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  • 11
    Electronic Resource
    Electronic Resource
    The role of hepatocyte growth factor in growth plate cartilage (1998)
    Springer
    Journal of bone and mineral metabolism 16 (1998), S. 170-177 
    Details
    ISSN: 1435-5604
    Keywords: Key words: HGF ; growth plate ; chondrocyte ; differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: To investigate the physiological role of hepatocyte growth factor (HGF) in endochondral bone formation, we examined the expression of HGF and its receptor c-met and the effects of HGF on growth plate chondrocytes. HGF was highly expressed in the prehypertrophic zone and hypertrophic zone in rat costal growth plate cartilage. The expression of HGF increased in rabbit chondrocytes as they matured in culture. Conversely, c-met expression was down regulated along maturation of growth plate chondrocytes. HGF had weak stimulatory effects on DNA and proteoglycan synthesis of growth plate chondrocytes. However, HGF strongly inhibited expression of terminal differentiation-related phenotypes, such as type X collagen and alkaline phosphatase (APase) synthesis and cartilage matrix mineralization. When HGF was removed from the cultures, cells quickly expressed type X collagen and APase. Once chondrocytes differentiated to mature chondrocytes, HGF did not inhibit further differentiation of these cells. These results suggested that HGF is a negative regulator of terminal differentiation of growth plate chondrocytes..
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007740050042
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  • 12
    Electronic Resource
    Electronic Resource
    Nuclear relaxation in the superconducting state of (MDT-TTF)2AuI2 (1994)
    Springer
    Journal of superconductivity 7 (1994), S. 663-666 
    Details
    ISSN: 1572-9605
    Keywords: Nuclear relaxation rate ; (MDT-TTF)2AuI2 ; organic superconductor ; field cycling NMR ; vortex creep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
    Notes: Abstract We report the results of our attempt to measure the proton nuclear relaxation rate, 1/T 1, in the superconducting state of the title material. The relaxation rate in the superconducting state at a field of 1 T was found much longer than that in the normal state, but it became clear that the dominant contribution came from the normal core region. The nuclear relaxation at zero field was examined by using the field cycling technique. An ln(t) term in the relaxation curve was observed at low temperatures, suggesting the contribution of the creeping motion of vortices. We discuss the possibility to determine the intrinsic temperature dependence of 1/T 1 in the superconducting state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00728481
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  • 13
    Electronic Resource
    Electronic Resource
    Systematic investigation of electronic structure in BEDT-TTF based organic superconductors withT c above 10 K; κ-(BEDT-TTF)2 X (X=Cu(NCS)2, Cu[N(CN)2]Br, and Cu(CN)[N(CN)2]) (1994)
    Springer
    Journal of superconductivity 7 (1994), S. 671-674 
    Details
    ISSN: 1572-9605
    Keywords: BEDT-TTF ; organic superconductor ; EPR ; g-value
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
    Notes: Abstract The electronic structure of the title superconductors has been investigated by electrical resistivity, complex susceptibility, and electron paramagnetic resonance (EPR) measurements. The superconducting properties (pressure dependence ofT c , magnetic penetration depth, upper critical field, and so on) of these three salts are similar to each other, while transport properties in the normal state have shown a large variety in the temperature dependence. In order to clarify the electronic structure in the normal state, the EPR parameters, the spin susceptibility (χ spin), and the linewidth (ΔH pp), are compared. An anomalous temperature dependence of theg-value has been observed below 150 K in the Cu(NCS)2 and Cu(CN)[N(CN)2] salts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00728483
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  • 14
    Electronic Resource
    Electronic Resource
    Expression of HGF and TGF-β1 mRNA after partial hepatectomy in rats with liver cirrhosis (1995)
    Springer
    Surgery today 25 (1995), S. 237-243 
    Details
    ISSN: 1436-2813
    Keywords: experimental cirrhotic liver ; partial hepatectomy ; HGF ; TGF-β1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hepatocyte growth factor (HGF) is a potent mitogen for the maturation of hepatocytes in vitro which plays a role in liver regeneration in vivo. In addition, transforming growth factor-β1 (TGF-β1) is also a potent regulator of liver regeneration. In attempting to clarify the mechanisms related to liver regeneration after partial hepatectomy, we investigated the expression of HGF and TGF-β1 in rats with liver cirrhosis (LC). A rat model of LC was prepared using carbon tetrachloride (CCl4). The expression of HGF mRNA in both the LC and control groups showed a similar time-course with the highest expression seen at 18 h after a 70% hepatectomy. The expression of TGF-β1 mRNA peaked at 18 h after partial hepatectomy in the LC group and at 48 h in the control group. The 5-bromo-2'-deoxyuridine (BrdU) labeling index for the LC group at 24, 48, and 72 h after partial hepatectomy was 9.2%, 5.9%, and 1.8%, while for the control group it was 7.0%, 11.7%, and 6.8%, respectively. The BrdU labeling index in the LC group was thus suppressed earlier than that in the control group. We therefore postulate that regeneration of the remnant liver in the presence of LC accelerates immediately after partial hepatectomy, but the extent of regeneration is insufficient because of an early cessation due to an early expression of TGF-β1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311534
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  • 15
    Electronic Resource
    Electronic Resource
    Contribution of Parenchymal and Non-Parenchymal Liver Cells to the Clearance of Hepatocyte Growth Factor From the Circulation in Rats (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1737-1740 
    Details
    ISSN: 1573-904X
    Keywords: hepatocyte growth factor ; receptor-mediated endocytosis ; pharmacokinetics ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The distribution of 125I-hepatocyte growth factor (HGF) to either liver parenchymal cells (PC) or non-parenchymal cells (NPC) was investigated in rats. Methods. After injection of a trace amount of 125I-HGF, the distribution of radioactivity determined by microautoradiography closely resembled that of 125I-epidermal growth factor which distributes mainly to PC. Results. The uptake clearance of 125I-HGF estimated by determining the radioactivity of isolated liver cells was three times higher for PC than for NPC. This suggests that HGF distributes mainly to PC at relatively low doses. On the other hand, the uptake clearance by PC fell on coadministering an excess (80 µg/kg) of unlabeled HGF, while no change was observed for NPC, indicating that a saturable process for the hepatic handling of HGF exists only in PC where the HGF receptor is expressed. Conclusions. At such a dose the uptake clearance was comparable for both PC and NPC showing that HGF distributes to both cell types although NPC have few HGF receptors. Since the distribution to NPC was relatively non-specific and heparin-sensitive, it may be that heparin-like substances, which are believed to exist on PC and/ or the extracellular matrix, also exist on NPC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016273907749
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  • 16
    Electronic Resource
    Electronic Resource
    Chromosomal localization of rat hepatocyte growth factor (Hgf) and HGF receptor (Met) and characterization of HGF receptor cDNA (1997)
    Springer
    Mammalian genome 8 (1997), S. 661-667 
    Details
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The Met protooncogene encodes the tyrosine kinase receptor for the hepatocyte growth factor (HGF), a potent mitogen for hepatocytes and other epithelial cells produced by mesenchymal cells. Many of the studies on the physiologic and neoplastic growth of the liver, as well as other organs, have been performed in the rat. Therefore, chromosomal mapping of the rat Hgf gene and the gene of its receptor is of particular value. To achieve this, a probe of the coding part of rat HGF cDNA was used to isolate four genomic probes from a lambda phage rat genomic library. These probes were used to map the Hgf gene to Chromosome (Chr) 4q12 by the FISH technique. To obtain a probe for the mapping of the HGF receptor/Met gene, we cloned the complete coding region of the rat HGF receptor mRNA. Complementary DNA (cDNA) was synthesized with reverse transcriptase from total RNA for use as a template for the PCR. The two PCR primers were designed based on human and mouse sequences and were located in the flanking regions of the open reading frame of the HGF receptor mRNA. Amplification resulted in a band of an estimated size of 4.1 kb, which was cloned and sequenced. The nucleotide sequence showed about 93% and 85% homology compared with mouse and human HGF receptor sequences, respectively. A full-length probe of the coding part of the cDNA was used to map the rat HGF receptor/Met gene to Chr 4q21 by the FISH technique. Therefore, the rat Hgf and HGF receptor/Met genes are located relatively close to each other, in a way similar to humans but not mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003359900533
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  • 17
    Electronic Resource
    Electronic Resource
    Expression of the hepatocyte growth factor gene during chick limb development (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Developmental Dynamics 202 (1995), S. 80-90 
    Details
    ISSN: 1058-8388
    Keywords: Hepatocyte growth factor ; c-met ; Gene expression ; Limb development ; In situ hybridization ; Chick embryo ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: It has been shown that mirrorimage duplications of the zeugopodia and digits are formed when MRC-5 fibroblasts producing hepatocyte growth factor (HGF) are applied to the anterior region of the chick limb bud (Yonei et al. [1993] Dev. Biol. 160:246-253). To evaluate the role of HGF in limb development, we observed the expression pattern of the HGF gene using in situ hybridization. The HGF gene was expressed in the mesoderm of the limb bud and in the central core region of mandibular arch and maxillary processes at stages 17 to 24. When both wing and leg buds begin to extend distally, the HGF gene is expressed in the mesenchymal cells, but not in the ectodermal cells and somites. Concomitant with establishment of the apical ectodermal ridge, distal mesenchymal cells of the limb bud express the HGF gene intensely with a gradient higher in the distal region. The HGF expression is later confined to the ventral and subapical mesenchyme of the limb bud, although no signal is detectable in the apical and non-ridge ectoderm. However, signal for the c-met proto-oncogene encoding the HGF receptor is not detectable in the limb bud at stages 17 to 24. These results suggest that HGF produced in the limb mesoderm may be involved in initial induction and maintenance of the apical ectoderm during limb development. © 1995 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aja.1002020108
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  • 18
    Electronic Resource
    Electronic Resource
    Enzyme leakage due to change of membrane permeability of primary cultured rat hepatocytes treated with various hepatotoxins and its prevention by glycyrrhizin (1985)
    Springer
    Cell biology and toxicology 1 (1985), S. 285-295 
    Details
    ISSN: 1573-6822
    Keywords: enzyme leakage ; glycyrrhizin ; hepatotoxins ; primary cultured hepatocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Various hepatotoxins were added to the medium of primary cultures of adult rat hepatocytes and the release of the cytosolic enzymes lactic dehydrogenase, glutamic-oxaloacetic and glutamic-pyruvic aminotransferases were measured 24 h later. CCl4 at low concentrations caused dose-dependent release of soluble enzymes into medium without appreciable cytolysis of the hepatocytes. Mitochondrial enzymes were not released under these conditions. At 5 mM CCl4, both soluble and mitochondrial glutamic-oxaloacetic aminotransferase were found in the culture medium. Glycyrrhizin, a triterpenoid glycoside of licorice roots, prevented the enzyme release caused by CCl4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00118193
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  • 19
    Electronic Resource
    Electronic Resource
    Hepatocyte growth factor stimulates the invasion of gallbladder carcinoma cell lines in vitro (1998)
    Springer
    Clinical & experimental metastasis 16 (1998), S. 74-82 
    Details
    ISSN: 1573-7276
    Keywords: c-MET ; gallbladder cancer cell line ; HGF ; invasion ; motility ; proteolytic enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human gallbladder cancer is highly malignant and its prognosis is usually poor depending on the extent of surrounding tissue invasion. We examined in vitro the invasive activity of four gallbladder cancer cell lines (GB-d1, GB-h3, GB-d2 and FU-GBC-1) in the absence or presence of hepatocyte growth factor (HGF). In type 1 collagen gel culture, HGF stimulated cell proliferation and induced an invasive phenotype of arborizing structures in GB-d1, GB-h3 and GB-d2. In a Matrigel invasion assay, invasion was also induced in three of these cell lines by HGF but not in FU-GBC-1. Cellular motility was, however, stimulated by HGF in all of the four cell lines to various extents. Zymography for proteolytic enzymes demonstrated high levels of type IV collagenase and urokinase-type plasminogen activator (u-PA) activity in GB-d1, GB-h3 and GB-d2 even in the absence of HGF. In the presence of HGF, the 72 kDa type IV collagenase (MMP-2) activity of GB-h3 and u-PA activities of GB-d1, GB-h3 and GB-d2 were enhanced. In contrast, the MMPs and PAs activities of FU-GBC-1 were faint irrespective of the addition of HGF. A Western blot analysis demonstrated higher levels of 190 kDa c-MET product (HGF receptor) of GB-d1, GB-h3 and GB-d2 than that of FU-GBC-1. The invasion in the Matrigel assay stimulated by HGF was inhibited by protease inhibitors, aprotinin and FOY-305, as well as by anti-HGF antibody. These results thus suggest that, in addition to the importance of the proteolytic activity, the cellular motility induced via the HGF/HGF-receptor system is essential for the invasive progression of gallbladder carcinoma cells. © Rapid Science 1998
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006516119518
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  • 20
    Electronic Resource
    Electronic Resource
    Inhibition of HGF/SF-induced breast cancer cell motility and invasion by the HGF/SF variant, NK4 (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 245-254 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; hepatocyte growth factor/scatter factor ; metastasis ; NK4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract NK4 is a variant form of HGF/SF, comprising the N-terminal and subsequent four kringle domains of mature HGF/SF. HGF/SF is a multifunctional cytokine that enhances the metastatic behaviour of tumour cells in vitro by stimulation of the c-met receptor tyrosine kinase and has been implicated in the development of tumour metastasis in vivo. The aims of this study were to further investigate the potential antagonistic effects of the recently described variant form of HGF/SF, NK4, on HGF/SF activity in breast cancer cells. All cell lines used expressed both the HGF/SF receptor gene and protein as shown by RT-PCR and Western blotting. NK4 inhibited HGF/SF-induced tumour cell invasion through an artificial basement membrane. Tumour cell motility and scattering induced by HGF/SF were also dramatically reduced by the inclusion of NK4. Immunoprecipitation studies revealed that NK4 inhibited the phosphorylation of the c-met receptor in response to HGF/SF. Treatment of these cells with NK4 alone did not have any significant effects on their metastatic behaviour. From this data we conclude that NK4 demonstrates significant antagonistic properties towards HGF/SF, inhibiting HGF/SF-stimulated breast tumour cell invasion, motility and migration. NK4 may therefore be of potential benefit in the development of anti-metastasis therapies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006348317841
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