PubMed Health⌕ Search

Biomedical subjects

E P Cronkite

Publications and source records attributed to E P Cronkite.

At least 19 recordsLinked to original sources
PubMed1990

In vivo toxicity of 3'-azido-3'-deoxythymidine (AZT) on CBA/Ca mice.

CBA/Ca male mice were given 3'-azido-3'-deoxythymidine (AZT) in drinking water (1 mg/ml) for up to 7 weeks. Water consumption and body weight decreased significantly. Neutropenia and lymphopenia were observed during and after exposure. Significant macrocytic anemia developed and disappeared as a function of red cell life span after stopping AZT intake. A microthrombocytosis was seen. Bone marrow cellularity and spleen colony-forming unit (CFU-s) content fell, but recovered completely and quickly after terminating AZT intake. Hemopoietic stem cell function measured by 2 different methods of rescuing fatally irradiated mice was normal 4 weeks after AZT exposure, suggesting that AZT treatment does not induce a long-lasting effect in genetic control of mitotic potential of stem cells. This is in marked contrast to exposure of CBA/Ca mice to benzene and ionizing radiation.

Administration, Oral↗
PubMed1990

Is natural background or radiation from nuclear power plants leukemogenic?

In view of the enormous number of base pair replications per annum in hemopoietic stem cells with the likelihood of coding errors, the rarity of the leukemogenic event at the cellular level after high doses of radiation, the infrequent occurrence of radiation events in cells at low-level exposure (large fraction of cells uninvolved), biological protective mechanisms and the realization that exposure of human populations to radiation from nuclear power plants is a very small fraction of natural radioactivity and will for the foreseeable future remain small and that populations exposed to high natural background radiation show no detectable harmful effects, it is concluded that either there is no effect, or for statistical reasons one cannot detect an effect.

Adult↗
PubMed1979

Relative number and proliferation kinetics of hemopoietic stem cells in the mouse.

A model calculation of the hemopoiesis of the mouse based on known hematologic data leads to the conclusion that approximately 3% of all nucleated bone marrow cells are stem cells (pluripotent plus committed stem cells). By a new 125IUdR labeling technique on radiation chimeras, a relative number of 2%-7% stem cells was determined. In previous studies with test systems for stem cells using colony formation in vivo or in vitro, a relative number of stem cells of at least one order of magnitude lower has been estimated. In this study the stem cells are found to have a turnover time of about 4.3 days in the donor mice. This turnover time remained unchanged even after transfusion of marrow cells into lethally irradiated recipient mice. Radiosensitivity determinations yielded a D0 of 80 rad for stem cells in S-phase and D0 of 185 rad for stem cells distributed throughout the entire cell cycle. The respective extrapolation numbers were 1.23 and 1.14. Experiments using an 3H-TdR suicide technique revealed different cell cycle parameters for bone marrow stem cells seeding to the spleens and to the femurs of lethally irradiated recipients, primarily a shortening of S-phase in cells seeding to femurs. The method described here provides a new approach to hematologic stem cell research.

Animals↗
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

Proliferation of human lymphocytes in culutre: determination by measurement of nuclear volume and cell number.

Proliferation of stimulated human lymphocytes was studied in cultures by determining cell counts and nuclear volume enlargement. DNA content and the nuclear volume increase before the cell divides. Volume-frequency curves were obtained of unstimulated and phytohemagglutinin (PHA) stimulated lymphocytes on 0, 3, 6 and 9 days of cultures with the Coulter Counter H4 system. As the number of lymphocytes in the cultures transformed and enlarged in volume, the area under the volume-frequency curve increased proportionately. The fraction of transforming cells was determined by comparing the area under the curve of the unstimulated and the stimulated lymphocytes. This method provides both the fraction of cells transformed and the increment of the number of cells in the culture and is therefore a better indicator of cell proliferation than the commonly used isotope-labeled thymidine uptake method which monitors the fraction of the cells in DNA synthesis phase only.

Cell Count↗
PubMed1979

Correlation of total body potassium and leukemic cell mass in patients with chronic lymphocytic leukemia.

Total body leukemic mass in patients with chronic lymphocytic leukemia (CLL) was measured by quantitation of total body potassium (TBK) with a whole-body counter. In addition, the predicted normal total body potassium (Kp) for each patient was calculated from an empirically derived relationship involving height, weight, age, and sex. Both the absolute TBK and the relative excess of total body potassium (TBK/Kp) were related to the stage of disease. Patients in the early stages of CLL were found to have lower TBK and TBK Kp than patients in the late stages of disease. Both of these parameters increased with the successively advanced stages of the disease. The clinically monitored reduction of leukemic cell mass following therapy was accompanied by reductions in TBK and TBK/Kp. Data presented support the notion that TBK/Kp is a useful indicator of the total body leukemic mass. Furthermore, the results of these studies quantitatively validate the proposed clinical staging system for CLL. Quantitation of TBK by a whole-body counter is an accurate and noninvasive procedure and does not require administration of isotopes.

Humans↗
PubMed1979

Proliferation kinetics of early hemopoietic precursor cells with self sustaining capacity in the mouse, studied with 125-I-labeled iodo-deoxyuridine.

With a new labeling technique in radiation chimeras, an attempt was made to determine the duration of the phases of the stem cell cycle including shortest and mean generation time and to estimate the number of hemopoietic stem cells per unit of bone marrow cellularity. The DNA of bone marrow cells in DNA synthesis was labeled with 5-125I-2'-deoxyuridine. The labeled cells were followed after being transfused into fatally irradiated mice. The stem cells were found to have a half-time of about 4.3 days in the donor mice. The average time in the population, i.e. the turnover time of the stem cells, was 6.2 days. The half-time did not change significantly even after transfusion of bone marrow into lethally irradiated recipient mice. Tritiated thymidine (3H-TdR) suicide technique revealed that bone marrow stem cells seeding to the spleens and to the femurs of lethally irradiated recipients behaved differently--S-phase in cells seeding to femurs being shorter. The radiosensitivity of stem cells in S-phase had a D0 of 80 rad whereas stem cells distributed throughout the whole cell cycle had a D0 of 185 rad. The respective extrapolation numbers were 1.23 and 1.14. It is calculated that 2--7% of all nucleated bone marrow cells belong to self renewing stem cell populations. The method described provides a new approach for the study of hematological stem cells.

Animals↗
PubMed1979

The effects of humoral factors on amplification of nonrecognizable erythrocytic and granulocytic precursors.

These studies were to evaluate the effects of humoral factors on amplification of nonrecognizable erythrocytic and granulocytic precursors by the in vivo plasma clot diffusion chamber and the in vitro plasma clot culture methods. Changes in the plasma erythropoietin levels in the reticulocyte concentration and hematocrits of irradiated and nonirradiated Long-Evans rats exposed to hypoxia were also determined. While erythropoietin plasma concentrations appeared to affect BFU-E and CFU-E growth, results suggest erythropoietin may not be the sole regulator of red cell production and that inhibitors of chalone-like mechanisms may be involved. Measurements made on granulocyte precursors treated with colony stimulating factor (CSF) containing L-cell-conditioned medium revealed granulocytic colonies and burst-like formations similar to those seen for erythrocytic growth. There is strong evidence suggesting that CSF is a regulator of granulopoiesis; however, it is not the sole regulator and it appears that inhibitors may play an in vivo role. Growth of colonies with cell numbers not a power of 2 implies either asymmetric mitosis due to loss of genetic information required for continuing division, or differences in concentrations of, or ability to recognize, inhibitory factors. These possibilities are examined in the light of results from in vivo and in vitro culture techniques.

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

Increased granulocytic, erythrocytic, and megakaryocytic progenitors in myelofibrosis with myeloid metaplasia.

Nucleated cells obtained from blood and/or bone marrow of patients with myelofibrosis with myeloid metaplasia (MMM) were cultured in diffusion chambers (DC) implanted into the peritoneal cavities of irradiated mice. A total of five blood studies and two bone marrow studies were performed using cells obtained from five patients. The DC were harvested at intervals from the host mice and the total and differential cellularity of DC contents were evaluated. The results obtained from MMM cultures were compared with those from similar cultures of blood cells and marrow cells of four and six normal individuals respectively. The proliferation and maturation of the granulocytic, erythrocytic, and megakaryocytic lines in MMM cultures occurred in an orderly fashion as they occur in vivo. The patterns of proliferation and maturation of the three cell lines in cultures after day 7 suggest that they primarily originate from progenitor cells. The numbers of granulocytes in the multiplicative pool, recognizable red cell precursors, and megakaryocytes recovered were significantly greater from the MMM cultures than those from the normal blood or marrow cultures. These results suggest that the blood and marrow cells of MMM patients have increased numbers of progenitors for granulocytes, erythrocytes, and megakaryocytes.

Adult↗
PubMed1978

The r.b.e. of different-energy neutrons as determined by human bone-marrow cell-culture techniques.

The effect of X-rays and different-energy neutrons on human bone-marrow cells was studied using two different cell-culture techniques--diffusion chamber (DC) growth and colony formation in vitro (CFU-C). Based on the survival of proliferative granulocytes in DC on day 13, the D0 value was 80 rad with X-rays, and 117 rad as measured by the CFU-C assay. The D0 values for neutrons depended on the radiation source and the energy level. The r.b.e. values, which dropped with increasing energy levels of mono-energetic neutrons, were (i) 0.44 MeV; DC 3.7, CFU-C 4.1; (ii) 6 MeV; DC 1.8, CFU-C 2.0; (iii) 15 MeV; DC 1.6, CFU-C 1.6; (iv) fission neutrons; DC 2.6, CFU-C 2.4.

Bone Marrow↗
PubMed1978

Radiation-induced damage to blood vessels: a study of dose--effect relationship with time after X-irradiation.

Radiation damage to the right femoral artery was studied in mice 7--8 weeks old. Single X-ray exposures of 500 to 10 000 rad were used. The animals, except for the right upper legs, were shielded from exposure. The unexposed left femoral arteries served as 'controls'. Animals were killed at post-irradiation times of up to 120 days. Pathological changes in the irradiated arteries were scored on an arbitrary scale of 0 to 5 for individual tunica. The overall arterial damage was scored on a scale of 0 to 15. Radiation doses of 1000 to 10 000 rad produced quantitative histological changes in the three individual tunica and the degree of damage was dose-dependent. The tunica adventitia showed the maximum radiation injury, followed by tunica media and tunica intima in decreasing magnitude of injury. The combined effects on the artery followed closely the effects on media and adventitia.

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↗