摘要:

AbstractGrowth hormone (GH) is known to regulate growth and development of skeletal tissues. This study examined the distribution of growth hormone receptor (GHR) expression in tibias from normal and osteopetrotictl/tlrats. For normal 2 week-old rats, GHR expression was detected immunocytochemically in cells of the articular and epiphyseal cartilage, primary and secondary ossification centres, zone of resting cartilage and bone marrow. Within the marrow, GHR immunopositive cells were concentrated in the central cone and largely excluded from the zone of immature progenitors at the periphery. For the marrow haemopoietic compartment, GHR expression was almost restricted to the nucleus in large mononuclear cells, adipocytes and megakaryocytes. A population of small lymphocyte-like cells in the marrow periphery expressed GHR on the plasma membrane. GHR was not detected in mature erythroid cells, macrophages, granulocytes, or osteoclasts. The expression of GHR was significantly reduced in bone marrow cells of thetl/tlrat (p<0.001) compared with normal animals. Injection of recombinant CSF-1 intotl/tlrats every 48 hours for 2 weeks from birth restored GHR-positive cells to the central core of the marrow space. The most striking change was the appearance of substantial numbers of mononuclear cells expressing abundant GHR on the cell surface. We infer that these cells are a novel subset of CSF-1 responsive cells involved in bone resorption. The differences in relative expression of GHR by bone marrow cells in untreated and CSF-1-treatedtl/tlrats suggests a CSF-1-dependent recruitment of cells bearing surface GHRs.

ISSN:0897-7194    

DOI:10.3109/08977199609034562

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractInsulin-like growth factor-I(IGF-I) has both metabolic and growth-promoting activities in many cell and tissue types. Although IGF-I is present in serum, it is also thought to have important autocrine and paracrine functions. Immunohistochemistry for IGF-I and its receptor have shown that IGF-I is synthesised locally by the tooth forming cells which exhibit both the IGF-I and the growth hormone receptors. This concept required to be tested byin situhybridization. Using a digoxigenin-labelled synthetic oligodeoxyribonucleotide probe for IGF-I, we investigated the distribution of IGF-I mRNA in the continuously erupting rat incisor by in situ hybridization. The distribution and intensity of the hybridization signal varied with the developmental stage of the rat incisor. The cells of the apical loop expressed a positive hybridization signal, but the earliest polarised odontoblasts and pre-ameloblasts did not show any positive signal. The onset of enamel secretion was accompanied by a strong hybridization signal in the secretory ameloblasts as well as the odontoblasts. Maturation ameloblasts also demonstrated IGF-I message in their cytoplasm as well as their nuclei. The cells of the pulp and the dental follicle were consistently negative. However, in the adjacent alveolar bone, the signal was high in the osteoblasts and osteoclasts. These findings support the notion of paracrine or autocrine function for IGF-I in tooth development.

ISSN:0897-7194    

DOI:10.3109/08977199609034563

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractThe important role of oncogene amplification and tumour suppressor gene deletion in human tumours is becoming increasingly apparent. However, extensive screening of human tumours is required before the prognostic significance of such genetic abnormalities can be fully appreciated. The present investigation describes a rapid non-radioactive and largely automated procedure for the analysis of aberrant gene copy number in large numbers of tissue samples of different human rumours. This procedure is based on the sequential use of the polymerase chain reaction (PCR) and high performance ion exchange liquid chromatography (HPIEX). Using this rapid PCR/HPIEX technique, we have identified amplification and deletion of the FGF-2 gene and the FGF-3, FGF-4 andc-erb-B2oncogenes in human tumours of the breast, ovary and endometrium. Comparison of the data with tumour pathology has revealed possible associations between aberrant gene copy number and tumour type, invasiveness and metastases.

ISSN:0897-7194    

DOI:10.3109/08977199609034564

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractThe effects,in vivo, of the exogenous administration of bFGF on myogenesis of regenerating skeletal muscle was assessed either morphometrically or autoradiographically in three separate models of muscle injury in mice: crush-injured, denervated, and dystrophic (mdx) muscles. The bFGF was administered at various doses and different time schedules, sometimes in combination with heparin, into injured tibialis anterior muscles of mice. Delivery of the bFGF was either by direct intramuscular injection or by the sustained release from polymers (Hydron or Elvax) implanted into the muscles. The bioactivity of bFGF was confirmedin vitroby measuring its ability to stimulate the proliferation of BALB/c-3T3 fibroblasts and muscle precursor cell lines. The ability of bFGF to stimulate angiogenesisin vivowas confirmed by the implantation of controlled-release polymers containing bFGF into the normally avascular cornea of rats. No measurable effect of bFGF was seen in any of the models of skeletal muscle injury under these experimental conditions, indicating that the availability of biologically active bFGF is not a limiting factor in the regeneration of skeletal muscle following injury.

ISSN:0897-7194    

DOI:10.3109/08977199609034565

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractNeovascularization is a feature of a variety of pathological processes. We compared the characteristics of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on migration and proliferation of human umbilical vein endothelium (HUVEC). Both VEGF and bFGF induced endothelial cell migration at similar concentrations (½max. VEGF =∼1.0 ng/ml, bFGF =∼5.0 ng/ml). However, VEGF-stimulated migration was two-fold greater than bFGF at 1 and 10 ng/ml (p<0.05). In contrast, bFGF induced proliferation four-fold more effectively than VEGF (½max. 1 ng/ml and 1.4 ng/ ml respectively). Checkerboard migration assays for bFGF showed a predominantly chemokinetic pattern, whereas VEGF was predominantly chemotactic. VEGF and bFGF were not synergistic in monolayer proliferation and migration assays. Three angiogenesis inhibitors, alpha-interferon, TNP-470, and platelet factor-4, inhibited VEGF and bFGF induced cell migration. These results indicate that VEGF and bFGF are chemoattractants that stimulate endothelial migration by different mechanisms and that both can be inhibited by known angiogenesis inhibitors.

ISSN:0897-7194    

DOI:10.3109/08977199609034566

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractWe have expressed and biologically characterized recombinant human growth/differentiation factor 5 (huGDF5). This protein is composed of a mature homodimer consisting of 15 kD subunits. Using recombinant expressed protein, we have demonstrated that huGDFSin vitrostimulated mesenchyme aggregation and chondrogenesis in rat limb bud cells.In vivo, partially purified huGDF5 induced cartilage and bone formation in muscular tissues of rodents. However, in contrast to the effects of other BMPs, as for example BMP-2, the osteoblastic MC3T3-E1 cells did not respond to huGDF5 as measured by alkaline phosphatase activity. These results suggest that the action of GDF5 may be relatively specific for chondrogenesis during the entire process of the endochondral bone formation. GDF5 may control the morphogenesis of cartilaginous tissue, including joints, in the skeletal development of limbs.

ISSN:0897-7194    

DOI:10.3109/08977199609034567

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractAcute graft-versus-host disease (GvHD) is an inflammatory disorder associated with generalised damage to epithelial tissues, including the gastrointestinal tract. There is increasing evidence that this pathology is due to the effects of cytokines on epithelial cell proliferation and differentiation. However, it is unclear whether factors derived from immune cells act directly on epithelial cells or via other mediators whose principal role is to regulate cell growth under normal or diseased conditions. We show here that the increased crypt cell turnover and lymphocytic infiltration which occurs in the jejunum of mice with graft-versus-host reaction (GvHR) is accompanied by decreased enterocyte expression of transforming growth factorβ2. Administration of exogenous TGFβinhibits the crypt hyperplasia of GvHR and reduces systemic manifestations of GvHR such as increased splenic natural killer (NK) cell activity. In parallel, neutralisation of endogenous TGFβby monoclonal antibody exacerbates both the proliferative and inflammatory components of intestinal and systemic GvHR. Thus, the immune system may induce epithelial pathology at least in part by altering the production of endogenous TGFβ. This cytokine may therefore prove a useful focus for therapeutic intervention in immunopathologies such as GvHD.

ISSN:0897-7194    

DOI:10.3109/08977199609034568

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractThe transforming growth factor beta (TGF-β) family of growth modulators play critical roles in tissue development and maintenance. Recent data suggest that individual TGF-βisoforms (TGF-β1, -β2 and -β3) have overlapping yet distinct biological actions and target cell specificities, both in developing and adult tissues. The TGF-β3 isoform was purified to homogeneity from both natural and recombinant sources and characterized by laser desorption mass spectrometry, by protein sequencing, by amino acid analysis and by biological activity. TGF-β3 was the major TGF-βisoform in umbilical cord (230 ng/g), and was physically and biologically indistinguishable from recombinant TGF-β3 and from the tumor growth inhibitory (TGI) protein found in umbilical cord. Immunohistochemistry using antipeptide TGF-β3 specific antibody showed TGF-β3 localization in perivascular smooth muscle.

ISSN:0897-7194    

DOI:10.3109/08977199609034569

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractAutocrine interleukin-3 (IL-3) expression of v-H-ras transformed mast cell tumors involves either IL-3 mRNA stabilization (class-I tumors) or enhanced IL-3 transcription (class-II tumors). Since calcium ionophores induce IL-3 expression in untransformed PB-3c cells by transcript stabilization, we asked whether class-I tumor could still respond to calcium ionophores. We found that ionomycin treatment further increased IL-3 mRNA expression of class-I tumor cells. Following ionomycin wash-out, IL-3 mRNA decay was slower in class-I tumor cells than in class-II tumor or precursor cell lines (t1,2>50 min versus<20 min, respectively). Somatic cell fusion of the class-I tumor cells with the non-tumorigenic PB-3c cells resulted in reversion to rapid decay after ionomycin wash-out. The data indicate that a recessive defect of IL-3 mRNA degradation can be revealed in class-I tumor cells by transient calcium ionophore stimulation. However, IL-3 mRNA stabilization operating constitutively in class-I tumor cells appears to be distinct from the ionomycin induced process.

ISSN:0897-7194    

DOI:10.3109/08977199609034570

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractOverexpression of transforming growth factor-α(TGF-α) in the gastric mucosa of metallothionein-TGFα(MT-TGFα) transgenic mice leads to a marked alteration in the ontogeny of the fundic cellular lineages. Induction of the transgene leads to the over-production of mucous cells with a concomitant diminution in the development of parietal cell and chief cell lineages. We have sought to define more precisely the mucous cell lineages involved in the mucous cell hyperplasia in MT-TGFαmice by investigating the expression of trefoil peptides in MT-TGFαmice. MT-TGFαmice and their non-transgenic littermates were treated with cadmium sulfate beginning at 13 days of age. Animals were then sacrificed at intervals over the following 2 weeks and gastric mucosa was examined for expression of trefoil peptides and TGFαby immunohistochemistry andin situhybridization. No TGFαmRNA expression could be demonstrated byin situhybridization in non-transgenic mice. In MT-TGFαmice,in situgrains for TGFαmRNA were detected at the base of fundic glands in 13 day old animals, whereas the expression was observed more widely in the mucosa of older animals (28 days). TGFαimmunoreactivity was observed in foveolar mucous cells and residual parietal cells in MT-TGFαmice at all ages. Byin situhybridization, pS2 mRNA was detected in the surface mucous cells in normal gastric mucosa. In MT-TGFαmice, pS2 mRNA was found throughout the expanded foveolar region. Byin situhybridization, spasmolytic peptide (SP) expression was observed in the region of the progenitor zone in both groups of mice. By immunohistochemistry, SP expression was noted in a broad band of mucous neck cells deep to the progenitor zone. No gastric expression of intestinal trefoil factor (ITF) was noted in either group of mice. The results demonstrate that the expansion of the foveolar mucous cell compartment in MT-TGFαmice is due to the hyperplasia of normal surface cells expressing their particular mucin-associated trefoil peptide, pS2.

ISSN:0897-7194    

DOI:10.3109/08977199609034571

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor