Biomedical subjects

J Xu

Publications and source records attributed to J Xu.

At least 541 records · Page 30Linked to original sources

PubMed1999

Mass spectral fragmentation patterns of 1a,3-diaryl-1,1,4, 4-tetrachloro-1a,2,3,4-tetrahydro-1H-azirino

The mass spectrometric behaviour of three 1a,3-diaryl-1,1,4, 4-tetrachloro-1a,2,3,4-tetrahydro-1H-azirino-[2,1-e][1, 6]benzothiazocines has been studied with the aid of mass-analyzed ion kinetic energy spectro--metry and exact mass measurements under electron impact ionization. All compounds show a tendency-to eliminate a neutral substituted/unsubstituted 1,1-dichlorostyrene from the eight-membered thiazocine ring to yield azirino[2,1-c][1, 4]benzothiazine ions, which can then lose a chlorine radical and a sulfur-atom to form azirino[2,1-c][1,4]benzothiazine ions and dihydroquinoline ions. All compounds could also eliminate a chlorine radical plus hydrogen chloride, stepwise or consecutively, to undergo a ring enlargement rearrangement to produce nine-membered 1, 7-benzothiazonine ions. The [M(+) - Cl] ions could undergo a four-membered ring rearrangement to yield 1,5-benzothiazepine ions by loss of 1,1-dichlorostyrene or styrene ions and HCl, and undergo alpha, alpha-cleavage to form benzothiazine ions by loss of arylchlorocyclopropane. The [M(+) - Cl - HCl] ions could further eliminate some atoms, small molecules or molecular fragments to form some abundant fragment ions. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗

PubMed1999

A polylinker-derived sequence, PL, highly increased translation efficiency in Escherichia coli.

Pokeweed (Phytolacca americana) antiviral protein (PAP) is a highly specific ribosome-inactivating glycosidase. The PAP gene was isolated and cloned in an expression vector containing a polylinker-derived sequence (PL) but devoid of a Shine-Dalgarno (SD) sequence. Surprisingly, E. coli cells transformed with this vector produced over twice the amount of PAP than that with the consensus SD sequence. Computer analysis of the 5' terminal region of PAP mRNA revealed a nucleotide sequence (ACCUACUCGAGUUAG) which was complementary to two domains in 16S rRNA. The heptanucleotide ACCUACU (box I) is complementary to nucleotides 1434-1440 and the GAGUUAG (box II) to nucleotides 507-513 in 16S rRNA of E. coli. To examine the role of this sequence in the translation of PAP mRNA, single or both boxes were mutated and the protein yield was measured. Mutation of box I and of box II resulted in a 2.7 and 5.3 fold decrease in protein yield respectively, indicating that the PAP gene expression was dependent on the presence of both boxes. To investigate whether PL also increases expression of other genes, human calcitonin monomeric and tetrameric genes were used as reporters. It was found that the expression level was doubled compared to that by SD. These results demonstrate that the PL is an efficient translational initiator and may be used for high level expression of certain genes in E. coli. The possible mechanisms for the high level expression are discussed.

Animals↗

PubMed1999

Evaluation of replication studies, combined data analysis, and analytical methods in complex diseases.

Due to genetic heterogeneity, phenocopies, incomplete penetrance, misdiagnosis, and unknown mode of inheritance, linkage studies of most complex diseases are unlikely to provide conclusive findings with unambiguously high lod scores. Typically, several marginally significant lod scores or elevated lod scores are observed in a genome-wide screen. However, it is usually difficult to differentiate these findings from false positives (type I errors). Two approaches are commonly used to guard against false positives: replication studies in independent samples and combined data analysis. In the current paper, we evaluated these two common approaches using simulated data where data from multiple groups were available and locations of disease genes were known. We found replication studies and combined data analysis performed similarly in terms of their ability to identify true and false positive linkages. Both approaches confirmed two true linkages and did not confirm any false positive linkages. The results also indicated that it is not appropriate to apply the criteria proposed for confirming significant evidence for linkage to confirm regions with only suggestive evidence for linkage. The current results support previous findings that parametric analysis using an incorrect genetic model can still identify a true linkage.

Environment↗

PubMed1999

Modulatory effects of human herpes virus-7 on cytokine synthesis and cell proliferation in human peripheral blood mononuclear cell cultures.

Human herpes virus-7 (HHV-7) infects cells of the immune system and thus may modulate their function. To investigate the potential immunomodulatory effects of this virus, we performed an in vitro study in which we investigated effects of HHV-7 on the synthesis of several key immunomodulatory cytokines, i.e. tumor necrosis factor alpha (TNF-alpha), interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-4, IL-6, and transforming growth factor beta (TGF-beta). This was examined after in vitro infection of human peripheral blood mononuclear cells (PBMC) with HHV-7. We found elevated levels of TNF-alpha, TGF-beta, and IFN-gamma in the supernatants of HHV-7-infected cells. By reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, using cytokine-specific primers, we found that levels of TNF-alpha, TGF-beta, and IFN-gamma mRNA were increased in the infected cells. The HHV-7 infection also significantly (P < 0.05) decreased the production of IL-2 from activated, IL-2-producing PBMC. Furthermore, mitogen- and cytokine-induced cellular proliferative responses of human PBMC were found to be significantly (P < 0.05) down-regulated by this virus. On the other hand, HHV-7 did not affect IL-4 and IL-6 synthesis. Overall, our results indicate that HHV-7 infection causes significant immunomodulatory effects with regard to cytokine synthesis in these cells as well as inhibiting lymphocyte proliferation by various stimuli.

Cell Division↗

PubMed1999

Evaluation of a guinea pig model to assess interference in the immunogenicity of different components of a combination vaccine comprising diphtheria, tetanus and acellular pertussis (DTaP) vaccine and haemophilus influenzae type b capsular polysaccharide conjugate vaccine.

A guinea pig model to assess the immunogenicity of a combination vaccine containing diphtheria, tetanus and acellular pertussis (DTaP) vaccine and Haemophilus influenzae type b (Hib) capsular polysaccharide conjugated to tetanus toxoid (HibT) was evaluated comparatively with the mouse immunogenicity test to study the effect of combining these antigens on the immunogenicity of various components. The immunogenicity test in mice was performed by subcutaneous injection of groups of 10 animals twice at an interval of four weeks with 1/10 of a single human dose of various formulations of combination vaccines, DTaP or HibT vaccine. The animals were bled at 4 and 6 weeks and IgG or total antibodies to various components were determined by ELISA or RIA. The guinea pig immunogenicity model included groups of animals injected subcutaneously twice at an interval of six weeks with 1.5 times the single human dose of various formulations. The animals were bled at 4, 6 and 8 weeks and serum samples were tested for antibodies to various components by ELISA, RIA and/or neutralization tests. Additionally, potency of tetanus and diphtheria components was assessed as per the US Food and Drug Administration's regulations. Aluminium phosphate (AIPO(4)) adsorbed HibT vaccine or HibT as a combination with AIPO(4)adsorbed DTaP vaccine showed significant increases in IgG antibodies to tetanus toxin in mice as well increased tetanus antitoxin levels in guinea pigs as compared to soluble HibT vaccine. In general, combining DTaP and HibT vaccines did not affect the antibody levels to tetanus and diphtheria toxoids whereas DTaP-HibT combination vaccine elicited significantly lower IgG antibodies to pertussis toxin and filamentous haemagglutinin than DTaP vaccine alone, particularly after first injection. Mice showed similar Hib antibody responses for the combination and HibT alone whereas guinea pigs consistently showed lower anamnestic responses to Hib for combination formulations than for HibT alone. Reducing the amount of HibT and/or tetanus toxoid in the combination formulations reduced this suppression of Hib antibody response in guinea pigs. Suppression of Hib antibody response in combination vaccines has also been reported from recent clinical trials. Based on the results from this study, it appears that the guinea pig model may be able to predict the human response to various components of combination vaccines.

Animals↗

PubMed1999

Immunohistochemical localization of kininogen in rat spinal cord and brain.

Kininogen localization has been determined by immunocytochemistry in rat spinal cord and brain using a kinin-directed kininogen monoclonal antibody. In the spinal cord, there were immunostained neurons and fibers in laminae I, II, VII, and IX, intensely stained fibers in the superficial layers of the dorsal horn, and immunoreactive glial and endothelial cells. Small neurons, satellite cells, and Schwann cells immunostained distinctly in the dorsal root ganglion. In the brain stem, there were immunoreactive neurons and fibers in the tractus solitarius and nucleus, trigeminal spinal tract and nuclei, periaqueductal gray matter, vestibular nuclei, cochlear nuclei, trapezoid body, medial geniculate nucleus, and red nucleus. Immunostained neurons and fibers were also found in cerebellum (dentate nucleus), cerebral cortex (layers III and V), hippocampus (pyramidal cell layer), and corpus callosum. Glia and endothelial cells stained in all brain regions. The widespread location of kininogen in neurons and their processes, as well as in glial and endothelial cells, indicates more than one functional role, including those proposed as a mediator, a calpain inhibitor, and a kinin precursor, in a variety of neural activities and responses.

Animals↗

PubMed1999

Determination of fluorescent probe orientations on biomolecules by conformational searching: algorithm testing and applications to the atomic model of myosin.

The ability of a localized conformational searching method to predict probe orientation was tested on model nucleic acid and protein structures and applied to the prediction of skeletal myosin integrity upon chemical modification of its reactive thiols. Double-stranded oligonucleotides were chemically labeled with donor and acceptor resonance energy transfer probes at each end for distance determinations. These measurements were made independently using a terbium chelate as a donor to each of four chemically and spectroscopically distinct acceptor probes from the xanthene and cyanine dye groups. The choice of acceptor significantly affected the separation distance measured. Conformational searching algorithms on the atomic model corrected for the differences to within 0.2 nm on average. Verifying its usefulness on proteins, the localized conformational searching method determined the orientation of a fluorescent probe on RNase A that corresponds closely to available crystallographic models of the labeled protein (RMS deviation = 0.1 nm). Also, analysis of the symmetry of the fluorophores' structures suggests why FRET orientation factors are often closer to their dynamic average value than might normally be expected. Furthermore, the computational method provides insights about FRET data that are important for assessing the stability of the alpha-helix separating the SH1 and SH2 reactive thiols in skeletal myosin.

Crystallography, X-Ray↗

PubMed1999

Tumor necrosis factor-alpha and ceramides in insulin resistance.

The present studies tested the hypothesis that some effects of tumor necrosis factor-alpha (TNF-alpha) are mediated by activation of sphingomyelinases and the production of ceramides. Differentiated 3T3-L1 adipocytes were incubated with short-chain ceramide analogs, (C2- and C6-ceramides: N-acetyl- and N-hexanoyl-sphingosines, respectively), and this treatment increased 2-deoxyglucose uptake in the absence of insulin progressively from 2-24 h. This effect was inhibited by blocking the activations of mitogen-activated protein kinase, phosphatidylinositol 3-kinase (PI 3-kinase), and ribosomal S6 kinase which mediated an increase in GLUT1 concentrations. Long-term increases in PI 3-kinase activity associated with insulin receptor substrate-1 (IRS-1) increased the proportion of GLUT1 and GLUT4 in plasma membranes. These events explain the increases in noninsulin-dependent glucose uptake and incorporation of this glucose into the fatty acid and glycerol moieties of triacylglycerol. The mechanisms by which TNF-alpha and ceramides increase PI 3-kinase activity were investigated further by using rat2 fibroblasts. Incubation for 20 min with TNF-alpha, bacterial sphingomyelinase, or C2-ceramides increased PI 3-kinase activity by about fivefold, and this effect depended upon a stimulation of tyrosine kinase activity and an increase in Ras-GTP. This demonstrates the existence of a novel signaling pathway for TNF-alpha that could contribute to the effects of this cytokine in stimulating basal glucose uptake. By contrast, treating the 3T3-L1 adipocytes for 2-24 h with C2-ceramide diminished insulin-stimulated glucose uptake by decreasing the insulin-induced translocation of GLUT1 and GLUT4 to plasma membranes. This inhibition was observed when there was no increase in basal glucose uptake, and it occurred downstream of PI 3-kinase. Our work provides further mechanisms whereby TNF-alpha and ceramides produce insulin resistance and decrease the effectiveness of insulin in stimulating glucose disposal from the blood. Conversely, TNF-alpha and ceramides increase the ability of adipocytes to take up glucose and store triacylglycerol in the absence of insulin.

3T3 Cells↗

PubMed1999

Involvement of lipid mediators on cytokine signaling and induction of secretory phospholipase A2 in immortalized astrocytes (DITNC).

Our previous studies demonstrated the ability of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta), to stimulate NFkappaB/DNA binding and synthesis of secretory phospholipase A2 (sPLA2) in immortalized astrocytes (DITNC). In this study, we examined possible involvement of lipid mediators in the cytokine action. Using [14C]serine to label sphingomyelin and ceramide in these cells, subsequent exposure of cells to cytokines did not result in alteration of sphingomyelin/ceramide ratio. Furthermore, neither exogenous sphingomyelinase nor cell-permeable ceramides could stimulate NFkappaB/DNA binding. On the other hand, C-2 ceramide (0.3 microM) as well as other lipid mediators, such as lysophosphatidylcholine and arachidonic acid, were able to elicit a small increase in sPLA2 and potentiate the induction of sPLA2 by TNF-alpha. When DITNC cells were prelabeled with [32P]Pi, an increase in labeled phosphatidic acid (PA) was observed on treatment of cells with IL-1beta (200 U/mL). However, despite the ability of phorbol myristate acetate (PMA) to stimulate phospholipase D (PLD) and synthesis of phosphatidylethanol (PEt) in these cells, PLD activity was not affected by IL-1beta. With the [32P]labeled cells, however, PA-phosphohydrolase inhibitors, such as chlorpromazine and propranolol, could elicit large increases in labeled PA, indicating active PA metabolism in these cells. Cytokines also caused an increase in levels of diacylglycerol (DG) in these cells, although the source of this lipid pool is presently not understood. Taken together, these results provide evidence for the participation of PA and DG in cytokine signaling activity. Furthermore, although cytokines did not cause the release of ceramide, lipid mediators, such as lysophospholipids, and AA could modulate cytokine-mediated induction of sPLA2 in astrocytes.

Animals↗

PubMed1999

The clinical study and HLA genotyping of 112 familial myasthenia gravis patients.

One hundred and twelve cases of familial myasthenia gravis (MG) from 44 families selected from 2100 patients with MG diagnosed since 1983 in the Department of Neurology were studied. The clinical pictures and immunological features of the patients showed a great resemblance to those of sporadic cases. The pedigree analysis disclosed that the hereditary patterns of familial patients were basically Mendellian autosomal inheritance. Many predisposing factors such as fever, infection, use of aminoglycoside or vaccines, played an important role in presenting the phenotype of subclinical cases. The HLA genotyping suggested that the complement polymorphism C4A * 4, the complotype S42, and the genes 0901 and 1301 of DRB1 allele, were related to the pathogenesis of MG. It was concluded that the phenotype of MG may be the result of interaction between hereditary defects and environmental factors.

Alleles↗

PubMed1999

Effects of GABA-mediated inhibition on direction-dependent frequency tuning in the frog inferior colliculus.

Earlier studies from our laboratory have shown that the frequency selectivity of neurons in the frog inferior colliculus is direction dependent. The goal of this study was to test the hypotheses that gamma-aminobutyric acid or GABA (but not glycine)-mediated synaptic inhibition was responsible for the direction-dependence in frequency tuning, and that GABA acted through creation of binaural inhibition. We performed single unit recordings and investigated the unit's free-field frequency tuning, and/or the unit's response to the interaural level differences (under dichotic stimulation), before and during local applications of antagonists specific to gamma-aminobutyric acid A and glycine receptors. Our results showed that application of bicuculline produced a broadening of free-field frequency tuning depending on sound direction, i.e., more pronounced at azimuths at which the unit exhibited narrower frequency tuning under the pre-drug condition, thereby typically abolishing direction dependence in tuning. Application of strychnine produced no change in frequency tuning. The results from dichotic stimulation further revealed that bicuculline typically elevated and/or flattened the unit's interaural-level-difference response function, indicating a reduction in the strength of binaural inhibition. Our study provides evidence that gamma-aminobutyric acid-mediated binaural inhibition is important for direction dependence in frequency tuning.

Acoustic Stimulation↗

PubMed1999

Measurement of serum circulating intercellular adhesion molecule-1 and its clinical significance in hepatocellular carcinoma: preliminary report.

Serum circulating intercellular adhesion molecule-1 (cICAM-1) was measured in 50 patients with hepatocellular carcinoma (HCC). The mean cICAM-1 level in the 50 patients was 2220 ng/ml and 43 patients (86%) had a high level of cICAM-1 - more than 1000 ng/ml. Comparative analysis of cICAM-1 and alpha-fetoprotein (AFP) levels in the HCC patients showed that serum AFP level was negative (<20 ng/ml) in five patients or "questionable positive" (20-90 ng/ml) in ten patients, while the levels of cICAM-1 in these patients were 1810 and 1710 ng/ml, respectively. Seven patients who underwent hepatectomy had tumor recurrences during a follow-up period of 6-18 months. Their serum AFP levels were lower than 200 ng/ml (mean value, 27 ng/ml), but their mean cICAM-1 level was 1956 ng/ml at the time tumor recurrence was diagnosed. We suggest that the measurement of serum cICAM-1 is not only useful for prediction of the progression and prognosis of HCC, but that it may also be an important marker for the early diagnosis of the disease, and for monitoring postoperative recurrence, particularly in patients with low levels of serum AFP.

Adolescent↗

PubMed1999

Structure and chromosomal locations of mouse steroid receptor coactivator gene family.

The newly recognized steroid receptor coactivators (SRC-1, SRC-2, and SRC-3) belong to a homologous gene family and are important transcriptional mediators for nuclear receptors. Through fluorescence in situ hybridization, we have mapped the mouse SRC-1, SRC-2, and SRC-3 genes to chromosomal locations 12A2-A3, 1A3-A5, and 2H2-H4, respectively. By screening a mouse genomic DNA library, performing long-range polymerase chain reaction and sequencing, we have cloned and characterized the mouse SRC-3 gene. The SRC-3 gene contains 19 exons and spans more than 38 kilobases (kb). Intron sizes are variable. Intron 1 (13.5 kb) and intron 15 (4.6 kb) contribute to almost half the total length of the gene. Among 20 exons identified, exon 10 is the largest (869 bp) and encodes the receptor interaction domain. The start and stop codons for translation are in exon 2 and 20, respectively. The relationship between SRC-3 gene structure and its functional protein domains suggests that many functional domains or subdomains are encoded by individual exons. The correlation between gene structure and alternative splice variants is also discussed. In summary, we have defined the structure of mouse SRC-3 gene and found that the genes in the SRC family are located in different mouse chromosomes. This information is important for developing valuable animal models harboring multiple disruptions of the SRC gene family to study their biological functions.

Animals↗

PubMed1999

Annealing accounts for the length of actin filaments formed by spontaneous polymerization.

We measured the lengths of actin filaments formed by spontaneous polymerization of highly purified actin monomers by fluorescence microscopy after labeling with rhodamine-phalloidin. The length distributions are exponential with a mean of approximately 7 microm (2600 subunits). This length is independent of the initial concentration of actin monomer, an observation inconsistent with a simple nucleation-elongation mechanism. However, with the addition of physically reasonable rates of filament annealing and fragmenting, a nucleation-elongation mechanism can reproduce the observed average length of filaments in two types of experiments: 1) filaments formed from a wide range of highly purified actin monomer concentrations, and 2) filaments formed from 24 microM actin over a range of CapZ concentrations.

Actins↗

PubMed1999

Diffusing wave spectroscopy microrheology of actin filament networks.

Filamentous actin (F-actin), one of the constituents of the cytoskeleton, is believed to be the most important participant in the motion and mechanical integrity of eukaryotic cells. Traditionally, the viscoelastic moduli of F-actin networks have been measured by imposing a small mechanical strain and quantifying the resulting stress. The magnitude of the viscoelastic moduli, their concentration dependence and strain dependence, as well as the viscoelastic nature (solid-like or liquid-like) of networks of uncross-linked F-actin, have been the subjects of debate. Although this paper helps to resolve the debate and establishes the extent of the linear regime of F-actin networks' rheology, we report novel measurements of the high-frequency behavior of networks of F-actin, using a noninvasive light-scattering based technique, diffusing wave spectroscopy (DWS). Because no external strain is applied, our optical assay generates measurements of the mechanical properties of F-actin networks that avoid many ambiguities inherent in mechanical measurements. We observe that the elastic modulus has a small magnitude, no strain dependence, and a weak concentration dependence. Therefore, F-actin alone is not sufficient to generate the elastic modulus necessary to sustain the structural rigidity of most cells or support new cellular protrusions. Unlike previous studies, our measurements show that the mechanical properties of F-actin are highly dependent on the frequency content of the deformation. We show that the loss modulus unexpectedly dominates the elastic modulus at high frequencies, which are key for fast transitions. Finally, the measured mean square displacement of the optical probes, which is also generated by DWS measurements, offers new insight into the local bending fluctuations of the individual actin filaments and shows how they generate enhanced dissipation at short time scales.

Actin Cytoskeleton↗

PubMed1999

A survey of blindness and cataract surgery in Doumen County, China.

PURPOSE: To assess blindness prevalence and that caused specifically by cataract in rural southern China. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 5342 persons older than 50 years of age. METHODS: Visual acuity and eye examinations were performed in the summer of 1997 in a random sample of villages in Doumen County. Differences in blindness prevalence associated with age, gender, and education were explored using logistic regression. The survey was preceded by a pilot study in which operational methods were refined and quality assurance measures were performed. MAIN OUTCOME MEASURES: Distance visual acuity and lens status. RESULTS: Bilateral blindness (presenting visual acuity < 0.10) was found in 4.37% (95% confidence interval, 3.67%-5.06%). Blindness was associated with increasing age (P < 0.001) and with the lack of education (P < 0.01). Cataract was the principal cause of blindness in at least one eye in 61.5% of blind people, with refractive error responsible for another 10%. An estimated 40% of the cataract blind were operated on; surgical coverage was lowest among the elderly, women, and those without schooling, although not at statistically significant levels. CONCLUSIONS: Despite the increased attention given to eye care in Doumen County, blindness remains a major public health problem. Cataract surgery is reaching fewer than half of those who could benefit from it.

Aged↗

PubMed1999

Visual acuity and quality of life in patients with cataract in Doumen County, China.

PURPOSE: To evaluate the effectiveness of cataract surgery in achieving sight restoration and vision-related quality-of-life (QOL) in patients from rural southern China. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 109 cataract operated persons (152 eyes) and 654 unoperated persons. METHODS: Cluster sampling was used in identifying a random sample of 5342 persons 50 years of age and older for visual acuity and eye examinations. Visual functioning (VF) and QOL questionnaires were administered to aphakic and pseudophakic individuals, unoperated persons with presenting visual acuity less than 0.10 in either eye, and a sample of those with normal vision. MAIN OUTCOME MEASURES: Distance visual acuity, VF, and QOL questionnaire scores. RESULTS: Among the cataract operated participants, 43 (39.4%) were bilaterally operated on, 32.1% had presenting visual acuity less than 0.10 in both eyes with 8.3% greater than or equal to 0.32 in both eyes. Of operated eyes, 52.6% presented with visual acuity less than 0.10, 23.7% greater than or equal to 0.32; with best correction, the corresponding percentages were 21.1% and 42.1%. Uncorrectable aphakia due to surgical complications was common. In a multivariate regression model, better visual acuity outcomes were associated with higher level surgeon practice settings and recent surgery. On a 0 to 100 scale, mean VF and QOL scores for the cataract operated population were 41.6 and 54.5, respectively. Mean scores ranged from 84.4 and 93.4, respectively, for the unoperated persons with normal vision, to 14.6 and 31.2, respectively, for those with visual acuity less than 0.05 in both eyes. The VF and QOL scores were closely correlated with presenting visual acuity in both cataract operated and unoperated populations (r = 0.49-0.64). Scores among the cataract operated population were not influenced by age, gender, or education level. Among the unoperated population, lack of education was associated with lower VF and QOL scores (P = 0.017 and P = 0.005, respectively), and older age was associated with lower QOL scores (P < 0.001). CONCLUSION: Patients in rural southern China are not realizing the full sight-restoring potential of modern-day cataract surgery. Remedial efforts are needed to improve the performance of local eye surgeons.

Aged↗

PubMed1999

Genomic structure, mapping, activity and expression of fibroblast growth factor 17.

Fibroblast growth factors are essential molecules for development. Here we characterize Fgfl7, a new member of the fibroblast growth factor (FGF) family. The Fgfl7 gene maps to mouse chromosome 14 and is highly conserved between mouse and human (93% identity). It exhibits 60% amino acid identity with Fgf8 and 50% identity with Fgf8. Both Fgf8 and Fgf17 have a similar structure and a similar pattern of alternative splicing in the 5' coding region. When expressed in 3T3 fibroblasts, mouse FGF17 is transforming, indicating that it can activate the 'c' splice form of either FGF receptor (FGFR) one or two. During midgestation embryogenesis, in situ hybridization analysis localized Fgf17 expression to specific sites in the midline structures of the forebrain, the midbrain-hindbrain junction, the developing skeleton and in developing arteries. Comparison to Fgf8 revealed a striking similarity in expression patterns, especially in the central nervous system (CNS), suggesting that both genes may be important for CNS development, although Fgf17 is expressed somewhat later than Fgf8. In the developing skeleton, both genes are expressed in costal cartilage while Fgf8 is preferentially expressed in long bones. In the developing great vessels Fgfl7 is preferentially expressed, suggesting that it may have a more prominent role in vascular growth.

3T3 Cells↗