Biomedical subjects

M Chedid

Publications and source records attributed to M Chedid.

At least 19 recordsLinked to original sources

PubMed2001

Ultrashort regimen of lansoprazole-amoxicillin-azithromycin for eradicating Helicobacter pylori.

The efficacy and safety of two ultrashort azithromycin-containing regimens for Helicobacter pylori infection were studied. Patients positive for H. pylori infection were assigned to receive either a three-day drug regimen (group A) or a five-day regimen (group B). In both groups, patients received lansoprazole 30 mg p.o. twice daily on day 1 and, on days 2 and 3, lansoprazole 30 mg p.o. twice daily, amoxicillin 1 g (of anhydrous amoxicillin) p.o. twice daily, and azithromycin 500 mg (of anhydrous azithromycin) p.o. twice daily. Group B patients received lansoprazole 30 mg p.o. twice daily and amoxicillin 1 g p.o. twice daily for two additional days. Gastric biopsy specimens were subjected to culture and susceptibility testing. A minimum of four weeks after the completion of therapy, the patients underwent a 14C-urea breath test to determine whether H. pylori had been eradicated. A total of 28 patients were enrolled (15 in group A and 13 in group B). Treatment was well tolerated. H. pylori was eradicated in 4 (36%) of 11 patients in group A and 2 (22%) of 9 group B patients (26.6% and 15.4%, respectively, in intention-to-treat analysis). None of the isolates of H. pylori showed resistance to amoxicillin or clarithromycin. Regimens consisting of lansoprazole plus two or four days of azithromycin and amoxicillin therapy eradicated H. pylori in 36% and 22% of patients, respectively.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Expression of group IIa secretory phospholipase A2 increases with prostate tumor grade.

PURPOSE: Arachidonate release contributes to prostate tumor progression as arachidonate is metabolized into prostaglandins and leukotrienes, potent mediators of immune suppression, cellular proliferation, tumor motility, and invasion. The group IIa sPLA2 (sPLA2-IIa) can facilitate arachidonate release from cellular phospholipids. We therefore sought to determine whether sPLA2-IIa expression might be related to the development or progression of prostatic adenocarcinoma (CaP). EXPERIMENTAL DESIGN: sPLA2-IIa expression was examined by Western blot analyses of CaP cells and xenografts and by immunohistochemistry of benign prostatic hyperplasias and primary human CaPs (n = 101) using a sPLA2-IIa-specific polyclonal antibody. RESULTS: sPLA2-IIa expression was increased dramatically in the androgen-independent CWR-22R and LNAI CaP cells versus the androgen-dependent CWR-22 and LNCaP cells. Immunohistochemical analyses revealed that sPLA2-IIa expression was also significantly increased with CaP development and advancing disease (trend analysis; Pearson correlation coefficient, P = 0.016). High-grade CaPs showed intense, uniform staining for sPLA2-IIa that was significantly different from that in adjacent benign prostatic hyperplasias (Fisher's exact test, P = 0.021) or low-grade CaP (P = 0.013), both of which showed only focal or weak sPLA2-IIa staining. Further, uniform sPLA2-IIa expression was directly related to the increased proliferative index that typifies advancing disease (P = 0.001). Most significantly, enhanced sPLA2-IIa expression was inversely related to 5-year patient survival (P = 0.015). CONCLUSIONS: These data show that sPLA2-IIa expression increases with progression to androgen-independence and is highest in the most poorly-differentiated, highest-grade primary human CaP samples.

Androgens↗

PubMed1998

Granulocyte colony-stimulating factor worsens the outcome of experimental Klebsiella pneumoniae pneumonia through direct interaction with the bacteria.

Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. We studied the effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae, an important gram-negative bacillary pulmonary pathogen. Using a highly reproducible murine model, we here show the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia. Administration of G-CSF promoted replication of bacteria in the liver and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in increased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Binding of 125I-G-CSF to K pneumoniae was displaced by an excess of unlabeled G-CSF, whereas an unrelated cytokine, interleukin-1alpha, did not compete with G-CSF binding to the bacteria. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes.

Animals↗

PubMed1997

Ligand-independent activation of fibroblast growth factor receptor-2 by carboxyl terminal alterations.

To assess the effect(s) of the C-terminal domain on FGFR2 function, we engineered a series of mutant FGFR2 cDNAs encoding deletions in the C-terminus of the receptor and compared their growth properties in NIH3T3 fibroblasts. In contrast to FGFR2-WT, receptors with C-terminal truncations induced ligand-independent transformation of NIH3T3 cells and transfectants expressing these mutant receptors efficiently formed colonies in semisolid medium. Introduction of point mutations (Y to F) into the C-terminus of FGFR2 at positions 813, 784 or 780 revealed that these mutant receptors also displayed activities similar to that of C-terminally truncated receptors. C-terminally altered FGF receptors did not show an increase in the basal level of receptor phosphorylation compared to that of FGFR2-WT suggesting that elevated receptor phosphorylation does not underlie the transforming activity of these receptors. Interestingly, expression of transforming FGFR2 derivatives, unlike H-Ras transformed cells, did not result in the activation of the mitogen-activated protein kinases (MAPKs), p42/ERK2 and p44/ERK1, indicating that this pathway is not constitutively active in FGFR2-transformed cells. Finally, we report the overexpression of FGFR2 mRNA and protein in several human tumor cell lines suggesting activation of the receptor in these tumors.

3T3 Cells↗

PubMed1997

Cloning and characterization of the mouse homolog of the human A6 gene.

The mouse homolog of a novel human protein tyrosine kinase encoding gene, A6, was cloned and characterized. The human A6 cDNA is unique in that its gene product exhibited in vitro kinase activity but its predicted amino acid (aa) sequence revealed no consensus motifs commonly found within the kinase domain of protein kinase family members. Here, we isolated a mouse A6 cDNA clone from a murine myeloid progenitor 32D cell library using a 1.1 kb cDNA probe containing the entire human A6 open reading frame (ORF). Determination of the mouse A6 cDNA nucleotide (nt) sequence revealed an ORF of 1050 nt encoding a protein of 350 aa and a molecular mass of 40,201 Da. The mouse and human A6 gene products shared 93% identity. In vitro translation, as well as immunoprecipitation of 32D cell lysates confirmed expression of mouse A6 as a 40 kDa protein. Northern blot analysis of total RNA from mouse cell lines derived from diverse tissues including NIH 3T3 fibroblasts, L cell fibroblasts, C2C12 myoblasts, M1 myeloblasts, BALB/MK cells, 70Z/3 preB lymphocytes, and p388D1 monocytes demonstrated widespread A6 mRNA expression. A6 mRNA was also ubiquitously expressed at varying levels in all tissues examined. The identification of a potential actin/phosphoinositide binding domain and consensus phosphorylation sites, coupled with A6's expression in a variety of cell types suggest that the A6 gene product may play a role in basic cellular processes.

Amino Acid Sequence↗

PubMed1997

Differential expression of the keratinocyte growth factor (KGF) and KGF receptor genes in human vascular smooth muscle cells and arteries.

Keratinocyte growth factor (KGF) is a secreted member of the fibroblast growth factor (FGF) family of heparin-binding proteins. Studies reported to date indicate that it functions primarily as an important paracrine mediator of epithelial cell growth and differentiation. KGF appears to act via binding to a specific FGF receptor-2 isoform generated by an alternative splicing mechanism. To determine whether KGF may play a role in vascular smooth muscle cell (SMC) biology, we investigated KGF and KGF receptor gene expression in human SMC cultured in vitro as well as in several human nonatherosclerotic artery and atheroma specimens. KGF mRNA but not KGF receptor mRNA was expressed by SMCs, as determined by Northern blot hybridization analysis or reverse transcription-polymerase chain reaction assays, respectively. Additional experiments demonstrated that 1) human SMCs produce and secrete mitogenically active KGF and that 2) the cytokine interleukin-1 increases KGF mRNA and protein levels in human SMCs. We also found that KGF transcripts but not KGF receptor transcripts were expressed in control and atherosclerotic human arteries. Taken together, these results indicate that KGF is unlikely to be involved in SMC growth regulation unless it can function intracellularly or interact with a presently unidentified KGF receptor.

Animals↗

PubMed1996

Mechanisms of hepatocyte growth factor stimulation of keratinocyte metalloproteinase production.

Matrix metalloproteinases participate in normal physiologic processes; however, their overproduction has been associated with connective tissue destruction in a variety of pathological states. Migrating basal keratinocytes transiently express collagenase-1 during normal cutaneous reepithelialization. However, the overexpression of both collagenase-1 and stromelysin-1 has been associated with the pathogenesis of chronic nonhealing ulcers. Aberrant expression of metalloproteinases in inflammation is mediated, at least in part, by soluble factors. Since hepatocyte growth factor/scatter factor (HGF/SF) has been reported to promote keratinocyte migration and proliferation, key events in wound repair, and since HGF/SF is produced by dermal fibroblasts and its c-Met receptor is expressed by basal keratinocytes in wounded skin, we have studied the effects of HGF/SF upon keratinocyte metalloproteinase expression. We have found that HGF/SF can stimulate keratinocyte collagenase-1 and stromelysin-1 production in a dose-dependent and matrix-dependent manner. Expression of 92-kDa gelatinase was not affected by HGF/SF. We determined that HGF/SF regulation of collagenase-1 expression is transcriptionally mediated and requires tyrosine kinase and protein kinase C activaties. HGF/NK1, a naturally occurring, truncated form of HGF/SF, also stimulates collagenase-1 production, but much less efficiently than does the parent molecule. However, HGF/NK2, another HGF/SF splice variant, as well as heparin, potently inhibit HGF/SF-induced collagenase-1 synthesis. These results indicate that HGF/SF and its naturally occurring splice variants have diverse biological effects on keratinocytes and suggest an additional mechanism whereby HGF/SF may regulate keratinocyte function during wound repair.

Adult↗

PubMed1996

Expression of alternative forms of Ras exchange factors GRF and SOS1 in different human tissues and cell lines.

DNA probes and antibodies specific for different coding regions of human SOS1 and GRF genes were used to screen expression of these genes in a variety of adult and fetal human tissues and cell lines. Despite previous reports of the exclusive expression of hGRF RNA in brain, we also observed expression of this gene in various other tissues including lung and pancreas, as well as several tumor cell lines. At least three different hGRF mRNA transcripts were observed depending on the probe used, with the larger transcripts being detected by probes corresponding to the 5' end of the gene while smaller transcripts were detected by probes corresponding to the 3' end. Expression of hSOS1-related transcripts was more ubiquitous and homogeneous than with hGRF, with similar levels of specific transcripts being detected in most tissues and cell fines tested. Three to five different transcripts were detected in human tissues when using probes for the 5' end and middle regions of this gene, whereas only two were detected with probes corresponding to the 3' end. Screening of multiple human tumor cell lines showed ubiquitous expression of three specific transcripts, although the level and ratio of each of these transcripts varied widely among individual cell lines. Consistent with the variety of transcripts detected, several protein forms were also identified in Western immunoblots with antisera raised against specific domains of hSOS1 and human Ras-GRF gene products. Fluorescence in situ chromosomal hybridization suggested that, in both cases, the multiple forms arise from single chromosomal loci. The heterogeneity of hGRF and hSOS1 gene products detected (which appear to retain in most cases a functional catalytic domain), suggests that differentially expressed, alternatively spliced hSOS1 and hGRF forms may contribute to fine regulation of Ras activation in different tissues or at different stages of development.

3T3 Cells↗

PubMed1996

Glucocorticoids inhibit keratinocyte growth factor production in primary dermal fibroblasts.

The participation of growth factors in wound healing and tissue repair has been well established. Previous studies demonstrated that the expression of keratinocyte growth factor (KGF) was greatly elevated shortly after injury and that topical application of KGF accelerated healing. Steroidal antiinflammatory agents, specifically glucocorticoids, markedly impair wound healing. The participation of KGF in wound healing led us to examine the effect of glucocorticoids on KGF production. The addition of dexamethasone significantly reduced the level of constitutively produced KGF messenger RNA, protein, and bioactivity in conditioned medium from dermal fibroblasts. This inhibitory effect was observed with a variety of glucocorticoids, whereas nonsteroidal antiinflammatory compounds had little effect on KGF synthesis. The mechanisms by which dexamethasone decreased KGF production include a combination of a diminished transcriptional rate and destabilization of the KGF messenger RNA. Cytokines such as interleukin-1 alpha, platelet-derived growth factor-BB, and transforming growth factor-alpha, typically up-regulated during wound healing, augment KGF expression by dermal fibroblasts. We determined that dexamethasone also blocked this inductive effect. These results suggest that glucocorticoids could inhibit KGF production in the setting of wound repair, which may contribute to the impairment of healing associated with glucocorticoid use.

Animals↗

PubMed1995

Modulation of keratinocyte growth factor and its receptor in reepithelializing human skin.

We investigated the expression and distribution of keratinocyte growth factor (KGF) (FGF-7) and its receptor (KGFR) during reepithelialization of human skin. KGF mRNA levels increased rapidly by 8-10-fold and remained elevated for several days. In contrast, KGFR transcript levels decreased early but were significantly elevated by 8-9 d. A KGF-immunoglobulin G fusion protein (KGF-HFc), which specifically and sensitively detects the KGFR, localized the receptor to differentiating keratinocytes of control epidermis, but revealed a striking decrease in receptor protein expression during the intermediate period of reepithelization. Suramin, which blocked KGF binding and stripped already bound KGF from its receptor, failed to unmask KGFRs in tissue sections from the intermediate phase of wound repair. The absence of KGFR protein despite increased KGFR transcript levels implies functional receptor downregulation in the presence of increased KGF. This temporal modulation of KGF and KGFRs provides strong evidence for the functional involvement of KGF in human skin reepithelialization.

Adult↗

PubMed1995

An unexpected transforming gene in calf-thymus carrier DNA: bovine hst.

During a search for transforming genes by transfecting a human cDNA expression library together with calf thymus carrier-DNA into NIH/3T3 cells, we found a focus which was induced by a plasmid containing a sequence highly homologous to human HST (a transforming gene from Human STomach cancer). However, PCR analysis identified the source of this sequence as calf thymus DNA. The deduced amino acid (aa) sequence of bovine HST shows 91 and 81% identity to the human and mouse HST aa sequences, respectively. These data suggest that the hst of calf thymus carrier-DNA could induce transformation of NIH/3T3 cells.

3T3 Cells↗

PubMed1995

Different fibroblast growth factor 1 (FGF-1) transcripts in neural tissues, glioblastomas and kidney carcinoma cell lines.

We have previously reported the tissue specific distribution of four different FGF-1 transcripts containing alternative 5' untranslated exons spliced to the first protein coding exon. The predominant transcript in brain is FGF-1.B and in kidney FGF-1.A. Others have shown, by in situ hybridization and immunohistochemical analysis, that expression of FGF-1 in the brain is exclusively in neural cells but not in glial cells. Here we have examined the distribution of FGF-1.B and FGF-1.A transcripts in glioblastoma and retinal tissues and in kidney carcinoma cell lines. Our results show that FGF-1.B is the predominant transcript in neural derived tissues including both the diabetic retina and normal retina tissues. Surprisingly, FGF-1.B transcript is highly expressed in glioblastoma tissues. In contrast, a normal brain glial cell line, CHII, expresses very low levels of FGF-1 mRNA. These results strongly implicate the role of FGF-1 in the etiology of glioblastoma. We also examined several kidney carcinoma derived cell lines for the expression of FGF-1 mRNA. Most of these kidney cell lines do not express any FGF-1 transcripts. An interpretation by deduction is that kidney adenocarcinomas are derived from cortex but medulla has been reported as the site of FGF-1 synthesis. Of the kidney derived cell lines which are positive for FGF-1 message, only one expressed FGF-1.A transcript. The data may suggest that the establishment of kidney cell lines results in a switch of promoter usage from the 1.A seen in kidney tissue. Similarly, culturing of glioma cell lines may result in a switch from FGF-1.B seen in glioma tissues to FGF-1.D seen in most glioma cell lines. Continued studies of the FGF-1 transcripts, their functional promoters and their tissues distribution will provide insight into the potential role of FGF-1 in cell growth, tissue differentiation and malignant transformation.

Alternative Splicing↗

PubMed1995

Cloning and characterization of the promoter region of the human keratinocyte growth factor gene.

Keratinocyte growth factor (KGF), a member of the fibroblast growth factor family of related proteins, is expressed by stromal fibroblasts and acts on epithelial cells in a paracrine fashion. To understand the mechanisms responsible for regulating normal KGF expression and how these might be altered in disease, the 5'-flanking region of this gene was cloned. The presence of two KGF transcription initiation sites was suggested by ribonuclease protection assay and confirmed by primer extension analysis. Examination of the genomic DNA sequence revealed the presence of the putative promoter sequences TATTTA and CCAAT, located 31 and 50 base pairs upstream, respectively, from the first of the two mRNA start points, and putative initiator sequences surrounding each transcription start site. Transient transfection into murine NIH/3T3 fibroblasts demonstrated that the region required for basal level KGF promoter activity was located between bases -225 and +190. Inclusion of sequences between -1503 and -775 markedly reduced promoter activation, indicating the presence of negative regulatory element(s) in this region. A similar pattern of promoter activation was detected in human fibroblasts and in murine C2C12 myoblasts. In contrast, no chloramphenicol acetyltransferase activity was observed in macrophages and epithelial and lymphoid cells transfected with the same constructs. Northern blot analysis revealed a strong correlation between KGF RNA expression and promoter activation in all cells tested. Activation of the KGF promoter could be induced by the proinflammatory cytokines interleukin 1 and interleukin 6 and by the adenylate cyclase activator forskolin. Taken together, these results indicate the existence of cis-acting element(s) responsible for selective activation of the KGF promoter only in cells that express KGF mRNA and may provide a mechanistic basis for KGF gene expression during inflammation.

Animals↗

PubMed1995

Keratinocyte growth factor.

Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family (FGF-7) with a distinctive pattern of target-cell specificity. Studies performed in cell culture suggested that KGF was mitogenically active only on epithelial cells, albeit from a variety of tissues. In contrast, KGF was produced solely by cells of mesenchymal origin, leading to the hypothesis that it might function as a paracrine mediator of mesenchymal-epithelial communication. Biochemical analysis and molecular cloning established that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2 gene. Many detailed investigations of KGF and KGFR expression in whole tissue and cell lines largely substantiated the pattern initially perceived in vitro of mesenchymal and epithelial distribution, respectively. Moreover, functional assays in organ culture and in vivo and studies of KGF regulation by sex steroid hormones reinforced the idea that KGF acts predominantly on epithelial cells to elicit a variety of responses including proliferation, migration and morphogenesis.

Animals↗

PubMed1995

Keratinocyte growth factor as a cytokine that mediates mesenchymal-epithelial interaction.

Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family (FGF-7) with a distinctive pattern of target-cell specificity. Studies performed in cell culture suggested that KGF was mitogenically active only on epithelial cells, though from a variety of tissues. In contrast, KGF was produced solely by cells of mesenchymal origin, leading to the hypothesis that it might function as a paracrine mediator of mesenchymal-epithelial communication. Biochemical analysis and molecular cloning established that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2 gene. Many detailed investigations of KGF and KGFR expression in whole tissue and cell lines largely substantiated the pattern initially perceived in vitro of mesenchymal and epithelial distribution, respectively. Moreover, functional assays in organ culture and in vivo and analysis of agents regulating KGF expression reinforced the idea that KGF acts predominantly on epithelial cells. While the data do not implicate a KGF autocrine loop in neoplasia, paracrine sources of factor or ligand-independent signaling by the KGFR might contribute to malignancy. Alternatively, because of its differentiation-promoting effects, KGF may retard processes that culminate in uncontrolled cell growth.

Animals↗

PubMed1994

Induction of WAF1/CIP1 by a p53-independent pathway.

The p53-inducible gene WAF1/CIP1 encodes a M(r) 21,000 protein (p21) that has been shown to arrest cell growth by inhibition of cyclin-dependent kinases. Induction of WAF1/CIP1 in cells undergoing p53-dependent G1 arrest or apoptosis supports the idea that WAF1/CIP1 is a critical downstream effector of p53. In the present study, we used embryonic fibroblasts from p53 "knock-out" mice to demonstrate p53-independent induction of WAF1/CIP1. We show that serum or individual growth factors such as platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor but not insulin are able to induce WAF1/CIP1 in quiescent p53-deficient cells as well as in normal cells. The kinetics of this transient induction, which is enhanced by cycloheximide, demonstrates that WAF1/CIP1 is an immediate-early gene the transcript of which reaches a peak at approximately 2 h following serum or growth factor stimulation. On the other hand, DNA damage elicited by gamma-irradiation induces WAF1/CIP1 in normal human and mouse fibroblasts but does not affect WAF1/CIP1 expression in p53-deficient cells. These results suggest the existence of two separate pathways for the induction of WAF1/CIP1, a p53-dependent one activated by DNA damage and a p53-independent one activated by mitogens at the entry into the cell cycle. The possible function of p21 at this early stage is discussed.

3T3 Cells↗

PubMed1994

Regulation of keratinocyte growth factor gene expression by interleukin 1.

Keratinocyte growth factor (KGF) is a stromally derived member of the fibroblast growth factor family (FGF7) with potent mitogenic activity on a variety of epithelial cells. To identify molecules that regulate the expression of this paracrine mediator of epithelial proliferation, we investigated the effects of various cytokines and growth factors on KGF production by fibroblasts. The proinflammatory cytokine interleukin 1 (IL1) strongly induced the expression of KGF RNA in fibroblasts from multiple sources. Platelet-derived growth factor BB, IL6, and transforming growth factor alpha caused a moderate elevation, while tumor necrosis factor alpha and basic FGF did not alter the level of KGF RNA expression. The induction by IL1 of KGF transcript levels was time and dose dependent and specifically blocked by anti-IL1 antibodies. Nuclear run on experiments indicated that IL1 stimulated KGF gene transcription. Western blot analysis and keratinocyte proliferation assays demonstrated a corresponding increase in mitogenically active KGF protein in conditioned medium obtained from IL1-treated fibroblasts. The stimulation of KGF expression by IL1 and other cytokines such as IL6, transforming growth factor alpha, and platelet-derived growth factor may provide a mechanism for KGF induction during inflammation that would support its proposed role as mediator of reepithelialization and wound healing.

Adult↗

PubMed1994

Keratinocyte growth factor functions in epithelial induction during seminal vesicle development.

Development of the seminal vesicle (SV) is elicited by androgens and is dependent on epithelial-mesenchymal interactions. Androgenic signal transmission from the androgen-receptor-positive mesenchyme to the epithelium has been postulated to involve paracrine factors. Keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, is produced by stromal/mesenchymal cells and acts specifically on epithelial cells. The KGF transcript was detected by reverse transcription-polymerase chain reaction in newborn mouse SVs and by Northern blot analysis of RNA from cultured neonatal SV mesenchymal cells. Newborn SVs placed in organ culture undergo androgen-dependent growth and differentiation. Addition of a KGF-neutralizing monoclonal antibody to this system caused striking inhibition of both SV growth and branching morphogenesis. This inhibition was due to a decline in epithelial proliferation and differentiation, as the mesenchymal layer was not affected by anti-KGF treatment. When KGF (100 ng/ml) was substituted for testosterone in the culture medium, SV growth was approximately 50% that observed with an optimal dose of testosterone (10(-7) M). All of these findings suggest that KGF is present during a time of active SV morphogenesis and functions as an important mediator of androgen-dependent development.

Animals↗