摘要:

AbstractGenomic clones encoding bovine TGF-αwere identified by hybridization with probes derived from human TGF-αsequence. Nucleotide sequence of the clones predicts that mature bovine TGF-αis a 50 amino acid polypeptide which shares 96% and 92% homology with human and rat TGF-α, respectively. Bovine TGF-αwith the predicted sequence was chemically synthesized and tested for activity. Synthetic bovine TGF-αcompetes in a radioreceptor assay with labelled mouse EGF with activity parallel to that of human TGF-αand mouse EGF. The mitogenic activity of bovine TGF-αis comparable to that of human EGF in causing proliferation of bovine mammary epithelial cells. An∼5.0 kilobase RNA transcript is observed in polyadenylated RNA from MDBK cells by Northern blot analysis. The polymerase chain reaction detects the presence of a TGF-αtranscript in many bovine tissues. These data indicate that bovine TGF-αmay be a normal regulator of cell growth in the bovine animal.

ISSN:0897-7194    

DOI:10.3109/08977199009003668

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

AbstractA new animal model to study secondary intention wound healing and the effects of topically applied rhTGF-β1 was developed. A time course study was performed of full thickness 6 mm punch wounds placed on the backs of anesthetized pigs and treated once with either 3% methylcellulose or rhTGF-β1 in 3% methylcellulose or left untreated. Wounds receiving rhTGF-β1 had enhanced tensile strength at days 4 and 7 compared to controls. Studies of the response on days 4 and 7 to graded doses of rhtGF-β1 showed that a dose of 250 or 2500 ng rhTGF-β1 gave a similar enhanced wound strength, while 25 ng rhTGF-β1 had no effect. Blood flow to treated granulating wounds as measured by141Ce microspherrs indicate an increase in flow in wounds treated with 250, 500 or 2500ng rhTGF-β1 compared to controls. These results indicate a possible use for rhTGF-β1 in enhancing wound healing clinically.

ISSN:0897-7194    

DOI:10.3109/08977199009003669

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

AbstractInduction of mesoderm in ectodermal explants of Xenopus laevis blastula embryos had previously been shown to respond selectively to TGF-β2, with TGF-βs 1 and 5 having no activity in this assay. As TGF-βs 1, 2, and 3 are frequently coexpressed in tissues, we wished to examine the activity of TGF-β3 relative to that of TGF-βs 1 and 2 in this assay as well as in other in vitro assays. We report here that when the activity of recombinant TGF-β3 is normalized to that of TGF-β1 in the assay for growth inhibition in CCL-64 cells, it is also equal to that of TGF-β1 in assays for stimulation of both anchorage-independent growth of rat NRK cells and chemotaxis of human monocytes. In contrast, in the assay for mesoderm induction, recombinant TGF-β3 is 10-fold more active than TGF-β2, inducing expression of muscle specificα-actin at concentrations as low as 1 ng/ml. These results suggest that more complex systems, in contrast to individual cell types, may respond selectively to the various TGF-βisoforms and that there might be biological consequences of TGF-βisoform switching in vivo.

ISSN:0897-7194    

DOI:10.3109/08977199009003670

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

AbstractHuman acidic fibroblast growth factor (aFGF) is a potent broad-spectrum mitogen that contains three Cys residues within its monomeric structure. We have found that sitedirected mutants in which any one of these Cys residues is converted to serine remain highly active, although variably dependent on heparin, so none of the three possible intramolecular disulfide bonds that can be formed are required for mitogenic activity. Furthermore, a dispensable disulfide bond that might stabilize the active conformation is not present since all three Cys residues are accessible to chemical modification in recombinant as well as brain-derived aFGFs. Finally, formation of a disulfide bond between the two Cys residues conserved among all seven known members of the FGF family results in a virtually inactive product that can subsequently be reactivated by reduction. Thus, despite the extracellular function of aFGF, its Cys residues do not form intramolecular disulfide bonds in the active conformation.

ISSN:0897-7194    

DOI:10.3109/08977199009003671

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

AbstractBiopsies of human endometrium were studied for the presence of basic fibroblast growth factor (bFGF). An immunoreactive Mr 18 000 bFGF-like molecule was detected at high levels both in ovulatory cycle and postmenopausal endometrium. This molecule was identified as bFGF on the basis of its molecular weight, its affinity for heparin, its capacity to induce plasminogen activator production and cell proliferation in endothelial GM 7373 cells, and its cross-reactivity with various anti-bFGF antibodies. The levels of endometrial bFGF do not change during the menstrual cycle but they increase significantly after menopause, as evaluated both by biological and immunological assays. Lower levels of an acidic FGF-like activity were also evident in ovulatory cycle endometrium but, at variance with bFGF, no significant increase of this activity was observed in postmenopausal endometrium. These data represent the first characterization of a polypeptide growth factor present in human endometrium.

ISSN:0897-7194    

DOI:10.3109/08977199009003672

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

AbstractInsulin-like growth factor I (IGF-I; somatomedin C) has previously been demonstrated, with immunohistochemical methods, to accumulate locally at the site of trauma of an injured peripheral nerve. In the experiments reported here a Y-shaped silicone-chamber system was used to test if local infusion of IGF-I had supportive effects on nerve regeneration. The proximal end of a cut sciatic nerve was inserted into one channel of the Y-shaped chamber and the length and growth direction of the regenerating myelinated axons were evaluated after 1 month. When IGF-I (250μ;g/ml 0.5μ;l/h) was infused into one channel by an osmotic pump, the length of the regenerating axons increased significantly compared to the control groups with no IGF-I added. In some instances the regenerating axons grew towards the osmotic pump. It is concluded that local infusion of IGF-I at appropriate concentration promotes regeneration of a peripheral nerve. It exerts a neuronotrophic but not a clear chemotactic effect.

ISSN:0897-7194    

DOI:10.3109/08977199009003673

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

AbstractPlatelet-derived growth factor (PDGF) receptor transfectants of a fibroblastoid cell line (BHK) have been used to investigate the ability of the three dimeric forms of PDGF to elicit a chemotactic response. Cells transfected with theβreceptor subunit were only responsive to PDGF-BB, whereas cells expressing theα-receptor subunit were equally responsive to all three dimeric forms, PDGF-AA, PDGF-AB, and PDGF-BB. A positive chemotactic response correlated with rearrangement of actin organization. In a study of human arterial smooth muscle cells that express both PDGF receptor subunits endogenously, we again found that recombinant PDGF-AA could elicit a chemotactic response. However, the two smooth muscle cell isolates we examined differed in their chemotactic response to PDGF-AA. This difference correlated closely with their ability to respond mitogenically to this PDGF dimeric form, and the magnitude of both chemotactic and mitogenic responses was related to the proportion of the two receptor subunit species at the cell surface.

ISSN:0897-7194    

DOI:10.3109/08977199009003674

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

AbstractThe expression of granulocyte colony-stimulating factor (G-CSF) mRNA was studied in human non-hematopoietic tumors, including 18 cases of lung cancers 10 cases of stomach cancers, three cases of glioblastomas, and one case each of breast phyllode sarcoma, thyroid cancer, and hepatocellular carcinoma. Northern blot analysis detected G-CSF mRNA in two of the lung cancer cases, in one of the glioblastoma cases, and in both the breast phyllode sarcoma and hepatocellular carcinoma cases. Since G-CSF receptors were not detected on the tumor cells by125-I-G-CSF binding assay, G-CSF autocrine loop are probably not involved in the growth of these G-CSF-producing tumors. Interestingly, granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA was concomitantly expressed in most of these G-CSF-producing tumors. No major gene deletions or rearrangements of G-CSF and GM-CSF genes were demonstrated by Southern blot analysis in the tumors expressing G-CSF and GM-CSF mRNAs except for one of the glioblastomas (G3) in which one chromosome 17 allele was deleted. Although the mechanism of the concomitant expression of G-CSF and GM-CSF mRNA is unknown, relatively high frequency of this phenomenon suggests the presence of common transcriptional factors acting on regulatory regions of G-CSF and GM-CSF genomes.

ISSN:0897-7194    

DOI:10.3109/08977199009003675

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor