PubMed Health⌕ Search

Biomedical subjects

J Fan

Publications and source records attributed to J Fan.

At least 19 recordsLinked to original sources
PubMed2002

Resonant self-trapping of high intensity Bessel beams in underdense plasmas.

We present a comprehensive report based on recent work [Phys. Rev. Lett. 84, 3085 (2000)] on resonant self-trapping and enhanced absorption of high power Bessel beams in underdense plasmas. The trapping resonance is strongly dependent on initial gas pressure, Bessel-beam geometry, and laser wavelength. Analytic estimates, and simulations using a one-dimensional Bessel-beam-plasma interaction code consistently explain the experimental observations. These results are for longer, moderate intensity pulses where the self-trapping channel is induced by laser-heated plasma thermal pressure. To explore the extension of this effect to ultrashort, intense pulsed Bessel beams, we perform propagation simulations using the code WAKE [Phys. Rev. E 53, R2068 (1996)]. We find that self-trapping can occur as a result of a plasma refractive index channel induced by the combined effects of relativistic motion of electrons and their ponderomotive expulsion.

Journal Article↗
PubMed2001

Chlamydial genovar distribution after community wide antibiotic treatment.

Major outer membrane protein sequences, determined from Chlamydia-positive eye swab samples collected in 2 Egyptian villages, were used to analyze the epidemiology of trachoma in an endemic setting. Samples were collected during the 1999 Azithromycin in Control of Trachoma trial, in which residents of villages were mass treated with either oral azithromycin or topical tetracycline and were followed up for nearly 2 years. Three genovar families (A, Ba, and C) and 12 genovars were detected, with 2 genovars (A1 and Ba1) comprising almost 75% of the samples. The presence of >1 genovar within households was common, with > or =24% of households having >1 genovar. Evidence consistent with reinfection and persistence as mechanisms of communitywide continued presence of trachoma was provided by data for individuals infected with rare genovars.

Anti-Bacterial Agents↗
PubMed2001

Nck/Dock: an adapter between cell surface receptors and the actin cytoskeleton.

In response to extracellular signals, cell surface receptors engage in connections with multiple intracellular signaling pathways, leading to the cellular responses such as survival, migration, proliferation and differentiation. The 'pY-->SH2/SH3-->effector' connection is a frequently used scheme by many cell surface receptors, in which SH2/SH3-containing adapters connect protein tyrosine phosphorylation to a variety of downstream effector pathways. Following the initial landmark finding that Grb2 adapter links the receptors to the Ras pathway leading to DNA synthesis, recent studies have revealed that the biological function of the SH2/SH3 adapter Nck/Dock is to link cell surface receptors to the actin cytoskeleton. For example, in the evolutionarily-conserved signaling network, GEF-Rac-Nck-Pak, Nck 'fixes up' the interaction of Pak with its upstream activator, Rac. The activated Pak then regulates the cytoskeletal dynamics. The fact that the majority of the more than 20 Nck-SH3-associated effectors are regulators of the actin cytoskeleton suggests that Nck/Dock regulates, via binding to distinct effectors, various cell type-specific motogenic responses. This review focuses on our current understanding of Nck/Dock function. Due to the number and complexity of the terminologies used in this review, a 'Glossary of Terms' is provided to help reduce confusions.

Actins↗
PubMed2001

Assessing the heritability of attentional networks.

BACKGROUND: Current efforts to study the genetics of higher functions have been lacking appropriate phenotypes to describe cognition. One of the problems is that many cognitive concepts for which there is a single word (e.g. attention) have been shown to be related to several anatomical networks. Recently we have developed an Attention Network Test (ANT) that provides a separate measure for each of three anatomically defined attention networks. In this small scale study, we ran 26 pairs of MZ and DZ twins in an effort to determine if any of these networks show sufficient evidence of heritability to warrant further exploration of their genetic basis. RESULTS: The efficiency of the executive attention network, that mediates stimulus and response conflict, shows sufficient heritability to warrant further study. Alerting and overall reaction time show some evidence for heritability and in our study the orienting network shows no evidence of heritability. CONCLUSIONS: These results suggest that genetic variation contributes to normal individual differences in higher order executive attention involving dopamine rich frontal areas including the anterior cingulate. At least the executive portion of the ANT may serve as a valid endophenotype for larger twin studies and subsequent molecular genetic analysis in normal subject populations.

Adolescent↗
PubMed2001

Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholesterolemia and atherosclerosis.

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of TG-rich lipoproteins. To elucidate the physiological roles of LPL in lipid and lipoprotein metabolism, we generated transgenic rabbits expressing human LPL. In postheparinized plasma of transgenic rabbits, the human LPL protein levels were about 650 ng/ml, and LPL enzymatic activity was found at levels up to 4-fold greater than that in nontransgenic littermates. Increased LPL activity in transgenic rabbits was associated with as much as an 80% decrease in plasma triglycerides and a 59% decrease in high density lipoprotein-cholesterol. Analysis of the lipoprotein density fractions revealed that increased expression of the LPL transgene resulted in a remarkable reduction in the level of very low density lipoproteins as well as in the level of intermediate density lipoproteins. In addition, LDL cholesterol levels in transgenic rabbits were significantly increased. When transgenic rabbits were fed a cholesterol-rich diet, the development of hypercholesterolemia and aortic atherosclerosis was dramatically suppressed in transgenic rabbits. These results demonstrate that systemically increased LPL activity functions in the metabolism of all classes of lipoproteins, thereby playing a crucial role in plasma triglyceride hydrolysis and lipoprotein conversion, and that overexpression of LPL protects against diet-induced hypercholesterolemia and atherosclerosis.

Animals↗
PubMed2001

Induction of human matrix metalloproteinase-12 gene transcriptional activity by GM-CSF requires the AP-1 binding site in human U937 monocytic cells.

Matrix metalloproteinase-12 (MMP-12) is critical for the migration of monocytes/macrophages into inflammatory sites through the basement membranes. We previously reported that MMP-12 expression was initially induced by granulocyte macrophage colony-stimulating factor (GM-CSF) in human peripheral blood monocytes and U937 monocytic cells. To further elucidate the molecular mechanism for the regulation of MMP-12 expression by GM-CSF in monocytes, we determined the sequence requirements for the MMP-12 gene transcriptional response of U937 monocytic cells to GM-CSF by using luciferase reporter and electrophoretic mobility shift assays. A series of 5'-deletion and site-directed mutation of the human MMP-12 promoter demonstrated that an AP-1 site spanning the -81 to -75-bp region is critical for the induction of MMP-12 promoter activity by GM-CSF. The electrophoretic mobility shift assay revealed that AP-1 binding activity was increased by GM-CSF treatment and that the AP-1 complex induced by GM-CSF consisted of multiple Jun and Fos isoforms. These results indicate that MMP-12 expression in U937 monocytes was initially induced by GM-CSF through the AP-1 binding activity.

5' Untranslated Regions↗
PubMed2001

Cytoprotection against mechanical forces delivered through beta 1 integrins requires induction of filamin A.

Cells in mechanically active environments can activate cytoprotective mechanisms to maintain membrane integrity in the face of potentially lethal applied forces. Cytoprotection may be mediated by expression of membrane-associated cytoskeletal proteins including filamin A, an actin-binding protein that increases the rigidity of the subcortical actin cytoskeleton. In this study, we tested the hypotheses that applied forces induce the expression of filamin A specifically and that this putative protective response inhibits cell death. Magnetically generated forces were applied to protein-coated magnetite beads bound to human gingival fibroblasts, cells with constitutively low basal levels of filamin A mRNA and protein. Forces applied through collagen or fibronectin, but not bovine serum albumin or poly-l-lysine-coated beads, increased mRNA and protein content of filamin A by 3-7-fold. Forces had no effect on the expression of other filamin isotypes or other cytoskeletal proteins. This effect was dependent on the duration of force and was blocked by anti-beta(1) integrin antibodies. Force also stimulated a 60% increase in expression of luciferase under the control of a filamin A promoter in transiently transfected Rat2 fibroblasts and was dependent on Sp1 transcription factor binding sites located immediately upstream of the transcription start site. Experiments with actinomycin D-treated cells showed that the increased filamin A expression after force application was due in part to prolongation of mRNA half-life. Antisense filamin oligonucleotides blocked force-induced filamin A expression and increased cell death by >2-fold above controls. The force-induced regulation of filamin A was dependent on intact actin filaments. We conclude that cells from mechanically active environments can couple diverse signals from forces applied through beta-integrins to up-regulate the production of cytoprotective cytoskeletal proteins, typified by filamin A.

Animals↗
PubMed2001

Self-assembly of frameworks with specific topologies: construction and anion exchange properties of M3L2 architectures by tripodal ligands and silver(I) salts.

Three five-component architectures, compounds 3, 4, and 5 were obtained by self-assembly of tripodal 1,3,5-tris(imidazol-1-ylmethyl )-2,4,6-trimethylbenzene (6) and 1,3,5-tris(benzimidazol-2-ylmethyl)benzene (7) ligands with silver(I) salts. The structures of these novel complexes have been determined by X-ray crystallography. The results of structural analysis indicate that these frameworks have same M3L2 components, but different structures. Compounds 3 and 4 are both M3L2 type cage-like complexes, while the 5 is an open trinuclear complex. The complex 3 is a cylindrical cage with simultaneous inclusion of a perchlorate anion inside of the cage as a guest molecule. Such guests can be exchanged for other anions through the open edge of the cage as evidenced by crystal structure of 4. The results demonstrate that the molecular M3L2 type cage can act as a host for anions and provide a nice example of supramolecular architectures with interesting properties and possible applications.

Journal Article↗
PubMed2001

[Expression rates of three angiogenic factors in hepatocellular carcinoma and their relation with microvessel density and portal vein tumor thrombosis].

OBJECTIVE: To investigate the expression rates of the three angiogenic factors-basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and platelet-derived endothelial cell growth factor (PD-ECGF) in hepatocellular carcinoma (HCC) and to investigate the relation of their expression rates to the microvessel density (MVD) of the tumor and to the formation of portal vein tumor thrombus (PVTT). METHODS: Immunohistochemical staining was conducted on 61specimens of hepatic cell carcinoma removed in operation. RESULTS: The expression rates of dFGF, VEGF, and PD-ECGF in HCC tissue were 45.9%, 75.4% and 70.5% respectively. The incidence rates of PVTT while all of the 3 angiogenic factor were negatively expressed, one of them was positively expressed, two of them were positively expressed, and all of them were positively expressed were 16.7%, 25.0%, 54.2% and 63.2% respectively (P < 0.05, test for trend). The MVD counts in HCC tissue in the above-mentioned four conditions were 99 +/- 56, 113 +/- 27, 140 +/- 347 and 194 +/- 52 respectively (P < 0.001, ANOVA test). CONCLUSION: As the number of positively expressed angiogenic factors in HCC tissue increases, the angiogenic capability of the tumor enhances greatly, and the incidence rate of PVTT increases too.

Adult↗
PubMed2001

Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma.

BACKGROUND: Recently, the implementation of screening programs using alpha-fetoprotein (AFP) and ultrasonography in high risk populations has identified increasing numbers of patients with small hepatocellular carcinoma (small HCC). The aim of this study was to summarize the authors' experience in patients who underwent hepatectomy for small HCC and the factors that influence or improve long term survival. METHODS: The study included 1000 patients who underwent hepatectomy for small HCC (< or = 5 cm) and compared them with 1366 patients who underwent hepatectomy for large HCC (> 5 cm) during the same period. A Cox proportional-hazards model was used for multivariate analysis of prognostic factors. RESULTS: Comparison between patients with small HCC (n = 1000 patients) and patients with large HCC (n = 1366 patients) revealed that those with small HCC had a higher resection rate (93.6% [1000 of 1068 patients] vs. 55.7% [1366 of 2451 patients]; P < 0.01), a higher curative resection rate (80.5% [805 of 1000 patients] vs. 60.7% [829 of 1366 patients]; P < 0.01), a lower operative mortality rate (1.5% [15 of 1000 patients] vs. 3.7% [50 of 1366 patients]; P < 0.01), better differentiation of tumor cells (Edmondson Grade 3-4; 14.9% vs. 20.1%; P < 0.01), a higher incidence of single nodule tumors (82.6% vs. 64.4%; P < 0.01), a higher proportion of well encapsulated tumors (73.3% vs. 46.3%; P < 0.01), a lower incidence of tumor emboli in the portal vein (4.9% vs. 20.8%; P < 0.01), and higher survival rates after undergoing resection (5 years: 62.7% vs. 37.1%; P < 0.01; 10 years: 46.3% vs. 29.2%; P < 0.01). No significant difference was found between survival after undergoing minor resection (n = 949 patients) or lobectomy (n = 51 patients) in patients with small HCC (P > 0.05). Reresection for subclinical recurrence or solitary pulmonary metastasis after small HCC resection was undertaken in 84 patients. CONCLUSIONS: Resection is still the modality of first choice for the treatment of patients with small HCC. Minor resection instead of lobectomy was the key to increasing resectability and decreasing operative mortality, and reresection for subclinical recurrence or solitary pulmonary metastasis was important approach to prolonging survival further.

Adolescent↗
PubMed2001

Antibodies to cytoplasmic dynein heavy chain map the surface and inhibit motility.

Polyclonal antibodies have been raised against four 16 residue peptides with sequences taken from the C-terminal quarter of the human cytoplasmic dynein heavy chain. The sites are downstream from a known microtubule-binding domain associated with the "stalk" that protrudes from the motor domain. The antisera were assayed using bacterially expressed proteins with amino acid sequences taken from the human cytoplasmic dynein heavy chain. Every antiserum reacted specifically with the appropriate expressed protein and with pig brain cytoplasmic dynein, whether the protein molecules were denatured on Western blots or were in a folded state. But, whereas three of the four antisera recognized freshly purified cytoplasmic dynein, the fourth reacted only with dynein that had been allowed to denature a little. After affinity purification against the expressed domains, whole IgG molecules and Fab fragments were assayed for their effect on dynein activity in in vitro microtubule-sliding assays. Of the three anti-peptides that reacted with fresh dynein, one inhibited motility but the others did not. The way these peptides are exposed on the surface is compatible with a model whereby the dynein motor domain is constructed from a ring of AAA protein modules, with the C-terminal module positioned on the surface that interacts with microtubules. We have tentatively identified an additional AAA module in the dynein heavy chain sequence, which would be consistent with a heptameric ring.

Amino Acid Sequence↗
PubMed2001

Selective sensitization of retinoblastoma protein-deficient sarcoma cells to doxorubicin by flavopiridol-mediated inhibition of cyclin-dependent kinase 2 kinase activity.

We examined the effects of flavopiridol (FP), a cyclin-dependent kinase inhibitor, on doxorubicin (DOX)-induced cell killing in an osteosarcoma cell line (SaOs-2) that lacks functional retinoblastoma protein (pRb). The IC50 value for DOX was 7-fold lower when combined with a low dose (100 nM) FP in pRb-deficient SaOs-2 cells than in the absence of FP. In contrast, the IC50 value for DOX was not decreased in the presence of 100 nM FP in pRb-restored SaOs-2 cells. Consistent with this, FP enhanced DOX-induced activation of caspase-3, which correlates with apoptosis, in pRb-deficient cells but not in pRb-restored cells. Additional studies showed that FP decreased DOX-induced cell accumulation in S phase in retinoblastoma-restored cells but not in pRb-deficient cells. An increased expression of p21 and inhibition of cyclin-dependent kinase 2 kinase activity by FP was also observed in pRb-deficient cells but not in retinoblastoma-restored SaOs-2 cells. We conclude that pRb plays a key role in determining whether FP selectively sensitizes DOX-induced cell killing in human sarcoma cells. Because lack of functional pRb is a common abnormality in human cancers, the combination of FP with DOX in tumors lacking pRb would be worthy of further investigation.

Antibiotics, Antineoplastic↗
PubMed2001

Local structures of mechanically alloyed Fe100-xCux solid solutions studied by X-ray absorption fine structure.

The local structures of the immiscible Fe(100-x)Cu(x) alloys (x= 0, 10, 20, 40, 60, 80 and 100) produced by mechanical alloying have been investigated by XAFS. For the Fe(100-x)Cu(x) (x > or = 40) solid solutions, the local structures around Fe atoms change from bcc structure to fcc one and the Cu atoms maintain the original coordination geometry after milling for 160 hours. On the contrary, the local structures around Cu atoms in both of Fe80Cu20 and Fe90Cu10 alloys appear a transition from fcc to bcc structure. We found that the Debye-waller factor sigma of fcc Fe-Cu phase is larger than that of bcc Fe-Cu phase, and the sigma (0.099 A) around Fe atoms is larger than that (0.089 A) of Cu in the Fe(100-x)Cu(x) (x > or = 40) solid solutions. This suggests that the mechanically alloyed Fe(100-x)Cu(x) supersaturated solid solution is not a homogeneous alloy, and consists of Fe-rich and Cu-rich regions for various compositions. A possible mechanism for bcc-to-fcc and fcc-to-bcc changes in Fe(100-x)Cu(x) solid solutions is discussed in relation to the interdiffusion and transition induced by the ball milling.

Journal Article↗
PubMed2001

Structural basis of diverse sequence-dependent target recognition by the 8 kDa dynein light chain.

Dyneins are multi-subunit molecular motors that translocate molecular cargoes along microtubules. Other than acting as an essential component of the dynein motor complex, the 89-residue subunit of dynein light chain (DLC8) also regulates a number of other biological events by binding to various proteins and enzymes. Currently known DLC8 targets include neuronal nitric oxide synthase; the proapoptotic Bcl-2 family member protein designated Bim; a Drosophila RNA localization protein Swallow, myosin V, neuronal scaffolding protein GKAP, and IkappaBalpha, an inhibitor of the NFkappaB transcription factor. The DLC8-binding domains of the various targets are confined within a short, continuous stretch of amino acid residues. However, these domains do not share any obvious sequence homology with each other. Here, the three-dimensional structures of DLC8 complexed with two peptides corresponding to the DLC8-binding domains of neuronal nitric oxide synthase and Bim, respectively, were determined by NMR spectroscopy. Although the two DLC8-binding peptides have entirely different amino acid sequences, both peptides bind to the protein with a remarkable similar conformation by engaging the symmetric DLC8 dimer through antiparallel beta-sheet augmentation via the beta2 strand of the protein. Structural comparison indicates that the two target peptides use different regions within the conformational flexible peptide-binding channels to achieve binding specificity. We have also re-determined the apo-form solution structure of DLC8 in this work. The structures of the DLC8/target peptide complexes, together with the dynamic properties of the protein, provide a molecular basis of DLC8's diverse amino acid sequence-dependent target recognition.

Amino Acid Sequence↗
PubMed2001

Onset of odorant receptor gene expression during olfactory sensory neuron regeneration.

Individual olfactory sensory neurons are thought to express only one odorant receptor gene from a repertoire of hundreds to thousands of genes. How do these sensory neurons choose just one specific odorant receptor to express during their differentiation? As an initial attempt toward understanding the process of odorant receptor gene regulation, we studied when odorant receptor expression is activated during sensory neuron regeneration. We find that receptor gene expression is activated in postmitotic neurons and can occur in the absence of the olfactory bulb. These results suggest that receptor expression is restricted to the terminal stages of olfactory neuron differentiation, and sensory neurons do not simply inherit the odorant receptor that is already expressed in mitotic precursor cells. Our results also support a model in which odorant receptor gene expression occurs independent of the olfactory bulb.

Animals↗
PubMed2001

Role of the oncogenic Raf-1 in orchestration of discrete nuclear factor-kappaB-activating pathways.

Raf-1, a key kinase in the Ras signaling pathway, plays critical roles in cell differentiation, proliferation, and tumorigenesis. However, knowledge of the Raf-1 in inflammation is limited. Using an inducible oncogenic Raf-1, we show that the Raf-1 orchestrates the discrete NF-kappaB activating pathways. While the Raf-1 activation induces a modest IkappaB degradation by enhancing the basal IkappaB kinase activity, it contradictorily suppresses the proinflammatory cytokine inducible IkappaB kinase complex, leading to an inhibition of TNF-alpha- and IL-1beta-induced NF-kappaB activation. Despite considerable degrees of overlap, LPS signaling is not affected by Raf-1. By either conditionally reducing Raf-1 activity or completely disrupting the Raf-1 signaling by PD98059, a specific inhibitor of MEK1, the otherwise inhibited cytokine responses can be restored. Moreover, when the activity of Raf-1 is up-regulated during the cell cycle progression from the G(0) phase to the late G(1) phase, the enhanced Raf-1 activity suffices to shift the TNF-alpha response from the sensitive to the insensitive state. Together, these studies elucidate a mechanism by which signaling outputs are shaped by the intracellular Raf-1, thus explaining the "cellular context"-dependent cytokine response.

Animals↗
PubMed2001

Regulated ectopic expression and allelic-replacement mutagenesis as a method for gene essentiality testing in Staphylococcus aureus.

Conditional expression systems were utilized for the ectopic induction of essential genes in Staphylococcus aureus. Resulting strains were then subjected to allelic-replacement mutagenesis of the native allele under inducing conditions for expression of the ectopic copy of the gene. This strategy produced test strains whereby cellular viability was uniquely dependent on the presence of inducer and provided a direct and absolute confirmation of genetic essentiality for each locus. The procedure is particularly useful for genes that are difficult to analyze by conventional inactivation strategies due to either small size or complex genomic organization.

Alleles↗