Search PubMed⌕ Search

Biomedical subjects

I Rich

Publications and source records attributed to I Rich.

8 recordsLinked to original sources

Assessment of G-CSF stimulated BM hematopoietic stem cells in normal donors.

BACKGROUND: The clinical use of G-CSF has recently been expanded to include mobilization of stem cells for both autologous and allogeneic transplantation. Most of the published studies have focused on stem cells released into the peripheral blood (PB) after G-CSF treatment. However, little is known about the effects of G-CSF on BM. This study evaluated the concurrent effects of short-term G-CSF on both BM and PB stem and progenitor cells in normal individuals. METHODS: Volunteers received 5 or 10 microg/kg of G-CSF for 5 consecutive days (Days 1-5). On Days 0, 3, 6, 9 and 15, BM and PB samples were obtained. Flow cytometry and functional assay were performed to analyze stem cells, subpopulations, adhesion molecules, colony-forming units and LTCIC. RESULTS: The total nucleated cells and absolute numbers of CD34(+)/mL showed a similar response pattern in both BM and PB, with a peak around Day 6 that returned to baseline levels by Day 15. However, there was a reciprocal change in the percentage of CD34(+) cells between BM and PB compartments. The expressions of adhesion molecule showed an up- and down-regulation of alpha4 and alpha5 integrin subunits, respectively, also correlated with the CD34(+) mobilization patterns. DISCUSSIONS: The functional characterization of integrins, and further clinical examination of G-CSF-stimulated BM is warranted. G-CSF-stimulated BM maybe considered as an alternative source of stem cells in transplantation.

Adult↗

Erythropoietin under real and simulated microgravity conditions in humans.

The aim of this study was to analyze the time course of erythropoietin (EPO) during Earth-bound microgravity simulations such as bed rest, isolation and confinement (IC), head-down tilt (HDT; -6 degrees), and immersion to evaluate which factors could contribute to alterations in EPO under real microgravity conditions during and after short- (< 10 days) and long-term (> 6 mo) spaceflights. During bed rest (24h), no significant changes in EPO could be observed. Subjects confined in a diving chamber facility for 60 days showed a decrease in EPO. In the recovery period a slight increase was observed, but EPO concentrations did not reach the pre-IC control level. In the control period before HDT, subjects showed normal resting values for EPO, but on day 2 of HDT the EPO concentrations were decreased (P < 0.01). Later the EPO levels remained below the control value and were increased after HDT (P < 0.05). After immersion (24 h) increased EPO concentrations could be determined (P < 0.05). During a short-term spaceflight the astronauts showed in-flight (day 4) decreased and unchanged EPO concentrations. During a long-term spaceflight, 24 h after recovery, the cosmonaut showed slightly elevated EPO concentration, which increased markedly during the following days. It is concluded that 1) HDT (-6 degrees) causes a rapid decrease in EPO in humans, 2) IC per se leads to diminished EPO concentrations, 3) EPO regulation in humans during short- and long-term spaceflights might be different, 4) changes in central blood volume, i.e., central venous pressure, seem to be involved in the modulation of EPO production and release under simulated and real microgravity conditions, and 5) the HDT (-6 degrees) Earth-bound simulation reflects mostly the changes in EPO production and release observed under real microgravity conditions in humans.

Adult↗

Shift working in the Chilean Andes (> 3,600 m) and its influence on erythropoietin and the low-pressure system.

It was hypothesized that, in shift workers with a history of intermittent hypoxic stress (working 10 days at > 3,600 m, then resting for 4 days at sea level) for > 5 yr, the initial erythropoietin (EPO) response and the changes in central venous pressure (CVP) are different from those in Caucasian lowlanders. We studied the kitchen personnel (n = 11) of a mine (3,600 m) and a group of Caucasian lowlanders (n = 5). Blood samples were taken, and CVP was determined several times before, during, and after a typical shift. At baseline data collection (BDC) before transition, the shift workers had EPO concentrations of 5.2 +/- 2.4 mU/ml, which increased at altitude (P < 0.01) and returned to BDC values on the recovery (day 16). The Caucasians showed the same time course. Serum transferrin receptor concentrations did not change in either group. CVP values were generally higher in the shift workers than in the Caucasians. In conclusion, the hypothesis that the initial EPO response to a hypoxic stimulus is altered in these shift workers has to be refuted. Higher hemoglobin concentrations and/or CVP values in shift workers might be responsible for the rather low EPO concentrations in shift workers at BDC.

Acclimatization↗

[Erythropoietin].

The production of red cells can be stimulated by pharmacologic doses of recombinant human erythropoietin (rHu-EPO), provided EPO-sensitive precursors and iron are available. Its side effects are negligible when used in patients with nonrenal anemia. Antibodies against rHu EPO are a rare event. Iron supplementation is routinely necessary in patients with low iron stores, since availability of iron is a rate-limiting cofactor for red cell production. The rationale for treating patients with anemia of cancer or chronic inflammation is to avoid homologous blood transfusion. However, it is not proven whether a raising of the hemoglobin concentration by 2 or 3 g% will improve the quality of life in these multimorbid patients who undergo palliative treatment. There is no evidence yet that rHu-EPO has reduced morbidity and mortality in such patients. Another question is the cost effectiveness of EPO particularly in patients who suffer from an incurable disease. EPO has also been used as an adjuvant in autologous preoperative transfusion programs and has increased the available volume of red cells for transfusion particularly in conjunction with intravenous iron supplementation. EPO given for 14 days preoperatively in patients with elective hip replacement reduced the need for transfusion by nearly 50%. A high dose of oral ferrous sulfate (300 mg) was given 11 days in advance of rHu EPO. Randomized trials are needed for patients with an initial low Hb (< 13.5 g/dl) to study the efficacy and cost effectiveness of different strategies avoiding homologous transfusion and also the risk-benefit ratio of such strategies versus homologous transfusions, since the risk of homologous transfusions has decreased considerably in recent years.

Anemia↗

The effect of erythropoietin and other factors on DNA synthesis by mouse spleen cells.

The effects of pure and crude human urinary erythropoietin, crude sheep plasma erythropoietin and other growth factors on the incorporation of labeled thymidine were studied using spleen cells from mice previously treated with phenylhydrazine hydrochloride. Erythropoietin at 400 mU/ml caused a 40-80 fold increase in the incorporation of the labeled nucleoside. The slope of the dose-response curve found for pure erythropoietin was not significantly different from that found for a crude urinary erythropoietin preparation or for crude sheep plasma erythropoietin. Colony-stimulating factor, interleukin 2, interleukin 3 and the lectin, concanavalin A were also stimulatory but at concentrations from one hundred to one million times higher than that found for erythropoietin.

Animals↗

A method for electron microscopic preparation of cultured cells (monolayer) in a new test chamber (TCSC-1).

A time-saving method is described for the preparation of cultivated cells (monolayer) for electron microscopy using a new test chamber system (TCSC-1). The versatile chamber is fitted with a screw-in PTFE-adapter which connects via a silicone ring gasket to the surface on which the cells grown. All procedures (fixation, staining, embedding) are performed directly in the chamber. The cells, in this particular communication epithelial liver cells, are grown as a monolayer on polyester foils. After embedding of the cells, the foil can be easily taken off. Removal of the foil does not in any way effect the quality of the first slice for electron microscopic examination. The resin block can also be easily pressed out from the PTFE-adapter.

Animals↗

Erythroid colony forming cells in aplastic anaemia.

The concentration and erythropoietin dependence of erythropoietic progenitor cells (CFU-E) were examined in 13 patients with aplastic anaemia at different stages of their disease. The CFU-E incidence was shown to be quantitatively diminished in aplastic anaemia but tended to recover to normal values if the disease recovered. In addition the CFU-E showed a qualitatively different response to stimulation by erythropoietin, being resistant to low concentrations but responsive to concentrations greater than 0.2 U/ml whereas there was a linear response in the controls up to 0.5 U/ml.

Adolescent↗