Biomedical subjects

C Liu

Publications and source records attributed to C Liu.

At least 91 records · Page 5Linked to original sources

PubMed2002

Rescue of the osteopetrotic defect in op/op mice by osteoblast-specific targeting of soluble colony-stimulating factor-1.

Soluble colony-stimulating factor-1 (sCSF-1) and membrane bound CSF-1 are synthesized by osteoblasts and stromal cells. However, the precise role of each form in osteoclastogenesis is unclear. In the op/op mouse, absence of osteoblast-derived CSF-1 leads to decreased osteoclasts and osteopetrosis. To determine whether sCSF-1 gene replacement can cure the osteopetrotic defect, we took advantage of the osteoblast specificity of the osteocalcin promoter to selectively express sCSF-1 in the bone of op/op mice. Transgenic mice harboring the human sCSF-1 cDNA under the control of the osteocalcin promoter were generated and cross-bred with heterozygous op/wt mice to establish op/op mutants expressing the transgene (op/opT). The op/op genotype and transgene expression were confirmed by PCR and Southern blot analysis, respectively. High levels of human sCSF-1 protein were selectively expressed in bone. At 2(1/2) wk, op/opT mice showed normal growth and tooth eruption. Femurs removed at 5 and 14 wk were analyzed by peripheral quantitative computed tomography and histomorphometry. The abnormal bone mineral density, cancellous bone volume, and growth plate width observed in op/op mice was completely reversed in op/opT mice by 5 wk, and this effect persisted at 14 wk, with measurements comparable with wt/wt mice at each time point. Correction of the skeletal abnormalities in the 5-wk-old op/opT mice correlated with a marked increase in the total osteoclast number, and their number per millimeter of bone surface compared with that of op/op mutants. Osteoclast number was maintained at 14 wk in op/opT mice and morphologically resembled wt/wt osteoclasts. These results indicate that sCSF-1 is sufficient to drive normal osteoclast development and that the osteocalcin promoter provides an efficient tool for delivery of exogenous genes to the bone. Moreover, targeting sCSF-1 to osteoblasts in the bone microenvironment may be a potentially useful therapeutic modality for treating bone disorders.

Acid Phosphatase↗

PubMed2001

[Effects of touch on growth and mentality development in normal infants].

OBJECTIVE: To determine the effects of conducting Touch to infants upon their growth and mental development, sleeping and disease conditions, as well as the difference of effects of conducting Touch among infants of different month age. METHODS: 310 normal full-term infants aged 0-6 months were divided randomly into Touch group (n = 208) and control group (n = 102). Parents of Touch group were asked to conduct Touch to their infants 2-3 times/day, lasting 15-20 minutes every time, for at least 3 months. Intelligence tests were performed to infants of both groups at the beginning of the experiment and 6 months later (CDCC measurement table was employed). Data such as height, weight, circumferences of head and chest, sleeping, feeding and disease conditions etc. were recorded each month in a successive period of 6 months. Statistical analysis was conducted using SPSS 10.0. RESULTS: (1) The average score of mental development (MDI) was 7.4 higher, with a statistically significant difference, among the infants who began to receive touch within 3 months after birth than those infants with the same age in control group. The average score of psychomotor development index (PDI) was 5.8 higher, with a statistically significant difference, among the infants who began to receive touch within 3 months after birth than those infants with the same age in control group. Infants who began to receive touch within 3 months after birth slept remarkably better than those in control group did. No significant difference was found in scores of MDI and PDI and sleeping condition between infants who began to receive touch 3 months after birth and the infants with the same age in the control group. (2) Weight gain and growth in chest circumference in infants receiving touch within one month after birth were significantly better compared with the infants of the same age in the control group. There was no significant difference in values of height and head circumference between the two groups. There was no significant difference in values of height and head circumference between the two groups. (3) No significant difference in the incidence rates of acute respiratory infection and diarrhea disease was found between the touch group and control group. CONCLUSION: (1) Growth and mental development of infants can be improved by touch. Tthe earlier to conduct touch the better the effects. (2) Touch helps improve sleeping condition in infants.

Body Height↗

PubMed2001

DNA mediated immunization with encoding the nucleoprotein gene of porcine transmissible gastroenteritis virus.

The immune response to a naked plasmid DNA encoding the nucleoprotein (N protein) of porcine transmissible gastroenteritis virus (TGEV) was investigated in this study. A complementary DNA of the entire N gene was amplified by RT-PCR, and inserted into a mammalian expression vector (pcDNA3.1) to construct a recombinant plasmid (pcDNA/N). To evaluate the immunogenicity of the construct, BALB/c mice were intramuscularly immunized with different doses (50, 100 and 200 microg/mouse) of pcDNA/N twice at a 5-week interval. An optimal antibody response was achieved with 100 microg of pcDNA/N. The response lasted at least 11 weeks after primary immunization. By western blotting analysis, the antibodies specifically recognized a 47 kDa protein corresponding to the viral N protein, but they did not reveal neutralizing activity against infectious TGEV in vitro. Immunoglobulin G2a was predominant among these antibodies, which was indicative of Th1 type cell activation in pcDNA/N immunized mice. Moreover, spleen cells from these mice showed stronger immune responses than those from live vaccine or parental vector immunized mice. These results suggest that the construct can elicit both humoral and cell-mediated immune (CMI) responses against TGEV N protein in mice.

Animals↗

PubMed2001

Interleukin-18 regulates acute graft-versus-host disease by enhancing Fas-mediated donor T cell apoptosis.

Interleukin (IL)-18 is a recently discovered cytokine that modulates both T helper type 1 (Th1) and Th2 responses. IL-18 is elevated during acute graft-versus-host disease (GVHD). We investigated the role of IL-18 in this disorder using a well characterized murine bone marrow transplantation (BMT) model (B6 --> B6D2F1). Surprisingly, blockade of IL-18 accelerated acute GVHD-related mortality. In contrast, administration of IL-18 reduced serum tumor necrosis factor (TNF)-alpha and lipopolysaccharide (LPS) levels, decreased intestinal histopathology, and resulted in significantly improved survival (75 vs. 15%, P < 0.001). Administration of IL-18 attenuated early donor T cell expansion and was associated with increased Fas expression and greater apoptosis of donor T cells. The administration of IL-18 no longer protected BMT recipients from GVHD when Fas deficient (lpr) mice were used as donors. IL-18 also lost its ability to protect against acute GVHD when interferon (IFN)-gamma knockout mice were used as donors. Together, these results demonstrate that IL-18 regulates acute GVHD by inducing enhanced Fas-mediated apoptosis of donor T cells early after BMT, and donor IFN-gamma is critical for this protective effect.

Acute Disease↗

PubMed2001

Evaluation of environmental effects on metal transport from capped contaminated sediment under conditions of submarine groundwater discharge.

Previous studies conducted in our laboratories have shown that submarine groundwater discharge (SGD) can significantly increase metal fluxes from capped contaminated sediment to the overlying water. Five columns were set up in the laboratory to evaluate the effects of environmental factors such as groundwater pH, sediment depth, and groundwater flow rate on metal transport from capped contaminated sediment under conditions of SGD. Acidified groundwater discharge was shown to enhance the mobility of all tested metals except Mo. Although much of the released metal was adsorbed by the capping material, significant increases of initial or steady-state fluxes to the overlying water were observed for Ni, Cu, Zn, Cd, Pb, and Mn. Additional sediment depth enhanced steady-state fluxes for all tested metals except Mo, Cd, and Pb. Increased SGD rates did not significantly change the average metal concentration in the outflow to the overlying water for most metals; however, all metal releases were higher due to the greater flow at increased SGD rates. The residence time and the redox conditions may be important in evaluating environmental effects on capping efficiency.

Adsorption↗

PubMed2001

Human endomucin is an endothelial marker.

The identification of novel endothelial markers is important in the study of angiogenesis, and may have potential uses in cancer diagnosis and treatment. We have isolated potential markers of tumor angiogenesis by screening human umbilical vein endothelial cells (HUVECs) treated with tumor conditioned media. Using suppression subtractive hybridization (SSH), we found endomucin, a potential cell surface marker upregulated in this system. Human endomucin is predicted to encode a 261-aa, 27.5-kDa protein with a transmembrane sequence and multiple glycosylation sites. Northern and in situ hybridization studies show that human endomucin expression is largely, if not uniquely, endothelial cell-specific. Human endomucin is present abundantly in highly vascular tissues such as heart, kidney, and lung. It is seen in human aortic endothelial cells (HAECs) as well as in human microvascular endothelial cells (HMVECs). Furthermore, its expression is increased when endothelial cells are proliferating or are stimulated by tumor-conditioned media or specific angiogenic factors such as bFGF (basic fibroblast growth factor) and TNFalpha (tumor necrosis factor), suggesting that endomucin may have a role in tumor angiogenesis.

Amino Acid Sequence↗

PubMed2001

Myr 8, a novel unconventional myosin expressed during brain development associates with the protein phosphatase catalytic subunits 1alpha and 1gamma1.

Directed neuronal, astroglial, and oligodendroglial cell migrations comprise a prominent feature of mammalian brain development. Because molecular motor proteins have been implicated in a wide spectrum of processes associated with cell motility, we initiated studies to define the pool of myosins in migrating cerebellar granule neurons and type-1 neocortical astrocytes. Our analyses identified two isoforms of a novel unconventional myosin, which we have cloned, sequenced, and designated myr 8a and 8b (eighth unconventional myosin from rat). Phylogenetic analysis indicates that myr 8 myosins comprise a new class of myosins, which we have designated class XVI. The head domain contains a large N-terminal extension composed of multiple ankyrin repeats, which are implicated in mediating an association with the protein phosphatase 1 (PP1) catalytic subunits 1alpha and 1gamma. The motor domain is followed by a single putative light-chain binding domain. The tail domain of myr 8a is comparatively short with a net positive charge, whereas the tail domain of myr 8b is extended, bears an overall neutral charge, and reveals several stretches of poly-proline residues. Neither the myr 8a nor the myr 8b sequence reveals alpha-helical coiled-coil motifs, suggesting that these myosins exist as monomers. Both immunoblot and Northern blot analyses indicate that myr 8b is the predominant isoform expressed in brain, principally at developmental time periods. The structural features and restricted expression patterns suggest that members of this novel class of unconventional myosins comprise a mechanism to target selectively the protein phosphatase 1 catalytic subunits 1alpha and/or 1gamma in developing brain.

Animals↗

PubMed2001

Synthesis and biological activity of D- and L-chiro-inositol 2,3,4,5-tetrakisphosphate: design of a novel and potent inhibitor of Ins(3,4,5,6)P4 1-kinase/Ins(1,3,4)P3 5/6-kinase.

The synthesis of a novel and potent Ins(3,4,5,6)P4 1-kinase/Ins(1,3,4)P3 5/6 kinase inhibitor and its enantiomer is described. D-chiro-Inositol 2,3,4,5-tetrakisphosphate [D-chiro-Ins(2,3,4,5)P4, 3, Figure 1] and L-chiro-inositol 2,3,4,5-tetrakisphosphate [L-chiro-Ins(2,3,4,5)P4, ent-3] were synthesized from D-1,6-di-O-benzyl-chiro-inositol and L-1,6-di-O-benzyl-chiro-inositol, respectively. We examined inhibition of the multifunctional Ins(3,4,5,6)P4 1-kinase/Ins(1,3,4)P3 5/6-kinase from bovine aorta by 3 and ent-3. Compound 3 was a potent inhibitor with an IC(50) of 1.5 microM, and ent-3 was more than 20-fold less active. The results are compared to those for other inhibitory inositol polyphosphates with structure-activity relationship discussion. Compound 3 is a useful lead for development of further inhibitors of this important enzyme, and ent-3 should find applications in the newly emerging Ins(1,4,5,6)P4 signaling pathway.

Animals↗

PubMed2001

Identification and characterization of hic-5/ARA55 as an hsp27 binding protein.

hsp27 has been reported to participate in a wide variety of activities, including resistance to thermal and metabolic stress, regulation of growth and differentiation, and acting as a molecular chaperone or a regulator of actin polymerization. We hypothesized that these diverse functions are regulated in a cell- or tissue-specific manner via interaction with various binding proteins. To investigate this hypothesis, we used hsp27 as a "bait" to screen a yeast two-hybrid cDNA library from rat kidney glomeruli and identified a novel hsp27 binding protein, hic-5 (also known as ARA55), a focal adhesion protein and steroid receptor co-activator. Biochemical interaction between hsp27 and hic-5 was confirmed by co-immunoprecipitation, and critical protein.protein interaction regions were mapped to the hic-5 LIM domains and the hsp27 C-terminal domain. Initial analysis of the functional role of hsp27.hic-5 interaction revealed that hic-5 significantly inhibited the protection against heat-induced cell death conferred by hsp27 overexpression in co-transfected 293T cells. In contrast, when a non-hsp27-interacting hic-5 truncation mutant (hic-5/DeltaLIM4) was co-expressed with hsp27, the hic-5 inhibition of hsp27 protection was absent. We conclude that hic-5 is a true hsp27 binding protein and inhibits the ability of hsp27 to provide protection against heat shock in an interaction-dependent manner.

Amino Acid Sequence↗

PubMed2001

Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules.

The innate immune system recognizes microorganisms through a series of pattern recognition receptors that are highly conserved in evolution. Insects have a family of 12 peptidoglycan recognition proteins (PGRPs) that recognize peptidoglycan, a ubiquitous component of bacterial cell walls. We report cloning of three novel human PGRPs (PGRP-L, PGRP-Ialpha, and PGRP-Ibeta) that together with the previously cloned PGRP-S, define a new family of human pattern recognition molecules. PGRP-L, PGRP-Ialpha, and PGRP-Ibeta have 576, 341, and 373 amino acids coded by five, seven, and eight exons on chromosomes 19 and 1, and they all have two predicted transmembrane domains. All mammalian and insect PGRPs have at least three highly conserved C-terminal PGRP domains located either in the extracellular or in the cytoplasmic (or in both) portions of the molecules. PGRP-L is expressed in liver, PGRP-Ialpha and PGRP-Ibeta in esophagus (and to a lesser extent in tonsils and thymus), and PGRP-S in bone marrow (and to a lesser extent in neutrophils and fetal liver). All four human PGRPs bind peptidoglycan and Gram-positive bacteria. Thus, these PGRPs may play a role in recognition of bacteria in these organs.

Amino Acid Sequence↗

PubMed2001

Suppression of platelet-type 12-lipoxygenase activity in human erythroleukemia cells by an RNA-cleaving DNAzyme.

Human platelet-type 12-lipoxygenase (12-LOX) and its metabolites play a crucial role in tumor angiogenesis. A "10-23" deoxyribozyme (DNAzyme) and its phosphorothioate-modified version were designed and synthesized against the 12-LOX mRNA. Both DNAzymes were able to cleave their substrate efficiently in a time- and concentration-dependent manner in vitro. Under a multiple turnover condition, both performed well at 37 degrees C, showing the k(cat) of 1 and 0.26 min(-1), respectively. The phosphorothioate modification of the DNAzyme significantly increased its stability in cells without a substantial loss of kinetic efficiency in vitro. In a cell culture system, transfection of the DNAzymes into HEL cells resulted in a significant down-regulation of the 12-LOX mRNA. Furthermore, the cell extracts from the DNAzyme-transfected cells exhibited a marked reduction in the 12-LOX enzyme activity. The present results indicated the potential use of DNAzyme technology for gene function study and cancer therapy.

Arachidonate 12-Lipoxygenase↗

PubMed2001

Kinetic analysis of the bacterial reduction of goethite.

The kinetics of dissimilatory reduction of goethite (alpha-FeOOH) was studied in batch cultures of a groundwater bacterium, Shewanella putrefaciens, strain CN32 in pH 7 bicarbonate buffer. The rate and extent of goethite reduction were measured as a function of electron acceptor (goethite) and donor (lactate) concentrations. Increasing goethite concentrations increased both the rate and extent of Fe(III) reduction when cell and lactate concentrations were held constant. However, constant initial reduction rates were observed after normalization to the Fe(II) sorption capacity of FeOOH, suggesting that the bacterial reduction rate was first orderwith respect to surface site concentration. Increasing the lactate concentration also increased the rate and extent of FeOOH reduction. Monod-type kinetic behaviorwas observed with respectto lactate concentration. Fe(II) sorption on FeOOH was well-described by the Langmuir sorption isotherm. However, the Fe(II) sorption capacities hyperbolically decreased with increasing FeOOH concentration (10-100 mM) implying aggregation, while the affinity constant between Fe(II) and goethite was constant (log K approximately equals 3). Evaluation of the end states of the variable FeOOH and lactate experiments when iron reduction ceased indicated a consistent excess in reaction free energy of -22.7 kJ/mol. This value was remarkably close to the minimum value reported for bacteria to mediate a given reaction (-20 kJ/mol). X-ray diffraction (XRD) and scanning electron microscopy (SEM) indicated that siderite (FeCO3) was the only biogenic Fe(II) solid formed upon FeOOH bioreduction. A kinetic biogeochemical model that incorporated Monod kinetics with respect to lactate concentration, first-order kinetics with respectto goethite surface concentration, a Gibbs free energy availability factor, the rates of Fe(II) sorption on goethite and siderite precipitation, and aqueous speciation reactions was applied to the experimental data. Using independently estimated parameters, the developed model successfully described bacterial goethite reduction with variable FeOOH and lactate concentrations.

Hydrogen-Ion Concentration↗

PubMed2001

Allelic structure and distribution of two STR loci, D8S580 and D22S442, in the Japanese population.

The allelic frequency and structural characteristics of two STR loci D8S580 and D22S442 were investigated using blood samples from 143 unrelated healthy Japanese individuals. Thirty-eight alleles in D8S580 locus and 13 alleles in D22S442 locus were identified. The discrimination power, heterozygosity, and the polymorphic information content of those loci displayed high values (0.98, 0.88, and 0.87 in D8S580 and 0.97, 0.86 and 0.85 in D22S442), and their frequency distributions met Hardy-Weinberg equilibrium expectations. The allelic pattern of D8S580 was complex and differentiated into three groups (group I: alleles 184-194bp; group II: alleles 203-223, 235, 239, 243, 252 and 255bp; group III: alleles 227-286bp). Most of their alleles contained five categories of repeat units (A: aaaag; B: aaag; C: aagg; D: caag; E: agaa). On the other hand, D22S442 contained only two types of repeat units (A: agga; B: aggg). The present study, hence, proves that both D8S580 and D22S442 are highly polymorphic and represent stable genetic markers applicable to forensic investigations.

Alleles↗

PubMed2001

Capping efficiency for metal-contaminated marine sediment under conditions of submarine groundwater discharge.

Theoretical estimations and laboratory studies suggest that capping can effectively retard contaminant transport from sediments under undisturbed conditions. However, contaminated near-shore areas, commonly selected as capping sites, are frequently subjected to submarine groundwater discharge (SGD). Column experiments were set up in the laboratory to simulate metal transport through sediment and capping material in the presence and absence of SGD. In the absence of SGD, capping enhanced Mo flux and initial Mn flux while having no effect in retarding Fe flux, presumably due to altered redox conditions. This effect was more pronounced in the presence of SGD (4.7 x 10(-4) m/h specific discharge). Capping enhanced Cd flux and initial fluxes of Ni, Cu, and Zn under conditions of simulated SGD, which may be caused by co-transport with Mn and Fe and oxidation of sulfide. Capping retarded Cr and Pb fluxes and steady-state Ni, Cu, Zn, and Fe fluxes in the presence of simulated SGD. However, capping efficiency decreased relative to that with no SGD. Elevated Mn concentration was detected at the capping surface with simulated SGD. Results indicate that advective flow may lead to significantly higher metal fluxes than those under undisturbed conditions.

Geologic Sediments↗

PubMed2001

Sol-gel synthesis of free-standing ferroelectric lead zirconate titanate nanoparticles.

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Journal Article↗

PubMed2001

Fine mapping supports previous linkage evidence for a bipolar disorder susceptibility locus on 13q32.

A region between D13S71 and D13S274 on 13q32 showed linkage to bipolar disorder (BP) based on a genome scan using markers with an average spacing of approximately 6 cM and an average heterozygosity of approximately 60% [Detera-Wadleigh et al., 1999: Proc Natl Acad Sci USA 96:5604-5609]. In an attempt to confirm this finding and achieve fine mapping of the susceptibility region, nine additional microsatellite markers with average heterozygosity of approximately 86%, located between D13S71 and D13S274, were typed in the same sample. The strongest linkage evidence was detected by multipoint linkage analysis (ASPEX program) around D13S779-D13S225 with maximum LOD score of 3.25 under Affection Status Model II (ASM II; P = 0.0000546). Data from additional nine markers resulted in a decrease of the 95% confidence interval of the linkage region. Association analyses with GASSOC TDT and ASPEX/sib_tdt detect potential linkage disequilibrium with several markers, including D13S280 (ASPEX TDT P = 0.0033, ASM I). These data generated using a higher marker density within the proposed susceptibility region strengthen the validity of our previous findings and suggest a finer localization of the susceptibility gene(s) on 13q32.

Bipolar Disorder↗

PubMed2001

Structural and immunological studies of a major polysaccharide from spores of Ganoderma lucidum (Fr.) Karst.

A polysaccharide isolated from spores of the fungus, Ganoderma lucidum, was found to be a complex glucan. On the basis of compositional and methylation analyses, periodate oxidation, Smith degradation, 1D and 2D NMR, and ESIMS experiments of the native polysaccharide and its degraded products, the polysaccharide was shown to have a backbone of beta-(1-->3)-linked D-glucopyranosyl residues, with branches of mono-, di- and oligosaccharide side chains substituting at the C-6 of the glucosyl residues in the main chain. Conformational analysis in aqueous solution and immunological activities of the native and degraded glucans were also investigated. The results suggested that the degree of substitution on the main chain and the length of side chains may be very important factors in determining the conformation and the biological activities of beta-(1-->3)-linked glucans.

Animals↗

PubMed2001

Fluorescence characterization of the transcription bubble in elongation complexes of T7 RNA polymerase.

The various kinetic and thermodynamic models for transcription elongation all require an understanding of the nature of the melted bubble which moves with the RNA polymerase active site. Is the general nature of the bubble system-dependent or are there common energetic requirements which constrain a bubble in any RNA polymerases? T7 RNA polymerase is one of the simplest RNA polymerases and is the system for which we have the highest-resolution structural information. However, there is no high-resolution information available for a stable elongation complex. In order to directly map melted regions of the DNA in a functionally paused elongation complex, we have introduced fluorescent probes site-specifically into the DNA. Like 2-aminopurine, which substitutes for adenine bases, the fluorescence intensity of the new probe, pyrrolo-dC, which substitutes for cytosine bases, is sensitive to its environment. Specifically, the fluorescence is quenched in duplex DNA relative to its fluorescence in single-stranded DNA, such that the probe provides direct information on local melting of the DNA. Placement of this new probe at specific positions in the non-template strand shows clearly that the elongation bubble extends about eight bases upstream of the pause site, while 2-aminopurine probes show that the elongation bubble extends only about one nucleotide downstream of the last base incorporated. The positioning of the active site very close to the downstream edge of the bubble is consistent with previous studies and with similar studies of the promoter-bound, pre-initiation complex. The results show clearly that the RNA:DNA hybrid can be no more than eight nucleotides in length, and characterization of different paused species suggests preliminarily that these dimensions are not sequence or position dependent. Finally, the results confirm that the ternary complex is not stable with short lengths of transcript, but persists for a substantial time when paused in the middle or at the (runoff) end of duplex DNA.

2-Aminopurine↗