood.

Animals↗
PubMed1995

Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic progenitor cells: increase of early hematopoietic progenitor cells in TNF receptor p55-deficient mice in vivo and potent inhibition of progenitor cell proliferation by TNF alpha in vitro.

Murine bone marrow cells with lineage phenotypes (Lin)-Sca-1+c-kit+ and Lin-Sca-1-c-kit+ cells represent primitive hematopoietic stem cells (HSCs) and committed hematopoietic progenitor cells, respectively. The number of Lin-Sca-1+c-kit+ HSCs in bone marrow was significantly increased in tumor necrosis factor (TNF) receptor p55-deficient (TNF-R55-1-) mice compared with the TNF-R55+/+ wild-type mice without a marked change in bone marrow cellularity. In both the methylcellulose culture and a single-cell proliferation assay, mouse TNF alpha (mTNF alpha) inhibited in vitro the proliferation of wild-type mouse-derived Lin-Sca-1+c-kit+ cells in response to a combination of multiple growth factors. The same is true for that of Lin-Sca-1+c-kit+ cells stimulated with granulocyte colony-stimulating factor (G-CSF) plus stem cell factor (SCF). Moreover, mTNF alpha significantly arrested the entry into S-phase from G0/G1 phase of Lin-Sca-1+c-kit+ cells stimulated with multiple growth factors and Lin-Sca-1-c-kit+ cells stimulated with G-CSF plus SCF. In contrast, mTNF alpha failed to affect the growth and cell cycle progression of Lin-Sca-1+c-kit+ cells and Lin-Sca-1-c-kit+ cells that were obtained from TNF-R55-deficient mice. These data suggest that TNF may be an important physiologic regulator of hematopoiesis and that TNF-R55 may be essentially involved in TNF-mediated inhibition of the growth of both primitive stem and more committed progenitor cells.

Animals↗
PubMed1979

Comparison of the sensitivities of human, canine, and murine hematopoietic precursor cells to adriamycin and N-trifluoroacetyladriamycin-14-valerate.

The sensitivities of leukocyte-committed stem cells of human, dog, and mouse bone marrow to an 18-hr exposure to Adriamycin (ADR) and N-trifluoroacetyladriamycin-14-valerate (AD32) were compared using the agar diffusion chamber assay. The survival of in situ mouse marrow stem cells following the drugs was also measured. The in vivo doses required to produce 37% survival of hematopoietic precursor cells for human, dog, mouse, and in situ mouse marrow stem cells for ADR were 9.5, 3.5, 8, and 8 mg/kg, respectively, while those for AD32 were 22, 17, 37, and 40 mg/kg. Mouse bone marrow cellularity was reduced to 50% by drug doses producing 3 and 7% stem cell survival. AD32 given i.p. to mice was less effective than i.v. drug in producing marrow stem cell death, reduction of marrow cellularity, or acute lethality. Although more AD32 than ADR was required to kill marrow stem cells from each species and canine marrow stem cells were the most sensitive to either drug, human stem cells were relatively more sensitive to AD32 than were mouse stem cells. The reverse was true for ADR. Granulocytopenia may be an important limiting toxicity in the clinical use of AD32.

Animals↗
PubMed1993

[Chemotherapy for older cancer patients].

The population of Japan is gradually aging. Since cancer is mainly a disease of older persons, the incidence of malignancies of all types is expected to increase during the coming decades. Until recently, studies about responses to treatment and toxicity in the elderly patients have been very limited. Many clinical trials have excluded elderly patients with advanced cancer because of decreased tolerance to chemotherapy. In some older cancer patients, however, such exclusion may be inappropriate. Aging is a highly individualized process that cannot be defined by chronological landmarks. The great variation that exists between individual patients in terms of tolerance and responsiveness to chemotherapy seems to be closely related with biological age rather than chronological age of elderly persons. In general, the patterns of disease and stages at diagnosis are not the same for elderly and younger cancer patients. Because bone marrow cellularity diminishes with age, older patients appear to have decreased tolerance to certain anti-cancer agents. Therefore, administration of G-CSF combined with chemotherapy is necessary for elderly patients. A decline in the function of other vital organs also may reduce the efficiency of drug metabolism and excretion, resulting in greater toxic potential. Recently, the use of single-agent oral etoposide has been shown to be an effective palliative therapy for older patients with small-cell lung cancer. The combination of 5-FU with leucovorin has seemed to bring about a good response rate without any remarkable side effect for older patients with gastrointestinal cancer. The oral administration of 5'-DFUR has shown a remarkable prolongation of survival period and improvement of the cachectic status in older cancer patients. Future studies of palliative cancer chemotherapy will be needed to focus on the unique requirement of maintaining QOL in older patients.

Aged↗
PubMedDate not supplied

[Role of alpha-interferon in the treatment of hairy cell leukemia].

Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder that is characterized clinically by splenomegaly, pancytopenia, and the presence of malignant tartrate-resistant acid phosphatase (TRAP)-positive lymphocytes displaying unique morphological features in the peripheral blood and bone marrow. In the past, splenectomy has been the mainstay of treatment, resulting in symptomatic palliation and hematological improvement in 90 percent of patients. However, most patients undergoing splenectomy eventually require additional therapy; hematologic parameters and the degree of bone marrow cellularity are now utilized to identify to identify subsets of patients who might derive long-term benefit from the procedure. 2'-Deoxycoformycin (DCF) and 2-chlorodeoxyadenosine (2-cda) are experimental agents that have demonstrated curative potential in HCL; however, unresolved concerns about the long-term toxicity of DCF currently preclude its routine use, and further studies are required to define the toxicity and duration of responses obtained with 2-cda. As a result, alpha-interferon (alpha IFN) presently represents the treatment of choice for most patients with HCL. While alpha IFN has not been shown to cure HCL, its advantages include a high rate of response, a favorable side effect profile, its ability to be used safely in patients with active infections, and its ability to re-induce remission in relapsing patients. The mechanisms underlying alpha IFN's effectiveness seem to involve its immunomodulatory actions, which decrease the frequency of infectious complications in the early stages of therapy, and its ability to induce hairy cells to differentiate into more mature cells less responsive to proliferative signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1996

Tumor necrosis factor administration is associated with increased endogenous production of M-CSF and G-CSF but not GM-CSF in human cancer patients.

In humans, tumor necrosis factor (TNF) treatment has been associated with characteristic changes in circulating white blood cell populations (leukopenia followed by leukocytosis) and increased cell-surface expression of integrins. A similar pattern of effects on leukocytes occurs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF treatment. To determine whether these effects were caused directly by TNF or as a result of secondary CSF release, G-GM-, and M-CSF levels were measured after TNF infusion (9.6 x 10(6) U/mg protein; < 5.0 endotoxin U/mg protein) in cancer patients during two phase I trials of TNF. One patient with aggressive fibromatosis was treated with TNF alone (200 micrograms/m2, days 1-5 every third week) and 10 patients (four colon cancer, four head and neck cancer; one melanoma; one sarcoma) received mitomycin C (15 mg/m2, day 1) followed by TNF (60-180 micrograms/m2, days 1-3) every sixth week. All treatments were given IV, mitomycin C over 5 minutes and TNF over 2 hours. Serum samples were collected at times 0 (before mitomycin C and TNF) and 1, 2, 4, 6, 12, and 24 hours after TNF initiation on day 1 and at similar times on subsequent treatment days. M-CSF samples were analyzed by radioimmunoassay (RIA) and G-CSF and GM-CSF by ELISA. The mean baseline M-CSF levels in normal control subjects (n = 12) was 158.4 +/- 36.2 (SD) U/mL, and in pretreatment cancer patients (n = 10) 235.7 +/- 60.9 U/mL (p = 0.004, Wilcoxon test). M-CSF levels increased 4 hours after TNF initiation (mean 354.7 +/- 96.3 U/mL; p = 0.020), remained elevated at 6 hours (305.6 +/- 45.4 U/mL; p = 0.004, Wilcoxon signed-rank test), and subsequently declined. This pattern was seen in all patients treated with TNF, whether treatment was TNF alone or TNF with mitomycin C. In patients treated with mitomycin C and TNF, G-CSF levels increased at 4 hours after TNF initiation (mean 3886 +/- 2009 pg/mL; p = 0.004), remained elevated at 6 hours (mean 2140 +/- 1131 pg/mL; p = 0.004), and subsequently declined. GM-CSF levels were not measurable before or after treatment with TNF. The changes in all three endogenous cytokines were not temporally related to the previously described leukopenia and integrin upregulation on circulating leukocytes and, therefore, appear to be unrelated to this event. However, release of endogenous G-CSF and M-CSF under the influence of TNF does temporally coincide with the previously described leukocytosis, suggesting a possible role for these endogenous cytokines in the release of bone marrow cellular stores.

Colonic Neoplasms↗
PubMed1977

Refractory sideroblastic and nonsideroblastic anemia: a review of 27 cases.

A study was done with 27 patients who met the following criteria: (1) anemia, (2) cellular bone marrow not diagnostic of leukemia, (3) absence of underlying disease that could account for the hematologic abnormalities at time of initial study and (4) absence of iron, B(12) or folate deficiency. Of the 27 patients, 13 had ringed sideroblasts and 14 did not. Eleven patients received corticosteroids, 18 received folate, 23 pyridoxine and 12 androgens. Two partial responses occurred in the sideroblastic group and were attributed to androgen therapy in one patient and pyridoxine therapy in the other. In the nonsideroblastic group, two partial responses occurred which were attributed to prednisone therapy. Transfusions were required in 23 patients. Leukemia developed in six patients. It is concluded that currently used treatments have little effect on refractory anemia and that in most patients continuing transfusions are required. In a small percentage of patients, there is transformation to leukemia.

Adolescent↗
PubMed1996

Use of Withania somnifera Dunal as an adjuvant during radiation therapy.

Withania somnifera popularly known as Aswagandha is used in several indigenous drug preparations. Administration of a 75% methanolic extract of the plant was found to significantly increase the total WBC count in normal Balb/c mice and reduce the leucopenia induced by sublethal dose of gamma radiation. Treatment with W. somnifera was found to increase the bone marrow cellularity significantly, the percentage increase being 146.3. Treatment with W. somnifera had normalised the ratio of normochromatic erythrocytes and polychromatic erythrocytes in mice after the radiation exposure. Major activity of W. somnifera seemed to be in the stimulation of stem cell proliferation.

Animals↗
PubMed1997

Inhibition of experimental murine tumors by MT81, a new mycotoxin from Penicillium nigricans.

Effects of a new mycotoxin MT81 obtained from the fungal strain Penicillium nigricans on the growth of two transplantable murine tumors and the life span of the hosts were studied. Remarkable decrease in tumor volume and viable tumor cell count was found in both the tumors. Antitumor effect of the compound was more pronounced in Sarcoma 180 (S180) than in Ehrlich ascites carcinoma (EAC). The tumor-inhibitory effect was also manifested by the reduction in mitotic activity and appearance of membrane blebbing and intracytoplasmic vacuoles in the treated tumor cells. MT81 treatment prolonged the life span of the EAC tumor host by 78% and more than 100% in S180 bearing mice. Tumor inhibition by MT81 was followed by improvements in hemoglobin, RBC values and bone marrow cellularity. Thus the results suggest that MT81 has significant antitumor property against experimental murine tumors and it does not adversely affect the hematological profile of the hosts.

Animals↗
PubMed1997

Antioxidant activity of Tinospora cordifolia and its usefulness in the amelioration of cyclophosphamide induced toxicity.

Extract of Tinospora cordifolia has been shown to inhibit the lipid peroxidation and superoxide and hydroxyl radicals in vitro. Concentration needed for 50% inhibition was 6 mg and 12.5 mg/ml, respectively. The extract was also found to reduce the toxic side effects of cyclophosphamide administration (25 mg/kg b.wt, 10 days) in mice hematological system by the free radical formation as seen from total white blood cell count, bone marrow cellularity and alpha-esterase positive cells. Moreover, administration of the extract partially reduced the elevated lipid peroxides in serum and liver as well as alkaline phosphatase and glutamine pyruvate transaminase. This indicates the use of Tinospora extract in reducing the chemotoxicity induced by free radical forming chemicals.

Animals↗
PubMed1975

[Bone marrow eythroid series cellular reaction to antigenic stimulation].

The authors describe changes in the cells of the erythroid series of the bone marrow against the background of immunization with diphtheria toxoid. Physiological saline was injected to control animals. Changes in the blood system were in one direction and were expressed in the erythroblastic reaction; this reaction was less pronounced in control than in the experimental animals.

Animals↗
PubMed1990

Normal age-related patterns of cellular and fatty bone marrow distribution in the axial skeleton: MR imaging study.

Knowledge of age-related distribution patterns of cellular and fatty marrow is critical to the interpretation of magnetic resonance (MR) imaging studies. To determine such patterns, the authors retrospectively evaluated 70 examinations each of the skull, cervical spine, thoracic spine, lumbar spine, pelvis, and proximal femur (420 examinations) in patients without known bone marrow abnormality who ranged in age from 6 months to older than 70 years. Two to four distinct patterns were identified in each anatomic area on spin-echo images obtained with a short repetition time and a short echo time. The relative frequency of the patterns for different age groups is consistent with the known physiologic conversion from cellular to fatty marrow with advancing age. Knowledge of these patterns should help in the interpretation of MR images of the axial skeleton.

Adult↗
PubMed2005

Absorbed fractions for alpha-particles in tissues of trabecular bone: considerations of marrow cellularity within the ICRP reference male.

UNLABELLED: Alpha-particles are of current interest in radionuclide therapy due to their short range and high rates of energy transfer to target tissues. Published values of alpha-particle absorbed fraction phi in the skeletal tissues, as needed for patient-specific dosimetry under the MIRD schema, do not generally account for its variation with particle energy or skeletal site. Furthermore, variations in alpha-particle absorbed fraction with marrow cellularity have yet to be fully considered. METHODS: In this study, a 3-dimensional (3D) chord-based radiation transport model (or 3D-CBIST) is presented, which combines (a) chord-based techniques for tracking alpha-particles across bone trabeculae, endosteum, and marrow cavities and (b) a spatial model of the marrow tissues that explicitly considers the presence of marrow adipocytes. Chord-length distributions are taken from a 44-y male subject (ICRP [International Commission on Radiological Protection] Reference Male) and are identical to those used currently for clinical dose estimates for beta-particle emitters. RESULTS: Values of phi(active marrow<--active marrow) given by the 3D-CBIST model are shown to be considerably lower than phi = 1.0 assumed under the ICRP Publication 30 and 2003 Eckerman bone models. For example, values of absorbed fraction for the self-dose to active bone marrow in the ribs, cervical vertebra, and parietal bone are 0.81, 0.80, and 0.55 for 6-MeV alpha-particles and are 0.74, 0.72, and 0.43 for 9-MeV alpha-particles, where each is evaluated at ICRP reference cellularities in the 3D-CBIST model (72%, 72%, and 42%, respectively, at age 25 y). CONCLUSION: Improvements in patient-specific dosimetry of skeletal tissues require explicit consideration of not only changes in target mass with variable patient marrow cellularity (i.e., active marrow) but also corresponding changes in values of the absorbed fraction. The data given in this study provide a more-firm basis for application of the MIRD schema to patient-specific dosimetry for newly developing therapies using alpha-particle emitters.

Adult↗
PubMed1986

Flow cytometry Coulter volume analysis of lead- and cadmium-induced cellular alterations in bone marrow obtained from young adult and aged Balb/c mice.

Flow cytometry Coulter volume analysis was used to examine the effects of an acute exposure to cadmium or lead on subpopulations of Balb/c bone marrow cells. A significant shift in the volume of Balb/c bone marrow cells was detected in response to a single i.p. injection of cadmium acetate (Cd) or lead acetate (Pb) compared to sodium acetate (Na)-treated mice. An increase in the relative number or size of myeloid/monocytic cells was noted in the bone marrow of cadmium or lead-treated mice. This effect was more pronounced in aged Balb/c mice than in young adults. These studies suggest the flow cytometry Coulter volume analysis may be a useful and sensitive technique for the assessment of cellular changes that occur in the bone marrow in response to xenobiotic exposure.

Aging↗