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Biomedical subjects

H Burlington

Publications and source records attributed to H Burlington.

At least 19 recordsLinked to original sources
PubMed1993

Anemia induced in splenectomized mice by administration of rhG-CSF.

Normal and splenectomized mice (SPLXM) were given rhG-CSF for 10 to 128 days and serial observations were made on blood counts for 128 days. After 10 days, mice were killed for histologic studies. All treatment schedules produced, in addition to elevated white blood counts, a macrocytic anemia which only partially responded to large doses of Epo. Stopping rhG-CSF treatment for 2 days resulted in the return of granulocytes, lymphocytes, monocytes, platelets and polychromatophilic erythrocytes to near normal levels, indicating a need for the continued presence of rhG-CSF to maintain peripheral blood increases. Treatment of normal and SPLXM with rhG-CSF induced marked granulocytic hyperplasia of the bone marrow with expansion of the granulocytic marrow into the adjoining muscle as in acute myelocytic leukemia. The hyperplasia is greater in the SPLXM than in the normal mouse where splenic hyperplasia occurs in all cell lines. The rhG-CSF also results in expansion of granulopoiesis into the normally fatty tail bone marrow in SPLXM. The rhG-CSF treatment produced marked increases in the assayable numbers of GM-CFU, G-CFU and M-CFU. The significance and mechanisms of induction of these changes are not clear. It is speculated that treatment with rhG-CSF has multicellular effects, suggesting that it initiates a cascade of molecular reactions that cause the effects observed.

Anemia↗
PubMed1983

Tumor-induced granulopoiesis unrelated to colony-stimulating factor.

A transplantable granulocytosis-inducing mammary adenocarcinoma of mice was used to provide evidence about the role of tumor-generated factors in granulopoiesis. The original tumor produced high levels of colony-stimulating factor (CSF) in culture as well as inhibitor to CSF. The tumor was passaged repeatedly, both in host mice and in culture, and eventually displayed a varying capacity to induce granulocytosis. Tumors that were associated with either the induction of extreme granulocytosis or near-normal granulocyte levels were selected and passaged intermittently in vivo and in culture. Two tumor lines were thus isolated: one, line C-4a, inducing granulocytosis, and the other, line 34-4H, failing to induce granulocytosis. Both lines grow at the same rate in host mice, but in culture, each displays a distinct morphology. Measurement of CSF and inhibitor produced by each line in culture showed that line 34-4H retained the capacity to produce CSF and inhibitor in spite of losing the ability to influence granulopoiesis in vivo. This suggests that the various factors shown to influence granulopoiesis in vitro may have little or no role as physiologic regulators in vivo.

Adenocarcinoma↗
PubMed1979

Relevance of specific activity in experimental erythrocytocide by 55Fe.

Iron loads between 0.20 microgram and 26 microgram, added to 5 mu Ci 59Fe, were followed for up to 150 days in mice. Relative organ uptake increased as a function of iron load in liver and kidneys while it decreased in bone marrow and blood. Several weeks after injection, all load-related differences disappeared.

Animals↗
PubMed1979

Forced differentiation of CFU-S by Iron-55 erythrocytocide.

Cascades of Auger electrons are emitted in the decay of 55Fe and absorbed in tissue within a 1 micrometer radius. Cytocidal amounts of 55Fe can therefore eliminate erythroid precursors with minimal damage to adjacent cells. A single intravenous injection leads to continued erythrocytocide in mice because the isotope is reutilized and has a 2.7 year half-life. The cytocide evokes an early compensatory response from morphologically unrecognizable precursors which differentiate into pronormoblasts. These early events leave the granuloid series undisturbed but they are accompanied by a precipitous fall in pluripotent stem cell (CFU-S) numbers in bone marrow, spleen, and blood. The pretreatment levels of CFU-S are not restored. Gradual decline of CFU-S is associated with intermittently increased turnover rates and reduced settings of cell production, yet the capacity for quick restoration of blood loss is unimpaired. The precipitous initial stem cell decrease is not caused by irradiation damage, as shown in a separate experimental series that used the frozen-storage cytocide technique. Only over several weeks could 55Fe radiation accumulate to lethal levels in nondividing stem cells. This irradiation is attributed to incorporation of small amounts of 55Fe into CFU-S, from where it is slowly cleared. The stem cell loss immediately following 55Fe injection is in our interpretation caused by rapid differentiation along the erythroid pathway in a response that involves all progenitor populations. Data are consistent with the hypothesis of limited cell renewal capacity which thereby gains further support.

Animals↗
PubMed1978

Hemopoietic effects in mice of a transplanted, granulocytosis-inducing tumor.

A transplanted tumor that induces granulocytosis and produces colony stimulating factor (CSF) was studied in mice during several passages. The sequence of events leading to granulocytosis was characterized. Band granulocytes were increased 3 days after tumor inoculation, while simultaneously CFU-s and CFU-c in bone marrow and spleen were transitorily low. This was followed by rapid accumulation of CFU-c and CFU-s in spleen, and by successive waves of increased mitotable and non-mitotable granulocytes in spleen and marrow. In contrast, marrow CFU-c and CFU-s remained normal or slightly decreased.

Animals↗
PubMed1977

Inappropriate erythropoietin secretion in polycythemia vera.

A patient with classical polycythemia vera (PV) was found to have an inappropriately elevated serum erythropoietin (Ep) level. Investigations did not reveal any lesion or blood abnormality known to be associated with excessive Ep production and erythrocytosis. Sudden withdrawal of blood to reduce the Hb and Hct from 18.5 gm% and 56% to 13.6 gm% and 41.5%, respectively, resulted in an increment of serum Ep to abnormal level. With iron treatment there was a brisk return of Hb and Hct to prebleeding levels which was associated with reduction in the serum Ep. The inverse relationship between the Ep and Hb or Hct is inconsistent with the presence of excessive Ep-producing lesion. These results suggested that the threshold for Ep secretion from normal Ep-secreting tissue to Hb and Hct levels is set at an abnormal level. This patient's marrow cells when cultured in vitro in the absence of Ep, unlike other PV patients' (except one) marrow cells, did not grow erythroid colonies. In the presence of Ep, however, the colonies comparable to those formed from normal marrow cultures were obtained. These results suggested that his marrow erythropoietic cells were neither Ep independent nor Ep-hyperresponsive, as has been suggested by some investigators for erythropoiesis in PV. This patient presents phenomena that hitherto have not been reported.

Animals↗
PubMed1977

Liver as the primary site of erythropoietin formation in the fetus.

Fetal sheep produced significant amounts of erythropoietin in response to bleeding. Bilateral nephrectomy prior to bleeding failed to influence the formation of erythropoietin. Removal of the spleen, in addition to kidneys, was also without effect. Subtotal hepatectomy prior to bleeding, however, inhibited erythropoietin formation in these fetuses. In situ perfusion of the liver, but not the kidney, resulted in the appearance of significant quantities of the hormone in the perfusate. These results suggest that the liver is the primary site of erythropoietin production in the mammalian fetus.

Animals↗
PubMed1976

Periodic oscillation of blood leukocytes, platelets, and reticulocytes in a patient with chronic myelocytic leukemia.

A patient with chronic myelocytic leukemia had a cyclic oscillation of blood neutrophils, eosinophils, monocytes, platelets, normoblasts, and reticulocytes but not of lymphocytes. The cycle interval was 53--69 days. Except for reticulocytes all other cells cycled with neutrophils. Plasma colony-stimulating factor (CSF) oscillated out of phase with neutrophils, suggesting that granulocytopoiesis is regulated through CSF by a feed-back mechanism. Plasma erythropoiesis-stimulating factor (ESF) also oscillated. ESF crests preceded or coincided with reticulocyte crests, indicating that the ESF elevation may have been responsible for the reticulocyte peaks. The relationship between neutrophils and reticulocytes and their oscillations with plasma CSF and ESF suggests that there is a common stem cell which differentiates along one cell line or the other depending upon the balance of regulatory stimuli. The fraction of blood neutrophilic precursors (myeloblasts, promyelocytes, and myelocytes) in DNA synthesis fluctuated with neutrophil level. The calculated generation time was shorter at the crests than at the troughs of the neutrophil cycles. This finding suggested that the rate of proliferation of the neutrophils changed periodically. This observation, along with a periodic increase in differentiation of the stem cell toward the neutrophilic cells, is the probable explanation of oscillation of the neutrophil count in the blood.

Aged↗
PubMed1975

Hayflick's hypothesis: an approach to in vivo testing.

The experimental evidence relating to the hypothesis of finite cellular life is reviewed. It is emphasized that even if somatic cell production were limited its total potential would have to be vast to provide for extensive cellular regeneration. The actual limit of reproductive cell life would therefore not likely be reached in a normal life-span. It is proposed to test the hypothesis by deliberate exhaustion of stem-cell reserve, and iron-55 cytocide is described as an experimental system that might be applicable.

Animals↗
PubMed1975

Selective damage to erythroblasts by 55-Fe.

The low energy and short range of 55-Fe Auger electrons were utilized in mice to deliver lethal intracellular radiation to iron-incorporating erythropoietic precursors with minimal radiation damage to other bone marrow cells. The ensuing intramedullary, selective erythropoietic death was demonstrated by absolute and differential bone marrow cell counts and by decreased blood uptake of 59-Fe. The decreased number of colony-forming units in spleen colony assay and the decreased ability of tranplanted bone marrow to protect fatally irradiated mice shows that the bone marrow was partially depleted of pluripotent stem cells. These data are interpreted to indicate an increased pluripotent stem cell utilization in response to increased demand for differentiation of stem cells along the erythropoietic pathway.

Animals↗