Biomedical subjects
Publications and source records attributed to Y Lu.
A method for the determination of trace amount of Pb and Cd in animal bone using GFAAS has been established. The samples were determined directly after being diluted by TMAH solution. The method is handy and fast. The recovery is 96.95-103.15%. The RSD is less than 4.81%.
The determination of microamount gadolinium(III) by fluorescence method was studied based on complex formation Gd(III)-CTMAB-TFA at pH7.2. Beer's law is obeyed in the range of 0. 005-0.04 microg/mL Gd(III). The detection limit is 0.003 microg/mL. The method is used to determine microamount gadolinium of rare-earth mine with satisfactory result, and compared with that of ICP-AES method.
The present study investigated whether spinal administration of S-(+)-3-isobutylgaba (S-(+)-3-IBG) or its stereoisomer, R-(-)-3-isobutylgaba (R-(-)-3-IBG), are effective in reducing the hyperalgesia and swelling observed after injection of kaolin and carrageenan into the knee joint of the rat. The effects of pretreatment and post-treatment of S-(+)-3-IBG, R-(-)-3-IBG and artificial cerebrospinal fluid (aCSF) on the swelling, pain-related behavior scores and the heat hyperalgesia induced by knee joint inflammation were compared. Infusion of either S-(+)-3-IBG or R-(-)-3-IBG through a microdialysis fiber, implanted in the dorsal horn of the spinal cord, for 1.5 h before injection of kaolin and carrageenan resulted in a 20 to 30% reduction in joint swelling compared with aCSF-treated controls, and prevented the development of heat hyperalgesia and spontaneous pain. In contrast, infusion of either stereoisomer after the development of inflammation reduced the hyperalgesia but did not reduce the amount of joint swelling compared with aCSF-treated animals. In summary, S-(+)-3-IBG and R-(-)-3-IBG are effective antihyperalgesic agents when administered both before and after joint inflammation. In addition, if administered before injection of kaolin and carrageenan into the knee joint this drug can attenuate joint inflammation. Both the antihyperalgesic and anti-inflammatory properties of this drug probably are mediated through a central neurogenic mechanism.
Several recent electrophysiological studies have demonstrated that nicotinic agonists stimulate the release of gamma-aminobutyric acid (GABA) from rodent brain tissue. Our studies used a neurochemical approach to characterize nicotinic receptor-stimulated [3H]-GABA release from mouse brain synaptosomes. Nicotine increased [3H]-GABA release from synaptosomes preloaded with [3H]-GABA in a concentration-dependent manner. This release appeared rapidly, was Ca++ dependent, and was partially (about 50%) blocked by 100 nM tetrodotoxin and totally blocked by mecamylamine and dihydro-beta-erythroidine. alpha-Bungarotoxin had no effect. Twelve nicotinic agonists were compared for their effects on [3H]-GABA release. The agonists differed in potency (EC50) and efficacy (Emax). The EC50 and Emax values were significantly correlated (r = 0.95, P <.001 for EC50; r = 0.93, P <.01 for Emax) to values obtained for these same agonists when 86Rb+ efflux was determined. A significant correlation (r = 0.84, P <.01) was found when the EC50 values for agonist-stimulated [3H]-GABA release and IC50 values for agonist inhibition of [3H]-L-nicotine binding were compared. Differences in [3H]-GABA release were detected in 12 brain regions and maximal release was significantly correlated with [3H]-nicotine binding. The pharmacological and regional comparisons suggest that the nAChR that stimulates [3H]-GABA release is the one that binds [3H]-nicotine with high affinity (alpha4beta2). Unequivocal evidence that the receptor that modulates nicotine-stimulated [3H]-GABA release contains a beta2 subunit was obtained in a study using wild-type, heterozygous and homozygous beta2 null mutant mice. [3H]-GABA release and [3H]-nicotine binding decreased along with the number of copies of the null mutant gene.
In the present study, direct projections from the lumbosacral cord to Barrington's nucleus in the rat were investigated by using retrograde and anterograde tracing techniques. After injection of cholera toxin B subunit (CTb) into Barrington's nucleus, a number of moderately CTb-labeled neurons were observed in the lumbosacral cord, with a slight ipsilateral dominance; most were located in the spinal parasympathetic and dorsal commissural nuclei of the lumbosacral cord. In addition, some retrogradely labeled neurons were found in the periaqueductal gray (PAG). These findings were confirmed by an anterograde labeling experiment. After biotinylated dextran amine (BDA) was injected into the lumbosacral cord, dense BDA-labeled axon terminals were found in Barrington's nucleus as well as in the PAG. Injection of BDA into the PAG resulted in many BDA-labeled terminals in Barrington's nucleus. The present results provided clear evidence for a direct projection from the spinal parasympathetic and dorsal commissural nuclei to Barrington's nucleus that could subserve conveying bladder-filling information from the lumbosacral cord to Barrington's nucleus in the micturition reflex of the rat.
Corneal dystrophy of the anterior basement membrane is a heterogeneous set of diseases characterized by painful, recurrent, bilateral erosions of the cornea, which often result in significant visual impairment. There are several similar but clinically distinct forms of anterior basement membrane/Bowman's membrane disease, including two autosomal dominant forms, Reis-Bücklers and Thiel-Behnke corneal dystrophy. Genes causing autosomal, nonsyndromic corneal dystrophy have been mapped to human chromosomes 1p, 5q, 12q, 16q, 17p, and 20p. Using microsatellite markers closely linked to the known corneal dystrophy loci, we excluded linkage between the known sites and the disease locus in a large, four-generation family with Thiel-Behnke corneal dystrophy. A genome-wide search using a panel of microsatellite markers demonstrated a maximum two-point lod score of 4.0 at 0% recombination between the disease locus in this family and the marker D10S1239, which maps to 10q23-q24. Testing with additional microsatellite markers from 10q places the disease locus between D10S677 and D10S1671, a distance of approximately 12.0 cM, with a maximum multipoint lod score of 5.5. Based on this evidence, we have identified another locus (CDB2) for corneal dystrophy of the anterior basement membrane/Bowman's membrane, Thiel-Behnke type, further demonstrating the exceptional genetic and phenotypic heterogeneity of these diseases.
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Clozapine (1-10 mg/kg s.c.) produces a selective increase in dopamine release in rat prefrontal cortex which is, in large part (approximately 50%), mediated via activation of 5-HT1A receptors. Clozapine is a moderately potent, partial 5-HT1A receptor agonist and activation of 5-HT1A receptors may contribute to its efficacy against negative symptoms and reduced extrapyramidal side effect liability. Agonist affinity for 5-HT1A receptors could thus be a desirable feature in the design of new antipsychotics.
Mammalian cardiac myocytes become postmitotic shortly after birth, and the subsequent myocardial growth in adaptation to increasing workloads becomes primarily dependent on hypertrophy of existing myocytes. Although hypertrophic growth of cardiac myocytes has been extensively studied by using both in vitro and in vivo models, the molecular mechanism controlling the switch from hyperplastic to hypertrophic growth of cardiac myocytes is largely unknown. Since the majority of terminally differentiated cardiac myocytes are growth-arrested in G1/G0 phase, it has been hypothesized that the retinoblastoma protein (Rb) or its related pocket proteins which block G1/S transition becomes constitutively active during myocardial terminal differentiation. To test this hypothesis, we studied the regulation of Rb activity by alpha-adrenergic stimulation in neonatal rat ventricular myocytes which are mostly postmitotic in culture. Our results demonstrate that Rb is predominantly in the active hypo-phosphorylated state in control neonatal ventricular myocytes. alpha-Adrenergic stimulation activates G1/S transition in foetal but not neonatal rate ventricular myocytes. Although alpha-adrenergic stimulation does not activate G1/S transition in neonatal myocytes, it induces hyperphosphorylation of Rb to the same extent as in proliferating skeletal-muscle myoblasts or foetal ventricles. Hyper- but not hypo-phosphorylated Rb in stimulated neonatal myocytes or proliferating skeletal-muscle myoblasts fails to bind to the transcription factor, E2F, suggesting that hyper-phosphorylated Rb is inactive. Therefore F1/S transition could also be blocked at steps in addition to Rb inactivation during terminal differentiation and these blockades are refractory to alpha-adrenergic stimulation.
Previous studies demonstrated that DBA/2J (DBA) mice performed poorly while C57BL/6J (C57) mice performed normally on a number of complex learning and memory tasks. Chronic oxiracetam treatment dramatically improved the performance of DBA mice but not that of C57 mice on the Morris water task and in contextual fear conditioning. The present study demonstrates that acute treatment with nootropics, oxiracetam (10-1000 mg/kg) or aniracetam (10-100 mg/kg), and N-methyl-D-Aspartate (NMDA) antagonists, (+)-MK-801 (0.1-3 microg/kg), CPP (0.01-0.3 mg/kg), and (+)-HA-966 (0.1-3 mg/kg), administered prior to training and testing, reversed the contextual learning impairment in DBA mice in a dose-dependent manner without affecting auditory cue conditioning. These effects appeared to be independent of testing order (context vs. auditory cue tests) and were not due to state-dependent learning. The inactive stereoisomers, (-)-MK-801 and (-)-HA-966, were incapable of increasing contextual freezing in DBA mice. In DBA mice, the effects of 30 mg/kg oxiracetam and 100 mg/kg aniracetam were inhibited by the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonists, NBQX, and GYKI-52466. The combined administration of 30 mg/kg oxiracetam and 1 microg/kg (+)-MK-801 produced an additive response. None of the pharmacological treatments altered performance in C57 mice at doses that were effective in DBA mice. These results suggest that DBA mice may be learning impaired due to altered glutamatergic receptor function.
Comparative calibration is the broad statistical methodology used to assess the calibration of a set of p instruments, each designed to measure the same characteristic, on a common group of individuals. Different from the usual calibration problem, the true underlying quantity measured is unobservable. Many authors have shown that this problem, in general, does not have a unique solution. Most commonly used assumptions to obtain a unique solution are (i) one instrument is the gold standard (that is, unbiased) and (ii) the measurement errors of the p instruments are independent. Such constraints, however, may not be valid for many clinical applications, for example, the universal standardization project for dual X-ray absorptiometry (DXA) scanners. In this paper, we propose a new approach to resolve the comparative calibration problem when a gold standard is unavailable. Instead of the usual assumptions, we use external information in addition to data from the p instruments, to solve the problem. We address statistical estimation, hypothesis testing and missing data problems. We apply the new method specifically to the universal standardization project data where a group of individuals have been measured for bone mineral density (BMD) by three DXA scanners. We compare the results of the new method to currently used methods and show that they have better statistical properties.
To investigate the functional relationship between the transforming ability of Ras and its role as an integral component of the differentiative insulin signaling pathway, we introduced a leu61-activated ras gene into a Ras-transformable, C3H10T1/2-derived preadipocytic cell line. The results demonstrate that rasleu61 expression in this line blocks differentiation and that this block appears at lower levels than required for full neoplastic transformation. In addition, to examine whether the inability of Rasleu61 to induce differentiation by replacing the insulin signal could be attributed to its transforming effect in this system, we examined the effect of Rasleu61 at levels below the baseline, by expressing rasleu61 in a series of preadipocytes which were rendered deficient in endogenous c-Ras activity. The results show that even very low Rasleu61 levels, insufficient to restore the growth rate of these cells to normal, blocked rather than enhanced differentiation, indicating that rasleu61 expression alone is not sufficient to promote adipocytic differentiation in this system, even in the absence of neoplastic transformation. Consistent with its established role as a downstream effector of Ras, v-Raf expression mirrored the v-Ras effects upon adipocytic differentiation and transformation.
A modified method was employed to prepare monodispersed colloidal particles of ferric (hydrous) oxide. The method contains three steps: (i) preparation of uniform nuclei of ferric hydrous oxide via a so-called instantaneous nucleation method; (ii) purification of the nuclei suspension via dialysis; (iii) aging of the purified nuclei suspension in a reflux reactor at certain pH. Cubic and pseudocubic alpha-Fe2O3 monodisperse particles which are much smaller than the cubic alpha-Fe2O3 particles obtained from the same reactant through a usual method were produced by aging needle like nuclei at a lower pH. A close-packed three-dimensional QDs (quantum dots) superlattice structure 40 nm in edge length with cubic geometry was formed by self-aggregation between spherical amorphous ferric hydrous oxide nuclei 3-5 nm in diameter. The growth processes of the two kind particles were also illustrated. This study showed an approach to prepare smaller particles from aqueous metal salt solutions in relatively higher concentration, and ordered QDs superlattice structure by controlled self-aggregation of QDs in hydrosol.
Reverse transcription-polymerase chain reaction (RT-PCR) was used for the enzymatic synthesis of cDNA sequences encompassing the open reading frame for the catalytic subunit of mouse kidney glutamate-cysteine ligase (Glclc). Comparison of the mouse Glclc cDNA sequence and predicted protein sequence with that of rat Glclc and human GLCLC revealed between 94.8% and 88.4% cDNA homology and 98.4% to 95% amino acid identity, respectively.
Both silica and lipopolysaccharide (LPS) induce a rapid degradation of I kappa B alpha, an intracellular inhibitor of the nuclear factor (NF)-kappa B transcription factor. In this report, we demonstrate that MG132, a relatively specific proteasome inhibitor, is capable of suppressing LPS-induced I kappa B alpha degradation and NF-kappa B activation in mouse macrophage line RAW 264.7 cells, but is unable to influence the same induction produced by silica. In contrast, the lysosome inhibitor chloroquine has little effect on I kappa B alpha degradation induced by either silica or LPS. In fact, chloroquine enhances the signal-induced nuclear expression of NF-kappa B p50/p65 heterodimer by inhibiting the resynthesis of I kappa B alpha. With the use of transient transfection of a plasmid that expresses calpastatin, a natural inhibitor for calpain, the silica-induced degradation of I kappa B alpha and NF-kappa B activation was attenuated. In contrast, no inhibition of LPS-induced I kappa B alpha degradation and NF-kappa B activation was observed by the overexpression of calpastatin. This suggests that calpain contributes to silica-induced I kappa B alpha degradation and NF-kappa B activation but not to LPS-induced I kappa B alpha degradation and NF-kappa B activation.
Failure of chemotherapy associated with expression of the multidrug resistance protein p170 frequently occurs in retinoblastoma (RB). Despite using cyclosporine, which inhibits p170 and improves our chemotherapy results, rare failures occur. In nonmetastatic primarily enucleated RBs, we show expression of p170 in 3 of 18 samples and expression of multidrug resistance protein (MRP), the second protein associated with resistance to chemotherapy, in 1 of 18 samples. All three RBs that failed chemotherapy without cyclosporine expressed MRP with p170. All three RBs that were enucleated immediately when chemotherapy failed despite the addition of cyclosporine expressed only MRP. One RB enucleated 2 years after failing chemotherapy with cyclosporine, despite radiation and salvage chemotherapy, expressed both p170 and MRP. Two metastatic RBs that expressed both p170 and MRP at diagnosis and at recurrence failed chemotherapy without cyclosporine, whereas one metastatic RB that expressed neither protein was cured by chemotherapy without cyclosporine. MRP may result in failure of chemotherapy despite the elimination of p170-expressing clones by cyclosporine.
Cellular tRNALys-3 serves as the primer for reverse transcription of human immunodeficiency virus, type 1 (HIV-1). tRNALys-3 interacts directly with HIV-1 reverse transcriptase, is packaged into viral particles and anneals to the primer-binding site (PBS) of the HIV-1 genome to initiate reverse transcription. Therefore, the priming step of reverse transcription is a potential target for antiviral strategies. We have developed a mutant tRNALys-3 derivative with mutations in the PBS-binding region such that priming specificity was re-directed to the highly conserved TAR stem-loop region. This mutant tRNA retains high-affinity binding to HIV-1 reverse transcriptase, viral encapsidation, and is able to prime at both the targeted TAR sequence and at the viral PBS. Constitutive expression of mutant tRNA in T-cells results in marked inhibition of HIV-1 replication, as determined by measurements of viral infectivity, syncytium formation, and p24 production. Inhibition of retroviral replication through interference with the normal process of priming constitutes a new anti-retroviral approach and also provides a novel tool for dissecting molecular aspects of priming.
Unlike the other silver halides, silver fluoride is positively charged in its saturated solution as determined by nonequilibrium electrophoresis measurements. In the absence of surface hydrolysis reactions, other fluoride salts (LiF, CaF2 , and MgF2 ) also are positively charged in their saturated solutions. Furthermore, the electrokinetic behavior of these fluoride salts is rather insensitive to the fluoride ion activity in neutral or acidic solutions, and reversal of the sign of the surface charge by fluoride addition is not possible. Based on FTIR transmission spectra to describe the water structure of ionic solutions, in situ FTIR/internal reflection spectroscopy (FTIR/IRS) has been used to spectroscopically characterize interfacial water at fluoride salt surfaces. The experimental spectra were examined by consideration of the O-H stretching region (3000-3800 cm-1 ) associated with the vibrational spectra of interfacial water. These results reveal a unique hydration state for fluorides and explain the anomalous electrokinetic behavior of fluoride salts such as LiF, CaF2 , and MgF2 , which show an unexpected insensitivity to the fluoride ion concentration in solution. It appears that this insensitivity is due to the formation of strong hydrogen bonding of the fluoride ions with water molecules. This hydration state prevents the accommodation of excess fluoride ions at surface lattice sites and accounts for the observed electrokinetic behavior.