scholarly journals Inhibition of Wool Growth in Merino Sheep following Administration of Mouse Epidermal Growth Factor and a Derivative

1982 ◽  
Vol 35 (2) ◽  
pp. 163 ◽  
Author(s):  
GPM Moore ◽  
BA Panaretto ◽  
D Robertson

The present study investigates the effects of dosage and different modes of delivery of mouse epidermal growth factor (EG F) on the production of breaks in the fleece and on wool growth in Merino wethers. Subcutaneous infusions of EGF of ~O� 25 mg kg- o.75 for 7-28 h resulted in a dose-dependent total or partial inhibition of wool production 2-4 weeks later. A complete break appeared in the fleece that was shed. Lower doses had lesser inhibitory effects on wool growth: the fleece was not shed but bore a zone of weakness, termed an incomplete break. Inclusion of the glucocorticoid analogue dexamethasone in the infusate did not alter the action of EGF on the fleece. Although a higher plane of nutrition increased the rate of fibre production, it did not alter the extent of inhibition of wool growth by EGF. Infusion of a peptide from EGF, which lacked eight of the C-terminal amino acids (EGFl _ 45), was as effective as the parent molecule in inhibiting wool growth. EGF administered as a single subcutaneous injection was less reliable as a method for producing breaks in the fleece. Of seven wethers that received EGF at a dose level between 0�27 and 0�32 mg kg- o. 7 5, only three shed their fleeces. The remainder either developed incomplete breaks in the wool or were not affected. Administration of EGF at a dose level of 0�56 mg kg- 0. 7 5 via a rumen tube to one sheep had no discernible inhibitory effect on wool growth.

1982 ◽  
Vol 94 (2) ◽  
pp. 191-202 ◽  
Author(s):  
B. A. Panaretto ◽  
G. P. M. Moore ◽  
D. M. Robertson

Twenty-four adult Merino wethers were given mouse epidermal growth factor (mEGF) subcutaneously at doses ranging from 0·02 to 0·12 mg/kg body weight or intravenously in the dose range 010 to 0·14 mg/kg body weight for periods ranging from 3 to 48 h. Plasma concentrations of mEGF were measured by radioimmunoassay and effects of treatment on food consumption and wool growth were observed. Plasma concentrations of the protein sustained for 15–24 h at about 20 ng mEGF/ml (or exceeding this) almost invariably caused feed rejection and casting of the fleeces. This last result clearly indicated disruption of proliferative activity among the replicating cells in wool follicles which regulate wool growth. The inhibitory effects on appetite and wool growth of smaller doses of the protein and of plasma concentrations equal to those above which were sustained for shorter periods have also been examined. Approximately 10% of the dose of mEGF appeared in the urine of three sheep 1 to 3 days after the start of s.c. infusions of 5 mg for 7 h.


1988 ◽  
Vol 41 (2) ◽  
pp. 261 ◽  
Author(s):  
RE Chapman ◽  
MH Hardy

Twice daily intradermal (ID) injections of mouse epidermal growth factor (mEGF) in sterile saline for 1-4 days into delineated areas of skin of Merino sheep produced dose-dependent changes in wool follicles and fibres, ranging from slight reduction in follicle bulb size and transient disturbance of cuticle formation on some fibres to the induction of catagen of follicles and shedding of fibres with distorted, tapered ends. Regeneration of follicles commenced by day 7. By contrast, ID injections of saline did not affect follicle activity. The epidermis became thicker and more parakeratotic after multiple injections of mEGF than after injection of saline, but was almost normal again by day 14. Persistent small increases in sebaceous gland size, additional to those induced by ID injections of saline, and delayed small increases in sweat gland size also occurred after multiple injections of mEGF.


2009 ◽  
Vol 27 (31) ◽  
pp. 5270-5277 ◽  
Author(s):  
Pravin T.P. Kaumaya ◽  
Kevin Chu Foy ◽  
Joan Garrett ◽  
Sharad V. Rawale ◽  
Daniele Vicari ◽  
...  

Purpose To evaluate the maximum-tolerated dose (MTD), safety profile, and immunogenicity of two chimeric, B-cell epitopes derived from the human epidermal growth factor receptor (HER2) extracellular domain in a combination vaccine with a promiscuous T-cell epitope (ie, MVF) and nor-muramyl-dipeptide as adjuvant emulsified in SEPPIC ISA 720. Patients and Methods Eligible patients with metastatic and/or recurrent solid tumors received three inoculations on days 1, 22, and 43 at doses of total peptide that ranged from 0.5 to 3.0 mg. Immunogenicity was evaluated by enzyme-linked immunosorbent assay, flow cytometry, and HER2 signaling assays. Results Twenty-four patients received three inoculations at the intended dose levels, which elicited antibodies able to recognize native HER2 receptor and inhibited both the proliferation of HER2-expressing cell lines and phosphorylation of the HER2 protein. The MTD was determined to be the highest dose level of 3.0 mg of the combination vaccine. There was a significant increase from dose level 1 (0.5 mg) to dose level 4 (3.0 mg) in HER2-specific antibodies. Four patients (one each with adrenal, colon, ovarian, and squamous cell carcinoma of unknown primary) were judged to have stable disease; two patients (one each with endometrial and ovarian cancer) had partial responses; and 11 patients had progressive disease. Patients with stable disease received 6-month boosts, and one patient received a 20-month boost. Conclusion The combination vaccines were safe and effective in eliciting antibody responses in a subset of patients (62.5%) and were associated with no serious adverse events, autoimmune disease, or cardiotoxicity. There was preliminary evidence of clinical activity in several patients.


1988 ◽  
Vol 8 (2) ◽  
pp. 557-563
Author(s):  
P P Di Fiore ◽  
J Falco ◽  
I Borrello ◽  
B Weissman ◽  
S A Aaronson

BALB/MK mouse epidermal keratinocytes require epidermal growth factor (EGF) for proliferation and terminally differentiate in response to high calcium concentrations. We show that EGF is an extremely potent mitogen, causing BALB/MK cultures to enter the cell cycle in a synchronous manner associated with a greater than 100-fold increase in DNA synthesis. Analysis of the expression of proto-oncogenes which have been reported to be activated during the cascade of events following growth factor stimulation of fibroblasts or lymphoid cells revealed a very rapid but transient 100-fold increase in c-fos RNA but little or no effect on the other proto-oncogenes analyzed. Exposure of EGF-synchronized BALB/MK cells to high levels of calcium was associated with a striking decrease in the early burst of c-fos RNA as well as the subsequent peak of cell DNA synthesis. Since the inhibitory effect of high calcium on c-fos RNA expression was measurable within 30 min, our studies imply that the EGF proliferative and calcium differentiation signals must interact very early in the pathway of EGF-induced proliferation. Our results also establish that c-fos RNA modulation is an important early marker of cell proliferation in epithelial as well as mesenchymal cells.


1988 ◽  
Vol 255 (4) ◽  
pp. C447-C451 ◽  
Author(s):  
D. A. Grosenbaugh ◽  
M. S. Amoss ◽  
D. M. Hood ◽  
S. J. Morgan ◽  
J. D. Williams

Epidermal growth factor (EGF) receptor binding kinetics and EGF-mediated stimulation of DNA synthesis and cellular proliferation were studied in cultured vascular smooth muscle cells (VSMC) from the equine thoracic aorta. Binding studies, using murine 125I-labeled EGF, indicate the presence of a single class of high-affinity binding sites (apparent KD = 2.8 X 10(-11) M), with an estimated maximal binding capacity of 5,800 sites/cell. EGF stimulated [3H]thymidine uptake in confluent quiescent monolayers in a dose-dependent fashion, half-maximal stimulation occurring at 7.5 X 10(-11) M. Likewise, EGF-mediated cellular proliferation was dose dependent (50% effective dose = 5 X 10(-11) M) under reduced serum concentrations. Equine VSMC contain specific receptors for EGF, and EGF can stimulate DNA synthesis and proliferation in these cultured cells, which suggests that EGF may participate in the proliferative changes observed in equine distal digital peripheral vascular disease.


1982 ◽  
Vol 93 (1) ◽  
pp. 1-4 ◽  
Author(s):  
D W Barnes

A medium consisting of a rich basal nutrient mixture supplemented with bovine insulin (10 micrograms/ml), human transferrin (10 micrograms/ml), human cold-insoluble globulin (5 micrograms/ml), and ethanolamine (0.5 mM) supported the growth of the A431 human epidermoid cell line in the absence of serum with a generation time equal to that of cells in serum-containing medium. Addition of epidermal growth factor (EGF) to this culture medium at concentration mitogenic for other cell types resulted in a marked inhibition of A431 cell growth. Inhibitory effects of EGF were observed at 1 ng/ml and near-maximal effects were observed at 10 ng/ml. The inhibitory effect of EGF could be reversed by the omission of EGF in subsequent medium changes and could be prevented by the addition of anti-EGF antibody to the culture medium. Inhibition of A431 cell growth by EGF also could be demonstrated in serum-containing medium.


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