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Biomedical subjects

M Eder

Publications and source records attributed to M Eder.

At least 73 records · Page 4Linked to original sources
PubMed1990

Effects of recombinant human interleukin-3 on human hematopoietic progenitor and precursor cells in vivo.

DNA-synthesis rates and concentrations of bone marrow (BM) and peripheral blood (PB) progenitor cells were studied in 22 patients treated with recombinant human interleukin-3 (rhIL3) as part of a clinical phase I/II study. Recombinant hIL3 at doses of 60 to 500 micrograms/m2 was administered by subcutaneous bolus injection for 15 days to 13 patients with solid tumors and preserved hematopoietic function and to nine patients with bone marrow failure, including five with myelodysplastic syndromes. Following treatment with rhIL3, the percentage of actively cycling BM erythroid (BFU-E) and multilineage (CFU-GEMM) progenitors in patients with preserved hematopoietic function increased from 16% to 36% (P less than .05) and from 10% to 40% (P less than .01), respectively. The DNA-synthesis rates of early and late granulocyte macrophage progenitor cells increased from 11% to 26% (CFU-GM day 14; P less than .02) and from 13% to 30% (CFU-GM day 7; P less than .05). There was an increase in BM cellularity from 37% to 58%, and of the myeloid to erythroid ratio from 1.4 to 3.2, while the concentration of marrow progenitors on a per cell basis was unchanged or slightly decreased. The frequencies of blast cells in the BM were unchanged. Mean levels of PB CFU-GM day 14 and CFU-GEMM were 100% and 72% above baseline values after 7 days of rhIL3 but only 25% and 28% above initial levels at the end of treatment. Peripheral blood BFU-E were reduced in the majority of patients with normal marrow after both 7 and 15 days of rhIL3. No augmentation of circulating BFU-E and CFU-GEMM was seen in 5 patients with MDS who had few or no PB BFU-E or CFU-GEMM initially. Total leukocyte, neutrophil, and eosinophil counts increased significantly (P less than .01) in 21 of 22 patients with a peak response after a median of 13 days of rhIL3. While a small increase in reticulocytes was not accompanied by an elevation of the hemoglobin or hematocrit, platelet counts increased by 50% in patients with preserved marrow function. Thus, rhIL3 induces a multilineage response in vivo, apparently by stimulating proliferation of multipotential and lineage-restricted progenitors. It remains to be determined whether this is due to direct or indirect effects on the progenitor cells.

Adult↗
PubMed1990

Effects of recombinant human interleukin-3 in aplastic anemia.

In a phase I/II study, nine patients with aplastic anemia were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biologic effects of this multipotential hematopoietic growth factor. Doses ranging from 250 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injections daily for 15 days. An increase in platelet counts from 1,000/microL to 31,000/microL was induced by rhIL-3 in one patient, and an increase in reticulocyte counts by more than 10,000/microL in four patients. The blood leukocyte counts temporarily increased in eight patients 1.5- to 3.3-fold (median, 1.8-fold), mainly due to an increase in the number of neutrophils, eosinophils, lymphocytes, and monocytes. In two patients, bone marrow cellularity increased from 7% to 33% and from 10% to 80%, respectively, but without resulting in a substantial improvement of peripheral blood counts. Mild side effects (headache and flushing) were observed in some patients, while low-grade fever occurred in all patients. Transient thrombocytopenia necessitating discontinuation of rhIL-3 treatment occurred in one patient. In conclusion, rhIL-3 can stimulate hematopoiesis in patients with aplastic anemia; however, no lasting effects were obtained.

Adolescent↗
PubMed1990

Effects of recombinant human interleukin-3 in patients with normal hematopoiesis and in patients with bone marrow failure.

In a phase I/II study, 19 patients with advanced tumors but normal hematopoiesis and nine patients with bone marrow failure and prolonged severe cytopenias were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biological effects of this multipotential hematopoietic growth factor. Doses ranging from 30 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injection daily for 15 days. A dose-dependent increase in platelet counts ranging from 1.3-fold at 60 micrograms/m2 to 1.9-fold at 250 micrograms/m2 was induced by rhIL-3 in 15 of 18 evaluable patients with normal hematopoiesis. An increase in reticulocyte counts was observed in 14 patients. The blood leukocyte counts dose dependently increased 1.4- to 3.0-fold. In patients with bone marrow failure, platelet counts increased by a mean of sixfold (range, 1.3-fold to 14.3-fold) in five of eight evaluable patients. Reticulocyte counts increased 4.4-fold in six patients, and neutrophil counts increased by a mean of 3.1-fold in all eight patients. Platelet transfusions could be discontinued after treatment with rhIL-3 in two of three transfusion-dependent patients. Only mild side effects, mainly fever, headache, and flushing, were observed. These results indicate that rhIL-3 functions as a multilineage hematopoietin in vivo in patients with normal bone marrow function and in patients with secondary bone marrow failure.

Adult↗
PubMed1990

Effects of recombinant human interleukin-3 in patients with myelodysplastic syndromes.

In a phase I-II study, nine patients with myelodysplastic syndromes and concomitant severe transfusion-dependent cytopenias were treated with recombinant human interleukin-3 (rhIL-3) to improve hematopoietic function. Doses of rhIL-3 ranged from 250 micrograms/m2 to 500 micrograms/m2 and were given as daily subcutaneous bolus injections for 15 days. Blood leucocyte counts increased 1.3- to 3.6-fold in all nine patients, including neutrophils, eosinophils, lymphocytes, basophils, and monocytes. The mean absolute neutrophil counts increased from 1,350/microL (range, 150 to 2,420) to 2,660/microL (range, 300 to 9,380) (P less than .05) immediately after the end of rhIL-3 therapy and to a maximum count of 4,096/microL (range, 350 to 10,820) (P less than .01). Platelet responses were seen in two of four profoundly thrombocytopenic patients, resulting in discontinuation of platelet transfusion. The requirements for red blood cell transfusion temporarily improved in one patient. Stimulation of plasma cells was evident by a significant increase in serum IgM and IgA levels. Mild side effects (fever, headache, local erythema, and bone pain) were observed in some patients, while transient thrombocytopenia developed in two patients. Disease progression with an increase in blast cells was seen in one patient. These results suggest that rhIL-3 is effective in stimulating hematopoiesis of all lineages in patients with myelodysplastic syndromes and may produce at least short-term hematologic improvement.

Adult↗
PubMed1990

[Histopathology of the retina, optic fascicle and lateral geniculate body in chronic, bilateral symmetric ischemic Schnabel's cavernous optic atrophy].

The paper is a unique pathological description of a bilateral, symmetric, anterior, temporal ischemic optic neuropathy with the morphological characteristics of cavernous optic atrophy initially described by Schnabel in glaucomatous eyes. The 80-year-old woman had suffered from cardiac insufficiency and diabetes mellitus for many years. She died from sepsis and circulatory collapse due to ischemic colitis, intestinal perforation, and peritonitis. There was widespread arteriosclerosis but no evidence of giant-cell arteritis. Cell loss was demonstrated in both retinas, the chiasm, and in the central lateral geniculate body. These represent a retrograde, descending and ascending optic atrophy, with transsynaptic degeneration in the LGB. A small craniopharyngioma was found by chance in the infundibulum. Neither clinically nor morphologically were there any signs of glaucoma.

Aged↗
PubMed1990

[In vitro and in vivo effects of recombinant human interleukin-3 on hematopoietic progenitor cells].

As part of a phase I/II clinical trial with recombinant human Interleukin-3 (rhIL-3), bone marrow and peripheral blood cells from patients treated with rhIL-3 were assessed in vitro for effects on the cycling status and frequencies of erythroid, myelomonocytic and multilineage progenitor cells. Treatment with rhIL-3 induced a pronounced increase in S-phase rate of BFU-E, CFU-GEMM and day 14 CFU-GM. Circulating CFU-GEMM and day 14 CFU-GM were increased on day 7 of therapy whereas circulating BFU-E were reduced in the majority of patients. After i.v. bolus injection of IL-3 an acute effect on the peripheral blood count with neutrophilia and, after an initial nadir, monocytosis was observed. IL-6 serum-levels increased in 5 out of 14 patients after IL-3 administration with concomitant side effects in 2 patients in whom IL-6 levels increased above 75 pg/ml. In the majority of the patients a stimulation of peripheral leukocytes and platelets was observed during the 15 day treatment course. In conclusion rhIL-3 induces a multilineage response in vivo by stimulating proliferation of hemopoietic progenitor cells with a resulting elevation in peripheral blood counts.

Bone Marrow↗
PubMed1990

Effects of recombinant human IL-7 on blast cell proliferation in acute lymphoblastic leukemia.

We investigated the effects of interleukin-7 (IL-7), a stromal cell derived cytokine known to stimulate proliferation of murine lymphoid precursor cells, alone and in combination with IL-3, IL-1, and IL-6 on proliferation of purified blast cells in acute lymphoblastic leukemia (ALL). After 7 days of liquid culture DNA-synthesis was induced in six of 10 cALL, three of five B-ALL, and two of seven T-ALL samples by IL-7 or IL-3 or both. Monitoring of leukemic cell populations in suspension culture by Southern blot analysis of immunoglobulin and T cell receptor gene rearrangements revealed preferential stimulation of the leukemic cell clone by both IL-7 or IL-3 in one cALL and one B-ALL sample. In these cases the combination of IL-7, IL-3, and IL-1 was as effective in stimulation of DNA-synthesis as the most potent cytokine alone. There was no evidence of lymphoid maturation during liquid culture as defined by immunophenotyping using flow cytometry. Stimulation of nonleukemic cell population seen in two other cases of cALL was associated with residual erythroid and granulocyte-macrophage colony forming cells after liquid culture as defined in parallel clonogenic assays in one and detection of CD 33+ and CD 13+ cells after culture in the other cALL sample. We conclude that IL-7 directly stimulates monoclonal growth of leukemic cells in a subset of ALL without evidence of concurrent maturation induction.

Adolescent↗
PubMed1988

Uptake and subcellular distribution of injected transferrin in rat liver.

Radioactively labelled transferrin was injected into rats intravenously and its uptake and subcellular distribution in the liver was investigated. The amount of radioactivity in the liver remained constant from 10 min after injection. It was not influenced by asialoglycoproteins. The radioactive label was identified as asialotransferrin. After subcellular fractionation by differential and zonal sucrose density-gradient centrifugation the label was enriched in a low-density endocytic compartment showing fluorescence quenching of acridine orange and N-ethylmaleimide-sensitive ATPase activity. The data fit into a model of continuous transferrin-receptor-mediated recycling through the hepatocyte's endocytic compartment.

Animals↗
PubMed1988

Metastatic patterns of renal carcinoma: an analysis of 687 necropsies.

The metastatic behaviour of renal cell carcinoma has been studied in a series of 687 necropsies. The observations were consistent with the concept of "metastatic inefficiency", in that in 295 cases, including 25 with renal vein invasion, there were no detectable metastases. In the present series, renal vein involvement was not an important prognostic factor in stage 1 or 2 disease. In 73% of cases without lung metastases there were none in other sites, and in 84% of those with lung metastases there were others elsewhere, consistent with a metastatic "cascade" in which metastases first developed in the lungs and were later detected in other organs. However, the observations did not permit discrimination between anatomic cascades, in which other organs were seeded from metastasizing pulmonary metastases, and temporal cascades, in which the other were seeded at the same time as the lungs, but with fewer cancer cells. The patterns of arterial metastasis were consistent with the "seed-and-soil" hypothesis, and a novel index was developed to quantify differential organ "soils". The contralateral kidney was not the best soil for metastases from renal carcinoma. Given the presence of lymph node metastasis, the probability of heamatogenous metastasis is 90%. However, in the absence of nodal metastasis, approximately half the cases had haematogenous metastasis.

Adult↗
PubMed1988

Cellular DNA content and metastasis pattern in colorectal carcinomas.

Tissue samples from primary tumours and metastases obtained from surgical specimens and autopsies were investigated by flow cytometry for their DNA content. Of the 149 cases investigated, 124 autopsy cases of colorectal carcinoma were suitable for study. The pattern of metastatic spread in each individual case was analysed with reference to the autopsy records. A subgroup of euploid primary tumours was observed which should be considered separately with regard to its biological behavior, tumour location and extent of metastases. In these tumours, the liver was the first and final organ of haematogenic metastatic spread at an above-random frequency and a grossly metastatic liver with less than 15% of residual normal parenchyma was present at the same time. Furthermore, we observed stem-lines deviating in ploidy from the primary tumour in the metastases of nine cases. This indicates the chromosomal heterogeneity of colorectal carcinomas.

Aged↗
PubMed1988

Characteristics of chylomicron remnant uptake into rat liver.

We have investigated uptake of 125I-labeled chylomicron remnants into livers of rats in the presence of lactoferrin. This glycoprotein possesses a cluster of four arginines at the N-terminus similar to the arginine rich binding sequence of apoprotein E (apoE) to the LDL-receptor. We found that this protein inhibits uptake of 125I-chylomicron remnant radioactivity by 50% when measured as accumulation of radioactivity into the intact organ, and even more pronounced, over 75%, when measured as uptake into an endosomal fraction prepared therefrom. Provided that the arginine rich sequence is responsible for the inhibition, a similarity in the characteristics of binding of apoE to the LDL (low density lipoprotein)- and chylomicron remnant-receptor is likely. Second, transferrin having sequence homologies with lactoferrin, but lacking the arginine cluster does not interfere with chylomicron remnant uptake. Third, lactoferrin does not inhibit the uptake of chylomicron remnants by the spleen, which is most likely mediated through scavenger cells by a mechanism different from the chylomicron remnant uptake system of the liver. We hypothesize from this that lactoferrin specifically interferes with the physiologically relevant chylomicron remnant uptake system of the liver. Investigation of the mechanism of this inhibition will provide information about the physical characteristics of the remnant receptor system.

Animals↗
PubMed1986

Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies.

The sequence of events in haematogenous metastasis from colonic carcinoma was analysed, using 1541 necropsy reports from 16 centres. The findings are consistent with the cascade hypothesis that metastases develop in discrete steps, first in the liver, next in the lungs and finally, in other sites. Deviations of necropsy findings from the cascade model are largely explained on the basis of false negative reports. In only 216 of 1194 cases was there suggestive evidence that metastatic patterns (excluding lymph nodes) were causally related to lymphatic or non-haematogenous pathways. The incidence of metastatic involvement in 'other' (quaternary) sites correlated with target organ blood-flow (ml min-) per g, only when bone marrow and thyroid were excluded. In the thyroid the incidence was lower than expected on the basis of blood flow per g tissue; this may indicate that the thyroid is an unfavourable site for metastatic growth of colonic carcinoma. In the bone marrow it is higher; the latter may be due to delivery of cancer cells via both arterial blood and the vertebral venous plexus. Recognition of this pattern of metastases in the bone marrow could be important with respect of diagnosis and therapy, in patients with colonic carcinoma.

Aged↗