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Biomedical subjects

F Li

Publications and source records attributed to F Li.

At least 91 records · Page 5Linked to original sources

Il-8((3-73))K11R is a high affinity agonist of the neutrophil CXCR1 and CXCR2.

In studies aimed at developing a high affinity IL-8 antagonist, our first objective was to generate a high-affinity IL-8 analogue. We targeted amino acids within the receptor-binding domain and found that IL-8((3-73))K11R induced significantly more neutrophil beta-glucuronidase release than either IL-8 or the alternate analogues and, in chemotaxis assays, induced 2-3-fold greater neutrophil responses than IL-8. Furthermore, in competitive radio- or biotinylated-ligand binding assays, IL-8((3-73))K11R was more effective than IL-8, IL-8((3-73)), or its T12S, H13F, and K11R/T12S/H13F analogues in blocking IL-8 binding to neutrophils; 1.8 pmol IL-8((3-73))K11R inhibited by 50% the binding of approximately 20 pmol (125)I-IL-8 to neutrophils. Both IL-8 (a CXCR1/CXCR2 ligand) and the CXCR2-specific ligand GROalpha differentially inhibited binding of (125)I-IL-8((3-73))K11R to neutrophils, albeit weakly, suggesting that IL-8((3-73))K11R is a high affinity ligand for both the CXCR1 and CXCR2. Thus IL-8((3-73))K11R is an excellent candidate for further studies aimed at generating a high affinity IL-8 antagonist.

Amino Acid Sequence↗

The replication timing program of the Chinese hamster beta-globin locus is established coincident with its repositioning near peripheral heterochromatin in early G1 phase.

We have examined the dynamics of nuclear repositioning and the establishment of a replication timing program for the actively transcribed dihydrofolate reductase (DHFR) locus and the silent beta-globin gene locus in Chinese hamster ovary cells. The DHFR locus was internally localized and replicated early, whereas the beta-globin locus was localized adjacent to the nuclear periphery and replicated during the middle of S phase, coincident with replication of peripheral heterochromatin. Nuclei were prepared from cells synchronized at various times during early G1 phase and stimulated to enter S phase by introduction into Xenopus egg extracts, and the timing of DHFR and beta-globin replication was evaluated in vitro. With nuclei isolated 1 h after mitosis, neither locus was preferentially replicated before the other. However, with nuclei isolated 2 or 3 h after mitosis, there was a strong preference for replication of DHFR before beta-globin. Measurements of the distance of DHFR and beta-globin to the nuclear periphery revealed that the repositioning of the beta-globin locus adjacent to peripheral heterochromatin also took place between 1 and 2 h after mitosis. These results suggest that the CHO beta-globin locus acquires the replication timing program of peripheral heterochromatin upon association with the peripheral subnuclear compartment during early G1 phase.

Animals↗

Bone morphogenetic protein 4 induces efficient hematopoietic differentiation of rhesus monkey embryonic stem cells in vitro.

A cell culture system consisting of mouse S17 stromal cells supplemented with cytokines was developed for hematopoietic differentiation of rhesus monkey embryonic stem (ES) cells. The differentiated colonies that formed contained clusters of hematopoietic-like cells, as well as structures similar in appearance to embryonic blood islands. When this culture system was supplemented with bone morphogenetic protein 4 (BMP-4), the numbers of primary hematopoietic clusters increased by an average of 15 fold. The primary hematopoietic clusters containing clonogenic precursors (expandable hematopoietic clusters) increased by 18 fold. Immunofluorescence analysis showed that a substantial percentage of the hematopoietic-like cells were CD34(+), with morphologic features of undifferentiated blast cells. Enrichment of the CD34(+) cells was associated with enhanced stromal-dependent, cytokine-driven formation of cobblestone colonies on secondary plating. The hematopoietic identity of the precursors was further indicated by their expression of genes associated with hematopoietic differentiation, as well as morphologic assessments that showed erythroid and myeloid lineages among the progeny cells. In addition, reverse transcriptase-polymerase chain reaction analysis of BMP-4-treated rhesus monkey ES cells demonstrated an up-regulation of early-expressed genes responsible for embryonic hematopoiesis and angiogenesis during the first 7 days of culture. These observations suggest that embryonic mesoderm regulatory protein may mimic physiologic signals that are required for the onset of embryonic hematopoiesis and stem cell formation in rhesus monkey ES cells.

Animals↗

Molecular cloning and characterization of chemokine-like factor 1 (CKLF1), a novel human cytokine with unique structure and potential chemotactic activity.

Cytokines are small proteins that have an essential role in the immune and inflammatory responses. The repertoire of cytokines is becoming diverse and expanding. Here we report the identification and characterization of a novel cytokine designated as chemokine-like factor 1 (CKLF1). The full-length cDNA of CKLF1 is 530 bp long and a single open reading frame encoding 99 amino acid residues. CKLF1 bears no significant similarity to any other known cytokine in its amino acid sequence. Expression of CKLF1 can be partly inhibited by interleukin 10 in PHA-stimulated U937 cells. Recombinant CKLF1 is a potent chemoattractant for neutrophils, monocytes and lymphocytes; moreover, it can stimulate the proliferation of murine skeletal muscle cells. These results suggest that CKLF1 might have important roles in inflammation and in the regeneration of skeletal muscle.

Amino Acid Sequence↗

Lymphotactin expression by engineered myeloma cells drives tumor regression: mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor.

The C chemokine lymphotactin has been characterized as a T cell chemoattractant both in vitro and in vivo. To determine whether lymphotactin expression within tumors could influence tumor growth, we transfected an expression vector for lymphotactin into SP2/0 myeloma cells and tested their ability to form tumors in BALB/c and nude mice. Transfection did not alter cell growth in vitro. Whereas SP2/0 cells gave rise to a 100% tumor incidence, lymphotactin-expressing SP2/0-Lptn tumors invariably regressed in BALB/c mice and became infiltrated with CD4(+) and CD8(+) T cells and neutrophils. Regression of the SP2/0-Lptn tumors was associated with a type 1 cytokine response and dependent on both CD4(+) and CD8(+) T cells, but not NK cells. Both SP2/0 and SP2/0-Lptn tumors grew in nude mice, but growth of the latter tumors was retarded and associated with heavy neutrophil responses; this retardation of SP2/0-Lptn tumor growth was reversed by neutrophil depletion of the mice. Our data also indicate that mouse neutrophils express the lymphotactin receptor XCR1 and that lymphotactin specifically chemoattracts these cells in vitro. Thus, lymphotactin has natural adjuvant activities that may augment antitumor responses via effects on both T cells and neutrophils and thereby could be important in gene transfer immunotherapies for some cancers.

Animals↗

Up-regulation of calcineurin Abeta mRNA in the Alzheimer's disease brain: assessment by cDNA microarray.

Recent advances in cDNA microarray technology have made it possible to analyze expression of more than 8000 genes. Using this technology, gene expression in the hippocampus containing neurofibrillary tangle-associated lesions from an Alzheimer's disease (AD) patient was compared with expression in the parietal cortex from the same patient that lacked these lesions. We also compared gene expression using a control brain. The top 20 named genes significantly up-regulated or down-regulated only in the AD brain were determined. The most up-regulated gene proved to be calcineurin Abeta mRNA (CAbeta). In situ hybridization histochemistry revealed that CAbeta was significantly up-regulated in pyramidal neurons of the hippocampus in the AD brain. RT-PCR analysis revealed that CAbeta was up-regulated in the hippocampus from two out of three AD brains while there were no changes in three control brains. Our study suggests that CAbeta may play a crucial role in the pathophysiological mechanisms in AD.

Aged↗

Release of hydrogen chloride from combustibles in municipal solid waste.

Study of the inorganic chlorides in municipal solid waste (MSW) shows that the main source of inorganic chlorides in MSW is food. The main organic source of HCl emission from MSW is plastic. But wood, textiles, and food also produce a large amount of HCl when they are combusted. Each combustible shows a different HCl releasing temperature range. At 973 K, there are 30-70% of the total chlorine left in the char of each combustibles in MSW.

Air Pollutants↗

[Effects of aspirin on ferritin expression and resistance to oxidative damage in endothelial cells].

OBJECTIVE: To explore the mechanism of Aspirin induced ferritin synthesis on resistance to oxidative damage in endothelial cells. METHODS: Using cultured endothelial cells, we measured the effect of aspirin with different incubative time (4 - 24 h) and different concentration (0.1 - 3 mmol/L), salicylic acid and indomethacin induced ferritin expression by ELISA kit, and observed the change of lactate dehydrogenase (LDH) release rate, malondialdehyde (MDA) and cellular viability after preincubating the cell for 8 h with aspirin on resistance to hydrogen peroxide toxicity. Statistical analysis using a one-way analysis of variance. RESULTS: Aspirin at low concentration (0.1 mmol/L) induced significant increase ferritin expression in a concentration-dependent fashion: (5.8 +/- 0.3) ng/10(6) cell (0.1 mmol/L As), (6.4 +/- 0.4) ng/10(6) cell (0.5 mmol/L As), (7.0 +/- 0.7) ng/10(6) cell (1 mmol/L As), (7.4 +/- 0.4) ng/10(6) cell (2 mmol/L As), (7.7 +/- 0.5) ng/10(6) cell (3 mmol/L As), significant for all values: P < 0.05 versus normal control. Induction of ferritin levels by aspirin (1 mmol/L) was also time dependent: (5.8 +/- 1.0) ng/10(6) cell (4 h, but P > 0.05 vs control), (6.5 +/- 1.0) ng/10(6) cell (8 h, P < 0.05 vs control) and (7.8 +/- 0.8) ng/10(6) cell (24 h). Preincubating the cells with aspirin (0.1 mmol/L) reduced LDH release rate by 50%, toxicity reduction by 40%, and significant decrease MDA production. Aspirin induced cytoprotection from H(2)O(2) damage was also in a concentration dependent fashion. The cytoprotection of aspirin was mimicked by exogenous iron-free apo-ferritin but not iron-load ferritin. Salicylic acid and indomethacin failed to increase ferritin expression. CONCLUSION: Aspirin could induce significant increase ferritin synthesis at low concentration (0.1 mmol/L). Ferritin induction by aspirin was specific in nonsteroidal anti-inflammatory drugs.

Antioxidants↗

The relationship between the interfacial properties of surfactants and their toxicity to aquatic organisms.

In previous work, the toxicity of several anionic and nonionic surfactants to rotifer (Brachionus calyciflorus) was shown to be highly correlated with interfacial activity. In this study, the relationship between interfacial properties of surfactants and their effects on aquatic organisms is extended to include the toxicity of the cationic surfactant class (homologues of alkyl trimethylammonium chloride and alkyl hydroxyethyl dimethylammonium chloride) to green algae (Selenastrum capricornutum) and the bioconcentration of linear alkylbenzene sulfonate (LAS) isomers and homologues by fish (Pimephales promelas and Ictalurus punctatus). In each case, the interfacial activity is expressed by the physicochemical parameter, delta G0ad/Amin, where delta G0ad is the standard free energy of adsorption of the surfactant at the air/solution interface and Amin is the minimum cross sectional area of the surfactant, or the analogous parameter, delta 1sG0ad/1sAmin, at the solid/liquid interface, where the solid is an immobilized artificial membrane (IAM) that mimics a biological cell membrane. The general nature of the relationship between interfacial activity of surfactants and their biological effects in aquatic systems indicates that sorption to biological membranes is a critical parameter for predicting and understanding environmental effects. While specific interactions probably occur once a surfactant has penetrated a membrane bilayer, nonspecific hydrophobic interactions appear to be driving the sorption process.

Animals↗

Neutrophils and B cells express XCR1 receptor and chemotactically respond to lymphotactin.

The C chemokine lymphotactin (Lptn) has been reported to act specifically on CD4(+) and CD8(+) T lymphocytes and natural killer (NK) cells, but not monocytes. However, the chemotactic effect of Lptn on other types of hematopoietic cells has not been well studied. In this study we investigated (i) the chemotactic influences of Lptn on T and B lymphocytes, neutrophils, monocytes, and dendritic cells, and (ii) the expression of the Lptn receptor (XCR1) by these cells, using RT-PCR. Our data showed that Lptn is chemotactic for B lymphocytes and neutrophils as well as T lymphocytes, but not for monocytes or dendritic cells, and that XCR1 expression is found only in association with T and B lymphocytes and neutrophils, but not monocytes or dendritic cells. Thus, this study is the first demonstration of a chemotactic effect of Lptn on neutrophils and confirms the association of this effect with expression of the XCR1 receptor on these cells. These data suggest that Lptn could potentially be an important protein in the regulation of T and B lymphocytes and neutrophil trafficking, and thereby also their roles in inflammatory and immunological responses.

Animals↗

Simultaneous induction of galectin-3 phosphorylated on tyrosine residue, p21(WAF1/Cip1/Sdi1), and the proliferating cell nuclear antigen at a distinctive period of repair of hepatocytes injured by CCl4.

The period of repair of hepatocytes injured by CCl4 and signaling proteins intrinsic to this period were examined. A 30 kDa polypeptide detected by immunoblot analysis using anti-phosphotyrosine antibody in livers from rats 48 to 72 h after administration of a single dose of CCl4 was identified as galectin-3 induced in cytoplasm of periportal hepatocytes and phosphorylated on tyrosine residue(s). Simultaneously, these hepatocytes induced p21(WAF1/Cip1/Sdi1) in the nucleus and the proliferating cell nuclear antigen in both the nucleus and the cytoplasm, suggesting that hepatocytes during this distinctive period are quiescent and repair cellular damage. Trabecular architecture of hepatocytes with the proliferating cell nuclear antigen only in the nucleus was found at 96 h. These findings indicate that galectin-3 is a novel member of signaling proteins downstream of tyrosine kinase, and suggest that it plays roles in supporting repair or survival of the injured hepatocytes rather than their proliferation that is likely to be initiated later than 72 h.

Animals↗

Results of three-year mass screening programme for lung cancer using mobile low-dose spiral computed tomography scanner.

The aim of this study was to evaluate the usefulness of annual screening for lung cancer by low-dose computed tomography (CT) and the characteristics of identified lung cancers. Subjects consisted of 5483 general population aged 40-74 years, who received initial CT scans in 1996, followed by repeat annual scans for most subjects in 1997 and 1998, with a total of 13 786 scans taken during 1996-1998. Work-up examinations for patients with suspicious lesions were conducted using diagnostic CTs. The initial screening in 1996 detected suspicious nodules in 279 (5.1%) of 5483 subjects, and 22 (8%) were confirmed surgically to have lung cancer. Corresponding figures in 1997 and 1998 screening studies were 173 (3.9%) of 4425 and 25 (14%) of 173, and 136 (3.5%) of 3878 and 9 (7%) of 136, respectively. The sensitivity and specificity of detecting surgically confirmed lung cancer were 55% (22/40) and 95% (4960/5199) in 1996 and 83% (25/30) and 97% (4113/4252) in 1997 screening, respectively. 88% (55/60) of lung cancers identified on screening and surgically confirmed were AJCC stage IA. Our trial allowed detection of nearly 11 times the expected annual number of early lung cancers. Repeat CT allowed the detection of more aggressive, rapidly growing lung cancers, compared to those in the initial screening.

Adult↗

Impaired regeneration of the peripheral B cell repertoire from bone marrow following lymphopenia in old mice.

Aging is associated with a decreased production of B cells by the bone marrow and an increased life-span of peripheral B cells. To determine whether the decreased bone marrow B cell production is linked to the increased life-span of B cells in old mice, B cell regeneration following lymphopenia was studied in young and old mice. The rate of bone marrow pre-B cell and of splenic B cell regeneration is slower in irradiated, old compared to irradiated, young recipients of young, congeneic bone marrow. This finding reflects an age-associated defect in the bone marrow microenvironment. As the bone marrow is the only source of a diverse population of B cells, we measured the diversity of the splenic B cell repertoire regenerated following drug-induced lymphopenia in old and young mice. The heterogeneity of mRNA size from IgH complementarity determining region 3 (CDR3) was more restricted in splenic B cells from old compared to young mice providing additional evidence for an age-associated impairment in B cell production by the bone marrow.

Aging↗

Determination of trimebutine maleate in rat plasma and tissues by using capillary zone electrophoresis.

A simple and rapid capillary zone electrophoresis method was developed for the determination of trimebutine maleate in rat plasma and tissues. Rat plasma and tissue homogenates were mixed with acetonitrile containing internal standard, ephedrine hydrochloride, and then centrifuged. The supernatant was dried under a stream of nitrogen, and the residue was reconstituted in methanol-water (1:1). The electrophoresis was performed in uncoated capillary with 30 mmol/L phosphate buffer of pH 6.0 as the separation electrolyte. The applied voltage was 10 kV and the UV detection was set at 214 nm. The peak height ratio vs concentration in plasma or homogenates was linear over the range of 5-500 ng/mL and the limit of quantitation was 5 ng/mL. The intra- and inter-day precision was RSD < 14% and <15%. The accuracy was relative error (RE) within +/- 14%. This method was applied to studying the pharmacokinetics and tissue distribution after a single dose of trimebutine maleate was administrated to the rats. The T(max), AUC, C(max) and t(1/2) were 30 min, 7.8 x 10(2) (ng/mL) min, 39 ng/mL and 1.7 x 10(2) min. The drug distribution was found in a decreasing order of liver, kidney, spleen, lung and heart.

Animals↗

Development of normal and injury-induced gene expression of aFGF, bFGF, CNTF, BDNF, GFAP and IGF-I in the rat retina.

Focal mechanical injury to the retina substantially increases basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF) mRNA expression, accompanied by a transient increase in FGFR-1 mRNA, and this response is thought to protect photoreceptors near the injury site from inherited and light-induced retinal degenerations. We have now examined retinal gene expression of the principal survival factors involved in the response to injury in normal rats as a function of postnatal age both in normal and injured retinas. Sprague-Dawley rats were injured in one eye by needle incision through the retina at postnatal day (P) 10, 22, 35, 60, 90, 120 and 180. The other eye was uninjured and served as the control. Retinas were taken 1 day post-injury. Northern blot analysis was performed to determine the mRNA expression of the following factors and receptors: bFGF and acidic fibroblast growth factors (aFGF) and FGF receptor-1 (FGFR-1); CNTF and CNTF receptor alpha (CNTFR-alpha); brain-derived neurotrophic factor (BDNF) and its receptor trk B; and insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR); glial fibrillary acidic protein (GFAP) and opsin. In the uninjured control eyes, mRNA expression of most of the factors increased with postnatal age, with little expression at P10 and maximal expression levels reached at P22 (opsin), P35 (aFGF), P60 (BDNF) or P90 (bFGF, FGFR-1, CNTF and GFAP). In contrast, IGF-1 mRNA rapidly decreased from a high level of expression at P10 to about 55% of that level by P22, reaching a stable 45-50% of the P10 level at P35 and thereafter. The response to injury of bFGF, FGFR-1, CNTF and GFAP mRNAs increased with postnatal age. Unexpectedly, only minimal increases in bFGF, FGFR-1, CNTF and GFAP over those seen in the control eyes were observed before P35. Thereafter, the increase of bFGF mRNA after injury reached a maximum of three-fold at P60, maintained this level to P120, and slightly decreased to 2.5-fold by P180. Expression of FGFR-1 mRNA showed a maximum increase of 2.6-fold at P90. Expression of CNTF and GFAP mRNAs followed a time course similar to that of bFGF. Mechanical injury did not alter the mRNA levels of aFGF, BDNF, IGF-I, and receptors, CNTFR-alpha, trk B and IGF-IR. These data show that the response to injury is minimal at early postnatal ages but increases with age and peaks at P60-90 for most potential survival factors.

Analysis of Variance↗

Protection of photoreceptor cells in adult rats from light-induced degeneration by adaptation to bright cyclic light.

Light history has been shown to affect the susceptibility of the albino rat retina to the damaging effects of constant light exposure. Retinas of animals raised in relatively bright cyclic light are protected against light-induced degeneration compared with dim-reared animals. These effects were observed in animals raised from birth in bright cyclic light and are part of an adaptive response that protects photoreceptors from stress-induced degeneration. To determine if retinas of adult animals are capable of such adaptive changes or flexibility by switching between different light environments which do not pathologically damage photoreceptor cells, albino rats were maintained in less than 250 lux cyclic light for more than 3 weeks. At 12-13 weeks of age, they were placed into 800 lux cyclic light for 1 week, after which they were exposed to constant illumination of 1500-lux for 1, 3 or 7 days. Retinal function was evaluated by electroretinography and photoreceptor cell death was quantified by measuring outer nuclear layer thickness. After 1 week in bright cyclic light, the retinas were completely protected against 1 day constant light exposure that significantly damaged retinas of animals without 800 lux cyclic light adaptation. Significant protection was also observed in 3 day constant light exposed animals; limited protection occurred after 7 days exposure. These results indicate that the retinas of adult rats adapted to bright cyclic light within certain ranges that did not significantly damage photoreceptor cells are protected from constant light challenge. This phenomenon is a post-developmental response that demonstrates a remarkable plasticity of the retina. The mechanism(s) underlying the ability of this adaptation/flexibility in protecting photoreceptors could involve endogenous molecules that encompass many aspects of retinal cell and molecular biology and physiology. Identification of these molecules may provide insight into the development of therapeutic approaches to treat retinal degeneration.

Adaptation, Ocular↗

Activation of connexin-43 hemichannels can elevate [Ca(2+)]i and [Na(+)]i in rabbit ventricular myocytes during metabolic inhibition.

ATP depletion due to ischemia or metabolic inhibition (MI) causes Na(+) and Ca(2+) accumulation in myocytes, which may be in part due to opening of connexin-43 hemichannels. Halothane (H) has been shown to reduce conductance of connexin-43 hemichannels and to protect the heart against ischemic injury. We therefore investigated the effect of halothane on [Ca(2+)]i and [Na(+)]i in myocytes during MI. Isolated rabbit left ventricular myocytes were loaded with 4 microM fluo-3 AM for 30 min, or with 5 microM sodium green AM for 60 min at 37 degrees C. After washing, the myocytes were exposed to: (1) Normal HEPES solution; (2) MI solution (2 mM NaCN, 20 mM 2-deoxy-D-glucose and 0-glucose); or (3) MI+H (0.95 mM, 4.7 mM) for 60 min. Propidium iodide (PI, 25 microM) was added to all samples before data acquisition. The fluorescence intensity was measured by flow cytometry with 488 nm excitation and 530 nm emission for fluo-3 or sodium green, and 670 nm for PI. The [Ca(2+)]i and [Na(+)]i were then calculated by calibration. In some experiments, the effect of 10 microM tetrodotoxin (TTX) and 20 microM nifedipine (NIF) were studied. Metabolic inhibition for 60 min caused a significant increase in [Ca(2+)]i and [Na(+)]i in myocytes when compared to controls, which was significantly reduced by halothane in a dose-dependent fashion. In the presence of TTX and NIF, halothane also significantly reduced the rise in the [Ca(2+)]i and [Na(+)]i in myocytes subjected to MI. 1-heptanol, another gap junction blocker, had similar effects. Thus, halothane reduced [Ca(2+)]i and [Na(+)]i overload produced by MI in myocytes. This effect is not solely due to block of voltage-gated Na(+) and Ca(2+) channels, and is likely mediated by inhibiting the opening of connexin-43 hemichannels.

Anesthetics, Inhalation↗

Atypical adenomatous hyperplasia of the lung: correlation between high-resolution CT findings and histopathologic features.

We describe herein the CT features of atypical adenomatous hyperplasia (AAH) of the lung and its histopathological characteristics. Among 17,919 individuals screened for lung cancer by CT scanning, ten AAH nodules were detected in nine asymptomatic subjects. On high-resolution CT, the lesions measured from 6 x 6 mm to 15 x 17 mm and their CT number ranged from -500 to -760 HU. The AAHs appeared as round nodules with smooth and distinct borders and showed a ground-glass opacity. Plain chest radiographs failed to identify all lesions. Histopathologically, AAH lesions showed atypical epithelial cell proliferation along slightly thickened alveolar septa. Whereas it is often easy to differentiate these nodules from inflammatory and benign lung lesions, histopathological examination remains at present the only method to differentiate AAH from lung cancers.

Adenoma↗