Coordination polymers: structural transformation from two to three dimensions through ligand conformation change.
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Journal Article↗
Biomedical subjects
L Gao
Publications and source records attributed to L Gao.
Selective elimination of leukemic CD34(+) progenitor cells by cytotoxic T lymphocytes specific for WT1.
Hematologic malignancies such as acute and chronic myeloid leukemia are characterized by the malignant transformation of immature CD34(+) progenitor cells. Transformation is associated with elevated expression of the Wilm's tumor gene encoded transcription factor (WT1). Here we demonstrate that WT1 can serve as a target for cytotoxic T lymphocytes (CTL) with exquisite specificity for leukemic progenitor cells. HLA-A0201- restricted CTL specific for WT1 kill leukemia cell lines and inhibit colony formation by transformed CD34(+) progenitor cells isolated from patients with chronic myeloid leukemia (CML), whereas colony formation by normal CD34(+) progenitor cells is unaffected. Thus, the tissue-specific transcription factor WT1 is an ideal target for CTL-mediated purging of leukemic progenitor cells in vitro and for antigen-specific therapy of leukemia and other WT1-expressing malignancies in vivo.
Adult↗
Blocking of CD44-hyaluronic acid interaction prolongs rat allograft survival.
BACKGROUND: Lymphocyte activation and infiltration into a transplanted organ is an integral component of the rejection process. Graft infiltration of lymphocytes requires adhesion of leukocytes to the endothelium, diapedesis, and transmigration. One of several proteins involved in this process is CD44, which is known to interact with endothelial hyaluronan (HA). Blockade of cell-matrix and cell-cell interactions have been used extensively for modulation of immune responses and graft rejection. Based on these observations, we evaluated the effects of blocking CD44-HA interactions in a transplantation model. METHODS: We used a low molecular weight hyaluronic acid formulation (LMWHA) for the treatment of rat renal and cardiac allograft recipients. LMWHA was administered intraperitoneally at 0.5-5 mg/kg for 5-10 days after transplantation with or without a subtherapeutic dose of cyclosporine. RESULTS: LMWHA monotherapy prolonged allograft survival significantly, but only for a few days. In combination with low-dose cyclosporine, long-term survival of allografts was observed in some of recipients. CONCLUSION: Further definition of the underlying mechanism of LMWHA therapy may provide a rationale for the development of novel, nontoxic, nonimmunogenic immunotherapies.
Animals↗
Structure and characterization of the murine p80 coilin gene, Coil.
Cajal bodies (coiled bodies, CBs) are nuclear organelles of unknown function and are characterized by a wide variety of components including various basal transcription and cell cycle proteins, the nucleolar proteins fibrillarin and Nopp140, numerous small nuclear ribonucleoproteins, the survival motor neuron protein complex, and the marker protein, p80 coilin. To gain insight into the role of p80 coilin in CBs, we have cloned the murine gene Coil and have mapped it to the distal portion of chromosome band 11D. The approximately 2.6-kb transcript is detectable in all tissues analyzed, with the highest levels in brain and testis. Sequence analysis shows that, like its human counterpart, the mouse coilin gene is composed of seven exons and spans nearly 30 kb of genomic DNA. The predicted amino acid sequence reveals two conserved N- and C-terminal domains, and comparison with the Xenopus SPH-1 protein reveals that these three genes are indeed orthologous. These results should facilitate gene disruption experiments aimed at creating a genetic model system to study CBs.
Amino Acid Sequence↗
Uptake of metabolites by gonococci grown with lactate in a medium containing glucose: evidence for a surface location of the sialyltransferase.
Promotion of uptake of essential metabolites is a possible reason for the general stimulation of gonococcal metabolism which is caused by lactate (1 mM) in a defined medium containing glucose (5 mM). However, although uptake of(14)C adenine by gonococci [strain BS4(agar)] held for 4 or 7 min at 37 degrees C in Hanks balanced salt solution was increased for lactate treated gonococci compared with control organisms, uptake of(14)C glucose and(14)C proline under these conditions was unaffected. Hence, there is no evidence that lactate produces general stimulation of metabolite uptake. Unlike the other metabolites, cytidine 5'-monophospho-(14)CN-acetyl neuraminic acid (CMP-(14)CNANA), the substrate for sialylation of gonococcal lipopolysaccharide (LPS), was adsorbed in substantial quantities by gonococci held on ice for 6 min. Also, the increase in uptake of CMP-(14)CNANA at 37 degrees C over that adsorbed at 0 degrees C was much smaller (less than two-fold) than for the other compounds (4-30-fold). The substantial adsorption at 0 degrees C suggested a surface receptor for CMP-(14)CNANA. It is probably the sialyltransferase because a sialyltransferase deficient mutant, JB1, did not absorb CMP-(14)CNANA at 0 degrees C or take it up at 37 degrees C, in contrast to its parent strain, F62, which behaved similarly to strain BS4 (agar). This supports previous evidence for a surface location of the sialyltransferase. There was a small increase in adsorption of CMP-(14)CNANA in lactate treated gonococci indicating a slight increase in the surface enzyme. This could enhance LPS sialylation and hence affect pathogenicity.
Adenine↗
Evidence for a role of the lumenal M3-M4 loop in skeletal muscle Ca(2+) release channel (ryanodine receptor) activity and conductance.
We tested the hypothesis that part of the lumenal amino acid segment between the two most C-terminal membrane segments of the skeletal muscle ryanodine receptor (RyR1) is important for channel activity and conductance. Eleven mutants were generated and expressed in HEK293 cells focusing on amino acid residue I4897 homologous to the selectivity filter of K(+) channels and six other residues in the M3-M4 lumenal loop. Mutations of amino acids not absolutely conserved in RyRs and IP(3)Rs (D4903A and D4907A) showed cellular Ca(2+) release in response to caffeine, Ca(2+)-dependent [(3)H]ryanodine binding, and single-channel K(+) and Ca(2+) conductances not significantly different from wild-type RyR1. Mutants with an I4897 to A, L, or V or D4917 to A substitution showed a decreased single-channel conductance, loss of high-affinity [(3)H]ryanodine binding and regulation by Ca(2+), and an altered caffeine-induced Ca(2+) release in intact cells. Mutant channels with amino acid residue substitutions that are identical in the RyR and IP(3)R families (D4899A, D4899R, and R4913E) exhibited a decreased K(+) conductance and showed a loss of high-affinity [(3)H]ryanodine binding and loss of single-channel pharmacology but maintained their response to caffeine in a cellular assay. Two mutations (G4894A and D4899N) were able to maintain pharmacological regulation both in intact cells and in vitro but had lower single-channel K(+) and Ca(2+) conductances than the wild-type channel. The results support the hypothesis that amino acid residues in the lumenal loop region between the two most C-terminal membrane segments constitute a part of the ion-conducting pore of RyR1.
Amino Acid Sequence↗
Neuromuscular paralysis as a pharmacodynamic probe to assess organ function during liver transplantation.
Potential for assessing liver function during liver transplantation surgery by monitoring muscle paralysis from nondepolarizing neuromuscular blockers that are hepatically cleared is critically assessed. Rocuronium is strongly favored as a promising pharmacodynamic probe for predicting allograft liver function because it is predominantly eliminated via the liver and its putative metabolites are not active. Prolongation of recovery from rocuronium paralysis is closely correlated with allograft liver function postoperatively. Vecuronium, pancuronium, and perhaps pipecuronium may also prove to be useful probes, but the two former blockers have active metabolites. Further prospective studies are necessary with more precise measurement of neuromuscular function to confirm the predictive value of this method. Alterations in neuromuscular blocker plasma concentrations that are correlated with changes in liver function and either the dose required or the intensity or duration of paralysis needs to be demonstrated for this technique to be clinically useful.
Androstanols↗
Hijacking of apoptotic pathwaysby bacterial pathogens.
Increasing evidence indicates that apoptosis of the host cell may constitute a defense mechanism to confine the infection by bacterial pathogens. Certain pathogens have developed elegant mechanisms to modulate the fate of the host cell, which include induction or blockage of apoptosis. These studies will promote our understanding of the pathogenesis of infectious diseases and aid the development of means for therapeutic intervention.
Animals↗
In a medium containing glucose, lactate carbon is incorporated by gonococci predominantly into fatty acids and glucose carbon incorporation is increased: implications regarding lactate stimulation of metabolism.
The reason for stimulation by lactate of metabolism of gonococci growing in a medium containing glucose, which enhances pathogenicity by increasing growth rate, lipopolysaccharide (LPS) synthesis and protein formation, has been investigated. Tricine dodecylpolyacrylamide gel electrophoresis (SDS-PAGE) and thin layer chromatography (TLC) on homogenates of gonococci grown in this medium with [14C]lactate showed that lactate carbon was preferentially incorporated into lipid and LPS. Nuclear magnetic resonance (NMR) spectroscopy on lipid extracted from gonococci grown in the glucose containing medium with [13C]lactate showed that lactate carbon was incorporated into fatty acid moieties and not into ethanolamine or glycerol moieties. In contrast, NMR on lipid from gonococci grown with [13C]glucose indicated glucose carbon in both moieties. When unlabelled lactate was added, lipid synthesis from [l3C]glucose was stimulated and small amounts of different fatty acids were formed. The NMR data shows that gluconeogenesis from lactate carbon does not occur in the presence of glucose, suggesting that lactate is used solely for rapid production, via pyruvate, of acetyl CoA, the precursor not only for fatty acid synthesis but also for the constituents and products of the citric acid cycle, including ATP. The rapid formation of a high level of acetyl CoA is the probable reason for the stimulation of metabolism and oxygen uptake by lactate. 14C label on LPS was detected in its fatty acids. Most proteins that stained with silver in tricine SDS-PAGE were not significantly labelled by [14C]lactate in the glucose-containing medium. Two of three appreciably labelled proteins were identified by N-terminal sequencing as GroEL and porin 1B, and one of the two less labelled proteins was similar to peroxiredoxin type proteins. There were no signs of specific induction of these proteins by lactate and their labelling was consistent with fatty acids in attached lipid.
Bacterial Proteins↗
The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42.
PAR (partitioning-defective) proteins, which were first identified in the nematode Caenorhabditis elegans, are essential for asymmetric cell division and polarized growth, whereas Cdc42 mediates establishment of cell polarity. Here we describe an unexpected link between these two systems. We have identified a family of mammalian Par6 proteins that are similar to the C. elegans PDZ-domain protein PAR-6. Par6 forms a complex with Cdc42-GTP, with a human homologue of the multi-PDZ protein PAR-3 and with the regulatory domains of atypical protein kinase C (PKC) proteins. This assembly is implicated in the formation of normal tight junctions at epithelial cell-cell contacts. Thus, Par6 is a key adaptor that links Cdc42 and atypical PKCs to Par3.
Adaptor Proteins, Signal Transducing↗
Nitric oxide-dependent vasodilatation of rabbit femoral artery by beta(2)-adrenergic stimulation or cyclic AMP elevation in vivo.
Some studies suggest that beta-adrenoceptor-mediated vasorelaxation is in part mediated through nitric oxide (NO) release. We wished to determine the contribution of the L-arginine / NO system to vasodilatation in response to beta-adrenoceptor stimulation with isoprenaline or cyclic adenosine-3',5'-monophosphate (cyclic AMP) elevation with forskolin and dibutyryl cyclic AMP in vivo, using a rabbit femoral artery constant perfusion model. Baseline femoral artery pressure was similar in rabbits receiving isoprenaline, forskolin or dibutyryl cyclic AMP. Isoprenaline, forskolin and dibutyryl cyclic AMP each decreased femoral artery pressure in a dose-dependent manner. The doses (mol kg(-1)) of isoprenaline, forskolin and dibutyryl cyclic AMP which decreased pressure by 10% from baseline, expressed as a negative logarithm (-log ED(10)) were: 10.0+/-0.2, 9.5+/-0.1 and 4.9+/-0.1 respectively (P<0.0001 for each). Use of beta-adrenoceptor subtype-selective antagonists showed that the vascular response to isoprenaline was purely due to stimulation of the beta(2)-adrenoceptor subtype. Injection of 1 micromol kg(-1) N(G)-nitro-L-arginine methyl ester (L-NAME) did not alter baseline pressure. However, it abolished the pressure response to isoprenaline (P<0.0001), and significantly attenuated the pressure responses to forskolin and dibutyryl cyclic AMP: -log ED(10) values for forskolin and dibutyryl cyclic AMP, in the presence of L-NAME, were 7.9+/-0.1 and 3.5+/-0.3 respectively (P<0.0001 for each, as compared with values in the absence of L-NAME). These results indicate that beta(2)-adrenergic stimulation and cylic AMP elevation activate the L-arginine/NO system in rabbit femoral artery in vivo, and that NO generation contributes importantly to the changes in vascular tone induced by agents which modulate beta-adrenoceptors or cyclic AMP.
Adrenergic beta-2 Receptor Agonists↗
Post-earthquake quality of life and psychological well-being: longitudinal evaluation in a rural community sample in northern China.
This study aims to observe longitudinal change of quality of life (QOL) and psychological well-being in a community sample affected by an earthquake and to examine the relationship between QOL and disaster exposure, post-disaster support and other related variables. The subjects, from two villages at different distances from the epicenter, were assessed using the brief version of the World Health Organization Quality of Life Assessment (WHOQOL-BREF) and three subscales of a symptoms checklist at 3 months (n=335) and 9 months (n=253) after the earthquake, respectively. Exposure to the earthquake was associated with multidimensional impairment in QOL, including physical, psychological and environmental domains at 3 months, and psychological and environmental domains at 9 months. The victims also suffered significantly more psychological distress in terms of depression, somatization and anxiety. At both assessment points the group that experienced lower initial exposure but then received less post-disaster help reported poorer QOL and psychological well-being. The two victim groups also differed significantly in changing trend along time. The group that received more support showed a general improvement in post-disaster well-being from 3 months to 9 months. The results confirm that post-disaster variables could be as important to post-disaster psychosocial outcomes as variables of pre-disaster vulnerability and disaster per se. A comprehensive and prospective assessment of disaster effects is imperative for the better organization of disaster relief programs and psychosocial interventions.
Adolescent↗
Down-regulation of GD3 ganglioside and its O-acetylated derivative by stable transfection with antisense vector against GD3-synthase gene expression in hamster melanoma cells: effects on cellular growth, melanogenesis, and dendricity.
The expression of gangliosides in hamster melanoma cells is closely related to cellular growth and degree of differentiation, with slow-growing, highly differentiated melanotic melanoma cells expressing GM3 and fast-growing, undifferentiated amelanotic Ab melanoma cells having a preponderance of GD3 and O-acetyl-GD3. We recently showed that down-regulation of O-acetyl-GD3 expression in hamster melanoma cells by introducing the influenza C virus O-acetylesterase cDNA into the cells resulted in induction of dendricity, with a concomitant increased expression of GD3. To examine the effect of the increased GD3 expression in the plasma membrane on the dendricity of the AbC-1 cells, we first established the cDNA coding for hamster GD3-synthase. We then targeted the sialyltransferase gene expression by the antisense knockdown experiment, and the results showed that inhibition of the expression of gangliosides GD3 and O-acetyl-GD3 induced dendricity in the hamster melanoma AbC-1 cell line. These GD3- and O-acetyl-GD3-depleted cells also demonstrated a decreased rate of cell growth, but their melanogenic potential was not affected. These results rule out the possibility that GD3 may serve as an active molecule for dendrite outgrowth in this cell line and suggest that the enhanced expression of O-acetyl-GD3 ganglioside may stimulate cellular growth and suppress certain differentiated phenotypes such as dendrite formation, but not melanogenesis, in our system.
Animals↗
Force between two spherical inclusions in a nonlinear host medium
In an attempt to investigate the effect of nonlinear characteristics on particle interactions, a self-consistent mean-field theory in combination with a multiple image method has been employed to compute the interparticle force. Taking the nonlinearity of the host medium into account, the interparticle force exhibits a nonmonotonic behavior as the applied electric field is increased. We show that the interparticle force increases initially at low fields, goes through a maximum at an optimal electric field, then decreases with increasing field, and vanishes at a critical electric field at which the effective dielectric contrast between the host and the inclusions becomes zero. The influence of a larger volume fraction of inclusions on the interparticle force is also investigated.
Journal Article↗
Genetic erosion in northern marginal population of the common wild rice Oryza rufipogon Griff. and its conservation, revealed by the change of population genetic structure.
In order to monitor genetic erosion within the northern marginal population of common wild rice Oryza rufipogon Griff. from Dongxiang, Jiangxi Province, China, allozyme diversity encoded by 22 loci was analyzed electrophoretically from all the existing subpopulations in 1980, 1985 and 1994. The sample collected from the nine large subpopulations in 1980 showed the highest levels of genetic diversity (A = 1.27, P = 18.20%, Ho = 0.042 and He = 0.049) and a slight deviation from Hardy-Weinberg expectation (F = 0.143), the sample from five moderate ones in 1985 displayed medium levels of genetic diversity (A = 1.14, P = 13.60%, Ho = 0.008 and He = 0.049) and a great deviation from Hardy-Weinberg expectation (F = 0.837), and the sample from two small ones in 1994 demonstrated the lowest levels of genetic diversity (A = 1.09, P = 9.10%, Ho = 0.000 and He = 0.043) and the largest deviation from Hardy-Weinberg expectation (F = 1.000). The results not only documented the genetic erosion stemmed from the extinction of the subpopulations, but also revealed the drastic change of the population genetic structure due to the reduction of the population. Finally, some conservation strategies for the population are proposed.
DNA, Plant↗
Longitudinal study of earthquake-related PTSD in a randomly selected community sample in north China.
OBJECTIVE: This study longitudinally described rates of posttraumatic stress disorder (PTSD) in two groups with different levels of severity of exposure to an earthquake in North China. The effects of diagnostic criteria on the frequency of detected PTSD were also examined. METHOD: Subjects were randomly sampled in two villages at different distances from the earthquake epicenter. A total of 181 and 157 subjects were assessed at 3 months and 9 months after the earthquake, respectively, for PTSD by using both DSM-IV and DSM-III-R criteria. The brief version of the World Health Organization Quality of Life Assessment and three subscales of the SCL-90-R were also administered at both assessment points. RESULTS: The village with a higher level of initial exposure to the earthquake and a higher level of postearthquake support had a lower frequency of PTSD than the village with a lower level of initial exposure and less postearthquake support. The rate of onset of DSM-IV PTSD within 9 months for the two villages was 19.8% and 30.3%, respectively. In both villages, the rate of onset of earthquake-related PTSD within 9 months was 24.2% by using DSM-IV criteria and 41.4% by using DSM-III-R criteria. The introduction in DSM-IV of a criterion requiring clinically significant distress or impairment in functioning for a diagnosis of PTSD was a major contributor to the lower rate of DSM-IV PTSD. CONCLUSIONS: PTSD may be as prevalent and persistent in disaster victims in China as in those elsewhere. Prompt and effective postdisaster intervention could mitigate the impact of initial exposure and reduce the probability of PTSD occurrence. Caution should be used in comparing rates of postdisaster PTSD identified by using different diagnostic criteria.
Adult↗
Potential use of pharmacological markers to quantitatively assess liver function during liver transplantation surgery.
Early functioning of the transplanted liver is of crucial importance to the recipient. This function may be assessed by measuring the disposition of substances that are mainly eliminated via the liver. None of the agents currently used is ideal for this purpose. Measurement of mono-ethyleneglycinexylidide (MEGX) formation from lignocaine is useful and has been widely used in liver transplantation to assess liver graft function. MEGX formation can be affected by the use of drugs that influence liver perfusion or interfere with the CYP450 enzyme system. Indocyanine green clearance is a convenient method but both blood flow and hepatocellular function affect the test results. Tests of caffeine clearance, galactose elimination capacity and antipyrine clearance all require time-consuming, technically cumbersome and expensive serial blood sampling. The aminopyrine breath test is non-invasive, but gastric emptying and the patient's physical state affect results. The potential hazard of exposure to radioactive compounds limits the wide clinical use of both aminopyrine and erythromycin breath tests. Monitoring the rate of recovery from neuromuscular blockade induced by vecuronium and rocuronium can provide valuable information on liver function.
Adult↗
Item-level and subscale-level factoring of Biggs' Learning Process Questionnaire (LPQ) in a mainland Chinese sample.
BACKGROUND: The learning process questionnaire (LPQ) has been the source of intensive cross-cultural study. However, an item-level factor analysis of all the LPQ items simultaneously has never been reported. Rather, items within each subscale have been factor analysed to establish subscale unidimensionality and justify the use of composite subscale scores. AIMS: It was of major interest to see if the six logically constructed items groups of the LPQ would be supported by empirical evidence. Additionally, it was of interest to compare the consistency of the reliability and correlational structure of the LPQ subscales in our study with those of previous cross-cultural studies. METHODS: Confirmatory factor analysis was used to fit the six-factor item level model and to fit five representative subscale level factor models. SAMPLE: A total of 1070 students between the ages of 15 to 18 years was drawn from a representative selection of 29 classes from within 15 secondary schools in Guangzhou, China. Males and females were almost equally represented. RESULTS: The six-factor item level model of the LPQ seemed to fit reasonably well, thus supporting the six dimensional structure of the LPQ and justifying the use of composite subscale scores for each LPQ dimension. However, the reliability of many of these subscales was low. Furthermore, only two subscale-level factor models showed marginally acceptable fit. Substantive considerations supported an oblique three-factor model. CONCLUSIONS: Because the LPQ subscales often show low internal consistency reliability, experimental and correlational studies that have used these subscales as dependent measures have been disappointing. It is suggested that some LPQ items should be revised and other items added to improve the inventory's overall psychometric properties.
Achievement↗