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S Meyer

Publications and source records attributed to S Meyer.

At least 19 recordsLinked to original sources
PubMed1996

Alpha-tocopherol as a reductant for Cu(II) in human lipoproteins. Triggering role in the initiation of lipoprotein oxidation.

Initiation of lipid peroxidation by Cu(II) requires reduction of Cu(II) to Cu(I) as a first step. It is unclear, however, whether this reaction occurs in the course of lipoprotein oxidation. It is also unknown which reductant, if any, can drive the reduction of Cu(II) in this case. We found that Cu(II) was rapidly reduced to Cu(I) by all major human lipoproteins (high, low, and very low density lipoproteins (HDL, LDL, and VLDL), and chylomicrons). Cu(II)-reducing activity was associated with a lipid moiety of the lipoproteins. The rates of Cu(II) reduction by different lipoproteins were similar when the lipoproteins were adjusted to similar alpha-tocopherol concentrations. Enriching lipoproteins with alpha-tocopherol considerably increased the rate of CU(II) reduction. CU(II) reduction by alpha-tocopherol-deficient LDL isolated from a patient with familial inherited vitamin E deficiency was found to occur much slower in comparison with LDL isolated from a donor with a normal plasma level of alpha-tocopherol. Initial rate of CU(II) reduction by alpha-tocopherol-deficient LDL was found to be zero. Enriching LDL with ubiquinol-10 to concentrations close to those of alpha-tocopherol did not influence the reaction rate. When LDL was treated with ebselen to eliminate preformed lipid hydroperoxides, the reaction rate was also not changed significantly. CU(II) reduction was accompanied by a consumption of lipoprotein alpha-tocopherol and accumulation of conjugated dienes in the samples. Increasing alpha-tocopherol content in lipoproteins slightly decreased the rate of conjugated diene accumulation in LDL and HDL and considerably increased it in VLDL. The results suggest that alpha-tocopherol plays a triggering role in the lipoprotein oxidation by CU(II), providing its initial step as follows: alpha TocH + CU(II) --> alpha Toc. + Cu(I) + H+. This reaction appears to diminish or totally eliminate the antioxidative activity of alpha-tocopherol in the course of lipoprotein oxidation.

Adult↗
PubMed1996

Nerve growth factor delivery by gene transfer induces differential outgrowth of sensory, motor, and noradrenergic neurites after adult spinal cord injury.

Several neurotrophic factors have been identified that influence neuronal populations during central nervous system development, maturation, and senescence. To examine the responsiveness of the intact and the lesioned adult mammalian spinal cord to neurotrophic factors, primary rat fibroblasts were genetically modified to produce and secrete human nerve growth factor (NGF). These NGF-producing cells were then grafted to nonlesioned or lesioned adult rat spinal cords for periods of up to 1 year in vivo. Robust outgrowth of sensory and noradrenergic neurites was elicited by grafts in the previously nonlesioned spinal cord. Equally robust growth of sensory and noradrenergic neurites was observed in the lesioned spinal cord; in addition, partial sprouting of local motor neurites was elicited in the lesioned spinal cord. Thus, multiple neuritic populations of the adult spinal cord respond to neurotrophic factors by extending neurites, and this responsiveness is maintained and extended after major injury. Nerve growth factor delivered by somatic gene transfer may be a useful means of promoting axon regrowth in the injured spinal cord.

Adrenergic Fibers↗
PubMed1995

Enhanced human Kupffer cell-mediated cytotoxicity after activation of the effector cells and modulation of the target cells by interferon-gamma: a mechanistic study at the cellular level.

In this study we demonstrate enhanced Kupffer cell (KC) cytotoxicity against several colorectal cell lines by activation of KC and by modulation of the targets (SW948, WiDR, HT29, and SW620) with IFN-gamma. We demonstrated that soluble TNF-alpha had no effect on these tumor cells, while cytotoxicity against SW948 and WiDR was blocked by anti-TNF-alpha. Experiments using a transwell system stressed the importance of close intercellular contact for this process. Anti-IL-1 did not inhibit cytotoxicity against SW948. Modulation of HT29, WiDR, and SW948 by IFN-gamma (500 U/ml) induced a significant increase in cytotoxicity. We conclude that cell-associated TNF-alpha may be responsible for KC cytotoxicity against SW948, a process requiring close intercellular contact. WiDR is only partly lysed by a TNF-alpha-dependent mechanism, whereas HT29 is not. Furthermore, IFN-gamma is involved in the regulation of tumor susceptibility.

Cytotoxicity, Immunologic↗
PubMed1995

Novel isolation and purification method permitting functional cytotoxicity studies of macrophages from milky spots in the greater omentum.

Milky spots in the greater omentum are well organized perivascular infiltrates of leukocytes which are probably involved in the clearance of tumor cells from the peritoneal cavity. In milky spots, macrophages are the predominant cell type forming a distinct population of cells. To investigate whether these macrophages have a function in the control of metastatic spread in the peritoneal cavity, a novel isolation and purification method was developed in order to study the functional cytotoxicity of macrophages from milky spots in the greater omentum against tumor cells in vitro. In order to obtain a cell suspension, greater omenta of unstimulated healthy male WAG/RIJ rats were incubated in collagenase/DNase suspension and filtered. Subsequently, macrophages were isolated and purified using flow cytometry by sorting unstained cells on the basis of size and internal complexity. Macrophages and other cells were identified by routine May-Grünwald-Giemsa staining and by immunophenotyping with the specific macrophage monoclonal antibody ED 1. Furthermore, macrophage subtypes were characterized by ultrastructural analysis. Functional cytotoxicity of the isolated macrophages was assayed against the syngeneic CC 531 tumor cell line in a colorimetric MTT assay. From three greater omenta of healthy rats 1.16 +/- 0.16 x 10(6) macrophages were isolated with a purity of 83 +/- 2% and a viability of > or = 96%. The macrophages were of the exudate (monocytic), exudate-resident and resident cell type and were in equal proportions. The contaminating cells were mainly mesothelial. A maximum cytotoxicity of approximately 30% was reached with the macrophage fraction at an effector-to-target ratio of 10. Furthermore, it was established that the mesothelial cells did not exhibit cytotoxicity.

Animals↗
PubMed1995

In vitro growth of factor-dependent multipotential hematopoietic cells is induced by the nuclear oncoprotein v-Ski.

Understanding how self renewal, commitment and differentiation are regulated in normal, multipotent hematopoietic progenitors is important for our understanding of underlying mechanisms involved in leukemogenesis. In addition, knowledge of progenitor cell biology is critical if these cells are to be used for gene therapy. In this communication, we demonstrate that the oncogenic transcription factor v-Ski, together with the ligand activated receptor tyrosine kinase c-Kit, induces the continuous in vitro self renewal of primary avian multipotent progenitors. These cells have an in vitro life span of > 100 generations. In addition they spontaneously differentiate into cells of the erythroid, monocytic and granulocytic lineages. If clonal strains of these multipotent progenitors are exposed to specific mixtures of growth factors and hormones, they develop into committed cells of either the erythroid or myeloid lineages. These committed cells underwent efficient terminal differentiation when they were treated with the relevant lineage-specific growth/differentiation factors, but underwent apoptosis when exposed to the incorrect factors for the respective lineage. While the committed cells coexpress marker proteins from different lineages, expression of the 'wrong' lineage marker is repressed during terminal differentiation. Our results indicate that a combination of v-Ski and activated c-Kit induces long-term self renewal in primary multipotent progenitors, which can be induced to commit and differentiate along specific lineages under different, defined conditions. Our data also suggest that growth factors and steroid hormones control terminal differentiation by a combined induction of commitment, growth and apoptosis, a process likely to be affected in stem cell leukemias.

Cell Division↗
PubMed1995

Primary, self-renewing erythroid progenitors develop through activation of both tyrosine kinase and steroid hormone receptors.

BACKGROUND: Self renewal in the hematopoietic system is thought to be restricted to a class of pluripotent stem cells. The capacity of cells with the properties of committed progenitors to self renew in many leukemias is thought to be an abnormal property resulting from the mutations responsible for leukemic transformation. It is not known how cells that can self-renew differ from cells that cannot. The notion that only pluripotent stem cells self renew has recently been challenged: normal committed erythroid progenitors capable of sustained self renewal have been described. These cells, called SCF/TGF alpha progenitors, co-express the c-Kit receptor tyrosine kinase and c-ErbB, the avian receptor for epidermal growth factor and transforming growth factor (TGF) alpha, and they undergo continuous self renewal in response to TGF alpha and estradiol. In contrast, common erythroid progenitors (termed SCF progenitors) express only c-Kit and undergo a limited number of cell divisions in response to the c-Kit ligand, stem cell factor (SCF). Both types of progenitor faithfully reproduce terminal erythroid differentiation in vitro when exposed to differentiation factors. Here, we have investigated the developmental origin of these two classes of self-renewing erythroid progenitors. RESULTS: We show that SCF progenitors can develop into SCF/TGF alpha progenitors. This developmental conversion requires 10-14 days and is accompanied by a gradual up-regulation of bioactive TGF alpha receptor. Using sera depleted of endogenous growth factors, we demonstrate that the development of SCF progenitors into SCF/TGF alpha progenitors absolutely requires the simultaneous presence of SCF, TGF alpha and estradiol, and is strongly enhanced by an unknown activity in chicken serum. CONCLUSIONS: SCF progenitors can be induced to develop into self-renewing SCF/TGF alpha progenitors. The development of self renewal is triggered by specific combinations of growth factors and hormones. This has important implications for understanding leukemogenesis, as the self renewal of leukemic cells may reflect the normal potential of certain committed progenitor cells and not, as has been thought, a unique abnormal property of leukemic cells.

Animals↗
PubMed1995

Identification of the binding site for the Shc protein to the avian erythroblastosis virus (AEV-H) v-erbB protein.

Activation of tyrosine kinase growth factor receptors leads to autophosphorylation of specific tyrosine residues within the intracellular region of the receptor. The phosphorylated tyrosines serve as binding sites for various cytoplasmic proteins. The Shc protein is one such protein. Upon activation of the chicken c-erbB protein by ligand Shc binds to the c-erbB protein and becomes phosphorylated on tyrosine. Similarly, Shc is found bound to the constitutively phosphorylated v-erbB protein encoded by the avian erythroblastosis virus strain H, AEV-H. Utilizing various mutant forms of the v-erbB protein, the residue equivalent to tyrosine 1154 in the chicken c-erbB protein was shown to serve as a binding site for the Shc protein to the AEV-H v-erbB protein. However, binding to this site was not essential for transformation since v-erbB oncoproteins which lacked this site still transform both erythroid cells and fibroblasts.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Cellular composition of milky spots in the human greater omentum: an immunochemical and ultrastructural study.

BACKGROUND: Milky spots in the greater omentum of some animals are well organized perivascular infiltrates of leucocytes, and are considered to have characteristics of secondary lymphoid tissue. To determine whether milky spots in the human greater omentum can also be regarded as secondary lymphoid tissue, we studied milky spots in an unstimulated state. METHODS: Patients were selected on the basis of absence of disease in the peritoneal cavity that might influence the state of the milky spots. Using monoclonal antibodies against macrophages, B-lymphocytes and T-lymphocytes, and immunoperoxidase labeling, the number of these cells and their location in milky spots were studied by light microscopy. However, the stromal components of the greater omentum, especially those within the milky spots, were studied by electron microscopy. RESULTS: Milky spots in the human greater omentum are relatively uniform vascularized accumulations of mononuclear cells comprising macrophages (67.9% +/- 9.4, mean +/- standard deviation), B-cells (10.1% +/- 3.4), T-cells (10.2% +/- 3.7), and mast cells. However, no special B-cell and T-cell areas could be distinguished. On the ultrastructural level it was demonstrated that macrophages are present in different stages of maturation and can enter or leave the milky spots. Furthermore, no cells characteristic of secondary lymphoid organs, such as interdigitating cells or follicular dendritic cells, were seen. CONCLUSIONS: These data indicate that unstimulated milky spots in the human greater omentum are to a great extent just a preformed specific accumulation of primarily macrophages within the stroma of the greater omentum, and therefore, cannot be regarded as true secondary lymphoid tissue. Milky spots could serve as a gateway for, as well as a provider of peritoneal macrophages when the intra-abdominal status so requires. Finally, the data from this study are compared with the data of other studies of human milky spots and those in animals.

Adolescent↗
PubMed1995

Fresh colorectal tumor cells isolated from individual patients differ in their susceptibility to monocyte mediated cytotoxicity.

Studies on monocyte/macrophage mediated cytotoxicity usually pertain to the use of cell lines that are liable to antigenic and structural changes. Therefore we compared monocyte mediated cytotoxicity against colorectal tumor cell lines (WiDR, HT29, SW620, and SW948) with fresh colorectal tumor cells from patients. Fresh tumor cells were isolated from surgical specimens by a short enzymatic treatment (Collagenase/DNAse). Monocytes were obtained from one healthy donor. Cytotoxicity was determined using the MTT-assay. Fresh colorectal tumor cells displayed a similar differential susceptibility to cytotoxic monocytes as cell lines. Cytotoxicity against fresh tumor cells ranged from 4.9% to 50.4% at E/T ratio 5 (n = 9). Activation of monocytes with Interferon-gamma (100 U/ml) induced an increase of 6.2% +/- 1.6 (n = 4, P = 0.06). In this study we demonstrate monocyte mediated cytotoxicity against colorectal tumor cells isolated from individual patients. This may be important in view of the development of adoptive immunotherapy and cell-directed immunotherapy.

Cell Separation↗
PubMed1995

The combination 5-fluorouracil/levamisole induces enhanced rat Kupffer cell-mediated cytotoxicity in vitro against the syngeneic colon adenocarcinoma cell line CC531.

The mode of action of the combination treatment 5-fluorouracil (5-FU) and levamisole in colorectal cancer patients is unknown. It is postulated that the beneficial effect may be explained by an immunomodulatory effect on Kupffer cell (KC) cytotoxicity. We evaluated the effect of levamisole (200 micrograms/ml) and 5-FU (10 microM) on rat KC cytotoxicity against syngeneic CC531 tumor cells. Viability of KCs was unaffected by 5-FU and/or levamisole. The combination did not enhance growth inhibition of CC531 compared to 5-FU alone. A significant increase in KC cytotoxicity was observed after 24-hr incubation with 5-FU/levamisole especially at an effector/target ratio of 10 (P < 0.05). 5-FU alone had no effect on KC cytotoxicity, while levamisole induced only a slight increase. Our in vitro data suggest that the additive effect of the combination 5-FU/levamisole on KC cytotoxicity may attribute to the beneficial effect of the adjuvant treatment in colorectal cancer patients.

Adenocarcinoma↗
PubMed1995

[Vasomotor disorders of the hand and carpal tunnel syndrome].

Clinical electrophysiological and chronothermodynamic examinations were performed on 71 patients with paresthesiae and pain of the hands. In 35 patients, the electromyographic examination confirmed the diagnosis of carpal tunnel syndrome on the basis of clear signs of chronic compression of the median nerve at the carpal tunnel. In the other 36 patients, the electro-physiological findings were normal. Twenty-nine patients with bilateral (n = 24) or unilateral (n = 5) carpal tunnel syndrome, and 29 patients without, this syndrome had chronothermodynamic abnormalities demonstrating the vascular origin of the disorders of the hands; in 18 patients, a Raynaud's syndrome was suspected on the basis of severe dysthermia. In 7 patients, the origin of pain and paresthesiae remained unknown. This study shows that (i) vascular disorders of the hand are very frequent in patients with paresthesiae and pain of the hands and may mimic a carpal tunnel syndrome, and (ii) clinical examination is insufficient to assess the diagnosis of carpal tunnel syndrome. Before deciding on any kind of therapy, this diagnosis has to be assessed on electrophysiological and chronothermodynamic examinations performed according to precise protocols.

Adult↗
PubMed1995

Pretreatment with enteral cholestyramine prevents suppression of the cellular immune system after partial hepatectomy.

OBJECTIVE: The authors tested the hypothesis that the beneficial effects of the endotoxin-binding agent cholestyramine on the postoperative course in rats that had undergone a partial hepatectomy was the result of improvement of cellular immune functions. SUMMARY BACKGROUND DATA: Major liver resection is associated with severe postoperative complications and a high incidence of systemic infections. Gut-derived endotoxins previously were shown to be involved in the pathogenic processes after partial hepatectomy in rats. In addition, enteral cholestyramine improved postoperative survival, but how its beneficial effects are mediated is not clear. METHODS: Rats that were force-fed for 7 days with either cholestyramine (150 mg/day) or 0.9% saline (equal volume) were randomized to undergo a partial hepatectomy or a sham operation. After 24 hours, the rats were killed and splenic mononuclear cells were tested in vitro for mitogenic responses and cytokine production. RESULTS: Proliferative responses of splenic B and T lymphocytes and lipopolysaccharide-stimulated production of tumor necrosis factor and interleukin-1 by splenocytes were lower in rats after partial hepatectomy than in sham-operated animals. An increased concanavalin A-stimulated production of interleukin-2 also was found after partial hepatectomy compared with sham levels. Pretreatment with enteral cholestyramine preserved cellular proliferative responsiveness of both B and T cells, and restored cytokine production by splenocytes to sham levels. CONCLUSION: Prophylactic treatment with enteral cholestyramine preserved cellular immune functions after partial hepatectomy in the rat, which may explain its beneficial effects on the postoperative course. Furthermore, the authors' results are consistent with the hypothesis that endotoxemia is involved in the pathogenesis of the cellular immune derangements after partial hepatectomy.

Administration, Oral↗
PubMed1995

Single-strand breaks in deoxyribonucleic acid in fire fighters accidentally exposed to o-nitroanisole and other chemicals.

OBJECTIVES: The aim of the study was to detect single-strand breaks in deoxyribonucleic acid (DNA) in mononuclear blood cells of fire fighters exposed to o-nitroanisole and other substances released into the environment during an accident in a chemical plant. METHODS: The level of DNA single-strand breaks in mononuclear blood cells was detected by alkaline elution. The results were compared for 16 fire fighters who worked in a contaminated area for about 8 h and two reference groups (one of fire fighters who had not worked in the contaminated area, group I, and one of persons without any apparent occupational exposure to genotoxic substances, group II). RESULTS: The mean normalized elution rate (nER) 19 d after the accident was slightly but statistically significantly (P < 0.05) higher for the exposed fire fighters [mean 1.48 +/- 95% confidence interval (95% CI) 0.21] than for reference group I (mean 1.21 +/- 95% CI 0.21) or reference group II (mean 1.17 +/- 95% CI 0.18). No statistically significant difference was found between reference groups I and II. Another analysis was performed three months after the first. The level of DNA single-strand breaks (mean nER 1.12 +/- 95% CI 0.11) was no longer increased in comparison with the levels of the reference groups. CONCLUSIONS: DNA single-strand breaks were increased in fire fighters exposed to o-nitroanisole and other substances. In comparison with the extent of DNA strand breaks found in other occupational groups the increase was only moderate. The observed decrease in DNA single-strand breaks to the reference level in exposed fire fighters three months later suggests a DNA repair mechanism for DNA single-strand breaks caused by o-nitroanisole.

Accidents↗
PubMed1995

Liver failure induces a systemic inflammatory response. Prevention by recombinant N-terminal bactericidal/permeability-increasing protein.

The observed increased susceptibility of patients with fulminant hepatic failure for local and systemic infections has been hypothesized to be due to a failure for the hepatic clearance function and subsequent leaking of endogenous endotoxins into the systemic circulation. However, experimental evidence for such a systemic inflammation during liver failure due to endogenous endotoxemia is lacking. Therefore, we designed a study to clarify whether circulating endotoxins due to liver failure could lead to the development of systemic inflammations. In a rat model for liver failure induced by a two-thirds partial hepatectomy, we evaluated the course of circulating tumor necrosis factor and interleukin-6, changes in blood chemistry and hemodynamics, and histopathological changes in the lungs. Partially hepatectomized animals, but not sham-operated animals, demonstrated cardiac failure, increased levels of creatinin and urea, metabolic acidosis, high plasma levels of tumor necrosis factor and interleukin-6, and an influx of PMNs in the lungs-together indicating the development of a systemic inflammatory response. Continuous infusion of recombinant N-terminal bactericidal/permeability-increasing protein (rBPI23), a well described endotoxin-neutralizing protein, prevented these inflammatory reactions. Ex vivo experiments with rat plasma samples confirmed the presence of circulating endotoxins in partially hepatectomized rats as opposed to those treated with rBPI23. Thus, our results indicate that the early phase of liver failure induces a systemic inflammatory response triggered by circulating endotoxins, which can be prevented by perioperative infusion of rBPI23.

Animals↗
PubMed1995

Apolipoprotein E isoforms and rare mutations: parallel reduction in binding to cells and to heparin reflects severity of associated type III hyperlipoproteinemia.

The LDL receptor-independent binding of human apolipoprotein E isoforms and rare apoE mutations were studied on LDL receptor-deficient human fibroblasts using chemical cross-linking and cell binding studies. The cross-linking experiments demonstrated that all apoE variants bind to the low density lipoprotein receptor-related protein, a potential receptor for remnant lipoproteins. In cell binding studies, the effect of the apoE variants on binding of beta-VLDL was investigated. Addition of normal apoE-3 to the binding assay resulted in a 12-fold increase of beta-VLDL particle binding, whereas this effect was reduced in the clinically defective variants: apoE-2, (Arg158-->Cys), 24.4% of apoE-3; apoE-1, (Gly127-->Asp, Arg158-->Cys), 49.2% of apoE-3; apoE-1(Lys146-->Glu), 18.2% of apoE-3. Heparin binding studies with the same variants showed a parallel reduction in proteoglycan binding (apoE-2(158), 58.2% of apoE-3; apoE-1(127,158), 37.9%; apoE-1(146), 20.6%). We conclude that LDL receptor-independent mechanisms contribute to remnant clearance. The functionally dominant mutation apoE-1(146) was most defective in heparin binding studies in vitro. In cell binding studies, apoE-1(146) did mediate lipoprotein binding only 18% compared to apoE-3. This indicates the important role of the apoE interaction with proteoglycans in vivo and could explain the development of type III hyperlipoproteinemia in patients with such apoE variants.

Animals↗
PubMed1995

[The German Cardiovascular Prevention Study: social gradient for the net effects in prevention of hypercholesterolemia].

Hypercholesterolemia is considered an important risk factor for cardiovascular disease. The net effects of 7 years of a community prevention programme using principally a high-risk strategy (screening, referrals to general practitioner) in the German Cardiovascular Prevention Study (GCP) are analysed according to socioeconomic status (SES). Cholesterol was measured in three subsequent cross-sectional population samples of adults (ages 25-69 years) in 1984-1985, 1988 and 1991-1992 in the regions of Berlin, Bremen, Stuttgart, Karlsruhe with Bruchsal/Mosbach, and Traunstein (n = 11,548, 8743, 8636), in the region of Stuttgart only (n = 1791, 1437, 1313) and in the entire West German population (n = 4790, 5335, 5311) as reference. SES was determine by an additive, multiple index. Variations of means for phases and regions and resultant net differences were calculated. From 1984-1985 to 1991-1992 cholesterol declined from 232.7 to 231.8 mg/dl in the overall regions, from 232.0 to 230.5 mg/dl in Stuttgart, but increased from 233.5 to 236.9 mg/dl in the reference region. In the combined regions net differences according to SES were -4.2%***1) for the upper class, -1.6%** for the middle class and -0.3% for the lower class. Similar results were found comparing Stuttgart with the reference region (-5.4%***, -1.4%, -0.1%). The GCP intervention for hypercholesterolemia was successful basically only for the upper class, if net differences for the means are calculated. Prevention of hypercholesterolemia increased the social gradient in the pooled intervention regions and in Stuttgart.

Adult↗
PubMed1995

Transformation of erythroid progenitors by viral and cellular tyrosine kinases.

Recently, two different normal avian erythroid progenitors were described. They differ in the receptor tyrosine kinases they express and in their ability to undergo self-renewal in culture. A common progenitor, termed stem cell factor (SCF) progenitor, expresses the receptor for avian SCF c-Kit, and undergoes short-term self-renewal when grown in the presence of avian SCF. A second progenitor, referred to as SCF/transforming growth factor-alpha progenitor, coexpresses c-Kit and the avian epidermal growth factor receptor homologue c-ErbB. These progenitors undergo sustained self-renewal when grown in the presence of transforming growth factor-alpha plus estradiol. The phenotype of the normal SCF/transforming growth factor-alpha progenitors closely corresponded to that of erythroid cells transformed by the tyrosine kinase oncogenes v-erbB or v-sea. This suggested that these cells, but not the SCF progenitors, would be the target cells for erythroblast transformation by these oncogenes. However, we demonstrate that both progenitor cells can be transformed by the v-erbB and v-sea oncogenes and also by the ligand-activated proto-oncogene product c-ErbB. We conclude that the target cell specificity of certain tyrosine kinase oncoproteins for erythroid cells is a reflection of their ability to provide signals for self-renewal that normally emanate from the endogenous c-ErbB protein.

Animals↗